FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Huang, K Huang, FL Shetty, PK AF Huang, K. Huang, F. L. Shetty, P. K. TI Oxidative stress-induced modifications of PKC by reactive sulfur species: glutathione disulfide S-oxides SO FREE RADICAL RESEARCH LA English DT Meeting Abstract CT 13th Biennial Meeting of the Society-for-Free-Radical-Research-International CY AUG 15-19, 2006 CL Davos, SWITZERLAND SP Soc Free Rad Res Int C1 NICHD, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2006 VL 40 SU 1 BP S76 EP S76 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086EG UT WOS:000240656000166 ER PT J AU Levine, M AF Levine, Mark TI Vitamin C and tight control: Consequences for health, disease, and disease treatment SO FREE RADICAL RESEARCH LA English DT Meeting Abstract CT 13th Biennial Meeting of the Society-for-Free-Radical-Research-International CY AUG 15-19, 2006 CL Davos, SWITZERLAND SP Soc Free Rad Res Int C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2006 VL 40 SU 1 BP S58 EP S58 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086EG UT WOS:000240656000092 ER PT J AU Miller, ERP AF Miller, E. R. P., III TI High dose Vitamin E supplementation and mortality: discussion of the results of a meta-analysis of randomized controlled clinical trial SO FREE RADICAL RESEARCH LA English DT Meeting Abstract CT 13th Biennial Meeting of the Society-for-Free-Radical-Research-International CY AUG 15-19, 2006 CL Davos, SWITZERLAND SP Soc Free Rad Res Int C1 Johns Hopkins Univ, NIA, Baltimore, MD 21218 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2006 VL 40 SU 1 BP S45 EP S45 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086EG UT WOS:000240656000040 ER PT J AU Noda, Y Berlett, B Stadtman, E Aponte, A Morgan, M Shen, RF AF Noda, Y. Berlett, B. Stadtman, E. Aponte, A. Morgan, M. Shen, R. F. TI Identification of enzymes and regulatory proteins in E. coli that are preferentially oxidized during nitrogen or carbon starvation SO FREE RADICAL RESEARCH LA English DT Meeting Abstract CT 13th Biennial Meeting of the Society-for-Free-Radical-Research-International CY AUG 15-19, 2006 CL Davos, SWITZERLAND SP Soc Free Rad Res Int C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Proteom Core Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2006 VL 40 SU 1 BP S130 EP S130 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086EG UT WOS:000240656000384 ER PT S AU Soula, H Beslon, G AF Soula, Hedi Beslon, Guillaume BE Nolfi, S Baldassarre, G Calabretta, R Hallam, JCT Marocco, D Meyer, JA Miglino, O Parisi, D TI Spike-timing dependent plasticity learning for visual-based obstacles avoidance SO FROM ANIMALS TO ANIMATS 9, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 9th International Conference on Simulation of Adaptive Behavior CY SEP 25-29, 2006 CL Italian Natl Res Council, Rome, ITALY SP Appl AI Syst Inc, European Network Adv Artificial Cognit Syst Cognit, Inst Cognit Sci & Technol, Italian Soc Cognit Sci, Int Soc Adapt Behav, Kteam, Lab Informat Paris 6, Univ Edinburgh, Univ Pierre Marie Curie, Univ SE Denmark HO Italian Natl Res Council ID NEURONAL NETWORKS; DYNAMICS; LOCKING AB In this paper, we train a robot to learn online a task of obstacles avoidance. The robot has at its disposal only its visual input from a linear camera in an arena whose walls are composed of random black and white stripes. The robot is controlled by a recurrent spiking neural network (integrate and fire). The learning rule is the spike-time dependent plasticity (STDP) and its counterpart - the so-called anti-STDP. Since the task itself requires some temporal integration, the neural substrate is the network's own dynamics. The behaviors of avoidance we obtain are homogenous and elegant. In addition, we observe the emergence of a neural selectivity to the distance after the learning process. C1 NIDDK, LBM, NIH, Bethesda, MD 20892 USA. Inst Natl Sci Appl, PRISMA, F-69621 Villeurbanne, France. RP Soula, H (reprint author), NIDDK, LBM, NIH, Bethesda, MD 20892 USA. RI Beslon, Guillaume/D-7369-2014 NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-38608-4 J9 LECT NOTES COMPUT SC PY 2006 VL 4095 BP 335 EP 345 PG 11 WC Computer Science, Artificial Intelligence; Robotics SC Computer Science; Robotics GA BFI94 UT WOS:000242125300028 ER PT S AU Cavelier, G Amzel, LM AF Cavelier, German Amzel, L. Mario BE ClementeGallardo, J Moreno, Y Lorenzo, JFS VelazquezCampoy, A TI Role of fluctuations in quinone reductase hydride transfer: a combined quantum mechanics and molecular dynamics study SO FROM PHYSICS TO BIOLOGY: THE INTERFACE BETWEEN EXPERIMENT AND COMPUTATION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 2nd International Conference on From Physics to Biology - The Interface Between Experiment and Computation (BIFI 2006) CY FEB 08-11, 2006 CL Zaragoza, SPAIN SP Univ Zaragoza, Govt Aragon, Ibercaja, Spanish Minist Sci & Educ, Megware Comp GmbH DE density functional; enzymes; flavoproteins; DT-diaphorase; isoalloxazine; quantum chemistry; protein fluctuations; molecular dynamics ID LIVER ALCOHOL-DEHYDROGENASE; ENZYME CATALYSIS; AB-INITIO; TRANSITION STRUCTURES; NAD(P)H-QUINONE REDUCTASE; STRUCTURAL-CHANGES; TRANSFER STEP; IN-VACUO; ENERGY; NADH AB Quinone Reductase is a cytosolie FAD-containing enzyme that carries out the obligatory two-electron reduction of quinones to hydroquinones. The first step in the mechanism consists of the reduction of the FAD by NAD(P)H via direct a hydride transfer. Combined QM/MM calculations show that the protein accelerates this step by a combination of effects that include charge stabilization and distortion. The calculations also show that dynamic effects play an important role in QR catalysis: the distance between the donor and the acceptor atoms of the hydride transfer, which is too long for transfer in the static Ad structure, becomes shorter than 3 angstrom 25% of the time due to motions of the protein and the cofactors. C1 [Cavelier, German; Amzel, L. Mario] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. [Cavelier, German] Off Interdisciplinary Res & Sci Technol, Div Neurosci & Basic Behav Sci, New Delhi, India. [Amzel, L. Mario] NIH, NIMH, Bethesda, MD 20892 USA. RP Amzel, LM (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. EM mario@neruda.med.jhmi.edu OI Amzel, L. Mario/0000-0002-0129-9572 FU National Institute of General Medical Sciences [GM 51362] FX Supported by Grant GM 51362 of the National Institute of General Medical Sciences. We thank the Supercomputing Center of the National Cancer Institute, Frederick, Md. NR 50 TC 0 Z9 0 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0350-3 J9 AIP CONF PROC PY 2006 VL 851 BP 1 EP + PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Cell Biology; Computer Science GA BFB53 UT WOS:000240796700001 ER PT J AU Risberg, J Grafman, J AF Risberg, Jarl Grafman, Jordan BE Risberg, J Grafman, J TI The Frontal Lobes Development, Function, and Pathology Introduction SO FRONTAL LOBES: DEVELOPMENT, FUNCTION, AND PATHOLOGY SE Series for the International Neuropsychological Society LA English DT Editorial Material; Book Chapter C1 [Risberg, Jarl] Univ Hosp, Dept Clin Neurophysiol, SE-22185 Lund, Sweden. [Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Risberg, J (reprint author), Univ Hosp, Dept Clin Neurophysiol, SE-22185 Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-67225-2 J9 SER INT NEUROPSYCHOL PY 2006 BP XI EP XIV DI 10.1017/CBO9780511545917.002 D2 10.1017/CBO9780511545917 PG 4 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA BXN05 UT WOS:000296459600002 ER PT J AU Grafman, J AF Grafman, Jordan BE Risberg, J Grafman, J TI Human prefrontal cortex: processes and representations SO FRONTAL LOBES: DEVELOPMENT, FUNCTION, AND PATHOLOGY SE Series for the International Neuropsychological Society LA English DT Article; Book Chapter ID FRONTAL-LOBE LESIONS; ANTERIOR CINGULATE CORTEX; FUNCTIONAL-MRI; ORBITOFRONTAL CORTEX; BRAIN ACTIVATION; DECISION-MAKING; WORKING-MEMORY; MENTAL REPRESENTATION; PARKINSONS-DISEASE; RECOGNITION MEMORY C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. NR 106 TC 4 Z9 4 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-67225-2 J9 SER INT NEUROPSYCHOL PY 2006 BP 69 EP 91 DI 10.1017/CBO9780511545917.005 D2 10.1017/CBO9780511545917 PG 23 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA BXN05 UT WOS:000296459600005 ER PT J AU Mughal, TI Goldman, JM AF Mughal, TI Goldman, JM TI Chronic myeloid leukemia: why does it evolve from chronic phase to blast transformation? SO FRONTIERS IN BIOSCIENCE LA English DT Article DE chronic myeloid leukemia; chronic phase; blast transformation; evolution; review ID CHRONIC MYELOGENOUS LEUKEMIA; MINIMAL RESIDUAL DISEASE; BCR-ABL ONCOPROTEINS; C-ABL; PHILADELPHIA-CHROMOSOME; STEM-CELLS; HEMATOPOIETIC-CELLS; KINASE-ACTIVITY; TYROSINE PHOSPHORYLATION; CONSTITUTIVE ACTIVATION AB Clinically chronic myeloid leukemia is a biphasic or triphasic disease that is usually diagnosed in the initial ` chronic', ` indolent' or ` stable' phase and then spontaneously evolves after some years into an advanced phase. This advanced phase can sometimes be subdivided into an earlier accelerated phase and a later blast phase or blast transformation - in about one- half of patients the chronic phase transforms unpredictably and abruptly to a blast phase, while in the other half of patients, the disease evolves somewhat more gradually, through an accelerated phase, which may last for months or years, before a blast phase ensues; this may have myeloblastic or lymphoblastic features. Although much is now known about the molecular biology of the disease, the molecular basis of disease progression is still obscure. The popular thinking has been that one or more probably a sequence of additional genetic events occurs in the BCR- ABL positive clone. When the critical combination of additional events is achieved, clinically definable transformation occurs. Here we review what is known of the mechanisms underlying the evolution of chronic myeloid leukemia from a chronic phase to a blast transformation. C1 Univ Massachusetts, Sch Med, Div Hematol & Oncol, Worcester, MA 01655 USA. NHLBI, Hematol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Mughal, TI (reprint author), Univ Massachusetts, Sch Med, Div Hematol & Oncol, 55 Lake Ave N, Worcester, MA 01655 USA. EM tmughal@freenet.co.uk NR 93 TC 18 Z9 18 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2006 VL 11 BP 198 EP 208 DI 10.2741/1791 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973MX UT WOS:000232528000017 PM 16146725 ER PT J AU Mughal, TI Goldman, JM AF Mughal, TI Goldman, JM TI Molecularly targeted treatment of chronic myeloid leukemia: beyond the imatinib era SO FRONTIERS IN BIOSCIENCE LA English DT Article DE CML; BCR-ABL; Philadelphia chromosome; imatinib; Gleevec ID CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; ABL-POSITIVE CELLS; BCR-ABL; CLINICAL RESISTANCE; PHILADELPHIA-CHROMOSOME; STI571 RESISTANCE; CYTOGENETIC REMISSION; INTERFERON-ALPHA AB Chronic myeloid leukemia cells contain a BCR-ABL oncoprotein with an enhanced tyrosine kinase activity, which is considered to be the principal ` cause' of the leukemia. Though the precise mechanisms underlying the leukemogenesis remains enigmatic, the use of imatinib to inhibit the dysregulated kinase activity has proved remarkably successful in clinical practice. Imatinib was the first small molecule developed to inhibit BCR- ABL tyrosine kinase activity and its success introduced the current era of molecularly targeted therapies for a number of other malignancies. In patients with chronic myeloid leukaemia who develop resistance to imatinib, the Bcr- Abl signaling pathway is often re- established. This has led to the emergence of a number of alternative treatment strategies designed to target the leukemic cell which are resistant to imatinib. C1 Univ Massachusetts, Sch Med, Div Hematol & Oncol, Worcester, MA 01655 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Mughal, TI (reprint author), Univ Massachusetts, Sch Med, Div Hematol & Oncol, 55 Lake Ave N, Worcester, MA 01655 USA. EM tmughal@freenet.co.uk NR 78 TC 5 Z9 5 U1 0 U2 1 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 2006 VL 11 BP 209 EP 220 DI 10.2741/1792 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973MX UT WOS:000232528000018 PM 16146726 ER PT J AU Mufson, RA AF Mufson, RA TI Tumor antigen targets and tumor immunotherapy SO FRONTIERS IN BIOSCIENCE LA English DT Article DE tumor; antigens; CTL; immunotherapy; tumor immunology; review ID METASTATIC MELANOMA; T-CELLS; CD8-T-CELL MEMORY; CD4-T-CELL HELP; IFN-GAMMA; ANTIBODY; CANCER; BLOCKADE; RECEPTORS; RESPONSES AB Tumor immunology and immunotherapy attempt to use the exquisite specificity and lytic capability of the immune system to treat malignant disease with a minimum of damage to normal tissue. Increasing knowledge of the identity of tumor antigens should point the way to effective therapeutic vaccines or more specific immunotherapeutic strategies. Tumors, however, have evolved mechanisms to inactivate cytolytic T-cells and other immune responses targeting tumor antigens. The current goal of immunotherapy research is to use contemporary advances in cellular and molecular immunology to develop strategies to overcome the disabling effects of the tumor microenvironment on the immune system attack against tumor antigen targets. This review will summarize our current knowledge of the spectrum of tumor antigen targets available for immune recognition in cancer, the obstacles to tumor immunotherapy, the use of adoptive immunotherapy to overcome some of these obstacles, the use of monoclonal antibodies to target tumor antigens for immunotherapy, and finally the potential use of heat shock proteins as targets for cancer immunotherapy. C1 NCI, Canc Immunol Hematol Branch, Bethesda, MD 20892 USA. RP Mufson, RA (reprint author), NCI, Canc Immunol Hematol Branch, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM mufsonr@mail.nih.gov NR 36 TC 7 Z9 10 U1 1 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2006 VL 11 BP 337 EP 343 DI 10.2741/1801 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973MX UT WOS:000232528000027 PM 16146735 ER PT J AU Hodge, JW Greiner, JW Tsang, KY Sabzevari, H Kudo-Saito, C Grosenbach, DW Gulley, JL Arlen, PM Marshall, JL Panicali, D Schlom, J AF Hodge, JW Greiner, JW Tsang, KY Sabzevari, H Kudo-Saito, C Grosenbach, DW Gulley, JL Arlen, PM Marshall, JL Panicali, D Schlom, J TI Costimulatory molecules as adjuvants for immunotherapy SO FRONTIERS IN BIOSCIENCE LA English DT Article DE vaccinia; fowlpox; immunotherapy; treatment; therapeutics; costimulation; TRICOM; B7-1; ICAM-1; LFA-3; review ID RECOMBINANT VACCINIA VIRUS; T-CELL-ACTIVATION; FAMILIAL ADENOMATOUS POLYPOSIS; HUMAN CARCINOEMBRYONIC ANTIGEN; MULTIPLE INTESTINAL NEOPLASIA; ANTITUMOR IMMUNITY; PHASE-I; METASTATIC MELANOMA; CYCLOOXYGENASE-2 INHIBITOR; DIVERSIFIED PRIME AB Tumor-associated antigens (TAAs) are by definition either weakly immunogenic or functionally nonimmunogenic. Therefore, efforts have concentrated on the development of vaccine strategies in which the presentation of TAAs to the immune system results in far greater activation of T cells than that occurring naturally in the host. Several strategies are being explored in our laboratory and others to enhance the immunogenicity of TAAs. These are: ( a) placing the gene coding for the tumor antigen, as a transgene, into poxvirus vectors. (b) The use of diversified prime and boost vaccine strategies employing two different types of poxvirus vectors. (c) The use of T-cell costimulation; accomplished by placing transgenes for different T-cell costimulation molecules into viral vectors along with the transgenes for the TAA. (d) Altering the amino acid sequence of the TAA to enhance the host immune response. (e) The use of cytokines, and in particular GM-CSF, as a biologic adjuvant. This review will focus on the current state of the use of costimulatory molecules as adjuvants for immunotherapy, and in particular, as immunomodulators for cancer vaccines. C1 NCI, Canc Res Ctr, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC USA. Ther Biol Corp, Cambridge, MA USA. RP Hodge, JW (reprint author), NCI, Canc Res Ctr, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM jh241d@nih.gov RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016 OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912 NR 55 TC 29 Z9 31 U1 0 U2 4 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2006 VL 11 BP 788 EP 803 DI 10.2741/1837 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973MX UT WOS:000232528000063 PM 16146771 ER PT J AU Thornton, AM AF Thornton, AM TI Signal transduction in CD4(+)CD25(+) regulatory T cells: CD25 and IL-2 SO FRONTIERS IN BIOSCIENCE LA English DT Article DE immune system; T cells; tolerance; autoimmunity; T lymphocytes; cytokine; IL-2; review ID IMMUNOLOGICAL SELF-TOLERANCE; RECEPTOR-DEFICIENT MICE; CUTTING EDGE; LETHAL AUTOIMMUNITY; NEONATAL THYMECTOMY; ALPHA-CHAIN; INTERLEUKIN-2; HOMEOSTASIS; CD4(+); GENE AB IL-2 was originally identified as a growth factor critical for T cell proliferation in vitro. Although the early studies of IL-2 strongly implied an obligate role of IL-2 in T cell growth, it was later shown that mice deficient in IL-2 or in IL-2R developed an unexpected lymphocytic hyperproliferation and subsequent autoimmune disease. In separate studies of autoimmunity, it was observed that a population of CD4(+) T cells suppressed the induction of autoimmunity in several in vivo models of autoimmune disease. It was not until the characterization of this subpopulation of CD4(+) T cells demonstrated that they co-expressed the IL-2R-alpha chain (CD25) that the puzzling phenotype observed in IL-2 deficient mice began to be truly explained. The constitutive expression of the IL-2R-alpha chain on CD4(+) CD25(+) T cells led to the obvious speculation that IL-2 signaling in CD4(+) CD25(+) T cells was important to these cells. Recent studies have examined the role of IL-2 in the generation, the expansion, the survival and the effector function of CD4(+) CD25+ T cells. It is now evident that IL-2 is critical for the development of CD4(+) CD25(+) T cells and the phenotype observed in IL-2 and IL-2R deficient mice is most readily explained by the absence of these potent suppressors. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Thornton, AM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N315,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM athornton@niaid.nih.gov NR 42 TC 16 Z9 21 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2006 VL 11 BP 921 EP 927 DI 10.2741/1848 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973MX UT WOS:000232528000074 PM 16146782 ER PT J AU Wang, Y Alexander, OB Woodward-Pu, YM Stahl, CE Borlongan, CV AF Wang, Y Alexander, OB Woodward-Pu, YM Stahl, CE Borlongan, CV TI Viral vector strategy for glial cell line-derived neurotrophic factor therapy for stroke SO FRONTIERS IN BIOSCIENCE LA English DT Article DE nervous system; brain; viral vector; treatment; therapeutics; neurotrophic factor; stroke; review ID CEREBRAL-ARTERY OCCLUSION; DELAYED NEURONAL DEATH; MIDBRAIN DOPAMINERGIC-NEURONS; TRANSIENT GLOBAL-ISCHEMIA; MICE LACKING GDNF; GENE-TRANSFER; FACTOR PROTECTS; BRAIN-INJURY; INDUCED EXCITOTOXICITY; TYROSINE-HYDROXYLASE AB Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta superfamily. Over the last decade, GDNF has been shown to promote regenerative and restorative effects on dopaminergic neurons. Accumulating evidence also demonstrates that administration of GDNF to areas of ischemic brain injury limits cerebral infarction and reduces damage to motor functions in animal models of stroke. Neurotrophic factor and anti-apoptotic mechanisms, among others, have been proposed to underlie the therapeutic effects of GDNF. A major obstacle for GDNF therapy is the protein delivery to the brain, as well as its sustained bioavailability over time. Gene therapy and the use of viral vectors offer a technique for longevity of GDNF expression within the brain. In this review, we consider the risks and benefits of GDNF gene therapy as it relates to the treatment of stroke. C1 NIDA, NIH, DHHS, Baltimore, MD 21224 USA. Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. Dwight D Eisenhower Army Med Ctr, Dept Internal Med, Ft Gordon, GA 30905 USA. Augusta VAMC, Res & Affiliat Serv Line, Augusta, GA 30912 USA. RP Wang, Y (reprint author), NIDA, NIH, DHHS, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov OI Borlongan, Cesar/0000-0002-2966-9782 NR 43 TC 4 Z9 4 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2006 VL 11 BP 1101 EP 1107 DI 10.2741/1866 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973MX UT WOS:000232528000092 PM 16146800 ER PT J AU Alesci, S Rodak, M Ilias, I Zhou, RL Manji, HK AF Alesci, Salvatore Rodak, Michelle Ilias, Ioannis Zhou, Rulun Manji, Husseini K. TI The genomics of mood disorders SO FUNCTIONAL GENOMICS AND PROTEOMICS IN THE CLINICAL NEUROSCIENCES SE PROGRESS IN BRAIN RESEARCH LA English DT Review ID BIPOLAR DISORDER; GENE-EXPRESSION; FUNCTIONAL GENOMICS; MICROARRAY ANALYSIS; MAJOR DEPRESSION; SODIUM VALPROATE; BRAIN; SCHIZOPHRENIA; NEUROBIOLOGY; DYSFUNCTION C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Patras, Fac Med, Dept Pharmacol, Rion, Greece. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. EM manjih@mail.nih.gov NR 51 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 J9 PROG BRAIN RES PY 2006 VL 158 BP 129 EP 139 DI 10.1016/S0079-6123(06)58006-9 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BGH63 UT WOS:000247003700006 PM 17027694 ER PT J AU Melani, R Sallustio, F Fardin, P Vanni, C Ognibene, M Ottaviano, C Melillo, G Varesio, L Eva, A AF Melani, Raffaella Sallustio, Fabio Fardin, Paolo Vanni, Cristina Ognibene, Marzia Ottaviano, Catherine Melillo, Giovanni Varesio, Luigi Eva, Alessandra TI Growth arrest-inducing genes are activated in Dbl-transformed mouse fibroblasts SO GENE EXPRESSION LA English DT Article DE microarray; Dbl oncogene; gene expression ID CELL-CYCLE PROGRESSION; RHO-FAMILY GTPASES; PROTO-DBL; SELECTIVE ACTIVATION; CHOP GADD153; MAP KINASE; C-JUN; PROTEINS; CDC42HS; RAC AB The Dbl oncogene is a guanine nucleotide exchange factor for Rho GTPases and its activity has been linked to the regulation of gene transcription. Dbl oncogene expression in NIH3T3 cells leads to changes in morphological and proliferative properties of these cells, inducing a highly transformed phenotype. To gain insights into Dbl oncogene-induced transformation we compared gene expression profiles between Dbl oncogene-transformed and parental NIH3T3 cells by cDNA microarray. We found that Dbl oncogene expression is associated with gene expression modulation involving upregulation of 51 genes and downregulation of 49 genes. Five of the overexpressed genes identified are known to exert antiproliferative functions. Our observations suggest that the expression of Dbl oncogene in NIH3T3 may lead to the induction of genes associated with cell cycle arrest, possibly through the activation of stress-induced kinases. C1 Ist Giannina Gaslini, Mol Biol Lab, I-16147 Genoa, Italy. NCI, DTP, Tumor Hypoxia Program, FCRF, Ft Detrick, MD 21702 USA. RP Eva, A (reprint author), Ist Giannina Gaslini, Mol Biol Lab, Largo G Gaslini 5, I-16147 Genoa, Italy. EM alessandraeva@ospedale-gaslini.ge.it RI Sallustio, Fabio/H-1587-2016; Eva, Alessandra/J-8268-2016; varesio, luigi/J-8261-2016; Sallustio, Fabio/D-2326-2011 OI Eva, Alessandra/0000-0003-2949-078X; varesio, luigi/0000-0001-5659-2218; Sallustio, Fabio/0000-0002-5132-6532 NR 39 TC 1 Z9 1 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 2006 VL 13 IS 3 BP 155 EP 165 DI 10.3727/000000006783991845 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 117XV UT WOS:000242907500003 PM 17193922 ER PT J AU Yoshikawa, T Piao, YL Zhong, JH Matoba, R Carter, MG Wang, YX Goldberg, I Ko, MSH AF Yoshikawa, T Piao, YL Zhong, JH Matoba, R Carter, MG Wang, YX Goldberg, I Ko, MSH TI High-throughput screen for genes predominantly expressed in the ICM of mouse blastocysts by whole mount in situ hybridization SO GENE EXPRESSION PATTERNS LA English DT Article DE preimplantation embryo; whole mount in situ hybridization; high-throughput screen; hybridization chamber; ICM; TE ID STEM-CELLS; PREIMPLANTATION DEVELOPMENT; GENOME-WIDE; GLOBAL VIEW; B-MYB; EMBRYOS; PLURIPOTENCY; EMBRYOGENESIS; MICROARRAY; PATHWAYS AB Mammalian preimplantation embryos provide an excellent opportunity to study temporal and spatial gene expression in whole mount in situ hybridization (WISH). However, large-scale studies are made difficult by the size of the embryos (similar to 60 mu m diameter) and their fragility. We have developed a chamber system that allows parallel processing of embryos without the aid of a microscope. We first selected 91 candidate genes that were transcription factors highly expressed in blastocysts, and more highly expressed in embryonic (ES) than in trophoblast (TS) stem cells. We then used the WISH to identify 48 genes expressed predominantly in the inner cell mass (ICM) and to follow several of these genes in all seven preimplantation stages. The ICM-predominant expressions of these genes suggest their involvement in the pluripotency of embryonic cells. This system provides a useful tool to a systematic genome-scale analysis of preimplantation embryos. Published by Elsevier B.V. C1 NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Carter, Mark/B-5089-2010; Goldberg, Ilya/H-5307-2011; Ko, Minoru/B-7969-2009 OI Goldberg, Ilya/0000-0001-8514-6110; Ko, Minoru/0000-0002-3530-3015 FU NIA NIH HHS [Z01 AG000655-07] NR 45 TC 64 Z9 64 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD JAN PY 2006 VL 6 IS 2 BP 213 EP 224 DI 10.1016/j.modgep.2005.06.003 PG 12 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 004QG UT WOS:000234766700013 PM 16325481 ER PT J AU Wang, J Voutetakis, A Papa, M Rivera, VM Clackson, T Lodde, BM Mineshiba, F Baum, BJ AF Wang, J Voutetakis, A Papa, M Rivera, VM Clackson, T Lodde, BM Mineshiba, F Baum, BJ TI Rapamycin control of transgene expression from a single AAV vector in mouse salivary glands SO GENE THERAPY LA English DT Article DE AAV; rapamycin; dimerizer; salivary glands; gene therapeutics ID RECOMBINANT ADENOASSOCIATED VIRUS; MEDIATED GENE-TRANSFER; HUMAN AIRWAY EPITHELIA; REGULATED EXPRESSION; SEROTYPE-2 VECTORS; THERAPEUTICS; PROTEIN; TRANSDUCTION; DELIVERY; THERAPY AB Salivary glands (SGs) appear to be a useful target site for gene therapeutics. The ability to control transgene expression is essential for clinical application. Previously, in a proof-of-concept study, we have shown that the rapamycin-inducible transcriptional regulation system can regulate protein expression after adenoviral-mediated gene transfer to SGs. To evaluate the potential ability to utilize this regulatory system for long-term control of transgene expression in this tissue, we employed a 'third generation', single adenoassociated serotype 2 viral (AAV2) vector encoding human erythropoietin (hEPO) under the control of a rapamycin-inducible promoter. The vector, rAAV-TF2.3-EPO (10(10) particles/animal), was delivered to mouse SGs. No detectable increase in serum hEPO or hematocrit levels was observed in the absence of rapamycin administration. However, rapamycin induced elevation of serum hEPO levels, as well as concomitant hematocrit changes, that were dose-dependent, completely reversible, and relatively stable over the course of this study (6 months), with no appreciable change in rapamycin responsiveness. Our results suggest that the rapamycin transcriptional regulation system delivered in a single AAV2 vector to SGs may be valuable for systemic protein replacement applications. C1 NIDCR, GTTB, DHHS, NIH, Bethesda, MD 20892 USA. NIDCR, ACU, DHHS, NIH, Bethesda, MD 20892 USA. ARIAD Gene Therapeut, Cambridge, MA USA. RP Baum, BJ (reprint author), NIDCR, GTTB, DHHS, NIH, Bldg 10,Room 1N113,MSC-1190,10 Ctr Dr, Bethesda, MD 20892 USA. EM bbaum@dir.nider.nih.gov OI Papa, Michele/0000-0002-6609-7453 NR 24 TC 25 Z9 25 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 2006 VL 13 IS 2 BP 187 EP 190 DI 10.1038/sj.gt.3302647 PG 4 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 999VH UT WOS:000234418300009 PM 16177817 ER PT J AU Buchholz, DR Paul, BD Fu, LZ Shi, YB AF Buchholz, DR Paul, BD Fu, LZ Shi, YB TI Molecular and developmental analyses of thyroid hormone receptor function in Xenopus laevis, the African clawed frog SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Review DE thyroid hormone receptor; frog metamorphosis; Xenopus laevis; developmental endocrinology ID ADULT EPITHELIAL DEVELOPMENT; II IODOTHYRONINE DEIODINASE; RANA-CATESBEIANA TADPOLES; GENE-EXPRESSION PROGRAM; IN-VIVO ANALYSIS; BETA-A GENE; AMPHIBIAN METAMORPHOSIS; TRANSCRIPTIONAL REGULATION; HISTONE ACETYLATION; COREPRESSOR COMPLEX AB The current review focuses on the molecular mechanisms and developmental roles of thyroid hormone receptors (TRs) in gene regulation and metamorphosis in Xenopus laevis and discusses implications for TR function in vertebrate development and diversity. Questions addressed are: (1) what are the molecular mechanisms of gene regulation by TR, (2) what are the developmental roles of TR in mediating the thyroid hormone (TH) signal, (3) what are the roles of the different TR isoforms, and (4) how do changes in these molecular and developmental mechanisms affect evolution? Even though detailed knowledge of molecular mechanisms of TR-mediated gene regulation is available from in vitro studies, relatively little is known about how TR functions in development in Vivo. Studies on TR function during frog metamorphosis are leading the way toward bridging the gap between in vitro and in vivo studies. In particular, a dual function model for the role of TR in metamorphosis has been proposed and investigated. In this model, TRs repress genes allowing tadpole growth in the absence of TH during premetamorphosis and activate genes important for metamorphosis when TH is present. Despite the lack of metamorphosis in most other vertebrates, TR has important functions in development across vertebrates. The underlying molecular mechanisms of TR in gene regulation are conserved through evolution, so other mechanisms involving TH-target genes and TH tissue-sensitivity and dependence underlie differences in role of TR across vertebrates. Continued analysis of molecular and developmental roles of TR in X. laevis will provide the basis for understanding how TR functions in gene regulation in vivo across vertebrates and how TR is involved in the generation of evolutionary diversity. Published by Elsevier Inc. C1 NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Buchholz, DR (reprint author), NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. EM dbuchholz@nih.gov NR 201 TC 99 Z9 102 U1 2 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD JAN 1 PY 2006 VL 145 IS 1 BP 1 EP 19 DI 10.1016/j.ygcen.2005.07.009 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 999CH UT WOS:000234365800001 PM 16266705 ER PT J AU Barnes, KC Grant, AV Baltadzhieva, D Zhang, S Berg, T Shao, L Zambelli-Weiner, A Anderson, W Nelsen, A Pillai, S Yarnall, DP Dienger, K Ingersoll, RG Scott, AF Fallin, MD Mathias, RA Beaty, TH Garcia, JGN Wills-Karp, M AF Barnes, KC Grant, AV Baltadzhieva, D Zhang, S Berg, T Shao, L Zambelli-Weiner, A Anderson, W Nelsen, A Pillai, S Yarnall, DP Dienger, K Ingersoll, RG Scott, AF Fallin, MD Mathias, RA Beaty, TH Garcia, JGN Wills-Karp, M TI Variants in the gene encoding C3 are associated with asthma and related phenotypes among African Caribbean families SO GENES AND IMMUNITY LA English DT Article DE asthma; C3; total IgE; IL-13; INF-gamma; haplotype ID INDUCED AIRWAY HYPERRESPONSIVENESS; SUSCEPTIBILITY LOCUS; INNATE IMMUNITY; CUTTING EDGE; COMPLEMENT; ANTIGEN; LINKAGE; SYSTEM; ANAPHYLATOXIN; RECEPTORS AB Proinflammatory and immunoregulatory products from C3 play a major role in phagocytosis, respiratory burst, and airways inflammation. C3 is critical in adaptive immunity; studies in mice deficient in C3 demonstrate that features of asthma are significantly attenuated in the absence of C3. To test the hypothesis that the C3 gene on chromosome 19p13.3-p13.2 contains variants associated with asthma and related phenotypes, we genotyped 25 single nucleotide polymorphism ( SNP) markers distributed at intervals of similar to 1.9 kb within the C3 gene in 852 African Caribbean subjects from 125 nuclear and extended pedigrees. We used the multiallelic test in the family-based association test program to examine sliding windows comprised of 2-6 SNPs. A five-SNP window between markers rs10402876 and rs366510 provided strongest evidence for linkage in the presence of linkage disequilibrium for asthma, high log[ total IgE], and high log[IL-13]/[ log[IFN-gamma] in terms of global P-values ( P = 0.00027, 0.00013, and 0.003, respectively). A three-SNP haplotype GGC for the first three of these markers showed best overall significance for the three phenotypes ( P = 0.003, 0.007, 0.018, respectively) considering haplotype-specific tests. Taken together, these results implicate the C3 gene as a priority candidate controlling risk for asthma and allergic disease in this population of African descent. C1 Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Childrens Hosp, Med Ctr, Childrens Hosp, Res Fdn,Div Immunobiol, Cincinnati, OH USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. Natl Human Genome Res Inst, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD USA. RP Barnes, KC (reprint author), Johns Hopkins Asthma & Allergy Ctr, 3A-62A,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM kbarnes@jhmi.edu RI Garcia, Joe/E-8862-2010 FU NHLBI NIH HHS [HL67736, R01 HL067736, R01 HL067736-04, U01 HL66583]; NIAID NIH HHS [R01 AI045221] NR 33 TC 22 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JAN PY 2006 VL 7 IS 1 BP 27 EP 35 DI 10.1038/sj.gene.6364267 PG 9 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 006KP UT WOS:000234896700004 PM 16355111 ER PT J AU Lieto, LD Maasho, K West, D Borrego, F Coligan, JE AF Lieto, LD Maasho, K West, D Borrego, F Coligan, JE TI The human CD94 gene encodes multiple, expressible transcripts including a new partner of NKG2A/B SO GENES AND IMMUNITY LA English DT Article DE CD94/NKG2A; inhibitory receptor; signaling transmission; NK cells; alternative transcripts; NK complex ID CELL IMMUNE SYNAPSES; NK CELLS; HLA-E; INHIBITORY RECEPTORS; T-CELLS; RECOGNITION; CD94/NKG2A; SIGNAL; MOLECULES; FORM AB CD94/NKG2A is an inhibitory receptor expressed by natural killer (NK) cells and a subset of CD8+ T cells. Ligation of CD94/NKG2A by its ligand HLA-E results in tyrosine phosphorylation of the NKG2A immunoreceptor tyrosine-based inhibitory motifs, and recruitment and activation of the SH2 domain-bearing tyrosine phosphatase-1, which in turn suppresses activation signals. The nkg2a gene encodes two isoforms, NKG2A and NKG2B, with the latter lacking the stem region. We identified three new alternative transcripts of the cd94 gene in addition to the originally described canonical CD94(Full). One of the transcripts, termed CD94-T4, lacks the portion that encodes the stem region. CD94-T4 associates with both NKG2A and NKG2B, but preferentially associates with the latter. This is probably due to the absence of a stem region in both CD94-T4 and NKG2B. CD94-T4/ NKG2B is capable of binding HLA-E and, when expressed in E6-1 Jurkat T cells, inhibits TCR mediated signals, demonstrating that this heterodimer is functional. Coevolution of stemless isoforms of CD94 and NKG2A that preferentially pair with each other to produce a functional heterodimer indicates that this may be more than a serendipitous event. CD94-T4/ NKG2B may contribute to the plasticity of the NK immunological synapse by insuring an adequate inhibitory signal. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Twinbrook 2,RM 205,12441 Parklawn Dr, Rockville, MD 20852 USA. EM Jcoligan@niaid.nih.gov FU Intramural NIH HHS NR 36 TC 11 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JAN PY 2006 VL 7 IS 1 BP 36 EP 43 DI 10.1038/sj.gene.6364268 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 006KP UT WOS:000234896700005 PM 16237464 ER PT J AU Mendrysa, SM O'Leary, KA McElwee, MK Michalowski, J Eisenman, RN Powell, DA Perry, ME AF Mendrysa, SM O'Leary, KA McElwee, MK Michalowski, J Eisenman, RN Powell, DA Perry, ME TI Tumor suppression and normal aging in mice with constitutively high p53 activity SO GENES & DEVELOPMENT LA English DT Article DE aging; tumor suppression; p53; Mdm2; apoptosis; cancer therapy ID MULTIPLE INTESTINAL NEOPLASIA; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; MDM2; PATHWAY; ACTIVATION; PROTEIN; RESCUE; MOUSE AB The p53 inhibitor murine double-minute gene 2 (Mdm2) is a target for potential cancer therapies, however increased p53 function can be lethal. To directly address whether reduced Mdm2 function can inhibit tumorigenesis without causing detrimental side effects, we exploited a hypomorphic murine allele of mdm2 to compare the effects of decreased levels of Mdm2 and hence increased p53 activity on tumorigenesis and life span in mice. Here we report that mice with decreased levels of Mdm2 are resistant to tumor formation yet do not age prematurely, supporting the notion that Mdm2 is a promising target for cancer therapeutics. C1 Univ Wisconsin, Dept Oncol, Madison, WI 53706 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Perry, ME (reprint author), Univ Wisconsin, Dept Oncol, Madison, WI 53706 USA. EM perryma@mail.nih.gov FU Intramural NIH HHS NR 25 TC 153 Z9 155 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2006 VL 20 IS 1 BP 16 EP 21 DI 10.1101/gad.1378506 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 010AG UT WOS:000235154600002 PM 16391230 ER PT J AU Ellis, NA Kirchhoff, T Mitra, N Ye, TZ Chuai, SK Huang, H Nafa, K Norton, L Neuhausen, S Gordon, D Struewing, JP Narod, S Offit, K AF Ellis, NA Kirchhoff, T Mitra, N Ye, TZ Chuai, SK Huang, H Nafa, K Norton, L Neuhausen, S Gordon, D Struewing, JP Narod, S Offit, K TI Localization of breast cancer susceptibility loci by genome-wide SNP linkage disequilibrium mapping SO GENETIC EPIDEMIOLOGY LA English DT Article DE single-nucleotide polymorphism; linkage disequilibrium mapping; breast cancer ID NONPOLYPOSIS COLORECTAL-CANCER; ASHKENAZI JEWISH POPULATION; NON-FOUNDER BRCA1; OVARIAN-CANCER; HAPLOTYPE FREQUENCIES; CHROMOSOME 8P12-P22; GERMLINE MUTATIONS; PHENOTYPE ANALYSIS; FAMILY HISTORY; RISK AB We studied the feasibility of a novel approach to localize breast cancer susceptibility genes, using a low-density genome-wide panel of single-nucleotide polymorphisms and taking advantage of large regions of linkage disequilibrium (LD) flanking Jewish disease genes in high-risk cases. With Affymetrix GeneChip arrays, we genotyped 8,576 polymorphisms in three sets of Ashkenazi Jewish breast cancer cases: a '' validation '' set of 27 breast cancer cases, all of whom carried the BRCA2*6174delT founder mutation; a '' field '' set of 19 breast cancer cases from male breast cancer kindreds, which simulated conditions for finding new genes; and a '' test '' set of 57 probands from breast cancer kindreds (4 or more cases/ kindred), in which mutations in BRCA1 and BRCA2 had been excluded. To identify associations, we compared the frequency of genotypes and haplotypes in cases vs. controls by the Fisher's exact test and a maximum likelihood ratio test. In the '' validation '' set, we demonstrated the presence of a region of linkage disequilibrium on BRCA2*6174delT chromosomes that spanned over 5 million bases. In the '' field '' set, we showed that this large region of linkage disequilibrium flanking BRCA2 was detectable despite the presence of heterogeneity in the sample set. Finally, in the '' test '' set, at least three regions of interest emerged that could contain novel breast cancer genes, one of which had been identified previously by linkage analysis. While these results demonstrate the feasibility of genome-wide association strategies, further application of this approach will critically depend on optimizing the density and distribution of SNPs and the size and type of study design. C1 Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Rockefeller Univ, Lab Stat Genet, Div Epidemiol, New York, NY 10021 USA. NCI, Lab Populat Genet, Bethesda, MD USA. Univ Toronto, Dept Publ Hlth Sci, Toronto, ON, Canada. RP Offit, K (reprint author), Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM offitk@mskcc.org RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013; OI Struewing, Jeffery/0000-0002-4848-3334; Norton, Larry/0000-0003-3701-9250; Kirchhoff, Tomas/0000-0002-9055-2364 FU NCI NIH HHS [CA 103394, R03 CA103500, R03 CA103500-02]; NHGRI NIH HHS [K01-HG-00055]; NHLBI NIH HHS [R01-HL56778]; NIMH NIH HHS [MH44292] NR 38 TC 12 Z9 12 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2006 VL 30 IS 1 BP 48 EP 61 DI 10.1002/gepi.20101 PG 14 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 999NO UT WOS:000234396500006 PM 16206141 ER PT J AU Redon, C Pilch, DR Bonner, WM AF Redon, C Pilch, DR Bonner, WM TI Genetic analysis of Saccharomyces cerevisiae H2A serine 129 mutant suggests a functional relationship between H2A and the sister-chromatid cohesion partners Csm3-Tof1 for the repair of topoisomerase I-induced DNA damage SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; HISTONE H2AX; S-PHASE; CHECKPOINT PATHWAY; REPLICATION STRESS; MISMATCH REPAIR; YEAST; MRC1; RECOMBINATION; MECHANISM AB Collision between a topoisomerase I-DNA intermediate and an advancing replication fork represents a unique form of replicative damage. We have shown previously that yeast H2A serine 129 is involved in the recovery from this type of damage. We now report that efficient repair also requires proteins involved in chromatid cohesion: Csm3; Tof1; Mrc1, and Dcc1. Epistasis analysis defined several pathways involving these proteins. Csm3 and Tof1 function in a same pathway and downstream of H2A. In addition, the pathway involving H2A/Csm3/Tof1 is distinct from the pathways involving the Ctf8/Ctf18/Dcc1 complex, the Rad9 pathway, and another involving Mrc1. Our genetic studies suggest a role for H2A serine 129 in the establishment of specialized cohesion structure necessary for the normal repair of topoisomerase I-induced DNA damage. C1 NCI, NIH, DBS, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Bonner, WM (reprint author), NCI, NIH, DBS, Mol Pharmacol Lab, Bldg 37,Room 5050A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wmbonner@helix.nih.gov NR 46 TC 22 Z9 24 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2006 VL 172 IS 1 BP 67 EP 76 DI 10.1534/genetics.105.046128 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 010MB UT WOS:000235197700007 PM 16219777 ER PT J AU Valenzuela, L Gangadharan, S Kamakaka, RT AF Valenzuela, L Gangadharan, S Kamakaka, RT TI Analyses of SUM1-1-mediated long-range repression SO GENETICS LA English DT Article ID ORIGIN RECOGNITION COMPLEX; MEIOTIC GENE-EXPRESSION; MATING-TYPE LOCUS; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL REPRESSION; EPIGENETIC INHERITANCE; POLYMERASE-EPSILON; SILENCED CHROMATIN; YEAST; TELOMERES AB In Saccharomyces cerevisiae, local repression is promoter specific and localized to a small region on the DNA, while silencing is promoter nonspecific, encompasses large domains of chromatin, and is stably inherited for multiple generations. Sum1p is a local repressor protein that mediates repression of meiosis-specific genes in mitotic cells while the Sir proteins are long-range repressors that stably silence genes at HML, HMR, and telomeres. The SUM1-1 mutation is a dominant neomorphic mutation that enables the mutant protein to be recruited to the HMR locus and repress genes, even in the absence of the Sir proteins. In this study we show that the Mutation in Sum1-1p enabled it to spread, and the native HAIR barrier blocked it from spreading. Thus, like the Sir proteins, Sum1-1p was a long-range repressor, but unlike the Sir proteins, Sum1-1p-mediated repression was more promoter specific, repressing certain genes better than others. Furthermore, repression mediated by Sum1-1p was not stably maintained or inherited and we therefore propose that Sum1-1p-mediated long-range repression is related but distinct from silencing. C1 NICHD, NIH, Unit Chromatin & Transcript, Bethesda, MD 20892 USA. RP NICHD, NIH, Unit Chromatin & Transcript, Bldg 18T,Room 106, Bethesda, MD 20892 USA. EM rohinton@helix.nih.gov FU Intramural NIH HHS NR 49 TC 7 Z9 7 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD JAN PY 2006 VL 172 IS 1 BP 99 EP 112 DI 10.1534/genetics.105.050427 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 010MB UT WOS:000235197700010 PM 16272409 ER PT J AU FitzGerald, PC Sturgill, D Shyakhtenko, A Oliver, B Vinson, C AF FitzGerald, Peter C. Sturgill, David Shyakhtenko, Andrey Oliver, Brian Vinson, Charles TI Comparative genomics of Drosophila and human core promoters SO GENOME BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; GENE-EXPRESSION; DNA METHYLATION; TRANSCRIPTION; SEQUENCES; DATABASE; ELEMENT; IDENTIFICATION; EVOLUTION; GERMLINE AB Background: The core promoter region plays a critical role in the regulation of eukaryotic gene expression. We have determined the non-random distribution of DNA sequences relative to the transcriptional start site in Drosophila melanogaster promoters to identify sequences that may be biologically significant. We compare these results with those obtained for human promoters. Results: We determined the distribution of all 65,536 octamer (8-mers) DNA sequences in 10,914 Drosophila promoters and two sets of human promoters aligned relative to the transcriptional start site. In Drosophila, 298 8-mers have highly significant (p <= 1 x 10(-16)) non-random distributions peaking within 100 base-pairs of the transcriptional start site. These sequences were grouped into 15 DNA motifs. Ten motifs, termed directional motifs, occur only on the positive strand while the remaining five motifs, termed non-directional motifs, occur on both strands. The only directional motifs to localize in human promoters are TATA, INR, and DPE. The directional motifs were further subdivided into those precisely positioned relative to the transcriptional start site and those that are positioned more loosely relative to the transcriptional start site. Similar numbers of non-directional motifs were identified in both species and most are different. The genes associated with all 15 DNA motifs, when they occur in the peak, are enriched in specific Gene Ontology categories and show a distinct mRNA expression pattern, suggesting that there is a core promoter code in Drosophila. Conclusion: Drosophila and human promoters use different DNA sequences to regulate gene expression, supporting the idea that evolution occurs by the modulation of gene regulation. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Genome Anal Unit, NIH, Bethesda, MD 20892 USA. NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM vinsonc@dc37a.nci.nih.gov FU Intramural NIH HHS [Z01 DK015600-12] NR 42 TC 81 Z9 82 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 7 AR R53 DI 10.1186/gb-2006-7-7-r53 PG 22 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 095QM UT WOS:000241322700010 PM 16827941 ER PT J AU Guimaraes, KS Jothi, R Zotenko, E Przytycka, TM AF Guimaraes, Katia S. Jothi, Raja Zotenko, Elena Przytycka, Teresa M. TI Predicting domain-domain interactions using a parsimony approach SO GENOME BIOLOGY LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORKS; COMPLEXES; DATABASE; MAP AB We propose a novel approach to predict domain-domain interactions from a protein-protein interaction network. In our method we apply a parsimony-driven explanation of the network, where the domain interactions are inferred using linear programming optimization, and false positives in the protein network are handled by a probabilistic construction. This method outperforms previous approaches by a considerable margin. The results indicate that the parsimony principle provides a correct approach for detecting domain-domain contacts. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Fed Pernambuco, Ctr Informat, BR-50732 Recife, PE, Brazil. Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. RP Przytycka, TM (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM przytyck@mail.nih.gov RI Guimaraes, Katia/C-5577-2008; Jothi, Raja/G-3780-2015; OI Zotenko, Elena/0000-0002-0256-3195 FU Intramural NIH HHS NR 31 TC 53 Z9 55 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 11 AR R104 DI 10.1186/gb-2006-7-11-r104 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132UF UT WOS:000243967000008 PM 17094802 ER PT J AU Iyer, LM Burroughs, AM Aravind, L AF Iyer, Lakshminarayan M. Burroughs, A. Maxwell Aravind, L. TI The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like beta-grasp domains SO GENOME BIOLOGY LA English DT Article ID MOLYBDENUM COFACTOR BIOSYNTHESIS; MULTIPLE SEQUENCE ALIGNMENT; ESCHERICHIA-COLI; DEUBIQUITINATING ENZYMES; THIAMIN BIOSYNTHESIS; COMPARATIVE GENOMICS; CRYSTAL-STRUCTURE; MOLYBDOPTERIN SYNTHASE; SUBSTRATE-SPECIFICITY; PROTEIN-DEGRADATION AB Background: Ubiquitin (Ub)-mediated signaling is one of the hallmarks of all eukaryotes. Prokaryotic homologs of Ub (ThiS and MoaD) and E1 ligases have been studied in relation to sulfur incorporation reactions in thiamine and molybdenum/tungsten cofactor biosynthesis. However, there is no evidence for entire protein modification systems with Ub-like proteins and deconjugation by deubiquitinating enzymes in prokaryotes. Hence, the evolutionary assembly of the eukaryotic Ub-signaling apparatus remains unclear. Results: We systematically analyzed prokaryotic Ub-related beta-grasp fold proteins using sensitive sequence profile searches and structural analysis. Consequently, we identified novel Ub-related proteins beyond the characterized ThiS, MoaD, TGS, and YukD domains. To understand their functional associations, we sought and recovered several conserved gene neighborhoods and domain architectures. These included novel associations involving diverse sulfur metabolism proteins, siderophore biosynthesis and the gene encoding the transfer mRNA binding protein SmpB, as well as domain fusions between Ub-like domains and PIN-domain related RNAses. Most strikingly, we found conserved gene neighborhoods in phylogenetically diverse bacteria combining genes for JAB domains (the primary de-ubiquitinating isopeptidases of the proteasomal complex), along with E1-like adenylating enzymes and different Ub-related proteins. Further sequence analysis of other conserved genes in these neighborhoods revealed several Ub-conjugating enzyme/E2-ligase related proteins. Genes for an Ub-like protein and a JAB domain peptidase were also found in the tail assembly gene cluster of certain caudate bacteriophages. Conclusion: These observations imply that members of the Ub family had already formed strong functional associations with E1-like proteins, UBC/E2-related proteins, and JAB peptidases in the bacteria. Several of these Ub-like proteins and the associated protein families are likely to function together in signaling systems just as in eukaryotes. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM aravind@mail.nih.gov FU Intramural NIH HHS NR 93 TC 88 Z9 91 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 7 AR R60 DI 10.1186/gb-2006-7-7-r60 PG 23 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 095QM UT WOS:000241322700017 PM 16859499 ER PT J AU Li, J Riehle, MM Zhang, Y Xu, JN Oduol, F Gomez, SM Eiglmeier, K Beatrix, MU Shabanowitz, J Donald, FH Ribeiro, JMC Vernick, KD AF Li, J Riehle, MM Zhang, Y Xu, JN Oduol, F Gomez, SM Eiglmeier, K Beatrix, MU Shabanowitz, J Donald, FH Ribeiro, JMC Vernick, KD TI Anopheles gambiae genome reannotation through synthesis of ab initio and comparative gene prediction algorithms SO GENOME BIOLOGY LA English DT Article ID DROSOPHILA-MELANOGASTER; PROTEIN DATABASE; DNA-SEQUENCE; BLOOD MEAL; MOSQUITO; ACCURACY; PROGRAMS; BLAST; TOOL AB Background: Complete genome annotation is a necessary tool as Anopheles gambiae researchers probe the biology of this potent malaria vector. Results: We reannotate the A. gambiae genome by synthesizing comparative and ab initio sets of predicted coding sequences (CDSs) into a single set using an exon-gene-union algorithm followed by an open-reading-frame-selection algorithm. The reannotation predicts 20,970 CDSs supported by at least two lines of evidence, and it lowers the proportion of CDSs lacking start and/or stop codons to only approximately 4%. The reannotated CDS set includes a set of 4,681 novel CDSs not represented in the Ensembl annotation but with EST support, and another set of 4,031 Ensembl-supported genes that undergo major structural and, therefore, probably functional changes in the reannotated set. The quality and accuracy of the reannotation was assessed by comparison with end sequences from 20,249 full-length cDNA clones, and evaluation of mass spectrometry peptide hit rates from an A. gambiae shotgun proteomic dataset confirms that the reannotated CDSs offer a high quality protein database for proteomics. We provide a functional proteomics annotation, ReAnoXcel, obtained by analysis of the new CDSs through the AnoXcel pipeline, which allows functional comparisons of the CDS sets within the same bioinformatic platform. CDS data are available for download. Conclusion: Comprehensive A. gambiae genome reannotation is achieved through a combination of comparative and ab initio gene prediction algorithms. C1 Univ Minnesota, Ctr Microbial & Plant Genom, St Paul, MN 55108 USA. Univ Minnesota, Dept Microbiol, St Paul, MN 55108 USA. Inst Pasteur, Unite Biochim & Biol Mol Insectes, F-75724 Paris 15, France. Inst Pasteur, CNRS, FRE 2849, F-75724 Paris 15, France. Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Vernick, KD (reprint author), Univ Minnesota, Ctr Microbial & Plant Genom, St Paul, MN 55108 USA. EM kvernick@umn.edu OI Gomez, Shawn/0000-0002-8251-4552; Ribeiro, Jose/0000-0002-9107-0818; Ueberheide, Beatrix/0000-0003-2512-0204 FU NIAID NIH HHS [R21 AI053777, AI42361, R01 AI042361, AI53777]; NIGMS NIH HHS [R01 GM037537, GM37537] NR 38 TC 15 Z9 17 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 3 AR R24 DI 10.1186/gb-2006-7-3-r24 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 039IH UT WOS:000237298700014 PM 16569258 ER PT J AU Marino-Ramirez, L Jordan, IK Landsman, D AF Marino-Ramirez, Leonardo Jordan, I. King Landsman, David TI Multiple independent evolutionary solutions to core histone gene regulation SO GENOME BIOLOGY LA English DT Article ID CELL-CYCLE EXPRESSION; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL REGULATION; ANGSTROM RESOLUTION; CHROMATIN-STRUCTURE; SEQUENCE ELEMENTS; DUPLICATE GENES; FISSION YEAST; SPT21 GENES; DNA-BINDING AB Background: Core histone genes are periodically expressed along the cell cycle and peak during S phase. Core histone gene expression is deeply evolutionarily conserved from the yeast Saccharomyces cerevisiae to human. Results: We evaluated the evolutionary dynamics of the specific regulatory mechanisms that give rise to the conserved histone regulatory phenotype. In contrast to the conservation of core histone gene expression patterns, the core histone regulatory machinery is highly divergent between species. There has been substantial evolutionary turnover of cis-regulatory sequence motifs along with the transcription factors that bind them. The regulatory mechanisms employed by members of the four core histone families are more similar within species than within gene families. The presence of species-specific histone regulatory mechanisms is opposite to what is seen at the protein sequence level. Core histone proteins are more similar within families, irrespective of their species of origin, than between families, which is consistent with the shared common ancestry of the members of individual histone families. Structure and sequence comparisons between histone families reveal that H2A and H2B form one related group whereas H3 and H4 form a distinct group, which is consistent with the nucleosome assembly dynamics. Conclusion: The dissonance between the evolutionary conservation of the core histone gene regulatory phenotypes and the divergence of their regulatory mechanisms indicates a highly dynamic mode of regulatory evolution. This distinct mode of regulatory evolution is probably facilitated by a solution space for promoter sequences, in terms of functionally viable cis-regulatory sites, that is substantially greater than that of protein sequences. C1 Natl Inst Hlth, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. RP Landsman, D (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Computat Biol Branch, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM landsman@ncbi.nlm.nih.gov RI Landsman, David/C-5923-2009; Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU Intramural NIH HHS [Z99 LM999999] NR 65 TC 24 Z9 26 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 12 AR R122 DI 10.1186/gb-2006-7-12-r122 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132UG UT WOS:000243967100016 PM 17184543 ER PT J AU Ryan, JF Burton, PM Mazza, ME Kwong, GK Mullikin, JC Finnerty, JR AF Ryan, Joseph F. Burton, Patrick M. Mazza, Maureen E. Kwong, Grace K. Mullikin, James C. Finnerty, John R. TI The cnidarian-bilaterian ancestor possessed at least 56 homeoboxes: evidence from the starlet sea anemone, Nematostella vectensis SO GENOME BIOLOGY LA English DT Article ID SUBUNIT RIBOSOMAL-RNA; GENE-EXPRESSION; PARAHOX GENES; HOX GENES; DNA-BINDING; PHYLOGENETIC ANALYSIS; HOMEODOMAIN PROTEINS; HOM/HOX GENES; EST ANALYSIS; HUMAN GENOME AB Background: Homeodomain transcription factors are key components in the developmental toolkits of animals. While this gene superclass predates the evolutionary split between animals, plants, and fungi, many homeobox genes appear unique to animals. The origin of particular homeobox genes may, therefore, be associated with the evolution of particular animal traits. Here we report the first near-complete set of homeodomains from a basal (diploblastic) animal. Results: Phylogenetic analyses were performed on 130 homeodomains from the sequenced genome of the sea anemone Nematostella vectensis along with 228 homeodomains from human and 97 homeodomains from Drosophila. The Nematostella homeodomains appear to be distributed among established homeodomain classes in the following fashion: 72 ANTP class; one HNF class; four LIM class; five POU class; 33 PRD class; five SINE class; and six TALE class. For four of the Nematostella homeodomains, there is disagreement between neighbor-joining and Bayesian trees regarding their class membership. A putative Nematostella CUT class gene is also identified. Conclusion: The homeodomain superclass underwent extensive radiations prior to the evolutionary split between Cnidaria and Bilateria. Fifty-six homeodomain families found in human and/or fruit fly are also found in Nematostella, though seventeen families shared by human and fly appear absent in Nematostella. Homeodomain loss is also apparent in the bilaterian taxa: eight homeodomain families shared by Drosophila and Nematostella appear absent from human (CG13424, EMXLX, HOMEOBRAIN, MSXLX, NK7, REPO, ROUGH, and UNC4), and six homeodomain families shared by human and Nematostella appear absent from fruit fly (ALX, DMBX, DUX, HNF, POUI, and VAX). C1 Boston Univ, Bioinformat Program, Boston, MA 02215 USA. NHGRI, Bethesda, MD 20892 USA. Boston Univ, Dept Biol, Boston, MA 02215 USA. RP Ryan, JF (reprint author), Boston Univ, Bioinformat Program, Cummington St, Boston, MA 02215 USA. EM jrf3@bu.edu RI Finnerty, John/B-6564-2011 FU Intramural NIH HHS NR 100 TC 100 Z9 100 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 7 AR R64 DI 10.1186/gb-2006-7-7-r64 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 095QM UT WOS:000241322700021 PM 16867185 ER PT J AU Thierry-Mieg, D Thierry-Mieg, J AF Thierry-Mieg, Danielle Thierry-Mieg, Jean TI AceView: a comprehensive cDNA-supported gene and transcripts annotation SO GENOME BIOLOGY LA English DT Article ID MESSENGER-RNA-DECAY; NON-AUG CODONS; CAENORHABDITIS-ELEGANS; TRANSLATION; INITIATION; GENOME; MECHANISM; SEQUENCE; PROJECT; EGASP AB Background: Regions covering one percent of the genome, selected by ENCODE for extensive analysis, were annotated by the HAVANA/Gencode group with high quality transcripts, thus defining a benchmark. The ENCODE Genome Annotation Assessment Project (EGASP) competition aimed at reproducing Gencode and finding new genes. The organizers evaluated the protein predictions in depth. We present a complementary analysis of the mRNAs, including alternative transcript variants. Results: We evaluate 25 gene tracks from the University of California Santa Cruz (UCSC) genome browser. We either distinguish or collapse the alternative splice variants, and compare the genomic coordinates of exons, introns and nucleotides. Whole mRNA models, seen as chains of introns, are sorted to find the best matching pairs, and compared so that each mRNA is used only once. At the mRNA level, AceView is by far the closest to Gencode: the vast majority of transcripts of the two methods, including alternative variants, are identical. At the protein level, however, due to a lack of experimental data, our predictions differ: Gencode annotates proteins in only 41% of the mRNAs whereas AceView does so in virtually all. We describe the driving principles of AceView, and how, by performing hand-supervised automatic annotation, we solve the combinatorial splicing problem and summarize all of GenBank, dbEST and RefSeq into a genome-wide non-redundant but comprehensive cDNA- supported transcriptome. AceView accuracy is now validated by Gencode. Conclusions: Relative to a consensus mRNA catalog constructed from all evidence-based annotations, Gencode and AceView have 81% and 84% sensitivity, and 74% and 73% specificity, respectively. This close agreement validates a richer view of the human transcriptome, with three to five times more transcripts than in UCSC Known Genes (sensitivity 28%), RefSeq (sensitivity 21%) or Ensembl (sensitivity 19%). C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Thierry-Mieg, D (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM mieg@ncbi.nlm.nih.gov RI THIERRY-MIEG, Jean/F-1975-2017 OI THIERRY-MIEG, Jean/0000-0002-0396-6789 NR 24 TC 247 Z9 252 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 SU 1 AR S12 DI 10.1186/gb-2006-7-s1-s12 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 189LU UT WOS:000247991200012 ER PT J AU Crawford, GE Holt, IE Whittle, J Webb, BD Tai, D Davis, S Margulies, EH Chen, YD Bernat, JA Ginsburg, D Zhou, DX Luo, SJ Vasicek, TJ Daly, MJ Wolfsberg, TG Collins, FS AF Crawford, GE Holt, IE Whittle, J Webb, BD Tai, D Davis, S Margulies, EH Chen, YD Bernat, JA Ginsburg, D Zhou, DX Luo, SJ Vasicek, TJ Daly, MJ Wolfsberg, TG Collins, FS TI Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS) SO GENOME RESEARCH LA English DT Article ID IDENTIFICATION; CHROMATIN; PROMOTERS; ELEMENTS; GENES AB A major goal in genomics is to Understand how genes are regulated in different tissues, stages of development, diseases, and species. Mapping DNase I hypersensitive (HS) sites within nuclear chromatin is a powerful and well-established method of identifying many different types of regulatory elements, but ill the past it has been limited to analysis of single loci. We have recently described a protocol to generate a genome-wide library of DNase HS sites. Here, we report high-throughput analysis, Using massively parallel signature sequencing (MPSS), of 230,000 tags from a DNase library generated from quiescent human CD4(+) T cells. Of the tags that uniquely map to the genome, we identified 14,190 clusters of sequences that group Within close proximity to each other. By using a real-time PCR strategy, we determined that the majority of these clusters represent valid DNase HS sites. Approximately 80% of these DNase HS Sites uniquely map within one or more annotated regions of the genome believed to contain regulatory elements, including regions 2 kb upstream of genes, CpG islands, and highly conserved sequences. Most DNase HS sites identified in CD4(+) T cells are also HS in CD8(+) T cells, B cells, hepatocytes, human umbilical vein endothelial cells (HUVECs), and HeLa cells. However, similar to 10% of the DNase HS sites are lymphocyte specific, indicating that this procedure call identify gene regulatory elements that control cell type specificity. This strategy, which call be applied to any cell line or tissue, will enable a better Understanding of how chromatin structure dictates cell function and fate. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Solexa Inc, Hayward, CA 94545 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM francisc@exchange.nih.gov OI Davis, Sean/0000-0002-8991-6458 FU Intramural NIH HHS; NHLBI NIH HHS [HL39639] NR 19 TC 237 Z9 245 U1 2 U2 11 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 2006 VL 16 IS 1 BP 123 EP 131 DI 10.1101/gr.4074106 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 016CJ UT WOS:000235598000014 PM 16344561 ER PT S AU Chen, DT Morse, BS Lowekamp, BC Yoo, TS AF Chen, David T. Morse, Bryan S. Lowekamp, Bradley C. Yoo, Terry S. BE Kim, MS Shimada, K TI Hierarchically partitioned implicit surfaces for interpolating large point set models SO GEOMETRIC MODELING AND PROCESSING - GMP 2006, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 4th International Conference on Geometric Modeling and Processing (GMP 2006) CY JUL 26-28, 2006 CL Pittsburgh, PA SP Carnegie Mellon Univ ID SCATTERED DATA AB We present a novel hierarchical spatial partitioning method for creating interpolating implicit surfaces using compactly supported radial basis functions (RBFs) from scattered surface data. From this hierarchy of functions we can create a range of models from coarse to fine, where a coarse model approximates and a fine model interpolates. Furthermore, our method elegantly handles irregularly sampled data and hole filling because of its multiresolutional approach. Like related methods, we combine neighboring patches without surface discontinuities by overlapping their embedding functions. However, unlike partition-of-unity approaches we do not require an additional explicit blending function to combine patches. Rather, we take advantage of the compact extent of the basis functions to directly solve for each patch's embedding function in a way that does not cause error in neighboring patches. Avoiding overlap error is accomplished by adding phantom constraints to each patch at locations where a neighboring patch has regular constraints within the area of overlap (the function's radius of support). Phantom constraints are also used to ensure the correct results between different levels of the hierarchy. This approach leads to efficient evaluation because we can combine the relevant embedding functions at each point through simple summation. We demonstrate our method on the Thai statue from the Stanford 3D Scanning Repository. Using hierarchical compactly supported RBFs we interpolate all 5 million vertices of the model. C1 Natl Lib Med, Bethesda, MD USA. Brigham Young Univ, Provo, UT 84602 USA. RP Chen, DT (reprint author), Natl Lib Med, Bethesda, MD USA. NR 18 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-36711-X J9 LECT NOTES COMPUT SC PY 2006 VL 4077 BP 553 EP 562 PG 10 WC Computer Science, Theory & Methods; Mathematics, Applied SC Computer Science; Mathematics GA BEU94 UT WOS:000239567900040 ER PT J AU Cesari, M Onder, G Russo, A Zamboni, V Barillaro, C Ferrucci, L Pahor, M Bernabei, R Landi, F AF Cesari, M Onder, G Russo, A Zamboni, V Barillaro, C Ferrucci, L Pahor, M Bernabei, R Landi, F TI Comorbidity and physical function: Results from the aging and longevity study in the Sirente geographic area (ilSIRENTE study) SO GERONTOLOGY LA English DT Article DE geriatrics; disability; comorbidity; comorbidity and physical function; ilSIRENTE study; physical performance; muscle strength measures; functional status measures ID LOWER-EXTREMITY FUNCTION; MINIMUM DATA SET; OLDER PERSONS; SUBSEQUENT DISABILITY; PERFORMANCE BATTERY; ELDERLY-PEOPLE; WOMENS HEALTH; RISK-FACTORS; COMMUNITY; MORTALITY AB Background: Physical function measures have gained increased importance in the evaluation of older persons. The presence of comorbidity is a major and growing issue in geriatrics. Objective: To evaluate the relationship between comorbidity and physical function in community-dwelling older persons. Methods: Data are from baseline evaluation of the ilSIRENTE study ( n = 364). Physical performance was assessed using the Short Physical Performance Battery ( SPPB) and the 4-meter walking test. Muscle strength was measured by handgrip strength. Functional performance was assessed using Basic and Instrumental Activities of Daily Living ( ADLs and IADLs, respectively). Comorbidity was defined as >= 3 clinical conditions. Analyses of covariance and linear regressions were performed to evaluate the relationship between comorbidity and physical function. Results: The mean age of participants was 85.9 ( SD = 4.9) years. About one third ( 37.4%) of participants reported 6 3 clinical conditions. Participants with comorbidity had significantly worse results in all the physical function tests. Participants with comorbidity had significantly lower adjusted results for the 4-meter walking test ( 0.444 m/s) and the SPPB score ( 6.131) compared to those without comorbidity ( 0.531 m/s and 7.221; all p = 0.001, respectively). Participants with comorbidity were more IADL-impaired ( 3.152) than participants without comorbidity ( 2.767; p = 0.04). No significant association of ADLs and hand-grip strength with comorbidity was reported. Similar strengths of association for the 4-meter walking test ( per SD increase, beta = - 0.280; p = 0.001) and the SPPB ( per SD increase, beta = - 0.285; p = 0.001) with comorbidity were reported. Conclusions: Physical function measures, especially walking speed and SPPB, are associated with comorbidity. Physical performance measures may improve the clinical evaluation of older persons. Copyright (c) 2006 S. Karger AG, Basel. C1 Univ Florida, Coll Med, Inst Aging, Dept Aging & Geriatr Res, Gainesville, FL 32608 USA. Natl Inst Hlth, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD USA. Univ Sacred Heart, Dept Gerontol Geriatr & Physiatry, I-00168 Rome, Italy. RP Cesari, M (reprint author), Univ Florida, Coll Med, Inst Aging, Dept Aging & Geriatr Res, 1329 SW 16th St,Rm 5372, Gainesville, FL 32608 USA. EM mcesari@aging.ufl.edu RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 38 TC 71 Z9 76 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PY 2006 VL 52 IS 1 BP 24 EP 32 DI 10.1159/000089822 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 007SU UT WOS:000234990800003 PM 16439821 ER PT J AU David, VA Sun, S Zhang, ZH Shen, FJ Zhang, GQ Zhang, HM Xie, Z Zhang, YP Ryder, OA Ellis, S Wildt, DE Zhang, AJ O'Brien, SJ AF David, Victor A. Sun, Shan Zhang, Zhihe Shen, Fujun Zhang, Guiquan Zhang, Hemin Xie, Zhong Zhang, Ya-Ping Ryder, Oliver A. Ellis, Susie Wildt, David E. Zhang, Anju O'Brien, Stephen J. BE Wildt, DE Zhang, A Zhang, H Janssen, DL Ellis, S TI Parentage assessment among captive giant pandas in China SO GIANT PANDAS: BIOLOGY, VETERINARY MEDICINE AND MANAGEMENT LA English DT Article; Book Chapter ID AILUROPODA-MELANOLEUCA; CONSERVATION GENETICS; PATERNITY; MICROSATELLITES; POPULATIONS; RELATEDNESS; MARKERS; CUBS C1 [David, Victor A.; Sun, Shan] NCI, Lab Genom Divers, NIH, Frederick, MD 21702 USA. [Shen, Fujun] Chengdu Res Base Giant Panda Breeding, Key Lab Reprod & Conservat Genet, Chengdu 610081, Sichuan Provinc, Peoples R China. [Zhang, Guiquan] China Res & Conservat Ctr Giant Panda, Wenchuan 623006, Sichuan Provinc, Peoples R China. [Zhang, Hemin] China Conservat & Res Ctr Giant Panda, Wenchuan 623006, Sichuan Provinc, Peoples R China. [Xie, Zhong] Chinese Assoc Zool Gardens, Beijing 100037, Peoples R China. [Zhang, Ya-Ping] Chinese Acad Sci, Key Lab Cellular & Mol Evolut, Kunming Inst Zool, Kunming 650223, Peoples R China. [Ryder, Oliver A.] Zool Soc San Diego, Escondido, CA 92027 USA. [Ellis, Susie] Conservat Int, Washington, DC 20036 USA. [Wildt, David E.] Smithsonian Inst, Natl Zool Pk, Conservat & Res Ctr, Front Royal, VA 22630 USA. [Zhang, Anju] Chengdu Giant Panda Breeding Res Fdn, Chengdu Res Base Giant Panda Breeding, Chengdu 610081, Sichuan Provinc, Peoples R China. [O'Brien, Stephen J.] NCI, Lab Genom Divers, NIH, Frederick, MD 21702 USA. RP David, VA (reprint author), NCI, Lab Genom Divers, NIH, Frederick, MD 21702 USA. NR 34 TC 6 Z9 7 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-83295-3 PY 2006 BP 245 EP 273 DI 10.1017/CBO9780511542244.011 D2 10.2277/ 0521832950 PG 29 WC Biodiversity Conservation; Veterinary Sciences; Zoology SC Biodiversity & Conservation; Veterinary Sciences; Zoology GA BXS85 UT WOS:000296964600011 ER PT J AU Ballou, JD Miller, PS Xie, Z Wei, RP Zhang, HM Zhang, AJ Huang, SQ Sun, S David, VA O'Brien, SJ Traylor-Holzer, K Seal, US Wildt, DE AF Ballou, Jonathan D. Miller, Philip S. Xie, Zhong Wei, Rongping Zhang, Hemin Zhang, Anju Huang, Shiqiang Sun, Shan David, Victor A. O'Brien, Stephen J. Traylor-Holzer, Kathy Seal, Ulysses S. Wildt, David E. BE Wildt, DE Zhang, A Zhang, H Janssen, DL Ellis, S TI Analysis of demographic and genetic trends for developing a captive breeding masterplan for the giant panda SO GIANT PANDAS: BIOLOGY, VETERINARY MEDICINE AND MANAGEMENT LA English DT Article; Book Chapter ID MAMMALIAN POPULATIONS; MANAGEMENT C1 [Ballou, Jonathan D.] Smithsonian Inst, Natl Zool Pk, Washington, DC 20008 USA. [Sun, Shan; David, Victor A.; O'Brien, Stephen J.] NCI, Lab Genom Divers, NIH, Frederick, MD 21702 USA. [Huang, Shiqiang] Beijing Zoo, Beijing 100044, Peoples R China. [Miller, Philip S.; Traylor-Holzer, Kathy; Seal, Ulysses S.] IUCN World Conservat Unions Species Survival Comm, Conservat Breeding Specialist Grp, Apple Valley, MN 55124 USA. [Wei, Rongping; Zhang, Hemin] China Conservat & Res Ctr Giant Panda, Wenchuan 623006, Sichuan Provinc, Peoples R China. [Wildt, David E.] Smithsonian Inst, Natl Zool Pk, Conservat & Res Ctr, Front Royal, VA 22630 USA. [Xie, Zhong] Chinese Assoc Zool Gardens, Beijing 100037, Peoples R China. [Zhang, Anju] Chengdu Giant Panda Breeding Res Fdn, Chengdu Res Base Giant Panda Breeding, Chengdu 610081, Sichuan Provinc, Peoples R China. RP Ballou, JD (reprint author), Smithsonian Inst, Natl Zool Pk, 3001 Connecticut Ave NW, Washington, DC 20008 USA. NR 28 TC 6 Z9 6 U1 1 U2 9 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-83295-3 PY 2006 BP 495 EP 519 DI 10.1017/CBO9780511542244.022 D2 10.2277/ 0521832950 PG 25 WC Biodiversity Conservation; Veterinary Sciences; Zoology SC Biodiversity & Conservation; Veterinary Sciences; Zoology GA BXS85 UT WOS:000296964600022 ER PT J AU Lawrence, DMP Seth, P Durham, L Diaz, F Boursiquot, D Ransohoff, RM Major, EO AF Lawrence, DMP Seth, P Durham, L Diaz, F Boursiquot, D Ransohoff, RM Major, EO TI Astrocyte differentiation selectively upregulates CCL2/monocyte chemoattractant protein-1 in cultured human brain-derived progenitor cells SO GLIA LA English DT Article DE MCP-1/CCL2; brain progenitor cells; differentiation; astrocyte ID NF-KAPPA-B; CORNEAL EPITHELIAL-CELLS; CENTRAL-NERVOUS-SYSTEM; ADULT-RAT BRAIN; GENE-EXPRESSION; CHEMOKINE RECEPTORS; CEREBROSPINAL-FLUID; GLIAL-CELLS; PROINFLAMMATORY CYTOKINES; TRANSCRIPTION FACTOR AB Chemokines (chemoattractant cytokines) and their receptors are present in the brain and may play roles in both neurodevelopment and neuropathology. Increased brain levels of monocyte chemoattractant protein-1 (MCP-1), also known as CCL2, are found in patients with human immunodeficiency virus type 1 (HIV-1)-associated dementia and other acute and chronic neurologic diseases. Although the function of CCL2 in the brain is unclear, it is believed that upregulation of this chemokine during neuropathologic or neuroinflammatory conditions leads to recruitment of activated monocytes into the brain, where they differentiate into macrophages producing neurotoxic and inflammatory molecules. We recently showed that human fetal brain-derived progenitor cells are susceptible to HIV-1 and JC virus infection, and that differentiation toward an astrocyte phenotype increased virus production from these cells. In the current study, we found that in the absence of infection, progenitors produced moderate levels of CCL2 (5.6 ng per million cells). Astrocyte differentiation over 3 weeks increased CCL2 protein levels 30-fold in a biphasic manner, whereas neuronal differentiation decreased production 20-fold. Electromobility shift assays (EMSAs) demonstrated increased nuclear NF-kappa B levels within 2 h of initiating astrocyte differentiation, and inhibitors of NF-kappa B activation partially blocked the CCL2 increase in differentiating astrocytes. Ti-ansfection of progenitors with mutated CCL2 promoter/CAT reporter constructs showed that the distal promoter region, containing NF-kappa B and NF-I binding sites, is important for differentiation-induced CCL2 upregulation. Together these results suggest that the transcription factor NF-kappa B, and possibly NF-I, contribute to the upregulation of CCL2 chemokine production during the differentiation of human progenitor cells toward an astrocyte phenotype. (c) 2005 Wiley-Liss, Inc. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 10,Room 3B14,10 Ctr Dr,MSC 1296, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov FU NINDS NIH HHS [R01 NS32151] NR 58 TC 33 Z9 33 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD JAN 1 PY 2006 VL 53 IS 1 BP 81 EP 91 DI 10.1002/glia.20261 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 984SL UT WOS:000233324500009 PM 16206198 ER PT S AU Sobhany, M Negishi, M AF Sobhany, Mack Negishi, Masahiko BE Fukuda, M TI Characterization of specific donor binding to a alpha 1,4-N-acetylhexosaminyltransferase EXTL2 using isothermal titration calorimetry SO GLYCOMICS SE Methods in Enzymology LA English DT Article; Book Chapter AB Glycosyltransferases encompass one of the largest families of enzymes found in nature. Their principle function is to catalyze the transfer of activated donor-sugar molecules to various acceptor substrates. The molecular basis that governs this specific transfer reaction, such as how a given transferase determines donor-sugar specificity, remains to be elucidated. Human alpha 1,4-N-acetylhexosaminyltransferase (EXTL2) transfers N-acetylglucosamine and N-acetylgalactosamine but does not transfer glucose or galactose. Isothermal titration calorimetry (ITC) is a powerful technique used to characterize various binding reactions, including both protein-ligand and protein-protein interactions. ITC provides the binding stoichiometry, affinity, and the thermodynamic parameters free energy (Delta G), enthalpy (Delta H), and entropy (Delta S) of these binding interactions. This chapter describes our ITC study demonstrating the two-step mechanism that regulates the specific binding of N-acetylhexosamines to EXTI-2. RP Sobhany, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z99 ES999999] NR 11 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182821-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 416 BP 3 EP 12 DI 10.1016/S0076-6879(06)16001-2 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFH60 UT WOS:000241889900001 PM 17113856 ER PT S AU Valdivia, RH Cormack, BP Falkow, S AF Valdivia, Raphael H. Cormack, Brendan P. Falkow, Stanley BE Chalfie, M Kain, SR TI THE USES OF GREEN FLUORESCENT PROTEIN IN PROKARYOTES SO GREEN FLUORESCENT PROTEIN: PROPERTIES, APPLICATIONS, AND PROTOCOLS, 2ND EDITION SE Methods of Biochemical Analysis LA English DT Article; Book Chapter ID BACTERIAL VIRULENCE GENES; BACILLUS-SUBTILIS; SUBCELLULAR-LOCALIZATION; SALMONELLA-TYPHIMURIUM; AEQUOREA-VICTORIA; CELL-DIVISION; EXPRESSION; SPORULATION; MARKER; GFP C1 [Valdivia, Raphael H.; Cormack, Brendan P.; Falkow, Stanley] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. [Falkow, Stanley] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Valdivia, RH (reprint author), Duke Univ, Dept Genet & Microbiol, Durham, NC 27708 USA. NR 52 TC 6 Z9 6 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0076-6941 BN 978-0-471-73949-4 J9 METHOD BIOCHEM ANAL PY 2006 VL 47 BP 163 EP 178 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYB77 UT WOS:000297845600010 PM 16335713 ER PT S AU Ward, TH Lippincott-Schwartz, J AF Ward, Theresa H. Lippincott-Schwartz, Jennifer BE Chalfie, M Kain, SR TI THE USES OF GREEN FLUORESCENT PROTEIN IN MAMMALIAN CELLS SO GREEN FLUORESCENT PROTEIN: PROPERTIES, APPLICATIONS, AND PROTOCOLS, 2ND EDITION SE Methods of Biochemical Analysis LA English DT Article; Book Chapter ID TO-GOLGI TRANSPORT; RESONANCE ENERGY-TRANSFER; LIFETIME IMAGING MICROSCOPY; SINGLE LIVING CELLS; EVANESCENT-WAVE MICROSCOPY; NUCLEAR-ENVELOPE BREAKDOWN; CROSS-CORRELATION ANALYSIS; DYNAMICS IN-VIVO; LIVE CELLS; ENDOPLASMIC-RETICULUM C1 [Ward, Theresa H.] London Sch Hyg & Trop Med, Dept Infect & Trop Dis, Immunol Unit, London WC1E 7HT, England. [Lippincott-Schwartz, Jennifer] NICHD, Dept Cell Biol & Metab, NIH, Bethesda, MD 20892 USA. RP Ward, TH (reprint author), London Sch Hyg & Trop Med, Dept Infect & Trop Dis, Immunol Unit, London WC1E 7HT, England. RI Ward, Theresa/E-9650-2013 OI Ward, Theresa/0000-0002-9881-8649 FU Medical Research Council [G0400373] NR 226 TC 19 Z9 25 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0076-6941 BN 978-0-471-73949-4 J9 METHOD BIOCHEM ANAL PY 2006 VL 47 BP 305 EP 337 PG 33 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYB77 UT WOS:000297845600016 PM 16335719 ER PT B AU Strober, W Mannon, PJ Fuss, IJ AF Strober, W Mannon, PJ Fuss, IJ BE Blumberg, RS Gangl, A Manns, MP Tilg, H Zeitz, M TI Abnormalities of cytokine regulation in the inflammatory bowel diseases SO Gut-Liver Interactions: Basic and Clinical Concepts SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 146 on Gut-Liver Interactions - Basic and Clinical Concepts CY MAR 11-12, 2005 CL Innsbruck, AUSTRIA ID NK-T-CELLS; CROHNS-DISEASE; EXPERIMENTAL COLITIS; ULCERATIVE-COLITIS; OXAZOLONE COLITIS; NOD2; ANTIBODIES; FLAGELLIN; MICE; ACTIVATION C1 NIAID, NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, NIH, Mucosal Immun Sect, CRC Bldg,Room 5W-3940, Bethesda, MD 20892 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-4143-8 J9 FALK SYMP PY 2006 VL 146 BP 15 EP 24 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BDS32 UT WOS:000235163500002 ER PT J AU Trimble, EL Christian, MC AF Trimble, EL Christian, MC TI Intraperitoneal chemotherapy for women with advanced epithelial ovarian carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID PHASE-III; CISPLATIN; CANCER C1 NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 6 TC 31 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2006 VL 100 IS 1 BP 3 EP 4 DI 10.1016/j.ygyno.2005.12.006 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 999UX UT WOS:000234417200002 PM 16368439 ER PT J AU Kuo, DYS Timmins, P Blank, SV Fields, AL Goldberg, GL Murgo, A Christos, P Wadler, S Runowicz, CD AF Kuo, DYS Timmins, P Blank, SV Fields, AL Goldberg, GL Murgo, A Christos, P Wadler, S Runowicz, CD TI Phase II trial of thalidomide for advanced and recurrent gynecologic sarcoma: A brief communication from the New York Phase II consortium SO GYNECOLOGIC ONCOLOGY LA English DT Article DE thalidomide; gynecologic sarcoma; advanced disease; recurrence ID MIXED MESODERMAL TUMORS; ONCOLOGY-GROUP; UTERINE SARCOMA; UTERUS; LEIOMYOSARCOMA; IFOSFAMIDE; CHEMOTHERAPY; CISPLATIN; ETOPOSIDE; MESNA AB Objective. To define the efficacy of thalidomide on the overall survival of patients with metastatic recurrent gynecologic sarcomas. Patients and methods. All patients with sarcoma or carcinosarcoma of gynecologic origin and documented recurrence or persistence of disease after appropriate surgery, radiation therapy and/or chemotherapy were recruited to the study. All patients were ambulatory and had measurable disease that Could be documented oil CT scan. Patients were started on 200 mg/day of thalidomide orally every night and escalated by 100-200 mg every 7 to 14 days. The length of the treatment was separated into 2 cycles with the first 84 days defined as the first cycle and the next 56 days as the second cycle. Common Toxicity Criteria were used to record toxicities. Because thalidomide was postulated to induce cytostasis, the end-points were progression-free and overall survival in this mixed group of patients. Results. Seventeen patients were enrolled. The drug was not well tolerated because of constipation, fatigue, worsening performance status, drowsiness and sleepiness. The total dosage of medication given to each patient ranged from 3200 mg to 40,500 mg. The maximum dosage reached in each patient ranged from 300 mg to 750 mg, with the total time of treatment ranging from 13 to 99 days. All patients had progression of disease with a median progression-free survival time of 1.84 months (CI 1.54-2.79 months) and a median overall survival of 6.64 months. Discussion. Thalidomide has no activity in patients with advanced or recurrent gynecologic sarcomas and was not well-tolerated. The overall survival was < 7 months. The progression-free survival was < 3 months, and, since the therapy was not tolerated well, we unanimously decided to close the Study at this point. Despite the poor result, we still believe in the strategy of anti-angiogenesis and will continue to pursue other potential treatment options using the same concept. (c) 2005 Elsevier Inc. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Obstet Gynecol, Div Gynecol Oncol, New York, NY 10021 USA. New York Oncol Hematol PC, Div Gynecol Oncol, Albany, NY 12208 USA. NYU, Med Ctr, Dept Obstet Gynecol, Div Gynecol Oncol, New York, NY 10016 USA. Yeshiva Univ Albert Einstein Coll Med, Montefiore Med Ctr, Div Gynecol Oncol, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10461 USA. NCI, CTEP, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Publ Hlth, Div Biostat & Epidemiol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Div Hematol & Med Oncol, New York, NY 10021 USA. Univ Connecticut, Ctr Hlth, Carole & Ray Neag Comprehens Canc Ctr, Farmington, CT 06032 USA. RP Kuo, DYS (reprint author), New York Presbyterian Hosp, 525 E 68th St J-130, New York, NY 10021 USA. EM dek2001@med.cornell.edu RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 30 TC 14 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2006 VL 100 IS 1 BP 160 EP 165 DI 10.1016/j.ygyno.2005.08.033 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 999UX UT WOS:000234417200029 ER PT J AU Aliyu, ZY Tumblin, AR Kato, GJ AF Aliyu, ZY Tumblin, AR Kato, GJ TI Current therapy of sickle cell disease SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material ID HEMOGLOBIN SC DISEASE; HYDROXYUREA THERAPY; NITRIC-OXIDE; PULMONARY-HYPERTENSION; PEDIATRIC-PATIENTS; STROKE-PREVENTION; FETAL-HEMOGLOBIN; ANEMIA; CHILDREN; TRANSFUSION C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Clin Res Trainning Program Off, NIH, Bethesda, MD 20892 USA. NHLBI, Sickle Cell Vasc Dis Unit, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. RP Aliyu, ZY (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM aliyuz@nhlbi.nih.gov; tumblina@mail.nih.gov; gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [Z99 HL999999, ZIA HL006014-02] NR 50 TC 14 Z9 15 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JAN PY 2006 VL 91 IS 1 BP 7 EP 11 PG 5 WC Hematology SC Hematology GA 006VK UT WOS:000234925500011 PM 16434364 ER PT J AU Jensen, RT Moody, TW AF Jensen, Robert T. Moody, Terry W. BE Kastin, AJ TI Bombesin-Related Peptides and Neurotensin: Effects on Cancer Growth/Proliferation and Cellular Signaling in Cancer SO HANDBOOK OF BIOLOGICALLY ACTIVE PEPTIDES LA English DT Article; Book Chapter ID GASTRIN-RELEASING-PEPTIDE; FOCAL ADHESION KINASE; DUCTAL PANCREATIC ADENOCARCINOMA; NEUROMEDIN-B RECEPTORS; GROWTH-FACTOR RECEPTOR; LUNG-CARCINOMA CELLS; AUTOCRINE GROWTH; PROSTATE-CANCER; FUNCTIONAL EXPRESSION; ANTAGONIST RC-3095 AB Mammalian bombesin-related peptides and neurotensin are regulatory peptides that have important roles in a number of physiological and pathological processes. In this chapter their effects on human cancer are briefly reviewed, including evidence that these peptides and/or their receptors occur in cancer, stimulate growth, are involved in cellular signaling cascades, and have potential roles in cancer treatment. C1 [Jensen, Robert T.] NIDDK, NIH, DDB, Bethesda, MD 20892 USA. [Moody, Terry W.] NCI, Off Director, CCR, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Bldg 10,Room 9C 103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 81 TC 21 Z9 21 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046379-7 PY 2006 BP 429 EP 434 DI 10.1016/B978-012369442-3/50064-7 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR53 UT WOS:000311102400063 ER PT B AU Cuttitta, F Portal-Nunez, S Falco, C Garayoa, M Pio, R Montuenga, LM Julian, M Martinez, A Zudaire, E AF Cuttitta, Frank Portal-Nunez, Sergio Falco, Christie Garayoa, Merche Pio, Ruben Montuenga, Luis M. Julian, Miguel Martinez, Alfredo Zudaire, Enrique BE Kastin, AJ TI Adrenomedullin: An Esoteric Juggernaut of Human Cancers SO HANDBOOK OF BIOLOGICALLY ACTIVE PEPTIDES LA English DT Article; Book Chapter ID SMOOTH-MUSCLE-CELLS; ANGIOGENIC FACTOR ADRENOMEDULLIN; POSSIBLE PROMOTION MECHANISM; TUMOR-GROWTH; IN-VIVO; HUMAN CARCINOGENESIS; HYPOTENSIVE PEPTIDE; GENE-TRANSCRIPTION; AUTOCRINE GROWTH; SURVIVAL FACTOR AB Recent discoveries have linked adrenomedullin (AM) with fetal development, wound repair, and cancer, underlying its importance in cellular proliferative events. In this chapter we examine the role of AM in human carcinogenesis, focusing on its ability to modulate cell growth, induce angiogenesis, suppress apoptosis, control cell migration/invasion, and regulate immune response mechanisms. We identify regulatory pathways that affect AM mRNA/protein expression and function as it relates to malignant disease and propose alternative therapeutic strategies for the clinical management of human cancers targeting this peptide. C1 [Cuttitta, Frank] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Portal-Nunez, Sergio; Falco, Christie; Zudaire, Enrique] NCI, Vasc Biol Fac, Ctr Canc Res, Bethesda, MD 20892 USA. [Garayoa, Merche; Pio, Ruben; Montuenga, Luis M.] Univ Navarra, Cellular & Pathol Dept, E-31080 Pamplona, Spain. [Julian, Miguel] Univ San Pablo CEU, Dept Chem, Madrid, Spain. [Martinez, Alfredo] CSIC, Inst Cajal, Dept Cell Biol & Neuroanat, E-28002 Madrid, Spain. RP Cuttitta, F (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RI Cuttitta, Frank/B-4758-2016 NR 52 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046379-7; 978-0-12-369442-3 PY 2006 BP 453 EP 458 DI 10.1016/B978-012369442-3/50068-4 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR53 UT WOS:000311102400067 ER PT J AU Moody, TW Jensen, RT AF Moody, Terry W. Jensen, Robert T. BE Kastin, AJ TI VIP and PACAP as Autocrine Growth Factors in Breast and Lung Cancer SO HANDBOOK OF BIOLOGICALLY ACTIVE PEPTIDES LA English DT Article; Book Chapter ID VASOACTIVE-INTESTINAL-PEPTIDE; ADENYLATE-CYCLASE; HIGH-AFFINITY; CELL-LINES; RECEPTOR ANTAGONIST; SIGNAL-TRANSDUCTION; FUNCTIONAL EXPRESSION; BIOLOGICAL-ACTIVITY; SPLICE VARIANTS; HUMAN TISSUES AB VIP and PACAP are synthesized by several human breast and lung cancer cell lines. These peptides bind to cell surface receptors and stimulate adenylylcyclase activity. This leads to increased expression of nuclear oncogenes such as c-fos and c-jun, ultimately leading to cellular proliferation. The growth of breast and lung cancer cell lines is inhibited by VIP receptor antagonists and VIP-chemotherapeutic conjugates. C1 [Moody, Terry W.] NCI, Off Director, CCR, Bethesda, MD 20892 USA. [Jensen, Robert T.] NIDDK, NIH, DDB, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI, Off Director, CCR, Bethesda, MD 20892 USA. NR 57 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046379-7 PY 2006 BP 473 EP 477 DI 10.1016/B978-012369442-3/50071-4 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR53 UT WOS:000311102400070 ER PT J AU Wang, JM Chen, KQ AF Wang, Ji Ming Chen, Keqiang BE Kastin, AJ TI Chemotactic Peptide Ligands for Formylpeptide Receptors Influencing Inflammation SO HANDBOOK OF BIOLOGICALLY ACTIVE PEPTIDES LA English DT Article; Book Chapter ID PROTEIN-COUPLED RECEPTOR; N-FORMYLPEPTIDE; NEUTROPHIL GRANULE; HUMAN PHAGOCYTES; CATHEPSIN-G; FORMYL; FPRL1; AGONIST; CELLS; 7-TRANSMEMBRANE AB Bacterial peptide fMet-Leu-Phe (fMLF) is one of the first identified chemoattractants for phagocytic leukocytes by interacting with two seven transmembrane, G protein-coupled formylpeptide receptors, FPR, and its variant FPRL1. Recently a number of novel and host-derived formylpeptide receptor agonist peptides have been identified. These agonists selectively activate one or more formylpeptide receptors including another FPR variant FPRL2. Activation of formylpeptide receptors by peptide agonists results in increased cell chemotaxis, phagocytosis, and release of proinflammatory mediators by leukocytes. Injection of peptide agonists in mice also promotes antibody responses. Therefore, formylpeptide receptor agonists may play important roles in the pathogenesis of inflammatory and immunological diseases. C1 [Wang, Ji Ming; Chen, Keqiang] NCI, LMI, CCR, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, LMI, CCR, Frederick, MD 21702 USA. NR 42 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046379-7 PY 2006 BP 547 EP 552 DI 10.1016/B978-012369442-3/50081-7 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR53 UT WOS:000311102400080 ER PT J AU Yang, D AF Yang, De BE Kastin, AJ TI Complement-Derived Inflammatory Peptides: Anaphylatoxins SO HANDBOOK OF BIOLOGICALLY ACTIVE PEPTIDES LA English DT Article; Book Chapter ID HUMAN C3A RECEPTOR; EXPRESSION CLONING; STRUCTURAL GENE; C5A RECEPTOR; GUINEA-PIG; COMPONENT; CELLS; ORGANIZATION; SEQUENCE; AGONIST AB Anaphylatoxins are complement-derived, 74 similar to 77 aa residue-long, cationic, inflammatory peptides that can cause anaphylactic reaction. This chapter covers various aspects of anaphylatoxins, with a particular focus on their genes, expression and generation, structure, and receptors, as well as or the biological actions responsible for their inflammatory activities and implications in diseases. C1 NCI, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA. RP Yang, D (reprint author), NCI, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046379-7 PY 2006 BP 553 EP 558 DI 10.1016/B978-012369442-3/50082-9 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR53 UT WOS:000311102400081 ER PT J AU Zhang, N Oppenheim, JJ AF Zhang, Ning Oppenheim, Joost J. BE Kastin, AJ TI Neuropeptides That Regulate Immune Responses SO HANDBOOK OF BIOLOGICALLY ACTIVE PEPTIDES LA English DT Article; Book Chapter ID CORTICOTROPIN-RELEASING-FACTOR; GENE-RELATED PEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; PITUITARY-ADRENAL AXIS; HUMAN MONONUCLEAR PHAGOCYTES; KILLER-CELL-ACTIVITY; INFLAMMATORY MEDIATOR; VASOPRESSIN-BINDING; OPIOID RECEPTORS; KININ RECEPTORS AB Increasing evidence has shown that many neuropeptides modulate immune responses in addition to their well-documented function in the central and peripheral nervous systems. RT-PCR, Western blotting, and functional assays reveal the production of these neuropeptides by the immune system and the expression of their receptors on the leukocyte surface. This chapter provides a brief summary of the immunological activities of neuropeptides. The nervous and immune systems are tightly integrated and orchestrated to serve complicated tasks of host sensation and response. A disturbance in one system often has a profound effect on the other. For example, activation of hypothalamo-pituitary-adrenal (HPA) axis by long-term stress often elicits suppression of both innate and adaptive immunity [17, 23, 61]. Conversely, inflammatory immune responses activate central nervous system sensory pain pathways [53, 58, 65, 66]. Increasing evidence suggests that a family of immunoactive neuropeptides provides key signals between these two systems. Beyond their well-characterized effects in the nervous system, these neuropeptides also interact with their receptors on leukocytes and thus modulate the function of these pivotal mediators of host defense. Furthermore, leukocytes are also capable of producing many of these peptides in the peripheral immune system. The structure, properties, and roles of neuropeptides in the central and peripheral nervous systems is discussed in other chapters of this book. This section briefly describes the immunological effects of these neuropeptides, as summarized in Table 1. Other actions of these peptides are discussed elsewhere in this book. Neuropeptides influence host immune defenses based on two mechanisms. First, these peptides indirectly regulate the immune response by activating the different pathways of the central nervous system. For example, Met-enkephalin, an endogenous opioid, stimulates the CNS-mediated production of corticosterone, a potent immunosuppressive hormone [35]. Opioids also activate the sympathetic nervous system, resulting in an increase in the level of circulating epinephrine from the adrenal medulla and secretion of the norepinephrine by sympathetic nerve terminals. Increased catecholamine levels have been linked to suppression of natural killer cell and lymphocyte function. Second, all the peptides listed in Table 1 are able to directly regulate the functions of receptor expressing leukocytes, independent of neuronal activities. Studies using RT-PCR or Western blotting analysis reveal the expression of a wide variety of neuropeptide receptors on various types of leukocytes. For example, all three subtypes of opioid receptors, mu-, delta-, and.kappa- receptors, have been detected on T cell, B cells, monocytes, neutrophils, and natural killer cells [40]. Stimulation of these neuropeptide receptors can modulate leukocyte production of proinflammatory cytokines. Most neuropeptide receptors are seven-transmembrane receptors which exert their function by activating heterotrimeric G protein. Neuropeptides are mainly expressed and active in the central and peripheral nervous system. However, these peptides can also be produced and are functional in other peripheral tissues. For example, adrenocorticotrophic hormone/corticotrophin (ACTH) is not only produced by pituitary cells, but also to a limited extent by leukocytes [7]. Endogenous opioids are expressed by leukocytes and play an important role in peripheral C1 [Zhang, Ning; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Zhang, N (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046379-7 PY 2006 BP 579 EP 584 DI 10.1016/B978-012369442-3/50086-6 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR53 UT WOS:000311102400085 ER PT J AU Leker, RR Constantini, S AF Leker, Ronen R. Constantini, Shlomi BE Tatlisumak, T Fisher, M TI In vivo models of traumatic brain injury SO HANDBOOK OF EXPERIMENTAL NEUROLOGY: METHODS AND TECHNIQUES IN ANIMAL RESEARCH LA English DT Article; Book Chapter ID CLOSED-HEAD-INJURY; CONTROLLED CORTICAL IMPACT; MAGNETIC-RESONANCE-SPECTROSCOPY; DIFFUSE AXONAL PATHOLOGY; COLD-INJURY; COGNITIVE DEFICITS; NEURONAL APOPTOSIS; APOLIPOPROTEIN-E; IMMATURE RAT; BLOOD-FLOW C1 [Leker, Ronen R.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Constantini, Shlomi] Tel Aviv Med Ctr & Sch Med, Dana Childrens Hosp, Dept Pediat Neurosurg, IL-64239 Tel Aviv, Israel. RP Leker, RR (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36,Room 3C12, Bethesda, MD 20892 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-83814-6 PY 2006 BP 366 EP 374 DI 10.1017/CBO9780511541742.021 D2 10.1017/CBO9780511541742 PG 9 WC Neurosciences; Veterinary Sciences SC Neurosciences & Neurology; Veterinary Sciences GA BXT09 UT WOS:000297007700021 ER PT J AU Smith, S Melvin, A Zeichner, SL McFarland, E Palumbo, P Aldrovandi, G AF Smith, Sherilyn Melvin, Ann Zeichner, Steven L. McFarland, Elizabeth Palumbo, Paul Aldrovandi, Grace BE Zeichner, SL Read, JS TI The scientific basis of pediatric HIV care SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; POLYMERASE-CHAIN-REACTION; LONG TERMINAL REPEAT; PERINATALLY INFECTED CHILDREN; PLASMACYTOID DENDRITIC CELLS; RISK UNINFECTED ADOLESCENTS; CELLULAR IMMUNE-RESPONSES; CD4(+) LYMPHOCYTE COUNT; HEAT-DENATURED PLASMA C1 [Smith, Sherilyn; Melvin, Ann] Childrens Hosp & Reg Med Ctr, Seattle, WA 98105 USA. [Zeichner, Steven L.] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [McFarland, Elizabeth] Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. [Palumbo, Paul] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. [Aldrovandi, Grace] Univ Alabama, Birmingham, AL 35294 USA. RP Smith, S (reprint author), Childrens Hosp & Reg Med Ctr, CH-32,4800 Sand Point Way, Seattle, WA 98105 USA. NR 299 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 3 EP 77 DI 10.1017/CBO9780511544781.003 D2 10.2277/ 0521529069 PG 75 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500003 ER PT J AU Zeichner, SL Read, JS AF Zeichner, Steven L. Read, Jennifer S. BE Zeichner, SL Read, JS TI Pediatric HIV Care Preface SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 [Zeichner, Steven L.] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Read, Jennifer S.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. RP Zeichner, SL (reprint author), NCI, HIV & AIDS Malignancy Branch, Bldg 10,Room 10S255,10 Ctr Dr,MSC1868, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP XXIX EP XXX DI 10.1017/CBO9780511544781.002 D2 10.2277/ 0521529069 PG 2 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500002 ER PT J AU Read, JS AF Read, Jennifer S. BE Zeichner, SL Read, JS TI Prevention of mother-to-child transmission of HIV SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIAL; VITAMIN-A SUPPLEMENTATION; SHORT-COURSE ZIDOVUDINE; 15 PROSPECTIVE COHORT; MATERNAL VIRAL LOAD; BREAST-FED CHILDREN; PERINATAL TRANSMISSION; VERTICAL TRANSMISSION; PREGNANT-WOMEN C1 NICHD, Pediat Adolescent & Maternal AIDS PAMA Branch, NIH, Bethesda, MD 20892 USA. RP Read, JS (reprint author), NICHD, Pediat Adolescent & Maternal AIDS PAMA Branch, NIH, Bethesda, MD 20892 USA. NR 102 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 107 EP 133 DI 10.1017/CBO9780511544781.006 D2 10.2277/ 0521529069 PG 27 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500006 ER PT J AU Chantry, CJ Moye, J AF Chantry, Caroline J. Moye, Jack, Jr. BE Zeichner, SL Read, JS TI Growth, nutrition, and metabolism SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED CHILDREN; ACTIVE ANTIRETROVIRAL THERAPY; RESTING ENERGY-EXPENDITURE; FACTOR-BINDING PROTEIN-3; BONE-MINERAL CONTENT; FAILURE-TO-THRIVE; FAT-FREE MASS; BODY-COMPOSITION; PROTEASE INHIBITOR C1 [Chantry, Caroline J.] Univ Calif Davis, Med Ctr, Dept Clin Pediat, Sacramento, CA 95817 USA. [Moye, Jack, Jr.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. RP Chantry, CJ (reprint author), Univ Calif Davis, Med Ctr, Dept Clin Pediat, 2516 Stockton Blvd,Ticon 2,Suite 334, Sacramento, CA 95817 USA. OI moye, john/0000-0001-9976-8586 NR 103 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 273 EP 308 DI 10.1017/CBO9780511544781.011 D2 10.2277/ 0521529069 PG 36 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500011 ER PT J AU Wolters, PL Brouwers, P AF Wolters, Pamela L. Brouwers, Pim BE Zeichner, SL Read, JS TI Neurobehavioral function and assessment of children and adolescents with HIV-1 infection SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; INFUSION ZIDOVUDINE THERAPY; CENTRAL-NERVOUS-SYSTEM; SCHOOL-AGE-CHILDREN; CEREBROSPINAL-FLUID; HEMOPHILIA GROWTH; DEMENTIA COMPLEX; VIRAL LOAD; NEUROLOGIC MANIFESTATIONS C1 [Wolters, Pamela L.] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Wolters, Pamela L.] Med Illness Counseling Ctr, Bethesda, MD 20892 USA. [Brouwers, Pim] Baylor Coll Med, Dept Pediat & Neurosci, Houston, TX 77030 USA. [Brouwers, Pim] Texas Childrens Canc Ctr, Houston, TX USA. [Brouwers, Pim] Sickle Cell Ctr, Houston, TX USA. RP Wolters, PL (reprint author), NCI, HIV & AIDS Malignancy Branch, 9030 Old Georgetown Rd,Bldg 82,Room 109, Bethesda, MD 20892 USA. NR 127 TC 2 Z9 2 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 309 EP 331 DI 10.1017/CBO9780511544781.012 D2 10.2277/ 0521529069 PG 23 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500012 ER PT J AU Worrell, CJ AF Worrell, Carol J. BE Zeichner, SL Read, JS TI Metabolic complications of antiretroviral therapy in children SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED CHILDREN; REVERSE-TRANSCRIPTASE INHIBITORS; MITOCHONDRIAL-DNA DEPLETION; NUCLEOSIDE-ANALOG THERAPY; PROTEASE INHIBITORS; LIPODYSTROPHY SYNDROME; BODY-COMPOSITION; INSULIN-RESISTANCE; PERIPHERAL LIPODYSTROPHY C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Worrell, CJ (reprint author), NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NR 60 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 382 EP 396 DI 10.1017/CBO9780511544781.015 D2 10.2277/ 0521529069 PG 15 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500015 ER PT J AU Maldarelli, F AF Maldarelli, Frank BE Zeichner, SL Read, JS TI HIV drug resistance SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; PROTEASE INHIBITORS; VIROLOGICAL RESPONSE; ANALOG RESISTANCE; CROSS-RESISTANCE; STERIC HINDRANCE; CLINICAL UTILITY; 3TC RESISTANCE; SUSCEPTIBILITY C1 NCI, HIV Drug Resistance Program 1, NIH, Bethesda, MD 20892 USA. RP Maldarelli, F (reprint author), NCI, HIV Drug Resistance Program 1, NIH, Bldg 10,Room 4A12, Bethesda, MD 20892 USA. NR 51 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 397 EP 414 DI 10.1017/CBO9780511544781.016 D2 10.2277/ 0521529069 PG 18 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500016 ER PT J AU Mofenson, LM Serchuck, LK AF Mofenson, Lynne M. Serchuck, Leslie K. BE Zeichner, SL Read, JS TI Initiating and changing antiretroviral therapy SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED CHILDREN; RANDOMIZED CONTROLLED-TRIAL; REVERSE-TRANSCRIPTASE INHIBITORS; 1-INFECTED CHILDREN; HIV-1-INFECTED CHILDREN; COMBINATION THERAPY; VIRAL LOAD; DISEASE PROGRESSION; PROTEASE INHIBITOR C1 [Mofenson, Lynne M.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20852 USA. [Serchuck, Leslie K.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. RP Mofenson, LM (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20852 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 415 EP 438 DI 10.1017/CBO9780511544781.017 D2 10.2277/ 0521529069 PG 24 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500017 ER PT J AU Civitello, L AF Civitello, Lucy BE Zeichner, SL Read, JS TI Neurologic problems SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYMPTOMATIC HIV DISEASE; TERM ZIDOVUDINE THERAPY; CENTRAL-NERVOUS-SYSTEM; ANTIRETROVIRAL THERAPY; NEUROPSYCHOLOGICAL FUNCTION; INFECTED CHILDREN; BRAIN-SCAN; ABNORMALITIES; DEMENTIA C1 [Civitello, Lucy] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Civitello, Lucy] NIH, Bethesda, MD 20892 USA. RP Civitello, L (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 49 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 503 EP 519 DI 10.1017/CBO9780511544781.021 D2 10.2277/ 0521529069 PG 17 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500021 ER PT J AU Fine, HF Lee, SS Robinson, MR AF Fine, Howard F. Lee, Susan S. Robinson, Michael R. BE Zeichner, SL Read, JS TI Ophthalmic problems SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; CYTOMEGALOVIRUS RETINITIS; OCULAR MANIFESTATIONS; RETINAL-DETACHMENT; PEDIATRIC-PATIENTS; HIV-INFECTION; VIRUS; AIDS; POPULATION C1 [Fine, Howard F.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Lee, Susan S.; Robinson, Michael R.] NEI, NIH, Bethesda, MD 20892 USA. RP Fine, HF (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600N Wolfe Dr,Wilmer B-20, Baltimore, MD 21205 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 520 EP 534 DI 10.1017/CBO9780511544781.022 D2 10.2277/ 0521529069 PG 15 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500022 ER PT J AU Atkinson, JC O'Connell, A AF Atkinson, Jane C. O'Connell, Anne BE Zeichner, SL Read, JS TI Oral health and dental problems SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID PEDIATRIC AIDS; CHILDREN BORN; INFECTION; WOMEN C1 [Atkinson, Jane C.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [O'Connell, Anne] Dept Publ & Child Dent Hlth, Dublin, Ireland. RP Atkinson, JC (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bldg 10,Room IN 117, Bethesda, MD 20892 USA. OI O'Connell, Anne C/0000-0002-1495-3983 NR 19 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 535 EP 542 DI 10.1017/CBO9780511544781.023 D2 10.2277/ 0521529069 PG 8 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500023 ER PT J AU Wood, LV AF Wood, Lauren V. BE Zeichner, SL Read, JS TI Pulmonary problems SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID IMMUNODEFICIENCY-VIRUS-INFECTION; HIV DISEASE; CHILDREN; LUNG; MANIFESTATIONS; MANAGEMENT; ASTHMA; AIDS C1 NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. RP Wood, LV (reprint author), NCI, Vaccine Branch, NIH, Bldg 10,Room 6B04, Bethesda, MD 20892 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 567 EP 587 DI 10.1017/CBO9780511544781.026 D2 10.2277/ 0521529069 PG 21 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500026 ER PT J AU Winter, HS Moye, J AF Winter, Harland S. Moye, Jack, Jr. BE Zeichner, SL Read, JS TI Gastrointestinal disorders SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; CHILDREN; GROWTH; TRANSMISSION; TRACT; BORN C1 [Winter, Harland S.] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. [Moye, Jack, Jr.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. [Moye, Jack, Jr.] NICHHD, Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. RP Winter, HS (reprint author), Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, 55 Fruit St, Boston, MA 02114 USA. OI moye, john/0000-0001-9976-8586 NR 17 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 602 EP 617 DI 10.1017/CBO9780511544781.028 D2 10.2277/ 0521529069 PG 16 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500028 ER PT J AU Tanawattanacharoen, S Kopp, JB AF Tanawattanacharoen, Somsak Kopp, Jeffrey B. BE Zeichner, SL Read, JS TI Renal disease SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-ASSOCIATED NEPHROPATHY; ACTIVE ANTIRETROVIRAL THERAPY; INDUCED HYPERKALEMIA; INFECTION; CHILDREN; AIDS; NEPHRITIS; PROTEINURIA; INHIBITION C1 [Tanawattanacharoen, Somsak; Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Tanawattanacharoen, S (reprint author), NIDDK, Kidney Dis Sect, Metab Dis Branch, NIH, Bldg 10,Room 3N116, Bethesda, MD 20892 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 618 EP 629 DI 10.1017/CBO9780511544781.029 D2 10.2277/ 0521529069 PG 12 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500029 ER PT J AU Little, RF AF Little, Richard F. BE Zeichner, SL Read, JS TI Neoplastic disease in pediatric HIV infection SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; EPSTEIN-BARR-VIRUS; NON-HODGKINS-LYMPHOMA; PEGYLATED-LIPOSOMAL DOXORUBICIN; ACTIVE ANTIRETROVIRAL THERAPY; KAPOSIS-SARCOMA; NATURAL-HISTORY; CLINICAL-TRIAL; M-BACOD; AIDS C1 NCI, HIV & AIDS Malignancy Branch, CCR, NIH, Bethesda, MD 20892 USA. RP Little, RF (reprint author), NCI, HIV & AIDS Malignancy Branch, CCR, NIH, Bldg 10,Room 10S255,MSC 1868, Bethesda, MD 20892 USA. NR 55 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 637 EP 649 DI 10.1017/CBO9780511544781.031 D2 10.2277/ 0521529069 PG 13 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500031 ER PT J AU Jankelevich, S AF Jankelevich, Shirley BE Zeichner, SL Read, JS TI Serious infections caused by typical bacteria SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; PSEUDOMONAS-AERUGINOSA; TRIMETHOPRIM-SULFAMETHOXAZOLE; CHILDREN; RESISTANCE; HIV; PATIENT; DISEASE; SEPSIS C1 NIAID, Pediat Med Branch, NIH, Bethesda, MD 20892 USA. RP Jankelevich, S (reprint author), NIAID, Pediat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 653 EP 673 DI 10.1017/CBO9780511544781.032 D2 10.2277/ 0521529069 PG 21 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500032 ER PT J AU Hazra, R AF Hazra, Rohan BE Zeichner, SL Read, JS TI Tuberculosis SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; CHILDREN; METAANALYSIS; DIAGNOSIS; WOMEN; RISK; BCG C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Hazra, R (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bldg 10,Room 10S255, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 674 EP 684 DI 10.1017/CBO9780511544781.033 D2 10.2277/ 0521529069 PG 11 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500033 ER PT J AU Serchuck, LK AF Serchuck, Leslie K. BE Zeichner, SL Read, JS TI Pneumocystis jiroveci pneumonia SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; CARINII-PNEUMONIA; HIV-INFECTION; INTERSTITIAL PNEUMONITIS; FIBEROPTIC BRONCHOSCOPY; RESPIRATORY-FAILURE; PULMONARY-FUNCTION; MALAWIAN CHILDREN; THERAPY C1 NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. RP Serchuck, LK (reprint author), NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. NR 51 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 740 EP 756 DI 10.1017/CBO9780511544781.037 D2 10.2277/ 0521529069 PG 17 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500037 ER PT J AU Chanock, SJ AF Chanock, Stephen J. BE Zeichner, SL Read, JS TI Medical issues related to the care of HIV-infected children in the home, daycare, school, and community SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 759 EP 771 DI 10.1017/CBO9780511544781.038 D2 10.2277/ 0521529069 PG 13 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500038 ER PT J AU Wiener, LS AF Wiener, Lori S. BE Zeichner, SL Read, JS TI Psychosocial factors associated with childhood bereavement and grief SO HANDBOOK OF PEDIATRIC HIV CARE, 2ND EDITION LA English DT Article; Book Chapter ID CHILDREN; FAMILY; DEATH C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Wiener, LS (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-52906-8 PY 2006 BP 781 EP 795 DI 10.1017/CBO9780511544781.040 D2 10.2277/ 0521529069 PG 15 WC Infectious Diseases; Pediatrics SC Infectious Diseases; Pediatrics GA BXT47 UT WOS:000297022500040 ER PT J AU Resnik, DB AF Resnik, DB TI Protection of human subjects and scientific progress: Can the two be reconciled? SO HASTINGS CENTER REPORT LA English DT Letter C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS NR 0 TC 0 Z9 0 U1 0 U2 0 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 2006 VL 36 IS 1 BP 4 EP 5 PG 2 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 008VX UT WOS:000235069900006 PM 16544825 ER PT J AU Bellizzi, KM Blank, TO AF Bellizzi, KM Blank, TO TI Predicting posttraumatic growth in breast cancer survivors SO HEALTH PSYCHOLOGY LA English DT Article DE breast cancer; posttraumatic growth; quality of life; psychological adjustment ID PSYCHOLOGICAL ADJUSTMENT; OPTIMISM; DISTRESS; WOMEN; UNCERTAINTY; ILLNESS; LONG AB Wide variability exists with respect to how breast cancer survivors respond to common psychological and psychosocial challenges of their disease, ranging from posttraumatic stress disorder to posttraumatic growth. This cross-sectional study examined contextual, disease-related, and intraindividual predictors of posttraumatic growth in 224 randomly selected breast cancer survivors. A series of hierarchical regression analyses found that age at diagnosis, marital status, employment, education, perceived intensity of disease, and active coping accounted for 34%, 35%. and 28% of the variance in growth in relationships with others, new possibilities, and appreciation for life. These findings suggest that a more comprehensive model of growth will be helpful in understanding the various factors that play a role in breast cancer survivors' perception of psychological and psychosocial growth. C1 Univ Connecticut, Sch Family Studies, Storrs, CT 06269 USA. RP Bellizzi, KM (reprint author), NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 404,MSC 8336, Bethesda, MD 20892 USA. EM bellizzk@mail.nih.gov NR 47 TC 159 Z9 174 U1 1 U2 19 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 2006 VL 25 IS 1 BP 47 EP 56 DI 10.1037/0278-6133.25.1.47 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 009PC UT WOS:000235123300007 PM 16448297 ER PT J AU Ruttens, B Kovac, P AF Ruttens, B Kovac, P TI Synthesis of a phosphorylated disaccharide fragment of the O-specific polysaccharide of Vibrio cholerae O139, functionalized for conjugation SO HELVETICA CHIMICA ACTA LA English DT Article ID CAPSULAR POLYSACCHARIDE; VIRULENCE DETERMINANTS; STRUCTURAL-ANALYSIS; VACCINE PROTOTYPE; CARBOHYDRATE; LIPOPOLYSACCHARIDE; PHOSPHATE; IMMUNOGENICITY; PROTEINS; EFFICACY AB The title disaccharide, 2-{2-{2-[(2-ethoxy-3,4-dioxocyclobut-1-en-1-yl)amino] ethoxy}ethoxy}ethyl 2-O-(3,6-dideoxy-alpha-L-xylo-hexopyranosyl)-beta-D-galactopyranoside cyclic 4,6-(potassium phosphate) (2), was synthesized from the two isomeric linker-equipped galactose acceptors 9 and 10, obtained by phosphorylation of 2-[2-(2-azidoethoxy)ethoxylethyl 3-O-benzyl-beta-D-galactopyranoside (8), which were glycosylated with ethyl 2,4-di-O-benzyl-3,6-dideoxy-1-thio-beta-L-xylo-hexopyranoside (12; Scheme). Mainly the fully protected alpha-(1 -> 2)-linked products 13 alpha and 14 alpha were formed. Catalytic hydrogenolysis/hydrogenation effected global deprotection, thereby removing the chirality at the P-atom, and simultaneously converted the azido group in the linker to an amino group (-> 15). Final treatment with diethyl squarate (=3,4-diethoxycyclobut-3-ene-1,2-dione) gave target compound 2, amenable for conjugation to proteins. C1 NIDDK, NIH, LMC, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, NIH, LMC, Bldg 8,Rm B1A25,8 Ctr Dr, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov NR 55 TC 7 Z9 7 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0018-019X J9 HELV CHIM ACTA JI Helv. Chim. Acta PY 2006 VL 89 IS 2 BP 320 EP 332 DI 10.1002/hlca.200690036 PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA 018CW UT WOS:000235742400017 ER PT J AU Adamo, R Saksena, R Kovac, P AF Adamo, Roberto Saksena, Rina Kovac, Pavol TI Studies towards a conjugate vaccine for anthrax: Synthesis of the tetrasaccharide side chain of the Bacillus anthracis exosporium SO HELVETICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 13th European Carbohydrate Symposium (EUROCARD 13) CY AUG 21-26, 2005 CL Bratislava, SLOVAKIA ID MAJOR GLYCOPROTEIN; STEREOSPECIFIC SYNTHESIS; RHAMNOPYRANOSYL LINKAGE; OLIGOSACCHARIDES; MANNOPYRANOSYL; ANTIGEN AB The first synthesis of beta-L-glycoside 17 of the tetrasaccharide beta-Ant-(1 -> 3)-alpha-L-Rhap-(1 -> 3)-alpha-L-Rhap-(1 -> 2)-L-Rhap is described (Schemes 1 - 3). Its spacer can be functionalized to make it amenable to conjugation to proteins by different conjugation methods. The synthesis was performed in a stepwise manner starting from the aglycon-bearing terminal saccharide with thioglycosides as glycosyl donors. To attach the upstream terminal anthrose residue, the assembled linker-equipped trisaccharide was glycosylated with ethyl 4-azido-3-O-benzyl-2-O-(bromoacetyl)-4,6-dideoxy-1-thio-beta-D-glucopyranoside (11). Further functionalization of the tetrasaccharide thus obtained, followed by deprotection gave the target substance 17. Synthesis of substructures of 17 equipped with the same spacer, namely beta-L-Rhap-1-O-(CH2)(5)COOMe (21), alpha-L-Rhap-(1 -> 2)-beta-L-Rhap-1-O-(CH2)(5)COOMe (22), and alpha-L-Rhap-(1 -> 3)-alpha-L-Rhap-(1 -> - 2)-beta-L-Rhap-1-O-(CH2)(5)COOMe (23), is also described (Scheme 4). C1 NIDDK, LMC, NIH, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, LMC, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov NR 18 TC 24 Z9 24 U1 2 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0018-019X J9 HELV CHIM ACTA JI Helv. Chim. Acta PY 2006 VL 89 IS 6 BP 1075 EP 1089 DI 10.1002/hlca.200690106 PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA 061FZ UT WOS:000238858000001 ER PT J AU Thorgeirsson, SS Grisham, JW AF Thorgeirsson, SS Grisham, JW TI Hematopoietic cells as hepatocyte stem cells: A critical review of the evidence SO HEPATOLOGY LA English DT Review ID BONE-MARROW-CELLS; LIVER-REGENERATION; MONOCLONAL-ANTIBODY; MOUSE HEPATOCYTES; PROGENITOR CELLS; STELLATE CELLS; ADULT LIVER; TRANSPLANTATION; REPOPULATION; PLASTICITY AB The authors reviewed 77 published reports available before August 1, 2005 that examined the ability of hematopoietic cells to generate hepatocytes in the liver. A list of these publications and a synopsis of each are available on-line. We interpret the evidence provided by this data set to suggest that one or more types of hematopoietic cells may rarely acquire the hepatocyte phenotype in the liver (frequency <= 10(-4)), although the nature of the hematopoietic cells involved and the mechanisms responsible for acquisition of a hepatocyte phenotype are still controversial. Hematopoietic stem cells do not appear to be direct precursors of hepatocytes, which, instead, can be generated from cells of the macrophage-monocyte lineage. Fusion between hepatocytes and transplanted hematopoietic cells has been substantiated as a mechanism by which hepatocytes that carry a bone marrow tag are generated, but direct transdifferentiation of hematopoietic cells has not been demonstrated. In conclusion, hematopoietic cells contribute little to hepatocyte formation under either physiological or pathological conditions, although they may provide cytokines and growth factors that promote hepatocyte functions by paracrine mechanisms. Cells of the endodermal hepatocyte lineage are far more potent generators of hepatocytes than are hematopoietic cells. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-91391suppmat/ index.html). C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 4146A,37 Convent Dr MSC 4262, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 35 TC 160 Z9 166 U1 0 U2 9 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 2006 VL 43 IS 1 BP 2 EP 8 DI 10.1002/hep.21015 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 000KH UT WOS:000234460000002 PM 16374844 ER PT J AU Umemura, T Wang, RYH Schechterly, C Shih, JWK Kiyosawa, K Alter, HJ AF Umemura, T Wang, RYH Schechterly, C Shih, JWK Kiyosawa, K Alter, HJ TI Quantitative analysis of anti-hepatitis C virus anti body-secreting B cells in patients with chronic hepatitis C SO HEPATOLOGY LA English DT Article ID IMMUNOGLOBULIN-M ANTIBODY; T-LYMPHOCYTE RESPONSE; IMMUNE-RESPONSES; VIRAL CLEARANCE; NEUTRALIZING ANTIBODY; INTERFERON-ALPHA; SURFACE-ANTIGEN; LIVER-DISEASE; ELISPOT ASSAY; CORE PROTEIN AB To investigate the quantitative characteristics of humoral immunity in patients with hepatitis C, we established an enzyme-linked immunosorbent spot (ELISpot) assay for detection of anti-hepatitis C virus (HCV)-secreting B cells. Receiver operating characteristic curve analysis demonstrated 100% specificity and 58% to 92% sensitivity for detecting B-cell responses to NS5b, NS3, E2, and core antigens. The median sum of anti-HCV-secreting B cells to all HCV antigens tested was significantly higher in 39 patients with chronic hepatitis C (47.3 spot forming cells [SFCs]/10(6) peripheral blood mononuclear cells [PBMCs]) than in 9 recovered subjects (15.3 SFCs/10(6) PBMCs; P = .05) or 11 uninfected controls (5-3 SFCs/10(6) PBMCs; P < .001); the significant difference (P = .018) in chronic versus recovered patients was in reactivity to nonstructural antigens NS3 and NS5b. Anti-HCV immunoglubulin M (IgM)-secreting B cells were also readily detected and persisted decades into HCV infection; there was no difference in IgM-positive cells between chronic and recovered patients. ELISpot reactivity to genotype 1-derived antigens was equivalent in patients of genotypes 1, 2, and 3. There was significant correlation between the numbers of anti-HCV IgG-secreting B cells and serum aminotransferase and to the level of circulating antibody. In conclusion, ELISpot assays can be adapted to study B-cell as well as T-cell responses to HCV. Measurement at the single-cell level suggests that humoral immunity plays a minor role in recovery from HCV infection and that B-cell immunity is strongest in those with persistent infection. C1 NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Shinshu Univ, Sch Med, Dept Med, Matsumoto, Nagano 390, Japan. RP Alter, HJ (reprint author), NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM halter@cc.nih.gov NR 47 TC 20 Z9 20 U1 1 U2 1 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 2006 VL 43 IS 1 BP 91 EP 99 DI 10.1002/hep.20917 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 000KH UT WOS:000234460000014 PM 16323211 ER PT S AU Betz, JM AF Betz, JM BE Wang, M Sang, S Hwang, LS Ho, CT TI Botanical quality initiatives at the office of dietary supplements, national institutes of health SO HERBS: CHALLENGES IN CHEMISTRY AND BIOLOGY SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc ID HERBAL MEDICINAL PRODUCTS; LIQUID-CHROMATOGRAPHY; COMMERCIAL GINKGO; HPLC-UV; COLCHICINE; ALKALOIDS AB Quality of botanical products is one of the biggest uncertainties that consumers, clinicians, regulators, and researchers face. Definitions of quality abound, and include specifications for sanitation, adventitious agents (pesticides, metals, weeds), and content of natural chemicals. Because dietary supplements (DS) are often complex mixtures, they pose analytical challenges and methods validation may be difficult. In response to product quality concerns and the need for validated and publicly available methods for DS analysis, the U.S. Congress directed the Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH) to accelerate an ongoing methods validation process. The Dietary Supplements Methods and Reference Materials Program was created. The program was constructed from stakeholder input and incorporates several federal procurement and granting mechanisms in a coordinated and interlocking framework. The framework facilitates validation of analytical methods, analytical standards, and reference materials. C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Betz, JM (reprint author), NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 28 TC 5 Z9 5 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3930-4 J9 ACS SYM SER PY 2006 VL 925 BP 2 EP 13 PG 12 WC Biochemistry & Molecular Biology; Plant Sciences; Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Plant Sciences; Pharmacology & Pharmacy; Chemistry GA BEC74 UT WOS:000236816500001 ER PT J AU Christie, BR Cameron, HA AF Christie, BR Cameron, HA TI Neurogenesis in the adult hippocampus SO HIPPOCAMPUS LA English DT Review DE cell proliferation; neurogenesis; cell division; bromodeoxyuridine; hippocampus; mitosis ID NEURAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; RAT DENTATE GYRUS; FIBROBLAST GROWTH FACTOR-2; POSTNATAL NEUROGENESIS; PROLIFERATING CELLS; TRITIATED THYMIDINE; VOLUNTARY EXERCISE; PROGENITOR CELLS; GRANULE CELLS AB The dentate gyrus (DG) contains one of the few neuronal populations in the mammalian brain that are generated throughout life. Research into the regulation and function of adult neurogenesis continues its rapid growth in popularity. With the researcher new to the field in mind, we review the processes that together constitute adult neurogenesis and some of the methods most commonly used for studying these processes. (c) 2006 Wiley-Liss, Inc. C1 Univ British Columbia, Dept Psychol, Vancouver, BC V6T 1Z4, Canada. NIMH, Unit Neuroplast, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Christie, BR (reprint author), Univ British Columbia, Dept Psychol, 2136 W Mall, Vancouver, BC V6T 1Z4, Canada. EM bchristie@psych.ubc.ca RI Cameron, Heather/E-6221-2011; OI Cameron, Heather/0000-0002-3245-5777; Christie, Brian/0000-0002-6830-0160 FU Intramural NIH HHS NR 72 TC 128 Z9 135 U1 3 U2 10 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 2006 VL 16 IS 3 BP 199 EP 207 DI 10.1002/hipo.20151 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 020LM UT WOS:000235910900001 PM 16411231 ER PT J AU Karten, YJG Jones, MA Jeurling, SI Cameron, HA AF Karten, YJG Jones, MA Jeurling, SI Cameron, HA TI GABAergic signaling in young granule cells in the adult rat and mouse dentate gyrus SO HIPPOCAMPUS LA English DT Article DE GABA-A receptors; adult neurogenesis; patch-clamp; maturation; immunohistochemistry ID DEVELOPING HYPOTHALAMIC NEURONS; RECEPTOR-ALPHA SUBUNITS; GABA(A) RECEPTOR; POSTNATAL-DEVELOPMENT; HIPPOCAMPAL-NEURONS; EXCITATORY ACTIONS; ACTION-POTENTIALS; PROGENITOR CELLS; CRITICAL PERIOD; OLFACTORY-BULB AB Throughout most of the developing brain, including the hippocampus, GABAergic synapses are the first to become functional. Several features of GABAergic signaling change across development, suggesting that this signaling in the immature brain may play important roles in the growth of young neurons and the establishment of networks. To determine whether GABA(A) receptor (GABA(A)R)-containing synapses in new neurons born in the adult dentate gyrus have similar immature features, we examined spontaneous and evoked GABA(A)R-mediated synaptic currents in young (POMC-EGFP or doublecortin-immunostained) granule cells in acute slice preparations from adult mice and rats. Spontaneous inhibitory postsynaptic currents (IPSCs) were observed in nearly all immature granule cells, but their frequency was considerably lower and their decay time constant was nearly two times longer than in neighboring mature (doublecortin-nonimmunoreactive or EGFP-nonexpressing) granule cells within the subgranular zone. Evoked IPSCs (eIPSCs) in mature granule cells, but not immature granule cells, were sensitive to zolpidem, suggesting a maturational increase in GABA(A)R alpha 1-subunit expression. Perforated-patch recording revealed that eIPSCs depolarized young neurons, but hyperpolarized mature neurons. The early establishment of synaptic GABAergic inputs slow IPSC decay time, and depolarizing action of eIPSCs are remarkably similar to features previously seen in neurons during development, suggesting that they are intrinsic features of immature neurons and not functions of the surrounding circuitry. These developmental features in adult-born granule cells could play a role in maturational processes such as developmental cell death. However, treatment of adult mice with GABA(A)R agonists and an inverse agonist did not significantly alter the number of 4- to 14-day-old BrdU-labeled cells. Published 2006 Wiley-Liss, Inc. C1 NIMH, Unit Neuroplast, NIH, Bethesda, MD 20892 USA. RP Cameron, HA (reprint author), NIMH, Unit Neuroplast, NIH, Bldg 35-3C915,35 Lincoln Dr, Bethesda, MD 20892 USA. EM heathercameron@mail.nih.gov RI Cameron, Heather/E-6221-2011 OI Cameron, Heather/0000-0002-3245-5777 NR 62 TC 44 Z9 46 U1 0 U2 3 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 2006 VL 16 IS 3 BP 312 EP 320 DI 10.1002/hipo.20165 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 020LM UT WOS:000235910900014 PM 16435314 ER PT J AU Belcher, AM Harrington, RA Malkova, L Mishkin, M AF Belcher, AM Harrington, RA Malkova, L Mishkin, M TI Effects of hippocampal lesions on the monkey's ability to learn large sets of object-place associations SO HIPPOCAMPUS LA English DT Article DE spatial memory; rhesus macaque; ibotenic acid; medial temporal lobe; hippocampus ID NONMATCHING-TO-SAMPLE; NEUROTOXIC LESIONS; VISUAL RECOGNITION; PERIRHINAL CORTEX; LOCATION MEMORY; RHESUS-MONKEYS; DAMAGE; NAVIGATION; DEFICITS; RECALL AB Earlier studies found that recognition memory for object-place associations was impaired in patients with relatively selective hippocampal damage (Vargha-Khadem et al., Science 1997; 277:376-380), but was unaffected after selective hippocampal lesions in monkeys (Malkova and Mishkin, J Neurosci 2003; 23:1956-1965). A potentially important methodological difference between the two studies is that the patients were required to remember a set of 20 object-place associations for several minutes, whereas the monkeys had to remember only two such associations at a time, and only for a few seconds. To approximate more closely the task given to the patients, we trained monkeys on several successive sets of 10 object-place pairs each, with each set requiring learning across days. Despite the increased associative memory demands, monkeys given hippocampal lesions were unimpaired relative to their unoperated controls, suggesting that differences other than set size and memory duration underlie the different outcomes in the human and animal studies. (c) 2005 Wiley-Liss, Inc.(inverted iota) C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. RP Mishkin, M (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,MSC 4400,49 Convent Dr, Bethesda, MD 20892 USA. EM mishkinm@mail.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [KO2 HD42269] NR 28 TC 9 Z9 9 U1 0 U2 1 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 2006 VL 16 IS 4 BP 361 EP 367 DI 10.1002/hipo.20147 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 032XT UT WOS:000236810600002 PM 16358315 ER PT J AU Saksida, LM Bussey, TJ Buckmaster, CA Murray, EA AF Saksida, LM Bussey, TJ Buckmaster, CA Murray, EA TI No effect of hippocampal lesions on perirhinal cortex-dependent feature-ambiguous visual discriminations SO HIPPOCAMPUS LA English DT Article DE medial temporal lobe; discrimination learning; object recognition; inferotemporal cortex; ventral visual stream; rhesus monkey ID MEDIAL TEMPORAL-LOBE; OBJECT-RECOGNITION MEMORY; SPATIAL MEMORY; FORNIX TRANSECTION; EPISODIC MEMORY; PARAHIPPOCAMPAL CORTEX; NEUROTOXIC LESIONS; POSTRHINAL CORTEX; LOCATION MEMORY; RHESUS-MONKEYS AB Previous studies have shown that perirhinal cortex lesions in monkeys impair visual discriminations with a high degree of "feature ambiguity," a property of visual discriminations that can emerge when features are a part of both rewarded and unrewarded stimuli. The effects of damage to the hippocampus on these perirhinal-dependent feature-ambiguous tasks are, however, unknown. Prominent theories of medial temporal lobe function predict similar effects of perirhinal cortex and hippocampal lesions on cognitive tasks. In contrast, our hypothesis is that perirhinal cortex, and not the hippocampus, is important for nonspatial complex feature-ambiguous discriminations. We sought to distinguish between these competing theories in a straightforward way, by testing rhesus monkeys with hippocampal lesions on the same feature-ambiguous tasks shown previously to depend on perirhinal cortex. It was found that hippocampal lesions had no effects on any of these tasks. The findings support the perceptual-mnemonic/feature conjunction model of perirhinal cortex function, and provide further evidence for heterogeneity of function within the putative medial temporal lobe memory system. (c) 2006 Wiley-Liss, Inc. C1 Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Saksida, LM (reprint author), Univ Cambridge, Dept Expt Psychol, Downing St, Cambridge CB2 3EB, England. EM lms42@cam.ac.uk RI Bussey, Timothy/M-2758-2016; Saksida, Lisa/M-2753-2016; OI Bussey, Timothy/0000-0001-7518-4041; Saksida, Lisa/0000-0002-8416-8171; Murray, Elisabeth/0000-0003-1450-1642 FU Medical Research Council [G0001354] NR 52 TC 41 Z9 42 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2006 VL 16 IS 4 BP 421 EP 430 DI 10.1002/hipo.20170 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 032XT UT WOS:000236810600007 PM 16463387 ER PT J AU Hussain, RJ Sturnpo, DJ Blackshear, PJ Lenox, RH Abel, T McNamara, RK AF Hussain, RJ Sturnpo, DJ Blackshear, PJ Lenox, RH Abel, T McNamara, RK TI Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation SO HIPPOCAMPUS LA English DT Article DE MARCKS; protein kinase C; mossy fibers; Schaffer collateral; filamentous actin; hippo- campus; LTP; paired-pulse facilitation; post-tetanic potentiation; synaptic plasticity ID FILAMENT CROSS-LINKING; RAT-BRAIN; NEUROTRANSMITTER RELEASE; SYNAPTIC PLASTICITY; ACTIN CYTOSKELETON; DENDRITIC SPINES; EXCITATORY SYNAPSES; PLASMA-MEMBRANE; GENE-EXPRESSION; PHORBOL ESTERS AB The myristoylated alanine-rich C kinase substrate (MARCKS) is a primary protein kinase C (PKC) substrate in brain thought to transduce PKC signaling into alterations in the filamentous (F) actin cytoskeleton. Within the adult hippocampus, MARCKS is highly expressed in the dentate gyrus (DG)-CA3 mossy fiber pathway, but is expressed at low levels in the CA3-CA1 Schaffer collateral-CA1 pathway. We have previously demonstrated that 50% reductions in MARCKS expression in heterozygous Marcks mutant mice produce robust deficits in spatial reversal learning, but not contextual fear conditioning, suggesting that only specific aspects of hippocampal function are impaired by reduction in MARCKS expression. To further elucidate the role of MARCKS in hippocampal synaptic plasticity, in the present study we examined basal synaptic transmission, paired-pulse facilitation, post-tetanic potentiation, and long-term potentiation (LTP) in the hippocampal mossy fiber-CA3 and Schaffer collateral-CA1 pathways of heterozygous Marcks mutant and wild-type mice. We found that LTP is significantly impaired in the mossy fiber-CA3 pathway, but not in the Schaffer collateral-CA1 pathway, in heterozygous Marcks mutant mice, whereas basal synaptic transmission, paired-pulse facilitation, and post-tetanic potentiation are unaffected in both pathways. These findings indicate that a 50% reduction in MARCKS expression impairs processes required for long-term, but not short-term synaptic plasticity in the mossy fiber-CA3 pathway. The implications of these findings for the role of the mossy fiber-CA3 pathway in hippocampus-dependent learning processes are discussed. (c) 2006 Wiley-Liss Inc. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Univ Penn, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. RP McNamara, RK (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 231 Albert Sabin Way,Med Sci Bldg, Cincinnati, OH 45267 USA. EM robert.mcnamara@psychiatry.uc.edu RI McNamara, Robert/J-4309-2014 FU NIA NIH HHS [R01 AG18199]; NICHD NIH HHS [HD26979, P30 HD026979]; NIMH NIH HHS [R01 MH060244-06A1, R01 MH59959, R01 MH060244, R01 MH60244] NR 89 TC 23 Z9 23 U1 0 U2 1 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 2006 VL 16 IS 5 BP 495 EP 503 DI 10.1002/hipo.20177 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 041BV UT WOS:000237428900009 PM 16572394 ER PT J AU Eastwood, SL Weickert, CS Webster, MJ Herman, MM Kleinman, JE Harrison, PJ AF Eastwood, Sharon L. Weickert, Cyndi Shannon Webster, Maree J. Herman, Mary M. Kleinman, Joel E. Harrison, Paul J. TI Synaptophysin protein and mRNA expression in the human hippocampal formation from birth to old age SO HIPPOCAMPUS LA English DT Review DE hippocampus; human brain; maturation; synaptic protein; synaptogenesis ID MEDIAL TEMPORAL-LOBE; CEREBRAL-CORTEX; DENTATE GYRUS; HUMAN BRAIN; SYNAPTIC PLASTICITY; GENE-EXPRESSION; PRESYNAPTIC PROTEINS; PREFRONTAL CORTEX; VISUAL-CORTEX; DIFFERENTIAL EXPRESSION AB In the human neocortex, progressive synaptogenesis in early postnatal life is followed by a decline in synaptic density, then stability from adolescence until middle age. No comparable data are available in the hippocampus. In this study, the integral synaptic vesicle protein synaptophysin, measured immuroautoradiographically, was used as an index of synaptic terminal abundance in the hippocampal formation of 37 subjects from 5 weeks to 86 yr old, divided into 4 age groups (10 infants, 15 adolescents/young adults, 6 adults, and 6 elderly). In all hippocampal subfields, synaptophysin was lowest in infancy, but did not differ significantly between the older age groups, except in dentate gyrus (DG) where the rise was delayed until adulthood. A similar developmental profile was found in the rat hippocampus. We also measured synaptophysin mRNA in the human subjects and found no age-related changes, except in parahippocampal gyrus wherein the mRNA declined from infancy to adolescence, and again in old age. The synaptophysin protein data demonstrate a significant presynaptic component to human postnatal hippocampal development. In so far as synaptophysin abundance reflects synaptic density, the findings support an increase in hippocampal and parahippocampal synapse formation during early childhood, but provide no evidence for adolescent synaptic pruning. The mRNA data indicate that the maturational increases in synaptophysin protein are either translational rather than transcriptional in origin, or else are secondary to mRNA increases in neurons, the cell bodies of which lie outside the hippocampal formation. Published 2006 Wiley-Liss, Inc. C1 Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Stanley Lab Brain Res, Bethesda, MD 20814 USA. RP Harrison, PJ (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Neurosci Bldg,, Oxford OX3 7JX, England. EM paul.harrison@psych.ox.ac.uk RI Shannon Weickert, Cynthia/G-3171-2011 NR 103 TC 22 Z9 24 U1 2 U2 5 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 2006 VL 16 IS 8 BP 645 EP 654 DI 10.1002/hipo.20194 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 074YG UT WOS:000239847900003 PM 16807900 ER PT J AU Gogtay, N Nugent, TF Herman, DH Ordonez, A Greenstein, D Hayashi, KM Clasen, L Toga, AW Giedd, JN Rapoport, JL Thompson, PM AF Gogtay, Nitin Nugent, Tom F., III Herman, David H. Ordonez, Anna Greenstein, Deanna Hayashi, Kiralee M. Clasen, Liv Toga, Arthur W. Giedd, Jay N. Rapoport, Judith L. Thompson, Paul M. TI Dynamic mapping of normal human hippocampal development SO HIPPOCAMPUS LA English DT Article DE hippocampus; subregions; hippocampal mapping technique; MRI; developmental trajectories ID MEDIAL TEMPORAL-LOBE; MILD COGNITIVE IMPAIRMENT; RHESUS-MONKEY; FUNCTIONAL-DIFFERENTIATION; ALZHEIMERS-DISEASE; DORSAL HIPPOCAMPUS; NOVELTY DETECTION; MACAQUE MONKEY; TAXI DRIVERS; MEMORY AB The hippocampus, which plays an important role in memory functions and emotional responses, has distinct subregions subserving different functions. Because the volume and shape of the hippocampus are altered in many neuropsychiatric disorders, it is important to understand the trajectory of normal hippocampal development. We present the first dynamic maps to reveal the anatomical sequence of normal human hippocampal development. A novel hippocampal mapping technique was applied to a database of prospectively obtained brain magnetic resonance imaging (MRI) scans (100 scans in 31 children and adolescents), scanned every 2 yr for, 6-10 yr between ages 4 and 25. Our results establish that the structural development of the human hippocampus is remarkably heterogeneous, with significant differences between posterior (increase over time) and anterior (loss over time) subregions. These distinct developmental trajectories of hippocampal subregions may parallel differences in their functional development. Published 2006 Wiley-Liss, Inc. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90024 USA. RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Rm 3N 202, Bethesda, MD 20892 USA. EM gogtayn@intra.nimh.nih.gov RI Gogtay, Nitin/A-3035-2008; 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 FU NCRR NIH HHS [P41 RR13642, R21 RR019771, U54 RR021813]; NIA NIH HHS [P50 AG016570]; NIBIB NIH HHS [R21 EB01651]; NIMH NIH HHS [R25 MH060482] NR 68 TC 181 Z9 184 U1 1 U2 27 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 2006 VL 16 IS 8 BP 664 EP 672 DI 10.1002/hipo.20193 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 074YG UT WOS:000239847900005 PM 16826559 ER PT J AU Stavreva, DA McNally, JG AF Stavreva, DA McNally, JG TI Role of H1 phosphorylation in rapid GR exchange and function at the MMTV promoter SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article DE glucocorticoid receptor; FRAP; transcription; regulation; chromatin ID GLUCOCORTICOID-RECEPTOR; LIVING CELLS; HISTONE H1; CHROMATIN-STRUCTURE; NUCLEAR RECEPTORS; MOLECULAR CHAPERONES; NATURAL PROMOTER; TRANSCRIPTION; TRAFFICKING; COMPLEXES AB Photobleaching technology has demonstrated in live cells that the glucocorticoid receptor (GR) exchanges rapidly at the mouse mammary tumor virus (MMTV) promoter. GR rapid exchange at MMTV depends on chaperone and proteasome activity, and as suggested by several in vitro and in vivo biochemical approaches, may also involve chromatin remodeling activity. Inhibition of H1 phosphorylation, chromatin remodeling and transcription from MMTV can be accomplished by long-term blocking of Cdk2 protein kinase activity. We find that Cdk2 is recruited by a tandem array of MMTV promoters, strengthening the model that this kinase has a specific role in MMTV transcription. We also demonstrate that following a brief Cdk2 inhibition by a selective cyclin-dependent kinase inhibitor (Roscovitine), transcription from MMTV drops and GR exchange at MMTV becomes slower, with a fraction of GR molecules now tightly bound at the promoter. This immobile fraction is absent elsewhere in the nucleus, suggesting a specific effect of Cdk2 inhibition on GR-MMTV interactions. These are the first live cell data suggesting a role for H1 phosphorylation, and by implication chromatin remodeling, in rapid exchange of GR at MMTV. C1 NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bldg 41,Room B516, Bethesda, MD 20892 USA. EM mcnallyj@exchange.nih.gov FU Intramural NIH HHS NR 25 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD JAN PY 2006 VL 125 IS 1-2 BP 83 EP 89 DI 10.1007/s00418-005-0086-9 PG 7 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 000JA UT WOS:000234456300009 PM 16397795 ER PT J AU Berman, DM AF Berman, DM TI Lack of agreement on predictors for metastasizing thin melanomas SO HISTOPATHOLOGY LA English DT Letter ID CUTANEOUS MALIGNANT-MELANOMA; AMERICAN JOINT COMMITTEE; 30-YEAR CLINICAL-EXPERIENCE; PROPOSED STAGING SYSTEM; VERTICAL GROWTH-PHASE; PROGNOSTIC-FACTORS; LETHAL CHARACTERISTICS; BIOLOGIC BEHAVIOR; NODE METASTASIS; SENTINEL NODE C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Berman, DM (reprint author), NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. NR 32 TC 4 Z9 4 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD JAN PY 2006 VL 48 IS 2 BP 217 EP 219 DI 10.1111/j.1365-2559.2005.02215.x PG 4 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 995GD UT WOS:000234087900019 PM 16405679 ER PT J AU Cantor, D AF Cantor, David BE Doel, RE Soderqvist, T TI The politics of commissioned histories (revisited) SO HISTORIOGRAPHY OF CONTEMPORARY SCIENCE, TECHNOLOGY, AND MEDICINE: WRITING RECENT SCIENCE SE Routledge Studies in the History of Science Technology and Medicine LA English DT Editorial Material; Book Chapter ID PHARMACEUTICAL-INDUSTRY; PHYSICIANS BEHAVIOR; MEDICAL HISTORIANS; COMMERCIAL SOURCES; TOBACCO INDUSTRY; DRUG C1 [Cantor, David] NCI, Bethesda, MD 20892 USA. [Cantor, David] Natl Lib Med, Hist Med Div, Bethesda, MD USA. RP Cantor, D (reprint author), NCI, Bethesda, MD 20892 USA. NR 89 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-32388-5 J9 ROUTL ST HIST SCI TE PY 2006 VL 23 BP 45 EP 66 PG 22 WC History & Philosophy Of Science SC History & Philosophy of Science GA BNA83 UT WOS:000274041500004 ER PT J AU Livadas, S Bourhis, J Voutetakis, A Xekouki, P Voutetakis, CD AF Livadas, Sarantis Bourhis, Jean Voutetakis, Antonis Xekouki, Paraskevi Voutetakis, Catherine Dacou TI Acute lymphoblastic leukemia (ALL) and bone marrow transplantation (BMT): hyperinsulinemia after graft versus host reaction (GvHR), improved by metformin SO HORMONE RESEARCH LA English DT Meeting Abstract C1 Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. Inst Gustave Roussy, Hematol Clin, Paris, France. NIDCR, NIH, GTTB, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2006 VL 65 SU 4 BP 125 EP 126 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071UY UT WOS:000239630600434 ER PT J AU Argall, BD Saad, ZS Beauchamp, MS AF Argall, BD Saad, ZS Beauchamp, MS TI Simplified intersubject averaging on the cortical surface using SUMA SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; group analysis; AC-PC surface averaging; SUMA software; surface model; intersubject averaging ID HUMAN CEREBRAL-CORTEX; COORDINATE SYSTEM; REGISTRATION; MRI; BRAIN; RECONSTRUCTION; IDENTIFICATION; VISUALIZATION; SEGMENTATION; LOCALIZATION AB Task and group comparisons in functional magnetic resonance imaging (fMRI) studies are often accomplished through the creation of intersubject average activation maps. Compared with traditional volume-based intersubject averages, averages made using computational models of the cortical surface have the potential to increase statistical power because they reduce intersubject variability in cortical folding patterns. We describe a two-step method for creating intersubject surface averages. In the first step cortical surface models are created for each subject and the locations of the anterior and posterior commissures (AC and PC) are aligned. In the second step each surface is standardized to contain the same number of nodes with identical indexing. An anatomical average from 28 subjects created using the AC-PC technique showed greater sulcal and gyral definition than the corresponding volume-based. average. When applied to an fMRI dataset, the AC-PC method produced greater maximum, median, and mean t-statistics in the average activation map than did the volume average and gave a better approximation to the theoretical-ideal average calculated from individual subjects. The AC-PC method produced average activation maps equivalent to those produced with surface-averaging methods that use high-dimensional morphing. In comparison with morphing methods, the AC-PC technique does not require selection of a template brain and does not introduce deformations of sulcal and gyral patterns, allowing for group analysis within the original folded topology of each individual subject. The tools for performing AC-PC surface averaging are implemented and freely available in the SUMA software package. C1 Univ Texas, Hlth Sci Ctr, Dept Neurobiol & Anat, Houston, TX 77030 USA. Carnegie Mellon Univ, Grad Program, Inst Robot, Pittsburgh, PA 15213 USA. NIMH, Intramural Res Program, Lab Brain & Cognit, Bethesda, MD 20892 USA. NIMH, Intramural Res Program, Sci & Stat Comp Core, Bethesda, MD 20892 USA. RP Beauchamp, MS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Neurobiol & Anat, 6431, Houston, TX 77030 USA. EM Michael.S.Beauchamp@uth.tmc.edu RI Argall, Brenna/G-2543-2011; OI Beauchamp, Michael/0000-0002-7599-9934 FU Intramural NIH HHS NR 39 TC 98 Z9 98 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2006 VL 27 IS 1 BP 14 EP 27 DI 10.1002/hbm.20158 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 001RJ UT WOS:000234553700002 PM 16035046 ER PT J AU Feinendegen, LE Neumann, RD AF Feinendegen, LE Neumann, RD TI The issue of risk in complex adaptive systems: the case of low-dose radiation induced cancer SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE complex adaptive systems; radiation risk; low-dose effects; adaptive responses; radiation damage vs. hormesis ID PROTECTIVE RESPONSES; CELLULAR-RESPONSES; CARCINOGENESIS; MECHANISMS; TOXICOLOGY; INDUCTION; HORMESIS; DAMAGE; DNA AB Living systems exist in hierarchical levels of biological organization, ascending from the basic atomic-molecular level, to the cellular level, the tissue-organ level, and the whole organism. All levels and elements at each level communicate with each other though intricate intra- and intercellular signaling through many specified molecular interactions. These regulate homeostasis between the system levels and their individual elements. The probability of a defined effect at the basic atomic-molecular level per impact increment of a toxic agent, such as ionizing radiation, at that level appears constant at low doses, even if the probability constant may change as a consequence of a previous exposure. Thus, at a given state of the system, the incidence of effect at the atomic-molecular level increases linearly with the number of impact increments in terms of energy deposition events. Primary effects may amplify to damage and there are immediate attempts at repairing the damage from an effect. Amplification and propagation of damage at, and from, the basic to higher levels of biological organization meets resistance, the degree of which per impact increment is not constant. It changes with the number of impact increments. This resistance encompasses both physicochemical and biochemical reactions. The corresponding biochemical reactions express the physiological system's capacity to respond to perturbations of homeostasis at and between the various levels. Types and degrees of these responses depend on the system and the degree of homeostatic perturbation. At relatively mild to moderate degrees of perturbation, protective responses appear with a delay of hours and may last for months, shield also against endogenous non-radiogenic damage, and in doing so may prevail over radiogenic damage. With increasing degrees of homeostatic perturbation, damage eventually overwhelms adaptive protection. Thus, systems do not respond in a linear function of impact increments at the lowest level of biological organization. For assessing the probability of radiation damage per absorbed dose, i.e., risk, in complex adaptive systems, both damaging and protecting responses need attention, and to exclude one for the other is scientifically unjustified and misleading. C1 Univ Dusseldorf, D-4000 Dusseldorf, Germany. Brookhaven Natl Lab, Upton, NY 11973 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Feinendegen, LE (reprint author), Univ Dusseldorf, D-4000 Dusseldorf, Germany. EM feinendegen@gmx.net NR 24 TC 6 Z9 6 U1 1 U2 2 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0960-3271 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD JAN PY 2006 VL 25 IS 1 BP 11 EP 17 DI 10.1191/096327106ht579oa PG 7 WC Toxicology SC Toxicology GA 007NU UT WOS:000234977200004 PM 16459709 ER PT J AU Naik, AM Chalikonda, S McCart, JA Xu, H Guo, ZS Langham, G Gardner, D Mocellin, S Lokshin, AE Moss, B Alexander, HR Bartlett, DL AF Naik, AM Chalikonda, S McCart, JA Xu, H Guo, ZS Langham, G Gardner, D Mocellin, S Lokshin, AE Moss, B Alexander, HR Bartlett, DL TI Intravenous and isolated limb perfusion delivery of wild type and a tumor-selective replicating mutant vaccinia virus in nonhuman primates SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; THYMIDINE KINASE; SOLID TUMORS; CANCER; ADENOVIRUS; NECROSUM; THERAPY; VECTOR; HYPERTHERMIA; METASTASES AB In this study we examine the safety, feasibility, and biodistribution of a tumor-selective mutant vaccinia ( vvDD) and wild-type WR ( vF13) vaccinia after delivery via intradermal or intravenous infection or isolated limb perfusion ( ILP) in rhesus macaques. By intradermal inoculation, 10(6) PFU of vvDD caused a minimal skin reaction whereas vF13 caused marked erythema and necrosis with a peak indurated area of 108 cm(2). By intravenous delivery, vvDD caused no clinical symptoms of viremia and no viral recovery from tissues, serum, saliva, urine, or feces. In contrast, vF13 caused symptoms of lethargy, anorexia, fever, and signs of viremia. Delivery of vF13 via ILP resulted in numerous cutaneous pox lesions localized solely to the perfused limb with high viral recovery in the perfused skin and muscle. ILP with vvDD resulted in no visible pox lesions and no clinical signs or symptoms of viremia. No long-term toxicity was identified after ILP with 10(9) PFU of vvDD, and no virus was recovered from any tissue, serum, saliva, urine, or fecal sample. These results suggest that vvDD appears to be safe in primates, and thus vvDD should be further investigated for clinical trial in human cancer patients. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA. Univ Pittsburgh, Dept Surg, Sch Med, Pittsburgh, PA 15232 USA. NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Div Anim Sci, Bethesda, MD 20892 USA. NIAID, Rocky Mt Labs, Rocky Mt Vet Branch, NIH, Hamilton, MT 59840 USA. Univ Pittsburgh, Div Hematol Oncol, Inst Canc, Pittsburgh, PA 15213 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), Univ Pittsburgh, Inst Canc, Canc Pavil,Room 460 5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM bartlettdl@upmc.edu NR 27 TC 21 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2006 VL 17 IS 1 BP 31 EP 45 DI 10.1089/hum.2006.17.31 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 003YY UT WOS:000234720400004 PM 16409123 ER PT J AU Witherspoon, DJ Marchani, EE Watkins, WS Ostler, CT Wooding, SP Anders, BA Fowlkes, JD Boissinot, S Furano, AV Ray, DA Rogers, AR Batzer, MA Jorde, LB AF Witherspoon, D. J. Marchani, E. E. Watkins, W. S. Ostler, C. T. Wooding, S. P. Anders, B. A. Fowlkes, J. D. Boissinot, S. Furano, A. V. Ray, D. A. Rogers, A. R. Batzer, M. A. Jorde, L. B. TI Human population genetic structure and diversity inferred from polymorphic L1 (LINE-1) and Alu insertions SO HUMAN HEREDITY LA English DT Article DE genetics/population genetics; evolution; bioinformatics/computational biology ID HUMAN GENOMIC DIVERSITY; INTERSPERSED ELEMENTS SINES; MULTILOCUS GENOTYPE DATA; HUMAN Y-CHROMOSOME; HUMAN-EVOLUTION; MOLECULAR SYSTEMATICS; AFRICAN POPULATIONS; WORLD POPULATIONS; HUMAN ORIGINS; PATTERNS AB Background/Aims: The L1 retrotransposable element family is the most successful self-replicating genomic parasite of the human genome. L1 elements drive replication of Alu elements, and both have had far-reaching impacts on the human genome. We use L1 and Alu insertion polymorphisms to analyze human population structure. Methods: We genotyped 75 recent, polymorphic L1 insertions in 317 individuals from 21 populations in sub-Saharan Africa, East Asia, Europe and the Indian subcontinent. This is the first sample of L1 loci large enough to support detailed population genetic inference. We analyzed these data in parallel with a set of 100 polymorphic Alu insertion loci previously genotyped in the same individuals. Results and Conclusion: The data sets yield congruent results that support the recent African origin model of human ancestry. A genetic clustering algorithm detects clusters of individuals corresponding to continental regions. The number of loci sampled is critical: with fewer than 50 typical loci, structure cannot be reliably discerned in these populations. The inclusion of geographically intermediate populations (from India) reduces the distinctness of clustering. Our results indicate that human genetic variation is neither perfectly correlated with geographic distance (purely clinal) nor independent of distance (purely clustered), but a combination of both: stepped clinal. Copyright (c) 2006 S. Karger AG, Basel. C1 Univ Utah, Dept Human Genet, Eccles Inst Human Genet, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD USA. Queens Coll, Dept Biol, Flushing, NY USA. Univ Utah, Dept Anthropol, Salt Lake City, UT 84112 USA. RP Witherspoon, DJ (reprint author), Univ Utah, Dept Human Genet, Eccles Inst Human Genet, Hlth Sci Ctr, 15 N 2030 E,Room 7225, Salt Lake City, UT 84112 USA. EM david.witherspoon@utah.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM-59290] NR 92 TC 43 Z9 45 U1 0 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2006 VL 62 IS 1 BP 30 EP 46 DI 10.1159/000095851 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 097OS UT WOS:000241458300004 PM 17003565 ER PT J AU Mathias, RA Hening, W Washburn, M Allen, RP Lesage, S Wilson, AF Earley, CJ AF Mathias, Rasika A. Hening, Wayne Washburn, Mystinna Allen, Richard P. Lesage, Suzanne Wilson, Alexander F. Earley, Christopher J. TI Segregation analysis of restless legs syndrome: Possible evidence for a major gene in a family study using blinded diagnoses SO HUMAN HEREDITY LA English DT Article DE restless legs syndrome; segregation analysis; blinded diagnosis ID SUSCEPTIBILITY LOCUS; PRIMARY-CARE; BRAIN IRON; POPULATION; PREVALENCE; SYMPTOMS; EPIDEMIOLOGY; CRITERIA; DISEASE; IDENTIFICATION AB Objective: The objective of this study was to ascertain the most likely inheritance pattern of restless legs syndrome (RLS) using segregation analysis. Methods: Probands were RLS patients presenting to the Neurology and Sleep clinics of the Johns-Hopkins Bayview medical center with willing first and second degree relatives. Blinded diagnosis was made in those who exhibited the four diagnostic features of RLS. Analysis was performed on RLS as a dichotomous trait and considering age of onset models on 590 phenotyped subjects from 77 pedigrees. Results: All non-genetic models were rejected considering RLS as a dichotomous trait. A single locus Mendelian dominant model with gender as a covariate had best fit with allele frequency of 0.077 and complete penetrance. RLS frequency in non-carrier subjects was estimated to be 0.14. Two underlying distributions of age of onset, with a possible dichotomy at 26.3 years, were identified. Contrary to the results for RLS as a dichotomous trait, age of onset models did not indicate single major gene inheritance. Conclusion: This segregation analysis suggests that the pattern of segregation is consistent with that of a single major locus, when RLS is treated as a dichotomous trait without considering age of onset. The high rate of phenocopies matches known population frequencies and taken with significant residual familial effects and the lack of evidence for a major gene controlling age of onset, indicates that non-genetic causes of RLS may exist and RLS is a complex disorder. Copyright (c) 2006 S. Karger AG, Basel. C1 NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. Johns Hopkins Univ, Div Clin Immunol, RLS Ctr, Johns Hopkins Asthma & Allergy Ctr,Dept Neurol, Baltimore, MD 21224 USA. RP Earley, CJ (reprint author), Johns Hopkins Univ, Div Clin Immunol, RLS Ctr, Johns Hopkins Asthma & Allergy Ctr,Dept Neurol, 5501 Hopkins Bayview Circle,Room 1B82, Baltimore, MD 21224 USA. EM cearley@jhmi.edu RI Wilson, Alexander/C-2320-2009 FU Intramural NIH HHS; NCRR NIH HHS [M01-RR02719, RR03655]; NIA NIH HHS [R01-AG16362] NR 47 TC 17 Z9 18 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2006 VL 62 IS 3 BP 157 EP 164 DI 10.1159/000096443 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 099SC UT WOS:000241614800004 PM 17063029 ER PT S AU Soldan, SS Goodman, AD Jacobson, S AF Soldan, Samantha S. Goodman, Andrew D. Jacobson, Steven BE Krueger, G Ablashi, D TI HHV-6 and the Central Nervous System SO HUMAN HERPESVIRUS-6: GENERAL VIROLOGY, EPIDEMIOLOGY AND CLINICAL PATHOLOGY, 2ND EDITION SE Perspectives in Medical Virology LA English DT Article; Book Chapter ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HUMAN-HERPESVIRUS 6; MULTIPLE-SCLEROSIS PATIENTS; MEMBRANE COFACTOR PROTEIN; MYELIN BASIC-PROTEIN; JC VIRUS; FEBRILE CONVULSIONS; HUMAN POLYOMAVIRUS; CELLULAR RECEPTOR; CROSS-REACTIVITY C1 [Soldan, Samantha S.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Goodman, Andrew D.] Univ Rochester, Dept Neurol, Rochester, NY 14642 USA. [Jacobson, Steven] NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Soldan, SS (reprint author), Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. NR 70 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-7069 BN 978-0-08-046128-1 J9 PERSP MED V JI Perspect. Med. Virol. PY 2006 VL 12 BP 213 EP 223 DI 10.1016/S0168-7069(06)12016-9 PG 11 WC Virology SC Virology GA BCS09 UT WOS:000311238200019 ER PT J AU Caggiari, L Simula, MP Marzotto, A Shiina, M Rehermann, B De Re, V AF Caggiari, L Simula, MP Marzotto, A Shiina, M Rehermann, B De Re, V TI Identification of novel chimpanzee MHC class I and II alleles using an improved sequence-based typing strategy SO HUMAN IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CELLS AB The chimpanzee (Pan troglodytes) is a valuable model for the study of infection with hepatitis C virus and hepatitis B virus, to which only humans and chimpanzees are Susceptible. Because the cellular immune response plays a crucial role in host defense against these viruses, the analysis of major histocompatibility complex (iMHC) (Patr) class I and II allele diversity in chimpanzees is essential for immune response analysis and vaccine development. In the present study, we report a novel, rapid, and sensitive sequence-based typing strategy to identify polymorphisms of the principal Patr class I (Patr-A and Patr-B) and Patr class II (Patr-DQB1 and Patr-DRB1) alleles. Using this method we identified seven novel Patr alleles in 17 chimpanzees, one of them present in 3 chimpanzees. Furthermore, we detected heterozygosity more rapidly and with higher sensitivity than was done with previous techniques that were based on reverse transcription and amplification of messenger RNA followed by molecular cloning and sequencing. C1 IRCCS, Div Expt Oncol 1, Dept Preclin & Epidemiol Res, Ctr Riferimento Oncol,Natl Ctr Inst, I-33081 Aviano, Italy. NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. RP De Re, V (reprint author), IRCCS, Div Expt Oncol 1, Dept Preclin & Epidemiol Res, Ctr Riferimento Oncol,Natl Ctr Inst, Via Pedemontana Occidentale 12, I-33081 Aviano, Italy. EM vdere@cro.it FU Intramural NIH HHS NR 17 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JAN-FEB PY 2006 VL 67 IS 1-2 BP 63 EP 72 DI 10.1016/j.humimm.2006.02.004 PG 10 WC Immunology SC Immunology GA 049AK UT WOS:000237987500009 PM 16698427 ER PT S AU Poulain, M Pes, GM Carru, C Ferrucci, L Baggio, G Franceschi, C Deiana, L AF Poulain, Michel Pes, Giovanni Mario Carru, Ciriaco Ferrucci, Luigi Baggio, Giovannella Franceschi, Claudio Deiana, Luca BE Robine, JM Crimmins, EM Horiuchi, S Yi, Z TI THE VALIDATION OF EXCEPTIONAL MALE LONGEVITY IN SARDINIA SO HUMAN LONGEVITY, INDIVIDUAL LIFE DURATION, AND THE GROWTH OF THE OLDEST-OLD POPULATION SE International Studies in Population LA English DT Article; Book Chapter ID EXTREME LONGEVITY; CENTENARIANS; MORTALITY; RATIO C1 [Poulain, Michel] Univ Catholique Louvain, FNRS GeDAP, Grp Etud Demog Appl, B-1348 Louvain, Belgium. [Pes, Giovanni Mario; Carru, Ciriaco; Deiana, Luca] Univ Sassari, Inst Clin Biochem, I-07100 Sassari, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Ferrucci, Luigi] INRCA, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. [Baggio, Giovannella] Univ Padua, Azienda Osped, Inst Internal Med, I-35100 Padua, Italy. [Franceschi, Claudio] Univ Bologna, Dept Expt Pathol, I-40126 Bologna, Italy. [Franceschi, Claudio] INRCA, Dept Gerontol Res, Ancona, Italy. RP Poulain, M (reprint author), Univ Catholique Louvain, FNRS GeDAP, Grp Etud Demog Appl, B-1348 Louvain, Belgium. NR 15 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-0395 BN 978-1-4020-4848-7 J9 INT STUD POPUL PY 2006 VL 4 BP 147 EP 166 D2 10.1007/978-1-4020-4848-7 PG 20 WC Demography; Gerontology; Public, Environmental & Occupational Health SC Demography; Geriatrics & Gerontology; Public, Environmental & Occupational Health GA BLK45 UT WOS:000270364100010 ER PT J AU Zhang, J Barrion, C Stark, S Garrett, A Weinberg, C Williams, M Chanock, S AF Zhang, J. Barrion, C. Stark, S. Garrett, A. Weinberg, C. Williams, M. Chanock, S. TI Conducting a familial genetic epidemiologic study. SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 NICHD, Epidemiol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2006 VL 25 SU 1 BP 87 EP 87 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 062KK UT WOS:000238942800129 ER PT S AU Gladwin, MT AF Gladwin, Mark T. BE Roach, RC Wagner, PD Hackett, PH TI Role of the red blood cell in nitric oxide homeostasis and hypoxic vasodilation SO HYPOXIA AND EXERCISE SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 14th International Hypoxia Symposium CY FEB 23-27, 2005 CL Lake Louise, CANADA DE SNO-Hb; hemoglobin; vasodilation; nitrite; nitric oxide; hemolysis; arginase ID ENDOTHELIUM-DEPENDENT RELAXATION; GUANYLATE-CYCLASE ACTIVATION; S-NITROSOHEMOGLOBIN; RELAXING FACTOR; PHYSIOLOGICAL CONDITIONS; XANTHINE OXIDOREDUCTASE; HEMOGLOBIN DERIVATIVES; PULMONARY-HYPERTENSION; VASCULAR INSTABILITY; BIOLOGICAL-ACTIVITY AB Nitric oxide (NO) regulates normal vasomotor tone and modulates important homeostatic functions such as thrombosis, cellular proliferation, and adhesion molecule expression. Recent data implicate a critical function for hemoglobin and the erythrocyte in regulating the bioavailability of NO in the vascular compartment. Under normoxic conditions the erythrocytic hemoglobin scavenges NO and produces a vasopressor effect that is limited by diffusional barriers along the endothelium and in the unstirred layer around the erythrocyte. In hemolytic diseases, intravascular hemolysis releases hemoglobin from the red blood cell into plasma (decompartmentalizes the hemoglobin), which is then able to scavenge endothelial derived NO 600-fold faster than erythrocytic hemoglobin, thereby dysregulating NO homoestasis. In addition to releasing plasma hemoglobin, the red cell contains arginase which when released into plasma further dysregulates arginine metabolism. These data support the existence of a novel mechanism of human disease, hemolysis associated endothelial dysfunction, that potentially participates in the vasculopathy of iatrogenic and hereditary hemolytic conditions. In addition to providing an NO scavenging role in the physiological regulation of NO-dependent vasodilation, hemoglobin and the erythrocyte may deliver NO as the hemoglobin deoxygenates. Two mechanisms have been proposed to explain this principle: 1) Oxygen linked allosteric delivery of S-nitrosothiols from S-nitrosated hemoglobin (SNO-Hb), and 2) a nitrite reductase activity of deoxygenated hemoglobin that reduces nitrite to NO and vasodilates the human circulation along the physiological oxygen gradient. The later newly described role of hemoglobin as a nitrite reductase is discussed in the context of hypoxic vasodilation, blood flow regulation and oxygen sensing. C1 NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mgladwin@mail.nih.gov NR 97 TC 34 Z9 35 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-387-34816-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 588 BP 189 EP 205 PG 17 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA BFF93 UT WOS:000241637100017 PM 17089890 ER PT B AU Azuaje, F Wang, HY Zheng, HR Bodenreider, O Chesneau, A AF Azuaje, Francisco Wang, Haiying Zheng, Huiru Bodenreider, Olivier Chesneau, Alban BE Tsumoto, S Clifton, CW Zhong, N Wu, XD Liu, JM Wah, BW Cheung, YM TI Predictive integration of gene ontology-driven similarity and functional interactions SO ICDM 2006: Sixth IEEE International Conference on Data Mining, Workshops LA English DT Proceedings Paper CT 6th IEEE International Conference on Data Mining CY DEC 18-22, 2006 CL Hong Kong, PEOPLES R CHINA SP IEEE ID EXPRESSION DATA; NETWORKS AB There is a need to develop methods to automatically incorporate prior knowledge to support the prediction and validation of novel functional associations. One such important source is represented by the Gene Ontology (GO)(TM) and the many model organism databases of gene products annotated to the GO. We investigated quantitative relationships between the GO-driven similarity of genes and their functional interactions by analyzing different types of associations in Saccharomyces cerevisiae and Caenorhabditis elegans. Interacting genes exhibited significantly higher levels of GO-driven similarity (GOS) in comparison to random pairs of genes used as a surrogate for negative interactions. The Biological Process hierarchy provides more reliable results for co-regulatory and protein-protein interactions. GOS represent a relevant resource to support prediction of functional networks in combination with other resources. C1 Univ Ulster, Sch Comp & Math, Coleraine BT52 1SA, Londonderry, North Ireland. Natl Lib Med, NIH, Bethesda, MD 20894 USA. EMBL, High Throughtput Prot Technologies Grp, Grenoble, France. RP Azuaje, F (reprint author), Univ Ulster, Sch Comp & Math, Coleraine BT52 1SA, Londonderry, North Ireland. NR 13 TC 0 Z9 0 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-2702-4 PY 2006 BP 114 EP 119 PG 6 WC Computer Science, Information Systems SC Computer Science GA BFZ38 UT WOS:000245603100022 ER PT J AU Madan, RA Arlen, PM AF Madan, RA Arlen, PM TI Abiraterone - Cougar Biotechnology SO IDRUGS LA English DT Article ID HUMAN CYTOCHROME P450(17-ALPHA); METASTATIC PROSTATE-CANCER; STEROIDAL INHIBITORS; IN-VITRO; 17-ALPHA-HYDROXYLASE/C-17,C-20-LYASE; KETOCONAZOLE; LYASE; VIVO AB Abiraterone is an oral, selective, steroidal inhibitor of cytochrome P450(17a) being developed by Cougar Biotechnology Inc for the potential treatment of prostate cancer. Phase I clinical trials of abiraterone have been conducted and the design of phase I/II clinical trials is being finalized. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Madan, RA (reprint author), NCI, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM pa52s@nih.gov NR 26 TC 16 Z9 16 U1 0 U2 2 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1369-7056 J9 IDRUGS JI IDrugs PD JAN PY 2006 VL 9 IS 1 BP 49 EP 55 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 005GN UT WOS:000234810700015 PM 16374734 ER PT J AU Schneider, TD AF Schneider, TD TI Claude Shannon: Biologist SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID BINDING-SITES; INFORMATION ANALYSIS; MOLECULAR MACHINES; MATHEMATICAL-THEORY; CHANNEL CAPACITY; SEQUENCE LOGOS; COMMUNICATION; MUTATIONS C1 NCI, Canc Res Ctr, Nanobiol Program, Mol Informat Theory Grp, Frederick, MD 21702 USA. RP Schneider, TD (reprint author), NCI, Canc Res Ctr, Nanobiol Program, Mol Informat Theory Grp, Frederick, MD 21702 USA. EM toms@ncifcrf.gov OI Schneider, Thomas/0000-0002-9841-1531 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC008396-17] NR 27 TC 7 Z9 8 U1 1 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JAN-FEB PY 2006 VL 25 IS 1 BP 30 EP 33 DI 10.1109/MEMB.2006.1578661 PG 4 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 004MI UT WOS:000234756500011 PM 16485389 ER PT J AU Mohan, A Bartesaghi, A Sapiro, G AF Mohan, A Bartesaghi, A Sapiro, G TI Constrained regularization of digital terrain elevation data SO IEEE GEOSCIENCE AND REMOTE SENSING LETTERS LA English DT Article DE absolute errors; constraints; elevation data; geometricm active surfaces; regularization AB A framework for geometric regularization of elevation maps is introduced in this letter. The framework takes into account errors in the data, which form part of standard elevation maps specifications, as well as possible additional user/application-dependent constraints. The algorithm is based on adapting the theory of geometric active surfaces to the problem of regularizing elevation maps. We present the underlying concepts and numerical experiments showing the effectiveness and potential of this theory. C1 Univ Minnesota, Dept Elect & Comp Engn, Minneapolis, MN 55455 USA. NIH, Bethesda, MD 20892 USA. RP Mohan, A (reprint author), Univ Minnesota, Dept Elect & Comp Engn, Minneapolis, MN 55455 USA. EM guille@ece.umn.edu NR 14 TC 1 Z9 1 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1545-598X J9 IEEE GEOSCI REMOTE S JI IEEE Geosci. Remote Sens. Lett. PD JAN PY 2006 VL 3 IS 1 BP 59 EP 62 DI 10.1109/LGRS.2005.856702 PG 4 WC Geochemistry & Geophysics; Engineering, Electrical & Electronic; Remote Sensing; Imaging Science & Photographic Technology SC Geochemistry & Geophysics; Engineering; Remote Sensing; Imaging Science & Photographic Technology GA 006LJ UT WOS:000234898700013 ER PT J AU Wang, SM Lee, R Teixeira, FL AF Wang, SM Lee, R Teixeira, FL TI Anisotropic-medium PML for vector FETD with modified basis functions SO IEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION LA English DT Article DE basis functions; finite-element methods; numerical stability; perfectly matched layer; reflection coefficient ID PERFECTLY MATCHED LAYER; WAVE-GUIDING STRUCTURES; TIME-DOMAIN SOLUTION; MAXWELLS EQUATIONS; NUMERICAL STABILITY; FDTD; SIMULATIONS; ABSORPTION; TRUNCATION; EVANESCENT AB A novel anisotropic-medium perfectly matched layer (PML) implementation is presented for boundary truncation in the three-dimensional vector finite-element time-domain (FETD) method. This approach utilizes a complex set of vector test and basis functions in the PML region, that recover the usual basis functions in the non-PML region. Numerical examples show that the proposed PML-FETD approach has small reflection errors and no observed late-time instabilities for simulations involving up to 10(6) time Steps. C1 Ohio State Univ, Electrosci Lab, Columbus, OH 43212 USA. Ohio State Univ, Dept Elect & Comp Engn, Columbus, OH 43212 USA. NIH, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP Wang, SM (reprint author), Ohio State Univ, Electrosci Lab, Columbus, OH 43212 USA. EM james.wang@ieee.org; lee@ee.eng.ohio-state.edu; teixeira@ee.eng.ohio-state.edu RI Lee, Robert/A-7632-2008; Teixeira, Fernando/F-9545-2011 OI Teixeira, Fernando/0000-0002-1562-1462 NR 38 TC 18 Z9 18 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-926X J9 IEEE T ANTENN PROPAG JI IEEE Trans. Antennas Propag. PD JAN PY 2006 VL 54 IS 1 BP 20 EP 27 DI 10.1109/TAP.2005.861523 PG 8 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 008CB UT WOS:000235016700003 ER PT J AU Huang, A Nielson, GM Razdan, A Farin, GE Baluch, DP Capco, DG AF Huang, A Nielson, GM Razdan, A Farin, GE Baluch, DP Capco, DG TI Thin structure segmentation and visualization in three-dimensional biomedical images: A shape-based approach SO IEEE TRANSACTIONS ON VISUALIZATION AND COMPUTER GRAPHICS LA English DT Article DE angiography; biomedical image processing; Hessian matrix; image enhancement; laser scanning confocal microscopy; multiscale filtering; segmentation; visualization ID CT COLONOGRAPHY; SURFACES; LINES AB This paper presents a shape-based approach in extracting thin structures, such as lines and sheets, from three-dimensional ( 3D) biomedical images. Of particular interest is the capability to recover cellular structures, such as microtubule spindle fibers and plasma membranes, from laser scanning confocal microscopic (LSCM) data. Hessian-based shape methods are reviewed. A synthesized linear structure is used to evaluate the sensitivity of the multiscale filtering approach in extracting closely positioned fibers. We find that the multiscale approach tends to fuse lines together, which makes it unsuitable for visualizing mouse egg spindle fibers. Single-scale Gaussian filters, balanced between sensitivity and noise resistance, are adopted instead. In addition, through an ellipsoidal Gaussian model, the eigenvalues of the Hessian matrix are quantitatively associated with the standard deviations of the Gaussian model. Existing shape filters are simplified and applied to LSCM data. A significant improvement in extracting closely positioned thin lines is demonstrated by the resultant images. Further, the direct association of shape models and eigenvalues makes the processed images more understandable qualitatively and quantitatively. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Arizona State Univ, Ira A Fulton Sch Engn, Dept Comp Sci & Engn, Tempe, AZ 85287 USA. Arizona State Univ, PRISM, Tempe, AZ 85287 USA. Arizona State Univ, Sch Life Sci, Dept Biol, Tempe, AZ 85287 USA. RP Huang, A (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C671,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. EM hhuang@cc.nih.gov; nielson@asu.edu; razdan@asu.edu; farin@asu.edu; page.baluch@asu.edu; dcapco@asu.edu NR 34 TC 20 Z9 20 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1077-2626 J9 IEEE T VIS COMPUT GR JI IEEE Trans. Vis. Comput. Graph. PD JAN-FEB PY 2006 VL 12 IS 1 BP 93 EP 102 DI 10.1109/TVCG.2006.15 PG 10 WC Computer Science, Software Engineering SC Computer Science GA 981MU UT WOS:000233093500009 PM 16382611 ER PT J AU Bailey, KR Rustay, NR Crawley, JN AF Bailey, KR Rustay, NR Crawley, JN TI Behavioral phenotyping of transgenic and knockout mice: Practical concerns and potential pitfalls SO ILAR JOURNAL LA English DT Article DE background strain; behavior; behavioral test suites; colony housing; general health; learning and memory; mouse; flanking genes ID INBRED MOUSE STRAINS; F-1 HYBRIDS IMPLICATIONS; TRAIT LOCI ANALYSES; ENVIRONMENTAL ENRICHMENT; LABORATORY MICE; ALZHEIMERS-DISEASE; DEFICIENT MICE; 129 SUBSTRAINS; SINGLE-GENE; RESPONSES AB New technologies in molecular genetics have dramatically increased the number of targeted gene mutations available to the biomedical research community. Many mutant mouse lines have been generated to provide animal models for human genetic disorders, offering insights into anatomical, neurochemical, and behavioral effects of aberrant gene expression. A variety of assays have been developed to identify and characterize phenotypic changes. In the behavioral domain, our phenotyping strategy involves a comprehensive standardized methodological approach that assesses general health, reflexes, sensory abilities, and motor functions. This assessment is followed by a series of complementary tasks in the specific behavioral domain(s) hypothesized to reveal the function( s) of the gene. Our multitiered approach minimizes intersubject variability by standardizing the experimental history for all animals, improves interlaboratory reliability by providing a clearly defined experimental protocol, and minimizes artifactual interpretations of behavioral data by careful preliminary assessments of basic behaviors, followed by multiple tests within the behavioral domain of interest. Despite meticulous attention to experimental protocol, attention to environmental factors is essential. Differences in noise, light, home cage environment, handling, and diet can dramatically alter behavior. Baseline differences in the behaviors of inbred strains used to generate targeted mutant mouse lines can directly influence the behavioral phenotype of the mutant line. Strategies aimed at minimizing environmental variability and contributions of background genes will enhance the robustness of mouse behavioral phenotyping assays. C1 NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. RP Bailey, KR (reprint author), NIMH, Lab Behav Neurosci, Bldg 35,Room 1C909 Mailstop 3730, Bethesda, MD 20892 USA. EM baileyka@mail.nih.gov NR 62 TC 64 Z9 65 U1 1 U2 7 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 2006 VL 47 IS 2 BP 124 EP 131 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 027BB UT WOS:000236387100005 PM 16547369 ER PT S AU Strober, W Fuss, IJ AF Strober, W Fuss, IJ BE Blumberg, RS Neurath, MF TI Experimental models of mucosal inflammation SO IMMUNE MECHANISMS IN INFLAMMATORY BOWEL DISEASE SE Advances in Experimental Medicine and Biology LA English DT Article ID CD4(+) T-CELLS; DEXTRAN SULFATE SODIUM; GROWTH-FACTOR-BETA; NF-KAPPA-B; IMMUNOLOGICAL SELF-TOLERANCE; INTESTINAL EPITHELIAL-CELLS; HAPTEN-INDUCED COLITIS; TUMOR-NECROSIS-FACTOR; ALPHA MUTANT MICE; EXPERIMENTAL ULCERATIVE-COLITIS C1 NIAID, Host Def Lab, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. RP NIAID, Host Def Lab, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. NR 221 TC 12 Z9 13 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 0-387-30831-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 579 BP 55 EP 97 PG 43 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BEC63 UT WOS:000236805000005 PM 16620012 ER PT J AU Leon, F Smythies, LE Smith, PD Kelsall, BL AF Leon, F Smythies, LE Smith, PD Kelsall, BL TI Involvement of dendritic cells in the pathogenesis of inflammatory bowel disease SO IMMUNE MECHANISMS IN INFLAMMATORY BOWEL DISEASE SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID HUMAN PEYERS-PATCHES; MESENTERIC LYMPH-NODES; COLONIC LAMINA PROPRIA; HUMAN SMALL-INTESTINE; TOLL-LIKE RECEPTORS; ANTIGEN-PRESENTING CELLS; REGULATORY T-CELLS; ULCERATIVE-COLITIS; IN-VIVO; DYING CELLS C1 NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Univ Alabama, Vet Adm Med Ctr, Div Gastroenterol & Hepatol, Birmingham, AL USA. NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Leon, F (reprint author), NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD-41361]; NIDDK NIH HHS [DK-64400, DK-54495, DK-47322] NR 133 TC 25 Z9 26 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 579 BP 117 EP 132 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BEC63 UT WOS:000236805000008 PM 16620015 ER PT J AU Subbarao, K Murphy, BR Fauci, AS AF Subbarao, K Murphy, BR Fauci, AS TI Development of effective vaccines against pandemic influenza SO IMMUNITY LA English DT Editorial Material ID M2 PROTEIN; VIRUS; HEMAGGLUTININ; INFECTION; EVOLUTION; H2N2 AB A key strategy to protect humans against an influenza pandemic is the development of an effective vaccine. However, the development of effective pandemic vaccines poses both practical and immunological challenges. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 17 TC 95 Z9 99 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2006 VL 24 IS 1 BP 5 EP 9 DI 10.1016/j.immuni.2005.12.005 PG 5 WC Immunology SC Immunology GA 005UT UT WOS:000234850200003 PM 16413916 ER PT J AU Gamero, AM Oppenheim, JJ AF Gamero, AM Oppenheim, JJ TI IL-1 can act as number one SO IMMUNITY LA English DT Editorial Material ID STAPHYLOCOCCUS-AUREUS; INTERLEUKIN-1; EXPRESSION C1 NCI, FCRF, Expt Immunol Lab, Ft Detrick, MD 21702 USA. NCI, FCRF, Mol Immunoregulat Lab, Canc Res Ctr, Ft Detrick, MD 21702 USA. RP Gamero, AM (reprint author), NCI, FCRF, Expt Immunol Lab, Ft Detrick, MD 21702 USA. NR 11 TC 16 Z9 18 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2006 VL 24 IS 1 BP 16 EP 17 DI 10.1016/j.immuni.2005.12.007 PG 2 WC Immunology SC Immunology GA 005UT UT WOS:000234850200006 PM 16413919 ER PT J AU Anderson, SK AF Anderson, SK TI Transcriptional regulation of NK cell receptors SO IMMUNOBIOLOGY OF NATURAL KILLER CELL RECEPTORS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID NATURAL-KILLER-CELLS; GENE-EXPRESSION; BONE-MARROW; CLONAL ACQUISITION; DNA METHYLATION; LY49 RECEPTORS; DUAL PROMOTERS; NK1.1 ANTIGEN; CD94 GENE; T-CELLS AB The stochastic expression of individual members of NK cell receptor gene families on subsets of NK cells has attracted considerable interest in the transcriptional regulation of these genes. Each receptor gene can contain up to three separate promoters with distinct properties. The recent discovery that an upstream Promoter can function as a probabilistic switch element in the Ly49 gene family has revealed a novel mechanism of variegated gene expression. An important question to be answered is whether or not the other NK cell receptor gene families contain probabilistic switches. The promoter elements currently identified in the Ly49, NKR-P1, CD94, NKG2A, and KIR gene families are described. C1 SAIC Frederick, Basic Res Program, Natl Canc Inst, Frederick, MD 21702 USA. RP Anderson, SK (reprint author), SAIC Frederick, Basic Res Program, Natl Canc Inst, Bldg 560,Rm 31-93, Frederick, MD 21702 USA. EM andersn@ncifcrf.gov RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-12400] NR 47 TC 17 Z9 18 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 298 BP 59 EP 75 PG 17 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BDS44 UT WOS:000235180500003 PM 16329185 ER PT J AU Carrington, M Martin, MP AF Carrington, M Martin, MP TI The impact of variation at the KIR gene cluster on human disease SO IMMUNOBIOLOGY OF NATURAL KILLER CELL RECEPTORS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTOR; IG-LIKE RECEPTORS; HUMAN NK CELLS; FALCIPARUM-INFECTED ERYTHROCYTES; CHRONIC MYELOGENOUS LEUKEMIA; AUTOLOGOUS DENDRITIC CELLS; SINGLE AMINO-ACID; HLA-C MOLECULES; COMPLEX CLASS-I AB Leukocyte behavior is controlled by a balance of inhibitory and stimulatory signals generated on ligand binding to a complex set of receptors located on the cell surface. The killer cell immunoglobulin-like receptor (KIR) genes encode one such family of receptors expressed by natural killer (NK) cells, key components of the innate immune system that participate in early responses against infected or transformed cells through production of cytokines and direct cytotoxicity. KIRs are also expressed on a subset of T cells, where they contribute to the intensity of acquired immune responses. Recognition of self HLA class I ligands by inhibitory KIR allows NK cells to identify normal cells, preventing an NK cell-mediated response against healthy autologous cells. Activation of NK cells through stimulatory receptors is directed toward cells with altered expression of class 1, a situation characteristic of some virally infected cells and tumor cells. The "missing self" model for NK cell activation was proposed to explain killing of cells that express little or no class 1, while cells expressing normal levels of class 1 are spared. Studies performed over the last several years have revealed extensive diversity at the KIR gene locus, which stems from both its polygenic (variable numbers of genes depending on KIR haplotype) and multiallelic polymorphism. Given the role of KIR in both arms of the immune response, their specificity for HLA class I allotypes, and their extensive genomic diversity, it is reasonable to imagine that KIR gene variation affects resistance and susceptibility to the pathogenesis of numerous diseases. Consequently, the evolution of KIR locus diversity within and across populations may be a function of disease morbidity and mortality. Here we review a growing body of evidence purporting the influence of KIR polymorphism in human disease. C1 SAIC Frederick Inc, Basic Res Program, Lab Genom Divers, NCI, Frederick, MD 21702 USA. RP Carrington, M (reprint author), SAIC Frederick Inc, Basic Res Program, Lab Genom Divers, NCI, Bldg 560 Rm 21-89,POB B, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 159 TC 81 Z9 86 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 298 BP 225 EP 257 PG 33 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BDS44 UT WOS:000235180500012 PM 16329188 ER PT J AU Peloponese, JM Yeung, ML Jeang, KT AF Peloponese, JM Yeung, ML Jeang, KT TI Modulation of nuclear Factor-kappa B by human T cell leukemia virus type 1 tax protein - Implications for oncogenesis and inflammation SO IMMUNOLOGIC RESEARCH LA English DT Review DE human T cell leukemia virus (HTLV-1); adult T cell leukemia (ATL); HTLV-1 tax; NF-kappa B; IKK; NIK; inflammation ID 1ST HUMAN RETROVIRUS; HTLV-I INFECTION; NF-KAPPA-B2 P100; IKK-ALPHA; DEFICIENT MICE; SIGNALING PATHWAY; SPLENIC MICROARCHITECTURE; TRANSCRIPTIONAL ACTIVITY; CONSTITUTIVE ACTIVATION; TRANSFORMING PROTEIN AB Activation of the nuclear factor kappa B (NF-kappa B) transcription factor family by different stimuli, such as inflammatory cytokines, stress inducers. or pathogens. results in innate and adaptive immunity. While the main function of NF-kappa B is to promote the host's immune response. the NF-kappa B pathway is frequently dysregulated by invading viral pathogens. Human T cell leukemia virus type 1 (HTLV-1) is the causative agent of a fatal malignancy known as adult T cell leukemia (ATL) and an inflammatory disease named tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). HTLV-1 encodes an oncoprotein, Tax. which plays a significant role in the initiation of cellular transformation and the elicitation of the host's inflammatory responses. Here, we review current thinking on how Tax may affect both diseases through activation of NF-kappa B signaling. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Peloponese, JM (reprint author), Bldg 4,Room 306,9000 Rockville, Bethesda, MD 20892 USA. EM kjeang@maid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 102 TC 39 Z9 40 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2006 VL 34 IS 1 BP 1 EP 12 DI 10.1385/IR:34:1:1 PG 12 WC Immunology SC Immunology GA 047BP UT WOS:000237855100001 PM 16720895 ER PT J AU Kehrl, JH AF Kehrl, John H. TI Chemoattractant receptor signaling and the control of lymphocyte migration SO IMMUNOLOGIC RESEARCH LA English DT Review DE lymphocytes; chemotaxis; migration; heterotrimeric G-protein; RGS proteins; photosphoinositide 3-kinases ID G-BETA-GAMMA; HETEROTRIMERIC G-PROTEINS; T-CELL-ACTIVATION; NUCLEOTIDE EXCHANGE FACTOR; TYROSINE KINASE; RGS PROTEINS; B-LYMPHOCYTES; IN-VIVO; PHOSPHOINOSITIDE 3-KINASES; INTRAVITAL MICROSCOPY AB This review focuses on mechanisms by which chemoattractant receptors activate downstream signaling pathways in lymphocytes. An emphasis is placed on heterotrimeric G protein signaling with a discussion of the specific heterotrimeric G-proteins involved in lymphocyte chemotaxis and motility and the role of regulator of G protein signaling (RGS) proteins in controlling the activation of downstream effectors. Also considered are those direct downstream effectors known to function in lymphocyte chemotaxis and/or motility. The consequences of targeting genes suspected, known, or serendipitously found to be involved in chemokine receptor signaling pathways form much of a basis for the review. When needed for clarification, reference to studies of chemoattractant signaling in model organisms and in neutrophils will be compared and contrasted to studies in lymphocytes. Finally, the emergence of tools to image lymphocyte in vitro and in vivo will be mentioned as they are increasing helpful for the analysis of lymphocyte trafficking and amendable to the study of chemokine receptor signaling. C1 NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 112 TC 37 Z9 38 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2006 VL 34 IS 3 BP 211 EP 227 DI 10.1385/IR:34:3:211 PG 17 WC Immunology SC Immunology GA 064DS UT WOS:000239070000003 PM 16891672 ER PT S AU Hagopian, WA Lernmark, A Rewers, MJ Simell, OG She, JX Ziegler, AG Krischer, JP Akolkar, B AF Hagopian, William A. Lernmark, Ake Rewers, Marian J. Simell, Olli G. She, Jin-Xiong Ziegler, Anette G. Krischer, Jeffrey P. Akolkar, Beena BE Sanjeevi, CB Hanafusa, T TI TEDDY- The environmental determinants of diabetes in the young - An observational clinical trial SO IMMUNOLOGY OF DIABETES IV: PROGRESS IN OUR UNDERSTANDING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th Meeting of the Immunology-of-Diabetes-Society CY OCT 06-09, 2005 CL Awaji Isl, JAPAN SP Immunol Diabet Soc DE type 1 diabetes; islet autoantibodies; HLA; virus ID SUSCEPTIBILITY; MELLITUS; TRENDS; ONSET AB The aim of the TEDDY study is to identify infectious agents, dietary factors, or other environmental agents, including psychosocial factors, which may either trigger islet autoimmunity, type 1 diabetes mellitus (T1DM), or both. The study has two end points: (a) appearance of islet autoantibodies and (b) clinical diagnosis of T1DM. Six clinical centers screen newborns for high-risk HLA genotypes. As of December 2005 a total of 54,470 newborns have been screened. High-risk HLA genotypes among 53,560 general population (GP) infants were 2576 (4.8%) and among 910 newborns with a first-degree relative (FDR) were 194 (21%). A total of 1061 children have been enrolled. The initial enrollment results demonstrate the feasibility of this complex and demanding a prospective study. C1 Univ Hosp MAS, Malmo 20522, Sweden. Pacific NW Res Inst, Seattle, WA 98122 USA. Univ Colorado, Denver, CO 80162 USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ Turku, Cent Hosp, FIN-20520 Turku, Finland. Diabet Res Inst, D-80804 Munich, Germany. Univ S Florida, Tampa, FL 33612 USA. NIH, Bethesda, MD 20892 USA. RP Lernmark, A (reprint author), Lund Univ, Univ Hosp MAS, Dept Clin Sci, SE-20502 Malmo, Sweden. EM Ake.lernmark@med.lu.se RI Ziegler, Anette-Gabriele/M-4614-2014 OI Ziegler, Anette-Gabriele/0000-0002-6290-5548 FU NIDDK NIH HHS [UC4 DK063821] NR 9 TC 46 Z9 48 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-641-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1079 BP 320 EP 326 DI 10.1196/annals.1375.049 PG 7 WC Endocrinology & Metabolism; Immunology; Multidisciplinary Sciences SC Endocrinology & Metabolism; Immunology; Science & Technology - Other Topics GA BFM87 UT WOS:000243126100049 PM 17130573 ER PT J AU Bornstein, MH Gini, M Putnick, DL Haynes, OM Painter, KM Suwalsky, JTD AF Bornstein, Marc H. Gini, Motti Putnick, Diane L. Haynes, O. Maurice Painter, Kathleen M. Suwalsky, Joan T. D. TI Short-term reliability and continuity of emotional availability in mother-child dyads across contexts of observation SO INFANCY LA English DT Article ID LABORATORY SETTINGS; INFANT INTERACTION; BEHAVIOR; PARENTS; HOME; 2-YEAR-OLDS; COMPETENCE; CONCURRENT; TODDLERS; DEFIANCE AB Emotional availability (EA) is a prominent index of socioemotional adaptation in the parent-child dyad. Is EA affected by context? In this methodological study, 34 mothers and their 2-year-olds were observed in 2 different settings (home vs. laboratory) 1 week apart. Significant cross-context reliability and continuity in EA as measured with the Emotional Availability Scales emerged. Because EA is not affected by context, cross-context generalizations about EA status in the dyad may be warranted. This work further documents the adequate psychometric properties of emotional availability. C1 NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, NIH, Dept Hlth & Human Serv, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov RI Putnick, Diane/B-1707-2009; OI Putnick, Diane/0000-0002-6323-749X NR 59 TC 34 Z9 34 U1 1 U2 8 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1525-0008 J9 INFANCY JI Infancy PY 2006 VL 10 IS 1 BP 1 EP 16 DI 10.1207/s15327078IN1001_1 PG 16 WC Psychology, Developmental SC Psychology GA 068ZZ UT WOS:000239415500001 ER PT J AU Nelson, DE Crane, DD Taylor, LD Dorward, DW Goheen, MM Caldwell, HD AF Nelson, DE Crane, DD Taylor, LD Dorward, DW Goheen, MM Caldwell, HD TI Inhibition of chlamydiae by primary alcohols correlates with the strain-specific complement of plasticity zone phospholipase D genes SO INFECTION AND IMMUNITY LA English DT Article ID TRYPTOPHAN SYNTHASE; GENOME SEQUENCE; C-TRACHOMATIS; D DEFINES; METABOLISM; PROTEIN; FAMILY; CELLS; PERSISTENCE; PNEUMONIAE AB Members of the genus Chlamydia are obligate intracellular pathogens that have a unique biphasic developmental cycle and interactions with host cells. Many genes that dictate host infection tropism and, putatively, pathogenic manifestations of disease are clustered in a hypervariable region of the genome termed the plasticity zone (PZ). Comparative genomics studies have determined that an uncharacterized family of PZ genes encoding orthologs of eukaryotic and prokaryotic members of the phospholipase D (PLD) enzyme family varies among chlamydiae. Here, we show that the PZ PLD (pzPLD) of Chlamydia trachomatis are transcribed during both normal and persistent infection and that the corresponding PLD proteins are predominately localized in reticulate bodies on the inner leaflet of the inclusion membrane. Further, we show that strains of chlamydiae encoding the pzPLD, but not a strain lacking these genes, are inhibited by primary alcohols, potent PLD inhibitors, during growth in HeLa 229 cells. This inhibitory effect is amplified approximately 5,000-fold during recovery from persistent infection. These findings suggest that the chlamydial pzPLD may be important, strain-specific, pathogenesis factors in vivo. C1 NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM hcaldwell@niaid.nih.gov NR 33 TC 32 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2006 VL 74 IS 1 BP 73 EP 80 DI 10.1128/IAI.74.1.73-80.2006 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 997VH UT WOS:000234276400007 PM 16368959 ER PT J AU Jeevan, A McFarland, CT Yoshimura, T Skwor, T Cho, H Lasco, T McMurray, DN AF Jeevan, A McFarland, CT Yoshimura, T Skwor, T Cho, H Lasco, T McMurray, DN TI Production and characterization of guinea pig recombinant gamma interferon and its effect on macrophage activation SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MYCOBACTERIUM-BOVIS BCG; MOUSE PERITONEAL-MACROPHAGES; MESSENGER-RNA EXPRESSION; NITRIC-OXIDE PRODUCTION; FACTOR-ALPHA; TUBERCULOSIS INFECTION; ALVEOLAR MACROPHAGES; IFN-GAMMA; MURINE MACROPHAGES AB Gamma interferon (IFN-gamma) plays a critical role in the protective immune responses against mycobacteria. We previously cloned a cDNA coding for guinea pig IFN-gamma (gpIFN-gamma) and reported that BCG vaccination induced a significant increase in the IFN-gamma mRNA expression in guinea pig cells in response to living mycobacteria and that the virulent H37Rv strain of Mycobacterium tuberculosis stimulated less IFN-gamma mRNA than did the attenuated H37Ra strain. In this study, we successfully expressed and characterized recombinant gpIFN-gamma with a histidine tag at the N terminus (His-tagged rgpIFN-gamma) in Escherichia coli. rgpIFN-gamma was identified as an 18-kDa band in the insoluble fraction; therefore, the protein was purified under denaturing conditions and renatured. N-terminal amino acid sequencing of the recombinant protein yielded the sequence corresponding to the N terminus of His-tagged gpIFN-gamma. The recombinant protein upregulated major histocompatibility complex class II expression in peritoneal macrophages. The antiviral activity of rgpIFN-gamma was demonstrated with a guinea pig fibroblast cell line (104C1) infected with encephalomyocarditis virus. Interestingly, peritoneal macrophages treated with rgpIFN-gamma did not produce any nitric oxide but did produce hydrogen peroxide and suppressed the intracellular growth of mycobacteria. Furthermore, rgpIFN-gamma induced morphological alterations in cultured macrophages. Thus, biologically active rgpIFN-gamma has been successfully produced and characterized in our laboratory. The study of rgpIFN-gamma will further increase our understanding of the cellular and molecular responses induced by BCG vaccination in the guinea pig model of pulmonary tuberculosis. C1 Texas A&M Univ, SHSC, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Jeevan, A (reprint author), Texas A&M Univ, SHSC, Dept Med Microbiol & Immunol, 407 Reynolds Med Bldg, College Stn, TX 77843 USA. EM ajeevan@medicine.tamhsc.edu FU NIAID NIH HHS [R01 AI 15495, R01 AI015495] NR 52 TC 34 Z9 34 U1 1 U2 3 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 2006 VL 74 IS 1 BP 213 EP 224 DI 10.1128/IAI.74.1.213-224.2006 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 997VH UT WOS:000234276400023 PM 16368975 ER PT J AU Roshick, C Wood, H Caldwell, HD McClarty, G AF Roshick, C Wood, H Caldwell, HD McClarty, G TI Comparison of gamma interferon-mediated antichlamydial defense mechanisms in human and mouse cells SO INFECTION AND IMMUNITY LA English DT Article ID NITRIC-OXIDE SYNTHASE; CHLAMYDIA-TRACHOMATIS INFECTION; GENITAL-TRACT INFECTION; INDOLEAMINE 2,3-DIOXYGENASE; IFN-GAMMA; TRYPTOPHAN CATABOLISM; KNOCKOUT MICE; REACTIVE OXYGEN; MCCOY CELLS; HOST-CELLS AB Gamma interferon (IFN-gamma)-induced effector mechanisms have potent antichlamydial activities that are critical to host defense. The most prominent and well-studied effectors are indoleamine dioxygenase (IDO) and nitric oxide (NO) synthase. The relative contributions of these mechanisms as inhibitors of chlamydial in vitro growth have been extensively studied using different host cells, induction mechanisms, and chlamydial strains with conflicting results. Here, we have undertaken a comparative analysis of cytokine- and lipopolysaccharide (LPS)-induced IDO and NO using an extensive assortment of human and murine host cells infected with human and murine chlamydial strains. Following cytokine (IFN-gamma or tumor necrosis factor alpha) and/or LPS treatment, the majority of human cell lines induced IDO but failed to produce NO. Conversely, the majority of mouse cell lines studied produced NO, not IDO. Induction of IDO in human cell lines inhibited growth of L2 and mouse pneumonitis agent, now referred to as Chlamydia muridarum MoPn equally in all but two lines, and inhibition was completely reversible by the addition of tryptophan. IFN-gamma treatment of mouse cell lines resulted in substantially greater reduction of L2 than MoPn growth. However, despite elevated NO production by murine cells, blockage of NO synthesis with the L-arginine analogue N-monomethyl-L-arginine only partially rescued chlamydial growth, suggesting the presence of another IFN-gamma-inducible antichlamydial mechanism unique to murine cells. Moreover, NO generated from the chemical nitric oxide donor sodium nitroprusside showed little direct effect on chlamydial infectivity or growth, indicating a natural resistance to NO. Finally, IFN-gamma-inducible IDO expression in human HeLa cells was inhibited following exogenous NO treatment, resulting in a permissive environment for chlamydial growth. In summary, cytokine- and LPS-inducible effectors produced by human and mouse cells differ and, importantly, these host-specific effector responses result in chlamydial strain-specific antimicrobial activities. C1 Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB R3E 3R2, Canada. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 3R2, Canada. RP McClarty, G (reprint author), Publ Hlth Agcy Canada, Natl Microbiol Lab, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada. EM mcclart@cc.umanitoba.ca FU NIAID NIH HHS [R21 AI 054875-02, R21 AI054875] NR 66 TC 78 Z9 84 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2006 VL 74 IS 1 BP 225 EP 238 DI 10.1128/IAI.74.1.225-238.2006 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 997VH UT WOS:000234276400024 PM 16368976 ER PT J AU Xu, L Li, HL Vuong, C Vadyvaloo, V Wang, JP Yao, YF Otto, M Gao, Q AF Xu, L Li, HL Vuong, C Vadyvaloo, V Wang, JP Yao, YF Otto, M Gao, Q TI Role of the luxS quorum-sensing system in biofilm formation and virulence of Staphylococcus epidermidis SO INFECTION AND IMMUNITY LA English DT Article ID POLYSACCHARIDE INTERCELLULAR ADHESIN; COAGULASE-NEGATIVE STAPHYLOCOCCI; ESCHERICHIA-COLI; GENE-EXPRESSION; VIBRIO-HARVEYI; SALMONELLA-TYPHIMURIUM; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; HELICOBACTER-PYLORI; MEDICAL DEVICES; ADHERENCE AB Nosocomial infections caused by Staphylococcus epidermidis are characterized by biofilm formation on implanted medical devices. Quorum-sensing regulation plays a major role in the biofilm development of many bacterial pathogens. Here, we describe luxS, a quorum-sensing system in staphylococci that has a significant impact on biofilm development and virulence. We constructed an isogenic Delta luxS mutant strain of a biofilm-forming clinical isolate of S. epidermidis and demonstrated that htxS signaling is functional in S. epidermidis. The mutant strain showed increased biofilm formation in vitro and enhanced virulence in a rat model of biofilm-associated infection. Genetic complementation and addition of autoinducer 2-containing culture filtrate restored the wild-type phenotype, demonstrating that luxS repressed biofilm formation through a cell-cell signaling mechanism based on autoinducer 2 secretion. Enhanced production of the biofilm exopolysaccharide polysaccharide intercellular adhesin in the mutant strain is presumably the major cause of the observed phenotype. The agr quorum-sensing system has previously been shown to impact biofilm development and biofilm-associated infection in a way similar to that of luxS, although by regulation of different factors. Our study indicates a general scheme of quorum-sensing regulation of biofilm development in staphylococci, which contrasts with that observed in many other bacterial pathogens. C1 Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Shanghai 200032, Peoples R China. Fudan Univ, Inst Med Microbiol, Shanghai 200032, Peoples R China. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Gao, Q (reprint author), Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Shanghai 200032, Peoples R China. EM qiangao@shmu.edu.cn OI Otto, Michael/0000-0002-2222-4115 NR 58 TC 104 Z9 122 U1 3 U2 39 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 2006 VL 74 IS 1 BP 488 EP 496 DI 10.1128/IAI.74.1.488-496.2006 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 997VH UT WOS:000234276400053 PM 16369005 ER PT J AU Pomerantsev, AP Sitaraman, R Galloway, CR Kivovich, V Leppla, SH AF Pomerantsev, AP Sitaraman, R Galloway, CR Kivovich, V Leppla, SH TI Genome engineering in Bacillus anthracis using Cre recombinase SO INFECTION AND IMMUNITY LA English DT Article ID PROTECTIVE ANTIGEN GENE; GRAM-POSITIVE BACTERIA; LOXP RECOMBINATION; SUBTILIS; SPORULATION; PLASMID; CAPSULE; CEREUS; PURIFICATION; PROTEASE AB Genome engineering is a powerful method for the study of bacterial virulence. With the availability of the complete genomic sequence of Bacillus anthracis, it is now possible to inactivate or delete selected genes of interest. However, many current methods for disrupting or deleting more than one gene require use of multiple antibiotic resistance determinants. In this report we used an approach that temporarily inserts an antibiotic resistance marker into a selected region of the genome and subsequently removes it, leaving the target region (a single gene or a larger genomic segment) permanently mutated. For this purpose, a spectinomycin resistance cassette flanked by bacteriophage P1 loxP sites oriented as direct repeats was inserted within a selected gene. After identification of strains having the spectinomycin cassette inserted by a double-crossover event, a thermo-sensitive plasmid expressing Cre recombinase was introduced at the permissive temperature. Cre recombinase action at the loxP sites excised the spectinomycin marker, leaving a single loxP site within the targeted gene or genomic segment. The Cre-expressing plasmid was then removed by growth at the restrictive temperature. The procedure could then be repeated to mutate additional genes. In this way, we sequentially mutated two pairs of genes: pepM and spo0A, and mcrB and mrr. Furthermore, loxP sites introduced at distant genes could be recombined by Cre recombinase to cause deletion of large intervening regions. In this way, we deleted the capBCAD region of the pXO2 plasmid and the entire 30 kb of chromosomal DNA between the mcrB and mrr genes, and in the latter case we found that the 32 intervening open reading frames were not essential to growth. C1 NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov OI Sitaraman, Ramakrishnan/0000-0002-4577-4224 FU Intramural NIH HHS NR 39 TC 55 Z9 57 U1 0 U2 4 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 2006 VL 74 IS 1 BP 682 EP 693 DI 10.1128/IAI.74.1.682-693.2006 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 997VH UT WOS:000234276400073 PM 16369025 ER PT J AU Peachman, KK Rao, M Alving, CR Burge, R Leppla, SH Rao, VB Matyas, GR AF Peachman, KK Rao, M Alving, CR Burge, R Leppla, SH Rao, VB Matyas, GR TI Correlation between lethal toxin-neutralizing antibody Titers and protection from intranasal challenge with Bacillus anthracis Ames strain spores in mice after transcutaneous immunization with recombinant anthrax protective antigen SO INFECTION AND IMMUNITY LA English DT Article ID SUSCEPTIBILITY; DISSEMINATION; PATCH AB Transcutaneous immunization of mice with recombinant protective antigen (rPA) of Bacillus anthracis resulted in significantly higher lethal toxin-neutralizing antibody titers than did intramuscular injection of alum-adsorbed rPA. Immunized mice were partially protected against intranasal challenge with 235,000 (10 50% lethal doses) Ames strain B. anthracis spores. A highly significant correlation was observed between toxin-neutralizing antibody titer and survival after challenge. Future experiments with rabbits and nonhuman primates should confirm the significance of protection by this vaccine strategy. C1 Walter Reed Army Inst Res, Dept Vaccine Prod & Delivery, Div Retrovirol, US Mil HIV Res Program, Rockville, MD 20850 USA. Walter Reed Army Inst Res, Div Biometr, Silver Spring, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Catholic Univ Amer, Washington, DC 20064 USA. RP Alving, CR (reprint author), Walter Reed Army Inst Res, Dept Vaccine Prod & Delivery, Div Retrovirol, US Mil HIV Res Program, 1600 E Gude Dr, Rockville, MD 20850 USA. EM calving@hivresearch.org FU NIAID NIH HHS [1U01 AI 056443-01] NR 13 TC 38 Z9 38 U1 0 U2 3 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 2006 VL 74 IS 1 BP 794 EP 797 DI 10.1128/IAI.74.1.794-797.2006 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 997VH UT WOS:000234276400091 PM 16369043 ER PT J AU Fuss, IJ Becker, C Yang, ZQ Groden, C Hornung, RL Heller, F Neurath, MF Strober, W Mannon, PJ AF Fuss, IJ Becker, C Yang, ZQ Groden, C Hornung, RL Heller, F Neurath, MF Strober, W Mannon, PJ TI Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE interleukin-12; interleukin-23; inflammatory bowel diseases ID INFLAMMATORY-BOWEL-DISEASE; AUTOIMMUNE INFLAMMATION; ULCERATIVE-COLITIS; CELLS; INTERLEUKIN-12; CYTOKINE; MACROPHAGES; EXPRESSION; INDUCTION; RESPONSES AB Background: Interleukin (IL)-12p70 and IL-23 are key T helper-1 (T(H)1) cytokines that drive the inflammation seen in numerous models of intestinal inflammation. These molecules contain an identical p40 chain that is bound to a p35 chain in IL-12 and a p19 chain in IL-23, making both potentially susceptible to modulation by an anti-IL12p40 monoclonal antibody (mAb). Methods: In the present study, we sought to determine whether active inflammation in Crohn's disease (CD) is associated with the increased synthesis of both of these cytokines and whether patients treated with an anti-IL-12p40 mAb down-regulate IL-23 as well as IL-12p70 as previous reported. Results: To this end we initially determined that IL-12p70 secretion by control and CD antigen-presenting cells (macrophages) in lamina propria mononuclear populations is optimized by stimulation with CD40L and interferon-gamma. In subsequent studies using these stimulation conditions we found that patients with CD manifested both increased IL-12p70 and IL-23 secretion before anti-IL-12p40 mAb treatment and normal levels of secretion of these cytokines following cessation of treatment. Antigen-presenting cells in lamina propria mononuclear cells from ulcerative colitis patients, in contrast, produced only baseline levels of IL-23. Finally, we found that IL-23-induced T cell production of IL-17 and IL-6 are also greatly reduced after antibody treatment. The latter data are parallel to those from previous studies showing that anti-IL-12p40 down-regulates IFN-gamma and tumor necrosis factor-a secretion. Conclusions: We conclude that CD but not ulcerative colitis is associated with high levels of both IL-12p70 and IL-23 secretion as well as the secretion of downstream effector cytokines, and that this cytokine production is down-regulated following administration of IL-12p40 mAb. C1 Natl Inst Allergy & Infect Dis, Lab Host Def, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. Univ Mainz, Immunol Lab, Mainz, Germany. Sci Applicat Int Corp Frederick Inc, Clin Serv Program, NCI, Frederick, MD USA. Univ Hosp, Charite, Div Gastroenterol, Berlin, Germany. RP Fuss, IJ (reprint author), Natl Inst Allergy & Infect Dis, Lab Host Def, Mucosal Immun Sect, NIH, CRC Bldg,10 Ctr Dr,Room 5W-3940, Bethesda, MD 20892 USA. EM ifuss@niaid.nih.gov RI Becker, Christoph/A-6694-2008; Becker, Christoph/L-2996-2016 OI Becker, Christoph/0000-0002-1388-1041; FU Intramural NIH HHS NR 20 TC 208 Z9 220 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2006 VL 12 IS 1 BP 9 EP 15 DI 10.1097/01.MIB.0000194183.92671.b6 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 000UV UT WOS:000234488800002 PM 16374252 ER PT J AU Dyers, L Que, SY VanDerveer, D Bu, XR AF Dyers, L Que, SY VanDerveer, D Bu, XR TI Synthesis and structures of new salen complexes with bulky groups SO INORGANICA CHIMICA ACTA LA English DT Article DE Schiff base ligand; salen; nickel complex; copper complex; palladium complex; iron complex; crystal structure ID SCHIFF-BASE COMPLEXES; MOLECULAR-STRUCTURE; COPPER(II); CRYSTAL; OXIDATION; CATALYSTS; POSITION AB A new series of Schiff base complexes [Fe(III), VO(II), Pd(II), Cu(II), and Ni(II)] has been developed. The ligand possesses bulky t-pentyl groups at the 3- and 5-positions. The iron (III) complex is obtained in monomeric form with a square-pyramidal configuration while the copper complex is with square-planar configuration. (c) 2005 Elsevier B.V. All rights reserved. C1 Clark Atlanta Univ, Dept Chem, Atlanta, GA 30314 USA. NIEHS, Free Rad Metab Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Clemson Univ, Dept Chem, Clemson, SC 29634 USA. RP Bu, XR (reprint author), Clark Atlanta Univ, Dept Chem, 223 James P Brawley Dr SW, Atlanta, GA 30314 USA. EM xbu@cau.edu NR 21 TC 27 Z9 27 U1 1 U2 6 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0020-1693 J9 INORG CHIM ACTA JI Inorg. Chim. Acta PD JAN 1 PY 2006 VL 359 IS 1 BP 197 EP 203 DI 10.1016/j.ica.2005.06.068 PG 7 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 002LU UT WOS:000234613800019 ER PT J AU Lapolla, JS Schultz, TR Kjer, KM Bischoff, JF AF Lapolla, John S. Schultz, Ted R. Kjer, Karl M. Bischoff, Joseph F. TI Phylogenetic position of the ant genus Acropyga Roger (Hymenoptera : Formicidae) and the evolution of trophophoresy SO INSECT SYSTEMATICS & EVOLUTION LA English DT Article ID HIGHER CLASSIFICATION; DNA-SEQUENCES; TROPHOBIONTS; MUTUALISM; SYMBIOSIS; MEALYBUGS; QUEENS; AMBER AB Trophophoresy is exhibited in two ant genera: Acropyga (Formicinae), in which all 37 species are thought to be trophophoretic, and Tetraponera (Pseudomyrmecinae), in which it has been observed in only one species, T binghami. This study analyses a dataset comprised of both morphological and molecular (D2 region of 28S rRNA and EF1-alpha) data. Evidence is presented in favor of Acropyga being monophyletic, hence trophophoresy has evolved only once within the Formicinae and twice within the ants overall. The data further suggests that Acropyga belongs within a clade containing Anoplolepis, Aphomomyrmex, and Petalomyrmex. Aphomomyrmex and Petalomyrmex were found to be the sister group to Acropyga. The results indicate that the Lasimi and Plagiolepidini are not monophyletic and are in need of reexamination. Given the extant pantropical distribution of Acropyga it is speculated that Acropyga maybe of Gondwanan origin and that trophobiosis was the first form of agriculture to evolve in the ants. C1 Natl Museum Nat Hist, Smithsonian Inst, Dept Entomol, Washington, DC 20013 USA. Rutgers State Univ, Dept Ecol & Evolut, New Brunswick, NJ 08901 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Lapolla, JS (reprint author), Natl Museum Nat Hist, Smithsonian Inst, Dept Entomol, Washington, DC 20013 USA. EM lapollaj@si.edu; schultz@lab.si.edu; kjer@aesop.rutgers.edu; bischoff@ncbi.nlm.nih.gov FU Intramural NIH HHS [Z01 LM000160-04] NR 38 TC 9 Z9 9 U1 0 U2 12 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 1399-560X EI 1876-312X J9 INSECT SYST EVOL JI Insect Syst. Evol. PY 2006 VL 37 IS 2 BP 197 EP 212 DI 10.1163/187631206788831083 PG 16 WC Evolutionary Biology; Entomology SC Evolutionary Biology; Entomology GA 065MT UT WOS:000239164700005 PM 18084637 ER PT S AU Birnbaumer, L Yildirim, E Liao, YH Abramowitz, J AF Birnbaumer, Lutz Yildirim, Eda Liao, Yanhong Abramowitz, Joel BE Conn, M Christen, Y TI Molecular and functional diversity of the TRPC family of ion channels - TRPC channels and their role in ROCE/SOCE SO INSIGHTS INTO RECEPTOR FUNCTION AND NEW DRUG DEVELOPMENT TARGETS SE Research and Perspectives in Endocrine Interactions LA English DT Proceedings Paper CT Conference Medicine and Research on Insights into Receptor Function and New Drug Development Targets CY DEC 05, 2005 CL Paris, FRANCE ID RECEPTOR POTENTIAL CHANNEL; STORE-OPERATED CHANNEL; CA2+-PERMEABLE CATION CHANNEL; PROTEIN-COUPLED RECEPTOR; CAPACITATIVE CA2+ ENTRY; NERVE GROWTH CONES; TRANSIENT RECEPTOR; CALCIUM-ENTRY; DROSOPHILA TRP; TYROSINE PHOSPHORYLATION C1 [Birnbaumer, Lutz; Yildirim, Eda; Liao, Yanhong; Abramowitz, Joel] NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. RP Birnbaumer, L (reprint author), NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM birnbau1@niehs.nih.gov RI Abramowitz, Joel/A-2620-2015 FU IntramuralResearch Program of theNIH; NIEHS FX Supported by the IntramuralResearch Program of theNIHand by NIEHS. NR 103 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1861-2253 BN 3-540-34446-2 J9 RES PERSPECT END INT JI Res. Perspect. End. Int. PY 2006 BP 1 EP + DI 10.1007/3-540-34447-0_1 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFD19 UT WOS:000241131400001 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI INTELLIGENCE AND SECURITY INFORMATICS (ISI): CHALLENGES AND OPPORTUNITIES SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 1 EP 14 D2 10.1007/0-387-30332-4 PG 14 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600002 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY Information Sharing and Data Mining PREFACE SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Editorial Material; Book Chapter ID SUPPORT VECTOR MACHINES; SPATIAL DATA-ANALYSIS; LAW-ENFORCEMENT; CRIME ANALYSIS; AUTHORSHIP ATTRIBUTION; SOCIAL NETWORKS; EXPERT-SYSTEM; URBAN-CRIME; INTEGRATION; KNOWLEDGE C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP XI EP + D2 10.1007/0-387-30332-4 PG 14 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600001 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI AN ISI RESEARCH FRAMEWORK: INFORMATION SHARING AND DATA MINING SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 15 EP 23 D2 10.1007/0-387-30332-4 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600003 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI ISI RESEARCH: LITERATURE REVIEW SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 25 EP 41 D2 10.1007/0-387-30332-4 PG 17 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600004 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI NATIONAL SECURITY CRITICAL MISSION AREAS AND CASE STUDIES SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 43 EP 53 D2 10.1007/0-387-30332-4 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600005 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI INTELLIGENCE AND WARNING SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 55 EP 73 D2 10.1007/0-387-30332-4 PG 19 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600006 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI BORDER AND TRANSPORTATION SECURITY SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 75 EP 83 D2 10.1007/0-387-30332-4 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600007 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI DOMESTIC COUNTER-TERRORISM SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 85 EP 104 D2 10.1007/0-387-30332-4 PG 20 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600008 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI PROTECTING CRITICAL INFRASTRUCTURE AND KEY ASSETS SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 105 EP 117 D2 10.1007/0-387-30332-4 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600009 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI DEFENDING AGAINST CATASTROPHIC TERRORISM SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 119 EP 129 D2 10.1007/0-387-30332-4 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600010 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI EMERGENCY PREPAREDNESS AND RESPONSE SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 131 EP 140 D2 10.1007/0-387-30332-4 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600011 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI THE PARTNERSHIP AND COLLABORATION FRAMEWORK SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Article; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 141 EP 151 D2 10.1007/0-387-30332-4 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600012 ER PT S AU Chen, HC AF Chen, Hsinchun BA Hsinchun, C BF Hsinchun, C TI INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY Information Sharing and Data Mining CONCLUSIONS AND FUTURE DIRECTIONS SO INTELLIGENCE AND SECURITY INFORMATICS FOR INTERNATIONAL SECURITY: INFORMATION SHARING AND DATA MINING SE Integrated Series in Information Systems LA English DT Editorial Material; Book Chapter C1 [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, NSF COPLINK Ctr, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Eller Coll Management, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Eller Coll Management, Artificial Intelligence Lab, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-30332-1 J9 INTEGR SER INFORM SY PY 2006 VL 10 BP 153 EP 156 D2 10.1007/0-387-30332-4 PG 4 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BLQ01 UT WOS:000270750600013 ER PT S AU Balaban, RS AF Balaban, Robert S. BE Sideman, S Beyar, R Landesberg, A TI Maintenance of the metabolic homeostasis of the heart - Developing a systems analysis approach SO INTERACTIVE AND INTEGRATIVE CARDIOLOGY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th Larry and Horti Fairberg Workshop on Interactive and Integrative Cardiology CY APR 23-27, 2006 CL Charleston, SC SP Cardiac Muscle Soc, Israel Inst Technol, Technion, Larry & Horti Fairberg Fund DE proteome; phosphoproteome; complex I; NADH; ED-FRAP; oxidative phosphorylation; modeling; protein phosphorylation ID MITOCHONDRIAL RESPIRATION; OXIDATIVE-PHOSPHORYLATION; PYRIDINE-NUCLEOTIDE; CREATINE-KINASE; REDOX STATE; IN-VIVO; OXYGEN-CONSUMPTION; SKELETAL-MUSCLE; RABBIT HEART; RAT-HEART AB The heart is almost unique in the body with a constant requirement to conduct work well beyond the normal maintenance of cellular integrity. With this constant workload, it is not surprising that cardiac energy conversion is highly specialized to maintain a constant supply of energy. This maintenance of cellular metabolites during alterations in workload has been termed metabolic homeostasis. Here we discuss our efforts to understand the cellular and mitochondrial control network that orchestrates the metabolic homeostasis of the heart. This begins with a better definition of the metabolic pathways, acute posttranslational control sites, and proper kinetic evaluation of the reaction steps in the intact mitochondrial environment. First, a quantitative model of mitochondrial energy conversion is presented and demonstrates several serious gaps in our knowledge of this process. Toward filling these gaps, screens of the entire mitochondrial proteome have been conducted to establish the metabolic pathways that need to be considered. In addition, the dynamic phosphoproteome of intact mitochondria, using 2D gel electrophoresis coupled to (32)p labeling, has revealed a remarkably extensive protein phosphorylation network throughout the mitochondrial metabolic network that has essentially been overlooked. Initial studies on evaluating the functional significance of these protein phosphorylations and the kinase-phosphatase system involved will be reviewed. One of the major deficits in the consensus quantitative model of oxidative phosphorylation to explain intact mitochondria activities is in complex 1, where even the initiation of Nicotinamide Adenine Dinucleotide (reduced) (NADH) oxidation is problematical using in vitro kinetic data. Studies will be described where the NADH binding and oxidation kinetics at complex I in the intact mitochondria were determined using fluorescence lifetime and enzyme dependent-fluorescence recovery after photo-oxidation (ED-FRAP) techniques. These later studies suggest that matrix NADH binding characteristics are much different (> 10(3) binding constant errors) than isolated proteins. In addition, complex I is far from equilibrium and may play an important role in regulating the rate of reducing equivalent delivery to the cytochromes. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10 Rm B1D-161,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsb@nih.gov RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 50 TC 22 Z9 22 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-651-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1080 BP 140 EP 153 DI 10.1196/annals.1380.013 PG 14 WC Cardiac & Cardiovascular Systems; Multidisciplinary Sciences SC Cardiovascular System & Cardiology; Science & Technology - Other Topics GA BFR89 UT WOS:000244100900012 PM 17132781 ER PT S AU Lakatta, EG Vinogradova, T Lyashkov, A Sirenko, S Zhu, W Ruknudin, A Maltsev, VA AF Lakatta, Edward G. Vinogradova, Tatiana Lyashkov, Alexey Sirenko, Syevda Zhu, Weizong Ruknudin, Abdul Maltsev, Victor A. BE Sideman, S Beyar, R Landesberg, A TI The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker SO INTERACTIVE AND INTEGRATIVE CARDIOLOGY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th Larry and Horti Fairberg Workshop on Interactive and Integrative Cardiology CY APR 23-27, 2006 CL Charleston, SC SP Cardiac Muscle Soc, Israel Inst Technol, Technion, Larry & Horti Fairberg Fund DE spontaneous local Ca2+ release; sarcoplasmic reticulum; Na+/Ca2+ exchanger; ryanodine receptor; cardiac pacemaker; normal automaticity ID RABBIT SINOATRIAL NODE; CARDIAC PURKINJE-FIBERS; RETICULUM CALCIUM RELEASE; NA+-CA2+ EXCHANGE CURRENT; SINO-ATRIAL NODE; CAT RIGHT ATRIUM; SARCOPLASMIC-RETICULUM; RYANODINE RECEPTOR; PROTEIN-KINASE; MATHEMATICAL-MODEL AB Although the ensemble of voltage- and time-dependent rhythms of surface membrane ion channels, the membrane "Clock", is the immediate cause of a sinoatrial nodal cell (SANC) action potential (AP), it does not necessarily follow that this ion channel ensemble is the formal cause of spontaneous, rhythmic APs. SANC also generates intracellular oscillatory spontaneous Ca2+ releases that ignite excitation (SCaRIE) of the surface membrane via Na+/Ca2+ exchanger activation. The idea that a rhythmic intracellular Ca2+ Clock might keep time for normal automaticity of SANC, however, has not been assimilated into mainstream pacemaker dogma. Recent experimental evidence, derived from simultaneous, confocal imaging of submembrane Ca2+ and membrane potential of SANC, and supported by numerical modeling, indicates that normal automaticity of SANC is entrained and stabilized by the tight integration of the SR Ca2+ Clock that generates rhythmic SCaRIE, and the surface membrane Clock that responds to SCaRIE to immediately produce APs of an adequate shape. Thus, tightly controlled, rhythmic SCaRIE does not merely fine tune SANC AP firing, but is the formal cause of the basal and reserve rhythms, insuring pacemaker stability by rhythmically integrating multiple Ca2+-dependent functions, and effects normal automaticity by rhythmic ignition of the surface membrane Clock. C1 NIA, Gerontol Res Ctr, Intramural Res Program, Cardiovasc Sci Lab,NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, Intramural Res Program, Cardiovasc Sci Lab,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov FU Intramural NIH HHS NR 73 TC 37 Z9 39 U1 2 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-651-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1080 BP 178 EP 206 DI 10.1196/annals.1380.016 PG 29 WC Cardiac & Cardiovascular Systems; Multidisciplinary Sciences SC Cardiovascular System & Cardiology; Science & Technology - Other Topics GA BFR89 UT WOS:000244100900015 PM 17132784 ER PT S AU Zdanov, A AF Zdanov, Alexander BE Litwack, G TI Structural studies of the interleukin-19 subfamily of cytokines SO INTERLEUKINS SE Vitamins and Hormones LA English DT Review; Book Chapter ID DIFFERENTIATION-ASSOCIATED GENE; VIRUS PROTEIN BCRF1; CELL-DERIVED IL-22; X-RAY-DIFFRACTION; CRYSTAL-STRUCTURE; MELANOMA DIFFERENTIATION; RECEPTOR COMPLEXES; INDUCIBLE FACTOR; TUMOR-SUPPRESSOR; SOLUBLE RECEPTOR AB The interleukin-19 (IL-19) subfamily of cytokines is part of a larger family of homologs of IL-10 that includes two groups of proteins: five viral cytokines, and eight cellular cytokines, having quite different biological activities. Among proteins of the latter group, IL-19, IL-20, IL-22, and IL-24 were suggested to form a structurally unique IL-19 subfamily characterized by their structural features and aggregation state as monomers. IFN-lambda 1, IFN-lambda 2, and IFN-lambda 3 are likely to belong to this subfamily, and it is still not clear whether IL-26 belongs to it or not. In spite of their differences in biological function, all cellular homologs of IL-10 used for signaling a set of five overlapping membrane-bound receptors: three long receptor chains (IL-20R1, IL-22R1, and IFN-lambda R) and two short receptor chains (IL-2OR2 and IL-10R2). Signal transduction is initiated when a cytokine binds two receptor chains, one long and one short, forming a ternary complex. Crystal structures of IL-19 and IL-22 showed that these cytokines consist of seven amphipathic helices of different length organized in helical bundle, covering an extensive hydrophobic core. Based on the similarity of the structures with the structure of a single domain of IL-10, and with the crystal structure of a binary IL-10/IL-10R1 complex, putative receptor binding sites on the surface of IL-19 and IL-22 were identified. This chapter summarizes the available structural data on the IL-19 subfamily of cytokines and their putative ligand/receptor complexes. (c) 2006 Elsevier Inc. C1 NCI, Macromol Crystallog Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Zdanov, A (reprint author), NCI, Macromol Crystallog Lab, Canc Res Ctr, Frederick, MD 21702 USA. FU Intramural NIH HHS NR 86 TC 10 Z9 10 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 0-12-709874-7 J9 VITAM HORM JI Vitam. Horm. PY 2006 VL 74 BP 61 EP 76 DI 10.1016/S0083-6729(06)74003-1 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BFK89 UT WOS:000242541700003 PM 17027511 ER PT J AU Kushnir-Sukhov, NM Brittain, E Reynolds, JC Akin, C Metcalfe, DD AF Kushnir-Sukhov, NM Brittain, E Reynolds, JC Akin, C Metcalfe, DD TI Elevated tryptase levels are associated with greater bone density in a cohort of patients with mastocytosis SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE mastocytosis; mast cell; tryptase; Z-score; dual-energy X-ray absorptiometry ID SYSTEMIC MASTOCYTOSIS; MINERAL DENSITY; OSTEOPOROSIS; DISEASE; INTERFERON-ALPHA-2B; DIAGNOSIS; FRACTURE; MARKERS; RISK AB Background: Mastocytosis is associated with a pathological increase in tissue mast cells. Associated skeletal problems include a decrease in bone density and pathological fractures. Methods: In order to explore the relationship between bone density and the severity of mastocytosis, 21 patients with mastocytosis who underwent dual-energy X-ray absorptiometry were entered into this study. Correlation coefficients were computed between Z-scores and demographic, clinical and laboratory data. Femoral neck Z-scores correlated with serum tryptase levels when all the patients were considered (p = 0.029). Results and Conclusion: Patients with less severe disease had significantly lower values at the L1-L4 spine (p = 0.046) and femoral neck (p = 0.029) Z-scores compared to patients with more severe disease. Most patients who had low Z-scores (between -1 and -2.5) were under 50 years of age, had less severe disease and had lower serum tryptase levels. A history of gastroesophageal reflux disease and a history of hypotensive episodes correlated with lower L1-L4 spine Z-scores (p < 0.05). Thus, patients with less severe disease and lower serum tryptase levels should in particular have their bone density determined with treatment appropriate to the findings. Copyright (C) 2006 S. Karger AG, Basel. C1 NIAID, NIH, LAD, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Kushnir-Sukhov, NM (reprint author), NIAID, NIH, LAD, 10 Ctr Dr MCS 1881,Bldg 10,Rm 11C208, Bethesda, MD 20892 USA. EM nkushnir@niaid.nih.gov OI Akin, Cem/0000-0001-6301-4520 NR 25 TC 21 Z9 21 U1 0 U2 1 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 2006 VL 139 IS 3 BP 265 EP 270 DI 10.1159/000091172 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 015WC UT WOS:000235581000011 PM 16449817 ER PT J AU Weiss, R Scheiblhofer, S Gabler, M Ferreira, F Leitner, WW Thalhamer, J AF Weiss, R Scheiblhofer, S Gabler, M Ferreira, F Leitner, WW Thalhamer, J TI Is genetic vaccination against allergy possible? SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Review DE type I allergy; DNA vaccination; genetic immunization ID T-CELL EPITOPE; IGE ANTIBODY-FORMATION; IMMUNOGLOBULIN-E SYNTHESIS; PLASMID DNA IMMUNIZATION; BIRCH-POLLEN ALLERGEN; RAS ONCOGENE PEPTIDE; DUST MITE ALLERGEN; IMMUNE-RESPONSE; AIRWAY INFLAMMATION; MURINE MODEL AB Genetic immunization has proven a powerful method to induce antiallergic immune responses. The underlying functional principle has been described to be based on the recruitment of allergen-specific Th1 cells, CD8+ cells and the establishment of a Th1 cytokine milieu, which prevent the development of a Th2-biased response in a protective setup and can balance an ongoing Th2-type response in a therapeutic situation. Genetic immunization with plasmid DNA offers innovative solutions to the major problems associated with protein immunization, such as crosslinking of pre-existing immunoglobulin E on mast cells/basophils or induction of de novo synthesis of immunoglobulin E by the protein immunization itself. It easily enables the routine production of hypoallergenic vaccines, which do not translate native allergens, thus avoiding potential anaphylactic side effects. DNA vaccines can also be applied as mixtures of single vaccines, making them interesting candidates for treatment based on component-resolved diagnosis, followed by an individualized therapy with the relevant allergens. In addition to the description of up-to-date allergen gene vaccine approaches, this review gives an overview of animal studies dealing with the following topics: danger signals as the inherent adjuvant properties, methods to optimize the vaccine immunogenicity, modulation of the immune response, nonparenteral applications and low-dose vaccination strategies. Copyright (C) 2006 S. Karger AG, Basel. C1 Salzburg Univ, Dept Mol Biol, Div Allergy & Immunol, A-5020 Salzburg, Austria. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Thalhamer, J (reprint author), Salzburg Univ, Dept Mol Biol, Div Allergy & Immunol, Hellbrunnerstr 34, A-5020 Salzburg, Austria. EM Josef.Thalhamer@sbg.ac.at RI Leitner, Wolfgang/F-5741-2011; Weiss, Richard/N-7279-2013; Thalhamer, Josef/E-5787-2011; Ferreira, Fatima/E-4889-2011 OI Leitner, Wolfgang/0000-0003-3125-5922; Weiss, Richard/0000-0003-3185-7253; Thalhamer, Josef/0000-0003-2285-6400; Ferreira, Fatima/0000-0003-0989-2335 FU Austrian Science Fund FWF [L 181] NR 101 TC 23 Z9 24 U1 1 U2 3 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 2006 VL 139 IS 4 BP 332 EP 345 DI 10.1159/000091946 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 020NL UT WOS:000235916300009 PM 16534215 ER PT J AU Patton, GW Powell, DA Hakki, A Friedman, H Pross, S AF Patton, GW Powell, DA Hakki, A Friedman, H Pross, S TI Nicotine modulation of cytokine induction by LPS-stimulated human monocytes and coronary artery endothelial cells SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE HCAEC; THP-1; nicotine; LPS; cytokines; chemokines ID ACETYLCHOLINE-RECEPTORS; CHLAMYDIA-PNEUMONIAE; IMMUNE-SYSTEM; ATHEROSCLEROSIS; INFLAMMATION; PROLIFERATION; ATHEROGENESIS; MACROPHAGES; ACTIVATION; EXPRESSION AB Nicotine, the major addictive component of tobacco, is an immunomodulator that impacts on many cells, including immune cells involved in inflammatory processes. Nicotine also induces oxidative damage to the vascular endothelium and accentuates lipid peroxidation, resulting in vascular cell dysfunction. Furthermore, vascular endothelial cells produce growth factors., such as cytokines and chemokines capable of stimulating and recruiting immune cells to atheromatous lesions. In addition, bacterial products including lipopolysaccharides (LPS), a major component of Grain negative bacterial cell walls, activate gene expression resulting in inflammatory cytokine production causing further damage to the vasculature. In the present study, the combined effects of nicotine and bacterial LPS on the expression of IL-6, IL-8. GRO-alpha and MCP-1 in cell lines of human coronary artery endothelial cells (HCAEC) and pulmonary monocytes (THP-1) were examined by quantitative real-time PCR and ELISA. Results showed that nicotine suppressed the LPS induced production of IL-6 and IL-8 in both cell lines. Since cytokines which alter homeostasis of both vascular endothelial and immune cells are critical for the atherogenic process, further studies are warranted to examine in detail the role of nicotine in terms of effects on inflammatory reactions, including those induced by bacterial infection. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ S Florida, Coll Med, Dept Med Microbiol & Immunol, Tampa, FL 33612 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. RP Pross, S (reprint author), Univ S Florida, Coll Med, Dept Med Microbiol & Immunol, MDC-10,12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM spross@hqc.usf.edu RI Patton, George/B-5246-2013 OI Patton, George/0000-0001-5039-8326 FU NIDA NIH HHS [2 T32 DA07245 12] NR 33 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JAN PY 2006 VL 6 IS 1 BP 26 EP 35 DI 10.1016/j.intimp.2005.07.005 PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 996FN UT WOS:000234159900004 PM 16332510 ER PT J AU Bian, XW Jiang, XF Chen, JH Bai, JS Dai, C Wang, QL Lu, JY Zhao, W Xin, R Liu, MY Shi, JQ Wang, JM AF Bian, XW Jiang, XF Chen, JH Bai, JS Dai, C Wang, QL Lu, JY Zhao, W Xin, R Liu, MY Shi, JQ Wang, JM TI Increased angiogenic capabilities of endothelial cells from microvessels of malignant human gliomas SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE angiogenesis; nordy; endothelium; glioma; vascular endothelial growth factor ID GROWTH-FACTOR; IN-VITRO; MATRIX; TUMORS; VEGF; EXPRESSION; MODELS; CANCER AB Vascular endothelial cells (ECs) that initiate tumor angiogenesis may acquire distinct properties after conditioning in tumor microenvironment as compared to ECs in non-malignant tissues. Thus far, most in vitro studies of angiogenesis used ECs isolated from normal tissues, which may not fully represent the nature of ECs in tumor vasculature. In this study, glioma-derived microvascular ECs (GDMEC) were purified from human glioma tissues by incubating with magnetic beads coated with anti-CD105 antibody and highly pure (98%) preparations of GDMEC were obtained. These cells exhibited typical EC phenotype, and proliferated rapidly in culture. Interestingly, GDMEC expressed higher levels of VEGF receptors, flt-1 and flk-1, as compared to an established human EC cell line ECV304 and primary human umbilical vascular EC (HUVEC). Functionally, GDMEC were capable of forming intercellular junctions and tubule-like structures (TLS) of various sizes. Stimulation by VEGF further promoted TLS formation with diverse tubular walls by GDMEC. In contrast, TLS formed by ECV304 and RUVEC showed significantly different features. We further observed that Nordy, a synthetic lipoxygenase inhibitor, potently inhibited TLS formation by GDMEC. The results suggest that isolation of highly pure ECs derived from tumor tissues is more appropriate for studies of tumor angiogenesis and for test of potential anti-cancer therapeutic targets. (c) 2005 Elsevier B.V. All rights reserved. C1 Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing, Peoples R China. Third Mil Med Univ, Southwest Hosp, Dept Pharm, Chongqing, Peoples R China. Third Mil Med Univ, Southwest Hosp, Dept Neurosurg, Chongqing, Peoples R China. NCI, Canc Res Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Bian, XW (reprint author), Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing, Peoples R China. EM bianxiuwu@263.net RI Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 NR 30 TC 30 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JAN PY 2006 VL 6 IS 1 BP 90 EP 99 DI 10.1016/j.intimp.2005.08.004 PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 996FN UT WOS:000234159900011 PM 16332517 ER PT J AU Knox, S Barnes, A Kiefe, C Lewis, CE Iribarren, C Matthews, KA Wong, ND Whooley, M AF Knox, S Barnes, A Kiefe, C Lewis, CE Iribarren, C Matthews, KA Wong, ND Whooley, M TI History of depression, race, and cardiovascular risk in CARDIA SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE depression; cardiovascular risk ID DENSITY-LIPOPROTEIN CHOLESTEROL; NUTRITION EXAMINATION SURVEY; NATIONAL-HEALTH; YOUNG-ADULTS; FOLLOW-UP; SYMPTOMS; MORTALITY; HYPERTENSION; DISEASE; AMERICANS AB Though previous data indicate a positive association between depression and coronary heart disease, the mechanisms mediating these associations remain unclear These prospective analyses assessed the association between history of Center for Epidemiologic Studies Depression Scale depression and possible mediators of cardiovascular risk at Year 15 of follow-up in African Americans (AA) and Caucasians (C) in the Coronary Artery Risk Development in Young Adults Study. Physiological assessments included plasma levels of low-density-lipoprotein cholestrol (LDL), high-density-lipoprotein cholestrol (HDL), total cholesterol, triglycerides and fasting glucose, diabetes and blood pressure. Behavioral risk factors included alcohol consumption, smoking, physical activity, and body mass index (BMI). AA's showed significant associations between history of depression and diabetes that did not exist in Cs and AA women had significantly more episodes of depression than any other group. However associations of depression with smoking, BMI, and physical activity were consistent across groups in the expected direction. HDL-cholesterol was positively and LDL-cholesterol inversely associated with depression in Cs, which was unexpected. These data indicate that in this still healthy cohort, there are already associations between depression and factors that predispose to cardiovascular risk. C1 NICHHD, Div Epidemiol Stat & Prevent, Bethesda, MD 20892 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Univ Calif San Francisco, Gen Internal Med Sect, San Francisco, CA 94143 USA. RP Knox, S (reprint author), NICHHD, Div Epidemiol Stat & Prevent, 6100 Execut Blvd,Room 5C01, Bethesda, MD 20892 USA. EM knoxss@mail.nih.gov FU NHLBI NIH HHS [N01-HC-95095, N01-HC-48047, N01-HC-48049, N01-HC-48050, N01-HC-48048] NR 28 TC 14 Z9 14 U1 2 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PY 2006 VL 13 IS 1 BP 44 EP 50 DI 10.1207/s15327558ijbm1301_6 PG 7 WC Psychology, Clinical SC Psychology GA 020WM UT WOS:000235943900006 PM 16503840 ER PT J AU LeRoith, D Gavrilova, O AF LeRoith, D Gavrilova, O TI Mouse models created to study the pathophysiology of Type 2 diabetes SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE type 2 diabetes; insulin resistance; mouse models; gene-deletion; transgenics ID CAUSES INSULIN-RESISTANCE; FACTOR-I RECEPTOR; ADIPOSE-TISSUE; TRANSGENIC MICE; BETA-CELLS; GLUCOSE-HOMEOSTASIS; TARGETED DISRUPTION; DEFICIENT MICE; MUSCLE; KNOCKOUT AB Obesity and Type 2 diabetes have become epidemics in the Western world. Understanding the pathophysiology of the disease should help in prevention and treatment of these disorders. A common theme is the presence of insulin resistance that eventually results in Type 2 diabetes. To understand the underlying mechanisms in the progression of the disease states, investigators have created mouse models by transgenic overexpression of a candidate gene or produced gene-deletion mouse models. This review will summarize many of the more appropriate models that study insulin resistance and Type 2 diabetes. (c) 2005 Elsevier Ltd. All rights reserved. C1 Natl Inst Hlth, Diabet Branch, Bethesda, MD 20892 USA. NIDDK, Mouse Metab Core Facil, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), Natl Inst Hlth, Diabet Branch, Room 8D12,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 38 TC 28 Z9 32 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2006 VL 38 IS 5-6 BP 904 EP 912 DI 10.1016/j.biocel.2005.01.019 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 028YX UT WOS:000236525800021 PM 16103004 ER PT J AU Mallon, BS Park, KY Chen, KG Hamilton, RS McKay, RDG AF Mallon, BS Park, KY Chen, KG Hamilton, RS McKay, RDG TI Toward xeno-free culture of human embryonic stem cells SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE human embryonic stem cells; MEF; feeder-free cell culture; matrigel ID PROLONGED UNDIFFERENTIATED GROWTH; FEEDER LAYERS; CONDITIONED MEDIUM; HUMAN BLASTOCYSTS; ES CELLS; PLURIPOTENCY; MAINTENANCE; SUPPORT; DIFFERENTIATION; LINES AB The culture of human embryonic stem cells (hESCs) is limited, both technically and with respect to clinical potential, by the use of mouse embryonic fibroblasts (MEFs) as a feeder layer. The concern over xenogeneic contaminants from the mouse feeder cells may restrict transplantation to humans and the variability in MEFs from batch-to-batch and laboratory-to-laboratory may contribute to some of the variability in experimental results. Finally, use of any feeder layer increases the work load and subsequently limits the large-scale culture of human ES cells. Thus, the development of feeder-free cultures will allow more reproducible culture conditions, facilitate scale-up and potentiate the clinical use of cells differentiated from hESC cultures. In this review, we describe various methods tested to culture cells in the absence of MEF feeder layers and other advances in eliminating xenogeneic products from the culture system. (c) 2006 Elsevier Ltd. All rights reserved. C1 NINDS, NIH, Stem Cell Unit, Bethesda, MD 20892 USA. RP Mallon, BS (reprint author), NINDS, NIH, Stem Cell Unit, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mallonb@mail.nih.gov; parkky@mail.nih.gov; cheng@mail.nih.gov; rebeccahamilton@mail.nih.gov; ronmckay@mail.nih.gov RI Chen, Kevin/D-6769-2011 OI Chen, Kevin/0000-0003-2983-6330 FU Intramural NIH HHS [Z99 NS999999] NR 40 TC 104 Z9 111 U1 3 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2006 VL 38 IS 7 BP 1063 EP 1075 DI 10.1016/j.biocel.2005.12.014 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 047VD UT WOS:000237905900007 PM 16469522 ER PT J AU Mack, AK Kato, GJ AF Mack, A. Kyle Kato, Gregory J. TI Sickle cell disease and nitric oxide: A paradigm shift? SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE sickle cell; nitric oxide; blood flow ID RED-BLOOD-CELLS; PULMONARY-HYPERTENSION; ENDOTHELIAL DYSFUNCTION; VASOOCCLUSIVE CRISIS; NO; HYDROXYUREA; HEMOGLOBIN; HEMOLYSIS; ARGININE; ANEMIA AB Traditionally the pathophysiology of sickle cell disease is thought to result from the polymerization of hemoglobin S in red cells, under hypoxic conditions, resulting in the occlusion of blood vessels. Adhesion of cells to the venular endothelium also appears to play a role. Recent studies have also suggested that in addition to the polymerization of hemoglobin S in the red blood cell, a deficiency of the endogenous vasodilator, nitric oxide may be involved. Hemoglobin released as a result of hemolysis rapidly consumes nitric oxide resulting in a whole program of events that inhibit blood flow. Therapies directed at decreasing the destruction of nitric oxide, increasing the production of nitric oxide, or amplifying the nitric oxide response may prove beneficial. Published by Elsevier Ltd. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Vasc Med Branch, Bethesda, MD USA. Ctr Clin, Dept Crit Care Med, NIH, Bethesda, MD USA. RP Mack, AK (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,MSC 1476, Bethesda, MD 20892 USA. EM kmack@mail.nih.gov; gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [Z99 HL999999, ZIA HL006014-02] NR 36 TC 47 Z9 53 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2006 VL 38 IS 8 BP 1237 EP 1243 DI 10.1016/j.biocel.2006.01.010 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 060ST UT WOS:000238822600002 PM 16517208 ER PT J AU Tominaga, Y Li, CL Wang, RH Deng, CX AF Tominaga, Yohei Li, Cuiling Wang, Rui-Hong Deng, Chu-Xia TI Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE Cdk1; Chk2; G2/M; apoptosis; genetic instability AB Wee1 kinase regulates the G2/M cell cycle checkpoint by phosphorylating and inactivating the mitotic cyclin-dependent kinase 1 (Cdk1). Loss of Wee1 in many systems, including yeast and drosophila, leads to premature mitotic entry. However, the developmental role of Wee1 in mammals remains unclear. In this study, we established Wee1 knockout mice by gene targeting. We found that Wee(-/-) embryos were defective in the G2/M cell cycle checkpoint induced by gamma-irradiation and died of apoptosis before embryonic (E) day 3.5. To study the function of Wee1 further, we have developed MEF cells in which Wee1 is disrupted by a tamoxifen inducible Cre-LoxP approach. We found that acute deletion of Wee1 resulted in profound growth defects and cell death. Wee1 deficient cells displayed chromosome aneuploidy and DNA damage as revealed by gamma-H2AX foci formation and Chk2 activation. Further studies revealed a conserved mechanism of Wee1 in regulating mitotic entry and the G2/M checkpoint compared with other lower organisms. These data provide in vivo evidence that mammalian Wee1 plays a critical role in maintaining genome integrity and is essential for embryonic survival at the pre-implantation stage of mouse development. C1 [Tominaga, Yohei; Li, Cuiling; Wang, Rui-Hong; Deng, Chu-Xia] NIDDK, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDK, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU intramural Research Program of National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA FX We thank members of Deng lab for critical discussion and reading of the manuscript. This work was supported by the intramural Research Program of National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA. NR 28 TC 41 Z9 43 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 2006 VL 2 IS 4 BP 161 EP 170 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA V39GJ UT WOS:000209399200001 PM 16810330 ER PT J AU De Soto, JA Wang, XY Tominaga, Y Wang, RH Cao, L Qiao, WH Li, CL Xu, XL Skoumbourdis, AP Prindiville, SA Thomas, CJ Deng, CX AF De Soto, Joseph A. Wang, Xianyan Tominaga, Yohei Wang, Rui-Hong Cao, Liu Qiao, Wenhui Li, Cuiling Xu, Xiaoling Skoumbourdis, Amanda P. Prindiville, Sheila A. Thomas, Craig J. Deng, Chu-Xia TI The Inhibition and Treatment of Breast Cancer with Poly (ADP-ribose) Polymerase (PARP-1) Inhibitors SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE PARP inhibitors; BRCA1; breast cancer; therapeutic treatment; tamoxifen AB BRCA1 and BRCA2 mutations are responsible for most familial breast carcinomas. Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA mutant cells with high specificity. Although these studies bring hope for BRCA mutation carriers, the effectiveness of PARP-1 inhibitors for breast cancer remains elusive. Here we present the first in vivo demonstration of PARP-1 activity in BRCA1-deficient mammary tumors and describe the effects of PARP-1 inhibitors (AG14361, NU1025, and 3-aminobenzamide) on BRCA1-deficient ES cells, mouse and human breast cancer cells. AG14361 was highly selective for BRCA1-/- ES cells; however, NU1025 and 3-aminobenzamide were relatively non-selective. In allografts of naive ES BRCA1-/- cells there was either partial or complete remission of tumors. However, in allografts of mouse, BRCA1-/- mammary tumors, there was no tumor regression or remission although a partial inhibition of tumor growth was observed in both the BRCA1-/- and BRCA1+/+ allografts. In human tumor cells, PARP-1 inhibitors showed no difference in vitro in limiting the growth of mammary tumors irrespective of their BRCA1 status. These results suggest that PARP-1 inhibitors may non-specifically inhibit the growth of mammary tumors. C1 [De Soto, Joseph A.; Wang, Xianyan; Tominaga, Yohei; Wang, Rui-Hong; Cao, Liu; Qiao, Wenhui; Li, Cuiling; Xu, Xiaoling; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Skoumbourdis, Amanda P.; Thomas, Craig J.] NIDDK, Chem Biol Core Facil, NIH, Bethesda, MD 20892 USA. [Prindiville, Sheila A.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDK, 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 intramural Research Program of National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA FX We thank Elise Kohn and members of Deng lab for critical discussion. This work was supported by the intramural Research Program of National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA. NR 23 TC 43 Z9 44 U1 1 U2 6 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 2006 VL 2 IS 4 BP 179 EP 185 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA V39GJ UT WOS:000209399200003 PM 16810332 ER PT J AU Wang, RH AF Wang, Rui-Hong TI The new portrait of mammary gland stem cells SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Letter C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Wang, RH (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM Rui-HongW@intra.niddk.nih.gov NR 5 TC 2 Z9 3 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 2006 VL 2 IS 4 BP 186 EP 187 PG 2 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA V39GJ UT WOS:000209399200004 PM 16810333 ER PT J AU Papaconstantinou, AD Shanmugam, I Shan, L Schroeder, IS Qiu, CP Yu, MS Snyderwine, EG AF Papaconstantinou, AD Shanmugam, I Shan, L Schroeder, IS Qiu, CP Yu, MS Snyderwine, EG TI Gene expression profiling in the mammary gland of rats treated with 7,12-dimethylbenz[a]anthracene SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE 7,12-dimethylbenz[a]anthracene (DMBA); rat mammary gland; microarray analysis; microtubule; heat shock protein ID HUMAN BREAST-CANCER; HEAT-SHOCK PROTEINS; FOOD-DERIVED CARCINOGEN; CYCLIN D1; MITOTIC-SPINDLE; DRUG-RESISTANCE; AURORA-A; IN-SITU; CELLS; STATHMIN AB Identification of molecular markers of early-stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed. Gene expression changes were further validated by a combination of techniques, including real-time PCR, RT-PCR, Western blotting and immunohistochemistry. An inhibition of differentiation in this early stage was suggested by the lower expression of P-casein and transferrin and higher expression of hsp27 in glands from DMBA-treated rats. Possible cell cycle deregulation was indicated by an increased expression of cyclin D1 and hsp86, a heat shock protein associated with cyclin D1. Prior to tumor development, DMBA increased cellular proliferation as detected by Ki-67 and stathmin immunostaining in histologically normal mammary gland. Genes regulating microtubule function, including stathmin, Ran, alpha-tubulin and hsp27, were all overexpressed in the mammary gland of DMBA-treated rats, raising the possibility that disruption of microtubule dynamics and abnormal mitosis may be critical events preceding breast cancer development. Several of the altered proteins, including hsp27, hsp86 and stathmin, may ultimately serve as markers of early breast cancer development. Published 2005 Wiley-Liss, Inc. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Sect Cellular & Mol Biol, Expt Carcinogenesis Lab, NIH, Bethesda, MD USA. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. EM elizabeth_snyderwine@nih.gov NR 51 TC 21 Z9 25 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2006 VL 118 IS 1 BP 17 EP 24 DI 10.1002/ijc.21247 PG 8 WC Oncology SC Oncology GA 985KJ UT WOS:000233376000004 PM 16003757 ER PT J AU Carreon, T Ruder, AM Schulte, PA Hayes, RB Rothman, N Waters, M Grant, DJ Boissy, R Bells, DA Kadlubar, FF Hemstreet, GP Yin, S Lemasters, GK AF Carreon, T Ruder, AM Schulte, PA Hayes, RB Rothman, N Waters, M Grant, DJ Boissy, R Bells, DA Kadlubar, FF Hemstreet, GP Yin, S Lemasters, GK TI NAT2 slow acetylation and bladder cancer in workers exposed to benzidine SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE bladder cancer; benzidine; arylamine N-acetyltransferase; glutathione S-transferase; case-control study ID N-ACETYLTRANSFERASE ACTIVITY; AROMATIC-AMINES; CIGARETTE-SMOKING; MOLECULAR EPIDEMIOLOGY; URINARY METABOLITES; OCCUPATIONAL-CANCER; RISK-FACTORS; DNA-ADDUCTS; HUMAN LIVER; PHENOTYPE AB This study expands a previous study of NAT2 polymorphisms and bladder cancer in male subjects occupationally exposed only to benzidine. The combined analysis of 68 cases and 107 controls from a cohort of production workers in China exposed to benzidine included 30 new cases and 67 controls not previously studied. NAT2 enzymatic activity phenotype was characterized by measuring urinary caffeine metabolite ratios. PCR-based methods identified genotypes for NAT2, NAT1 and GSTM1. NAT2 phenotype and genotype data were consistent. A protective association was observed for the slow NAT2 genotype (bladder cancer OR = 0.3; 95% CI = 0.1 = 1.0) after adjustment for cumulative benzidine exposure and lifetime smoking. Individuals carrying NAT1wt/*10 and NAT1*10/*10 showed higher relative risks of bladder cancer (OR = 2.8,95% CI = 0.8-10.1 and OR = 2.2,95% CI = 0.6-8.3, respectively). No association was found between GSTM1 null and bladder cancer. A metaanalysis risk estimate of case-control studies of NAT2 acetylation and bladder cancer in Asian populations without occupational arylamine exposures showed an increased risk for slow acetylators. The lower limit of the confidence interval (OR = 1.4; 95% 11 = 1.0-2.0) approximated the upper confidence interval for the estimate obtained in our analysis. These results support the earlier finding of a protective association between slow acetylation and bladder cancer in benzidine-exposed workers, in contrast to its established link as a risk factor for bladder cancer in people exposed to 2-naphthylamine and 4-aminobiphenyl. Study findings suggest the existence of key differences in the metabolism of mono- and diarylamines. Published 2005 Wiley-Liss, Inc. C1 NIOSH, Div Surveillance, Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. NIOSH, Educ & Informat Div, Cincinnati, OH 45226 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Natl Inst Environm Hlth Sci, Environm Gen Sect, Res Triangle Pk, NC USA. Natl Ctr Toxicol Res, Div Pharmacogen & Mol Epidemiol, Jefferson, AR 72079 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Urol, Oklahoma City, OK 73104 USA. Chinese Acad Prevent Med, Dept Toxicol, Beijing, Peoples R China. RP Carreon, T (reprint author), NIOSH, Div Surveillance, Hazard Evaluat & Field Studies, 4676 Columbia Pkway,Mailstop R-16, Cincinnati, OH 45226 USA. EM carreota@ucmail.uc.edu RI Carreon, Tania/A-6548-2008; Waters, Martha/B-7441-2011; Ruder, Avima/I-4155-2012; OI Ruder, Avima/0000-0003-0419-6664; Hayes, Richard/0000-0002-0918-661X NR 62 TC 36 Z9 36 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2006 VL 118 IS 1 BP 161 EP 168 DI 10.1002/ijc.21308 PG 8 WC Oncology SC Oncology GA 985KJ UT WOS:000233376000021 PM 16003747 ER PT J AU Khadka, D Luo, T Sargent, TD AF Khadka, D Luo, T Sargent, TD TI Msx1 and Msx2 have shared essential functions in neural crest but may be dispensable in epidermis and axis formation in Xenopus SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE homeodomain factor; morpholino antisense oligonucleotide ID BONE MORPHOGENETIC PROTEINS; TRANSCRIPTION FACTOR AP-2; LAEVIS EMBRYOGENESIS; DLX HOMEOPROTEINS; DORSOVENTRAL AXIS; GENE; INDUCTION; ORGANIZER; EXPRESSION; EMBRYOS AB The homeodomain factors Msx1 and Msx2 are expressed in essentially identical patterns in the epidermis and neural crest of Xenopus embryos during neurula stages. Disruption of Msx1 and Msx2 RNA splicing with antisense morpholino oligonucleotides shows that both factors are also required for expression of the neural crest gene Slug. Loss of Msx1 can be compensated by overexpression of Msx2 and vice versa. Loss of Msx factors also leads to alterations in the expression boundaries for neural and epidermal genes, but does not prevent or reduce expression of epidermal keratin in ventrolateral ectoderm, nor is there a detectable effect on dorsal mesodermal marker gene expression. These results indicate that Msx1 and Msx2 are both essential for neural crest development, but that the two genes have the same function in this tissue. If Msx genes have important functions in epidermis or axial mesoderm induction, these functions must be shared with other regulatory proteins. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Sargent, TD (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. EM tsargent@nih.gov FU Intramural NIH HHS NR 40 TC 16 Z9 17 U1 0 U2 0 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2006 VL 50 IS 5 BP 499 EP 503 DI 10.1387/ijdb.052115dk PG 5 WC Developmental Biology SC Developmental Biology GA 046BT UT WOS:000237787100008 PM 16586351 ER PT J AU Wittchen, HU AF Wittchen, Hans-Ulrich TI Editorial: small journal but significant impact! SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Editorial Material ID REPLICATION NCS-R; EPIDEMIOLOGY; DEPRESSION; DISORDERS; INTERVIEW; AIMS C1 TUD, Dresden, Germany. NIMH, Bethesda, MD USA. RP Wittchen, HU (reprint author), TUD, Dresden, Germany. EM wittchen@psychologie.tu-dresden.de RI Wittchen, Hans-Ulrich/A-8507-2014 NR 10 TC 0 Z9 0 U1 0 U2 0 PU WHURR PUBLISHERS LTD PI LONDON PA 19B COMPTON TERRACE, LONDON N1 2UN, ENGLAND SN 1049-8931 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PY 2006 VL 15 IS 3 BP 105 EP 106 DI 10.1002/mpr.192 PG 2 WC Psychiatry SC Psychiatry GA 087JX UT WOS:000240739800001 PM 17019894 ER PT J AU Zhu, YL Singh, B Hewitt, S Liu, AY Gomez, B Wang, AT Clarke, R AF Zhu, YL Singh, B Hewitt, S Liu, AY Gomez, B Wang, AT Clarke, R TI Expression patterns among interferon regulatory factor-1, human X-box binding protein-1, nuclear factor kappa B, nucleophosmin, estrogen receptor-alpha and progesterone receptor proteins in breast cancer tissue microarrays SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE immunohistochemistry; antiestrogen; Faslodex; tamoxifen; gene network ID HORMONE-INDEPENDENT GROWTH; NECROSIS-FACTOR-ALPHA; TRANSCRIPTION FACTOR XBP-1; CELL-ADHESION MOLECULE-1; GENE-EXPRESSION; ANTIESTROGEN RESISTANCE; ACQUIRED-RESISTANCE; FACTOR IRF-1; DNA-DAMAGE; APOPTOSIS AB Interferon regulatory factor-1 (IRF-1), human X-box binding protein-1 (hXBP-1), nuclear factor kappa B p65 (NF kappa B p65) and nucleophosmin (NPM) have been implicated in a signaling network of endocrine responsiveness. Expression of these proteins was measured by immunohistochemistry in tissue microarrays of 54 breast tumors. Correlations between each protein and established prognostic markers were assessed by Spearman's rank order correlation coefficient and partial correlation coefficient analyses. Moderate/strong staining is seen for hXBP-l (79% of tumors) and NF kappa B p65 (57%). NPM exhibits nuclear staining (95%); IRF-1 exhibits both cytosolic (IRF-1c; 90%) and nuclear staining (IRF-1n; 51%). IRF-1c is associated with age (p=0.034); IRF-1n and PgR expression are correlated (p=0.014). NF kappa B p65 shows a borderline association with S phase (p=0.062). Coexpression of IRF-1c and hXBP1 (p=0.001), IRF-1c and NF kappa B (p=0.002), and hXBP-l and NF kappa B (p=0.018) is observed. An inverse correlation exists between IRF-1n and NF kappa B (p=0.034). All four proteins are detected in breast tumors and their expression patterns support their role(s) in a key signaling network. C1 Georgetown Univ, Sch Med, Dept Oncol, Med Ctr,Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Georgetown Univ, Sch Med, Dept Biostat, Med Ctr,Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Georgetown Univ, Sch Med, Dept Biomath, Med Ctr,Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. NYU, Sch Med, Dept Pathol, New York, NY USA. NCI, Ctr Canc Res, Tissue Array Res Program, Pathol Lab, Bethesda, MD 20892 USA. NICHD, Biometry & Math Stat Branch, NIH, Bethesda, MD USA. RP Clarke, R (reprint author), Georgetown Univ, Sch Med, Dept Oncol, Med Ctr,Lombardi Comprehens Canc Ctr, Room W405A Res Bldg,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM clarker@georgetown.edu RI Clarke, Robert/A-6485-2008; OI Clarke, Robert/0000-0002-9278-0854; Hewitt, Stephen/0000-0001-8283-1788; Liu, Aiyi/0000-0002-6618-5082 FU NCI NIH HHS [R01-CA096483-01, P30-CA51008-14, R01-CA/AG58022-10] NR 76 TC 27 Z9 28 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JAN PY 2006 VL 28 IS 1 BP 67 EP 76 PG 10 WC Oncology SC Oncology GA 996UU UT WOS:000234201400007 PM 16327981 ER PT J AU Zhuang, ZP Huang, S Kowalak, JA Shi, Y Lei, JQ Furuta, M Lee, YS Lubensky, IA Rodgers, GP Cornelius, AS Weil, RJ Teh, BT Vortmeyer, AO AF Zhuang, ZP Huang, S Kowalak, JA Shi, Y Lei, JQ Furuta, M Lee, YS Lubensky, IA Rodgers, GP Cornelius, AS Weil, RJ Teh, BT Vortmeyer, AO TI From tissue phenotype to proteotype: Sensitive protein identification in microdissected tumor tissue SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE proteomics; RCC; profiling ID LASER CAPTURE MICRODISSECTION; MASS-SPECTROMETRY; CELL CARCINOMA; DNA; PROTEOMICS; ALGORITHM; CANCER; URINE; SERUM; GELS AB Correlation of disease phenotype with protein profile (proteotype) is a significant challenge for biomedical research. The main obstacles have been the need to insure sufficient quantities of pure protein sample, the reproducibility of protein display, and rapid and accurate protein identification. We present a modified approach that combines enhanced detection sensitivity with tissue microdissection from frozen primary renal cancer tissues of different histological subtypes, followed by 2D gel analysis and protein identification with MALDI mass spectrometry. We obtained reliable and highly consistent results in phenotypically similar tumors of each individual subtype by performing strict morphological control of the analyzed tumor cells without physical or chemical alteration of the frozen tissue samples. By application of nonoxidizing silver staining, proteins were resolved and identified with high levels of specificity and sensitivity. This new combination of techniques allows not only for sensitive identification of specific protein patterns that correspond to a histological tumor phenotype, but also for identification of specific disease-associated protein targets. C1 NINDS, NIH, Surg Neurol Branch, Bethesda, MD 20892 USA. NIMH, Mass Spectrometry Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Transmedix Corp, Rockville, MD 20850 USA. DoVos Childrens Hosp, Div Pediat Hematol Oncol, Grand Rapids, MI USA. Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA. RP Vortmeyer, AO (reprint author), NINDS, NIH, Surg Neurol Branch, 10 Ctr Dr,Bldg 10,Rm 4N242, Bethesda, MD 20892 USA. EM vortmeyera@ninds.nih.gov NR 20 TC 11 Z9 13 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JAN PY 2006 VL 28 IS 1 BP 103 EP 110 PG 8 WC Oncology SC Oncology GA 996UU UT WOS:000234201400011 PM 16327985 ER PT J AU Ball, GDC Huang, TTK Cruz, ML Shaibi, GQ Weigensberg, MJ Goran, MI AF Ball, Geoff D. C. Huang, Terry T. -K Cruz, Martha L. Shaibi, Gabriel Q. Weigensberg, Marc J. Goran, Michael I. TI Predicting abdominal adipose tissue in overweight Latino youth SO INTERNATIONAL JOURNAL OF PEDIATRIC OBESITY LA English DT Article DE overweight; anthropometry; Hispanic; child; magnetic resonance imaging ID TOTAL-BODY FAT; SIMPLE ANTHROPOMETRIC MEASUREMENTS; VISCERAL FAT; INSULIN SENSITIVITY; OBESE CHILDREN; RISK-FACTORS; WAIST CIRCUMFERENCE; METABOLIC SYNDROME; PUBERTAL CHILDREN; AFRICAN-AMERICAN AB Objectives. 1) Examine associations between visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and anthropometric and demographic variables; 2) generate and cross-validate prediction equations for estimating VAT and SAAT in overweight Latino children. Study design. Cross-sectional. Participants. 196 overweight 8-13-year-old Latino youth. Two-thirds (n =131) were randomly assigned to a development group to generate prediction equations for VAT and SAAT; one-third (n=65) was used as a cross-validation group. Methods and procedures. Anthropometric measurements (height, weight, skinfold thicknesses, and circumferences) were performed. VAT and SAAT were measured using magnetic resonance imaging (MRI). Results. The strongest univariate correlate for VAT was waist circumference (WC) (r = 0.65, p <0.01) while the strongest correlate for SAAT was hip circumference (r = 0.88, p <0.001). Regression analyses showed similar to 50% of the variance in VAT was explained by WC (43.8%), Tanner stage (4.2%) and calf skinfold (1.7%). Variance in the SAAT model was explained by WC (77.8%), triceps skinfold (4.2%) and gender (2.3%). Residual analyses showed no bias in either equation. Though mean differences between measured and predicted VAT and SAAT were small, there was a large degree of variability at the individual level especially for VAT. Conclusions. Both VAT and SAAT prediction equations performed well at the group level, but the relatively high degree of variability suggests limited clinical utility of the VAT equation. MRI is currently required to derive an accurate measure of VAT at the individual level. C1 Univ Alberta, Aberhart Ctr 1, Fac Med & Dent, Dept Pediat & Child Hlth, Edmonton, AB T6G 2J3, Canada. NICHHD, NIH, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA USA. RP Ball, GDC (reprint author), Univ Alberta, Aberhart Ctr 1, Fac Med & Dent, Dept Pediat & Child Hlth, Room 8213,11402 Univ Ave, Edmonton, AB T6G 2J3, Canada. EM geoff.ball@ualberta.ca FU NIDDK NIH HHS [R01 DK 59211] NR 39 TC 16 Z9 18 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1747-7166 J9 INT J PEDIATR OBES JI Int. J. Pediatr. Obes. PY 2006 VL 1 IS 4 BP 210 EP 216 DI 10.1080/17477160600913578 PG 7 WC Pediatrics SC Pediatrics GA 148OJ UT WOS:000245084200002 PM 17907327 ER PT J AU Barra, S Foppiano, F Guenzi, M Franzone, P Giannelli, F Amara, L Garelli, S Piergentili, M Garre, M Vitale, V AF Barra, S. Foppiano, F. Guenzi, M. Franzone, P. Giannelli, F. Amara, L. Garelli, S. Piergentili, M. Garre, M. Vitale, V. TI Clinical results in 46 pediatric patients treated by craniospinal technique in supine position using asymetric half fields SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 Natl Canc Inst, Genoa, Italy. SS Antonio Biagio Hosp, Alessandria, Italy. 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 2006 VL 66 IS 3 SU S MA 2580 BP S532 EP S532 DI 10.1016/j.ijrobp.2006.07.993 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221602092 ER PT J AU Cooper, JS Pajak, TF Forastiere, AA Jacobs, J Campbell, B Saxman, S Kish, J Cmelak, A Kim, H Fu, K AF Cooper, J. S. Pajak, T. F. Forastiere, A. A. Jacobs, J. Campbell, B. Saxman, S. Kish, J. Cmelak, A. Kim, H. Fu, K. TI Long-term survival results of a phase III intergroup trial (RTOG 95-01) of surgery followed by radiotherapy vs. radiochemotherapy for resectable high risk squamous cell carcinoma of the head and neck SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 Maimonides Canc Ctr, New York, NY 53226 USA. Radiat Therapy Oncol Grp Headquarters, Philadelphia, PA USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Wayne State Univ, Sch Med, Detroit, MI USA. Med Coll Wisconsin, Milwaukee, WI USA. Natl Canc Inst, Bethesda, MD USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Vanderbilt Canc Ctr, Nashville, TN USA. Univ Calif San Francisco, San Francisco, CA USA. NR 2 TC 5 Z9 5 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 2006 VL 66 IS 3 SU S MA 25 BP S14 EP S15 DI 10.1016/j.ijrobp.2006.07.1338 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221600030 ER PT J AU Flickinger, JC Recht, A DeCamp, M Fritz, A Varlotto, J AF Flickinger, J. C. Recht, A. DeCamp, M. Fritz, A. Varlotto, J. TI Multivariate and subgroup analysis of radiotherapy in surgical patients with non-small cell lung cancer from the SEER database SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 Univ Pittsburgh, Sch Med, Dept Radiat Oncol, Pittsburgh, PA USA. Harvard Med Sch, Dept Radiat Oncol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Med Sch, Dept Surg, Boston, MA USA. Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2006 VL 66 IS 3 SU S MA 113 BP S64 EP S65 DI 10.1016/j.ijrobp.2006.07.144 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221600109 ER PT J AU Hariri, G Zhang, Y Fu, A Han, Z Brechbiel, M Peterson, T Hallahan, D AF Hariri, G. Zhang, Y. Fu, A. Han, Z. Brechbiel, M. Peterson, T. Hallahan, D. TI Radiation guided anti-P-selectin antibody to tumor microvascular endothelium SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA. Vanderbilt Univ, Dept Radiat Oncol, Nashville, TN USA. Natl Canc Inst, Bethesda, MD USA. Vanderbilt Univ, Dept Radiol, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2006 VL 66 IS 3 SU S MA 2662 BP S577 EP S578 DI 10.1016/j.ijrobp.2006.07.1077 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221602174 ER PT J AU Li, G Xie, H Ning, H Citrin, D Capala, J Guion, P Arora, B Camphausen, K Coleman, N Miller, R AF Li, G. Xie, H. Ning, H. Citrin, D. Capala, J. Guion, P. Arora, B. Camphausen, K. Coleman, N. Miller, R. TI High accuracy of the 3D volumetric image registration: Correction of misalignment in cranial PET/CT images due to patient movement for stereotactic treatment planning SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 NIH, Natl Canc Inst, 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 2006 VL 66 IS 3 SU S MA 2775 BP S643 EP S644 DI 10.1016/j.ijrobp.2006.07.1192 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221602286 ER PT J AU Metz, JM Smith, D Mick, R Lustig, R Steal, B Mitchell, J Cherakuri, M Glatstein, E Hahn, SM AF Metz, J. M. Smith, D. Mick, R. Lustig, R. Steal, B. Mitchell, J. Cherakuri, M. Glatstein, E. Hahn, S. M. TI A phase I/II study of the safety, pharmacokinetics, and preliminary efficacy of MTS-01 for the prevention of alopecia induced by whole brain radiotherapy (WBRT) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Univ Arizona, Tucson, AZ USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2006 VL 66 IS 3 SU S MA 2588 BP S537 EP S538 DI 10.1016/j.ijrobp.2006.07.1001 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221602100 ER PT J AU Petereit, DG Mehta, MP Kaur, JS Govern, F Coleman, CN Ritter, MA Koscik, R Moser, AR Burhansstipanov, L Rogers, D AF Petereit, D. G. Mehta, M. P. Kaur, J. S. Govern, F. Coleman, C. N. Ritter, M. A. Koscik, R. Moser, A. R. Burhansstipanov, L. Rogers, D. TI Methods to address cancer disparities in special populations SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 John T Vucurevich Canc Ctr Inst, Rapid City, SD USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. Mayo Clin, Ctr Comprehens Canc, Rochester, MN USA. NCI, Radiat Res Program, Bethesda, MD 20892 USA. Native Amer Canc Res Corp, Pine, CO 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 2006 VL 66 IS 3 SU S MA 1014 BP S136 EP S137 DI 10.1016/j.ijrobp.2006.07.278 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221600229 ER PT J AU Sharp, HJ Morris, JC VanWaes, C Guis, D Karimpour, SE Cooley-Zgela, T Singh, AK AF Sharp, H. J. Morris, J. C. VanWaes, C. Guis, D. Karimpour, S. E. Cooley-Zgela, T. Singh, A. K. TI A high incidence of oral dysesthesias unrelated to mucositis in a pilot trial of gelitinib, paclitaxel and concurrent external beam radiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 NIH, Natl Canc Inst, Ctr Canc Res, Radiat Oncol Branch, Bethesda, MD USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Chevy Chase, MD USA. NIH, Natl Canc Inst, Ctr Canc Res, Metab Branch, Bethesda, MD USA. NIH, Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2006 VL 66 IS 3 SU S MA 1101 BP S188 EP S189 DI 10.1016/j.ijrobp.2006.07.366 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221600316 ER PT J AU Singh, AK Rader, JS Dehdashti, F Mutic, S Zoberi, I Grigsby, PW AF Singh, A. K. Rader, J. S. Dehdashti, F. Mutic, S. Zoberi, I. Grigsby, P. W. TI Prospective trial of concurrent chemoradiation with IMRT to 60 Gy for positive para-aortic lymph nodes in carcinoma of the cervix SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO 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 2006 VL 66 IS 3 SU S MA 1056 BP S162 EP S162 DI 10.1016/j.ijrobp.2006.07.321 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221600271 ER PT J AU Smart, DK Bradbury, CM Zhao, S Chuang, EY Robbins, M Gius, D AF Smart, D. K. Bradbury, C. M. Zhao, S. Chuang, E. Y. Robbins, M. Gius, D. TI Microarray analysis of differential gene expression in cerebral microvasculature of C3H mice following whole brain radiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 NIH DHHS, Natl Canc Inst, Ctr Canc Res, Radiat Oncol Branch, Bethesda, MD USA. NR 0 TC 0 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 2006 VL 66 IS 3 SU S MA 2701 BP S598 EP S599 DI 10.1016/j.ijrobp.2006.07.1117 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221602212 ER PT J AU Soule, BP Simone, NL Brown, J Metcalfe, D Mitchell, JB AF Soule, B. P. Simone, N. L. Brown, J. Metcalfe, D. Mitchell, J. B. TI Mast cells are radioresistant and exhibit inhibition of function but not apoptosis in response to ionizing radiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Radiat Biol Branch, Bethesda, MD USA. NCI, Radiat Oncol Branch, Bethesda, MD USA. NIH, NIAID, Lab Allerg Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2006 VL 66 IS 3 SU S MA 2621 BP S555 EP S555 DI 10.1016/j.ijrobp.2006.07.1035 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221602133 ER PT J AU Wang, TJ Bar-Sela, G Huang, L Sun, L Nguyen, P Pennington, J Gius, D AF Wang, T. J. Bar-Sela, G. Huang, L. Sun, L. Nguyen, P. Pennington, J. Gius, D. TI BORIS and CTCF Yin Yang epigenetically regulated transcription factors regulating proliferation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Radiat Oncol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2006 VL 66 IS 3 SU S MA 2627 BP S558 EP S559 DI 10.1016/j.ijrobp.2006.07.1041 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EF UT WOS:000241221602139 ER PT J AU Wong, RSL Brechbiel, MW AF Wong, Rosemary S. L. Brechbiel, Martin W. TI National cancer institute perspectives SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Systemics Targeted Radionuclide Therapy Symposium (STaRT) CY NOV 12-13, 2005 CL La Jolla, CA SP Amer Soc Therapeut Radiolo & Oncol DE targeted radionuclide therapy; radioinummotherapy; NCI funding mechanisms; program announcements ID DISSEMINATED PERITONEAL DISEASE; MONOCLONAL-ANTIBODY; RADIOIMMUNOTHERAPY; RECEPTOR; ANTIGEN; HER2 AB The National Cancer Institute (NCI) Perspectives this year presented information on the systemic targeted radionuclide therapy (STaRT) research projects: (1) being investigated at the NCI's Intramural Center for Cancer Research; (2) funded by NCI's Radiation Research Program and other extramural programs; and (3) the appropriate National Institutes of Health/NCI funding mechanisms applicable to researchers for obtaining funds for STaRT projects. (c) 2006 Elsevier Inc. C1 NCI, Radiat Res Program, Radiotherapy Dev Branch, NIH, Rockville, MD 20852 USA. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Rockville, MD 20852 USA. RP Wong, RSL (reprint author), NCI, Radiat Res Program, Radiotherapy Dev Branch, NIH, 6130 Execut Blvd,EPN 6016, Rockville, MD 20852 USA. EM rw26f@nih.gov FU Intramural NIH HHS NR 10 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 2006 VL 66 IS 2 SU S BP S96 EP S99 DI 10.1016/j.ijrobp.2006.04.057 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 088IP UT WOS:000240805700018 PM 16979449 ER PT J AU Citrin, D Menard, C Camphausen, K AF Citrin, D Menard, C Camphausen, K TI Combining radiotherapy and angiogenesis inhibitors: Clinical trial design SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT RTOG Symposium on Anti-Angiogenic Therapy - Maximizing Therapeutic Gain CY JUN 25, 2004 CL Washington, DC SP Radiat Therapy Oncol Grp, AstraZeneca Pharmaceut, Millennium Pharmaceut Inc, Ortho Biotech Prod LP, Sanofi Aventis DE angiogenesis; radiotherapy; antiangiogenic therapy; angiogenesis inhibitor ID ENDOTHELIAL GROWTH-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; SQUAMOUS-CELL CARCINOMA; PHASE-II TRIAL; HUMAN TUMOR XENOGRAFTS; BREAST-CANCER PATIENTS; ANTIANGIOGENIC AGENT SU5416; LYMPH-NODE METASTASIS; LEWIS LUNG-CARCINOMA; PROGNOSTIC-SIGNIFICANCE AB Radiotherapy (RT) plays a vital role in the multimodality treatment of cancer. Recent advances in RT have primarily involved improvements in dose delivery. Future improvements in tumor control and disease outcomes will likely involve the combination of RT with targeted therapies. Preclinical evaluations of angiogenesis inhibitors in combination with RT have yielded promising results with increased tumor "cure." It remains to be seen whether these improvements in tumor control in the laboratory will translate into improved outcomes in the clinic. Multiple differences between these agents and cytotoxic chemotherapy must be taken into account when designing clinical trials evaluating their effectiveness in combination with RT. We discuss important considerations for designing clinical trials of angiogenesis inhibitors with RT. (c) 2006 Elsevier Inc. C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. Univ Toronto, Princess Margaret Hosp, Radiat Med Program, Toronto, ON, Canada. RP Citrin, D (reprint author), NCI, Radiat Oncol Branch, Bldg 10,Rm B2-3561,10 Ctr Dr,MSC 1682, Bethesda, MD 20892 USA. EM citrind@mail.nih.gov NR 127 TC 26 Z9 32 U1 1 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. PD JAN 1 PY 2006 VL 64 IS 1 BP 15 EP 25 DI 10.1016/j.ijrobp.2005.03.065 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 000DX UT WOS:000234442200004 PM 16377411 ER PT J AU Kwon, M Libutti, SK AF Kwon, M Libutti, SK TI Advances in understanding angiogenesis through molecular studies SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT RTOG Symposium on Anti-Angiogenic Therapy - Maximizing Therapeutic Gain CY JUN 25, 2004 CL Washington, DC SP Radiat Therapy Oncol Grp, AstraZeneca Pharmaceut, Millennium Pharmaceut Inc, Ortho Biotech Prod LP, Sanofi Aventis DE angiogenesis; microarray analysis; molecular pathways; antiangiogenic factors; tumor-host interaction ID ENDOTHELIAL GROWTH-FACTOR; HUMANIZED MONOCLONAL-ANTIBODY; CELL-BRANCHING MORPHOGENESIS; ACTIVATED PROTEIN-KINASE; TUMOR-GROWTH; SIGNAL-TRANSDUCTION; HUMAN ENDOSTATIN; VEGF EXPRESSION; DOWN-SYNDROME; SOLID TUMORS AB Tumors, in most cases, need angiogenesis for their sustained growth. A great deal of evidence has suggested that the process of angiogenesis is regulated by the balance between proangiogenic and antiangiogenic factors. Thus, the inhibition of tumor angiogenesis has been considered to be one of the key targets in anticancer therapy, and more than 60 antiangiogenic compounds are currently under clinical evaluation in cancer patients. However, the molecular mechanisms responsible for the activity of many of these antiangiogenic compounds are still not well understood. The recent development of microarray technology has allowed us to investigate the mechanism of action of these inhibitors more rapidly and extensively. With the use of microarray technology, novel molecules and pathways are shown to play a role in angiogenesis. This article also reviews new experimental approaches combined with microarray analysis to identify the molecular pathways involved in tumor-host interactions. Elucidation of the pathways that mediate both angiogenic and antiangiogenic responses will help us to develop better anticancer therapies. (c) 2006 Elsevier Inc. C1 NCI, Ctr Canc Res, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Ctr Canc Res, Surg Branch, NIH, 10 Ctr Dr,Room 4W-5940, Bethesda, MD 20892 USA. EM steven_libutti@nih.gov NR 65 TC 2 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2006 VL 64 IS 1 BP 26 EP 32 DI 10.1016/j.ijrobp.2005.03.024 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 000DX UT WOS:000234442200005 PM 16377412 ER PT J AU Castillo, M Sanjuan, A Perez, N Zanon, G Bons, N Vilanova, M Vanrell, JA Merino, MJ Fernandez, PL AF Castillo, M Sanjuan, A Perez, N Zanon, G Bons, N Vilanova, M Vanrell, JA Merino, MJ Fernandez, PL TI Fibrous histiocytoma-like spindle-cell proliferation in the nipple after body-piercing SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE nipple; piercing; spindle-cell proliferation; fibrous histiocytoma ID DERMATOFIBROMA; MASTITIS AB We report the case of a 19-year-old pregnant woman who presented with a nipple tumor. The lesion consisted in a spindle-cell proliferation with histologic features similar to those of fibrous histiocytoma, with a highly vascularized stroma. Although it showed low mitotic activity, scattered marked atypical cells with prominent nucleoli were identified, thus raising concern about the benign nature of the tumor. Immunohistochemical evaluation revealed that the spindle cells were diffusely positive for vimentin, focally positive for CD68, and negative for all the other tested antibodies. The patient had a total excision of the lesion and she is free of disease after 30 months. To our knowledge this is the first reported case of a lesion of this type in the nipple after body-piercing. C1 NCI, Dept Surg Pathol, NIH, Bethesda, MD 20892 USA. Hosp Nostra Senyora de Meritxell, Dept Obstet & Gynecol, Andorra, Spain. Univ Barcelona, Hosp Clin, Dept Pathol, Andorra, Spain. Univ Barcelona, Hosp Clin, Dept Obstet & Gynecol, Andorra, Spain. RP Fernandez, PL (reprint author), Hosp Clin Barcelona, Dept Pathol, Villarroel 170, E-08036 Barcelona, Spain. RI Castillo-Martin, Mireia/H-6152-2013 NR 13 TC 2 Z9 2 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JAN PY 2006 VL 14 IS 1 BP 89 EP 93 DI 10.1177/106689690601400118 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 009CC UT WOS:000235087700018 PM 16501844 ER PT S AU Grivennikov, SI Kuprash, DV Liu, ZG Nedospasov, SA AF Grivennikov, Sergei I. Kuprash, Dmitry V. Liu, Zheng-Gang Nedospasov, Sergei A. BE Jeon, KW TI Intracellular signals and events activated by cytokines of the tumor necrosis factor superfamily: From simple paradigms to complex mechanisms SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 252 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review; Book Chapter DE TNFR superfamily; signal transduction; apoptosis; gene activation; adaptor molecules; caspases; transcriptional factors ID NF-KAPPA-B; FACTOR-RECEPTOR SUPERFAMILY; TRAIL-INDUCED APOPTOSIS; CELL-SURFACE ANTIGEN; DEATH DOMAIN KINASE; TNF-RECEPTOR; JNK ACTIVATION; FAS LIGAND; ECTODERMAL DYSPLASIA; CRYSTAL-STRUCTURE AB Tumor necrosis factor (TNF) and several related cytokines can induce opposite effects such as cell activation and proliferation or cell death. How the cell maintains the balance between these seemingly mutually exclusive pathways has long remained a mystery. TNF receptor I (TNFRI) initially emerged as a potent activator of NF kappa B and AP-1 transcription factors, while the related CD95 (Fas, Apo-1) was recognized as a prototype death receptor. Advances in research have uncovered critical molecular players in these intracellular processes. They have also revealed a much more complex picture than originally thought. Several new signaling pathways, including the alternative NF kappa B activation cascade, have been uncovered, and previously unknown modes of cross-talk between intracellular signaling molecules were revealed. It also turned out that signaling mechanisms mediated by the TNF receptor superfamily members can operate not only in the immune system but also in organ development. C1 Russian Acad Sci, Engelhardt Inst Mol biol, Lab Mol Immunol, Moscow 119991, Russia. NCI, Basic Res Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. NCI, Cell & Canc Biol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Grivennikov, SI (reprint author), Russian Acad Sci, Engelhardt Inst Mol biol, Lab Mol Immunol, Moscow 119991, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 154 TC 61 Z9 63 U1 2 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 BN 978-0-12-364656-9 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2006 VL 252 BP 129 EP + DI 10.1016/S0074-7696(06)52002-9 PG 38 WC Cell Biology SC Cell Biology GA BFV20 UT WOS:000244749600003 PM 16984817 ER PT S AU Pavlov, YI Shcherbakova, PV Rogozin, IB AF Pavlov, Youri I. Shcherbakova, Polina V. Rogozin, Igor B. BE Jeon, KW TI Roles of DNA polymerases in replication, repair, and recombination in eukaryotes SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 255 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review; Book Chapter DE DNA polymerase; DNA damage; replication; repair; recombination; fidelity; mutagenesis; evolution; human disease ID CELL NUCLEAR ANTIGEN; DOUBLE-STRAND-BREAK; BASE EXCISION-REPAIR; INTERSTRAND CROSS-LINKS; CLASS SWITCH RECOMBINATION; YEAST SACCHAROMYCES-CEREVISIAE; HUMAN MISMATCH REPAIR; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; GENE SOMATIC HYPERMUTATION; DAMAGE-INDUCED MUTAGENESIS AB The functioning of the eukaryotic genome depends on efficient and accurate DNA replication and repair. The process of replication is complicated by the ongoing decomposition of DNA and damage of the genome by endogenous and exogenous factors. DNA damage can alter base coding potential resulting in mutations, or block DNA replication, which can lead to double-strand breaks (DSB) and to subsequent chromosome loss. Replication is coordinated with DNA repair systems that operate in cells to remove or tolerate DNA lesions. DNA polymerases can serve as sensors in the cell cycle checkpoint pathways that delay cell division until damaged DNA is repaired and replication is completed. Eukaryotic DNA template-dependent DNA polymerases have different properties adapted to perform an amazingly wide spectrum of DNA transactions., In this review, we discuss the structure, the mechanism, and the evolutionary relationships of DNA polymerases and their possible functions in the replication of intact and damaged chromosomes, DNA damage repair, and recombination. C1 Univ Nebraska, Med Ctr, Epilepsy Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. RP Pavlov, YI (reprint author), Univ Nebraska, Med Ctr, Epilepsy Inst Res Canc & Allied Dis, 600 S 42nd St, Omaha, NE 68198 USA. NR 534 TC 75 Z9 79 U1 3 U2 14 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 BN 0-12-373599-8 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2006 VL 255 BP 41 EP + DI 10.1016/S0074-7696(06)55002-8 PG 98 WC Cell Biology SC Cell Biology GA BFO35 UT WOS:000243406000002 PM 17178465 ER PT J AU FitzGerald, MP Brensinger, C Brubaker, L Propert, K AF FitzGerald, MP Brensinger, C Brubaker, L Propert, K CA ICDB Study Grp TI What is the pain of interstitial cystitis like? SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article AB To describe the characteristics of pain experienced by patients with interstitial cystitis (IC) in terms of pain site, severity, and character, we performed a secondary analysis of data from the IC database (ICDB), which was a prospective, longitudinal, cohort study of IC patients. We analyzed the cross-sectional baseline data from 629 patients who had a completed baseline symptom questionnaire. Patients answered questions about whether they had pain or discomfort associated with urinary symptoms over the past 4 weeks and if so, about the location, characteristics, intensity, and frequency of their pain. Logistic regression examined associations between pain location and the presence of urinary symptoms. Analyses were performed using SAS version 8.2 (SAS Institute, Cary, NC, USA) and considered significant at the 5% level. Five hundred and eighty-nine (94%) patients with a mean age of 45 years (SD 14 years) reported baseline pain or discomfort associated with their urinary symptoms. The most common baseline pain site was lower abdominal (80%), with urethral (74%) and low back pain (65%) also commonly reported. The majority of patients described their pain as intermittent, regardless of the pain site. Most patients reported moderate pain intensity, across all pain sites. There was a statistically significant link between pain in the urethra, lower back, and lower abdomen, and urinary symptoms. Patients with IC report pain at several sites other than the bladder, possibly arising from the previously well-described myofascial abnormalities of pelvic floor and abdominal wall present in patients with IC and other chronic pelvic pain syndromes. C1 Loyola Univ, Med Ctr, Dept Urol, Div Pelv Med & Reconstruct Pelv Surg, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NIDDK, ICDB Study Grp, Bethesda, MD USA. RP FitzGerald, MP (reprint author), Loyola Univ, Med Ctr, Dept Urol, Div Pelv Med & Reconstruct Pelv Surg, 2160 S 1st Ave,Bldg 103,Room 1004, Maywood, IL 60153 USA. EM m.fitzg8@lumc.edu FU NIDDK NIH HHS [U01-DK-44998, U01-DK-45026, U01-DK-45859, U01-DK-45022, U01-DK-45021, U01-DK-54127, U01-DK-45013] NR 5 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD JAN PY 2006 VL 17 IS 1 BP 69 EP 72 DI 10.1007/s00192-005-1344-z PG 4 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 992EW UT WOS:000233868200015 PM 15995791 ER PT S AU Antani, S Cheng, J Long, J Long, LR Thoma, GR AF Antani, Sameer Cheng, Jing Long, Jonathan Long, L. Rodney Thoma, George R. BE Santini, S Schettini, R Gevers, T TI Medical validation and CBIR of spine X-ray images over the Internet SO INTERNET IMAGING VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Internet Imaging VII CY JAN 18-19, 2006 CL San Jose, CA SP Soc Imaging Sci & Technol, SPIE DE CBIR; medical image retrieval; validation; shape similarity; client-server; NHANES II; spine x-ray; bone morphometry; medical multimedia database ID RETRIEVAL AB As found in the literature. most Internet-based prototype Content-Based Image Retrieval (CBIR) systems focus on stock photo collections and do not address challenges of large specialized image collections and topics such as medical information retrieval by image content. Even fewer have medically validated data to evaluate retrieval quality in terms of precision and relevance. To date. our research has reported over 75% relevant spine X-ray image retrieval tested on 888 validated vertebral shapes from 207 images using our prototype CBIR system operating within our local network. As a next step. we have designed and developed an Internet-based medical validation tool and a CBIR retrieval tool in MATLAB and JAVA that can remotely connect to our database. The retrieval tool supports hybrid text and image queries and also provides partial shape annotation for pathology-specific querying. These tools are initially developed for domain experts. such as radiologists and educators. to identify design issues for improved workflow. This article describes the tools and design considerations in their development. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, DHHS, Bethesda, MD 20894 USA. RP Antani, S (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, DHHS, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 11 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 0-8194-6101-6 J9 PROC SPIE PY 2006 VL 6061 AR 60610J DI 10.1117/12.649372 PG 9 WC Computer Science, Information Systems; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BEF56 UT WOS:000237101500018 ER PT J AU Payette, PJ Ma, XY Weeratna, RD McCluskie, MJ Shapiro, M Engle, RE Davis, HL Purcell, RH AF Payette, PJ Ma, XY Weeratna, RD McCluskie, MJ Shapiro, M Engle, RE Davis, HL Purcell, RH TI Testing of CpG-optimized protein and DNA vaccines against the hepatitis B virus in chimpanzees for immunogenicity and protection from challenge SO INTERVIROLOGY LA English DT Article DE HBV vaccines; plasmid DNA; CpG motifs; CpG ODN; chimpanzees ID IMMUNE-RESPONSES; SURFACE-ANTIGEN; BACTERIAL-DNA; ACTIVATION; MOTIFS; OLIGODEOXYNUCLEOTIDE; IMMUNIZATION; INFECTION; ADJUVANT; ROUTE AB Despite the existence for some time of effective prophylactic vaccines, hepatitis B virus (HBV) infection remains an important global concern. Improvements on existing vaccines could be beneficial, especially in situations where it is desirable or necessary to induce protective immunity more rapidly or with fewer doses. We have compared, in chimpanzees, a current HBV vaccine that contains recombinant hepatitis B surface antigen HBsAg) adsorbed to alum, with two novel vaccine strategies that have proven superior to the current vaccine in mice. The first approach was the use of oligodeoxynucleotides containing CpG motifs ( CpG ODN) as an adjuvant to Engerix-B(R), a commercial HBV vaccine. The addition of CpG ODN to Engerix-B greatly improved the kinetics and magnitude of the humoral response, suggesting that CpG ODN might allow induction of protective immunity in humans more quickly and with fewer vaccine doses. All animals receiving either control or CpG-containing subunit vaccines at 0 and 4 weeks attained titers of HBsAg-specific antibody (anti-HBs) considered protective (>= 10 mIU/ml) and were indeed protected from challenge at 8 weeks with 10(3.5) 50% chimp infectious doses (CID50) of intravenous HBV. The second approach was a DNA vaccine with a plasmid vector optimized for content of immunostimulatory CpG motifs. Despite the fact that earlier studies had shown four doses of a similar DNA vaccine ( except not optimized for CpG content) to induce strong humoral responses in 1 of 2 chimpanzees, in this study two doses of DNA vaccine ( at 0 and 4 weeks) did not generate any detectable anti-HBs in either of 2 chimpanzees, although it did protect 1 that rapidly developed anti-HBs during the incubation period, suggesting priming of an antibody response. The poor results may be due to an inadequate number of doses or amount of plasmid DNA in these larger animals, but nevertheless point to the need to improve delivery methods for DNA vaccines for use in larger animals such as primates. Copyright (C) 2006 S. Karger AG, Basel. C1 Coley Pharmaceut Canada, Ottawa, ON K2K 3A2, Canada. Bioqual Inc, Rockville, MD USA. NIAID, Bethesda, MD 20892 USA. RP Davis, HL (reprint author), Coley Pharmaceut Canada, 340 Terry Fox Dr,Suite 200, Ottawa, ON K2K 3A2, Canada. EM hdavis@coleypharma.com NR 28 TC 15 Z9 20 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PY 2006 VL 49 IS 3 BP 144 EP 151 DI 10.1159/000089375 PG 8 WC Virology SC Virology GA 005NF UT WOS:000234829200004 PM 16428890 ER PT J AU Malyukova, I Lee, HS Fariss, RN Tomarev, SI AF Malyukova, I Lee, HS Fariss, RN Tomarev, SI TI Mutated mouse and human myocilins have similar properties and do not block general secretory pathway SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; RETINAL-PIGMENT EPITHELIUM; TRABECULAR MESHWORK CELLS; SEQUENCE TAG ANALYSIS; NEIBANK PROJECT; WILD-TYPE; HUMAN EYE; OLFACTOMEDIN; LOCALIZATION; PROTEINS AB PURPOSE. The present study compared properties of wild-type and mutated mouse and human myocilin (Myoc) proteins as a prerequisite for development of a mouse model of glaucoma. METHODS. cDNA encoding full- length mouse Myoc was cloned into the p3XFLAG-CMV-14 vector. Tyr423His and Ile463Ser mutations were introduced into the mouse Myoc protein by in vitro mutagenesis. Intracellular localization and secretion of wild-type and mutated mouse Myoc proteins were studied in immunostaining and Western blotting experiments, respectively, after transfection into COS-7 cells. RESULTS. Similar to human MYOC, wild-type and mutated mouse Myoc demonstrated vesicular staining in transfected cells. However, while wild-type human and mouse Myoc were preferentially located in both the endoplasmic reticulum and Golgi, mutated human and mouse Myoc were located mainly in the endoplasmic reticulum and were excluded from Golgi. Similar to mutations in human MYOC, mutations in mouse Myoc dramatically reduced its secretion from transfected cells. Secretion of mutated Myoc was partially restored by culturing cells at 30 degrees C instead of 37 degrees C. The presence of mutated human MYOC prevented secretion of wild-type mouse Myoc but did not dramatically affect secretion of alkaline phosphatase, thrombospondin, Timp3 or olfactomedin-1. CONCLUSIONS. Properties of the mouse Myoc protein are similar to those of the human MYOC. The presence of mutated mouse or human Myoc does not block a general secretory pathway. Expression of mutated Myoc in the eye in mice may mimic human glaucoma and lead to development of a genetic mouse model of glaucoma. C1 NEI, NIH, Biol Imaging Core, Bethesda, MD 20892 USA. NEI, Sect Mol Mechanisms Glaucoma, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tomarev, SI (reprint author), NEI, NIH, Biol Imaging Core, Bldg 7,Room 103,7 Mem Dr MSC 0704, Bethesda, MD 20892 USA. EM tomarevs@nei.nih.gov FU Intramural NIH HHS NR 51 TC 21 Z9 22 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2006 VL 47 IS 1 BP 206 EP 212 DI 10.1167/iovs.05-0220 PG 7 WC Ophthalmology SC Ophthalmology GA 998AH UT WOS:000234289700029 PM 16384964 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI On the origin of cells and viruses: A comparative-genomic perspective SO ISRAEL JOURNAL OF ECOLOGY & EVOLUTION LA English DT Article; Proceedings Paper CT International Conference Workshop on New Horizons in Evolutionary Biology CY JAN 23-25, 2007 CL Univ Haifa, Haifa, ISRAEL HO Univ Haifa DE comparative genomics; evolution of cells; evolution of viruses; origin of membranes; viral hallmark genes ID UNIVERSAL COMMON ANCESTOR; DNA-REPLICATION PROTEINS; TRANSFER-RNA SYNTHETASES; HORIZONTAL GENE-TRANSFER; CELLULAR EVOLUTION; LIFE; TREE; WORLD; ROOT; ORGANIZATION AB It is proposed that the pre-cellular stage of biological evolution, including the Last Universal Common Ancestor (LUCA) of modern cellular life forms, occurred within networks of inorganic compartments that hosted a diverse mix of virus-like genetic elements. This viral model of cellular origin recapitulates the early ideas of J.B.S. Haldane, sketched in his 1928 essay on the origin of life. However, unlike in Haldane's day, there is substantial empirical support for this scenario from three major lines of evidence provided by comparative genomics: (i) the lack of homology among the core components of the DNA replication systems between the two primary lines of descent of cellular life forms, archaea and bacteria, (ii) the similar lack of homology between the enzymes of lipid biosynthesis in conjunction with distinct membrane chemistries in archaea and bacteria, and (iii) the spread of several viral hallmark genes, which encode proteins with key functions in viral replication and morphogenesis, among numerous and extremely diverse groups of viruses, in contrast to their absence in cellular life forms. Under the viral model of pre-cellular evolution, the key elements of cells including the replication apparatus, membranes, molecular complexes involved in membrane transport and translocation, and others originated as components of virus-like entities. This model alleviates, at least in part, the challenge of the emergence of the immensely complex organization of modern cells. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.go NR 84 TC 6 Z9 6 U1 1 U2 3 PU SCIENCE FROM ISRAEL-DIVISION OF LASER PAGES PUBL LTD PI JERUSALEM PA PO BOX 35409, JERUSALEM 91352, ISRAEL SN 0021-2210 J9 ISR J ECOL EVOL JI Isr. J. Ecol. Evol. PY 2006 VL 52 IS 3-4 BP 299 EP 318 DI 10.1560/IJEE_52_3-4_299 PG 20 WC Ecology; Evolutionary Biology SC Environmental Sciences & Ecology; Evolutionary Biology GA 233RC UT WOS:000251107000007 ER PT J AU Costin, GE Birlea, SA AF Costin, GE Birlea, SA TI Is there an answer? What is the mechanism for melasma that so commonly accompanies human pregnancy? SO IUBMB LIFE LA English DT Article ID MELANOCYTE-STIMULATING HORMONE; ESTROGEN-RECEPTOR; SKIN; BETA; DISORDERS; EFFICACY; TISSUE; ALPHA; ACID C1 NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Zalau Hosp, Zalau, Romania. RP Costin, GE (reprint author), Avon Prod Inc, New Technol Dept, 1 Avon Pl, Suffern, NY 10901 USA. EM costin_emilia@hotmail.com NR 24 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JAN PY 2006 VL 58 IS 1 BP 55 EP 57 DI 10.1080/15216540500417020 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 021KG UT WOS:000235981500008 PM 16540433 ER PT J AU Mehta, SH Gupta, A Sahay, S Godbole, SV Joshi, SN Reynolds, SJ Celentano, DD Risbud, AT Mehendale, SM Bollinger, RC AF Mehta, SH Gupta, A Sahay, S Godbole, SV Joshi, SN Reynolds, SJ Celentano, DD Risbud, AT Mehendale, SM Bollinger, RC TI High HIV prevalence among a high-risk subgroup of women attending sexually transmitted infection clinics in Pune, India SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; AIDS; women; sexually transmitted diseases; prevalence; India ID IMMUNODEFICIENCY-VIRUS TYPE-1; TRANSMISSION AB Objective: To investigate changes over a decade in prevalence and correlates of HIV among high-risk women attending sexually transmitted infection (STI) clinics in Pune, India, who deny a history of commercial sex work (CSW). Design: Cross-sectional. Methods: From 1993 to 2002, 2376 women attending 3 STI clinics ill Pune were offered HIV screening. Women who denied CSW were included (n = 1020). Results: Of 1020 women, 21% were HIV infected. The annual HIV prevalence increased from 14% in 1993 to 29% in 2001-2002 (P < 0.001). The change in HIV prevalence over time was paralleled by changes in clinic visitor characteristies; in later periods, women were older, more often employed, less likely to be currently married, and more likely to report condom use. In multivariate analysis, factors independently associated with HIV were calendar period (adjusted odds ratio [AOR], 1.9 for 1997-1999 vs. 1993-1996; 95% CI, 1.2-3.0; AOR, 2.3 for 2000-2002 vs. 1993-1996; 95% CI, 1.5-3.6), lack of formal education (AOR, 2.0; 95% CI, 1.4-2.9), having been widowed (AOR, 3.1; 95% CI, 1.6-6.1), Current employment (AOR, 1.8; 95% CI, 1.2-2.6), and genital ulcer disease oil examination (AOR, 1.8; 95% Cl, 1.2-2.7). Conclusions: Women attending STI clinics in India who deny a history of CSW represent a small, hidden subgroup, likely put at risk for HIV because of high-risk behavior of their male partners, generally their husbands. Educational and awareness efforts that have targeted other subgroups in India (men and CSWs) should also focus on these hard-to-reach women. Risk reduction in this subgroup of Indian women would also be expected to reduce perinatal infections in India. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Natl AIDS Res Inst, Pune, Maharashtra, India. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. RP Mehta, SH (reprint author), 615 N Wolfe St,E6537, Baltimore, MD 21202 USA. EM shmetha@jhsph.edu FU FIC NIH HHS [D43 TW00010-AITRP]; NIAID NIH HHS [1R01-AI41369, 1R21-AI3387901, AI 35173] NR 21 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2006 VL 41 IS 1 BP 75 EP 80 DI 10.1097/01.qai.0000174653.17911.4a PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 000CM UT WOS:000234438500012 PM 16340477 ER PT J AU De la Rosa, M Rugh, D Rice, C AF De La Rosa, Mario Rugh, Douglas Rice, Christopher TI An analysis of risk domains associated with drug transitions of active Latino gang members SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE substance abuse; adolescents; risks; gangs; ethnography ID SUBSTANCE USE; MEXICAN-AMERICAN; AFRICAN-AMERICAN; SCHOOL DROPOUTS; BEHAVIOR; DELINQUENCY; ADOLESCENTS; VIOLENCE; YOUTH AB Alcohol and illicit drug abuse is a serious problem among male Latino gang members. Research indicates that gang members increase their drug use while they are members, and use more drugs after they leave the gangs. This manuscript reports on data reflecting the influences of individual, familial, peer, and community factors on the number of drug use transitions that Latino gang members undergo during their drug using careers. Data from this study were collected from interviews conducted with seventy-six active Latino gang members. The study's results indicate that acre at the time of interview and lower age of drug onset were associated with a greater number of drug use transitions. Positive family attitudes toward deviance, friend drug use, school truancy, conflict with parents, and living in neighborhoods with a high level of crime were also found to be associated with increased drug use transitions. C1 Florida Int Univ, Sch Social Work, Miami, FL 33199 USA. NIDA, Bethesda, MD 20892 USA. RP De la Rosa, M (reprint author), Florida Int Univ, Sch Social Work, PCA 354B,11200 SW 8th St, Miami, FL 33199 USA. EM delarosa@fiu.edu RI Bowyer, Jade/H-1930-2012 FU NIDA NIH HHS [R24 DA014260] NR 24 TC 2 Z9 2 U1 1 U2 3 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 2006 VL 25 IS 4 BP 81 EP 90 DI 10.1300/J069v25n04_08 PG 10 WC Substance Abuse SC Substance Abuse GA 116YN UT WOS:000242839800008 PM 17088228 ER PT J AU Denisco, RA AF Denisco, Richard A. TI Comments by Richard A. Denisco SO JOURNAL OF ADDICTIVE DISEASES LA English DT Editorial Material ID ANESTHESIOLOGISTS; ABUSE C1 NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Denisco, RA (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. EM deniscor@nida.nih.gov NR 6 TC 2 Z9 2 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 2006 VL 25 IS 4 BP 137 EP 137 DI 10.1300/J069v25n04_15 PG 1 WC Substance Abuse SC Substance Abuse GA 116YN UT WOS:000242839800015 PM 17088235 ER PT J AU D'Angelo, LJ Samples, C Rogers, AS Peralta, L Friedman, L AF D'Angelo, LJ Samples, C Rogers, AS Peralta, L Friedman, L TI HIV infection and AIDS in adolescents: An update of the position of the Society for Adolescent Medicine SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REACH; DESIGN; AGE; ADHERENCE; HIV/AIDS; PROJECT; GIRLS; CARE AB The Society reaffirms its call for accurate and comprehensive monitoring of HIV infection in youth. The Society endorses efforts to expand knowledge of HIV infection to youth from all countries and recognizes that priorities in this regard need to be based on local needs, not externally developed policies. The Society supports research into HIV care and treatment initiatives that are focused on youth. The Society supports expansion of testing and counseling efforts that utilize state-of-the-art techniques and an immediate linkage to comprehensive care for positive or concerned youth. The Society endorses community based HIV/AIDS prevention and education that recognizes the importance of abstinence but that is comprehensive and sensitive to the needs of all adolescents, including those who are gay, lesbian, bisexual, transgender or questioning. The Society supports continued research focusing on the antecedents of HIV infection and important preventive tools such as microbicides and vaccines. C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Hosp, Boston, MA 02115 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Miami, Miami, FL 33152 USA. RP D'Angelo, LJ (reprint author), Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 25 TC 13 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JAN PY 2006 VL 38 IS 1 BP 88 EP 91 DI 10.1016/j.jadohealth.2005.10.001 PG 4 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 000XS UT WOS:000234496300014 PM 16387258 ER PT J AU Simons-Morton, BG Hartos, JL Leaf, WA Preusser, DF AF Simons-Morton, BG Hartos, JL Leaf, WA Preusser, DF TI Increasing parent limits on novice young drivers cognitive mediation of the effect of persuasive messages SO JOURNAL OF ADOLESCENT RESEARCH LA English DT Article DE protection motivation theory; adolescents; parenting; cars ID TEEN DRIVING PRIVILEGES; 16-YEAR-OLD DRIVERS; CRASH RISK; RESTRICTIONS; PASSENGERS; LICENSURE; PERSISTENCE; STATES AB This report describes intervention effects on parent-imposed driving limits on novice young drivers at licensure. Parent-adolescent dyads (4,344) completed baseline surveys at permit and were randomly assigned to intervention or comparison groups. Intervention families received persuasive communications related to protection motivation theory variables including threat appraisal regarding high-risk adolescent driving and coping appraisal regarding restrictions on high-risk driving conditions during the early months of adolescent licensure. Comparison families received standard information on driving, vehicles, and road safety. Among the 4,344 families, 3,786 adolescents obtained licenses, and 3,398 parent-adolescent dyads completed surveys at licensure. Significant treatment group differences favoring the Checkpoints Program were found at licensure for driving limits,, perceived risk, expected limits, and outcome expectations. Perceived risk and outcome expectations partially mediated and expected limits fully mediated treatment effects. The results provide evidence that persuasive materials can alter threat and coping appraisal and expectations, thereby, increasing parent-imposed driving limits at licensure. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Univ N Carolina, Coll Hlth & Human Serv, Charlotte, NC 28223 USA. Preusser Res Grp Inc, Trumbull, CT USA. RP Simons-Morton, BG (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 39 TC 27 Z9 27 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0743-5584 J9 J ADOLESCENT RES JI J. Adolesc. Res. PD JAN PY 2006 VL 21 IS 1 BP 83 EP 105 DI 10.1177/0743558405282282 PG 23 WC Psychology, Developmental SC Psychology GA 036WY UT WOS:000237109200005 ER PT J AU Li, HL Romieu, I Sienra-Monge, JJ Ramirez-Aguilar, M del Rio-Navarro, BE Kistner, EO Gjessing, HK Lara-Sanchez, ID Chiu, GY London, SJ AF Li, HL Romieu, I Sienra-Monge, JJ Ramirez-Aguilar, M del Rio-Navarro, BE Kistner, EO Gjessing, HK Lara-Sanchez, ID Chiu, GY London, SJ TI Genetic polymorphisms in arginase I and II and childhood asthma and atopy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE ARG1; ARG2; genetic predisposition to disease; SNP; polymorphism; single nucleotide; respiratory hypersensitivity; skin tests; asthma; tobacco smoke pollution ID CASE-PARENT TRIADS; NITRIC-OXIDE; BRONCHIAL HYPERRESPONSIVENESS; AIRWAY HYPERREACTIVITY; POSITIONAL CLONING; QUANTITATIVE TRAIT; GUINEA-PIGS; ARGININE; IDENTIFICATION; RELAXATION AB Background: A recent microarray study implicated arginase I (ARGI) and arginase II (ARG2) in mouse allergic asthma models and human asthma. Objectives: To examine the association between genetic variation in ARGI and ARG2 and childhood asthma and atopy risk. Methods: We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif). Results: ARGI SNPs and haplotypes were not associated with asthma, but all 4 ARGI SNPs were associated with the number of positive skin tests (P = .007-.018). Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI = 1.1-2.1 for arg2s1; RR = 1.6, 95% CI = 1.1-2.3 for arg2s2). The association was slightly stronger among children with a smoking parent (arg2s1 RR 2.1, 95% CI = 1.2 - 3.9 with a smoking parent; RR = 1.2, 95% CI = 0.8-1.9 without; interaction P = .025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests (P = .027). C1 Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Div Intramural Res, NIH,Dept Hlth & Human Sci, Res Triangle Pk, NC 27709 USA. Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. Norwegian Inst Publ Hlth, Oslo, Norway. Westat Corp, Res Triangle Pk, NC USA. RP London, SJ (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov RI Gjessing, Hakon/A-5871-2012; OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES049019, Z01 ES049019-10] NR 43 TC 54 Z9 54 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2006 VL 117 IS 1 BP 119 EP 126 DI 10.1016/j.jaci.2005.09.026 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 017IK UT WOS:000235687100019 PM 16387594 ER PT J AU Hardy, J AF Hardy, John TI Alzheimer's disease: The amyloid cascade hypothesis: An update and reappraisal SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article AB Here I recap the scientific and personal background of the delineation of the amyloid cascade hypothesis for Alzheimer's disease that I wrote with Gerry Higgins and the events leading to the writing of that influential review. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Porter Neurosci Bldg 35,Convent Dr, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov FU Medical Research Council [G0701075] NR 16 TC 116 Z9 122 U1 9 U2 40 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2006 VL 9 SU 3 BP 151 EP 153 PG 3 WC Neurosciences SC Neurosciences & Neurology GA V33DM UT WOS:000208999500017 PM 16914853 ER PT J AU Irwin, RD AF Irwin, RD TI A review of evidence leading to the prediction that 1,4-butanediol is not a carcinogen SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Review DE 1.4-butanediol; carcinogenicity; gamma-butyrolactone; gamma-hydroxybutyric acid; metabolism ID GAMMA-HYDROXYBUTYRIC ACID; GENERALIZED ABSENCE SEIZURES; RAT-BRAIN; AMINOBUTYRIC ACID; DEPENDENT OXIDOREDUCTASE; SUCCINIC SEMIALDEHYDE; INBORN ERROR; BUTYROLACTONE; METABOLISM; NEUROTRANSMITTER AB 1,4-Butanediol is an industrial chemical used primarily as an intermediate in the manufacture of other organic chemicals. It has recently been associated with deaths, addiction and withdrawal related to its promotion and use as a dietary supplement. The rapid absorption and conversion of 1,4-butanediol to gamma-hydroxybutyric acid (GHB, or date rape drug) in animals and humans is well documented and is the basis for its abuse potential. A disposition and metabolism study conducted in F344 rats by the National Toxicology Program (NTP) confirmed the rapid conversion of 1-C-14-1,4-butanediol to (CO2)-C-14. Because of this, the toxicological profile of 1,4-butanediol resembles that of gamma-hydroxybutyric acid. Gamma-hydroxybutyric acid occurs naturally in the brain and peripheral tissues and is converted to succinate and metabolized through the TCA cycle. Although the function of gamma-hydroxvbutyric acid in peripheral tissues is not known, the presence of specific high affinity receptors for gamma-hydroxybutyric acid suggests that it functions as a neuromodulator in the brain and neuronal tissue. Gamma-hydroxybutyric acid readily crosses the blood-brain barrier and elicits characteristic neuropharmacologic responses after oral, i.p., or i.v. administration. The same responses are observed after administration of 1,4-butanediol. The cyclic lactone of gamma-hydroxybutyric acid, gamma-butyrolactone, is also rapidly converted to gamma-hydroxybutyric acid by enzymes in the blood and liver in animals and humans, and produces pharmacological effects identical to those produced by 1,4-butanediol and gamma-hydroxybutyric acid. gamma-Butyrolactone was previously evaluated by the NTP in 14-day and 13-week prechronic toxicology studies and in 2-year chronic toxicology and carcinogenesis studies in F344 rats and B6C3F(1) mice. No organ specific toxicity occurred. In the carcinogenesis studies there was an equivocal response in male mice based on a marginal increase in the incidence of pheochromocytomas of the adrenal medulla. Because the absence of chronic toxicity and significant carcinogenicity of gamma-hydroxybutyric acid were established in NTP prechronic and chronic studies with gamma-butyrolactone, it is concluded that similar results would be obtained in a 2-year study with 1,4-butanediol, and that 1,4-butanediol is not a carcinogen. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Irwin, RD (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM irwin@niehs.nih.gov NR 71 TC 2 Z9 2 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD JAN-FEB PY 2006 VL 26 IS 1 BP 72 EP 80 DI 10.1002/jat.1110 PG 9 WC Toxicology SC Toxicology GA 009FG UT WOS:000235096300011 PM 16193534 ER PT J AU Brindle, TJ Uhl, TL Nitz, AJ Shapiro, R AF Brindle, TJ Uhl, TL Nitz, AJ Shapiro, R TI The influence of external loads on movement precision during active shoulder internal rotation movements as measured by 3 indices of accuracy SO JOURNAL OF ATHLETIC TRAINING LA English DT Article DE proprioception; kinesthesia; shoulder function ID JOINT POSITION SENSE; TENDON ORGANS; KINESTHETIC INFORMATION; REACHING MOVEMENTS; MUSCLE-CONTRACTION; HUMAN HAND; PROPRIOCEPTION; RESPONSES; AFFERENTS; RECEPTORS AB Context Using constant, variable, and absolute error to measure movement accuracy might provide a more complete description of joint position sense than any of these values alone. Objective: To determine the effect of loaded movements and type of feedback on shoulder joint position sense and movement velocity. Design: Applied study with repeated measures comparing type of feedback and the presence of a load. Setting: Laboratory. Patients or Other Participants: Twenty healthy subjects (age = 27.2 +/- 3.3 years, height = 173.2 +/- 18.1 cm, mass = 70.8 +/- 14.5 kg) were seated with their arms in a custom shoulder wheel. Intervention(s): Subjects internally rotated 27 degrees in the plane of the scapula, with either visual feedback provided by a video monitor or proprioceptive feedback provided by prior passive positioning, to a target at 480 of external rotation. Subjects performed the internal rotation movements with video feedback and proprioceptive feedback and with and without load (5% of body weight). Main Outcome Measure(s): High-speed motion analysis recorded peak rotational velocity and accuracy. Constant, variable, and absolute error for joint position sense was calculated from the final position. Results: Unloaded movements demonstrated significantly greater variable error than for loaded movements (2.0 +/- 0.7 degrees and 1.5 +/- 0.4 degrees, respectively) (P < .05), but there were no differences in constant or absolute error. Peak velocity was greater for movements with proprioceptive feedback (45.6 +/- 2.9 degrees/s) than visual feedback (39.1 +/- 2.1 degrees/s) and for unloaded (47.8 +/- 3.6 degrees/s) than loaded (36.9 +/- 1.0 degrees/s) movements (P < .05). Conclusions: Shoulder joint position sense demonstrated greater variable error unloaded versus loaded movements. Both visual feedback and additional loads decreased peak rotational velocity. C1 NIH, Phys Disabilities Branch, Bethesda, MD 20892 USA. Univ Kentucky, Lexington, KY USA. RP Brindle, TJ (reprint author), NIH, Phys Disabilities Branch, Bldg 10 CRC,Room 1-1469 MCS 1604, Bethesda, MD 20892 USA. EM tbrindle@cc.nih.gov RI Lempereur, Mathieu/G-5470-2012 NR 45 TC 9 Z9 9 U1 0 U2 5 PU NATL ATHLETIC TRAINERS ASSOC INC PI DALLAS PA 2952 STEMMONS FREEWAY, DALLAS, TX 75247 USA SN 1062-6050 J9 J ATHL TRAINING JI J. Athl. Train. PD JAN-MAR PY 2006 VL 41 IS 1 BP 60 EP 66 PG 7 WC Sport Sciences SC Sport Sciences GA 029WT UT WOS:000236595800010 PM 16619096 ER PT J AU Guo, YC Eichler, GS Feng, Y Ingber, DE Huang, S AF Guo, Yuchun Eichler, Gabriel S. Feng, Ying Ingber, Donald E. Huang, Sui TI Towards a holistic, yet gene-centered analysis of gene expression profiles: A case study of human lung cancers SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Article ID SELF-ORGANIZING MAPS; MOLECULAR CLASSIFICATION; INTEGRATIVE ANALYSIS; MICROARRAY DATA; BREAST-CANCER; DATA SETS; TUMOR; PATTERNS; LYMPHOMA; ADENOCARCINOMA AB Genome-wide gene expression profile studies encompass increasingly large number of samples, posing a challenge to their presentation and interpretation without losing the notion that each transcriptome constitutes a complex biological entity. Much like pathologists who visually analyze information-rich histological sections as a whole, we propose here an integrative approach. We use a self-organizing maps-based software, the gene expression dynamics inspector (GEDI) to analyze gene expression profiles of various lung tumors. GEDI allows the comparison of tumor profiles based on direct visual detection of transcriptome patterns. Such intuitive "gestalt" perception promotes the discovery of interesting relationships in the absence of an existing hypothesis. We uncovered qualitative relationships between squamous cell tumors, small-cell tumors, and carcinoid tumor that would have escaped existing algorithmic classifications. These results suggest that GEDI may be a valuable explorative tool that combines global and gene-centered analyses of molecular profiles from large-scale microarray experiments. C1 Harvard Univ, Sch Med, Vasc Biol Program, Dept Surg,Childrens Hosp, Boston, MA 02115 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Guo, YC (reprint author), Harvard Univ, Sch Med, Vasc Biol Program, Dept Surg,Childrens Hosp, Boston, MA 02115 USA. OI Guo, Yuchun/0000-0003-2357-1546 FU NCI NIH HHS [R01 CA055833] NR 44 TC 31 Z9 31 U1 0 U2 4 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 2006 AR 69141 DI 10.1155/JBB/2006/69141 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 113FL UT WOS:000242583700001 PM 17489018 ER PT J AU Hruska, KS Goker-Alpan, O Sidransky, E AF Hruska, Kathleen S. Goker-Alpan, Ozlem Sidransky, Ellen TI Gaucher disease and the synucleinopathies SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Review ID MUTANT ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; GLUCOCEREBROSIDASE GENE; ASHKENAZI-JEWS; MUTATIONS; ASSOCIATION; NEURONS; RISK AB Several recent observations suggest a connection between Gaucher disease, the inherited deficiency of glucocerebrosidase, and the synucleinopathies. Rare patients have been observed who develop both Gaucher disease and parkinsonism. Autopsy studies on these subjects reveal synuclein-positive Lewy bodies and inclusions. An increased incidence of synucleinopathies also has been noted in relatives of Gaucher probands. In complementary studies, screening of patients with parkinsonism has identified a greater than expected frequency of glucocerebrosidase mutations. These glucocerebrosidase mutation carriers have a wide spectrum of associated parkinsonian phenotypes, ranging from classic L-dopa-responsive Parkinson disease to a phenotype more characteristic of Lewy body dementia. Despite this association, the vast majority of Gaucher carriers and patients with Gaucher disease never develop parkinsonism. However, mutations in this gene are likely to be a contributing risk factor in subjects otherwise prone to developing synucleinopathies. C1 NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Hruska, KS (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 38 TC 25 Z9 25 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 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2006 AR 78549 DI 10.1155/JBB/2006/78549 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 106IF UT WOS:000242093500001 ER PT J AU Walsh, JD Lee, D Yu, P Migliorini, M Strickland, DK Wang, YX AF Walsh, Joseph D. Lee, Donghan Yu, Ping Migliorini, Molly Strickland, Dudley K. Wang, Yun-Xing TI NMR assignment of domain 2 of the receptor-associated protein SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article C1 NCI, Frederick Canc Res & Dev Ctr, Prot Nucl Acid Interact Sect, Struct Biophys Lab, Frederick, MD 21702 USA. Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Strickland, DK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Prot Nucl Acid Interact Sect, Struct Biophys Lab, Frederick, MD 21702 USA. EM dstrickland@som.umaryland.edu; wangyu@ncifcrf.gov RI Lee, Donghan/B-6893-2011; OI Lee, Donghan/0000-0002-3971-986X; Lee, Donghan/0000-0002-6530-8060 NR 2 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PY 2006 VL 36 SU 1 BP 54 EP 54 DI 10.1007/s10858-006-9034-9 PG 1 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 116XG UT WOS:000242836500054 PM 16865416 ER PT J AU Lee, DH Walsh, JD Yu, P Migliorini, M Wu, YB Strickland, DK Wang, YX AF Lee, Donghan Walsh, Joseph D. Yu, Ping Migliorini, Molly Wu, Yibing Strickland, Dudley K. Wang, Yun-Xing TI NMR assignment of domain 3 of the receptor-associated protein (RAP) SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article C1 NCI, Prot Nucl Acid Interact Sect, Struct Biophys Lab, Canc Res Ctr,NIH, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Strickland, DK (reprint author), NCI, Prot Nucl Acid Interact Sect, Struct Biophys Lab, Canc Res Ctr,NIH, Frederick, MD 21702 USA. EM dstrickland@som.umaryland.edu; wangyu@ncifcrf.gov RI Lee, Donghan/B-6893-2011; OI Lee, Donghan/0000-0002-3971-986X; Lee, Donghan/0000-0002-6530-8060 NR 2 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PY 2006 VL 36 SU 1 BP 56 EP 56 DI 10.1007/s10858-006-9036-7 PG 1 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 116XG UT WOS:000242836500056 PM 17016671 ER PT J AU Reiter, NJ Lee, D Wang, YX Tonelli, M Bahrami, A Cornilescu, CC Butcher, SE AF Reiter, Nicholas J. Lee, Donghan Wang, Yun-Xing Tonelli, Marco Bahrami, Arash Cornilescu, Claudia C. Butcher, Samuel E. TI Resonance assignments for the two N-terminal RNA recognition motifs (RRM) of the S-cerevisiae pre-mRNA processing protein Prp24 SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article C1 Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. NCI, Frederick, MD 21701 USA. NMRFAM, Madison, WI 53706 USA. RP Butcher, SE (reprint author), Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. EM butcher@biochem.wisc.edu RI Lee, Donghan/B-6893-2011; Cornilescu, Claudia/H-1959-2012; Cornilescu, Claudia/K-1981-2015; OI Cornilescu, Claudia/0000-0002-2401-7806; Lee, Donghan/0000-0002-3971-986X; Lee, Donghan/0000-0002-6530-8060 NR 1 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PY 2006 VL 36 SU 1 BP 58 EP 58 DI 10.1007/s10858-006-9039-4 PG 1 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 116XG UT WOS:000242836500058 PM 17131032 ER PT J AU Ingkanisorn, WP Paterson, DI Calvo, KR Rosing, DR Schwartzentruber, DJ Fuisz, AR Arai, AE AF Ingkanisorn, WP Paterson, DI Calvo, KR Rosing, DR Schwartzentruber, DJ Fuisz, AR Arai, AE TI Cardiac magnetic resonance appearance of myocarditis caused by high dose IL-2: Similarities to community-acquired myocarditis SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE myocarditis; magnetic resonance imaging; interleukin-2; gadolinium; troponin ID ENDOMYOCARDIAL BIOPSY; METASTATIC MELANOMA; INTERLEUKIN-2; THERAPY; CARDIOTOXICITY; DIAGNOSIS; INDUCTION; RATS AB The purposecv of this study was to describe and compare the cardiac magnetic resonance (CMR) characteristics of myocarditis caused by high dose interleukin-2 (7 patients) with community-acquired myocarditis (14 patients). A total of 21 patients with suspected myocarditis and elevated cardiac enzymes underwent cine CMR followed by delayed enhancement. The mean ejection fraction was mildly decreased in both groups. The location, pattern, and extent of DE were similar in both groups of patients. The CMR similarities between these two populations suggest that cytokine-mediated cytotoxicity may play an important role in community-acquired myocarditis. C1 NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D-416, Bethesda, MD 20892 USA. EM araia@nih.gov RI Calvo, Katherine/A-8109-2009; OI Calvo, Katherine/0000-0002-0771-4191 FU Intramural NIH HHS NR 22 TC 17 Z9 17 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2006 VL 8 IS 2 BP 353 EP 360 DI 10.1080/10976640500452000 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 018AQ UT WOS:000235735500005 PM 16669178 ER PT J AU Williams, RRE Azuara, V Perry, P Sauer, S Dvorkina, M Jorgensen, H Roix, J McQueen, P Misteli, T Merkenschlager, M Fisher, AG AF Williams, RRE Azuara, V Perry, P Sauer, S Dvorkina, M Jorgensen, H Roix, J McQueen, P Misteli, T Merkenschlager, M Fisher, AG TI Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus SO JOURNAL OF CELL SCIENCE LA English DT Article DE chromatin; transcription; replication timing; nuclear organization; neurogenesis; epigenetics; proneural ID EMBRYONIC STEM-CELLS; NUCLEAR-ORGANIZATION; GENE-EXPRESSION; DNA-REPLICATION; CENTROMERIC HETEROCHROMATIN; DROSOPHILA-MELANOGASTER; CHROMOSOME TERRITORIES; ES CELLS; DIFFERENTIATION; TRANSCRIPTION AB Determining how genes are epigenetically regulated to ensure their correct spatial and temporal expression during development is key to our understanding of cell lineage commitment. Here we examined epigenetic changes at an important proneural regulator gene Mash1 (Ascl1), as embryonic stem (ES) cells commit to the neural lineage. In ES cells where the Mash1 gene is transcriptionally repressed, the locus replicated late in S phase and was preferentially positioned at the nuclear periphery with other late-replicating genes (Neurod, Sprr2a). This peripheral location was coupled with low levels of histone H3K9 acetylation at the Mash1 promoter and enhanced H3K27 methylation but surprisingly location was not affected by removal of the Ezh2/Eed HMTase complex or several other chromatin-silencing candidates (G9a, SuV39h-1, Dnmt-1, Dnmt-3a and Dnmt-3b). Upon neural induction however, Mash1 transcription was upregulated (> 100-fold), switched its time of replication from late to early in S phase and relocated towards the interior of the nucleus. This spatial repositioning was selective for neural commitment because Mash1 was peripheral in ES-derived mesoderm and other non-neural cell types. A bidirectional analysis of replication timing across a 2 Mb region flanking the Mash1 locus showed that chromatin changes were focused at Mash1. These results suggest that Mash1 is regulated by changes in chromatin structure and location and implicate the nuclear periphery as an important environment for maintaining the undifferentiated state of ES cells. C1 Hammersmith Hosp, Lymphocyte Dev Grp, MRC, Ctr Clin Sci,Imperial Coll London, London W12 0NN, England. MIT, Canc Res Ctr, Cambridge, MA 02139 USA. Ctr Informat Technol, Div Computat Biosci, Math & Stat Comp Lab, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Williams, RRE (reprint author), Hammersmith Hosp, Lymphocyte Dev Grp, MRC, Ctr Clin Sci,Imperial Coll London, Du Cane Rd, London W12 0NN, England. EM ruth.williams@csc.mrc.ac.uk; amanda.fisher@csc.mrc.ac.uk OI Jorgensen, Helle/0000-0002-7909-2977; Azuara, Veronique/0000-0003-4608-3713; Merkenschlager, Matthias/0000-0003-2889-3288 FU Medical Research Council [MC_U120027516]; Parkinson's UK [G-4045] NR 60 TC 193 Z9 196 U1 1 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN 1 PY 2006 VL 119 IS 1 BP 132 EP 140 DI 10.1242/jcs.02727 PG 9 WC Cell Biology SC Cell Biology GA 006MI UT WOS:000234901200016 PM 16371653 ER PT J AU Seftor, EA Meltzer, PS Kirschmann, DA Margaryan, NV Seftor, REB Hendrix, MJC AF Seftor, Elisabeth A. Meltzer, P. S. Kirschmann, D. A. Margaryan, N. V. Seftor, R. E. B. Hendrix, Mary J. C. TI The epigenetic reprogramming of poorly aggressive melanoma cells by a metastatic microenvironment SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Review DE melanoma; plasticity; vasculogenic mimicry; 3-dimensional matrix; epigenetic; tumor microenvironment ID HEPATOCYTE GROWTH-FACTOR; CUTANEOUS MALIGNANT-MELANOMA; LAMININ-5 GAMMA-2 CHAIN; HUMAN UVEAL MELANOMA; VASCULOGENIC MIMICRY; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; IN-VIVO; AMINOPEPTIDASE-N; TUMOR MICROENVIRONMENT AB A dynamic, complex relationship exists between tumor cells and their microenvironment, which plays a pivotal role in cancer progression, yet remains poorly understood. Particularly perplexing is the finding that aggressive melanoma cells express genes associated with multiple cellular phenotypes, in addition to their ability to form vasculogenic-like networks in three-dimensional matrix - called vasculogenic mimicry, which is illustrative of tumor cell plasticity. This study addressed the unique epigenetic effect of the microenvironment of aggressive melanoma cells on the behavior of poorly aggressive melanoma cells exposed to it. The data show significant changes in the global gene expression of the cells exposed to 3-D matrices preconditioned by aggressive melanoma cells, including the acquisition of a vasculogenic cell phenotype, upregulation of ECM remodeling genes, and increased invasive ability - indicative of an epigenetic, microenvironment-induced reprogramming of poorly aggressive melanoma cells. However, this epigenetic effect was completely abrogated when a highly cross-linked collagen matrix was used, which could not be remodeled by the aggressive melanoma cells. These findings offer an unique perspective of the inductive properties associated with an aggressive melanoma microenvironment that might provide new insights into the epigenetic regulation of tumor cell plasticity and differentiation, as well as mechanisms that could be targeted for novel therapeutic strategies. C1 Northwestern Univ, Childrens Mem Res Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Hendrix, MJC (reprint author), 2300 Childrens Plaza,Box 222, Chicago, IL 60614 USA. EM mjchendrix@childrensmemorial.org FU NCI NIH HHS [CA59702, CA80318] NR 118 TC 25 Z9 33 U1 1 U2 4 PU CAROL DAVILA UNIV PRESS PI BUCHARESST PA 8 EROILOR SANITARI BLVD, BUCHARESST 76241, ROMANIA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD JAN-MAR PY 2006 VL 10 IS 1 BP 174 EP 196 DI 10.1111/j.1582-4934.2006.tb00299.x PG 23 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 074FR UT WOS:000239798600016 PM 16563230 ER PT J AU Shah, BH Neithardt, A Chu, DB Shah, FB Catt, KJ AF Shah, BH Neithardt, A Chu, DB Shah, FB Catt, KJ TI Role of EGF receptor transactivation in phosphoinositide 3-kinase-dependent activation of MAP kinase by GPCRs SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; GONADOTROPIN-RELEASING-HORMONE; RICH TYROSINE KINASE-2; VASCULAR SMOOTH-MUSCLE; PHOSPHOINOSITIDE 3-KINASE; SIGNALING PATHWAY; ANGIOTENSIN-II; PHOSPHATIDYLINOSITOL 3-KINASE; LYSOPHOSPHATIDIC ACID; REGULATED KINASE-1 AB ManyG protein coupled receptors (GPCRs) cause phosphorylation of MAP kinases through transactivation of the epidermal growth factor receptor (EGF-R), leading to increased cell survival and growth, motility, and migration. Phosphoinositide 3-kinase (PI3K) is one of the important cell survival signaling molecules activated by EGF-R stimulation. However, the extent to which EGF-R transactivation is essential for GPCR agonist-stimulated PI3K activation is not known. Here we examined the mechanism of PI3K activation that elicits GPCR-mediated ERK1/2 activation by pathways dependent and/or independent of EGF-R transactivation in specific cell types. Immortalized hypothalamic neurons (GT1-7 cells) express endogenous gonadotropin-releasing hormone receptors (GnRH-R) and their stimulation causes marked phosphorylation of ERK1/2 and Akt (Ser473) through transactivation of the EGF-R and recruitment of PI3K. In C9 hepatocytes, agonist activation of AT(1) angiotensin 11 (AT(1)-R), lysophosphaticlic acid (LPA), and EGF receptors caused phosphorylation of Akt through activation of the EGF-R in a PI3K-dependent manner. However, ERK1/2 activation by these agonists in these cells was independent of PI3K activation. In contrast, agonist stimulation of HEK 293 cells stably expressing AT(1)-R caused ERK1/2 phosphorylation thatwas independent of EGF-R transactivation but required PI3K activation. LPA signaling in these cells showed partial and complete dependence on EGF-R and PI3K, respectively. These data indicate that GPCR induced ERK1/2 phosphorylation is dependent or independent of PI3K in specific cell types, and that the involvement of PI3K during ERK1/2 activation is not dependent solely on agonist-induced transactivation of the EGF-R. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Shah, BH (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bld 49,Rm 6A36, Bethesda, MD 20892 USA. EM shahb@mail.nih.gov NR 46 TC 38 Z9 38 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2006 VL 206 IS 1 BP 47 EP 57 DI 10.1002/jcp.20423 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 989QX UT WOS:000233689900006 PM 15920762 ER PT J AU Wallqvist, A Huang, RL Thanki, N Covell, DG AF Wallqvist, A Huang, RL Thanki, N Covell, DG TI Evaluating chemical structure similarity as an indicator of cellular growth inhibition SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article; Proceedings Paper CT 4th Indo-US Workshop on Mathematical Chemistry CY JAN 08-12, 2005 CL Univ Pune, Pune, INDIA HO Univ Pune ID NATIONAL-CANCER-INSTITUTE; DRUG DISCOVERY DATABASES; TUMOR-SCREENING DATABASE; GENE-EXPRESSION; ELLIPTICINE ANALOGS; BIOLOGICAL-ACTIVITY; CLUSTER-ANALYSIS; IN-VITRO; LINES; IDENTIFICATION AB Chemical variations of small compounds are commonly used to probe biological systems and potentially discover lead-like compounds with selective target activity. Molecular probes are either generated by synthesis or acquired through directed searches of commercially available compound libraries. The data generated when testing the probes in various biological systems constitutes a structure/activity analysis. The ability to detect variations and classify biological responses requires the analysis of a compound in multiple assays. While the concept of a structure/activity relationship is straightforward, its implementation can vary considerably depending on the biological system under study and the probe library selected for testing. The analysis presented here will focus on the accumulated compound library used to screen for growth inhibition across the National Cancer Institute's panel of 60 tumor cells. The considerable chemical and biological diversity inherent in these data offers an opportunity to establish a quantifiable connection between chemical structure and biological activity. We find that the connection between structure and biological response is not symmetric, with biological response better at predicting chemical structure than vice versa. Structurally and functionally similar compounds can have distinguishable biological responses reflecting different mechanisms of action. C1 Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Screening Technol Branch, Frederick, MD 21702 USA. RP Wallqvist, A (reprint author), Sci Applicat Int Corp, POB B, Frederick, MD 21702 USA. EM wallqvist@ncifcrf.gov OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-12400] NR 42 TC 16 Z9 16 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD JAN-FEB PY 2006 VL 46 IS 1 BP 430 EP 437 DI 10.1021/ci0501544 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 008DU UT WOS:000235021200046 PM 16426077 ER PT J AU Hoffmann, KM Gibril, F Entsuah, LK Serrano, J Jensen, RT AF Hoffmann, KM Gibril, F Entsuah, LK Serrano, J Jensen, RT TI Patients with multiple endocrine neoplasia type 1 with gastrinomas have an increased risk of severe esophageal disease including stricture and the premalignant condition, Barrett's esophagus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; LONG-TERM; REFLUX DISEASE; HIATAL-HERNIA; MANAGEMENT; PERFORATION; PREVALENCE; CIMETIDINE; SECRETION AB Context: Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (MEN1/ZES). Although esophageal reflux symptoms are common in these patients, little is known about long-term occurrence of severe peptic esophageal disease including strictures and Barrett's esophagus ( BE). Objective: The objective of the study was to prospectively analyze the frequency of severe peptic esophageal disease in ZES patients with and without MEN1. Setting: The study was conducted at a tertiary care research center. Patients: Two hundred ninety-five patients ( 80 = MEN1/ZES, 215 = sporadic ZES) participated in a prospective study. Interventions and Outcome Measures: Assessment of MEN1, acid hypersecretion, upper gastrointestinal endoscopy/biopsies, and tumor status were measured initially and at each follow-up. Esophageal manometry was performed in 89 patients. Frequency and type of esophageal disease were correlated with clinical/laboratory/ tumoral features of ZES/MEN1. Results: In MEN1/ZES patients, esophageal stricture was 3-fold higher, BE 5-fold higher, and dysplasia 8-fold higher, and one patient died of esophageal adenocarcinoma. Esophageal symptoms were more frequent or severe in MEN1/ZES, but known risk factors for severe esophageal disease and ZES-specific features did not differ between MEN1/ZES and sporadic ZES. In MEN1/ZES, the onset of ZES was 10 yr earlier, and H(2)-antagonists were used longer and at lower doses. MEN1/ZES patients with esophageal disease differed from those without in that ZES diagnosis was delayed longer, esophageal symptoms were more frequent or severe, hiatal hernias were more frequent, esophagitis or pyloric scarring was more common, basal acid output was higher, and hyperparathyroidism was underdiagnosed. Conclusions: This study shows that MEN1/ZES patients have a higher incidence of severe esophageal disease including the premalignant condition BE and identifies factors important for their pathogenesis that need to be incorporated into their long-term treatment. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov NR 61 TC 17 Z9 17 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 2006 VL 91 IS 1 BP 204 EP 212 DI 10.1210/jc.2005-1349 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 000VN UT WOS:000234490600035 PM 16249283 ER PT J AU Batista, D Gennari, M Riar, J Chang, R Keil, MF Oldfield, EH Stratakis, CA AF Batista, D Gennari, M Riar, J Chang, R Keil, MF Oldfield, EH Stratakis, CA TI An assessment of petrosal sinus sampling for localization of pituitary microadenomas in children with Cushing disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INFERIOR PETROSAL; ADRENOCORTICOTROPIC HORMONE; DIFFERENTIAL-DIAGNOSIS; ADOLESCENTS; ADENOMAS; ACCURACY; TUMORS AB Context: Pituitary adenomas in Cushing disease ( CD) are usually small and difficult to visualize. Bilateral inferior petrosal venous sampling (BIPSS) before and after ovine CRH stimulation is reserved for patients who have ACTH-dependent Cushing syndrome and negative magnetic resonance imaging (MRI) or positive MRI but inconsistent biochemical data. Objective: The objective of the study was to evaluate the usefulness of BIPSS as a tool for localization of a pituitary adenoma in children with CD. Design: The study was a retrospective review of the records of 141 children who were admitted for evaluation of CD from 1982 to 2004. Setting: The study was conducted at a tertiary care center. Interventions and Outcome Measures: Lateralization of ACTH secretion during BIPSS was compared with MRI and surgical findings for the localization of a microadenoma. Results: A total of 94 patients, 49 males and 45 females with an age range of 5.3 to 18.7 yr ( 13 +/- 3.2 yr), underwent BIPSS. Localization of a microadenoma by BIPSS agreed with surgical location in only 58% of the cases (95% confidence interval, 43 - 66). The combined use of information from the MRI and inferior petrosal venous sampling did not predict the location of the tumor more frequently than MRI alone ( P > 0.1), which in this study localized a lesion in 39% of the patients ( 95% confidence interval, 28 - 50). The procedure was completed successfully in all patients, and no serious complications were recorded. Conclusions: Although BIPSS was safe and well tolerated in an experienced center, lateralization of the ACTH gradient during BIPSS was a poor predictor of the site of the adenoma in children with CD. C1 NICHHD, Sect Genet & Endocrinol, Dev Endocrinol Branch, Clin Res Ctr,East Labs,NIH, Bethesda, MD 20892 USA. NICHHD, Pediat Endocrinol Interinst Training Program, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Bologna, S Orsola Hosp, Dept Pediat Endocrinol, I-40138 Bologna, Italy. RP Stratakis, CA (reprint author), NICHHD, Sect Genet & Endocrinol, Dev Endocrinol Branch, Clin Res Ctr,East Labs,NIH, Bldg 10,Room I-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural NIH HHS NR 22 TC 41 Z9 44 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 2006 VL 91 IS 1 BP 221 EP 224 DI 10.1210/jc.2005-1096 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 000VN UT WOS:000234490600037 PM 16219718 ER PT J AU Maggio, M Basaria, S Ble, A Lauretani, F Bandinelli, S Ceda, GP Valenti, G Ling, SM Ferrucci, L AF Maggio, M Basaria, S Ble, A Lauretani, F Bandinelli, S Ceda, GP Valenti, G Ling, SM Ferrucci, L TI Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ANDROGEN RECEPTOR; SEX-HORMONES; SERUM; CYTOKINES; INCHIANTI; DISEASE AB Context: An age-associated decline in testosterone (T) levels and an increase in proinflammatory cytokines contribute to chronic diseases in older men. Whether and how these changes are related is unclear. Objective: We hypothesized that T and inflammatory markers are negatively correlated in older men. Design: This was a cross-sectional study. Setting: A population-based sample of older men was studied. Participants and Measures: After excluding participants taking glucocorticoids or antibiotics or those with recent hospitalization, 467 men, aged 65 yr or older, had complete determinations of total T, bioavailable T, SHBG, albumin, IL-6, soluble IL-6 receptor (sIL-6r), TNF-alpha, IL-1 beta, and C-reactive protein. Results: After adjusting for potential confounders, sIL-6r was significantly and inversely correlated with total T (r = -0.20; P < 0.001) and bioavailable T (r = -0.12; P < 0.05). T was not correlated with any other inflammatory marker. Conclusions: These preliminary findings suggest an inverse relationship between T and sIL-6r. Longitudinal studies are needed to establish the causality of this association. C1 NIA, Longitudinal Studies Sect, Clin Res Branch,Intramural Res Program, NIH, Baltimore, MD 21225 USA. NIA, Translat Res & Med Support Sect, Clin Res Branch,Intramural Res Program, NIH, Baltimore, MD 21225 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol,Bayview Med Ctr, Baltimore, MD 21205 USA. Tuscany Reg Hlth Agcy, I-50134 Florence, Italy. Azienda Sanitaria Firenze, I-50125 Florence, Italy. Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy. RP Ferrucci, L (reprint author), NIA, Adv Studies Translat Res Aging Harbor Hosp, 3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; Lauretani, Fulvio/K-5115-2016; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295 FU NIMHD NIH HHS [263-MD-821336, 263-MD-916413] NR 20 TC 96 Z9 98 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2006 VL 91 IS 1 BP 345 EP 347 DI 10.1210/jc.2005-1097 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 000VN UT WOS:000234490600057 PM 16263825 ER PT J AU Aiello, EJ Taplin, S Reid, R Hobbs, M Seger, D Kamel, H Tufano, J Ballard-Barbash, R AF Aiello, EJ Taplin, S Reid, R Hobbs, M Seger, D Kamel, H Tufano, J Ballard-Barbash, R TI In a randomized controlled trial, patients preferred electronic data collection of breast cancer risk-factor information in a mammography setting SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE screening mammography; survey; health informatics; patient acceptance; age; data quality ID QUALITY-OF-LIFE; PAPER; PROGRAM; MONITOR; VERSION AB Background and Objective: We evaluated patient acceptance of an electronic questionnaire to collect breast cancer risk-factor data in a mammography setting. Methods: We developed an electronic questionnaire on a tablet computer incorporating prefilled answers and skip patterns. Using a randomized controlled study design, we tested the survey in a mammography clinic that administers a paper risk-factor questionnaire to every woman at her screening mammogram. We randomized 160 women to use the electronic survey (experimental group, n = 86) or paper survey (control group, n = 74). We evaluated patient acceptance and data completeness. Results: Overall, 70.4% of the experimental group women thought the survey was very easy to use, compared to 55.6% of women in the control group. Ninety percent of experimental group women preferred using the tablet, compared to the paper questionnaire. Preference for the tablet did not differ by age; however, women >= 60 years did not find the tablet as easy to use as did women < 60 years. The proportion of missing data was significantly lower on the tablet compared to the paper questionnaire (4.6% vs. 6.2%, P = .04). Conclusion: Electronic questionnaires are feasible to use in a mammography setting, can improve data quality, and are preferred by women regardless of age. (c) 2006 Elsevier Inc. All rights reserved. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Natl Canc Inst, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD USA. Grp Hlth Cooperat Puget Sound, Dept Prevent Care, Seattle, WA USA. Univ N Carolina, Carolina Mammog Project, Chapel Hill, NC USA. WrinkleBrain Inc, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Aiello, EJ (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM aiello.e@ghc.org NR 20 TC 19 Z9 19 U1 1 U2 4 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 2006 VL 59 IS 1 BP 77 EP 81 DI 10.1016/j.jclinepi.2005.07.007 PG 5 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 000HJ UT WOS:000234451600011 PM 16360564 ER PT J AU Peng, X Kraus, MS Wei, HJ Shen, TL Pariaut, R Alcaraz, A Ji, GJ Cheng, LH Yang, QL Kotlikoff, MI Chen, J Chien, K Gu, H Guan, JL AF Peng, X Kraus, MS Wei, HJ Shen, TL Pariaut, R Alcaraz, A Ji, GJ Cheng, LH Yang, QL Kotlikoff, MI Chen, J Chien, K Gu, H Guan, JL TI Inactivation of focal adhesion kinase in cardiomyocytes promotes eccentric cardiac hypertrophy and fibrosis in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PRESSURE-OVERLOAD; CELL MOTILITY; DILATED CARDIOMYOPATHY; SIGNALING PATHWAYS; HEART-FAILURE; MYOCYTES; ACTIVATION; GROWTH; DISEASE; MYOCARDIUM AB Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays a major role in integrin signaling pathways. Although cardiovascular defects were observed in FAK total KO mice, the embryonic lethality prevented investigation of FAK function in the hearts of adult animals. To circumvent these problems, we created mice in which FAK is selectively inactivated in cardiomyocytes (CFKO mice). We found that CFKO mice develop eccentric cardiac hypertrophy (normal LV wall thickness and increased left chamber dimension) upon stimulation with angiotensin H or pressure overload by transverse aortic constriction as measured by echocardiography. We also found increased heart/body weight ratios, elevated markers of cardiac hypertrophy, multifocal interstitial fibrosis, and increased collagen I and VI expression in CFKO mice compared with control littermates. Spontaneous cardiac chamber dilation and increased expression of hypertrophy markers were found in the older CFKO mice. Analysis of cardiomyocytes isolated from CFKO mice showed increased length but not width. The myocardium of CFKO mice exhibited disorganized myofibrils with increased nonmyofibrillar space filled with swelled mitochondria. Last, decreased tyrosine phosphorylation of FAK substrates p130Cas and paxillin were observed in CFKO mice compared with the control littermates. Together, these results provide strong evidence for a role of FAK in the regulation of heart hypertrophy in vivo. C1 Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA. Cornell Univ, Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA. Cornell Univ, Coll Vet Med, Dept Biomed Genet, Ithaca, NY 14853 USA. Morehouse Sch Med, Inst Cardiovasc Res, Atlanta, GA 30310 USA. Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. NIAID, Immunol Lab, NIH, Rockville, MD USA. Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA. RP Guan, JL (reprint author), Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA. EM jg19@cornell.edu RI Shen, Tang-Long/C-7460-2011; Chen, Ju/E-5579-2011; OI Shen, Tang-Long/0000-0001-6264-3608 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL066100, HL66100, HL73394, R01 HL073394] NR 67 TC 93 Z9 102 U1 0 U2 4 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 2006 VL 116 IS 1 BP 217 EP 227 DI 10.1172/JCI24497 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 000UU UT WOS:000234488700026 PM 16374517 ER PT J AU Ohyama, M Terunuma, A Tock, CL Radonovich, MF Pise-Masison, CA Hopping, SB Brady, JN Udey, MC Vogel, JC AF Ohyama, M Terunuma, A Tock, CL Radonovich, MF Pise-Masison, CA Hopping, SB Brady, JN Udey, MC Vogel, JC TI Characterization and isolation of stem cell-enriched human hair follicle bulge cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LABEL-RETAINING CELLS; HUMAN FETAL SKIN; KERATINOCYTES; EXPRESSION; NICHE; RECEPTOR; CYCLE; CD200; MICE; DIFFERENTIATION AB The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell-surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSCs. In this study, we determined the distribution of label-retaining cells to define the human anagen bulge. Using navigated laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and activin/bone morphogenic protein signaling were overrepresented in the bulge, while genes responsible for cell proliferation were underrepresented, consistent with the existence of quiescent noncycling KSCs in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1, while CD24, CD34, CD71, and CD146 were preferentially expressed by nonbulge keratinocytes. Importantly, CD200(+) cells (CD200(hi)CD24(lo)CD34(lo)CD71(lo)CD146(lo)) obtained from hair follicle suspensions demonstrated high colony-forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. The stem cell behavior of enriched bulge cells and their utility for gene therapy and hair regeneration will need to be assessed in in vivo assays. C1 NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Ctr Cosmet Surg, Washington, DC USA. RP Vogel, JC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM jonvogel@mail.nih.gov RI Ohyama, Manabu/J-5524-2014; Duello, Theresa/P-5752-2015 OI Ohyama, Manabu/0000-0002-2662-5717; FU Intramural NIH HHS NR 49 TC 316 Z9 347 U1 2 U2 25 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 2006 VL 116 IS 1 BP 249 EP 260 DI 10.1172/JCI26043 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 000UU UT WOS:000234488700029 PM 16395407 ER PT J AU Kasai, M Francesconi, A Petraitiene, R Petraitis, V Kelaher, AM Kim, H Meletiadis, J Sein, T Bacher, J Walsh, TJ AF Kasai, M Francesconi, A Petraitiene, R Petraitis, V Kelaher, AM Kim, H Meletiadis, J Sein, T Bacher, J Walsh, TJ TI Use of quantitative real-time PCR to study the kinetics of extracellular DNA released from Candida albicans, with implications for diagnosis of invasive candidiasis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; PULMONARY ASPERGILLOSIS; NOSOCOMIAL CANDIDEMIA; IN-VITRO; INFECTION; ASSAY; IDENTIFICATION; AMPLIFICATION; MORTALITY; PATHOGENS AB Quantitative real-time PCR (qPCR) is considered one of the most sensitive methods to detect low levels of DNA from pathogens in clinical samples. To improve the design of qPCR for the detection of deeply invasive candidiasis, we sought to develop a more comprehensive understanding of the kinetics of DNA released from Candida albicans in vitro and in vivo. We developed a C. albicans-specific assay targeting the rRNA gene complex and studied the kinetics of DNA released from C. albicans alone, in the presence of human blood monocytes (H-MNCs), and in the bloodstream of rabbits with experimental disseminated candidiasis. The analytical qPCR assay was highly specific and sensitive (10 fg). Cells of C. albicans incubated in Hanks balanced salt solution (+/- 10% bovine serum albumin [BSA]) or RPMI (+/- 10% BSA) showed a significant release of DNA at T equal to 24 h compared to T equal to 0 h (P <= 0.01). C. albicans incubated with H-MNCs exhibited a greater release of DNA than C. albicans cells alone over 24 h (P = 0.0001). Rabbits with disseminated candidiasis showed a steady increase of detectable DNA levels in plasma as disease progressed. Plasma cultures showed minimal growth of C. albicans, demonstrating that DNA extracted from plasma reflected fungal cell-free DNA. In summary, these studies of the kinetics of DNA release by C. albicans collectively demonstrate that cell-free fungal DNA is released into the bloodstream of hosts with disseminated candidiasis, that phagocytic cells may play an active role in increasing this release over time, and that plasma is a suitable blood fraction for the detection of C. albicans DNA. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10-CRC,Rm 1-5740, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 30 TC 32 Z9 33 U1 2 U2 6 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 2006 VL 44 IS 1 BP 143 EP 150 DI 10.1128/JCM.44.1.143-150.2006 PG 8 WC Microbiology SC Microbiology GA 008NT UT WOS:000235048400021 PM 16390962 ER PT J AU Rustin, GJS Timmers, P Nelstrop, A Shreeves, G Bentzen, SM Baron, B Piccart, MJ Bertelsen, K Stuart, G Cassidy, H Eisenhauer, E AF Rustin, GJS Timmers, P Nelstrop, A Shreeves, G Bentzen, SM Baron, B Piccart, MJ Bertelsen, K Stuart, G Cassidy, H Eisenhauer, E TI Comparison of CA-125 and standard definitions of progression of ovarian cancer in the intergroup trial of cisplatin and paclitaxel versus cisplatin and cyclophosphamide SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SOLID TUMORS; GUIDELINES; CARCINOMA; EVALUATE; RE AB Purpose A definition for progression of ovarian cancer has been proposed based on either a confirmed doubling of CA-125 levels from the upper limit of normal or from the nadir level if levels are persistently elevated. Retrospectively, we determined whether the use of this CA-125 definition in a randomized trial would have shown the same magnitude of difference between the treatment arms as was shown when the standard progression definition was used. Patients and Methods A retrospective analysis was performed on 680 patients in the Taxol Intergroup Trial with advanced epithelial ovarian carcinoma, of whom 628 were assessable according to CA-125. The date of progression according to clinical or radiologic criteria was compared with the date of progression according to CA-125. Results Of the 628 patients assessable for both definitions, 556 clinical or radiologic progressions were determined compared with 389 according to the CA-125 definition. There was a highly significant difference in the hazard of progression between the paclitaxel and cisplatin arm (TP) compared with the cyclophosphannide and cisplatin arm (CP) when either standard or CA-125 criteria were used to define progression (standard, P =.002; CA-125, P =.011). The hazard ratio of TP/CP over time was similar when comparing the different methods of defining progression. Conclusion The results of this analysis show that the magnitude of the therapeutic benefit was similar whether CA-125 or standard criteria were used to define progression. C1 Mt Vernon Canc Ctr, Dept Med Oncol, Northwood HA6 2RN, Middx, England. Mt Vernon Hosp, Gray Canc Inst, Northwood HA6 2RN, Middx, England. Western Infirm & Associated Hosp, Scottish Grp Data Ctr, Beatson Oncol Ctr, Glasgow, Lanark, Scotland. Eortc Data Ctr, European Org Res Treatment Canc, Gynecol Canc Cooperat Grp, Brussels, Belgium. Odense Univ Hosp, Nord Gynecol Canc Study Grp Ctr, Odense, Denmark. Queens Univ, Clin Trials Grp Data Ctr, NCI, Kingston, ON, Canada. RP Rustin, GJS (reprint author), Mt Vernon Canc Ctr, Dept Med Oncol, Northwood HA6 2RN, Middx, England. EM grustin@nhs.net RI Bentzen, Soren/E-3997-2012 OI Bentzen, Soren/0000-0002-7444-7564 NR 15 TC 66 Z9 66 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2006 VL 24 IS 1 BP 45 EP 51 DI 10.1200/JCO.2005.01.2757 PG 7 WC Oncology SC Oncology GA 998QS UT WOS:000234334700010 PM 16382112 ER PT J AU Guerrieri-Gonzaga, A Robertson, C Bonanni, B Serrano, D Cazzaniga, M Mora, S Gulisano, M Johansson, H Intra, M Latronico, A Franchi, D Pelosi, G Johnson, K Decensi, A AF Guerrieri-Gonzaga, A Robertson, C Bonanni, B Serrano, D Cazzaniga, M Mora, S Gulisano, M Johansson, H Intra, M Latronico, A Franchi, D Pelosi, G Johnson, K Decensi, A TI Preliminary results on safety and activity of a randomized, double-blind, 2 X 2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention in premenopausal women SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID GROWTH-FACTOR-I; SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; QUALITY-OF-LIFE; LONG-TERM; RECEIVING TAMOXIFEN; MAMMARY-CANCER; RISK; CHEMOPREVENTION; THERAPY AB Purpose To determine whether low-dose tamoxifen and fenretinide have a synergistic effect on surrogate biomarkers, including circulating insulin-like growth factor I (IGF-I) and mammographic density, in premenopausal women at risk for breast cancer and to study drug safety. Patients and Methods Premenopausal women (n = 235) were randomly assigned in a double-blind four-arm trial to receive tamoxifen 5 mg/d, fenretinide 200 mg/d, both agents, or placebo for 2 years. The present analysis refers to preliminary data on safety, IGF-I, and breast cancer events. Results Patients were included if they had an excised ductal carcinoma-in-situ (57%), lobular carcinomain-situ (13%), minimal invasive breast cancer (7%), or a 5-year Gail risk >= 1.3% (23%). After a median follow-up of 40 months, there was a reduction of 13%, 2%, 20%, and 1% in IGF-I levels for patients on tamoxifen, fenretinide, tamoxifen plus fenretinide, and placebo, respectively. Recruitment was stopped based on the lack of an interaction on IGH-I levels, which was a primary end point for the study. Thirty-six patients have dropped out of the study, 17 because of adverse events and 19 for various other reasons. One stage I endometrial cancer occurred in a patient on fenretinide, and one optic nerve ischemia and one deep venous thrombosis occurred on tamoxifen. There was no difference in menopausal symptoms, endometrial thickness, polyps, or ovarian cysts among treatment arms, To date, 24 breast cancers have been observed, without differences among arms. Conclusion The combination of low-dose tamoxifen and fenretinide is safe but not synergistic in lowering IGF-I levels in premenopausal women. The clinical implications require further follow-up. C1 European Inst Oncol, Div Chemoprevent, I-20141 Milan, Italy. European Inst Oncol, Div Breast Surg, I-20141 Milan, Italy. European Inst Oncol, Div Breast Diagnost, I-20141 Milan, Italy. European Inst Oncol, Div Gynaecol Surg, I-20141 Milan, Italy. European Inst Oncol, Div Pathol, I-20141 Milan, Italy. EO Osped Galliera, Div Med & Prevent Oncol, Genoa, Italy. Osped S Bortolo, Div Med Oncol, Vicenza, Italy. Univ Strathclyde, Dept Stat & Modelling Sci, Glasgow, Lanark, Scotland. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Decensi, A (reprint author), European Inst Oncol, Div Chemoprevent, Via Ripamonti,435, I-20141 Milan, Italy. EM andrea.decensi@ieo.it FU NCI NIH HHS [CA-77188] NR 47 TC 33 Z9 33 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2006 VL 24 IS 1 BP 129 EP 135 DI 10.1200/JCO.2005.02.9934 PG 7 WC Oncology SC Oncology GA 998QS UT WOS:000234334700022 PM 16382122 ER PT J AU Bernstein, ML Devidas, M Lafreniere, D Souid, AK Meyers, PA Gebhardt, M Stine, K Nicholas, R Perlman, EJ Dubowy, R Wainer, IW Dickman, PS Link, MP Goorin, A Grier, HE AF Bernstein, ML Devidas, M Lafreniere, D Souid, AK Meyers, PA Gebhardt, M Stine, K Nicholas, R Perlman, EJ Dubowy, R Wainer, IW Dickman, PS Link, MP Goorin, A Grier, HE TI Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric oncology group/children's cancer group phase II study 9457 - A report from the children's oncology group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PRIMITIVE NEUROECTODERMAL TUMOR; SOLID TUMORS; SARCOMA; CYCLOPHOSPHAMIDE; BONE; AMIFOSTINE; TOPOTECAN; ETOPOSIDE; MESNA; TRIAL AB Purpose Prognosis is poor for Ewing sarcoma patients with metastasis at diagnosis. We intensified a five-drug therapy (ifosfamide, etoposide alternated with vincristine, doxorubicin, and cyclophosphamide) using filgrastim but not stem-cell support, We studied topotecan alone and combined with cyclophosphamide in therapeutic windows before the five-drug therapy, A randomly assigned proportion of patients received amifostine as a cytoprotective agent. Patients and Methods Eligible patients were <= 30 years old and had histologically proven Ewing sarcoma or primitive neuroectodermal tumor (PNET) and metastasis at diagnosis, Chemotherapeutlic cycles began every 21 days, after recovery from toxicities. Results One hundred ten of the 117 patients enrolled were eligible. Thirty-six patients received initial topotecan. Three had partial responses (PRs), and 17 had progressive disease (PD), Thirty-seven patients were administered topotecan and cyclophosphamide; 21 of these patients achieved PR, and one patient had PD. In a randomly assigned group of 69 patients, amifostine did not provide myeloprotection, which was measured by absolute neutrophil count, platelet count, or cycle intervals. The best responses to the overall therapy included 45 complete responses, 41 PRs, stable disease in 14 patients, and PD in five patients, For all patients, the 2-year event-free survival (EFS) rate was 24% ( +/- 4%), and the overall survival rate was 46% ( +/- 5%). For the 39 patients with isolated pulmonary metastases, the 2-year EFS rate was 31% ( +/- 7%) compared with 20% ( +/- 5%) for patients with more widespread disease. Conclusion Topotecan had limited activity in patients with Ewing sarcoma or PNET metastatic at diagnosis. The topotecan-cyclophosphamide combination was active. Arnifostine was not myeloprotective, Overall results showed no improvement compared with previous Studies. C1 Hop St Justine, Montreal, PQ H3T 1C5, Canada. Ctr Data, Childrens Oncol Grp, Gainesville, FL USA. SUNY Upstate Med Univ, Syracuse, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Arkansas, Little Rock, AR 72204 USA. Childrens Mem Med Ctr Chicago, Chicago, IL USA. NIA, NIH, Ctr Gerontol Res, Baltimore, MD 21224 USA. Childrens Hosp, Phoenix, AZ USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. RP Bernstein, ML (reprint author), Hop St Justine, 3174 Cote Ste Catherine Rd, Montreal, PQ H3T 1C5, Canada. EM bernstm@magellan.umontreal.ca OI Meyers, Paul/0000-0001-6146-6101 NR 30 TC 54 Z9 63 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2006 VL 24 IS 1 BP 152 EP 159 DI 10.1200/JCO.2005.02.1717 PG 8 WC Oncology SC Oncology GA 998QS UT WOS:000234334700026 PM 16382125 ER PT J AU Alegria, M Canino, G Stinson, FS Grant, BF AF Alegria, M Canino, G Stinson, FS Grant, BF TI Nativity and DSM-IV psychiatric disorders among Puerto Ricans, Cuban Americans, and non-Latino whites in the United States: Results from the national epidemiologic survey on alcohol and related conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SUBSTANCE USE DISORDERS; INTERVIEW SCHEDULE AUDADIS; III-R; MEXICAN-AMERICANS; DRUG-USE; ANXIETY DISORDERS; NOSOLOGICAL COMPARISONS; LIFETIME PREVALENCE; CLINICAL DIAGNOSES; ICD-10 ALCOHOL AB Objective: This study examined the risk of lifetime substance use disorders and mood and anxiety disorders between Island-born Puerto Ricans, foreign-born Cuban Americans, and foreign-born non-Latino whites and their U.S.-born counterparts. Method: Data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 43,093) were used to derive lifetime prevalence rates of specific DSM-IV psychiatric disorders by subethnicity and nativity group. Logistic regression models were constructed to detect variation in the odds of each psychiatric disorder across groups. Results: A protective effect of foreign-born nativity in risk for psychiatric disorders was present for all groups but varied according to the assessed disorder. For non-Latino whites, the effect was observed for most specific psychiatric disorders, whereas, for Puerto Ricans and Cuban Americans, the effect was only evident for specific substance use disorders. Conclusion: The protective effect of nativity against psychiatric morbidity found in other studies among Mexican Americans and non-Latino whites does not entirely generalize to Puerto Ricans and Cuban Americans and may not generalize to individuals of other origins. The results of this study are discussed in terms of potential mechanisms involved in variations in the risk of specific psychiatric disorders among groups defined by nativity and race-ethnicity and the importance of identifying specific cultural components that may serve as risk and protective factors of psychiatric morbidity. C1 Natl Inst Alcohol Abuse & Alcoholism, Div Intramural Clin & Biol Res, Dept Hlth & Human Serv,Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Ctr Multicultural Mental Hlth Res, Cambridge, MA USA. Univ Puerto Rico, Behav Sci Res Inst, Puerto Real, Spain. RP Grant, BF (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Div Intramural Clin & Biol Res, Dept Hlth & Human Serv,Lab Epidemiol & Biometry, NIH, MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov NR 47 TC 108 Z9 108 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2006 VL 67 IS 1 BP 56 EP 65 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 009ZA UT WOS:000235151000009 PM 16426089 ER PT J AU Post, RM Kowatch, RA AF Post, RM Kowatch, RA TI The health care crisis of childhood-onset bipolar illness: Some recommendations for its amelioration SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID LIFE-CHART METHOD; COMORBIDITY SURVEY REPLICATION; DIVALPROEX SODIUM; MENTAL-DISORDERS; NATURAL-HISTORY; CLINICAL-TRIALS; THERAPEUTIC DILEMMAS; TREATMENT GUIDELINES; DEPRESSIVE DISORDER; ADOLESCENT MANIA AB Objective: To describe new data on the incidence and impact of childhood- and adolescent-onset bipolar illness and make recommendations to help accelerate the acquisition of knowledge in this area. Data Sources: Two large, multicenter outpatient studies in adults with DSM-IV bipolar disorder-the Systematic Treatment Enhancement Program for Bipolar Disorder and the Bipolar Collaborative Network-were the primary sources of retrospective data on age at onset. Study Selection: We focused on the 2 retrospective studies because they supplied more immediate data on age at onset and long-term prognosis than current prospective studies. Data Synthesis: The 2 studies revealed that 15% to 28% of adults experienced an onset of their illness prior to age 13 years. Those with childhood versus adult onset had a more severe, complicated, and adverse course of bipolar illness, assessed retrospectively and confirmed prospectively during naturalistic treatment. The time lag from onset of first symptoms to first treatment was strongly inversely related to age at onset and averaged 16.8 +/- 10 years in those with childhood onset. Recommendations include defining temporary consensus threshold criteria for each bipolar subtype and their prodromes; conducting studies using less onerous than traditional designs, including randomized open comparisons to acquire preliminary data in this age cohort; and forming clinical and academic treatment outcome networks to more quickly acquire treatment outcome data in this understudied population. Conclusions: The data reveal a very substantial rate of childhood-onset bipolar illness, extraordinary delays in onset to first treatment, and a very adverse long-term outcome. Several approaches to accelerating the rate of acquisition of treatment outcome data in this cohort are outlined. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Med Ctr, Dept Psychiat, Cincinnati Childrens Hosp, Cincinnati, OH 45267 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3S329,10 Ctr Dr,MSC-1272, Bethesda, MD 20892 USA. EM robert.post@nih.gov FU Intramural NIH HHS NR 107 TC 50 Z9 50 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2006 VL 67 IS 1 BP 115 EP 125 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 009ZA UT WOS:000235151000018 PM 16426098 ER PT J AU Tomchik, SM Lu, ZM AF Tomchik, SM Lu, ZM TI Auditory physiology and anatomy of octavolateral efferent neurons in a teleost fish SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE anatomy; hearing; otolith; physiology; vestibular ID ACOUSTIC PARTICLE MOTION; CROSSED OLIVOCOCHLEAR BUNDLE; GOBY DORMITATOR-LATIFRONS; FREE-SWIMMING TOADFISH; OPSANUS-TAU; LATERAL-LINE; RESPONSE PROPERTIES; SLEEPER GOBY; INNER-EAR; SACCULAR AFFERENTS AB Vertebrate hair cell systems receive innervation from efferent neurons in the brain. Here we report the responses of octavolateral efferent neurons that innervate the inner ear and lateral lines in a teleost fish, Dormitator latifrons, to directional linear accelerations, and compare them with the afferent responses from the saccule, the main auditory organ in the inner ear of this species. Efferent neurons responded to acoustic stimuli, but had significantly different response properties than saccular afferents. The efferents produced uniform, omnidirectional responses with no phase-locking. Evoked spike rates increased monotonically with stimulus intensity. Efferents were more broadly tuned and responsive to lower frequencies than saccular afferents, and efferent modulation of the otolithic organs and lateral lines is likely more pronounced at lower frequencies. The efferents had wide dynamic ranges, shallow rate-level function slopes, and low maximum discharge rates. These findings support the role of the efferent innervation of the otolithic organs as part of a general arousal system that modulates overall sensitivity of the peripheral octavolateral organs. In addition, efferent feedback may help unmask biologically relevant directional stimuli, such as those emitted by a predator, prey, or conspecific, by reducing sensitivity of the auditory system to omnidirectional ambient noise. C1 Univ Miami, Dept Biol, Coral Gables, FL 33146 USA. Univ Miami, Neurosci Program, Miami, FL 33101 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. RP Tomchik, SM (reprint author), Univ Miami, Dept Biol, 1301 Mem Dr, Coral Gables, FL 33146 USA. EM stomchik@bio.miami.edu FU NIDCD NIH HHS [R01DC03275] NR 59 TC 8 Z9 8 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD JAN PY 2006 VL 192 IS 1 BP 51 EP 67 DI 10.1007/s00359-005-0050-0 PG 17 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 996XJ UT WOS:000234208700005 PM 16180037 ER PT J AU O'Connor, SD Summers, RM Choi, JR Pickhardt, PJ AF O'Connor, SD Summers, RM Choi, JR Pickhardt, PJ TI Oral contrast adherence to polyps on CT colonography SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CT colonography; polyps; oral contrast; virtual colonoscopy ID COMPUTED-TOMOGRAPHY COLONOGRAPHY; HIGH-GRADE DYSPLASIA; COLORECTAL ADENOMAS; PERFORMANCE-CHARACTERISTICS; CONVENTIONAL COLONOSCOPY; VIRTUAL COLONOSCOPY; INVASIVE-CARCINOMA; CANCER; PATIENT; NEOPLASIA AB Although oral contrast agents are known to improve the accuracy of CT colonography (CTC) by tagging fluid and stool, it is not well recognized that oral contrast also adheres to the surface of polyps. The authors' objective was to quantitate the frequency of contrast adhering to polyps. Three hundred thirty-eight optical colonoscopy-proven polyps were identified on CTC of all of the 216 patients with polyps in a larger cohort of screening patients. CT scans of polyps were analyzed for adherent contrast (ie, a thin coat/adherent drops) in at least one view (prone/supine). Forty-six percent of the 312 polyps not touching a contrast pool had adherent contrast. Polyps with villous histology were significantly more likely to have adherent contrast (77% [20/26] vs. 43% [124/286], P < 0.001). Oral contrast agents often tag polyp surfaces in a pattern that is distinct from internal tagging of adherent stool, which must be recognized during CTC interpretation. Polyps with villous histology show a higher rate of contrast adherence than nonvillous polyps. C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Natl Naval Med Res Inst, Bethesda, MD USA. RP Summers, RM (reprint author), NIH, Dept Radiol, 10 Ctr Dr,Bldg 10,Rm 1C660,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 33 TC 26 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 2006 VL 30 IS 1 BP 51 EP 57 DI 10.1097/01.rct.0000191686.35968.f1 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 001KO UT WOS:000234532200009 PM 16365572 ER PT J AU Hoehner, CM Williams, DE Sievers, ML Knowler, WC Bennett, PH Nelson, RG AF Hoehner, CM Williams, DE Sievers, ML Knowler, WC Bennett, PH Nelson, RG TI Trends in heart disease death rates in diabetic and nondiabetic Pima Indians SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE heart disease; type 2 diabetes; American Indians ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; US ADULTS; MORTALITY; PREVALENCE; DECLINE; MINNESOTA AB Background: Secular trends over 34 years (1965-1998) in overall and cause-specific mortality were examined in 4623 Pima Indians >= 35 years old. Methods: The underlying and contributing causes of the 1363 deaths were determined from a review of all available clinical records; 540 of the deaths occurred in the 2528 nondiabetic, participants and 823 in the 2095 participants who had diabetes during all or part of the study period. Age/sex-adjusted death rates were calculated across four 8.5-year time intervals. Results: In the nondiabetic participants, the rate of death from natural causes declined gradually over time (20.4, 17.3, 17.3, and 16.0 deaths per 1000 persons/year; P=.11); deaths from ischemic heart disease (HID) were uncommon (n=22), and the rate did not change appreciably, remaining as the fifth leading natural cause of death. In the diabetic participants, the rate of death from natural causes was unchanged over time, but the rate of death from IHD (n=141) increased nearly twofold (3.3, 4.2, 6.4, and 6.4 deaths per 1000 persons/year; P <.01), becoming the leading cause of death in the third and fourth time intervals. Conclusions: The rate of death from IHD remained stable in nondiabetic Pima Indians but increased among those with diabetes. This finding suggests that, in the absence of diabetes, the underlying susceptibility to IHD in this population has not changed. (c) 2006 Elsevier Inc. All rights reserved. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Nelson, RG (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. EM rgnelson@mail.nih.gov RI Nelson, Robert/B-1470-2012 NR 31 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JAN-FEB PY 2006 VL 20 IS 1 BP 8 EP 13 DI 10.1016/j.jdiacomp.2005.06.003 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 009ZU UT WOS:000235153200002 PM 16389161 ER PT J AU Dudko, OK Szabo, A Ketter, J Wightman, RM AF Dudko, OK Szabo, A Ketter, J Wightman, RM TI Analytic theory of the current at inlaid planar ultramicroelectrodes: Comparison with experiments on elliptic disks SO JOURNAL OF ELECTROANALYTICAL CHEMISTRY LA English DT Article DE chronoamperometry; ultramicroelectrode; ellipse; ring ID LIGAND-BINDING; DIFFUSION; MICROELECTRODES; ELECTRODES; RECEPTORS; DOPAMINE AB Accurate analytic expressions are obtained for the chronoamperometric current and the general (quasi-reversible) i-E characteristics of planar inlaid microelectrodes. These expressions involve the area and the perimeter of the electrode and the steady-state diffusion-limited current. The latter can be expressed analytically exactly for circular and elliptic disk electrodes and to an excellent approximation for microelectrodes with any simply connected shape. Our results are tested experimentally for circular disks and for elliptic disks that are produced when a glass-encased carbon fiber is polished at an angle. (c) 2005 Elsevier B.V. All rights reserved. C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Dudko, OK (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, 12 South Dr,Bldg 12A,Room 2007, Bethesda, MD 20892 USA. EM dudko@mail.nih.gov RI Szabo, Attila/H-3867-2012 NR 16 TC 8 Z9 8 U1 2 U2 4 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-0728 J9 J ELECTROANAL CHEM JI J. Electroanal. Chem. PD JAN 1 PY 2006 VL 586 IS 1 BP 18 EP 22 DI 10.1016/j.jelechem.2005.09.016 PG 5 WC Chemistry, Analytical; Electrochemistry SC Chemistry; Electrochemistry GA 987MC UT WOS:000233521000003 ER PT J AU Sundy, JS Wood, WA Watt, JL Kline, JN Schwartz, DA AF Sundy, JS Wood, WA Watt, JL Kline, JN Schwartz, DA TI Safety of incremental inhaled lipopolysaccharide challenge in humans SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article DE lipopolysaccharide; endotoxin; inhalation challenge; systemic responses ID INFLAMMATORY RESPONSE; COTTON DUST; GRAIN DUST; ENDOTOXIN; INHALATION; RESPONSIVENESS; EXPOSURE; ASTHMA; SEVERITY; SYMPTOMS AB Background: Inhalation of environmental endotoxin is important in the pathogenesis of asthma and other environmental airway diseases. Inhaled airway challenge using lipopolysaccharide in humans has been performed for over 20 years to assess the airway response to endotoxin. However, there are no published data on the short-term safety of endotoxin inhalation protocols. Objective: To characterize the safety and tolerability of incremental inhaled lipopolysaccharide challenge in humans. Patients and Methods: We performed a retrospective analysis of data obtained from 119 subjects who underwent inhaled challenge with up to 41.5 mu g of lipopolysaccharide. We measured pulmonary function, temperature, mean arterial pressure, heart rate, and systemic symptoms for 3 h after challenge. Results: Fever occurred in 30% of subjects and was associated with a higher cumulative dose of lipopolysaccharide. Reduced mean arterial pressure occurred in 21% of subjects and was dose-related. There was no association between fever or decreased mean arterial pressure and airway responsiveness to inhaled lipopolysaccharide. Common symptoms reported by subjects included: chills (64%), malaise (56%), cough (56%), chest tightness (49%), headache (43%), and myalgias (27%). None of the subjects experienced delayed discharge or a serious adverse event. Conclusions: Inhaled lipopolysaccharide causes dose-related systemic responses that include fever, reduced blood pressure, and constitutional symptoms that are not associated with the airway response to inhaled lipopolysaccharide. Systemic responses to inhaled lipopolysaccharide should be expected and subjects undergoing inhaled lipopolysaccharide challenge in the research setting should be carefully monitored for non-pulmonary adverse events for several hours after challenge. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Massachusetts Gen Hosp, Harvard Comined Med Pediat Training Program, Boston, MA 02114 USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Sundy, JS (reprint author), Duke Univ, Med Ctr, Dept Med, Box 3278,014 Baker House, Durham, NC 27710 USA. EM sundy001@mc.duke.edu FU NCRR NIH HHS [RR00059]; NIEHS NIH HHS [ES005605, ES07498, ES 11185, ES 11375, ES 12496] NR 31 TC 4 Z9 4 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 2006 VL 12 IS 2 BP 113 EP 119 DI 10.1179/096805106X102174 PG 7 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 038MV UT WOS:000237226900005 PM 16690014 ER PT J AU Shoenfelt, JL Fenton, MJ AF Shoenfelt, Joanna L. Fenton, Matthew J. TI TLR2- and TLR4-dependent activation of STAT1 serine phosphorylation in murine macrophages is protein kinase C-delta-independent SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article DE TLR4; TLR2; signal transduction; interferon ID TOLL-LIKE RECEPTOR-2; NF-KAPPA-B; IFN-GAMMA; GENE-EXPRESSION; I INTERFERONS; CELLS; PATHWAY; TRANSCRIPTION; IMMUNITY; INNATE AB Engagement of Toll-like receptor (TLR) proteins activates multiple signal transduction pathways. Previous studies demonstrated that TLR2 and TLR4 engagement leads to rapid phosphorylation of the transcription factor STAT1 at serine 727 (Ser-727 STAT1) in murine macrophages. Only TLR4 engagement induced STAT1 phosphorylation at tyrosine 701, although this response was delayed compared with Ser-727 STAT1 phosphorylation. Unlike other cell types, the p38 mitogen-activated protein kinase was necessary, but not sufficient, for TLR-induced phosphorylation of Ser-727 STAT1 in macrophages. We and others had previously shown that Ser-727 STAT1 phosphorylation could be blocked by rottlerin, an inhibitor of protein kinase C-delta (PKC-delta). Here we report that peritoneal exudate macrophages from PKC-delta-deficient mice can be activated through TLR2 and TLR4 to elicit rapid phosphorylation of Ser-727 STAT1, which was blocked by both rottlerin and the p38 inhibitor SB203580, but not by the pan-PKC inhibitor bisindoylmaleamide. Furthermore, both normal and PKC-delta-deficient macrophages secreted comparable amounts of IL-6, IP-10, and RANTES following TLR engagement. In contrast, IFN-gamma-induced STAT1 serine phosphorylation was independent of both PKC-delta and p38. Overall, these studies demonstrate that a PKC-delta-independent signaling pathway downstream of both TLR2 and TLR4 is necessary for Ser-727 STAT1 phosphorylation in primary murine macrophages. C1 Univ Maryland, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov FU NIAID NIH HHS [AI057490] NR 35 TC 7 Z9 7 U1 0 U2 0 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 2006 VL 12 IS 4 BP 231 EP 240 DI 10.1179/096805106X102219 PG 10 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 077IL UT WOS:000240022400004 PM 16953975 ER PT J AU Bell, JK Botos, I Hall, PR Askins, J Shiloach, J Davies, DR Segal, DM AF Bell, Jessica K. Botos, Istvan Hall, Pamela R. Askins, Janine Shiloach, Joseph Davies, David R. Segal, David M. TI The molecular structure of the TLR3 extracellular domain SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article DE Toll-like receptors; innate immunity; protein structure ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; INNATE IMMUNITY; RECOGNITION; ACTIVATION; LIGAND AB Toll-like receptors (TLRs), type I integral membrane receptors, recognize pathogen associated molecular patterns (PAMPs). PAMP recognition occurs via the N-terminal ectodomain (ECD) which initiates an inflammatory response that is mediated by the C-terminal cytosolic signaling domain. To understand the molecular basis of PAMP recognition, we have begun to define TLR-ECD structurally. We have solved the structure of TLR3-ECD, which recognizes dsRNA, a PAMP associated with viral pathogens. TLR3-ECD is a horseshoe-shaped solenoid composed of 23 leucine-rich repeats (LRRs). The regular LRR surface is disrupted by two insertions at LRR 12 and LRR20 and 11 N-linked carbohydrates. Of note, one side of the ECD is carbohydrate-free and could lform an interaction interface. We have shown that TLR3-ECD binds directly to pI:pC, a synthetic dsRNA ligand, but not to p(dI):p(dC). Without a TLR3-dsRNA complex structure, we can only speculate how ligand binds. Analysis of the unliganded structure reveals two patches of basic residues and two binding sites for phosphate backbone mimics, sulfate ions, that may be capable of recognizing ligand. Mutational and co-crystallization studies are currently underway to determine how TLR3 binds its ligand at the molecular level. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. NIDDKD, Biotechnol Unit, Bethesda, MD 20892 USA. RP Segal, DM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36,10 Ctr Dr,MSC 1360, Bethesda, MD 20892 USA. EM dave_segal@nih.gov RI Bell, Jessica/I-3893-2013; Hall, Pamela/O-5402-2016 OI Bell, Jessica/0000-0003-1455-3274; Hall, Pamela/0000-0003-2367-3382 FU Intramural NIH HHS NR 18 TC 22 Z9 25 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 2006 VL 12 IS 6 BP 375 EP 378 DI 10.1179/096805106X118780 PG 4 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 115EF UT WOS:000242716900007 PM 17254392 ER PT J AU Spencer, HB Hussein, WR Tchounwou, PB AF Spencer, HB Hussein, WR Tchounwou, PB TI Growth inhibition in Japanese medaka (Oryzias latipes) fish exposed to tetrachloroethylene SO JOURNAL OF ENVIRONMENTAL BIOLOGY LA English DT Article DE tetrachloroethylene; toxicity; Japanese medaka; growth inhibition ID EMBRYOS AB A recent study in our laboratory has demonstrated that tetrachloroethylene (TCE) is acutely toxic to Japanese medaka (Oryzias latipes) larvae with a 96 hr-LC50 of 18 (17-19) mg/mL (Spencer et al., 2002). In the present study we hypothesize that TCE exposure induces a developmental effect in Japanese medaka. Growth and age specific sensitivity of Japanese medaka larvae were studied with four age groups (7, 14, 21 and 28 days old) to determine tetrachloroethylene effects on these parameters, The medaka larvae were exposed for 96 hours in a single concentration (10 mg/mL) of TCE The toxic endpoints evaluated were larvae weight, length, water content and protein concentration. The study revealed that exposure of medaka larvae to this sub-acute concentration of TCE significantly reduced length and weight in the treated group. The difference in growth between control and treated groups was more obvious in age versus length, than in age versus weight. The dry weight-fresh weight ratio (dw/fw) was shown to be higher in the control group. Water content in TCE-treated medaka was higher than in the control group, and younger fry had more water content than older ones. A higher protein concentration was also observed in TCE-treated medaka compared to the control group. These results indicate that TCE has a profound effect on the growth and development of Japanese medaka larvae. C1 Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth, Jackson, MS 39217 USA. Mississippi Valley State Univ, Dept Nat Sci & Environm Hlth, Itta Bena, MS 38941 USA. Jackson State Univ, Sch Sci & Technol, Dept Chem, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth, POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu NR 18 TC 2 Z9 2 U1 2 U2 5 PU TRIVENI ENTERPRISES PI LUCKNOW PA C/O KIRAN DALELA, 1/206 VIKAS NAGAR, KURSI RD, LUCKNOW 226 022, INDIA SN 0254-8704 J9 J ENVIRON BIOL JI J.Environ.Biol. PD JAN PY 2006 VL 27 IS 1 BP 1 EP 5 PG 5 WC Environmental Sciences SC Environmental Sciences & Ecology GA 005HD UT WOS:000234812300001 PM 16850867 ER PT J AU Vermeulen, R Lan, Q Li, GL Rappaport, SM Kim, S de Joode, BV Shen, M Xu, BH Smith, MT Zhang, LP Yin, SN Rothman, N AF Vermeulen, Roel Lan, Qing Li, Guilan Rappaport, Stephen M. Kim, Sungkyoon de Joode, Berna van Wendel Shen, Min Xu Bohong Smith, Martyn T. Zhang, Luoping Yin, Songnian Rothman, Nathaniel TI Assessment of dermal exposure to benzene and toluene in shoe manufacturing by activated carbon cloth patches SO JOURNAL OF ENVIRONMENTAL MONITORING LA English DT Article ID URINARY; METABOLISM; BIOMARKERS AB Objectives: The aim of this investigation was to use activated carbon cloth ( ACC) patches to study the probability and extent of dermal exposure to benzene and toluene in a shoe factory. Methods: Inhalation and dermal exposure loading were measured simultaneously in 70 subjects on multiple days resulting in 113 observations. Dermal exposure loading was assessed by ACC patches attached to likely exposed skin areas ( e. g. the palm of the hand and abdomen). A control patch at the chest and an organic vapor monitor ( OVM) were used to adjust the hand and abdomen patches for the contribution from the air through passive absorption of benzene and toluene on the ACC patches. Systemic exposure was assessed by quanti. cation of unmetabolized benzene ( UBz) and toluene ( UTol) in urine. Results: Mean air concentrations for the study population were 1.5 and 7.5 ppm for benzene and toluene, respectively. Iterative regression analyses between the control patch, OVM and the dermal patches showed that only a small proportion of the ACC patches at the hand had likely benzene ( n = 4; mean 133 mu g cm(-2) h(-1)) or toluene ( n = 5; mean 256 mg cm(-2) h(-1)) contamination. Positive patches were exclusively observed among subjects performing the task of gluing. Significant dermal exposure loading to the abdomen was detected only for toluene ( n = 2; mean 235 mg cm(-2) h(-1)). No relation was found between having a positive hand or abdomen ACC patch and UBz or UTol levels. In contrast a strong association was found between air levels of benzene ( p = 0.0016) and toluene ( p < 0.0001) and their respective urinary levels. Conclusions: ACC patches are shown to be a useful technique for quantifying the probability of dermal exposure to organic solvents and to provide estimates of the potential contribution of the dermal pathway to systemic exposure. Using ACC patches we show that dermal exposure to benzene and toluene in a shoe manufacturing factory is probably rare, and when it occurred exposures were relatively low and did not significantly contribute to systemic exposure. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands. China CDC, Natl Inst Occupat Hlth & Poison Control, Beijing, Peoples R China. Univ N Carolina, Chapel Hill, NC 27599 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Vermeulen, R (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. EM R.Vermeulen@iras.uu.nl RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU Intramural NIH HHS; NIEHS NIH HHS [P30ES10126, P30ES01896, P42ES04705, P42ES05948, R01ES06721] NR 19 TC 4 Z9 4 U1 0 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1464-0325 J9 J ENVIRON MONITOR JI J. Environ. Monit. PY 2006 VL 8 IS 11 BP 1143 EP 1148 DI 10.1039/b608076f PG 6 WC Chemistry, Analytical; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA 100DT UT WOS:000241648500006 PM 17075621 ER PT J AU Murray, EA Gaffan, D AF Murray, EA Gaffan, D TI Prospective memory in the formation of learning sets by rhesus monkeys (Macaca mulatta) SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-ANIMAL BEHAVIOR PROCESSES LA English DT Article DE macaque; visual learning; reward ID ACQUISITION AB In conventional discrimination learning-set formation, it is possible that rhesus monkeys (Macaca mulatta) learn to lay down prospective memories by anticipating the next trial and deciding in advance what choice will be made. To test this hypothesis, the authors administered discrimination problems with 24-hr intertrial intervals, predicting that these long intervals would disrupt or prevent the putative anticipation of the next trial. Confirming their expectation, the authors found no indication of learning-set formation under these conditions. C1 Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Murray, EA (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England. EM gaffan@psy.ox.ac.uk OI Murray, Elisabeth/0000-0003-1450-1642 FU Intramural NIH HHS NR 12 TC 18 Z9 18 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0097-7403 J9 J EXP PSYCHOL ANIM B JI J. Exp. Psychol.-Anim. Behav. Process. PD JAN PY 2006 VL 32 IS 1 BP 87 EP 90 DI 10.1037/0097-7403.32.1.87 PG 4 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental; Zoology SC Psychology; Behavioral Sciences; Zoology GA 003PZ UT WOS:000234695400008 PM 16435968 ER PT J AU Hoppin, JA Ulmer, R Calafat, AM Barr, DB Baker, SV Meltzer, HM Ronningen, KS AF Hoppin, JA Ulmer, R Calafat, AM Barr, DB Baker, SV Meltzer, HM Ronningen, KS TI Impact of urine preservation methods and duration of storage on measured levels of environmental contaminants SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE sample storage and shipment; cohort studies; analytical chemistry; urine ID TANDEM MASS-SPECTROMETRY; DIALKYL PHOSPHATE METABOLITES; ORGANOPHOSPHORUS PESTICIDES; QUANTITATIVE DETECTION; PHTHALATE METABOLITES; QUANTIFICATION AB Collection of urine samples in human studies involves choices regarding shipping, sample preservation, and storage that may ultimately influence future analysis. As more studies collect and archive urine samples to evaluate environmental exposures in the future, we were interested in assessing the impact of urine preservative, storage temperature, and time since collection on nonpersistent contaminants in urine samples. In spiked urine samples stored in three types of urine vacutainers (no preservative, boric acid, and chlorhexidine), we measured five groups of contaminants to assess the levels of these analytes at five time points ( 0, 24, 48, and 72 h, and 1 week) and at two temperatures (room temperature and 4 degrees C). The target chemicals were bisphenol A (BPA), metabolites of organophosphate (OP), carbamate, and pyrethroid insecticides, chlorinated phenols, and phthalate monoesters, and were measured using five different mass spectrometry-based methods. Three samples were analyzed at each time point, with the exception of BPA. Repeated measures analysis of variance was used to evaluate effects of storage time, temperature, and preservative. Stability was summarized with percent change in mean concentration from time 0. In general, most analytes were stable under all conditions with changes in mean concentration over time, temperature, and preservative being generally less than 20%, with the exception of the OP metabolites in the presence of boric acid. The effect of storage temperature was less important than time since collection. The precision of the laboratory measurements was high allowing us to observe small differences, which may not be important when categorizing individuals into broader exposure groups. C1 NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. WESTAT Corp, Res Triangle Pk, NC USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, DHHS, Atlanta, GA USA. CODA Res, Res Triangle Pk, NC USA. Norwegian Inst Publ Hlth, Oslo, Norway. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, NIH, DHHS, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov RI Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013; OI Meltzer, Helle Margrete/0000-0002-3591-7017 FU Intramural NIH HHS NR 14 TC 17 Z9 17 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD JAN PY 2006 VL 16 IS 1 BP 39 EP 48 DI 10.1038/sj.jea.7500435 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 015CB UT WOS:000235528400005 PM 16007114 ER PT J AU Holmes-Rovner, M Price, C Rovner, DR Kelly-Bloke, K Lillie, J Wills, C Bonham, VL AF Holmes-Rovner, M Price, C Rovner, DR Kelly-Bloke, K Lillie, J Wills, C Bonham, VL TI Men's theories about benign prostatic hyperplasia and prostate cancer following a benign prostatic hyperplasia decision aid SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 2nd International Shared Decision Making Meeting CY SEP 02-04, 2003 CL Swansea, WALES DE decision aids; benign prostatic hyperplasia; prostate cancer; shared decision making ID MAKING PROGRAM; BREAST-CANCER; RISK AB OBJECTIVE: To use qualitative methods to explore audiotape evidence of unanticipated confusion between benign prostatic hyperplasia (BPH) and prostate cancer in using a videotape BPH treatment decision aid (DA). DESIGN: Qualitative analysis of semi-structured interviews and surveys originally collected to study men's interpretation of a DA. SETTING AND PARTICIPANTS: Community sample of college and noncollege educated African American and white men (age >= 50; n=188). MEASURES: Transcript analysis identified themes in men's comments about BPH and cancer. Surveys measured BPH general and prostate cancer-specific knowledge, literacy (Short Test of Functional Health Literacy in Adults), BPH symptoms. and demographics. RESULTS: In transcript analysis, 18/188 men spontaneously talked about BPH and cancer as being related to each other, despite explicit statements to the contrary in the video. Survey data suggest that up to 126/188 men (67%) persisted in misconceptions even after viewing the DA video. Three themes were identified in the transcripts: (1) BPH and cancer are equated, (2) BPH surgery is for the purpose of removing cancer, and (3) BPH leads to cancer. CONCLUSIONS: Overall knowledge increases with DA use may mask incorrect theories of disease process. Further research should identify decision support designs and clinical counseling strategies to address persistence of beliefs contrary to new information presented in evidence-based DAs. C1 Michigan State Univ, Coll Human Med, Dept Med, E Lansing, MI 48824 USA. Michigan State Univ, Coll Human Med, Ctr Eth, E Lansing, MI 48824 USA. Michigan State Univ, Dept Anthropol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Commun Arts & Sci, E Lansing, MI 48824 USA. Michigan State Univ, Coll Nursing, E Lansing, MI 48824 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Holmes-Rovner, M (reprint author), Michigan State Univ, Coll Human Med, Dept Med, C203 E Fee Hall, E Lansing, MI 48824 USA. EM mholmes@msu.edu RI Wills, Celia/D-4242-2013 FU AHRQ HHS [R01 HS010608, R01 HS10608]; NIMH NIH HHS [K08 MH001721, K08 MH01721] NR 25 TC 6 Z9 6 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2006 VL 21 IS 1 BP 56 EP 60 DI 10.1111/j.1525-1497.2005.00280.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 010CD UT WOS:000235163600009 PM 16423124 ER PT J AU Clark, RH Kenyon, JC Bartlett, NW Tscharke, DC Smith, GL AF Clark, RH Kenyon, JC Bartlett, NW Tscharke, DC Smith, GL TI Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CHEMOKINE-BINDING-PROTEIN; ATTENUATED MVA STRAIN; T-CELL INDUCTION; SMALLPOX VACCINE; HOST-RANGE; INFLAMMATORY RESPONSE; ANKARA; INFECTION; IMMUNIZATION; PROTECTION AB Vaccinia virus (VACV) is the vaccine that was used to eradicate smallpox and is being developed as a recombinant vaccine for other pathogens. Removal of genes encoding immunomodulatory proteins expressed by VACV may enhance virus immunogenicity and improve its potential as a vaccine. Protein A41 is a candidate for removal, having sequence similarity to the VACV chemokine-binding protein, vCKBP, and an association with reduced inflammation during dermal infection. Here, it is shown that, at low doses, VACV strain Western Reserve (WR) lacking A41L (v Delta A41L) was slightly more virulent than wild-type and revertant controls after intranasal infection of BALB/c mice. The primary immune response to v Delta A41L was marked by an increase in the percentage of VACV-specific gamma interferon-producing CD8(+) T cells and enhancement of cytotoxic T-cell responses in the spleen. However, this augmentation of cellular response was not seen in lung infiltrates. Splenic CD8(+) T-cell responses were also enhanced when VACV strain modified vaccinia virus Ankara (MVA) lacking A41L was used to immunize mice. Lastly, immunization with VACV MVA lacking A41L provided better protection than control viruses to subsequent challenge with a 300 LD50 dose of VACV WR. This study provides insight into the immunomodulatory role of A41 and suggests that MVA lacking A41 may represent a more efficacious vaccine. C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Virol, London W2 1PG, England. NIAID, Viral Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Queensland Inst Med Res, EBV Biol Lab, Div Immunol & Infect Dis, Herston, Qld 4006, Australia. RP Smith, GL (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Virol, Norfolk Pl, London W2 1PG, England. EM glsmith@imperial.ac.uk RI Tscharke, David/C-9133-2009; OI Tscharke, David/0000-0001-6825-9172; Bartlett, Nathan/0000-0002-2715-5163 FU Medical Research Council [G0501257]; Wellcome Trust NR 50 TC 52 Z9 52 U1 0 U2 1 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 2006 VL 87 BP 29 EP 38 DI 10.1099/vir.0.81417-0 PN 1 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 002YI UT WOS:000234647800004 PM 16361415 ER PT J AU Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG AF Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG TI Rehabilitation medicine summit - Building research capacity SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE coalition; physical medicine and rehabilitation; rehabilitation science; researech capacity AB The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The 5 elements of research capacity that guided the discussions were (1) researchers; (2) research culture, environment, and infrastructure; (3) funding; (4) partnerships; and (5) metrics. The 100 participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. The small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Simmit, multiorganizational initiative is called to pursue the agendas outlined in this article. C1 Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. Boston Univ, Boston, MA 02215 USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Florida, Gainesville, FL USA. Powers Pyles Sutter & Verville PC, Washington, DC USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Rehabil Inst Chicago, Chicago, IL 60611 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Frontera, WR (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, 125 Nashua St, Boston, MA 02114 USA. EM wfrontera@partners.org NR 3 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2006 VL 21 IS 1 BP 1 EP 7 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 004WW UT WOS:000234784300001 PM 16456387 ER PT J AU Viswanath, K Breen, N Meissner, H Moser, RP Hesse, B Steele, WR Rakowski, W AF Viswanath, K Breen, N Meissner, H Moser, RP Hesse, B Steele, WR Rakowski, W TI Cancer knowledge and disparities in the information age SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID AREA SOCIOECONOMIC PATTERNS; HEALTH INTERVIEW SURVEY; NEWS MEDIA COVERAGE; MASS MEDIA; GAP; WOMEN; MAMMOGRAPHY; PREVALENCE; MORTALITY; BEHAVIOR AB Increasing information flow often leads to widening gaps in knowledge between different socioeconomic status (SES) groups as higher SES groups are more likely to acquire this new information at a faster rate than lower SES groups. These gaps in knowledge may offer a partial but robust explanation for differential risk behaviors and health disparities between different social groups. Drawing on the Health Information National Trends Survey (HINTS 2003), a national survey of communication behaviors conducted by the National Cancer Institute (NCI), we examine the relationship between publicity and knowledge gaps on two cancer topics that received different levels of publicity: knowledge about tobacco and sun exposure and their respective links to cancer. Analyses of the HINTS 2003 data suggest that differential knowledge levels of causes of cancer between SES groups are one potential explanation of cancer disparities that have been extensively reported in the literature. It is evident that high income and high education are associated with awareness about causes of major cancers such as lung and skin, and may allow people to protect themselves and minimize their risks. The data also show that heavier media attention could attenuate the knowledge gaps though moderate publicity or lack of news coverage may actually widen them. Last, the findings in this article suggest that it is necessary to take into account the SES variation within different racial and ethnic groups rather than mask them by treating the groups as one. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. Brown Univ, Providence, RI 02912 USA. RP Viswanath, K (reprint author), Dana Farber Canc Inst, SM251,Smith Bldg,44 Binney St, Boston, MA 02115 USA. EM vish_viswanath@dfci.harvard.edu OI Hesse, Bradford/0000-0003-1142-1161 NR 45 TC 151 Z9 153 U1 3 U2 25 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 2006 VL 11 SU 1 BP 1 EP 17 DI 10.1080/10810730600637426 PG 17 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 046ZV UT WOS:000237850500004 PM 16641071 ER PT J AU Hesse, BW Moser, RM Rutten, LJF Kreps, GL AF Hesse, BW Moser, RM Rutten, LJF Kreps, GL TI The Health Information National Trends Survey: Research from the baseline SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID SURVEY HINTS; CANCER CONTROL; COMMUNICATION; DISSEMINATION; SCIENCE; DESIGN; TRANSDISCIPLINARY; CHALLENGES; STRATEGIES; INTERNET AB The decades surrounding the turn of the millennium will be remembered as a time of extraordinary opportunity in cancer communication. In 1990, the number of age-adjusted deaths due to cancer in the U.S. population began a slow steady decline after a century of disparaging increase. Reasons for this decline have been attributed to long-awaited successes in primary prevention, especially related to tobacco, and early detection for cervical, breast, prostate, and colorectal cancers, as well as advances in treatment. This was also a time of unparalleled change in the cancer communication environment. Scientific health discoveries escalated with the completion of the Human Genome project in 2003, and penetration of the Internet made health information available directly to consumers. To seize the opportunity afforded by these changes, the National Cancer Institute (NCI) launched the Health Information National Trends Survey (HINTS). Fielded for the first time in 2003, the HINTS is a nationally representative, general population survey of non-institutionalized adults in the United States 18 years and older. This supplement contains a compilation of original research conducted using the data generated by the first administration of the HINTS telephone interviews. Covering topics in cancer knowledge, cancer cognition, risk perception, and information seeking, the articles represent an interdisciplinary view of cancer communication at the turn of the millennium and offer insight into the road ahead C1 NCI, Bethesda, MD 20892 USA. SAIC, Rockville, MD USA. George Mason Univ, Fairfax, VA 22030 USA. RP Hesse, BW (reprint author), NCI, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 46 TC 37 Z9 37 U1 2 U2 8 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 2006 VL 11 SU 1 BP VII EP XVI DI 10.1080/10810730600692553 PG 10 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 046ZV UT WOS:000237850500003 PM 16641070 ER PT J AU Freimuth, VS Massett, HA Meltzer, W AF Freimuth, VS Massett, HA Meltzer, W TI A descriptive analysis of 10 years of research published in the Journal of Health Communication SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article AB This article describes the contents of the articles from the first decade of The Journal of Health Communication (JOHC). Three hundred and twenty-one published articles were reviewed and coded to determine the characteristics of the researchers, the types of research presented, the common health topics covered, and the research designs used. The results led to the following profile of a typical article. Its primary author is a U. S. academic. It probably focuses on smoking, HIV/AIDS, or cancer. It is an empirical research study, more likely to use quantitative, specifically survey methods, rather than qualitative methods. It probably is not driven by theory. It is much more likely to examine mass media communication than interpersonal communication. Its purpose is just as likely to be audience analysis as message design, as evaluation of a planned communication intervention. If its purpose is to evaluate a planned communication intervention however, that intervention is almost certainly a successful one. C1 Univ Georgia, Grady Coll Journalism & Mass Commun, Dept Speech Commun, Atlanta, GA 30333 USA. NCI, Bethesda, MD 20892 USA. George Washington Univ, Ctr Global Hlth, Washington, DC 20052 USA. RP Freimuth, VS (reprint author), Univ Georgia, Grady Coll Journalism & Mass Commun, Dept Speech Commun, Atlanta, GA 30333 USA. NR 2 TC 14 Z9 14 U1 0 U2 2 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. PD JAN-FEB PY 2006 VL 11 IS 1 BP 11 EP 20 DI 10.1080/10810730500461042 PG 10 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 005SZ UT WOS:000234845400003 PM 16546916 ER PT J AU Han, PKJ Moser, RP Klein, WMP AF Han, PKJ Moser, RP Klein, WMP TI Perceived ambiguity about cancer prevention recommendations: Relationship to perceptions of cancer preventability, risk, and worry SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID SHARED DECISION-MAKING; BREAST-CANCER; PROSTATE-CANCER; INFORMED-CONSENT; INDIVIDUAL-DIFFERENCES; SCREENING MAMMOGRAPHY; UNCERTAINTY; WOMEN; INFORMATION; CHOICE AB In this study, we apply the concept of "ambiguity," as developed in the decision theory literature, to an analysis of potential psychological consequences of uncertainty about cancer prevention recommendations. We used Health Information National Trends Survey (HINTS) 2003 data to examine how perceived ambiguity about cancer prevention recommendations relates to three other cognitive variables known to influence cancer-protective behavior: perceived cancer preventability, perceived cancer risk, and cancer-related worry. Using logistic regression analyses, we tested several predictions derived from a review of literature on the effects of ambiguity perceptions on decision making, cognitions, and emotions. We found perceived ambiguity to have a strong negative relationship with perceived cancer preventability, consistent with "ambiguity aversion"-a pessimistic bias in the interpretation of ambiguity. Cancer worry moderated this relationship; ambiguity aversion increased with higher levels of worry. At the same time, perceived ambiguity was positively related to both perceived cancer risk and cancer worry. Furthermore, perceived risk partially mediated the relationship between perceived ambiguity and worry. These findings suggest that perceived ambiguity about cancer prevention recommendations may have broad and important effects on other health cognitions. We discuss ethical implications of these findings for health communication efforts, and propose a tentative causal model to guide future research. C1 NCI, Basic & Biobehav Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. RP Han, PKJ (reprint author), NCI, Basic & Biobehav Res Branch, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4097,MSC 7363, Bethesda, MD 20892 USA. EM hanp@mail.nih.gov OI Han, Paul/0000-0003-0165-1940 FU Intramural NIH HHS [Z99 HG999999] NR 85 TC 57 Z9 57 U1 0 U2 14 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 2006 VL 11 SU 1 BP 51 EP 69 DI 10.1080/10810730600637541 PG 19 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 046ZV UT WOS:000237850500007 PM 16641074 ER PT J AU Squiers, L Bright, MA Rutten, LJF Atienza, AA Treiman, K Moser, RP Hesse, B AF Squiers, L Bright, MA Rutten, LJF Atienza, AA Treiman, K Moser, RP Hesse, B TI Awareness of the National Cancer Institute's Cancer Information Service: Results from the Health Information National Trends Survey (HINTS) SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID INTERNET AB Established in 1975, the National Cancer Institute's (NCI's) Cancer Information Service (CIS) is a national information and education network that serves the nation by providing the latest scientific cancer information to the American public. The purpose of this study was to determine the public's awareness of the CIS and other national cancer and health organizations by analyzing data from the NCI's Health Information National Trends Survey (HINTS 2003). This study also examined sociodemographic, health, and communication correlates of awareness of CIS and other national health organizations: American Cancer Society (ACS), National Institutes of Health (NIH), and NCI. Results indicated that awareness of the CIS was low (32.8%). Some subgroups were more likely to be aware of the CIS than others. When comparing awareness levels of the four national health organizations, marked differences in patterns of awareness among specific subgroups emerged for many sociodemogrophic variables. For example, minority groups were significantly more aware of the CIS than Whites; however, for all three other organizations a greater percentage of Whites were aware of each organization. For the NIH, NCI, and A CS, respondents in the highest income group were most aware Of each organization and, as income level increased awareness also increased. The CIS, respondents with the lowest income levels, however, were more aware of the CIS compared with middle- and high-income groups. A similar pattern was found for other sociodemographic variables. Results of this study will guide the development of a targeted promotional campaign for the CIS. C1 NCI, Off Canc Informat Serv, Rockville, MD 20850 USA. NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci,SAIC Frederick Inc, Frederick, MD USA. NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Canc Informat Serv, Bethesda, MD 20892 USA. RP Squiers, L (reprint author), NCI, Off Canc Informat Serv, 6116 Execut Blvd, Rockville, MD 20850 USA. EM squiersl@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 16 TC 19 Z9 19 U1 0 U2 1 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 2006 VL 11 SU 1 BP 117 EP 133 DI 10.1080/10810730600637517 PG 17 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 046ZV UT WOS:000237850500011 PM 16641078 ER PT J AU Rutten, LJF Augustson, E Wanke, K AF Rutten, LJF Augustson, E Wanke, K TI Factors associated with patients' perceptions of health care providers' communication behavior SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID COMMUNITY FAMILY-PRACTICE; SERVICES TASK-FORCE; DECISION-MAKING; CONSENSUS STATEMENT; CENTERED CARE; OUTCOMES; CANCER; INTERVENTIONS; LITERACY; QUALITY AB We examined patients' ratings of communication with health care providers by sociodemographic characteristics, health care access, and health status. Data were from a national, population-based survey, the 2003 Health Information National Trends Survey (HINTS). The survey was administered to 6,369 adults from a representative sample of U.S. households. Linear regression analysis was conducted using SUDAAN. None of the sociodemographic variables were significantly associated with patients' ratings of providers' communication behavior in the linear model. Ratings of health care providers' communication behavior, however, were significantly higher among respondents with health insurance (p = 0.007) and those with a usual source of health care from whom they consistently sought care (p < 0.001). Ratings of provider communication were significantly lower among respondents who perceived their general health to be fair or poor (p < 0. 001) and among those respondents with greater depressive symptoms (p < 0.001). Differences in patient ratings of health care providers' communication by health care access and health status suggest the potential for disparities in health outcomes. C1 NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci,SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Tobacco Control Res Branch, Div Canc Control & Populat Sci, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Rutten, LJF (reprint author), 6130 Execut Blvd,Rm 4051A,MSC 7365, Bethesda, MD 20892 USA. EM finneyl@mail.nih.gov NR 48 TC 42 Z9 42 U1 2 U2 8 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 2006 VL 11 SU 1 BP 135 EP 146 DI 10.1080/10810730600639596 PG 12 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 046ZV UT WOS:000237850500012 PM 16641079 ER PT J AU Rutten, LJF Squiers, L Hesse, B AF Rutten, LJF Squiers, L Hesse, B TI Cancer-related information seeking: Hints from the 2003 Health Information National Trends Survey SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID INTERVIEW SURVEY; SERVICE; IMPACT; KNOWLEDGE; PREVENTION; EXPERIENCE; STRATEGY; NEEDS; MODEL; RISK AB Few nationally representative surveys have assessed the cancer-related information seeking behavior of the American public. Data for our analysis were from the 2003 Health Information National Trends Survey (HINTS). The goals of our analysis were to characterize cancer information seekers (3,011) and nonseekers (3,348) in terms of sociodemographic, health care access, and health status variables, and to describe the nature of the cancer-related information being sought by information seekers. Significant and independent associations with seeking status were identified for gender, age, race, income, education, personal and family history of cancer, and having a usual source of health care. Information seekers were less likely to be male (OR = .51); aged 65 or older (OR = .40); Hispanic (OR = .60); to have a usual source of health care (OR = .70); and more likely to have incomes greater than $50,000 (OR = 1.50), some college (OR = 1.87) or a college degree (OR = 2.95), a prior cancer diagnosis (OR = 3.57), or a family history of cancer (OR = 2.17). Among cancer information seekers, the most frequently searched topic was cancer site-specific information (50.2%). Individuals who reported searching for cancer site-specific information were most frequently looking for information about breast cancer (23.8%), prostate cancer (11.5%), and skin cancer (11.3%). The HINTS survey provides a unique opportunity to explore the characteristics of information seekers and nonseekers and the content of information being sought by the public in a nationally representative sample; understanding gained from this effort provides generalizable and policy-relevant information about the American public's information needs. C1 NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci,SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Canc Informat Serv, Bethesda, MD 20892 USA. NCI, Hlth Commun & Informat Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Rutten, LJF (reprint author), 6130 Execut Blvd,Rm 4051A,MSC 7365, Bethesda, MD USA. EM finneyl@mail.nih.gov NR 30 TC 116 Z9 118 U1 4 U2 11 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 2006 VL 11 SU 1 BP 147 EP 156 DI 10.1080/10810730600637574 PG 10 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 046ZV UT WOS:000237850500013 PM 16641080 ER PT J AU El-Serag, HB Siegel, AB Davila, JA Shaib, YH Cayton-Woody, M McBride, R McGlynn, KA AF El-Serag, HB Siegel, AB Davila, JA Shaib, YH Cayton-Woody, M McBride, R McGlynn, KA TI Treatment and outcomes of treating of hepatocellular carcinoma among Medicare recipients in the United States: A population-based study SO JOURNAL OF HEPATOLOGY LA English DT Article DE outcomes; SEER-Medicare; resection; transplant; treatment; HCC ID SURVIVAL AB Background/Aims: There are several treatment alternatives available for patients diagnosed with hepatocellular carcinoma (HCC). Yet, neither the extent to which potentially curative or palliative therapy is used to treat HCC, nor the determinants of using such therapies are known. Further, it is unclear how effective different modalities are for treating HCC. Methods: We used the linked SEER-Medicare dataset to identify patients diagnosed with HCC between 1992 and 1999. We identified 2963 patients with continuous Medicare enrollment who were not enrolled in a Medicare-HMO. HCC treatments were categorized as potentially curative therapy (resection, transplant, local ablation), or palliative (trans-arterial chemoembolization (TACE), chemotherapy), and no therapy. Demographic (age, sex, race, geographic region), clinical (comorbidity, risk factors and severity of liver disease) and tumor factors (tumor size, extent of disease) were examined as potential determinants of therapy, as well as survival in univariate and multivariable analyses. Survival curves were also generated and compared among the different treatment modalities. Results: The median age at diagnosis was 74 years (range: 32-105), and most patients (91%) were older than 65 years. Approximately 68% were White, 10% Black, 4% Hispanic, 8% Asian, and 9% were of other race. Thirteen percent of the patients received potentially curative therapy (transplant 0.9%, resection 8.2%, local ablation 4.1%), 4% received TACE,57% received other palliative therapy, and 26% received no specific therapy. Only 34% of 513 patients with single lesions, and 34% of 143 patients with lesions < 3.0 cm received potentially curative therapy. However, 19.2% of patients with unfavorable tumor features (lesion > 10.0 cm) received such therapy. Among patients who received potentially curative therapy (n = 392), resection was the most common procedure (n = 243,62%) followed by local ablation (n = 122, 31%) and finally transplantation (n = 27, 7%). In regression analyses, geographic variations in the extent and type of curative therapy persisted after adjusting for demographic, clinical, and tumor features. Median overall survival was 104 days following HCC diagnosis with the longest survival in the transplant group (852 days) and the shortest survival in the group with no treatment (58 days). In the survival analysis, transplantation led to the longest survival, followed by resection. Neither ablation nor TACE yielded prolonged survival (3 year survival was less than 10%). Conclusions: In this predominantly 65 years and older Medicare population, there are marked geographic variations in the management of HCC that seem to be at least as important as clinical and tumor-related features in determining the extent and type of HCC therapy. There is underutilization of potentially curative therapy, even among those with favorable tumor features. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. C1 Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Gastroenterol Sect, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. Columbia Univ, Coll Phys & Surg, Div Canc Epidemiol & Genet, NCI,DHHS, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Columbia Univ, Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, New York, NY USA. Columbia Univ, Coll Phys & Surg, Mailman Sch Publ Hlth, New York, NY USA. RP El-Serag, HB (reprint author), Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 13 TC 139 Z9 139 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JAN PY 2006 VL 44 IS 1 BP 158 EP 166 DI 10.1016/j.jhep.2005.10.002 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 000FG UT WOS:000234445700026 PM 16290309 ER PT J AU Torgan, CE Daniels, MP AF Torgan, CE Daniels, MP TI Calcineurin localization in skeletal muscle offers insights into potential new targets SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE calcineurin; skeletal muscle; triad; nucleolus; nucleus; ryanodine receptor; myoblast ID HEAVY-CHAIN EXPRESSION; PROTEIN-KINASES; CA2+ SIGNALS; NUCLEUS; HYPERTROPHY; PATHWAY; CELLS; DIFFERENTIATION; PHOSPHATASES; ASSOCIATION AB The Ca2+/calmodulin-activated protein phosphatase, calcineurin, is believed to regulate the development and function of skeletal and cardiac muscle. Striated muscle contains many calcineurin substrates, a few of which have been colocalized or found in molecular complexes with calcineurin. We examined the subcellular distribution of calcineurin in developing rat skeletal muscle cells and adult mouse skeletal muscle fibers by immunofluorescence microscopy. We found low levels of calcineurin immunoreactivity in the cytoplasm of myoblasts and higher levels in cytoplasmic vesicles of myotubes. Most of these vesicles were not immunoreactive for ryanodine receptors and, those that were, represented a small fraction of nascent triad junctions. In adult myofibers, calcineurin was largely associated with triads. Weaker calcineurin immunoreactivity occurred in the sarcoplasmic reticulum at the level of the M line. Unexpectedly, we found tiny clusters of calcineurin associated with nucleoli of developing myofiber nuclei. There were one to three clusters per nucleolus, either within or at the edges of fibrillar centers where ribosomal genes are transcribed. This suggests a role for calcineurin in regulating ribosome synthesis. Our findings suggest a variety of potential new targets and pathways through which calcineurin could regulate skeletal muscle development and plasticity and underscore the importance of spatial specificity in this regulation. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Daniels, MP (reprint author), NHLBI, Cell Biol Lab, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM danielsm2@mail.nih.gov NR 39 TC 10 Z9 12 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JAN PY 2006 VL 54 IS 1 BP 119 EP 128 DI 10.1369/jhc.5A6769.2005 PG 10 WC Cell Biology SC Cell Biology GA 998WZ UT WOS:000234351900014 PM 16174789 ER PT J AU Kellermayer, R Hsu, AP Stankovics, J Balogh, P Hadzsiev, K Vojcek, A Marodi, L Kajtar, P Kosztolanyi, G Puck, JM AF Kellermayer, Richard Hsu, Amy P. Stankovics, Jozsef Balogh, Peter Hadzsiev, Kinga Vojcek, Agnes Marodi, Laszlo Kajtar, Pa Kosztolanyi, Gyorgy Puck, Jennifer M. TI A novel IL2RG mutation associated with maternal T lymphocyte engraftment in a patient with severe combined immunodeficiency SO JOURNAL OF HUMAN GENETICS LA English DT Article DE severe combined immunodeficiency; IL2RG; chimerism; maternal cells; engraftment AB Severe combined immunodeficiency (SCID) represents a genetically heterogeneous group of primary immunodeficiency disorders. Irrespective of the genetic defect, patients with SCID may be engrafted with transplacentally derived maternal T-lymphocytes that in a subset of cases may be responsive to phytohemagglutinin. Here, we present, from a genetic perspective, an SCID patient who not only harbored a novel mutation in the gene encoding the common gamma chain (gamma c) of the IL-2 receptor (IL2RG), but also carried reactive maternal T lymphocytes that produced a karyotype that was initially perplexing. C1 Univ Pecs, Dept Med Genet & Child Dev, H-7623 Pecs, Hungary. DHHS, Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. Univ Pecs, Dept Pediat, Pecs, Hungary. Univ Pecs, Dept Immunol & Biotechnol, Pecs, Hungary. Univ Debrecen, Dept Infect Dis & Pediat Immunol, Debrecen, Hungary. MTA PTE Clin Genet Res Grp, Pecs, Hungary. RP Kellermayer, R (reprint author), Univ Pecs, Dept Med Genet & Child Dev, Jozsef A 7, H-7623 Pecs, Hungary. EM richard.kellermayer@aok.pte.hu FU Intramural NIH HHS NR 6 TC 8 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 EI 1435-232X J9 J HUM GENET JI J. Hum. Genet. PY 2006 VL 51 IS 5 BP 495 EP 497 DI 10.1007/s10038-006-0386-5 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 048KW UT WOS:000237947000017 PM 16601912 ER PT J AU Uehara, S Hayes, SM Li, LQ El-Khoury, D Canelles, M Fowlkes, BJ Love, PE AF Uehara, S Hayes, SM Li, LQ El-Khoury, D Canelles, M Fowlkes, BJ Love, PE TI Premature expression of chemokine receptor CCR9 impairs T cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROGENITOR LOCALIZATION; POSITIVE THYMOCYTES; POSTNATAL THYMUS; DIFFERENTIATION; EMIGRATION; MICE; MICROENVIRONMENT; PROLIFERATION; REQUIREMENT; MATURATION AB During thymocyte development, CCR9 is expressed on late CD4(-)CD8(-) (double-negative (DN)) and CD4(+)CD8(+) (double-positive) cells, but is subsequently down-regulated as cells transition to the mature CD4(+) or CD8(+) (single-positive (SP)) stage. This pattern of expression has led to speculation that CCR9 may regulate thymocyte trafficking and/or export. In this study, we generated transgenic mice in which CCR9 surface expression was maintained throughout T cell development. Significantly, forced expression of CCR9 on mature SP thymocytes did not inhibit their export from the thymus, indicating that CCR9 down-regulation is not essential for thymocyte emigration. CCR9 was also expressed prematurely on immature DN thymocytes in CCR9 transgenic mice. Early expression of CCR9 resulted in a partial block of development at the DIN stage and a marked reduction in the numbers of double-positive and SP thymocytes. Moreover, in CCR9-transgenic mice, CD25(high) DN cells were scattered throughout the cortex rather than confined to the subcapsular region of the thymus. Together, these results suggest that regulated expression of CCR9 is critical for normal development of immature thymocytes, but that down-regulation of CCR9 is not a prerequisite for thymocyte emigration. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NIAID, Lab Mol & Cellular Immunol, NIH, Bethesda, MD 20892 USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. EM lovep@mail.nih.gov NR 36 TC 18 Z9 21 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2006 VL 176 IS 1 BP 75 EP 84 PG 10 WC Immunology SC Immunology GA 997QU UT WOS:000234262600012 PM 16365398 ER PT J AU Hel, Z Tsai, WP Tryniszewska, E Nacsa, J Markham, PD Lewis, MG Pavlakis, GN Felber, BK Tartaglia, J Franchini, G AF Hel, Z Tsai, WP Tryniszewska, E Nacsa, J Markham, PD Lewis, MG Pavlakis, GN Felber, BK Tartaglia, J Franchini, G TI Improved vaccine protection from simian AIDS by the addition of nonstructural simian immunodeficiency virus genes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; PRIMARY HIV-1 INFECTION; IMMUNE-RESPONSES; ANTIRETROVIRAL TREATMENT; CELL RESPONSES; CYNOMOLGUS MONKEYS; NEF PROTEIN; TAT PROTEIN; EXPRESSION KINETICS; VIRAL REPLICATION AB An HIV-1 vaccine able to induce broad CD4(+) and CD8(+) T cell responses may provide long-term control of viral replication. In this study we directly assess the relative benefit of immunization with vaccines expressing three structural Ags (Gag, Pol, and Env), three early regulatory proteins (Rev, Tat, and Nef), or a complex vaccine expressing all six Ags. The simultaneous administration of all six Ags during vaccination resulted in Ag competition manifested by a relative reduction of CD8(+) T cell and lymphoproliferative responses to individual Ags. Despite the Ag competition, vaccination with all six Ags resulted in a delay in the onset and a decrease in the extent of acute viremia after mucosal challenge exposure to highly pathogenic SIVmac251. Reduced levels of acute viremia correlated with lower post-set point viremia and long-term control of infection. In immunized animals, virus-specific CD4(+) T cell and lymphoproliferative responses were preserved during acute viremia, and the maintenance of these responses predicted the long-term virological outcome. Taken together, these results suggest that the breadth of the immune response is probably more important than high frequency responses to a limited number of epitopes. These data provide the first clear evidence of the importance of nonstructural HIV Ags as components of an HIV-1 vaccine. C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. Univ Alabama, Dept Pathol, Ctr AIDS Res, Birmingham, AL 35249 USA. Med Univ Bialystok, Dept Pediat 3, Waszyngtona, Poland. Adv BioSci Labs, Kensington, MD 20895 USA. Bioqual, Rockville, MD 20850 USA. NCI, Human Retrovirus Sect, Frederick, MD 21702 USA. NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. Sanofi Pasteur, Toronto, ON, Canada. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov OI Hel, Zdenek/0000-0002-4923-4794 FU Intramural NIH HHS; NIAID NIH HHS [N01-AI-15429] NR 79 TC 45 Z9 46 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2006 VL 176 IS 1 BP 85 EP 96 PG 12 WC Immunology SC Immunology GA 997QU UT WOS:000234262600013 PM 16365399 ER PT J AU Sugita, S Ng, TF Lucas, PJ Gress, RE Streilein, JW AF Sugita, S Ng, TF Lucas, PJ Gress, RE Streilein, JW TI B7(+) iris pigment epithelium induce CD8(+) T regulatory cells; Both suppress CTLA-4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; OCULAR IMMUNE PRIVILEGE; ACTIVATION IN-VITRO; TGF-BETA; AQUEOUS-HUMOR; CILIARY BODY; MICE; PARTICIPATION; EYES; IMMUNOSUPPRESSION AB Ocular pigment epithelia contribute to immune privilege by suppressing T cell activation and converting T cells into regulatory T regulatory cells (Tregs) that inhibit bystander T cell activation. Iris pigment epithelium (IPE) does so through direct cell-cell contact with naive T cells, and this suppressive contact is via interactions between 137 expressed constitutively on IPE cells and CTLA-4 expressed on a subpopulation of CD8(+) T cells. We have now examined whether TGF beta is required in this process. We report that IPE produces both soluble and membrane-bound active TGF beta, but that only the latter is actually delivered to CD8+ T cells. In turn, these T cells become IPE Tregs by up-regulating their own expression of B7-1/B7-2 and soluble and membrane-bound TGF beta. IPE Tregs through their expression of B7 are able to engage CTLA-4(+) bystander T cells, and thus precisely, target delivery of membrane-bound TGF beta. We propose that this mechanism of suppression via TGF beta ensures that soluble active TGF beta is not released into the ocular microenvironment where it can have unregulated and deleterious effects, including elevation of intraocular pressure and development of glaucoma. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Tokyo, Japan. RP Streilein, JW (reprint author), Care of Dr Stein Streilein Joan, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM jstein@vision.eri.harvard.edu FU NEI NIH HHS [EY 05678] NR 35 TC 38 Z9 42 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2006 VL 176 IS 1 BP 118 EP 127 PG 10 WC Immunology SC Immunology GA 997QU UT WOS:000234262600016 PM 16365402 ER PT J AU Fujigaki, H Saito, K Lin, F Fujigaki, S Takahashi, K Martin, BM Chen, CY Masuda, J Kowalak, J Takikawa, O Seishima, M Markey, SP AF Fujigaki, H Saito, K Lin, F Fujigaki, S Takahashi, K Martin, BM Chen, CY Masuda, J Kowalak, J Takikawa, O Seishima, M Markey, SP TI Nitration and inactivation of IDO by peroxynitrite SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; INDOLEAMINE 2,3-DIOXYGENASE EXPRESSION; INTERFERON-INDUCED BACTERIOSTASIS; HUMAN UROEPITHELIAL CELLS; IFN-GAMMA; TRYPTOPHAN DEGRADATION; PROTEIN NITRATION; TYROSINE NITRATION; MICROGLIAL CELLS; PROLIFERATION AB IDO induction can deplete L-tryptophan in target cells, an effect partially responsible for the antimicrobial activities and antiallogeneic T cell responses of IFN-gamma in human macrophages, dendritic cells, and bone marrow cells. L-Tryptophan depletion and NO production are both known to have an antimicrobial effect in macrophages, and the interaction of these two mechanisms is unclear. In this study we found that IDO activity was inhibited by the peroxynitrite generator, 3-(4-morpholinyl)sydnonimine, in PMA-differentiated cytokine-induced THP-1 (acute monocytic leukemia) cells and IFN-gamma-stimulated PBMCs, whereas IDO protein expression was unaffected compared with that in untreated cells. Nitrotyrosine was detected in immunoprecipitated (IP)-IDO from PMA-differentiated cytokine-induced THP-1 cells treated with 3-(4-morpholinyl)sydnonimine, but not from untreated cells. Treatment of IP-IDO and recombinant IDO (rIDO) with peroxynitrite significantly decreased enzyme activity. Nitrotyrosine was detected in both peroxynitrite-treated IP-IDO and rIDO, but not in either untreated IP-IDO or rIDO. Peptide analysis by liquid chromatography/electrospray ionization and tandem mass spectrometry demonstrated that Tyr(15), Tyr(345), and Tyr(313) in rIDO were nitrated by peroxynitrite. The levels of Tyr nitration and the inhibitory effect of peroxynitrite on IDO activity were significantly reduced in the Tyr(15)-to-Phe mutant. These results indicate that IDO is nitrated and inactivated by peroxynitrite and that nitration of Tyr(15) in IDO protein is the most important factor in the inactivation of IDO. C1 Gifu Univ, Grad Sch Med, Dept Informat Clin Med, Gifu 5011194, Japan. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. Hokkaido Univ, Dept Pharmacol, Sapporo, Hokkaido, Japan. RP Saito, K (reprint author), Gifu Univ, Grad Sch Med, Dept Informat Clin Med, 1-1 Yanagido, Gifu 5011194, Japan. EM saito@cc.gifu-u.ac.jp FU Intramural NIH HHS NR 45 TC 45 Z9 46 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2006 VL 176 IS 1 BP 372 EP 379 PG 8 WC Immunology SC Immunology GA 997QU UT WOS:000234262600044 PM 16365430 ER PT J AU Morimoto, M Morimoto, M Zhao, AP Madden, KB Dawson, H Finkelman, FD Mentink-Kane, M Urban, JF Wynn, TA Shea-Donohue, T AF Morimoto, M Morimoto, M Zhao, AP Madden, KB Dawson, H Finkelman, FD Mentink-Kane, M Urban, JF Wynn, TA Shea-Donohue, T TI Functional importance of regional differences in localized gene expression of receptors for IL-13 in murine gut SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPITHELIAL-CELL FUNCTION; STAT6; COLITIS; MICE; RECEPTOR-ALPHA-2; INFLAMMATION; DISEASE AB IL-13 induces a STAT6-dependent hypercontractility of intestinal smooth muscle that is mediated by binding to the IL-13R alpha 1 component of the type 2 IL-4R that is linked to STAT6. IL-13 also binds to the IL-13R alpha 2 that is not linked to STAT6 and functions to limit the effects of IL-13 in vivo. In this study we assessed the contributions of regional and cellular differences in the distribution of the IL-13R components to the physiological regulation of smooth muscle function in wild-type mice and mice deficient in STAT6 or IL-13R alpha 2. The expression of IL-13 and IL-13R alpha 2 was higher in colon than in small intestine. Laser capture microdissection of specific cell types revealed that the expression of IL-13R alpha 2 was higher in the smooth muscle layer compared with levels in the epithelial cells of the mucosa. In contrast, there was a uniform distribution of 11-13 alpha 1 in smooth muscle, epithelia, and myenteric neurons. The significant hypercontractility of smooth muscle in mice deficient in IL-13R alpha 2, but not in STAT6, shows the physiological importance of IL-13 binding to IL-13R alpha 2. The pronounced differences in the expression of IL-13R alpha 2 suggest that the gut has developed sophisticated mechanisms for controlling the physiological and pathophysiological activities of IL-13. C1 Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA. USDA, Agr Res Serv, Nutrit Requirements & Funct Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. Yamaguchi Univ, Fac Agr, Lab, Yamaguchi 753, Japan. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. Univ Cincinnati, Dept Med, Cincinnati, OH 45267 USA. Univ Cincinnati, Dept Pediat, Cincinnati, OH 45267 USA. Cincinnati Vet Adm Med Ctr, Cincinnati, OH 45220 USA. NIAID, Div Parasitol, NIH, Bethesda, MD 20892 USA. RP Shea-Donohue, T (reprint author), Univ Maryland, Sch Med, Mucosal Biol Res Ctr, 20 Penn St,HSFII,Room S351, Baltimore, MD 21201 USA. EM tdonohue@mbrc.umaryland.edu RI Wynn, Thomas/C-2797-2011; Dawson, Harry/H-8242-2013; OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [R01 AI049316, R01AI/DK-49316]; NIDDK NIH HHS [R01 DK049316] NR 18 TC 43 Z9 43 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2006 VL 176 IS 1 BP 491 EP 495 PG 5 WC Immunology SC Immunology GA 997QU UT WOS:000234262600056 PM 16365442 ER PT J AU Rai, G Ray, S Shaw, RE DeGrange, PF Mage, RG Newman, BA AF Rai, G Ray, S Shaw, RE DeGrange, PF Mage, RG Newman, BA TI Models of systemic lupus erythematosus: Development of autoimmunity following peptide immunizations of noninbred pedigreed rabbits SO JOURNAL OF IMMUNOLOGY LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; DOUBLE-STRANDED DNA; ANTI-DNA; IMMUNE-RESPONSE; MURINE MODELS; ANIMAL-MODELS; 60-KDA RO; HUMAN SLE; AUTOANTIBODIES; ANTIBODIES AB Reported in this study are the initial results from studies to develop rabbit models of systemic lupus erythematosus (SLE) by immunizations using two distinct peptides on branched polylysine backbones (multiple Ag peptide)-peptides. Eleven rabbits received a peptide from the Sm B/B' spliceosomal complex previously shown to be immunogenic in rabbits, and 13 rabbits received a peptide from the rabbit N-methyl-D-aspartate receptor NR2b. All 24 animals in different generations of pedigreed, noninbred rabbits produced peptide-specific responses. Anti-nuclear autoantibody responses, including anti-dsDNA, were seen in 17 of 24 rabbits. To date, two rabbits have been observed to have seizure-like events and a third nystagmus. A model for eliciting development of SLE in genetically related yet heterogeneous rabbits may more closely resemble development of human SLE than do some models in inbred mice. Through selective breeding, it may also ultimately provide additional information about the genetics and etiology of SLE and serve as a model for assessing new treatment options. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Spring Valley Labs, Woodbine, MD 21797 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC1892, Bethesda, MD 20892 USA. EM rmage@niaid.nih.gov; bnewman@niaid.nih.gov FU Intramural NIH HHS NR 76 TC 10 Z9 12 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2006 VL 176 IS 1 BP 660 EP 667 PG 8 WC Immunology SC Immunology GA 997QU UT WOS:000234262600076 PM 16365462 ER PT J AU Dong, YJ Qian, JH Ibrahim, R Berzofsky, JA Khleif, SN AF Dong, YJ Qian, JH Ibrahim, R Berzofsky, JA Khleif, SN TI Identification of H-2D(b)-specific CD8(+) T-cell epitopes from mouse VEGFR2 that can inhibit angiogenesis and tumor growth SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE VEGFR2 (FLK-1, KDR); MHC Class 1 epitopes; angiogenesis; immunotherapy; cytotoxic T lymphocytes; cancer vaccine ID ENDOTHELIAL PROGENITOR CELLS; TYROSINE KINASE; ANTIANGIOGENIC THERAPY; RECEPTOR; EXPRESSION; ACTIVATION; FLT-1; MICE; SURVIVAL; KDR AB Vascular endothelial growth factor receptor 2 (VEGFR2/KDR) plays a crucial role in tumor-associated angiogenesis and vascularization. It has been established that monoclonal antibodies against VEGFR2 can inhibit angiogenesis. In this study, two naturally processed CD8 T-cell epitopes (VILTNPISM and FSNSTNDILI) were identified from murine KDR. Cytotoxic T lymphocytes targeting endothelial cells could be directly monitored by KDR2 and KDR3 Elispots or major histocompatibility complex class I tetramer staining. Immunization with these two peptides effectively reduced angiogenesis and inhibited tumor growth in mouse models. Thus, vaccination with KDR peptides alone or in combination with other anti-angiogenesis agents may afford a novel immunotherapy for inhibition of tumor growth. C1 NCI, NNMC, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Khleif, SN (reprint author), NCI, NNMC, Vaccine Branch, Ctr Canc Res,NIH, Bldg 8,Room 5101, Bethesda, MD 20892 USA. EM khleifs@navmed.nci.nih.gov NR 41 TC 15 Z9 15 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JAN-FEB PY 2006 VL 29 IS 1 BP 32 EP 40 DI 10.1097/01.cji.0000175494.13476.56 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 000UZ UT WOS:000234489200004 PM 16365598 ER PT J AU Shrestha, S Strathdee, SA Galai, N Oleksyk, T Fallin, MD Mehta, S Schaid, D Vlahov, D O'Brien, SJ Smith, MW AF Shrestha, S Strathdee, SA Galai, N Oleksyk, T Fallin, MD Mehta, S Schaid, D Vlahov, D O'Brien, SJ Smith, MW TI Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CA SP Amer Soc Human Genet ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG USERS; DISEASE PROGRESSION; LINKAGE DISEQUILIBRIUM; AIDS PROGRESSION; SEX WORKERS; HAPLOTYPE FREQUENCIES; IMMUNE-RESPONSES; TYPE-1 INFECTION; CCR5 EXPRESSION AB Background. Some individuals are readily infected with low human immunodeficiency virus type 1 (HIV-1) exposure, whereas others appear less susceptible, suggesting that host genetics plays a role in the viral entry pathway. The matched case-control study design with measured risk exposures provides an avenue for discovering genes involved in susceptibility to infection. Methods. We conducted a nested case-control study of African Americans (266 HIV-1 seroconverter cases and 532 seronegative controls from the AIDS Link to Intravenous Experience cohort), to examine the association between 50 single-nucleotide polymorphisms (SNPs) in 9 candidate genes (CCR5, CCR2, RANTES, MIP1A, MCP2, IL10, IFNG, MCSF, and IL2) and susceptibility to HIV-1 infection. To account for differential exposure propensities, risk behavior self-reported during semiannual visits was used to estimate a standardized cumulative risk exposure ( SCRE). Individual SNPs were evaluated using conditional logistic-regression models, and the inferred haplotypes were assessed in the haplotype trend regression analyses after adjusting for age and SCRE. Results. Four SNPs ( CCR2-V64I, CCR5-2459, MIP1A+954, and IL2+3896) and specific haplotypes in the IL2 and CCR2/CCR5 regions were significantly associated with HIV- 1 infection susceptibility in different genetic models. Conclusions. Our results suggest that genetic variants in associated host genes may play an important role in susceptibility to HIV- 1 infection. C1 NCI, SAIC, Lab Gen Divers, NIH, Ft Detrick, MD 21702 USA. NCI, SAIC, Basic Res Program, Ft Detrick, MD 21702 USA. Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Calif San Diego, Div Int Hlth & Cross Cultural Med, San Diego, CA 92103 USA. Mayo Clin Coll Med, Dept Hlth Sci Res, Rochester, MN USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. RP Smith, MW (reprint author), NCI, SAIC, Lab Gen Divers, NIH, Bldg 560,Rm 21-74, Ft Detrick, MD 21702 USA. EM smithm@ncifcrf.gov RI Strathdee, Steffanie/B-9042-2009; Smith, Michael/B-5341-2012; Taras, Oleksyk/J-8805-2013 OI Taras, Oleksyk/0000-0002-8148-3918 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NIDA NIH HHS [DA8009, DA09225, DA12568] NR 85 TC 39 Z9 42 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2006 VL 193 IS 1 BP 16 EP 26 DI 10.1086/498532 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 996OF UT WOS:000234182800005 PM 16323127 ER PT J AU Gutacker, MM Mathema, B Soini, H Shashkina, E Kreiswirth, BN Graviss, EA Musser, JM AF Gutacker, MM Mathema, B Soini, H Shashkina, E Kreiswirth, BN Graviss, EA Musser, JM TI Single-nucleotide polymorphism-based population genetic analysis of Mycobacterium tuberculosis strains from 4 geographic sites SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID COMPLETE GENOME SEQUENCE; MOLECULAR EPIDEMIOLOGY; GLOBAL DISSEMINATION; BEIJING FAMILY; IS6110; EVOLUTION; IDENTIFICATION; RESOLUTION; NUMBERS; CLUSTER AB We studied genetic relationships among 5069 Mycobacterium tuberculosis strains recovered from patients enrolled in 4 population-based studies in the United States and Europe, by analysis of 36 synonymous single-nucleotide polymorphisms (SNPs). All strains were assigned to 1 of 9 major genetic clusters based on sSNP profile. The same 9 genetic clusters were revealed by analysis of 227 nonsynonymous SNPs, 121 intergenic SNPs, and concatenated profiles of 578 SNPs available for a subset of 48 representative strains. IS6110 profiles, spoligotypes, and mycobacterial interspersed repetitive unit patterns were nonrandomly associated with SNP-based phylogenetic lineages, together indicating a strongly clonal population structure. Isolates of the 9 genetic clusters were not distributed with equal frequency in all localities, reflecting geographic subdivision. The SNP-based phylogenetic framework provides new insight into the worldwide evolution of M. tuberculosis and a gateway for investigating genotype-disease phenotype relationships in large samples of strains. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Biol Labs, NIH, Hamilton, MT USA. Publ Hlth Res Inst, TB Ctr, Newark, NJ USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. Baylor Coll Med, Dept Pathol, Ctr Human Infect Dis Res, Houston, TX 77030 USA. KTL Natl Publ Hlth Inst, Mycobacterial Reference Lab, Turku, Finland. RP Musser, JM (reprint author), Methodist Hosp, Res Inst, 6565 Fannin St, Houston, TX 77030 USA. EM jmmusser@tmh.tmc.edu FU Intramural NIH HHS NR 43 TC 141 Z9 150 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2006 VL 193 IS 1 BP 121 EP 128 DI 10.1086/498574 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 996OF UT WOS:000234182800018 PM 16323140 ER PT J AU Ghosh, K Wu, WH Antoine, AD Bottazzi, ME Valenzuela, JG Hotez, PJ Mendez, S AF Ghosh, K Wu, WH Antoine, AD Bottazzi, ME Valenzuela, JG Hotez, PJ Mendez, S TI The impact of concurrent and treated Ancylostoma ceylanicum hookworm infections on the immunogenicity of a recombinant hookworm vaccine in hamsters SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-RESPONSES; GOLDEN-HAMSTERS; SCHISTOSOMA-MANSONI; TETANUS VACCINATION; CYTOKINE PRODUCTION; MYCOBACTERIAL ANTIGENS; MESOCRICETUS-AURATUS; HUMAN ONCHOCERCIASIS; NEMATODE INFECTIONS; HELMINTH INFECTIONS AB Background. The effect of concurrent (active) and treated hookworm infections on the immunogenicity of vaccination with the recombinant fusion protein Ay- Ancylostoma-secreted protein 2 was analyzed in the Golden Syrian hamster. Methods. Hamsters were infected with the hookworm Ancylostoma ceylanicum and vaccinated with the recombinant protein, with Quil A used as adjuvant. As controls, hookworm-infected hamsters were treated with the anthelmintic drug pyrantel pamoate before vaccination. Naive hamsters (i. e., those with neither previous hookworm infections nor treatment) were also vaccinated. Results. The proliferation capacities of carboxyfluorescein diacetate succinimidyl ester-positive lymphocytes from the hookworm-infected vaccinated group were reduced by 50% relative to the capacities of lymphocytes from uninfected or treated vaccinated hamsters; capacities were comparable to the rates observed in lymphocytes from the hamsters vaccinated with the adjuvant alone. Immunoglobulin G1 antibody responses were also reduced in the actively infected, untreated hamsters, and interferon-gamma and interleukin-4 cytokine mRNAs were downregulated. Conversely, interleukin-10 and tumor necrosis factor-alpha mRNAs were up-regulated in those hamsters. Conclusions. These results suggest that hookworm infections have an immunomodulatory effect by impairing the immune response to an exogenous antigen during infection. The hookworm-associated immunodepression may have important implications for design of clinical trials of human vaccines and vaccination strategies. C1 George Washington Univ, Med Ctr, Dept Microbiol & Trop Med, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Sabin Vaccine Inst, Washington, DC 20037 USA. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Mendez, S (reprint author), George Washington Univ, Med Ctr, Dept Microbiol & Trop Med, Ross Hall,Rm 726,2300 Eye St NW, Washington, DC 20037 USA. EM mtmsxm@gwumc.edu OI Hotez, Peter/0000-0001-8770-1042 NR 49 TC 24 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2006 VL 193 IS 1 BP 155 EP 162 DI 10.1086/498528 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 996OF UT WOS:000234182800022 PM 16323144 ER PT J AU Lindsay, RL Arnold, LE Aman, MG Vitiello, B Posey, DJ McDougle, CJ Scahill, L Pachler, M McCracken, JT Tierney, E Bozzolo, D AF Lindsay, Ronald L. Arnold, L. Eugene Aman, Michael G. Vitiello, Benedetto Posey, David J. McDougle, Christopher J. Scahill, Lawrence Pachler, Maryellen McCracken, James T. Tierney, Elaine Bozzolo, Dawn TI Dietary status and impact of risperidone on nutritional balance in children with autism: A pilot study SO JOURNAL OF INTELLECTUAL & DEVELOPMENTAL DISABILITY LA English DT Article DE risperidone; nutrition; autism; children; adolescents AB Background Risperidone may be effective in improving tantrums, aggression, or self- injurious behaviour in children with autism, but often leads to weight gain. Method Using a quantitative Food Frequency Questionnaire (FFQ), we prospectively examined the nutritional intake of 20 children with autism participating in a randomised placebo-controlled trial of risperidone for disruptive behaviours. Results At baseline, the mean intakes for macronutrients, vitamins and minerals exceeded Dietary Reference Intakes (DRIs). However there was substantial inter-participant variability, with individual deficiencies (80% of DRI) in the intake of calcium (9 of 20 participants), pantothenic acid (6 of 20), vitamin D (5 of 20) and vitamin K (8 of 20). For the participants for whom FFQs were available, there was an increase in weight and an increase in vitamin K intake after 2 months of risperidone treatment (n=59) compared to placebo (n=58). An additional 4 months of risperidone treatment (n=58) did not result in significant changes in reported nutritional balance. Conclusion These pilot data suggest that treatment with risperidone did not significantly affect the nutritional balance of this small group of children. C1 St Josephs Hosp, Childrens Hlth Ctr, Arizona Child Study Ctr, Phoenix, AZ 85013 USA. Ohio State Univ, Columbus, OH 43210 USA. NIMH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Yale Univ, New Haven, CT 06520 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Kennedy Krieger Inst, Baltimore, MD USA. RP Lindsay, RL (reprint author), St Josephs Hosp, Childrens Hlth Ctr, Arizona Child Study Ctr, 3600 N 3rd Ave, Phoenix, AZ 85013 USA. EM rlindsay@chw.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU NCRR NIH HHS [M01RR00034, M01RR00052, M01RR00750, M01RR06022]; NIMH NIH HHS [MH01805, N01MH70001, N01MH70009, N01MH70010, N01MH80011] NR 10 TC 20 Z9 20 U1 1 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1366-8250 J9 J INTELLECT DEV DIS JI J. Intellect. Dev. Dis. PY 2006 VL 31 IS 4 BP 204 EP 209 DI 10.1080/13668250601006924 PG 6 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 145KX UT WOS:000244865000003 PM 17178532 ER PT J AU Nakanishi, G Kim, YS Nakajima, T Jetten, AM AF Nakanishi, Gen Kim, Yong-Sik Nakajima, Takeshi Jetten, Anton M. TI Regulatory role for Kruppel-like zinc-finger protein Gli-similar 1 (Glis1) in PMA-treated and psoriatic epidermis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID HAIR FOLLICLE MORPHOGENESIS; HEDGEHOG SIGNALING PATHWAY; BASAL-CELL CARCINOMAS; SONIC-HEDGEHOG; INTERFERON-GAMMA; STEM-CELLS; SKIN; EXPRESSION; DIFFERENTIATION; CANCER AB In this study, we analyze the expression and potential function of the Kruppel-like zinc-finger protein Gli-similar protein 1 (Glis1) in normal and inflammatory skin and in the differentiation of epidermal keratinocytes. Glis1 mRNA is not expressed in normal human epidermis, but is significantly induced in psoriatic epidermis and in mouse skin upon treatment with the tumor promoter phorbol-12-myristate-13-acetate (PMA). The expression of Glis1 is restricted to the suprabasal layers. These observations suggest that Glis1 expression is associated with hyperplastic, inflammatory epidermis. Consistent with these findings, Glis1 mRNA is not expressed in undifferentiated or differentiated normal human epidermal keratinocytes (NHEK) in culture, but is dramatically induced after the addition of PMA or interferon g. A similar induction of Glis1 mRNA by PMA treatment was observed in the immortalized epidermal keratinocyte cell line NHEK-HPV, whereas PMA did not induce Glis1 in HaCaT cells or in several squamous cell carcinoma cell lines. To obtain insight into its function, Glis1 and a C-terminal deletion mutant Glis1 Delta C were expressed in NHEK-HPV cells and changes in epidermal differentiation and gene expression examined. Microarray analysis revealed that Glis1DC promoted PMA-induced epidermal differentiation, as indicated by increased expression of many differentiation-specific genes. This, in association with its induction in psoriasis, suggests that transcriptional factor Glis1 is involved in the regulation of aberrant differentiation observed in psoriatic epidermis. C1 NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES100485-04] NR 57 TC 12 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2006 VL 126 IS 1 BP 49 EP 60 DI 10.1038/sj.jid.5700018 PG 12 WC Dermatology SC Dermatology GA 062KU UT WOS:000238943900012 PM 16417217 ER PT J AU Leverkus, M Jochim, RC Schad, S Brocker, EB Andersen, JF Valenzuela, JG Trautmann, A AF Leverkus, Martin Jochim, Ryan C. Schaed, Susanne Broecker, Eva-Bettina Andersen, John F. Valenzuela, Jesus G. Trautmann, Axel TI Bullous allergic hypersensitivity to bed bug bites mediated by IgE against salivary nitrophorin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CIMEX-LECTULARIUS; COMMON BEDBUG; APOPTOSIS; ERUPTION; DISEASE; PROTEIN; KERATINOCYTES; PURIFICATION; ANAPHYLAXIS; ACTIVATION AB In Central Europe, bites from the common bed bug ( Cimex lectularius) are nowadays rather uncommon. Nevertheless, infestations are sometimes observed in old framehouses and by immigration due to international travel and migration. The clinical picture of bug bites substantially varies between individuals, depending upon previous exposure and the degree of an immune response. The host immune response and potential protein antigens present in the saliva of C. lectularius or specific antibodies have not been characterized thus far. We describe a patient with bullous bite reactions after sequential contact with C. lectularius over a period of 1 year. In skin tests, we observed immediate reactions to the salivary gland solution of C. lectularius, which were followed by a pronounced partially blistering late-phase response. Immunoblot analysis of the patient's serum with salivary gland extracts and recombinant C. lectularius saliva proteins revealed specific IgE antibodies against the 32 kDa C. lectularius nitrophorin, but not to 37 kDa C. lectularius apyrase. Our data demonstrate that bullous cimicosis may be the late-phase response of an allergic IgE-mediated hypersensitivity to C. lectularius nitrophorin. C1 Otto Von Guericke Univ, Dept Dermatol & Venerol, Lab Expt Dermatol, D-39120 Magdeburg, Germany. Univ Wurzburg, Dept Dermatol, D-8700 Wurzburg, Germany. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Leverkus, M (reprint author), Otto Von Guericke Univ, Dept Dermatol & Venerol, Lab Expt Dermatol, Leipziger Str 44, D-39120 Magdeburg, Germany. EM leverkus@medizin.uni-magdeburg.de RI Jochim, Ryan/C-6756-2013 NR 30 TC 47 Z9 50 U1 3 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2006 VL 126 IS 1 BP 91 EP 96 DI 10.1038/sj.jid.5700012 PG 6 WC Dermatology SC Dermatology GA 062KU UT WOS:000238943900018 PM 16417223 ER PT J AU Kotchen, TA Lindquist, T Sostek, AM Hoffmann, R Malik, K Stanfield, B AF Kotchen, TA Lindquist, T Sostek, AM Hoffmann, R Malik, K Stanfield, B TI Outcomes of national institutes of health peer review of clinical grant applications SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE clinical research; grant applications; peer review; research funding ID NIH; INVESTIGATOR; CRISIS AB Purpose: We previously reported that National Institutes of Health (NIH) peer review outcomes in 2002 were slightly but significantly less favorable for grant applications for clinical research than for laboratory research. The present analysis was undertaken to determine if factors related to the review process might contribute to this difference. Methods: The impact of each of the following factors on median priority scores and funding rates for clinical and nonclinical R01 grant applications was evaluated: (1) the percentage of clinical applications assigned for review to a study section, (2) the requested direct costs, and (3) the clinical research experience of the reviewers. Results: Confirming our previous observation, in both 1994 and 2004, median priority scores and funding rates for R01 applications were less favorable for clinical research. In 1994, clinical applications did not fare as well in study sections reviewing relatively low percentages of clinical applications. This was not the case in 2004. Although requested direct costs were greater for clinical than for nonclinical R01 applications, median priority scores within each category were actually more favorable for applications requesting greater funding. Assignment of priority scores was not different for reviewers with or without experience conducting clinical research. Conclusion: These data do not support the hypothesis that the less favorable review outcomes for clinical applications are related to these review factors. We suggest that peer review outcomes for clinical research will benefit from the recent refinement of NIH review criteria, emphasizing the unique contributions of clinical investigation, and from increased training opportunities for clinical investigators. C1 Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Biostat, Milwaukee, WI 53226 USA. NIH, Ctr Sci Review, Bethesda, MD USA. RP Kotchen, TA (reprint author), Med Coll Wisconsin, Dept Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM tkotchen@mcw.edu NR 14 TC 13 Z9 13 U1 0 U2 3 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2006 VL 54 IS 1 SU S BP 13 EP 19 DI 10.2310/6650.2005.05026 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 011XH UT WOS:000235301500008 PM 16409886 ER PT J AU Halloran, DR McClure, B Chomba, E Wright, LL Carlo, WA AF Halloran, DR McClure, B Chomba, E Wright, LL Carlo, WA TI Birth asphyxia survivors in a developing country. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC C1 St Louis Univ, St Louis, MO 63103 USA. Res Triangle Inst, Durham, NC USA. Univ Zambia, Lusaka, Zambia. NICHHD, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2006 VL 54 IS 1 SU S MA 296 BP S309 EP S309 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 011XH UT WOS:000235301501295 ER PT J AU Johnsen, JA Lupu, VD Floeter, MK AF Johnsen, JA Lupu, VD Floeter, MK TI Sub-fatiguing exercise stimulates intracortical facilitation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC C1 Western Univ Hlth Sci, Coll Osteopath Med, Pomona, CA USA. NINDS, EMG Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2006 VL 54 IS 1 SU S MA 356 BP S141 EP S141 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 011XH UT WOS:000235301500369 ER PT J AU Tang, C Wu, A Leong, F Fears, T Azzi, R O'Shannessy, D Lin, A AF Tang, C Wu, A Leong, F Fears, T Azzi, R O'Shannessy, D Lin, A TI Detection, analysis and significance of guanylyl cyclase C in the lymph nodes from patients with colorectal cancer. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Calif Los Angeles, Los Angeles, CA USA. Targeted Diagnost & Therapeut Inc, W Chester, PA USA. NCI, NIH, Bethesda, MD 20892 USA. Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2006 VL 54 IS 1 SU S MA 272 BP S126 EP S126 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 011XH UT WOS:000235301500285 ER PT J AU Chin, FT Morse, CL Shetty, HU Pike, VW AF Chin, FT Morse, CL Shetty, HU Pike, VW TI Automated radiosynthesis of [F-18]SPA-RQ for imaging human brain NK1 receptors with PET SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE [F-18]SPA-RQ; Fluorine-18; automation; radioligand; neurokinin type-1; receptor ID SUBSTANCE-P RECEPTORS; ALZHEIMERS-DISEASE; QUANTITATION; PARKINSONS; IODIDE; CORTEX AB [F-18]SPA-RQ is an effective radioligand for imaging brain neurokinin type-1 (NK1) receptors in clinical research and drug discovery with positron emission tomography. For the automated regular production of [18F]SPA-RQ for clinical use in the USA under an IND we chose to use a modified commercial synthesis module (TRACERlab FXF-N; GE Medical Systems) with an auxiliary custom-made robotic cooling-heating reactor, after evaluating several alternative radiosynthesis conditions. The automated radiosynthesis and its quality control are described here. [F-18]SPA-RQ was regularly obtained within 150 min from the start of radiosynthesis in high radiochemical purity (> 99%) and chemical purity and with an overall decay-corrected radiochemical yield of 15 +/- 2% (mean +/- S.D.; n = 10) from cyclotron-produced [F-18]fluoride ion. The specific radioactivity of [F-18]SPA-RQ at the end of synthesis ranged from 644 to 2140 mCi/mu mol (23.8-79.2 GBq/mu mol). Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Stanford Univ, Sch Med, Lucas MRS Ctr, Mol Imaging Program, Stanford, CA 94305 USA. NIMH, Mol Imaging Branch, PET Radiopharmaceut Sci Sect, NIH, Bethesda, MD 20892 USA. RP Chin, FT (reprint author), Stanford Univ, Sch Med, Lucas MRS Ctr, Mol Imaging Program, MC 5484, Stanford, CA 94305 USA. EM chinf@stanford.edu NR 21 TC 20 Z9 20 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JAN PY 2006 VL 49 IS 1 BP 17 EP 31 DI 10.1002/jlcr.1016 PG 15 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 011SG UT WOS:000235287800003 ER PT J AU Nakayama, T Mutsuga, N Yao, L Tosato, G AF Nakayama, T Mutsuga, N Yao, L Tosato, G TI Prostaglandin E-2 promotes degranulation-independent release of MCP-1 from mast cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE inflammation; chemokine; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; BONE-MARROW ANGIOGENESIS; TUMOR NECROSIS FACTOR; EPSILON RECEPTOR-I; COLON-CANCER CELLS; PROSTANOID RECEPTORS; CHEMOKINE RECEPTORS; CHRONIC INFLAMMATION; SIGNAL-TRANSDUCTION AB Mast cells (MCs) are common components of inflammatory infiltrates and a source of proangiogenic factors. Inflammation is often accompanied by vascular changes. However, little is known about modulation of MC-derived proangiogenic factors during inflammation. In this study, we evaluated the effects of the proinflammatory mediator prostaglandin E-2 (PGE(2)) on MC expression and release of proangiogenic factors. We report that PGE(2) dose-dependently induces primary MCs to release the proangiogenic chemokine monocyte chemoattractant protein-1 (MCP-1). This release of MCP-1 is complete by 2 h after PGE(2) exposure, reaches levels of MCP-1 at least 15-fold higher than background, and is not accompanied by degranulation or increased MCP-1 gene expression. By immunoelectron microscopy, MCP-1 is detected within MCs at a cytoplasmic location distinct from the secretory granules. Dexamethasone and cyclosporine A inhibit PGE(2)-induced MCP-1 secretion by similar to 60%. Agonists of PGE(2) receptor subtypes revealed that the EP1 and EP3 receptors can independently mediate MCP-1 release from MCs. These observations identify PGE(2)-induced MCP-1 release from MCs as a pathway underlying inflammation-associated angiogenesis and extend current understanding of the activities of PGE(2). C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD USA. RP Nakayama, T (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bldg 10,Room 12C205,10 Ctr Dr 1907, Bethesda, MD 20892 USA. EM Nakayamt@mail.nih.gov FU Intramural NIH HHS NR 98 TC 37 Z9 39 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2006 VL 79 IS 1 BP 95 EP 104 DI 10.1189/jlb.0405226 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 000HL UT WOS:000234451800012 PM 16275896 ER PT J AU Zhang, YH Wahl, LM AF Zhang, YH Wahl, LM TI Synergistic enhancement of cytokine-induced human monocyte matrix metalloproteinase-1 by C-reactive protein and oxidized LDL through differential regulation of monocyte chemotactic protein-1 and prostaglandin E-2 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE tumor necrosis factor alpha; granulocyte macrophagecolony stimulating factor; inflammation; atherosclerosis ID LOW-DENSITY-LIPOPROTEIN; CHEMOATTRACTANT PROTEIN-1-MEDIATED CHEMOTAXIS; PLATELET-ACTIVATING-FACTOR; MATRIX METALLOPROTEINASES; SCAVENGER RECEPTOR; CARDIOVASCULAR-DISEASE; TUMORICIDAL ACTIVITY; INCREASED EXPRESSION; GENE-EXPRESSION; STATIN THERAPY AB C-reactive protein (CRP) and oxidized LDL (ox-LDL) are associated with inflammatory lesions, such as coronary artery disease, in which monocytes and matrix metalloproteinases (MMPs) may play a major role in the rupture of atherosclerotic plaques. Monocytes are recruited to inflammation sites by monocyte chemoattractant protein-1 (MCP-1), which may also participate in the activation of monocytes. The objective of this study was to compare the individual and combined effect of CRP and ox-LDL on human monocyte MMP-1 and the role of MCP-1 in this effect. Although CRP or ox-LDL failed to induce MMP-1 in control monocytes, these molecules enhanced MMP-1 production induced by tumor necrosis factor alpha (TNF-alpha) and granulocyte macrophage-colony stimulating factor (GM-CSF) with a synergistic increase in MMP-1 occurring in the presence of both mediators. Enhancement of MMP-1 by CRP and ox-LDL was attributable to a differential increase in MCP-1 and prostaglandin E-2 (PGE(2)). CRP, at physiological concentrations, induced high levels of MCP-1 and relatively low levels of PGE(2), whereas ox-LDL caused a significant enhancement of PGE2 with little affect on MCP-1. Accordingly, CRP- and ox-LDL-induced MMP-1 production by monocytes was inhibited by anti-MCP-1 antibodies and indomethacin, respectively. Moreover, addition of exogenous MCP-1 or PGE2 enhanced MMP-1 production by TNF-alpha- and GM-CSF-stimulated monocytes. These results show that the combination of CRP and ox-LDL can cause a synergistic enhancement of the role of monocytes in inflammation, first, by increasing MCP-1, which attracts more monocytes and directly enhances MMP-1 production by activated monocytes, and second, by elevating PGE2 production, which also leads to higher levels of MMP-1. C1 NIDCR, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. RP Wahl, LM (reprint author), NIDCR, Immunopathol Sect, NIH, 30 Convent Dr,Bldg 30,Room 3A-300, Bethesda, MD 20892 USA. EM lwahl@dir.nidcr.nih.gov FU Intramural NIH HHS NR 54 TC 9 Z9 13 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2006 VL 79 IS 1 BP 105 EP 113 DI 10.1189/jlb.0505241 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 000HL UT WOS:000234451800013 PM 16244112 ER PT J AU North, KE Goring, HHH Cole, SA Diego, VP Almasy, L Laston, S Cantu, T Howard, BV Lee, ET Best, LG Fabsitz, RR MacCluer, JW AF North, KE Goring, HHH Cole, SA Diego, VP Almasy, L Laston, S Cantu, T Howard, BV Lee, ET Best, LG Fabsitz, RR MacCluer, JW TI Linkage analysis of LDL cholesterol in American Indian populations: the Strong Heart Family Study SO JOURNAL OF LIPID RESEARCH LA English DT Article DE genetics; lipids; low density lipoprotein ID APOLIPOPROTEIN-E POLYMORPHISM; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE RISK; QUANTITATIVE TRAIT LOCUS; E GENE; ENVIRONMENTAL CONTRIBUTIONS; MYOCARDIAL-INFARCTION; TRIGLYCERIDE LEVELS; MEXICAN-AMERICANS; REVEALS EVIDENCE AB Previous studies have demonstrated that low density lipoprotein cholesterol (LDL-C) concentration is influenced by both genes and environment. Although rare genetic variants associated with Mendelian causes of increased LDL-C are known, only one common genetic variant has been identified, the apolipoprotein E gene (APOE). In an attempt to localize quantitative trait loci (QTLs) influencing LDL-C, we conducted a genome-wide linkage scan of LDL-C in participants of the Strong Heart Family Study (SHFS). Nine hundred eighty men and women, age 18 years or older, in 32 extended families at three centers (in Arizona, Oklahoma, and North and South Dakota) were phenotyped for LDL-C concentration and other risk factors. Using a variance component approach and the program SOLAR, and after accounting for the effects of covariates, we detected a QTL influencing LDL-C on chromosome 19, nearest marker D19S888 at 19q13.41 [logarithm of odds (LOD) 54.3] in the sample from the Dakotas. This region on chromosome 19 includes many possible candidate genes, including the APOE/C1/C4/C2 gene cluster. In follow-up association analyses, no significant evidence for an association was detected with the APOE*epsilon 2 and APOE*epsilon 4 alleles (P = 0.76 and P = 0.53, respectively). Suggestive evidence of linkage to LDL-C was detected on chromosomes 3q, 4q, 7p, 9q, 10p, 14q, and 17q. These linkage signals overlap positive findings for lipid-related traits and harbor plausible candidate genes for LDL-C. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. MedStar Res Inst, Washington, DC USA. Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. RP North, KE (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. EM kari_north@unc.edu OI Diego, Vincent/0000-0002-0007-2085 FU NHLBI NIH HHS [U01 HL-65520, U01 HL-41642, U01 HL-65521, U01 HL065520, U01 HL-41652, U01 HL-41654]; NIMH NIH HHS [MH-059490] NR 68 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2006 VL 47 IS 1 BP 59 EP 66 DI 10.1194/jlr.M500395-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 998AW UT WOS:000234291300006 PM 16264198 ER PT J AU DeMar, JC Ma, KZ Bell, JM Igarashi, M Greenstein, D Rapoport, SI AF DeMar, JC Ma, KZ Bell, JM Igarashi, M Greenstein, D Rapoport, SI TI One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats SO JOURNAL OF LIPID RESEARCH LA English DT Article DE docosahexaenoic; locomotor; rat; activity; behavior; diet ID ALPHA-LINOLENIC ACID; PLACEBO-CONTROLLED TRIAL; DOCOSAHEXAENOIC ACID; BRAIN PHOSPHOLIPIDS; DOUBLE-BLIND; ARACHIDONIC-ACID; NUTRITIONAL DEPRIVATION; BIPOLAR DISORDER; ANTIDEPRESSANT TREATMENTS; POSTPARTUM DEPRESSION AB Male rat pups at weaning (21 days of age) were subjected to a diet deficient or adequate in n-3 polyunsaturated fatty acids (n-3 PUFAs) for 15 weeks. Performance on tests of locomotor activity, depression, and aggression was measured in that order during the ensuing 3 weeks, after which brain lipid composition was determined. In the n-3 PUFA-deprived rats, compared with n-3 PUFA-adequate rats, docosahexaenoic acid (22:6n-3) in brain phospholipid was reduced by 36% and docosapentaenoic acid (22:5n-6) was elevated by 90%, whereas brain phospholipid concentrations were unchanged. N-3 PUFA-deprived rats had a significantly increased (P = 0.03) score on the Porsolt forced-swim test for depression, and increased blocking time (P = 0.03) and blocking number (P = 0.04) scores ( uncorrected for multiple comparisons) on the isolation-induced resident intruder test for aggression. Large effect sizes (d > 0.8) were found on the depression score and on the blocking time score of the aggression test. Scores on the open-field test for locomotor activity did not differ significantly between groups, and had only small to medium effect sizes. This single-generational n-3 PUFA-deprived rat model, which demonstrated significant changes in brain lipid composition and in test scores for depression and aggression, may be useful for elucidating the contribution of disturbed brain PUFA metabolism to human depression, aggression, and bipolar disorder. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM sir@helix.nih.gov RI Wilkinson, Stuart/C-2802-2013 NR 87 TC 134 Z9 137 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2006 VL 47 IS 1 BP 172 EP 180 DI 10.1194/jlr.M500362-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 998AW UT WOS:000234291300017 PM 16210728 ER PT J AU Lee, H Zhang, YQ Lee, FY Nelson, SF Gonzalez, FJ Edwards, PA AF Lee, H Zhang, YQ Lee, FY Nelson, SF Gonzalez, FJ Edwards, PA TI FXR regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine SO JOURNAL OF LIPID RESEARCH LA English DT Article DE farnesoid X receptor; chenodeoxycholic acid; 3-(2,6-dichlorophenyl)-4-(3 ' carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole ID FARNESOID-X-RECEPTOR; ACID-BINDING-PROTEIN; SALT EXPORT PUMP; BILE-ACID; NUCLEAR RECEPTOR; ACTIVATED RECEPTOR; LIPID HOMEOSTASIS; ORPHAN RECEPTORS; TARGET GENES; OST-BETA AB Expression of the farnesoid X receptor (FXR; NR1H4) is limited to the liver, intestine, kidney, and adrenal gland. However, the role of FXR in the latter two organs is unknown. In the current study, we performed microarray analysis using RNA from H295R cells infected with constitutively active FXR. Several putative FXR target genes were identified, including the organic solute transporters alpha and beta (OST alpha and OST beta). Electromobility shift assays and promoter-reporter studies identified functional farnesoid X receptor response elements ( FXREs) in the promoters of both human genes. These FXREs are conserved in both mouse genes. Treatment of wild-type mice with 3-(2, 6-dichlorophenyl)-4-(3'-carboxy-2-chloro-stilben-4-yl)oxymethyl- 5-isopropyl-isoxazole (GW4064), a synthetic FXR agonist, induced OST alpha and OST beta mRNAs in the intestine and kidney. Both mRNAs were also induced when wild-type, but not FXR-deficient (FXR-/-), adrenals were cultured in the presence of GW4064. OST alpha and OST beta mRNA levels were also induced in the adrenals and kidneys of wild-type, but not FXR-/-, mice after the increase of plasma bile acids in response to the hepatotoxin alpha-naphthylisothiocyanate. Finally, overexpression of human OST alpha and OST beta facilitated the uptake of conjugated chenodeoxycholate and the activation of FXR target genes. These results demonstrate that OST alpha and OST beta are novel FXR target genes that are expressed in the adrenal gland, kidney, and intestine. C1 Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. RP Edwards, PA (reprint author), Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. EM pedwards@mednet.ucla.edu RI Nelson, Stanley/D-4771-2009 FU NHLBI NIH HHS [HL-30568, HL-68445, R01 HL-072367]; NIGMS NIH HHS [GM-07185] NR 44 TC 83 Z9 85 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2006 VL 47 IS 1 BP 201 EP 214 DI 10.1194/jlr.M500417-JLR200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 998AW UT WOS:000234291300020 PM 16251721 ER PT J AU Inoue, Y Yu, AM Yim, SH Ma, XC Krausz, KW Inoue, J Xiang, CC Brownstein, MJ Eggertsen, G Bjorkhem, I Gonzalez, FJ AF Inoue, Y Yu, AM Yim, SH Ma, XC Krausz, KW Inoue, J Xiang, CC Brownstein, MJ Eggertsen, G Bjorkhem, I Gonzalez, FJ TI Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4 alpha SO JOURNAL OF LIPID RESEARCH LA English DT Article DE conditional knockout mice; sterol 12 alpha-hydroxylase; oxysterol 7 alpha-hydroxylase; sterol carrier protein x; cholic acid ID 12-ALPHA-HYDROXYLASE GENE CYP8B1; NEGATIVE FEEDBACK-REGULATION; STEROL 27-HYDROXYLASE GENE; OXYSTEROL 7-ALPHA-HYDROXYLASE GENE; CARRIER PROTEIN-2 GENE; I ALPHA-GENE; CHOLESTEROL 7-ALPHA-HYDROXYLASE; MICE LACKING; TRANSCRIPTIONAL REGULATION; LIPID HOMEOSTASIS AB Hepatocyte nuclear factor 4 alpha (HNF4 alpha) regulates many genes that are preferentially expressed in liver. Mice lacking hepatic expression of HNF4 alpha (HNF4 alpha(Delta L)) exhibited markedly increased levels of serum bile acids (BAs) compared with HNF4 alpha-floxed (HNF4 alpha(F/F)) mice. The expression of genes involved in the hydroxylation and side chain beta-oxidation of cholesterol, including oxysterol 7 alpha-hydroxylase, sterol 12 alpha-hydroxylase (CYP8B1), and sterol carrier protein x, was markedly decreased in HNF4 alpha(Delta L) mice. Cholesterol 7 alpha-hydroxylase mRNA and protein were diminished only during the dark cycle in HNF4(Delta L) mice, whereas expression in the light cycle was not different between HNF4 alpha(Delta L) and HNF4 alpha(F/F) mice. Because CYP8B1 expression was reduced in HNF4 alpha(Delta L) mice, it was studied in more detail. In agreement with the mRNA levels, CYP8B1 enzyme activity was absent in HNF4 alpha(Delta L) mice. An HNF4 alpha binding site was found in the mouse Cyp8b1 promoter that was able to direct HNF4 alpha-dependent transcription. Surprisingly, cholic acid-derived BAs, produced as a result of CYP8B1 activity, were still observed in the serum and gallbladder of these mice. These studies reveal that HNF4 alpha plays a central role in BA homeostasis by regulation of genes involved in BA biosynthesis, including hydroxylation and side chain beta-oxidation of cholesterol in vivo. C1 NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. Huddinge Univ Hosp, Karolinska Inst, Dept Med Lab Sci & Technol, Stockholm, Sweden. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov OI Bjorkhem, Ingemar/0000-0001-6087-9190 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005561-18] NR 55 TC 71 Z9 73 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2006 VL 47 IS 1 BP 215 EP 227 DI 10.1194/jlr.M500430-JLR200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 998AW UT WOS:000234291300021 PM 16264197 ER PT J AU Shinomiya, K Ito, Y AF Shinomiya, K Ito, Y TI Countercurrent chromatographic separation of biotic compounds with extremely hydrophilic organic-aqueous two-phase solvent systems and organic-aqueous three-phase solvent systems SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE countercurrent chromatography; separation; organic-aqueous two-phase solvent system; organic-aqueous three-phase solvent system; protein; sugar; water-soluble carboxylic acid; vitamin; water-soluble vitamin; fat-soluble vitamin ID COIL PLANET CENTRIFUGE; ASSEMBLIES; VITAMINS; SUGARS; ACID AB Highly polar organic-aqueous two-phase and three-phase solvent systems were applied to the countercurrent chromatographic (CCC) separation of biotic compounds. The ethanol/2 M ammonium sulfate (3:5) system was used for protein separation between human serum albumin and lysozyme, and also for separations of sugars including D-(+)-glucose and L-(-)-fucose, D-(+)-xylose and alpha-L-rhamnose, and alpha-D-galacturonic acid, mannuronic acid lactone and D-(+)-glucoronolactone. When using the acetonitrile/1 M sodium chloride (5:4) system for applying water-soluble carboxylic acids, 2-naphthoic acid, p -methyl hippuric acid and p -amino hippuric acid were well separated with upper phase mobile, and maleic acid and fumaric acid were resolved with lower phase mobile. An organic-aqueous three-phase solvent system composed of n-hexane/methyl t -butyl ether/acetonitrile/water (5:5:7.5:5) was also applied to the simultaneous CCC separation of fat-soluble vitamins and water-soluble vitamins. Using the middle phase as the stationary phase, the separation of thiamine hydrochloride and nicotinamide was achieved first with the lower mobile phase and then vitamin K1 and K3 were eluted after the mobile phase was switched to the upper phase reversing the direction of elution. The overall results demonstrated that both extremely hydrophilic organic-aqueous two-phase solvent systems and organic-aqueous three-phase solvent systems are useful for the CCC separations of polar compounds. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. EM kshino@pha.nihon-u.ac.jp NR 17 TC 23 Z9 24 U1 2 U2 24 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2006 VL 29 IS 5 BP 733 EP 750 DI 10.1080/10826070500509298 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 015LL UT WOS:000235552800009 ER PT J AU Yun, W Ito, Y AF Yun, W Ito, Y TI Isolation of imperatorin, oxypeucedanin, and isoimperatorin from Angelica dahurica (Fisch ex Hoffm) Benth. et Hook by stepwise flow rate high-speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE imperatorin; oxypeucedanin; isoimperatorin; Angelica dahurica; high-speed countercurrent chromatography; stepwise flow ID SEPARATION AB Stepwise flow rate preparative high-speed countercurrent chromatography (HSCCC) was successfully used for isolation and purification of imperatorin, oxypeucedanin, and isoimperatorin from a crude root extract of Angelica dahurica (Fisch. ex Hoffm) Benth. et Hook. The separation was performed with a two-phase solvent system composed of n-hexane-ethylacetate-methanol-water at volume ratio of 5: 5: 4: 6, v/v/v/v, which had been selected by analytical HSCCC. About a 600 mg amount of the crude extract was separated in a one step operation, yielding 35.6 mg of imperatorin, 16.4 mg of oxypeucedanin, and 22.7 mg of isoimperatorin, all at a high purity of over 98%. C1 Beijing Univ Chem Technol, Dept Appl Chem, Fac Sci, Beijing 100029, Peoples R China. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Yun, W (reprint author), Beijing Univ Chem Technol, Dept Appl Chem, Fac Sci, 15 Beisanhuan Donglu,Chaoyang Dist, Beijing 100029, Peoples R China. EM weiyun@mail.buct.edu.cn NR 13 TC 1 Z9 2 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2006 VL 29 IS 11 BP 1609 EP 1618 DI 10.1080/10826070600678340 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 042SQ UT WOS:000237550200007 ER PT J AU Waybright, TJ Van, QN Muschik, GM Conrads, TP Veenstra, TD Issaq, HJ AF Waybright, Timothy J. Van, Que N. Muschik, Gary M. Conrads, Thomas P. Veenstra, Timothy D. Issaq, Haleem J. TI LC-MS in metabonomics: Optimization of experimental conditions for the analysis of metabolites in human urine SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE metabonomics; metabolomics; urine; mass spectrometry; HPLC-MS ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MULTIVARIATE STATISTICAL-ANALYSIS; CLINICALLY IMPORTANT METABOLITES; TANDEM MASS-SPECTROMETRY; RAT URINE; METABOLOMICS; NMR; SAMPLES; IDENTIFICATION; DIAGNOSIS AB The analysis of metabolic pathways for dysfunction has been used for many years in the scientific and medical community to determine overall health. Metabonomics (metabolomics), the global profiling of metabolites, has experienced a rekindling of interest due, in part, to advances in analytical instrumentation for conducting measurements and informatics available for interpretation of the data acquired in this area of biomedical research. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) based approaches are two primary analytical methods of choice for conducting metabonomic measurements. To overcome the complexity and wide dynamic range of concentrations of metabolites present in biological samples, a common practice is to couple online an analytical separation, typically high performance liquid chromatography (HPLC), with the mass spectrometer. Hence, of critical importance are not only the MS acquisition parameters, but also optimization of those variables that impact the analytical HPLC separation as well. A systematic investigation of a number of variables related to HPLC, such as mobile phase composition and flow rate, gradient time, column dimensions, and packing material properties has been conducted. The results of this study show that 10 cm long x 1 mm inner diameter (i.d.), C-18 reversed-phase columns provide higher resolution than C-8 or C-4 columns for the analysis of urine samples. The results also show that longer columns and extended mobile phase gradients allowed detection of a greater number of metabolites. As expected, MS analysis of the same urine sample using positive and negative ionization modes resulted in detection of a different ensemble of metabolites. Though prior dilution of rat and mouse urine is a common practice in conducting HPLC-MS metabonomic analyses, our results suggest that a greater number of species may be observed using undiluted urine. The matrix ( composition) of urine collected from different individuals affected the reproducibility of retention times. The variability in metabolite retention times using internal standards, although improved, was not completely corrected. C1 NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. EM issaqh@mail.ncifcrf.gov NR 35 TC 14 Z9 16 U1 3 U2 32 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2006 VL 29 IS 17 BP 2475 EP 2497 DI 10.1080/10826070600914638 PG 23 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 081YA UT WOS:000240352300001 ER PT J AU Du, QZ Wang, DJ Ito, Y AF Du, Qizhen Wang Daijie Ito, Yoichiro TI Preparation of solanesol from a tobacco leaf extract using high speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE solanesol; tobacco leaves; separation; high speed countercurrent chromatography AB Separation of solanesol from the tobacco leaves extract was performed by high speed countercurrent chromatography using a solvent system composed of petroleum ether-ethanol-methanol (200:1:100, v/v). In each separation, one gram of the tobacco leaves extract was injected to the multilayer coil separation column to yield 121 mg of solanesol with a purity of 90.7%. The obtained solanesol was identified by ESI-MS, H-1, and C-13-NMR. C1 NHLBI, Lab Biophys Chem, NIH, Ctr Biochem & Biophys, Bethesda, MD 20892 USA. Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou, Peoples R China. RP Ito, Y (reprint author), NHLBI, Lab Biophys Chem, NIH, Ctr Biochem & Biophys, Bldg 50,Room 3334,50 S Dr MSC 8014, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 12 TC 10 Z9 11 U1 3 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2006 VL 29 IS 17 BP 2587 EP 2592 DI 10.1080/10826070600915197 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 081YA UT WOS:000240352300009 ER PT J AU Goto, T Ito, Y Yamada, S Matsumoto, H Oka, H Nagase, H Ito, Y AF Goto, Tomomi Ito, Yuko Yamada, Sadaji Matsumoto, Hiroshi Oka, Hisao Nagase, Hisamitsu Ito, Yoichiro TI High throughput analysis of N-methyl carbamate pesticides in cereals and beans by dual countercurrent chromatography and liquid chromatography electrospray ionization tandem mass spectrometry SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE high throughput analysis; N-methyl carbamate pesticides; beans; cereals; dual CCC; ESI LC/MS/MS ID SHORT COLUMN; RESIDUES; VEGETABLES; FRUITS AB We developed a new analytical method for analysis of N-methyl carbamate pesticides in cereals and beans using dual counter-current chromatography (dual CCC) and liquid chromatography-electrospray ionization tandem mass spectrometry (ESI LC/MS/MS). After pesticides were extracted from cereals and beans with ethyl acetate, each extract was cleaned up by dual CCC using a non-aqueous binary solvent system composed of n-hexane-acetonitrile and analyzed by ESI LC/MS/MS with a short column. The average recoveries from cereals and beans fortified at the level of 0.01 ppm ranged from 73.9 to 119.6%, with the coefficients of variation from 0.7 to 6.8%. At the fortified level of 0.5 ppm, the recoveries ranged from 72.1 to 117.1% with coefficients of variation from 0.4 to 9.3%. The present analytical method of N-methyl carbamate pesticides in cereals and beans is considered to be useful for monitoring the pesticide residues in cereals and beans. C1 Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 4628576, Japan. Kinjo Gakuin Univ, Fac Pharm, Moriyama Ku, Nagoya, Aichi, Japan. Gifu Pharmaceut Univ, Gifu, Japan. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Goto, T (reprint author), Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 4628576, Japan. EM tomomi_3_gotou@pref.aichi.lg.jp NR 8 TC 8 Z9 9 U1 3 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2006 VL 29 IS 18 BP 2651 EP 2661 DI 10.1080/10826070600923068 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 083XH UT WOS:000240491000004 ER PT J AU Wei, MH Toure, O Glenn, GM Pithukpakorn, M Neckers, L Stolle, C Choyke, P Grubb, R Middelton, L Turner, ML Walther, MM Merino, MJ Zbar, B Linehan, WM Toro, JR AF Wei, MH Toure, O Glenn, GM Pithukpakorn, M Neckers, L Stolle, C Choyke, P Grubb, R Middelton, L Turner, ML Walther, MM Merino, MJ Zbar, B Linehan, WM Toro, JR TI Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID COLLECTING DUCT CARCINOMA; TUMOR-SUPPRESSOR PROTEIN; FUMARASE DEFICIENCY; UTERINE FIBROIDS; GROWTH-FACTOR; GENE; HYDRATASE; ENCEPHALOPATHY; PARAGANGLIOMA AB Background: Hereditary leiomyomatosis and renal cell cancer ( HLRCC; OMIM 605839) is the predisposition to develop smooth muscle tumours of the skin and uterus and/ or renal cancer and is associated with mutations in the fumarate hydratase gene ( FH). Here we characterise the clinical and genetic features of 21 new families and present the first report of two African- American families with HLRCC. Methods: Using direct sequencing analysis we identified FH germline mutations in 100% ( 21/ 21) of new families with HLRCC. Results: We identified 14 germline FH mutations ( 10 missense, one insertion, two nonsense, and one splice site) located along the entire length of the coding region. Nine of these were novel, with six missense ( L89S, R117G, R190C, A342D, S376P, Q396P), one nonsense ( S102X), one insertion ( 111insA), and one splice site ( 138+ 1G > C) mutation. Four unrelated families had the R58X mutation and five unrelated families the R190H mutation. Of families with HLRCC, 62% ( 13/ 21) had renal cancer and 76% ( 16/ 21) cutaneous leiomyomas. Of women FH mutation carriers from 16 families, 100% ( 22/ 22) had uterine fibroids. Our study shows that expression of cutaneous manifestations in HLRCC ranges from absent to mild to severe cutaneous leiomyomas. FH mutations were associated with a spectrum of renal tumours. No genotype- phenotype correlations were identified. Conclusions: In combination with our previous report, we identify 31 different germline FH mutations in 56 families with HLRCC ( 20 missense, eight frameshifts, two nonsense, and one splice site). Our FH mutation detection rate is 93% ( 52/ 56) in families suspected of HLRCC. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Urolog Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20894 USA. Childrens Hosp Philadelphia, Mol Genet Lab, Philadelphia, PA 19104 USA. NCI, NCI Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20894 USA. NCI, Immunobiol Lab, Ft Detrick, MD 21702 USA. RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Plaza S,Room 7012, Bethesda, MD 20892 USA. EM toroj@mail.nih.gov RI Pithukpakorn, Manop/K-9825-2013 OI Pithukpakorn, Manop/0000-0003-3611-5718 NR 31 TC 116 Z9 119 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2006 VL 43 IS 1 BP 18 EP 27 DI 10.1136/jmg.2005.033506 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 999QZ UT WOS:000234406700003 PM 15937070 ER PT J AU Laud, K Marian, C Avril, MF Barrois, M Chompret, A Goldstein, AM Tucker, MA Clark, PA Peters, G Chaudru, V Demenais, F Spatz, A Smith, MW Lenoir, GM Bressac-de Paillerets, B AF Laud, K Marian, C Avril, MF Barrois, M Chompret, A Goldstein, AM Tucker, MA Clark, PA Peters, G Chaudru, V Demenais, F Spatz, A Smith, MW Lenoir, GM Bressac-de Paillerets, B CA French Hereditary Melanoma Study G TI Comprehensive analysis of CDKN2A (p16(INK4A)/p14(ARF)) and CDKN2B genes in 53 melanoma index cases considered to be at heightened risk of melanoma SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; METHYLTHIOADENOSINE PHOSPHORYLASE; SUSCEPTIBILITY LOCUS; GERMLINE MUTATIONS; MALIGNANT-MELANOMA; FAMILIAL MELANOMA; LINKAGE ANALYSIS; CHROMOSOME 9P21; DOSAGE ASSAY; INK4 LOCUS AB Objective: Comprehensive analysis of the 9p21 locus including the CDKN2A, ARF, and CDKN2B genes in 53 individuals from melanoma index cases considered to be at heightened risk of melanoma. Methods and Results: Using a combination of DNA sequencing, gene copy number by real time quantitative PCR, linkage analysis, and transcript analysis in haploid somatic cell hybrids, we found no evidence for germline alteration in either coding or non- coding domains of CDKN2A and CDKN2B. However, we identified a p14(ARF) exon 1 beta missense germline mutation ( G16D) in a melanoma- neural system tumour syndrome ( CMM+ NST) family and a 8474 bp germline deletion from 196 bp upstream of p14(ARF) exon 1 beta initiation codon to 11233 bp upstream of exon 1 alpha of p16(INK4A) in a family with five melanoma cases. For three out of 10 families with at least three melanoma cases, the disease gene was unlinked to the 9p21 region, while linkage analysis was not fully conclusive for seven families. Conclusions: These data reinforce the hypothesis that ARF is a melanoma susceptibility gene and suggest that germline deletions specifically affecting p14(ARF) may not be solely responsible for NST susceptibility. Predisposition to CMM+ NST could either be due to complete disruption of the CDKN2A locus or be the result of more complex genetic inheritance. In addition, the absence of any genetic alteration in 50 melanoma prone families or patients suggests the presence of additional tumour suppressor genes possibly in the 9p21 region, and on other chromosomes. C1 Inst Gustave Roussy, Serv Genet, F-94800 Villejuif, France. Inst Gustave Roussy, Dept Med, F-94800 Villejuif, France. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Lincolns Inn Fields Labs, Canc Res UK, London Res Inst, London WC2A 3PX, England. Univ Evry, INSERM, F-91034 Evry, France. Inst Gustave Roussy, Serv Anatomopathol, F-94800 Villejuif, France. NCI, Lab Genom Divers, Ctr Canc Res, SAIC Frederick,NIH,DHHS, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Basic Res Program, SAIC Frederick,NIH,DHHS, Frederick, MD 21702 USA. RP Bressac-de Paillerets, B (reprint author), Inst Gustave Roussy, Serv Genet, 39 Rue Camille Desmoulins, F-94805 Villejuif, France. EM bressac@igr.fr RI Smith, Michael/B-5341-2012; Demenais, Florence/G-3298-2013; Tucker, Margaret/B-4297-2015; Marian, Catalin/B-1750-2012; OI Demenais, Florence/0000-0001-8361-0936; Marian, Catalin/0000-0002-7749-1384 NR 47 TC 29 Z9 31 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2006 VL 43 IS 1 BP 39 EP 47 DI 10.1136/jmg.2005.033498 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 999QZ UT WOS:000234406700005 PM 15937071 ER PT J AU Struewing, JP Pineda, MA Sherman, ME Lissowska, J Brinton, LA Peplonska, B Bardin-Mikolajczak, A Garcia-Closas, M AF Struewing, JP Pineda, MA Sherman, ME Lissowska, J Brinton, LA Peplonska, B Bardin-Mikolajczak, A Garcia-Closas, M TI Skewed X chromosome inactivation and early-onset breast cancer SO JOURNAL OF MEDICAL GENETICS LA English DT Article AB Background: Skewed X chromosome inactivation may be more common in women with epithelial ovarian cancer and early-onset breast cancer. We tested this hypothesis in a group of 235 breast cancer patients and 253 controls ( mean age 45.8 years) from a larger population based case control study. Methods: We measured X chromosome inactivation with the AR gene assay in lymphocyte DNA digested with the methylation specific enzyme HpaII. We judged skewness using an adjusted measure ( relative to the undigested sample) with a cut point of 75%, and an unadjusted measure where skewed was defined as >90% of the signal from one allele in the HpaII digested sample. Results: There were no significant differences in any of the skewing measures between cases and controls. Using the adjusted skewing measure among pre-menopausal subjects under the age of 50, 14% of cases versus 11% of controls were skewed, OR= 1.2, 95% CI 0.6 to 2.3; using the unadjusted measure, OR= 0.9, 95% CI 0.4 to 2.0. Conclusions: While we cannot rule out a subtle difference of approximately twofold or less, we have failed to find a significant difference in the prevalence of skewed X chromosome inactivation in younger women with breast cancer compared to controls. C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. RP Struewing, JP (reprint author), NCI, Lab Populat Genet, NIH, 41 Lib Dr,Room D702, Bethesda, MD 20892 USA. EM js140a@nih.gov RI Struewing, Jeffery/C-3221-2008; Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Struewing, Jeffery/I-7502-2013; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Struewing, Jeffery/0000-0002-4848-3334; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS; NCI NIH HHS [N01-CP-91013, Z01 CP010138-08] NR 11 TC 9 Z9 10 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2006 VL 43 IS 1 BP 48 EP 53 DI 10.1136/jmg.2005.033134 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 999QZ UT WOS:000234406700006 PM 15923273 ER PT J AU Izmirlian, G AF Izmirlian, Grant TI Response to 'Receiver operating characteristics of the prostate-specific antigen test in an unselected population' SO JOURNAL OF MEDICAL SCREENING LA English DT Letter ID CANCER SCREENING TRIAL; LUNG C1 US Natl Canc Inst, Bethesda, MD 20892 USA. RP Izmirlian, G (reprint author), US Natl Canc Inst, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM izmirlig@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2006 VL 13 IS 4 BP 214 EP 214 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 129CL UT WOS:000243705900010 PM 17217612 ER PT J AU Franco, R Bortner, CD Cidlowski, JA AF Franco, R. Bortner, C. D. Cidlowski, J. A. TI Potential roles of electrogenic ion transport and plasma membrane depolarization in apoptosis SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Review DE apoptotic volume decrease; ATPases; cell death; cell signaling; cell volume; electrogenic transport; ion channels; ion flux; ion transporters; ionic gradients; ionic homeostasis; plasma membrane potential ID PROGRAMMED CELL-DEATH; SMOOTH-MUSCLE-CELLS; CULTURED CORTICAL-NEURONS; LEISHMANIA-DONOVANI PROMASTIGOTES; NONSELECTIVE CATION CHANNELS; HUMAN HEPATOBLASTOMA CELLS; DEPENDENT SODIUM-CHANNELS; CEREBELLAR GRANULE CELLS; SENSITIVE CA2+ CHANNELS; BOVINE CHROMAFFIN CELLS AB Apoptosis is characterized by the programmed activation of specific biochemical pathways leading to the organized demise of cells. To date, aspects of the intracellular signaling machinery involved in this phenomenon have been extensively dissected and characterized. However, recent studies have elucidated a novel role for changes in the intracellular milieu of the cells as important modulators of the cell death program. Specially, intracellular ionic homeostasis has been reported to be a determinant in both the activation and progression of the apoptotic cascade. Several apoptotic insults trigger specific changes in ionic gradients across the plasma membrane leading to depolarization of the plasma membrane potential (PMP). These changes lead to ionic imbalance early during apoptosis. Several studies have also suggested the activation and/or modulation of specific ionic transport mechanisms including ion channels, transporters and ATPases, as mediators of altered intracellular ionic homeostasis leading to PMP depolarization during apoptosis. However, the role of PMP depolarization and of the changes in ionic homeostasis during the progression of apoptosis are still unclear. This review summarizes the current knowledge regarding the causes and consequences of PMP depolarization during apoptosis. We also review the potential electrogenic ion transport mechanisms associated with this event, including the net influx/efflux of cations and anions. An understanding of these mechamisms could lead to the generation of new therapeutic approaches for a variety of diseases involving apoptosis. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. EM cidlowski@niehs.nih.gov RI Franco, Rodrigo/D-9470-2013 OI Franco, Rodrigo/0000-0003-3241-8615 NR 224 TC 53 Z9 58 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JAN PY 2006 VL 209 IS 1 BP 43 EP 58 DI 10.1007/s00232-005-0837-5 PG 16 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 041PJ UT WOS:000237467800005 PM 16685600 ER PT J AU Ricci, AJ Kachar, B Gale, J Van Netten, SM AF Ricci, A. J. Kachar, B. Gale, J. Van Netten, S. M. TI Mechano-electrical transduction: New insights into old ideas SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Review DE mechanotransduction; hair cells; auditory; mechanically-gated ID AUDITORY HAIR-CELLS; GUINEA-PIG COCHLEA; TIP LINKS; MECHANOTRANSDUCER CHANNEL; MECHANICAL TRANSDUCTION; MECHANOSENSITIVE CHANNELS; BULLFROGS SACCULUS; BUNDLE MECHANICS; MYOSIN VIIA; SENSORY TRANSDUCTION AB The gating-spring theory of hair cell mechanotransduction channel activation was first postulated over twenty years ago. The basic tenets of this hypothesis have been reaffirmed in hair cells from both auditory and vestibular systems and across species. In fact, the basic findings have been reproduced in every hair cell type tested. A great deal of information regarding the structural, mechanical, molecular and biophysical properties of the sensory hair bundle and the mechanotransducer channel has accumulated over the past twenty years. The goal of this review is to investigate new data, using the gating spring hypothesis as the framework for discussion. Mechanisms of channel gating are presented in reference to the need for a molecular gating spring or for tethering to the intra- or extracellular compartments. Dynamics of the sensory hair bundle and the presence of motor proteins are discussed in reference to passive contributions of the hair bundle to gating compliance. And finally, the molecular identity of the channel is discussed in reference to known intrinsic properties of the native transducer channel. C1 Louisiana State Univ, Med Ctr, Ctr Neurosci, New Orleans, LA 70112 USA. Natl Inst Deafness & Other Communicat Disorders, Bethesda, MD 20892 USA. UCL, Ear Inst, Ctr Auditory Res, London WC1X 8EE, England. Univ Groningen, Dept Neurobiophys, NL-9747 AG Groningen, Netherlands. RP Ricci, AJ (reprint author), Louisiana State Univ, Med Ctr, Ctr Neurosci, New Orleans, LA 70112 USA. EM aricci2@earthlink.net FU NIDCD NIH HHS [DC03896, R01 DC003896] NR 132 TC 30 Z9 33 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 EI 1432-1424 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JAN PY 2006 VL 209 IS 2-3 BP 71 EP 88 DI 10.1007/s00232-005-0834-8 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 053GG UT WOS:000238293000002 PM 16773495 ER PT J AU Arnesen, SJ AF Arnesen, SJ TI Environmental health information resources: Healthy environments for healthy women and children SO JOURNAL OF MIDWIFERY & WOMENS HEALTH LA English DT Article DE environmental health; information services; Internet; National Library of Medicine (US); toxicology AB Because of concerns about exposure (e.g., from pesticides in the garden to how much fish is safe to eat), health professionals are often asked to address the effect of environmental agents on women's health. Numerous environmental health resources are available on the Internet, but with so many Web sites, it can be difficult to identify high-quality, accurate information oriented toward a wide variety of needs and users. This article describes environmental health and toxicology databases and resources from the National Library of Medicine (NLM) and other government agencies and organizations, that contain valuable information on potential environmental risks to women. C1 Natl Lib Med, Specialized Informat Serv Div, Bethesda, MD 20892 USA. RP Arnesen, SJ (reprint author), Natl Lib Med, Specialized Informat Serv Div, 6707 Democracy Blvd,Suite 510, Bethesda, MD 20892 USA. EM stacey_arnesen@nlm.nih.gov NR 5 TC 4 Z9 4 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1526-9523 J9 J MIDWIFERY WOM HEAL JI J. Midwifery Women Health PD JAN-FEB PY 2006 VL 51 IS 1 BP 35 EP 38 DI 10.1016/j.jmwh.2005.08.013 PG 4 WC Nursing SC Nursing GA 005FW UT WOS:000234809000006 PM 16399608 ER PT J AU Kummer, W Wiegand, S Akinci, S Schinkel, AH Wess, J Koepsell, H Haberberger, RV Lips, KS AF Kummer, Wolfgang Wiegand, Silke Akinci, Sibel Schinkel, Alfred H. Wess, Juergen Koepsell, Hermann Haberberger, Rainer Viktor Lips, Katrin Susanne TI Role of acetylcholine and muscarinic receptors in serotonin-induced bronchoconstriction in the mouse SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 12th International Symposium on Cholinergic Mechanismd CY 2003 CL Alicante, SPAIN SP Univ Miguel Hernandez, Caja Ahorros Mediterraneo, Ayuntamiento Alicante, Patronato Meunicipal Turismo Playas Alicante, Soc Espanola Bioquim Biol Mole, Soc Biofis Espana, Soc Espanola Neurocienc, Int Brain Res Org, Lipotec S A, DiverDrug S L, Targacept Inc, Grunenthal, Ctr Clin Dermatol Alicante, Viajes Hispan ID AIRWAYS; RAT C1 Univ Giessen, Inst Anat & Cell Biol, D-35385 Giessen, Germany. Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands. NIDDK, Bioorgan Chem Lab, Rockville, MD 20852 USA. Univ Wurzburg, Inst Anat & Cell Biol, D-97070 Wurzburg, Germany. RP Kummer, W (reprint author), Univ Giessen, Inst Anat & Cell Biol, D-35385 Giessen, Germany. EM Wolfgang.Kummer@anatomie.med.uni-giessen.de OI Haberberger, Rainer Viktor/0000-0001-8043-3786 NR 6 TC 17 Z9 17 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2006 VL 30 IS 1-2 BP 67 EP 68 DI 10.1385/JMN/30:1-2:67 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 111DS UT WOS:000242432200031 PM 17192631 ER PT J AU Cautam, D Duttaroy, A Cui, YH Han, SJ Deng, CX Seeger, T Alzheimer, C Wess, J AF Cautam, Dinesh Duttaroy, Alokesh Cui, Yinghong Han, Sung-Jun Deng, Chuxia Seeger, Thomas Alzheimer, Christian Wess, Juergen TI M-1-M-3 muscarinic acetylcholine receptor-deficient mice SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 12th International Symposium on Cholinergic Mechanismd CY 2003 CL Alicante, SPAIN SP Univ Miguel Hernandez, Caja Ahorros Mediterraneo, Ayuntamiento Alicante, Patronato Meunicipal Turismo Playas Alicante, Soc Espanola Bioquim Biol Mole, Soc Biofis Espana, Soc Espanola Neurocienc, Int Brain Res Org, Lipotec S A, DiverDrug S L, Targacept Inc, Grunenthal, Ctr Clin Dermatol Alicante, Viajes Hispan ID PANCREATIC ACINAR-CELLS; CHOLINERGIC STIMULATION; HIPPOCAMPAL PLASTICITY; KNOCKOUT MICE; MEMORY; INNERVATION; EXPRESSION; SECRETION; SUBTYPE; GENE C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Bundeswehr Inst Pharmacol & Toxicol, D-80937 Munich, Germany. Univ Kiel, Dept Physiol, D-24098 Kiel, Germany. RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov RI Han, Sung-Jun/B-9547-2012 NR 19 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2006 VL 30 IS 1-2 BP 157 EP 160 DI 10.1385/JMN/30:1-2:157 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 111DS UT WOS:000242432200065 ER PT J AU Sahir, N Brenneman, DE Hill, JM AF Sahir, Nadia Brenneman, Douglas E. Hill, Joanna M. TI Neonatal mice of the down syndrome model, Ts65Dn, exhibit upregulated VIP measures and reduced responsiveness of cortical astrocytes to VIP stimulation SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE down syndrome; vasoactive intestinal peptide; VPAC-I; VPAC-2; VIP-binding sites; real time PCR; neuronal survival; Ts65Dn segmental trisomy ID VASOACTIVE-INTESTINAL-PEPTIDE; ACTIVATING POLYPEPTIDE PACAP; MOUSE MODEL; ALZHEIMERS-DISEASE; EMBRYONIC GROWTH; NEUROPROTECTIVE PEPTIDE; CHOLINERGIC PHENOTYPE; CALCIUM HOMEOSTASIS; NEUROTROPHIC ACTION; REFERENCE MEMORY AB The Ts65Dn segmental mouse model of Down syndrome (DS) possesses a triplication of the section of chromosome 16 that is most homologous to the human chromosome 21 that is trisomic in DS. This model exhibits many of the characteristics of DS including small size, developmental delays, and a decline of cholinergic systems and cognitive function with age. Recent studies have shown that vasoactive intestinal peptide (VIP) systems are upregulated in aged Ts65Dn mice and that VIP dysregulation during embryogenesis is followed by the hypotonia and developmental delays as seen in both DS and in Ts65Dn mice. Additionally, astrocytes; from aged Ts65Dn brains do not respond to VIP stimulation to release survival-promoting substances. To determine if VIP dysregulation is age-related in Ts65Dn mice, the current study examined VIP and VIP receptors (VPAC-1 and VPAC-2) in postnatal day 8 Ts65Dn mice. VIP and VPAC-1 expression was significantly increased in the brains of trisomic mice compared with wild-type mice. VIP-binding sites were also significantly increased in several brain areas of young Ts65Dn mice, especially in the cortex, caudate/putamen, and hippocampus. Further, in vitro treatment of normal neurons with conditioned medium from VIP-stimulated Ts65Dn astrocytes from neonatal mice did not enhance neuronal survival. This study indicates that VIP anomalies are present in neonatal Ts65Dn mice, a defect occurs in the signal transduction mechanism of the VPAC-1 VIP receptor, cortical astrocytes from neonatal brains are dysfunctional, and further, that VIP dysregulation may play a significant role in DS. C1 NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. Johnson & Johnson Pharmaceut Res & Dev, Spring House, PA USA. NICHD, Sec Dev & Mol Pharmacol, NIH, Bethesda, MD 20892 USA. RP Hill, JM (reprint author), NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. EM hilljoa@mail.nih.gov FU Intramural NIH HHS NR 81 TC 10 Z9 10 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2006 VL 30 IS 3 BP 329 EP 340 DI 10.1385/JMN/30:03:329 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 130EL UT WOS:000243782200008 PM 17401158 ER PT J AU Maloney, B Ge, YW Greig, NH Lahiri, DK AF Maloney, B Ge, YW Greig, NH Lahiri, DK TI Characterization of the human beta-secretase 2 (BACE2) 5 '-flanking region - Identification of a 268-bp region as the basal BACE2 promoter SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE amyloid; aging; dementia; secretase; promoter; transcription factors; neurons ID AMYLOID PRECURSOR PROTEIN; BETA-SECRETASE; ALZHEIMERS-DISEASE; CELL-LINES; TRANSCRIPTIONAL REGULATION; ASPARTYL PROTEASE; PLAQUE PATHOLOGY; DOWNS-SYNDROME; MESSENGER-RNA; EXPRESSION AB The main characteristic of Alzheimer's disease (AD) is brain deposition of the P-amyloid (A beta) peptide, generated endoproteolytically from A beta precursor protein (APP) by beta- and gamma-secretases. A transmembrane aspartyl protease, beta-APP-cleaving enzyme (BACE1), was identified as beta-secretase. Although BACE1 cleaves APP at the P-secretase site, the role of its homolog, P-secretase 2 (BACE2) is poorly understood. We report the mRNA expression profile, DNA sequence, and molecular characterization of the BACE2 gene, located on chromosome 21 q22.3. The BACE2 gene expresses more strongly in peripheral tissues, although BACE2 mRNA is found in the majority of brain regions, including the postcentral gyrus and temporal lobe. Characterization of 2932 bp of the BACE2 5'-flanking region (GC content of 55%), reveals the absence of canonical CCAAT and TATA boxes within 1 kb of the transcription start site (TSS). The sequence lacks significant internal repeats and has a housekeeping gene structure. Two active regions of the BACE2 promoter determine its basal expression and cell-type specificity. The proximal region (-31/+238) likely determines general basal expression, and the distal region (-2618/-1513), cell-type specificity. Several putative transcription factor sites, particularly SP1, Oct-1, and HES-1, are predicted to be within I kb of the TSS. On either side of the proximal promoter region, two negative regulatory domains might reduce BACE2 expression under an induced condition. The BACE2 5'-flanking region is likely to be highly regulated and expressed in a tissue type-specific manner. C1 Indiana Univ, Sch Med, Dept Psychiat, Lab Mol Neurogenet,Inst Psychiat Res, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Lab Mol Neurogenet,Inst Psychiat Res, Indianapolis, IN 46202 USA. NIA, Sect Drug Design & Delivery, Neurosci Lab, Baltimore, MD 21224 USA. RP Lahiri, DK (reprint author), Indiana Univ, Sch Med, Dept Psychiat, Lab Mol Neurogenet,Inst Psychiat Res, Indianapolis, IN 46202 USA. EM dlahiri@iupui.edu RI Maloney, Bryan/C-4924-2011 OI Maloney, Bryan/0000-0003-2364-9649 FU NIA NIH HHS [AG18379, AG18884] NR 41 TC 13 Z9 16 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2006 VL 29 IS 1 BP 81 EP 99 DI 10.1385/JMN/29:01:81 PG 19 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 048FQ UT WOS:000237933400009 PM 16757812 ER PT J AU Moody, TW Nakagawa, T Kang, Y Jakowlew, S Chan, D Jensen, RT AF Moody, TW Nakagawa, T Kang, Y Jakowlew, S Chan, D Jensen, RT TI Bombesin/gastrin-releasing peptide receptor antagonists increase the ability of histone deacetylase inhibitors to reduce lung cancer proliferation SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE GRP receptors; antagonists; HDAC inhibitors; lung cancer; proliferation ID SIGNAL-TRANSDUCTION; TRICHOSTATIN-A; CLONAL GROWTH; CELL-LINES; CARCINOMA; APOPTOSIS; PROTEIN; KINASE; COMBINATION; ACTIVATION AB The effects of a bombesin/gastrin releasing peptide (BB/GRP) receptor antagonist, PD176252, and histone deacetylase (HDAC) inhibitor, MS-275, were investigated on human lung cancer cell lines. Using the MTT assay, PD176252 and MS-275 inhibited the proliferation of NCI-H1299 cells with IC50 values of 7 and 5 mu g/mL, respectively. Using MS-275 and PD176252 together, the ability to inhibit lung cancer cellular growth increased significantly. The combination index for MS-275 and PD176252 was < 0.2, indicating that the compounds are highly synergistic in inhibiting lung cancer cellular growth. Also, MS-275 and PD176252 together strongly inhibited the clonal growth of NCI-H345 or NCI-H1299 cells. MS-275 had little effect on the expression of lung cancer cellular GRP or GRP receptors, but increased expression of transforming growth factor-beta receptor II (TGF-beta RII). These results indicate that GRP receptor antagonists may potentiate the action of histone deacetylase inhibitors on lung cancer cellular proliferation by increasing expression of tumor suppressor genes. C1 NCI, Dept Hlth & Human Serv, Off Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD USA. NCI, Cell & Canc Biol Branch, Rockville, MD USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Moody, TW (reprint author), NCI, Dept Hlth & Human Serv, Off Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov FU Intramural NIH HHS NR 38 TC 19 Z9 19 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2006 VL 28 IS 3 BP 231 EP 238 DI 10.1385/JMN/28:03:231 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 037BB UT WOS:000237120600001 PM 16691010 ER PT J AU Blanco, I Arbesu, D Al Kassam, D de Serres, FJ Fernandez-Bustillo, E Rodriguez, C AF Blanco, Ignacio Arbesu, Daniel Al Kassam, Daniel de Serres, Frederick J. Fernandez-Bustillo, Enrique Rodriguez, Carmen TI Alphal-antitrypsin polymorphism in fibromyalgia syndrome patients from the Asturias Province in Northern Spain: A significantly higher prevalence of the PI*Z deficiency allele in patients than in the general population SO JOURNAL OF MUSCULOSKELETAL PAIN LA English DT Article DE alpha1-antitrypsin; alpha1-antitrypsin allelic polymorphism; SERPINA1; fibromyalgia syndrome ID ALPHA(1)-ANTITRYPSIN DEFICIENCY; PUBLISHED SURVEYS; ALPHA-1-ANTITRYPSIN; FREQUENCIES; HYPOTHESIS; DISEASES; EUROPE AB Background: Recent evidence suggests that the alpha 1-antitrypsin [AT] gene may play a role in the pathogenesis of the fibromyalgia syndrome [FMS]. The objective of the present study is to compare the AT gene frequency between FMS patients and the general population [GP] from the central region of the Asturias Province in Northern Spain. Method: The AT proteinase inhibitor phenotypes were characterized by isoelectric focusing on serum from a cohort of 250 individual FMS subjects, who fulfilled the American College of Rheumatology criteria for FMS, and on serum from a control cohort of 1, 111 GP subjects. The FMS subjects [238 females and 12 males] were enlisted from an outpatient hospital clinic setting. The mean age of the FMS cohort was of 49.02 years. The GP control cohort [45 percent males and 55 percent females] was enrolled using an epidemiological technique of simple random sampling in the general population from the same region of Asturias. The GP sample size was 1, 111, the mean age was of 46.2 years. Mean outcome measures were AT-PI phenotyping characterization [performed by isoelectric focusing] and AT serum concentration [measured by nephelometry]. Results: Calculated mean allele frequencies for PI*S and PI*Z [the two most frequent AT deficiency alleles] were 64 [95 percent confidence interval [Cl]: 45-90] and 40 [Cl: 25-62] per 1,000, respectively, for the FMS cohort, as compared with 100 [Cl: 88-113] and 19.7 [Cl: 14.5-26.6] per 1,000 for the GP cohort. Calculated prevalences [Hardy-Weinberg statistics formula] were 1/14 in FMS versus 1/29 in GP for MZ; 1/195 in FMS versus 1/254 in GP for SZ; and 1/625 in FMS versus 1/2,573 in GP for ZZ. For PI*Z, the calculated odd ratio among FMS versus GP was 2.06 [Cl: 1.16-3.63]. A binomial proof [contrast hypothesis] stated that FMS AT-Z gene frequency differed significantly from the GP Z gene frequency [P = 0.007]. Conclusion: The most common AT severe-deficient allele [i.e., PI*Z] has been found with a two-fold higher frequency in the FMS cohort than in the GP cohort. The high odds ratio found for PI*Z indicates a significant difference for PI*Z frequency in the FMS cohort as compared with the GP cohort. Our findings suggest that AT deficiency might play an important role in FMS development and clinical expression in, at least, a subset of FMS subjects. C1 Hop Valle Nalon, Dept Internal Med, Sama De Langreo 33920, Principado Astu, Spain. Hop Valle Nalon, Dept Rehabil, Sama De Langreo 33920, Principado Astu, Spain. Hop Valle Nalon, Dept Clin Biochem, Sama De Langreo 33920, Principado Astu, Spain. NIEHS, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Hosp Univ Cent Asturias, Dept Clin Biochem, Inst Nacl Silicosis, Oviedo 33006, Spain. RP Blanco, I (reprint author), Hop Valle Nalon, Dept Internal Med, Sama De Langreo 33920, Principado Astu, Spain. EM ignacio.blanco@sespa.princast.es NR 24 TC 11 Z9 11 U1 0 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1058-2452 J9 J MUSCULOSKELET PAIN JI J. Musculoskelet. Pain PY 2006 VL 14 IS 3 BP 5 EP 12 DI 10.1300/J094v14n03_02 PG 8 WC Rehabilitation; Rheumatology SC Rehabilitation; Rheumatology GA 094UB UT WOS:000241263500002 ER PT J AU Harding, WW Schmidt, M Tidgewell, K Kannan, P Holden, KG Gilmour, B Navarro, H Rothman, RB Prisinzano, TE AF Harding, WW Schmidt, M Tidgewell, K Kannan, P Holden, KG Gilmour, B Navarro, H Rothman, RB Prisinzano, TE TI Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID KAPPA-OPIOID-RECEPTOR; IN-VITRO; AGONIST; ANALOGS; LIGANDS; TRANS; C(2) AB Salvinorin A (1) is a hallucinogenic neoclerodane diterpene isolated from the widely available psychoactive plant Salvia divinorum and is the first example of a non-nitrogenous opioid receptor ligand. At present, there is little information available as to why this compound is selective for K opioid receptors. One approach to better understanding the mode of binding of I at K receptors is to systematically alter the structure of 1 and examine the effects on opioid receptor affinity and activity. Currently, there is a paucity of methods described for the preparation of analogues derived from 1. Here, we report the investigation of several chemical transformations of 1 isolated from S. divinorum. In particular, this work provides a semisynthesis of salvinicins A (2) and B (3) and has identified 10a as the first neoclerodane diterpene with 6 opioid antagonist activity. C1 Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Holden Labs, Carmel, CA 93923 USA. NIDA, Clin Psychopharmacol Sect, IRP, DHHS, Baltimore, MD 21224 USA. RP Prisinzano, TE (reprint author), Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. EM thomas-prisinzano@uiowa.edu RI Prisinzano, Thomas/B-7877-2010; OI Kannan, Pavitra/0000-0002-9170-6062; Tidgewell , Kevin/0000-0002-0501-2604 FU Intramural NIH HHS; NIDA NIH HHS [DA-018151-2, R01 DA018151, R01 DA018151-01A2] NR 27 TC 36 Z9 37 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 2006 VL 69 IS 1 BP 107 EP 112 DI 10.1021/np050398i PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 009IZ UT WOS:000235106500022 PM 16441078 ER PT J AU Kopin, IJ AF Kopin, I. J. TI The relationship of early studies of monoamine oxidase to present concepts SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article ID O-METHYLATION; PARKINSONS-DISEASE; TYRAMINE OXIDASE; MULTIPLE FORMS; AMINE OXIDASE; L-DOPA; NOREPINEPHRINE; EPINEPHRINE; METABOLISM; INHIBITION AB The development of our understanding of monoamine oxidase (MAO), of its role in the metabolism of an-tines and of the therapeutic usefulness of MAO inhibitors (MAOIs) have evolved, slowly at times and rapidly at other times, with leaps propelled by new discoveries, new techniques and new insights. Moussa Youdim was one of the major contributors to propulsion of several of these leaps, including the detection of multiple forms of MAO. the descriptions of their properties, active sites and substrates, the use of MAOIs for enhancement of DOPA in treating Parkinson's disease and the evolution of MAO-B inhibitors from mere enzyme inhibitors to lead compounds in the discovery of neuroprotective agents for use in degenerative neurological diseases. Since others will be describing the more recent developments in this field, I thought it would be of interest and instructive to recount the unfolding of our early understanding of MAO, dating from its discovery until the events that first suggested that drugs that inhibit MAO might be neuroprotective. While even the earliest observations about MAO were valid they were often misinterpreted or confusing, whereas others were predictive of several of our newer concepts of MAO and of side effects encountered in patients treated with MAOIs. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Kopin, IJ (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM kopini@ninds.nih.gov NR 86 TC 2 Z9 5 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 2006 IS 71 BP 79 EP 86 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 089HE UT WOS:000240870400011 PM 17447418 ER PT J AU Bandyopadhyay, S Huang, X Cho, H Greig, NH Youdim, MB Rogers, JT AF Bandyopadhyay, S. Huang, X. Cho, H. Greig, N. H. Youdim, M. B. Rogers, J. T. TI Metal specificity of an iron-responsive element in Alzheimer's APP mRNA 5 ' untranslated region, tolerance of SH-SY5Y and H4 neural cells to desferrioxamine, clioquinol, VK-28, and a piperazine chelator SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article ID AMYLOID PRECURSOR PROTEIN; 5'-UNTRANSLATED REGION; IN-VIVO; PARKINSONS-DISEASE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; CLINICAL-TRIAL; BRAIN IRON; BETA; COPPER AB Iron closely regulates the expression of the Alzheimer's Amyloid Precursor Protein (APP) gene at the level of message translation by a pathway similar to iron control of the translation of the ferritin L- and H mRNAs by Iron-responsive Elements in their 5'untranslated regions (5'UTRs). Using transfection based assays in SH-SY5Y neuroblastoma cells we tested the relative efficiency by which iron, copper and zinc up-regulate IRE activity in the APP 5'UTR. Desferrioxamine (high affinity Fe3+ chelator). (ii) clioquinol (low affinity Fe/Cu/Zn chelator), (iii) piperazine-1 (oral Fe chelator), (iv) VK-28 (oral Fe chelator), were tested for their relative modulation of AFP 5'UTR directed translation of a luciferase reporter gene. Iron chelation based therapeutic strategies for slowing the progression of Alzheimer's disease (and other neurological disorders that manifest iron imbalance) are discussed with regard to the relative neural toxic action of each chelator in SH-SY5Y cells and in H4 glioblastoma cells. C1 MGH, Genet & Aging Res Unit, Dept Psychiat, Neurochem Lab, Charlestown, MA 02129 USA. NIA, Baltimore, MD 21224 USA. Technion Israel Inst Technol, Haifa, Israel. RP Rogers, JT (reprint author), MGH, Genet & Aging Res Unit, Dept Psychiat, Neurochem Lab, Charlestown, MA 02129 USA. EM Jrogers@partners.org FU NIA NIH HHS [AG18884, AG21081]; NIMH NIH HHS [5K01MH002001] NR 71 TC 27 Z9 28 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 2006 IS 71 BP 237 EP 247 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 089HE UT WOS:000240870400027 PM 17447434 ER PT J AU Goldstein, DS AF Goldstein, D. S. TI Cardiovascular aspects of Parkinson disease SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article; Proceedings Paper CT 16th International Congress on Parkinsons Disease and Related Disorders CY JUN 05-09, 2005 CL Berlin, GERMANY ID IDIOPATHIC ORTHOSTATIC HYPOTENSION; CARDIAC SYMPATHETIC DENERVATION; AUTONOMIC FAILURE; DYSFUNCTION AB This chapter provides an update about cardiovascular aspects of Parkinson disease (PD), with the following topics: (1) Orthostatic hypotension (OH) as an early finding in PD; (2) neurocirculatory abnormalities in PD + OH independent of levodopa treatment; (3) cardiac and extracardiac noradrenergic denervation in PD + OH; (4) progressive loss of cardiac sympathetic innervation in PD without OH. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10 Room 6N252, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov NR 18 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 2006 IS 70 BP 339 EP 342 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 081PH UT WOS:000240329000052 PM 17017550 ER PT J AU Qian, L Hong, JS Flood, PM AF Qian, L. Hong, J. -S. Flood, P. M. TI Role of microglia in inflammation-mediated degeneration of dopaminergic neurons: neuroprotective effect of Interleukin 10 SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article; Proceedings Paper CT 16th International Congress on Parkinsons Disease and Related Disorders CY JUN 05-09, 2005 CL Berlin, GERMANY ID CNS AB Inflammation in the brain has been recognized to play an increasingly important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Inflammation-mediated neurodegeneration involves activation of the brain's resident immune cells, the microglia, which produce proinflammatory and neurotoxic factors including cytokines, reactive oxygen species (ROS), nitric oxide, and eicosanoids that directly or indirectly cause neurodegeneration. In this study, we report that IL-10, an immunosuppressive cytokine, reduced the inflammation-mediated degeneration of dopaminergic (DA) neurons through the inhibition of microglial activation. Pretreatment of rat mesencephalic neuronglia cultures with IL-10 significantly attenuated the lipopolysaccharide (LPS) induced DA neuronal degeneration. The neuroprotective effect of IL-10 was attributed to inhibition of LPS-stimulated microglial activation. IL-10 significantly inhibited the microglial production of tumor necrosis factor alpha (TNF-alpha), nitric oxide, ROS and superoxide free radicals after LPS stimulation. C1 Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Qian, L (reprint author), Univ N Carolina, Comprehens Ctr Inflammatory Disorders, CB 7455, Chapel Hill, NC 27599 USA. EM Pat_Flood@dentistry.unc.edu NR 11 TC 37 Z9 38 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 2006 IS 70 BP 367 EP 371 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 081PH UT WOS:000240329000057 PM 17017555 ER PT J AU Hallett, M AF Hallett, M. TI Pathophysiology of dystonia SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article; Proceedings Paper CT 16th International Congress on Parkinsons Disease and Related Disorders CY JUN 05-09, 2005 CL Berlin, GERMANY ID FOCAL HAND DYSTONIA; SURROUND INHIBITION; BLEPHAROSPASM; CORTEX; MODEL AB Understanding of the pathophysiology of dystonia derives primarily from studies of focal dystonias. Physiological investigations have revealed a number of abnormalities that may reflect the genetic substrate that predisposes certain individuals to develop dystonia. There is a loss of inhibition in the central nervous system, and a loss of surround inhibition specifically. Plasticity is increased, and there are sensory abnormalities. Which of these disorders is primary is uncertain. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD USA. EM hallettm@ninds.nih.gov NR 10 TC 52 Z9 53 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 2006 IS 70 BP 485 EP 488 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 081PH UT WOS:000240329000073 PM 17017571 ER PT J AU Shah, BH Shah, FB Catt, KJ AF Shah, BH Shah, FB Catt, KJ TI Role of metalloproteinase-dependent EGF receptor activation in alpha(1)-adrenoceptor-stimulated MAP kinase phosphorylation in GT1-7 neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE epidermal growth factor receptor; matrix metalloproteinases; mitogen-activated protein kinases; phenylephrine; receptor tyrosine kinase; receptor transactivation ID EPIDERMAL-GROWTH-FACTOR; GONADOTROPIN-RELEASING-HORMONE; PROTEIN-COUPLED RECEPTORS; VASCULAR SMOOTH-MUSCLE; ANGIOTENSIN-II; CARDIAC-HYPERTROPHY; MATRIX METALLOPROTEINASES; HYPOTHALAMIC NEURONS; REGULATED KINASE-1; SIGNALING PATHWAYS AB Adrenoceptors (ARs) are involved in the regulation of gonadotropin-releasing hormone (GnRH) release from native and immortalized hypothalamic (GT1-7) neurons. However, the AR-mediated signaling mechanisms and their functional significance in these cells are not known. Stimulation of GT1-7 cells with the alpha(1)-AR agonist, phenylephrine (Phe), causes phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) mitogen-activated protein (MAP) kinases that is mediated by protein kinase C (PKC)-dependent transactivation of the epidermal growth factor receptor (EGF-R). Phe stimulation causes shedding of the soluble ligand, heparin-binding EGF (HB-EGF), as a consequence of matrix metalloproteinase (MMP) activation. Phe-induced phosphorylation of the EGF-R, and subsequently of Shc and ERK1/2, was attenuated by inhibition of MMP or HB-EGF with the selective inhibitor, CRM197, or by a neutralizing antibody. In contrast, phosphorylation of the EGF-R, Shc and ERK1/2 by EGF and HB-EGF was independent of PKC and MMP activity. Moreover, inhibition of Src attenuated ERK1/2 responses by Phe, but not by HB-EGF and EGF, indicating that Src acts upstream of the EGF-R. Consistent with a potential role of reactive oxygen species (ROS), Phe-induced phosphorylation of EGF-R was attenuated by the antioxidant, N-acetylcysteine. These data suggest that activation of the alpha(1)-AR causes phosphorylation of ERK1/2 through activation of PKC, ROS and Src, and shedding of HB-EGF, which binds to and activates the EGF-R. C1 NICHD, ERRB, NIH, Bethesda, MD 20892 USA. RP Shah, BH (reprint author), NICHD, ERRB, NIH, Bld 49,Rm 6A36, Bethesda, MD 20892 USA. EM shahb@mail.nih.gov FU Intramural NIH HHS NR 62 TC 23 Z9 25 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2006 VL 96 IS 2 BP 520 EP 532 DI 10.1111/j.1471-4159.2005.03585.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 994JX UT WOS:000234029100022 PM 16336626 ER PT J AU Liu, Y Kalintchenko, N Sassone-Corsi, P Aguilera, G AF Liu, Y Kalintchenko, N Sassone-Corsi, P Aguilera, G TI Inhibition of corticotrophin-releasing hormone transcription by inducible cAMP-early repressor in the hypothalamic cell line, 4B SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE corticotropin-releasing hormone; transcription; CREM; ICER; phospho-CREB ID STRESS-INDUCED ACTIVATION; PITUITARY-ADRENAL AXIS; PARAVENTRICULAR NUCLEUS; GENE-EXPRESSION; NEUROSECRETORY NEURONS; RESPONSIVE ELEMENT; ACTH-SECRETION; MESSENGER-RNA; ATT-20 CELLS; CYCLIC-AMP AB We have shown recently that the rapid decline in corticotrophin-releasing hormone (CRH) transcription following activation by stress is associated with induction and binding to the CRH promoter of the repressor isoforms of cAMP responsive element modulator (CREM), inducible cAMP early repressor (ICER). The ability of ICER to inhibit CRH transcription was examined in the hypothalamic cell line, 413, which expresses CRH. Co-transfection of the inhibitory isoforms of CREM, ICER I and II and CREM beta, and CRH promoter-lucif erase constructs in 4B cells blunted basal and forskolin-stimulated CRH promoter activity, an effect which was abolished by mutation of the CRE of the CRH promoter. Western blot analyses and electromobility gel-shift and super-shift showed increases in endogenous ICER after 3 h of incubation with forskolin. Consistent with an inhibitory effect of CREM on CRH transcription, chromatin immunoprecipitation assays in cells transfected with ICER I revealed recruitment of CREM by the CRH promoter in conjunction with decreases in Pol II association. The study shows that generation of ICER following prolonged stimulation with forskolin, or transfection of an ICER expression vector in hypothalamic cell lines expressing CRH, is associated with CREM binding to the CRH promoter and transcriptional repression. The data support the hypothesis that induction of repressor isoforms of CREM is part of an intracellular feedback mechanism contributing to the termination of CRH transcription during stimulation. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, Bethesda, MD 20892 USA. Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, Room 1-3330,MSC 1303, Bethesda, MD 20892 USA. RI Sassone-Corsi, Paolo/H-6182-2011 NR 38 TC 22 Z9 22 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JAN PY 2006 VL 18 IS 1 BP 42 EP 49 DI 10.1111/j.1365-2826.2005.01383-x PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 014ME UT WOS:000235483500005 PM 16451219 ER PT J AU Strong, MJ Kesavapany, S Pant, HC AF Strong, MJ Kesavapany, S Pant, HC TI Letter to the editor - To the editor - Response SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Letter ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; FRONTOTEMPORAL DEMENTIA; GLIAL INCLUSIONS; TAU; ALS C1 Univ Western Ontario, Robarts Res Inst, London, ON, Canada. Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada. NINDS, Neurochem Lab, Cytosekeletal Prot Regulat Sect, NIH, Bethesda, MD 20892 USA. RP Strong, MJ (reprint author), Univ Western Ontario, Robarts Res Inst, London, ON, Canada. RI Strong, Michael/H-9689-2012 NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JAN PY 2006 VL 65 IS 1 BP 97 EP 98 DI 10.1097/01.jnen.0000195945.26948.f5 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 005PQ UT WOS:000234836700012 ER PT J AU Chub, N Mentis, GZ O'Donovan, MJ AF Chub, N Mentis, GZ O'Donovan, MJ TI Chloride-sensitive MEQ fluorescence in chick embryo motoneurons following manipulations of chloride and during spontaneous network activity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INTRACELLULAR CL-REGULATION; SPINAL-CORD PREPARATION; LIVING BRAIN-SLICES; EXCITATORY ACTIONS; SYNAPTIC DRIVE; NERVOUS-SYSTEM; NEURONS; RAT; GABA; COMMUNICATION AB Chloride-sensitive MEQ fluorescence in chick embryo motoneurons following manipulations of chloride and during spontaneous network activity. J Neurophysiol 95: 323-330, 2006. First published September 28, 2005; doi: 10.1152/jn.00162.2005. Intracellular Cl- ([Cl-] in) homeostasis is thought to be an important regulator of spontaneous activity in the spinal cord of the chick embryo. We investigated this idea by visualizing the variations of [Cl-] in in motoneurons retrogradely labeled with the Cl-sensitive dye 6-methoxy-N-ethylquinolinium iodide (MEQ) applied to cut muscle nerves in the isolated E10-E12 spinal cord. This labeling procedure obviated the need for synthesizing the reduced, cell-permeable dihydro-MEQ (DiH-MEQ). The specificity of motoneuron labeling was confirmed using retrograde co-labeling with Texas Red Dextran and immunocytochemistry for choline acetyltransferase (ChAT). In MEQ-labeled motoneurons, the GABA(A) receptor agonist isoguvacine (100 mu M) increased somatic and dendritic fluorescence by 7.4 and 16.7%, respectively. The time course of this fluorescence change mirrored that of the depolarization recorded from the axons of the labeled motoneurons. Blockade of the inward Na+/K-/2Cl(-) co- transporter (NKCC1) with bumetanide (20 mu M) or with a low-Na+ bath solution (12 mM), increased MEQ fluorescence by 5.3 and 11.4%, respectively, consistent with a decrease of [Cl-] in. After spontaneous episodes of activity, MEQ fluorescence increased and then declined to the pre-episode level during the interepisode interval. The largest fluorescence changes occurred over motoneuron dendrites (19.7%) with significantly smaller changes (5.2%) over somata. Collectively, these results show that retrogradely loaded MEQ can be used to detect [Cl-] in in motoneurons, that the bumetanide-sensitive NKCC1 co-transporter is at least partially responsible for the elevated [Cl-] in of developing motoneurons, and that dendritic [Cl-](in) decreases during spontaneous episodes and recovers during the inter-episode interval, presumably due to the action of NKCC1. C1 NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP Chub, N (reprint author), NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Rm 3BC911,35 Convent Dr, Bethesda, MD 20892 USA. EM chubn@ninds.nih.gov RI o'donovan, michael/A-2357-2015 OI o'donovan, michael/0000-0003-2487-7547 FU Intramural NIH HHS NR 42 TC 40 Z9 40 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2006 VL 95 IS 1 BP 323 EP 330 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 991OB UT WOS:000233822200029 PM 16192339 ER PT J AU Kotaleski, JH Plenz, D Blackwell, KT AF Kotaleski, JH Plenz, D Blackwell, KT TI Using potassium currents to solve signal-to-noise problems in inhibitory feedforward networks of the striatum SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SPINY PROJECTION NEURONS; FAST-SPIKING INTERNEURONS; NEOCORTICAL PYRAMIDAL NEURONS; NEOSTRIATAL NEURONS; SYNAPTIC INPUT; BASAL GANGLIA; DOPAMINERGIC MODULATION; NUCLEUS-ACCUMBENS; DENDRITIC CALCIUM; NMDA RECEPTORS AB Using potassium currents to solve signal-to-noise problems in inhibitory feedforward networks of the striatum. J Neurophysiol 95: 331 - 341, 2006. First published September 28, 2005; doi: 10.1152/jn. 00063.2005. Fast-spiking (FS) interneurons provide the main route of feedforward inhibition from cortex to spiny projection neurons in the striatum. A steep current-firing frequency curve and a dense local axonal arbor suggest that even small excitatory inputs could translate into powerful feedforward inhibition, although such an arrangement is also sensitive to amplification of spurious synaptic inputs. We show that a transient potassium (KA) current allows the FS interneuron to strike a balance between sensitivity to correlated input and robustness to noise, thereby increasing its signal-to-noise ratio (SNR). First, a compartmental FS neuron model was created to match experimental data from striatal FS interneurons in cortex - striatum - substantia nigra organotypic cultures. Densities of sodium, delayed rectifier, and KA channels were optimized to replicate responses to somatic current injection. Spontaneous alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and gamma-aminobutyric acid ( GABA) synaptic currents were adjusted to the experimentally measured amplitude, rise time, and interevent interval histograms. Second, two additional adjustments were required to emulate the remaining experimental observations. GABA channels were localized closer to the soma than AMPA channels to match the synaptic population reversal potential. Correlation among inputs was required to produce the observed firing rate during up-states. In this final model, KA channels were essential for suppressing down-state spikes while allowing reliable spike generation during up-states. This mechanism was particularly important under conditions of high dopamine. Our results suggest that KA channels allow FS interneurons to operate without a decrease in SNR during conditions of increased dopamine, as occurs in response to reward or anticipated reward. C1 George Mason Univ, Sch Computat Sci, Fairfax, VA 22030 USA. George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA. Royal Inst Technol, Sch Comp Sci & Commun, Stockholm, Sweden. NIMH, Lab Syst Neurosci, Unit Neural Network Physiol, NIH, Bethesda, MD 20892 USA. RP Kotaleski, JH (reprint author), George Mason Univ, Sch Computat Sci, MS 2A1, Fairfax, VA 22030 USA. EM avrama@gmu.edu FU Intramural NIH HHS; NIAAA NIH HHS [R01 AA016022] NR 60 TC 13 Z9 14 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2006 VL 95 IS 1 BP 331 EP 341 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 991OB UT WOS:000233822200030 PM 16192340 ER PT J AU Oldfield, EH AF Oldfield, EH TI Pituitary pseudocapsule - Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID ADENOMAS C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2006 VL 104 IS 1 BP 2 EP 3 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 001OX UT WOS:000234547300002 ER PT J AU Oldfield, EH Vortmeyer, AO AF Oldfield, EH Vortmeyer, AO TI Development of a histological pseudocapsule and its use as a surgical capsule in the excision of pituitary tumors SO JOURNAL OF NEUROSURGERY LA English DT Article DE pituitary; pseudocapsule; pituitary tumor; Cushing disease ID CUSHINGS-DISEASE; CLONAL ORIGIN; ADENOMAS; SURGERY; GLAND; RESECTION; REMOVAL AB Object. The presence of a histological pseudocapsule around pituitary tumors was noted in the early 1900s. Since that time there has been no emphasis on the sequence of the stages of its development or on the relationship between these stages and the capacity to identify very small pituitary tumors at surgery in patients in whom preoperative imaging has been nondiagnostic. In addition, limited emphasis has been given to the pseudocapsule's use for selective and complete resection of pituitary adenomas. Methods. The development of the pseudocapsule was examined by performing histological analysis of portions of pituitary glands removed during 805 operations for Cushing disease. Twenty-five adenomas, each measuring between 0.25 and 4 mm in maximum diameter, were detected in the excised specimens; 17 were adenocorticotrophic hormone-positive adenomas and eight were incidental tumors (four prolactin-secreting and four nonsecreting lesions). In 16 tumors the size of the adenoma could be established. The distribution of tumor-size in relation to the presence of a histological pseudocapsule indicates a transition from the absence of a reticulin capsule (tumor diameter <= 1 mm) through the initial compression of surrounding tissue (tumor diameter 2-3 mm). Conclusions. The absence of a reticulin capsule in cases of very small tumors may contribute to limited localization of these lesions during surgical exploration of the pituitary gland. In this article the authors describe surgical techniques in which the histological pseudocapsule is used as a surgical capsule during pituitary surgery. In their experience, recognition of this surgical capsule and its use at surgery has contributed to the identification of microadenomas buried in the pituitary gland, aided the recognition of subtle invasion of the pituitary capsule and the contiguous dura mater, and enhanced the consistency of complete tumor excision with small and large tumors. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM oldfielde@ninds.nih.gov NR 32 TC 72 Z9 80 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2006 VL 104 IS 1 BP 7 EP 19 DI 10.3171/jns.2006.104.1.7 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 001OX UT WOS:000234547300005 PM 16509142 ER PT J AU Bachis, A Nosheny, RL Andrews, P Major, E Mocchetti, I AF Bachis, Alessia Nosheny, Rachel L. Andrews, Peter Major, Eugene Mocchetti, Italo TI Axonal transport of human immunodeficiency virus-1 envelope protein GP120 causes neuronal apoptosis SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. Georgetown Univ, Dept Cell Biol, Med Ctr, Washington, DC 20057 USA. NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P13 BP 6 EP 6 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300014 ER PT J AU Bandaru, VVR Sacktor, N McArthur, JC Cutler, RG Knapp, EL Mattson, MP Haughey, NJ AF Bandaru, Veera Venkata Ratnam Sacktor, Ned McArthur, Justin C. Cutler, Roy G. Knapp, Edward L. Mattson, Mark P. Haughey, Norman J. TI Associative and predictive biomarkers of changing cognitive status in HIV-1 infected patients SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P14 BP 6 EP 6 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300015 ER PT J AU Gagnon, SJ Yao, K Akyani, N Williams, E Stuve, O Monson, N Racke, M Jacobson, S AF Gagnon, Susan J. Yao, Karen Akyani, Nahid Williams, Elizabeth Stuve, Olaf Monson, Nancy Racke, Michael Jacobson, Steven TI Reactivation of HHV-6 in natalizumab treated MS patients SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P65 BP 28 EP 28 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300066 ER PT J AU Grant, CW Oh, U Takenouchi, N Yamano, Y Yao, K Jacobson, S AF Grant, Christian W. Oh, Unsong Takenouchi, Norihiro Yamano, Yoshihisa Yao, Karen Jacobson, Steven TI HTLV-1 Tax down-regulates expression regulatory T cell-specific Foxp3 SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 NINDS, NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. Kagoshima City Hosp, Dept Neurol, Kagoshima, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P72 BP 31 EP 31 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300073 ER PT J AU Knapp, EL Wang, Y Bandaru, VVR Wheeler, D Cottingham, P Morris, M Mattson, M Haughey, NJ AF Knapp, Edward L. Wang, Yue Bandaru, V. V. Ratnam Wheeler, David Cottingham, Patrick Morris, Michael Mattson, Mark Haughey, Norman J. TI TNF-alpha modulates NMDA receptor trafficking by increasing the ceramide content of neuronal membranes SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P95 BP 40 EP 41 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300096 ER PT J AU Oh, U Grant, CW Caitlin, G Takenouchi, N Jacobson, S AF Oh, Unsong Grant, Christian W. Caitlin, Griffith Takenouchi, Norihiro Jacobson, Steven TI Analysis of Foxp3 protein expression in HTLV-1 infection SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P148 BP 63 EP 64 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300149 ER PT J AU Pandya, D Grant, C Nonnemacher, M Jain, P Wigdahl, B AF Pandya, Devanshi Grant, Christian Nonnemacher, Michael Jain, Pooja Wigdahl, Brian TI CCAAT/enhancer-binding proteins modulate human T cell leukemia virus type 1 long terminal repeat activation SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P151 BP 65 EP 65 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300152 ER PT J AU Ramanathan, MP Pankhong, P Kutzler, MA Chambers, CA Kim, JJ Gunasekaran, G Pierson, TC Weiner, DB AF Ramanathan, Mathura P. Pankhong, Pankhong Kutzler, Michele A. Chambers, Chambers A. Kim, J. Joseph Gunasekaran, Gunasekaran Pierson, Theodore C. Weiner, David B. TI Protein kinase CK2: A potential target in the development of novel therapeutics against West Nile virus SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 Viral Genom Inc, BlueBell, Philadelphia, PA USA. NIH, Bethesda, MD 20892 USA. UPENN Med Sch, Philadelphia, PA USA. Mahidol Univ, Bangkok 10700, Thailand. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P162 BP 69 EP 69 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300163 ER PT J AU Venkatesan, A Haughey, NJ Cadet, JL Song, H Nath, A AF Venkatesan, Arun Haughey, Norman J. Cadet, Jean Lud Song, Hongjun Nath, Avindra TI Impairment of adult hippocampal neurogenesis by methamphetamine and HIV-Tat protein SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Drexel Univ, Dept Microbiol & Immunology, Office Dean, Temple Univ, Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirol C1 Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. NIDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P201 BP 85 EP 85 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300202 ER PT J AU Yao, K Gagnon, S Akhyani, N Honarmand, S Glaser, C Jacobson, S AF Yao, Karen Gagnon, Susan Akhyani, Nahid Honarmand, Somayeh Glaser, Carol Jacobson, Steven TI HHV-6 reactivation in patients with encephalitis of unknown origin SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. Viral & Rickettsial Dis Lab, Richmond, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P217 BP 92 EP 92 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300218 ER PT J AU Cropley, VL Fujita, M Musachio, JL Hong, J Ghose, S Sangare, J Nathan, PJ Pike, VW Innis, RB AF Cropley, VL Fujita, M Musachio, JL Hong, J Ghose, S Sangare, J Nathan, PJ Pike, VW Innis, RB TI Whole-body biodistribution and estimation of radiation-absorbed doses of the dopamine D-1 receptor radioligand C-11-NNC 112 in humans SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE C-11-NNC 112; PET; D-1 receptor; dosimetry; effective dose ID DOSIMETRY; PET; D-1-DOPAMINE; LIGAND; BRAIN AB The present study estimated radiation-absorbed doses of the dopamine D, receptor radioligand [C-11]((+)-8-chloro-5-(7-benzofuranyl)-7-hydroxy-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine) (NNC 112)in humans, based on dynamic whole-body PET in healthy subjects. Methods: Whole-body PET was performed on 7 subjects after injection of 710 +/- 85 MBq of (CNNC)-C-11 112. Fourteen frames were acquired for a total of 120 min in 7 segments of the body. Regions of interest were drawn on compressed planar images of source organs that could be identified. Radiation dose estimates were calculated from organ residence times using the OLINDA 1.0 program. Results: The organs with the highest radiation-absorbed doses were the gallbladder, liver, lungs, kidneys, and urinary bladder wall. Biexponential fitting of mean bladder activity demonstrated that 15% of activity was excreted via the urine. With a 2.4-h voiding interval, the effective dose was 5.7 mu Sv/MBq (21.1 mrem/mCi). Conclusion: C-11-NNC 112 displays a favorable radiation dose profile in humans and would allow multiple PET examinations per year to be performed on the same subject. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Monash Univ, Dept Physiol, Monash Ctr Brain & Behav, Clayton, Vic 3168, Australia. RP Cropley, VL (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 1,Room B3-10,1 Ctr Dr,MSC 0135, Bethesda, MD 20892 USA. EM cropleyv@mail.nih.gov RI Ghose, Subroto/J-6732-2016 FU Intramural NIH HHS NR 20 TC 14 Z9 15 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2006 VL 47 IS 1 BP 100 EP 104 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 003JZ UT WOS:000234679300020 PM 16391193 ER PT J AU Horne, MK McCloskey, DJ AF Horne, MK McCloskey, DJ TI Factor V Leiden as a common genetic risk factor for venous thromboembolism SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE FVL; APC-resistance; thrombophilia ID ACTIVATED PROTEIN-C; ORAL-CONTRACEPTIVE USERS; INHERITED RESISTANCE; PROTHROMBIN 20210A; PREGNANT-WOMEN; FETAL LOSS; LONG-TERM; THROMBOSIS; MUTATION; THROMBOPHILIA AB Purpose: To increase nurses' knowledge of the Factor V Leiden (FVL) genetic trait for venous thromboembolism. Organizing Framework: An overview of the history, prevalence, and predisposition of the FVL genetic mutation, including who should be tested and how and in what circumstances people with FVL should be treated. Findings: FVL is the most commonly recognized genetic trait associated with venous thrombosis. It is found predominantly in Caucasian populations. Biochemically it causes "activated protein C resistance (APCR)." The decision to test for FVL depends on whether the information gained will potentially improve the health care of the person or family. For people who have had deep venous thrombosis, testing for FVL will likely not alter treatment approaches. Currently the advantage for testing is primarily limited to asymptomatic family members who carry FVL and who have had deep vein thrombosis. Close relatives who also carry the mutated gene might benefit from prophylactic anticoagulation when their risk of thrombosis is increased by temporary factors such as surgery. Conclusions: Nurses are in a unique position to provide accurate information and counseling when patients and their family members are presented with the results of thrombophilia testing. C1 Natl Inst Hlth, NINR, Bethesda, MD 20892 USA. Natl Inst Hlth, Dept Lab Med, Bethesda, MD 20892 USA. RP McCloskey, DJ (reprint author), Natl Inst Hlth, NINR, 31 Ctr Dr,Rm 5B-13, Bethesda, MD 20892 USA. EM mccloskd@mail.nih.gov NR 51 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2006 VL 38 IS 1 BP 19 EP 25 DI 10.1111/j.1547-5069.2006.00072.x PG 7 WC Nursing SC Nursing GA 011GU UT WOS:000235257000010 PM 16579319 ER PT J AU Calzone, KA Lea, DH Masny, A AF Calzone, Kathleen A. Lea, Dale Halsey Masny, Agnes TI Non-Hodgkin's lymphoma as an exemplar of the effects of genetics and genomics SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE cancer genetics; genetic testing; genetics; genomics; lymphoma; oncology nursing ID B-CELL LYMPHOMA; CANCER; EXPRESSION; GENES; RISK; EPIDEMIOLOGY; STRATEGIES; PREDICTION; RITUXIMAB; DIAGNOSIS AB Purpose: To discuss the interface of genetics and genomics science in the identification and management of non-Hodgkin's lymphoma. The field of oncology is an exemplar of how the genomic revolution is influencing more individualized care and treatment of people with cancer and their families. Design: Integrated review of the cancer genetics and genomics literature. Methods: Published peer-reviewed research, conference proceedings, and peer-reviewed internet sites regarding the genetics and genomics of cancer and non-Hodgkin's lymphoma were reviewed, analyzed, and data synthesized. Findings: All malignancies have a genetic and genomic basis. Genetic and genomic breakthroughs are rapidly being applied to all aspects of cancer care including: (a) identification of at-risk individuals before disease occurs, (b) diagnosis and characterization of disease and its aggressiveness when it appears via gene expression, (c) and individualization of therapies over the disease course based on these new molecular technologies. Conclusions: Oncology nurses in every role, clinical subspecialty, and type of education are among the first nurses to integrate genetic and genomic information in such a broad context. This experience shows how genetic and genomic discoveries will interface with other health conditions and ultimately, will affect the practice of all nurses. C1 NCI, Canc Res Ctr, Genet Branch, NIH, Bethesda, MD 20889 USA. Fdn Blood Res, Div Genet, Scarborough, ME 04074 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Calzone, KA (reprint author), NCI, Canc Res Ctr, Genet Branch, NIH, 8901 Wisconsin Ave,Bldg 8,RM 5101, Bethesda, MD 20889 USA. EM calzonek@mail.nih.gov NR 49 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2006 VL 38 IS 4 BP 335 EP 343 DI 10.1111/j.1547-5069.2006.00124.x PG 9 WC Nursing SC Nursing GA 111WR UT WOS:000242487100005 PM 17181081 ER PT J AU Corwin, RL Hartman, TJ Maczuga, SA Graubard, BI AF Corwin, RL Hartman, TJ Maczuga, SA Graubard, BI TI Dietary saturated fat intake is inversely associated with bone density in humans: Analysis of NHANES III SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2002 Annual Meeting CY APR 20-24, 2002 CL NEW ORLEANS, LA DE bone density; osteoporosis; dietary fat; saturated fat; NHANES ID NUTRITION EXAMINATION SURVEY; GAMMA-LINOLENIC ACID; 3RD NATIONAL-HEALTH; TOTAL-ENERGY-INTAKE; MINERAL DENSITY; OLDER-ADULTS; OSTEOPOROTIC FRACTURES; OXIDATIVE STRESS; UNITED-STATES; HIP FRACTURE AB Mounting evidence indicates that the amount and type of fat in the diet can have important effects on bone health. Most of this evidence is derived from animal studies. Of the few human studies that have been conducted, relatively small numbers of subjects and/or primarily female subjects were included. The present study assessed the relation of dietary fat to hip bone mineral density (BMD) in men and women using NHANES III data (n = 14,850). Multivariate models using SAS-callable SUDAAN were used to adjust for the sampling scheme. Models were adjusted for age, sex, weight, height, race, total energy and calcium intakes, smoking, and weight-bearing exercise. Data from women were further adjusted for use of hormone replacement therapy. Including dietary protein, vitamin C, and beta-carotene in the model did not influence the outcome. Analysis of covariance was used to generate mean BMD by quintile of total and saturated fat intake for 4 sex/age groups. Saturated fat intake was negatively associated with BMD at several hip sites. The greatest effects were seen among men < 50 y old (linear trend P = 0.004 for the femoral neck). For the femoral neck, adjusted mean BMD was 4.3% less among men with the highest compared with the lowest quintile of saturated fat intake (BMD, 95% Cl: highest quintile: 0.922 g/cm(2), 0.909-0.935; lowest quintile: 0.963 g/cm(2), 95% Cl: 0.950-0.976). These data indicate that BMD is negatively associated with saturated fat intake, and that men may be particularly vulnerable to these effects. C1 Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. Penn State Univ, Populat Res Inst, University Pk, PA 16802 USA. NCI, Biostat Branch, DCEG, Bethesda, MD 20892 USA. RP Corwin, RL (reprint author), Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. EM rxc13@psu.edu NR 57 TC 67 Z9 70 U1 1 U2 8 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2006 VL 136 IS 1 BP 159 EP 165 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 998RS UT WOS:000234337600028 PM 16365076 ER PT J AU Ray, AL Semba, RD Walston, J Ferrucci, L Cappola, AR Ricks, MO Xue, QL Fried, LP AF Ray, AL Semba, RD Walston, J Ferrucci, L Cappola, AR Ricks, MO Xue, QL Fried, LP TI Low serum selenium and total carotenoids predict mortality among older women living in the community: The Women's Health and Aging Studies SO JOURNAL OF NUTRITION LA English DT Article DE aging; carotenoids; mortality; selenium women ID CARDIOVASCULAR-DISEASE; MEDITERRANEAN DIET; VEGETABLE INTAKE; BETA-CAROTENE; RISK; CANCER; ASSOCIATION; INFLAMMATION; ANTIOXIDANTS; POPULATION AB Selenium and the carotenoids play an important role in antioxidant defenses and in the redox regulation involved in inflammation. We tested the hypothesis that low selenium and carotenoids predict mortality in older women living in the community. Women who were enrolled in the Women's Health and Aging Studies I and 11 in Baltimore, MD (n = 632; 70-79 y old) had serum selenium and carotenoids measured at baseline and were followed for mortality over 60 mo. Median (minimum, maximum) serum selenium and carotenoids were 1.53 (0.73, 2,51) mu mol/L and 1.67 (0.13, 9.10) mu mol/L; 14.1% of the women died. The 5 major causes of death were heart disease (32.6%), cancer (118.0%), stroke (9.0%), infection (6.7%), and chronic obstructive pulmonary disease (5.6%). Adjusting for age, education, smoking, BMI, poor appetite, and chronic diseases, higher serum selenium [hazard ratio (HR) 0.71, 95% Cl 0.56-0.90/1 SD increase in log. selenium; P = 0.005] and higher serum total carotenoids (HR 0.77, 95% Cl 0.64-0.84/1 SD increase in log, total carotenolds; P = 0.009) were associated with a lower risk of mortality. Women living in the community who have higher serum selenium and carotenoids are at a lower risk of death. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. RP Ferrucci, L (reprint author), Johns Hopkins Med Inst, Baltimore, MD 21205 USA. EM rdsemba@jhmi.edu FU NCRR NIH HHS [RR00722]; NIA NIH HHS [R01 AG027012, N01-AG12112, R01 AG027012-01, R01 AG11703-01A1, R37 AG019905]; NIAID NIH HHS [R01 AI41956] NR 40 TC 71 Z9 73 U1 0 U2 5 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2006 VL 136 IS 1 BP 172 EP 176 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 998RS UT WOS:000234337600030 PM 16365078 ER PT J AU Radican, L Wartenberg, D Rhoads, GG Schneider, D Wedeen, R Stewart, P Blair, A AF Radican, L Wartenberg, D Rhoads, GG Schneider, D Wedeen, R Stewart, P Blair, A TI A retrospective occupational cohort study of end-stage renal disease in aircraft workers exposed to trichloroethylene and other hydrocarbons SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID SOCIOECONOMIC-STATUS; MAINTENANCE FACILITY; HEART-DISEASE; LIVER-DISEASE; UNITED-STATES; GLOMERULONEPHRITIS; MORTALITY; EPIDEMIOLOGY; EXPOSURES; SOLVENTS AB Objective: Case-control studies suggest hydrocarbons increase end-stage renal disease (ESRD) risk. No cohort studies have been conducted. Methods: An occupational database was matched to the U.S. Renal Data System, and the outcome of all-cause ESRD was examined using multivariable Cox regression. Sixteen individual hydrocarbons were studied, although exposures were not mutually exclusive. Results: For the 1973-2000 period, there was an approximate twofold increased risk of ESRD among workers exposed to trichloroethylene, 1,1,1-trichloroethane, and JP4 gasoline compared with unexposed subjects (all P < 0.05). Relative risk was greater than unity (P > 0.05) for several other hydrocarbons. Associations attenuated (all P > 0.05) when 2001-2002 data were included in the analyses. Conclusions: Certain hydrocarbons may increase all-cause ESRD risk. Uncertainty, regarding the mechanism for increased risk and the observed attenuation in risk in 2001-2002, as well as the overlap of exposures, complicates interpretation. Additional research is needed. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Prevent Med & Community Hlth, Newark, NJ 07103 USA. Dept Vet Affairs New Jersey Hlth Care Syst, Res & Dev, Newark, NJ USA. Rutgers State Univ, Piscataway, NJ 08855 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Environm & Occupat Med, Div Environm Epidemiol, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, Sch Publ Hlth, Newark, NJ 07103 USA. RP Radican, L (reprint author), Merck & Co Inc, Worldwide Outcomes Res, WS 2E 50,1 Merck Dr, Whitehouse Stn, NJ 08889 USA. EM larry_radican@merck.com FU Intramural NIH HHS; NCI NIH HHS [Z01 CP010120-10]; NIEHS NIH HHS [ES05022, P30 ES005022] NR 32 TC 12 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2006 VL 48 IS 1 BP 1 EP 12 DI 10.1097/01.jom.0000190300.51629.e0 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 003GD UT WOS:000234668900001 PM 16404204 ER PT J AU Baccarelli, A Tretiakova, M Gorbanev, S Lomtev, A Klimkina, I Tchibissov, V Averkina, O Dosemeci, M AF Baccarelli, A Tretiakova, M Gorbanev, S Lomtev, A Klimkina, I Tchibissov, V Averkina, O Dosemeci, M TI Risk of lung cancer and exposure to industrial acids, solvents, and metals in Leningrad Province, Russia SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OCCUPATIONAL EXPOSURE; RESPIRATORY CANCER; MORTALITY; WORKERS; CHROMIUM; PLATERS; TOLUENE; COHORT; PLANT; MISTS AB Objective: We sought to investigate the association of occupational exposure to industrial acids, solvents, and metals with lung cancer in Leningrad Province, Russia, where an excess of occupationally related lung cancer was reported recently. Methods: We identified 540 pathologically diagnosed lung cancer cases and 582 controls from the 1993-1998 autopsy records of the 88 Leningrad Province hospitals. Lifetime job-specific exposure measurements were available for 12 industrial acids, 15 solvents, and 17 metals. Results: Exposures were frequent in the study group and mostly occurred after World War II. However, lung cancer risks for industrial acids (odds ratio [OR] = 1.2; 95% confidence interval [CI] = 0.8-1.7), solvents (OR = 0.8; 95% CI = 0.6-1.2), and metals (OR = 0.8; 95% CI = 0.5-1.0) were not increased. Also, no significant excess risk was found for any of the specific agents investigated. Conclusions: The excess of occupationally related lung cancer in the Province is not explained by exposure to the agents investigated. C1 Leningrad Oblast Pathol Bur, St Petersburg, Russia. Reg Ctr Hyg & Sanitat, St Petersburg, Russia. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Milan, Maggiore Hosp, IRCCS Fdn, Milan, Italy. Univ Milan, EPOCA Epidemiol Res Ctr, Dept Occupat Hlth, Clin Lavoro L Devoto, Milan, Italy. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Baccarelli, A (reprint author), Univ Milan, EPOCA Res Ctr Occupat Clin & Environm Epidemiol, Dept Environm & Occupat Hlth, Clin L Devoto, Via San Barnaba 8, I-20122 Milan, Italy. EM andrea.baccarelli@unimi.it OI Baccarelli, Andrea/0000-0002-3436-0640 NR 39 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2006 VL 48 IS 1 BP 48 EP 55 DI 10.1097/01.jom.0000184880.53887.cc PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 003GD UT WOS:000234668900006 PM 16404209 ER PT J AU Herrington, CS Douek, DC AF Herrington, CS Douek, DC TI Infection and disease: cause and cure SO JOURNAL OF PATHOLOGY LA English DT Editorial Material DE infection; pathology; microbiology; immunology; vaccination; diagnosis; treatment ID ACUTE RESPIRATORY SYNDROME; GENE-THERAPY STRATEGIES; HUMAN-PAPILLOMAVIRUS; SARS CORONAVIRUS; CERVICAL-CANCER; PATHOGENESIS; SYPHILIS; TISSUE; PREVALENCE; PROTEIN AB Much can be learnt about the mechanisms by which micro-organisms cause disease from the ways that they interact with cells and tissues. This issue of The Journal of Pathology contains articles that address the roles that cell and tissue biology and pathology are playing in the elucidation of these mechanisms. A review of variant Creutzfeldt-Jakob disease is followed by a discussion of severe acute respiratory syndrome (SARS). Two articles on human papillomavirus (HPV) infection address the association between viral infection and neoplasia, as do reviews on viruses and lymphoma/leukaemia, and Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8, HHV8). The section on viral disease concludes with an article on morbilli viruses. The intracellular effects of bacteria are addressed in a review of Listeria infection and a further review outlines recent advances in our knowledge of syphilis. Reviews on Helicobacter and gastric neoplasia, innate defences against methicillin-resistant Staphylococcus aureus (MRSA) infection, and the function of granulomas in tuberculosis also address aspects of tissue responses to bacterial infection. Following a review of the function of immunoglobulin A in defence against infection, a group of articles considers vaccination and gene therapy approaches, the latter involving consideration of both viral and bacterial strategies. The reviews assembled here bridge several gaps: between microbiology and cellular pathology; between host and infecting organism; and between disease and therapy. It is clear that cell and tissue pathology approaches are of value in all of these spheres, providing cell and tissue relevance to microbiological and immunological observations. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 Univ St Andrews, Bute Med Sch, St Andrews KY16 9TS, Fife, Scotland. NIAID, NIH, Human Immunol Sect, Vaccine Res Ctr, Bethesda, MD 20874 USA. RP Herrington, CS (reprint author), Univ St Andrews, Bute Med Sch, Westburn Lane, St Andrews KY16 9TS, Fife, Scotland. EM csh2@st-andrews.ac.uk OI Herrington, C Simon/0000-0001-9177-8165 NR 26 TC 2 Z9 2 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2006 VL 208 IS 2 BP 131 EP 133 DI 10.1002/path.1912 PG 3 WC Oncology; Pathology SC Oncology; Pathology GA 006BX UT WOS:000234871200001 PM 16362991 ER PT J AU Jacobson, SW Carr, LG Croxford, J Sokol, RJ Li, TK Jacobson, JL AF Jacobson, SW Carr, LG Croxford, J Sokol, RJ Li, TK Jacobson, JL TI Protective effects of the alcohol dehydrogenase-ADH1B allele in children exposed to alcohol during pregnancy SO JOURNAL OF PEDIATRICS LA English DT Article ID PRENATAL ALCOHOL; REACTION-TIME; MATERNAL AGE; BRAIN-DAMAGE; POLYMORPHISMS; PHARMACOKINETICS; PERFORMANCE; POPULATION; INFANCY; MEMORY AB Objectives To examine alcohol use for mothers with and without an ADH1B*3 allele and the moderating effects of the maternal and child ADH1B*3 allele on a broad range of infant and 7.5-year outcomes. Study design Blood samples from 263 black mother/child pairs (217 mothers and 239 children) were analyzed to determine incidence of the ADH1B allele and the relation of the maternal allele to pregnancy drinking assessed at every prenatal clinic visit. Moderating effects of ADH1B were examined by dichotomizing the moderator variable and performing regression analyses on the 2 groups. Results Pregnancy drinking at conception was less frequent in the presence of the ADH1B*3 allele, and virtually no adverse effects were found in children whose mothers had at least one ADH1B*3 allele. By contrast to the maternal allele, we found no consistent pattern of greater vulnerability in children lacking the ADH1B*3 allele. Conclusions These data are consistent with the hypothesis that the maternal ADH1B*3 allele provides some protection to the fetus from prenatal alcohol exposure. C1 Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48207 USA. Wayne State Univ, Sch Med, Dept Psychol, Detroit, MI 48207 USA. Indiana Univ, Sch Med, Dept Med & Pharmacol, Bloomington, IN 47405 USA. NIAAA, Bethesda, MD 20892 USA. RP Jacobson, SW (reprint author), Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, 2751 E Jefferson,Room 460, Detroit, MI 48207 USA. EM sjacobs@med.wayne.edu FU NCRR NIH HHS [S06-RR08167]; NIAAA NIH HHS [P50-AA07606, R01-AA06966, R01-AA09524] NR 39 TC 48 Z9 48 U1 2 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2006 VL 148 IS 1 BP 30 EP 37 DI 10.1016/j.jpeds.2005.08.023 PG 8 WC Pediatrics SC Pediatrics GA 007FV UT WOS:000234954900009 PM 16423594 ER PT J AU Sutton, EJ Young, J McInerney-Leo, A Bondy, CA Gollust, SE Biesecker, BB AF Sutton, EJ Young, J McInerney-Leo, A Bondy, CA Gollust, SE Biesecker, BB TI Truth-telling and Turner syndrome: The importance of diagnostic disclosure SO JOURNAL OF PEDIATRICS LA English DT Article ID BREAKING BAD-NEWS; PARENTS; CHILDREN AB Objective A targeted analysis with transcript data from previous research was designed to study the perceived effects of secret-keeping on individuals with Turner syndrome (TS). Study design Girls and women (n = 97) and 21 parents participated in the initial interview study. Transcripts were coded and analyzed for constructs related to secret-keeping. Results Thirty percent of participants spontaneously mentioned that their health care providers (HCP) or parents had withheld all or part of their TS diagnosis. Of those, 15 individuals were not informed of the infertility component of their diagnosis. Individuals reporting secret-keeping were more likely to have had a negative perception of the HCP's role in the disclosure process compared with those participants who did not report that a secret had been kept (P <.025). Conclusion The prevalence of secret-keeping within this sample population suggests it is likely an existing concern in the greater TS population. How HCPs disclose a TS diagnosis may affect whether secrets are kept. Conversely, secret-keeping may result in a negative disclosure experience. These observations suggest the need for interventions aimed at helping HCPs disclose health-related information to parents and their children in a timely, caring, and sensitive manner. C1 NHGRI, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Biesecker, BB (reprint author), NHGRI, NIH, 10 Ctr Dr 10-10C101, Bethesda, MD 20892 USA. EM barbarab@mail.nih.gov FU Intramural NIH HHS NR 22 TC 15 Z9 16 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2006 VL 148 IS 1 BP 102 EP 107 DI 10.1016/j.jpeds.2005.08.022 PG 6 WC Pediatrics SC Pediatrics GA 007FV UT WOS:000234954900022 PM 16423607 ER PT J AU Okada, Y Li, T Miyazaki, A Fujita, Y Shiotani, K Tsuda, Y Yokoi, T Ambo, A Sasaki, Y Jinsmaa, Y Bryant, SD Marczak, E Li, Q Swarztwelder, HS AF Okada, Y. Li, T. Miyazaki, A. Fujita, Y. Shiotani, K. Tsuda, Y. Yokoi, T. Ambo, A. Sasaki, Y. Jinsmaa, Y. Bryant, S. D. Marczak, E. Li, Q. Swarztwelder, H. S. TI Development of unique and potent mu-opioid agonists and antagonists containing DMT SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 65121, Japan. Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 65121, Japan. Tohoku Pharmaceut Univ, Dept Biochem, Aoba Ku, Sendai, Miyagi, Japan. Natl Inst Environm Hlth Sci, Med Chem Grp, LPC, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC USA. VA Med Ctr, Neurobiol Res Lab, Durham, NC USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2006 VL 12 SU S BP 180 EP 180 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 075SN UT WOS:000239905600384 ER PT J AU Shiotani, K Li, T Miyazaki, A Fujita, Y Tsuda, Y Yokoi, T Ambo, A Sasaki, Y Jinsmaa, Y Bryant, SD Marczak, E Lazarus, LH Okada, Y AF Shiotani, K. Li, T. Miyazaki, A. Fujita, Y. Tsuda, Y. Yokoi, T. Ambo, A. Sasaki, Y. Jinsmaa, Y. Bryant, S. D. Marczak, E. Lazarus, L. H. Okada, Y. TI The role of 2',6'-dimethyl-L-tyrosine (Dmt) for manifestation of high mu-opioid receptor binding affinity in opioidmimetics SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Med Chem, Kobe, Hyogo, Japan. Kobe Gakuin Univ, Grad Sch Food & Med Sci, Kobe, Hyogo 65121, Japan. Tohoku Pharmaceut Univ, Dept Biochem, Sendai, Miyagi, Japan. Natl Inst Environm Hlth Sci, LPC, Med Chem Grp, Res Triangle Pk, NC USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2006 VL 12 SU S BP 181 EP 181 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 075SN UT WOS:000239905600387 ER PT J AU Tsuda, Y Kawakami, T Fujita, Y Yamada, T Isozaki, K Shimohigashi, Y Lazarus, LH AF Tsuda, Y. Kawakami, T. Fujita, Y. Yamada, T. Isozaki, K. Shimohigashi, Y. Lazarus, L. H. TI Synthesis and binding profiles of endomorphin-2 the analogues containing conformationally constrained moiety SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, Hyogo 65121, Japan. Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 65121, Japan. Konan Univ, Fac Sci & Engn, Dept Chem, Higashinada Ku, Kobe, Hyogo, Japan. Kyushu Univ, Lab Struct Funct Biochem, Fac Sci, Fukuoka 812, Japan. Kyushu Univ, Lab Struct Funct Biochem, Grad Sch Sci, Fukuoka 812, Japan. NIEHS, LPC, Med Chem Grp, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2006 VL 12 SU S BP 183 EP 183 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 075SN UT WOS:000239905600395 ER PT J AU Guiotto, A Calderan, A Ruzza, P Biondi, B Rubini, C Osler, A Mattson, MP AF Guiotto, A. Calderan, A. Ruzza, P. Biondi, B. Rubini, C. Osler, A. Mattson, M. P. TI Carnosine analogues: Alpha, beta-unsaturated aldehyde scavengers based on the histidyl hydrazide moiety SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 CNR, Inst Biomol Chem, Padova Unit, Padua, Italy. Natl Inst Aging, Intramural Res Program, Neurosci Lab, Baltimore, MD USA. RI Guiotto, Andrea/A-4720-2009; Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2006 VL 12 SU S BP 212 EP 212 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 075SN UT WOS:000239905600512 ER PT J AU Espinoza, J Romero, R Kim, YM Kusanovic, JP Hassan, S Erez, O Gotsch, F Than, NG Papp, Z Kim, CJ AF Espinoza, Jimmy Romero, Roberto Kim, Yeon Mee Kusanovic, Juan Pedro Hassan, Sonia Erez, Offer Gotsch, Francesca Than, Nandor Gabor Papp, Zoltan Kim, Chong Jai TI Normal and abnormal transformation of the spiral arteries during pregnancy SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE atherosis; immunohistochemistry; impedance to blood flow; integrin; physiologic transformation of the spiral arteries; placental bed ID UTEROPLACENTAL BLOOD-FLOW; FETAL GROWTH-RETARDATION; GESTATIONAL-AGE INFANTS; VELOCITY WAVE-FORMS; HUMAN PLACENTAL BED; FULL-TERM PLACENTA; TROPHOBLASTIC INVASION; DOPPLER ULTRASOUND; IV COLLAGENASE; 1ST TRIMESTER AB This article reviews the anatomy and physiology of the uterine circulation, with emphasis on the remodeling of spiral arteries during normal pregnancy, and the timing and anatomical pathways of trophoblast invasion of the spiral arteries. We review the definitions of the placental bed and basal plate of the placenta, their relevance to the study of the physiologic transformation of the spiral arteries, as well as the methods to obtain and examine placental bed biopsy specimens. We also examine the role of the extravillous trophoblast in normal and abnormal pregnancies, and the criteria used to diagnose failure of physiologic transformation of the spiral arteries. Finally, we comment on the use of uterine artery Doppler velocimetry as a surrogate marker of chronic uteroplacental ischemia. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Semmelweis Univ, Dept Obstet & Gynecol 1, Budapest, Hungary. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, Intramural Div, NIH DHHS,Hutzel Womens Hosp, 4th Floor 3990 John R, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS NR 105 TC 55 Z9 59 U1 0 U2 7 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2006 VL 34 IS 6 BP 447 EP 458 DI 10.1515/JPM.2006.089 PG 12 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 120FV UT WOS:000243070800003 PM 17140293 ER PT J AU He, Y Tabibi, E Yalkowsky, SH AF He, Y Tabibi, E Yalkowsky, SH TI Solubilization of two structurally related anticancer drugs: XK-469 and PPA SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE solubility; XK-469; PPA; formulation vehicle; combination; pH adjustment; cosolvency; surfactant; complexation; excipients ID HP-BETA-CD; COMPLEXATION; PH; CYCLODEXTRINS; COSOLVENTS; XK469; FLAVOPIRIDOL; COMBINATION; DISSOLUTION AB The efficiency of a solubilization technique is determined by the physical-chemical properties of the drug. This study investigates the solubilization on two structurally related anticancer drugs, XK-469 and PPA. XK-469 is much less polar than PPA with an intrinsic solubility of 0.000274 mg/mL, which is about 10000 fold less than that of PPA. Fortunately, its physical-chemical properties make it much more formulatable. An ionizable drug can be solubilized. by pH adjustment with cosolvency, micellization, or complexation. Both XK-469 and PPA are weak acids with pKa values of 2.7 and 2.9, respectively. Thus, they can be solubilized by pH adjustment. At pH 4.55, neither cosolvency, micellization nor complexation has much effect on the solubility of PPA. However, these techniques can significantly increase the solubility of XK-469. In fact, the solubility of XK-469 in 20% HP beta CD at pH 4.55 is 5.85 mg/mL, which is more than 20000 times greater than its intrinsic solubility. With the solubilization descriptors obtained from the experimental data for both unionized and ionized drug species atpH 1.0 and pH 4.55, the solubility of each drug at any pH and excipient concentration can be estimated. Then, a solubilization technique can be chosen for preparing a desired final drug concentration. (c) 2005Wiley-Liss, Inc. C1 Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. NCI, Bethesda, MD 20892 USA. RP He, Y (reprint author), Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. EM yhe@rdg.boehringer-ingelheim.com FU NCI NIH HHS [CM-77109] NR 24 TC 7 Z9 7 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JAN PY 2006 VL 95 IS 1 BP 97 EP 107 DI 10.1002/jps.20500 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 000FE UT WOS:000234445500013 PM 16315229 ER PT J AU Waterhouse, DJ Saavedra, JE Davies, KM Citro, ML Xu, X Powell, DA Grimes, GJ Potti, GK Keefer, LK AF Waterhouse, DJ Saavedra, JE Davies, KM Citro, ML Xu, X Powell, DA Grimes, GJ Potti, GK Keefer, LK TI Injectable formulation of disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), an ultrafast nitric oxide donor prodrug SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE nitric oxide; analytical chemistry; lyophilization; stabilization; prodrugs; targeted drug delivery; solvate; kinetics; chirality; chemical stability ID N-NITROSAMINO ACIDS; AMINO-ACIDS; SODIUM-NITRITE; RATS; NITROSOPROLINE; NITROSATION; INFUSION; MICE AB PROLI/NO is an agent of structure XN(O)=NONa (X=L-prolyl) whose 2-s half-life for nitric oxide (NO) release at physiological pH makes it an excellent prodrug for localizing NO's therapeutic effects at the site of application, but a difficult one to formulate and certify as pure. Despite its extraordinary thermal and hydrolytic instability, however, PROLI/NO could be formulated as an injectable drug by dissolving it in cold 0.1 M sodium hydroxide containing 5% D-mannitol, then quickly ultrafiltering and lyophilizing it in evacuated septum vials. No evidence for decomposition was seen in the contents of these evacuated vials when stored at -20 degrees C over a 140-day observation period, as judged by quantifying NO release in simulated infusate solutions (10 MM carbonate/bicarbonate, pH 10.5). The only hydrolysis products detected were NO, nitrite ion, proline, and N-nitrosoproline, all products of normal human physiological processes. (c) 2005 Wiley-Liss, Inc. C1 Natl Canc Inst, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Data Management Serv Inc, Ft Detrick, MD 21702 USA. NCI, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. RP Keefer, LK (reprint author), Natl Canc Inst, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. EM keefer@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-46002, N01-CO-12400] NR 29 TC 13 Z9 13 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JAN PY 2006 VL 95 IS 1 BP 108 EP 115 DI 10.1002/jps.20486 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 000FE UT WOS:000234445500014 PM 16315224 ER PT J AU Holmes, A AF Holmes, A. TI Exploring functional interactions between SERT and BDNF in the mediation of emotional behavior using mutant mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 6th IUPHAR Satellite Meeting on Serotonin CY JUN 27-30, 2006 CL Hokkaido Univ, Sapporo, JAPAN SP Serotonin Club HO Hokkaido Univ DE BDNF; serotonin transporter; depression; mouse C1 NIAAA, Lab Integrat Neurosci, Sect Behav Sci & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2006 VL 101 SU 1 BP 13 EP 13 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 059UU UT WOS:000238758500011 ER PT J AU Innis, BR AF Innis, BR TI Molecular imaging studies in rodents with PET SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 79th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 08-10, 2006 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2006 VL 100 SU 1 BP 58P EP 58P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 020LV UT WOS:000235911800171 ER PT J AU Unno, T Sakamoto, T Matsuyama, H Yamada, M Wess, J Komori, S AF Unno, T Sakamoto, T Matsuyama, H Yamada, M Wess, J Komori, S TI Membrane potential and current responses to carbachol in longitudinal smooth muscle cells of mice ileum genetically lacking M-2 or M-3 subtype of muscarinic receptors SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 79th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 08-10, 2006 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Gifu Univ, Dept Vet Med, Pharmacol Lab, Gifu 5011193, Japan. Gifu Univ, United Grad Sch, Dept Pathogen Vet Med, Gifu 5011193, Japan. RIKEN, Brain Sci Inst, Wako, Saitama 3510198, Japan. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2006 VL 100 SU 1 BP 121P EP 121P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 020LV UT WOS:000235911800417 ER PT J AU Ide, S Minami, M Uhl, GR Ishihara, K Sora, I Ikeda, K AF Ide, S Minami, M Uhl, GR Ishihara, K Sora, I Ikeda, K TI (-)-Pentazocine thermal and mechanical antinociception are eliminated and chemical antinociception reduced in mu-opioid receptor knockout mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 79th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 08-10, 2006 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Hiroshima Int Univ, Dept Pharmaceut Sci, Neuropharmacol Lab, Kure 7370112, Japan. Tokyo Inst Psychiat, Tokyo 1568585, Japan. Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sapporo, Hokkaido 0600812, Japan. NIDA, MNB, IRP, Baltimore, MD 21224 USA. Tohoku Univ, Grad Sch Med, Dept Neurosci, Div Psychobiol, Sendai, Miyagi 9808574, Japan. RI Ide, Soichiro/D-5472-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2006 VL 100 SU 1 BP 254P EP 254P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 020LV UT WOS:000235911801397 ER PT J AU Maltsev, VA Vinogradova, TM Lakatta, EG AF Maltsev, VA Vinogradova, TM Lakatta, EG TI The emergence of a general theory of the initiation and strength of the heartbeat SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Review DE cardiac excitation; contractility; pacemaker mechanism; calcium cycling; heart rate regulation ID RABBIT SINOATRIAL NODE; CARDIAC PURKINJE-FIBERS; SINO-ATRIAL NODE; EMBRYONIC STEM-CELLS; RECTIFIER POTASSIUM CURRENT; RAT VENTRICULAR MYOCYTES; SUSTAINED INWARD CURRENT; SPONTANEOUS DIASTOLIC DEPOLARIZATION; INTRACELLULAR CA2+ RELEASE; RETICULUM CALCIUM RELEASE AB Sarcoplasmic reticulum (SR) Ca2+ cycling, that is, the Ca2+ clock, entrained by externally delivered action potentials has been a major focus in ventricular myocyte research for the past 5 decades. In contrast, the focus of pacemaker cell research has largely been limited to membrane-delimited pacemaker mechanisms (membrane clock) driven by ion channels, as the immediate cause for excitation. Recent robust experimental evidence, based on confocal cell imaging, and supported by numerical modeling suggests a novel concept: the normal rhythmic heart beat is governed by the tight integration of both intracellular Ca2+ and membrane clocks. In pacemaker cells the intracellular Ca2+ clock is. manifested by spontaneous, rhythmic submembrane local Ca2+ releases from SR, which are tightly controlled by a high degree of basal and reserve PKA-dependent protein phosphorylation. The Ca2+ releases rhythmically activate Na+/Ca2+ exchange inward currents that ignite action potentials, whose shape and ion fluxes are tuned by the membrane clock which, in turn, sustains operation of the intracellular Ca2+ clock. The idea that spontaneous SR Ca2+ releases initiate and regulate normal automaticity provides the key that reunites pacemaker and ventricular cell research, thus evolving a general theory of the initiation and strength of the heartbeat. C1 NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, Intramural Res Program,NIH, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov FU Intramural NIH HHS NR 220 TC 71 Z9 73 U1 1 U2 14 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2006 VL 100 IS 5 SI SI BP 338 EP 369 DI 10.1254/jphs.CR060018 PG 32 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 058WX UT WOS:000238696400007 PM 16799255 ER PT J AU Bow, DAJ Perry, JL Simon, JD Pritchard, JB AF Bow, DAJ Perry, JL Simon, JD Pritchard, JB TI The impact of plasma protein binding on the renal transport of organic anions SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ASPERGILLUS OCHRACEUS WILH; HUMAN SERUM-ALBUMIN; PERFUSED-RAT-LIVER; OCHRATOXIN-A; PERITUBULAR TRANSPORT; MOLECULAR-CLONING; PROXIMAL TUBULES; ESTRONE SULFATE; PHENOL RED; KIDNEY AB Drugs and xenobiotics bind to plasma proteins with varying degrees of affinity, and the amount of binding has a direct effect on free drug concentration and subsequent pharmacokinetics. Multiple active and facilitative transport systems regulate the excretion of anionic compounds from the blood in excretory and barrier tissues. Assumptions are made about in vivo substrate affinity and route of elimination based on data from plasma protein-free in vitro assays, particularly following expression of cloned transporters. Ochratoxin A ( OTA), a fungal mycotoxin, is a high-affinity substrate for several renal secretory organic anion transporters ( OATs), and literature suggests that this elimination pathway is the route of entry leading to proximal tubule-targeted toxicity. However, OTA is known to bind to several plasma proteins with a high affinity, particularly serum albumin, which may impact elimination. In this study, we have systematically examined the handling of OTA and other organic anions, estrone sulfate ( ES) and methotrexate ( MTX), by OATs in the presence of serum albumin. Increasing concentrations of albumin markedly reduced uptake of OTA by both Xenopus laevis oocytes expressing OATs 1, 3, and 4 and organic anion-transporting polypeptide 1. For all transporters tested, virtually all mediated OTA uptake was eliminated by an albumin concentration equivalent to 10% of that present in the blood plasma. Thus, OTA uptake is dependent on the free substrate concentration and severely limited by binding to human serum albumin. MTX and ES uptake were likewise dependent on free concentration. C1 Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Dept Chem & Biochem, Durham, NC 27706 USA. RP Pritchard, JB (reprint author), Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Mail Drop F1-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM pritcha3@niehs.nih.gov FU Intramural NIH HHS NR 43 TC 24 Z9 25 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2006 VL 316 IS 1 BP 349 EP 355 DI 10.1124/jpet.105.093070 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 995YE UT WOS:000234140400042 PM 16195420 ER PT J AU Carlezon, WA Beguin, C DiNieri, JA Baumann, MH Richards, MR Todtenkopf, MS Rothman, RB Ma, ZZ Lee, DYW Cohen, BM AF Carlezon, WA Beguin, C DiNieri, JA Baumann, MH Richards, MR Todtenkopf, MS Rothman, RB Ma, ZZ Lee, DYW Cohen, BM TI Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ELEMENT-BINDING PROTEIN; NUCLEUS-ACCUMBENS SHELL; FORCED SWIM TEST; PRECIPITATED MORPHINE-WITHDRAWAL; SALVIA-DIVINORUM; DOPAMINE RELEASE; SELF-STIMULATION; COCAINE; DYNORPHIN; CREB AB Endogenous opioids seem to play a critical role in the regulation of mood states. For example, there is accumulating evidence that stimulation of kappa-opioid receptors, upon which the endogenous opioid dynorphin acts, can produce depressive-like behaviors in laboratory animals. Here we examined whether systemic administration of salvinorin A ( SalvA), a potent and highly selective kappa-opioid agonist, would produce depressive-like effects in the forced swim test ( FST) and intracranial self-stimulation ( ICSS) test, which are behavioral models often used to study depression in rats. We extracted, isolated, and purified SalvA from Salvia divinorum plant leaves and examined its effects on behavior in the FST and ICSS test across a range of doses ( 0.125 - 2.0 mg/kg) after systemic ( intraperitoneal) administration. SalvA dose dependently increased immobility in the FST, an effect opposite to that of standard antidepressant drugs. Doses of SalvA that produced these effects in the FST did not affect locomotor activity in an open field. Furthermore, SalvA dose dependently elevated ICSS thresholds, an effect similar to that produced by treatments that cause depressive symptoms in humans. At a dose that caused the depressive-like effects in both the FST and ICSS assays, SalvA decreased extracellular concentrations of dopamine ( DA) within the nucleus accumbens ( NAc), a critical component of brain reward circuitry, without affecting extracellular concentrations of serotonin ( 5-HT). These data provide additional support for the hypothesis that stimulation of brain kappa-opioid receptors triggers depressive-like signs in rats and raise the possibility that decreases in extracellular concentrations of DA within the NAc contribute to these effects. C1 Harvard Univ, Sch Med, McLean Hosp, Behav Genet Lab, Belmont, MA USA. Harvard Univ, Sch Med, McLean Hosp, Mol Pharmacol Lab, Belmont, MA USA. Harvard Univ, Sch Med, McLean Hosp, Bioorgan & Nat Prod Lab, Belmont, MA USA. Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA USA. NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD USA. RP Carlezon, WA (reprint author), McLean Hosp, Dept Psychiat, MRC 217,115 Mill St, Belmont, MA 02478 USA. EM bcarlezon@mclean.harvard.edu RI Richards, Mickey/E-8140-2011 OI Richards, Mickey/0000-0002-1973-5678 FU NCRR NIH HHS [RR 11213]; NIMH NIH HHS [MH 63266] NR 40 TC 214 Z9 218 U1 3 U2 25 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2006 VL 316 IS 1 BP 440 EP 447 DI 10.1124/jpet.105.092304 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 995YE UT WOS:000234140400052 PM 16223871 ER PT J AU Wan, J Ernstgard, L Song, BJ Shoaf, SE AF Wan, J Ernstgard, L Song, BJ Shoaf, SE TI Chlorzoxazone metabolism is increased in fasted Sprague-Dawley rats SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID N-NITROSODIMETHYLAMINE DEMETHYLASE; CYTOCHROME P4502E1; PROTEIN STABILIZATION; CYP2E1 ACTIVITY; INDUCTION; ACETONE; ACTIVATION; HUMANS; PROBE; 2E1 AB Earlier data showed that men fasted for 38 h had a reduced rate of chlorzoxazone metabolism, suggesting a decreased level of cytochrome P450 2E1 (CYP2E1). In contrast, the level of CYP2E1 in fasted rats had been shown to be elevated. In this study, we have investigated whether chlorzoxazone metabolism in fasted rats was changed by determining the pharmacokinetics of chlorzoxazone and its metabolite, 6-hydroxychlorzoxazone (6-OHCZ), as a CYP2E1 probe, and by measuring liver CYP2E1 using immunoblot techniques. Chlorzoxazone was administered by gavage (50 mg kg(-1)) or intravenously (25 mg kg(-1)) to control (nine for oral and three for intravenous) and 24 h-fasted (nine for oral and four for intravenous) male Sprague-Dawley rats. Following sampling of blood through a jugular vein cannula, chlorzoxazone and 6-OHCZ plasma concentrations were measured by HPLC with UV detection. Pharmacokinetic parameters for chlorzoxazone and 6-OHCZ in each treatment group were determined by model fitting and non-compartmental analysis. in parallel with the increased liver CYP2E1 level, the elimination of chlorzoxazone and 6-OHCZ was significantly increased in fasted rats in the oral and the intravenous study. A multiple analysis of variance covariance analysis and a multiple regression analysis revealed a significant correlation between 1/t1/2 and CYP2E1 level and aniline hydroxylase activity. However, the correlation between 1/t1/2 and pentoxyresorufin O-dealkylase, ethoxyresorufin O-dealkylase and erythromycin N-demethylase was not significant. Therefore the contribution of other P450s to chlorzoxazone metabolism seemed to be minor in the concentration range that we tested. In conclusion, fasting rats for 24 h caused a measurable induction of CYP2E1, which produced a significant increase in the rate of chlorzoxazone metabolism and elimination. C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Wan, J (reprint author), Suzhou Med Coll, Affiliated Hosp 2, Hosp 416, Dept Neurol, Chengdu 610051, Sichuang, Peoples R China. EM jwan2@yahoo.com FU Intramural NIH HHS; NIAAA NIH HHS [Z01 AA000036-19] NR 38 TC 11 Z9 11 U1 1 U2 1 PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD JAN PY 2006 VL 58 IS 1 BP 51 EP 61 DI 10.1211/jpp.58.1.0007 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 005PZ UT WOS:000234837600006 PM 16393464 ER PT J AU Jackson, SN Wang, HYJ Yergey, A Woods, AS AF Jackson, SN Wang, HYJ Yergey, A Woods, AS TI Phosphate stabilization of intermolecular interactions SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE phosphate groups; guanidinium groups; electrostatic interactions; dimers; binding energies; heteromerization ID ASSISTED-LASER-DESORPTION/IONIZATION; GAS-PHASE BASICITIES; MASS-SPECTROMETRY; COMPLEXES; PEPTIDES; HETEROMERIZATION; PHOSPHORYLATION; ARGININE AB Receptor heteromerization is an important phenomenon that results from the interaction of epitopes on two receptors. Previous studies have suggested the possibility of Dopamine D-2-NMDA receptors' interaction. We believe that the interaction is through an acidic epitope of the NMDA NR1 subunit (KVNSEEEEEDA) and a basic epitope of the D-2 third intracellular loop (VLRRRRKRVN), which was shown to also interact with the Adenosine A(2)A receptor. In previous work, we highlighted the role of certain amino acid residues, mainly two or more adjacent arginine on one peptide and two or more adjacent glutamate, or aspartate, or a phosphorylated residue on the other in the formation of noncovalent complexes (NCX) between epitopes. In the present work, we use the phosphorylated (KVNSpEEEEEDA), nonphosphorylated (KVNSEEEEEDA) and modified (KVNpSAAAAAAA) forms of the NMDA epitope that possibly interact with the D-2 epitope to investigate the gas-phase stability of the NCXs as a function of the nominal energy given to the NCX ion as it enters the collision cell. In addition to theoretical calculations, the experimental data was used to calculate the stability of each electrostatic complex versus that of the dimer of KVNSpEEEEEDA. Our results demonstrate the importance of the phosphate group in stabilizing molecular interactions and that appreciably higher collision energies are required to completely dissociate any of the three different NCX ions that are formed through electrostatic interaction in comparison to the energy required to dissociate the KVNpSEEEEEDA dimer ion, which is, mainly kept together by hydrogen bonding. This study emphasizes ionic bonds stability and their importance to protein structure as their potent electrostatic attractions can in the gas-phase surpass the :strength of covalent bonds. C1 NIDA, IRP, NIH, Baltimore, MD 21224 USA. NICHD, LCMB, NIH, Bethesda, MD 20892 USA. RP Woods, AS (reprint author), NIDA, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 23 TC 50 Z9 50 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JAN PY 2006 VL 5 IS 1 BP 122 EP 126 DI 10.1021/pr0503578 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 003FX UT WOS:000234668300012 PM 16396502 ER PT J AU Schulze, TG McMahon, FJ Rietschel, M AF Schulze, TG McMahon, FJ Rietschel, M TI Phenotype definition in psychiatric genetics: A framework for systematic genotype-phenotype studies SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Heidelberg, Div Genet Epidemiol Psychiat, Cent Inst Mental Hlth, D-6800 Mannheim, Germany. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RI McMahon, Francis/A-7290-2009; Schulze, Thomas/H-2157-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2006 VL 20 IS 2 BP 110 EP 110 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 050IK UT WOS:000238080700053 ER PT J AU Pietrini, P Ricciardi, E Guazzelli, M Furey, M AF Pietrini, P. Ricciardi, E. Guazzelli, M. Furey, M. TI Neuronal correlates of cholinergic enhancement on cognitive function: In vivo PET and fMRI studies in humans SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Pisa, Lab Clin Biochem & Mol Biol, Pisa, Italy. Univ Pisa, Chair Gen Psychol, Pisa, Italy. NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD USA. RI Furey, Maura/H-5273-2013; Ricciardi, Emiliano/E-6929-2011 OI Ricciardi, Emiliano/0000-0002-7178-9534 NR 0 TC 1 Z9 1 U1 0 U2 1 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2006 VL 20 IS 3 BP 214 EP 214 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 087SI UT WOS:000240762200016 ER PT J AU Bandettini, P AF Bandettini, P. TI Functional MRI in perspective SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Bandettini, Peter/F-5871-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2006 VL 20 IS 4 BP 315 EP 315 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 102LU UT WOS:000241813500010 ER PT J AU Niebauer, RT White, JF Fei, ZZ Grisshammer, R AF Niebauer, Ronald T. White, Jim F. Fei, Zhizhong Grisshammer, Reinhard TI Characterization of monoclonal antibodies directed against the rat neurotensin receptor NTS1 SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article; Proceedings Paper CT 10th Swiss Receptor Workshop CY MAR 12-15, 2006 CL Univ Basel, Pharmacenter, Basel, SWITZERLAND HO Univ Basel, Pharmacenter DE G protein-coupled receptor; Monoclonal Antibody; cocrystallization; neurotensin receptor; antibody receptor complex ID PROTEIN-COUPLED RECEPTOR; YEAST SACCHAROMYCES-CEREVISIAE; LARGE-SCALE PURIFICATION; HIGH-LEVEL EXPRESSION; ESCHERICHIA-COLI; MEMBRANE-PROTEINS; BOVINE RHODOPSIN; SYNTHETIC PEPTIDES; GPCR FUNCTION; K+ CHANNEL AB G protein-coupled receptors (GPCRs) are integral membrane proteins that mediate cellular responses to a variety of ligands and represent major drug targets. Despite their medical importance, detailed structural information is limited because only one GPCR has been crystallized and its structure determined. To develop tools to aid in the formation of well-ordered crystals, we generated monoclonal antibodies with high affinity to the rat neurotensin receptor. All antibodies bound to the C-terminus of the receptor, which may reflect the selection strategy used to identify high-affinity binders. Further characterization revealed that some antibodies bound to the receptor in a sodium chloride sensitive manner, but others did not. Epitope mapping revealed distinct antigenic regions within the receptor C-terminus. Tight binding of Fab fragments to the receptor was verified by size exclusion chromatography. C1 NIDDK, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Grisshammer, R (reprint author), NIDDK, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM rkgriss@helix.nih.gov RI Grisshammer, Reinhard/C-3089-2015 FU Intramural NIH HHS NR 49 TC 6 Z9 6 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PY 2006 VL 26 IS 5-6 BP 395 EP 415 DI 10.1080/10799890600928228 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103BZ UT WOS:000241862000004 PM 17118789 ER PT J AU Bernatsky, SR Cooper, GS Mill, C Ramsey-Goldman, R Clarke, AE Pineau, CA AF Bernatsky, SR Cooper, GS Mill, C Ramsey-Goldman, R Clarke, AE Pineau, CA TI Cancer screening in patients with systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; cancer screening; malignancy ID CERVICAL DYSPLASIA; REVISED CRITERIA; WOMEN; CARE; GUIDELINES; COHORT; CLASSIFICATION; ADHERENCE AB Objective. To examine whether patients with systemic lupus erythernatosus (SLE) undergo cancer screening according to established guidelines, to compare their reported screening practices with information from the general population, and to examine potential predictors of screening within our SLE sample. Methods. We conducted a patient survey of cancer screening practices within the Montreal General Hospital lupus cohort. We compared self-reported frequency of cancer screening to guidelines suggested for the general population, and to figures for cancer screening reported in the general population. We also developed logistic regression models to establish potential predictors of screening for patients with SLE, with cervical cancer screening being the outcome of interest in our primary analyses. Results. Of 48 women aged 50-69, 53% (95% confidence interval, CI: 38-68) had had a mammogram in the past 12 months, compared to 74% (95% CI: 73-75) for similarly aged Quebec women. Of 51 subjects aged 50 and older, only 18% (95% CI: 8-34) reported screening (fecal occult blood check with or without endoscopy) within the recommended time frame, compared to 48% (95% CI: 45-51) for colorectal screening for persons > 50 in the general population. Only 9 of 27 patients with SLE aged less than 30 had Pap tests in the past 12 months (33%, 95% CI: 19-52), compared with a general population rate of 56% (95% CI: 53-59) for similarly aged Quebec women. Our logistic regression model suggested that, among the SLE patients, non-whites, those with lower education, and those with higher disease damage scores were less likely to undergo cervical Pap testing. Conclusion. These data suggest that appropriate cancer screening may be overlooked in patients with SLE. C1 McGill Univ, Ctr Hlth, Montreal Gen Hosp, Res Inst,Dept Rheumatol, Montreal, PQ, Canada. McGill Univ, Ctr Hlth, Montreal Gen Hosp, Div Clin Immunol, Montreal, PQ, Canada. McGill Univ, Ctr Hlth, Montreal Gen Hosp, Div Allergy & Clin Epidemiol, Montreal, PQ, Canada. NIEHS, NIH, Dept Hlth & Human Resources, Durham, NC USA. Northwestern Univ, Dept Med, Div Rheumatol, Chicago, IL 60611 USA. RP Bernatsky, SR (reprint author), 1650 Cedar Ave,Room L10-520, Montreal, PQ H3G 1A4, Canada. FU Intramural NIH HHS; NIAMS NIH HHS [AR02138, AR 48098] NR 25 TC 28 Z9 28 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2006 VL 33 IS 1 BP 45 EP 49 PG 5 WC Rheumatology SC Rheumatology GA 000HE UT WOS:000234451100009 PM 16331804 ER PT J AU Simons-Morton, BG Hartos, JL Leaf, WA Preusser, DF AF Simons-Morton, BG Hartos, JL Leaf, WA Preusser, DF TI The effects of the checkpoints program on parent-imposed driving limits and crash outcomes among Connecticut novice teen drivers at 6-months post-licensure SO JOURNAL OF SAFETY RESEARCH LA English DT Article DE intervention; persuasion; adolescents; parenting ID RESTRICTIONS; PASSENGERS; RISK; PERSISTENCE; PRIVILEGES; RATES AB Introduction: Because crash rates are highly elevated during the first months of licensure, it is advisable for parents to limit teen driving so that teens can gain independent driving experience under less dangerous driving conditions. This report describes the effect of the Checkpoints Program on parent limits on novice teen driving through six months post-licensure. Methods: Nearly one-quarter of all Connecticut teens who obtained a learner's permit over a 9-month period were recruited, providing a final sample of 3,743 who obtained licenses within the next 16 months. Families were randomized to the intervention or comparison condition. Intervention families received by mail a series of persuasive communications related to high-risk teen driving and a parent-teen driving agreement, while on the same schedule comparison families received standard information on driver safety. Results: Families who participated in the Checkpoints Program reported significantly greater limits on teen driving at licensure, 3-months, and 6-months post-licensure. However, there were no differences in reported risky driving behavior, violations, or crashes. Conclusion: This is the first statewide study testing the efficacy of the Checkpoints Program. The results indicate that it is possible to foster modest increases in parental restrictions on teen driving limits during the first six months of licensure using passive persuasive communications, but that the levels of restriction obtained were not sufficient to protect against violations and crashes. (c) 2005 National Safety Council and Elsevier Ltd. All rights reserved. C1 NICHD, Prevent Res Branch, DESPR, Bethesda, MD 20892 USA. Univ N Carolina, Dept Hlth Behav & Adm, Charlotte, NC 28223 USA. Preusser Res Grp Inc, Trumbull, CT 06611 USA. RP Simons-Morton, BG (reprint author), NICHD, Prevent Res Branch, DESPR, 6100 Execut Blvd 7B13M, Bethesda, MD 20892 USA. EM Mortonb@mail.nih.gov; jlhartos@email.uncccedu; wleaf@preussergroup.com; dpreusser@preussergroup.com OI Simons-Morton, Bruce/0000-0003-1099-6617 FU NICHD NIH HHS [1-HD-8-3285] NR 26 TC 13 Z9 13 U1 5 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-4375 J9 J SAFETY RES JI J. Saf. Res. PY 2006 VL 37 IS 1 BP 9 EP 15 DI 10.1016/j.jsr.2005.10.015 PG 7 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 027QT UT WOS:000236431000002 PM 16469334 ER PT J AU Williams, AF Leaf, WA Simons-Morton, BG Hartos, JL AF Williams, Allan F. Leaf, William A. Simons-Morton, Bruce G. Hartos, Jessica L. TI Parents' views of teen driving risks, the role of parents, and how they plan to manage the risks SO JOURNAL OF SAFETY RESEARCH LA English DT Article DE teen driving risks; parent attitudes; driving restrictions; GDL; parenting ID UNITED-STATES; DRIVERS; TEENAGERS; LIMITS AB Problem: There is limited information about how parents view teen driving risks and intend to handle these risks during the licensing process, and how they will respond to graduated licensing provisions. Methods: Parents in Connecticut were interviewed when their teens got their learner's permit. The survey was undertaken when the state did not have a midnight restriction or a passenger restriction. Results: Generally, parents were well aware of teen driving risks, thought parents should be thoroughly involved in the licensing process, and plan to be active participants themselves. Discussion: Parents were concerned about the risk of driving after midnight and already restrict that behavior. However, parents do not seem to see or understand the risks of having even one teen passenger in the vehicle. Impact on Industry: The views and existing practices of parents need to be taken into account in deciding on the provisions of graduated licensing legislation and how to best ensure acceptance and compliance. (c) 2006 National Safety Council and Elsevier Ltd. All rights reserved. C1 Preusser Res Grp Inc, Trumbull, CT 06611 USA. NICHHD, Bethesda, MD 20892 USA. Univ N Carolina, Charlotte, NC 28223 USA. RP Leaf, WA (reprint author), Preusser Res Grp Inc, 7100 Main St, Trumbull, CT 06611 USA. EM wleaf@preussergroup.com OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 18 TC 29 Z9 29 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-4375 J9 J SAFETY RES JI J. Saf. Res. PY 2006 VL 37 IS 3 BP 221 EP 226 DI 10.1016/j.jsr.2006.04.002 PG 6 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 081LX UT WOS:000240320200001 PM 16822526 ER PT J AU Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG AF Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG TI Rehabilitation Medicine Summit: Building Research Capacity SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE rehabilitation research; medical; disability; National Institutes of Health; grant funding AB The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The five elements of research capacity that guided the discussions were: 1) researchers; 2) research culture, environment, and infrastructure; 3) funding; 4) partnerships; and 5) metrics. The 100 participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. The small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Summit, multi-organizational initiative is called to pursue the agendas outlined in this report. C1 Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Boston Univ, Hlth & Disabil Res Inst, Boston, MA 02215 USA. NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Pittsburgh, Sch Hlth & Rehabil, Human Engn Res Labs, Pittsburgh, PA 15213 USA. Univ Florida, Coll Publ Hlth & Hlth Profess, Brooks Ctr, Gainesville, FL USA. Powers Pyles Sutter & Verville PC, Washington, DC USA. Univ Texas, Med Branch, Div Rehabil Sci, Galveston, TX 77550 USA. Case Western Reserve Univ, Cleveland, OH USA. Northwestern Univ, Sch Med, Rehabil Inst Chicago, Dept Phys Med & Rehabil, Chicago, IL USA. Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. RP Frontera, WR (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM wfrontera@partners.org NR 3 TC 5 Z9 6 U1 0 U2 0 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PY 2006 VL 29 IS 1 BP 70 EP 81 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 027KG UT WOS:000236413900014 PM 16572568 ER PT J AU Hoggle, LB Michael, MA Houston, SM Ayres, EJ AF Hoggle, LB Michael, MA Houston, SM Ayres, EJ TI Nutriton informatics SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID AMERICAN-DIETETIC-ASSOCIATION; PHYSICIAN ORDER ENTRY; DIGITAL COMPUTER; SYSTEM; FUTURE; MANAGEMENT; COSTS; CARE C1 Hlth Pathways Inc, Gaithersburg, MD 20878 USA. NIH, Ctr Clin, Clin Nutr Serv, Bethesda, MD 20892 USA. RP Hoggle, LB (reprint author), Hlth Pathways Inc, 101 Orchard Ridge Dr, Gaithersburg, MD 20878 USA. EM LHoggle@healthpathways.com NR 64 TC 7 Z9 8 U1 0 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2006 VL 106 IS 1 BP 134 EP 139 DI 10.1016/j.jada.2005.10.025 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 998LZ UT WOS:000234321600022 PM 16390678 ER PT J AU Simonsick, EM Fan, E Fleg, JL AF Simonsick, EM Fan, E Fleg, JL TI Estimating cardiorespiratory fitness in well-functioning older adults: Treadmill validation of the Long Distance Corridor Walk SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aerobic fitness testing; validation; walking test; aged ID PEAK OXYGEN-CONSUMPTION; HEALTHY-ADULTS; HEART-FAILURE; EXERCISE; PERFORMANCE; WOMEN; INDEPENDENCE; CAPACITY; 6-MINUTE; DISEASE AB OBJECTIVES: To determine criterion validity of the 400-m walk component of the Long Distance Corridor Walk (LDCW) and develop equations for estimating peak oxygen consumption (VO2) from 400-m time and factors intrinsic to test performance (e.g., heart rate (HR) and systolic blood pressure (SBP) response) in older adults. DESIGN: Cross-sectional validation study. SETTING: Gerontology Research Center, National Institute on Aging, Baltimore, Maryland. PARTICIPANTS: Healthy volunteers (56 men and 46 women) aged 60 to 91 participating in the Baltimore Longitudinal Study of Aging between August 1999 and July 2000. MEASUREMENTS: The LDCW, consisting of a 2-minute walk followed immediately by a 400-m walk "done as quickly as possible" over a 20-m course was administered the day after maximal treadmill testing. HR and SBP were measured before testing and at the end of the 400-m walk. Weight, height, activity level, perceived effort, and stride length were also acquired. RESULTS: Peak VO2 ranged from 12.2 to 31.1 mL oxygen/kg per minute, and 400-m time ranged from 2 minutes 52 seconds to 6 minutes 18 seconds. Correlation between 400-m time and peak VO2 was -0.79. The estimating equation from linear regression included 400-m time (partial coefficient of determination (R-2)=0.625), long versus short stride (partial R-2=0.090), ending SBP (partial R-2=0.019), and a correction factor for fast 400-m time (< 240 seconds; partial R-2=0.020) and explained 75.5% of the variance in peak VO2 (correlation coefficient=0.87). CONCLUSION: A 400-m walk performed as part of the LDCW provides a valid estimate of peak VO2 in older adults. Incorporating low-cost, safe assessments of fitness in clinical and research settings can identify early evidence of physical decline and individuals who may benefit from therapeutic interventions. C1 NIA, ASTRA, Clin Res Branch, Baltimore, MD 21225 USA. NIA, Cardiovasc Sci Lab, Baltimore, MD 21225 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. RP Simonsick, EM (reprint author), NIA, ASTRA, Clin Res Branch, Harbor Hosp 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM simonsickel@mail.nih.gov FU Intramural NIH HHS NR 28 TC 71 Z9 72 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2006 VL 54 IS 1 BP 127 EP 132 DI 10.1111/j.1532-5415.2005.00530.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 999QF UT WOS:000234404300019 PM 16420209 ER PT J AU Zeng, QT Tse, T AF Zeng, QT Tse, T TI Exploring and developing consumer health vocabularies SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID MEDICAL INFORMATICS; E-MAIL; COMMUNICATION; DESIGN; IMPACT; VIEWS; UMLS AB Laypersons ("consumers") often have difficulty finding, understanding, and acting on health information due to gaps in their domain knowledge. Ideally, consumer health vocabularies (CHVs) would reflect the different ways consumers express and think about health topics, helping to bridge this vocabulary gap. However, despite the recent research on mismatches between consumer and professional language (e.g., lexical, semantic, and explanatory), there have been few systematic efforts to develop and evaluate CHVs. This paper presents the point of view that CHV development is practical and necessary for extending research on informatics-based tools to facilitate consumer health information seeking, retrieval, and understanding. In support of the view, we briefly describe a distributed, bottom-up approach for (1) exploring the relationship between common consumer health expressions and professional concepts and (2) developing an open-access, preliminary (draft) "first-generation" CHV. While recognizing the limitations of the approach (e.g., not addressing psychosocial and cultural factors), we suggest that such exploratory research and development will yield insights into the nature of consumer health expressions and assist developers in creating tools and applications to support consumer health information seeking. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Decis Syst Grp, Boston, MA 02115 USA. Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Decis Syst Grp, Thorn 309,75 Francis St, Boston, MA 02115 USA. EM qzeng@dsg.bwh.harvard.edu FU Intramural NIH HHS; NLM NIH HHS [R01 LM007222, R01 LM07222] NR 40 TC 80 Z9 81 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN-FEB PY 2006 VL 13 IS 1 BP 24 EP 29 DI 10.1197/jamia.M1761 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 004AI UT WOS:000234724000005 PM 16221948 ER PT J AU Demner-Fushman, D Few, B Hauser, SE Thoma, G AF Demner-Fushman, D Few, B Hauser, SE Thoma, G TI Automatically identifying health outcome information in MEDLINE records SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CLINICAL QUESTIONS; STRATEGIES; EDUCATION; RELEVANCE; ARTICLES; MEDICINE; NEEDS AB Objective: Understanding the effect of a given intervention on the patient's health outcome is one of the key elements in providing optimal patient care. This study presents a methodology for automatic identification of outcomes-related information in medical text and evaluates its potential in satisfying clinical information needs related to health care outcomes. Design: An annotation scheme based on an evidence-based medicine model for critical appraisal of evidence was developed and used to annotate 633 MEDLINE citations. Textual, structural, and meta-information features essential to outcome identification were learned from the created collection and used to develop an automatic system. Accuracy of automatic outcome identification was assessed in an intrinsic evaluation and in an extrinsic evaluation, in which ranking of MEDLINE search results obtained using PubMed Clinical Queries relied on identified outcome statements. Measurements: The accuracy and positive predictive value of outcome identification were calculated. Effectiveness of the outcome-based ranking was measured using mean average precision and precision at rank 10. Results: Automatic outcome identification achieved 88% to 93% accuracy, The positive predictive value of individual sentences identified as outcomes ranged from 30% to 37%. Outcome-based ranking improved retrieval accuracy, tripling mean average precision and achieving 389% improvement in precision at rank 10. Conclusion: Preliminary results in outcome-based document ranking show potential validity of the evidence-based medicine-model approach in timely delivery of information critical to clinical decision support at the point of service. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Commun Engn Branch, NIH, Bethesda, MD 20894 USA. RP Demner-Fushman, D (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Commun Engn Branch, NIH, Bethesda, MD 20894 USA. EM ddemner@mail.nih.gov NR 47 TC 10 Z9 10 U1 1 U2 4 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN-FEB PY 2006 VL 13 IS 1 BP 52 EP 60 DI 10.1197/jamia.M1911 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 004AI UT WOS:000234724000008 PM 16221937 ER PT J AU Humphrey, SM Rogers, WJ Kilicoglu, H Demner-Fushman, D Rindflesch, TC AF Humphrey, SM Rogers, WJ Kilicoglu, H Demner-Fushman, D Rindflesch, TC TI Word sense disambiguation by selecting the best semantic type based on journal descriptor indexing: Preliminary experiment SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY LA English DT Article ID DOCUMENTS; TEXT AB An experiment was performed at the National Library of Medicine (R) (NLM (R)) in word sense disambiguation (WSD) using the Journal Descriptor Indexing (JDI) methodology. The motivation is the need to solve the ambiguity problem confronting NLM's MetaMap system, which maps free text to terms corresponding to concepts in NLM's Unified Medical Language System (R) (UMLS (R)) Metathesaurus(D. If the text maps to more than one Metathesaurus concept at the same high confidence score, MetaMap has no way of knowing which concept is the correct mapping. We describe the JDI methodology, which is ultimately based on statistical associations between words in a training set of MEDLINE (R) citations and a small set of journal descriptors (assigned by humans to journals per se) assumed to be inherited by the citations. JDI is the basis for selecting the best meaning that is correlated to UMLS semantic types (STs) assigned to ambiguous concepts in the Metathesaurus. For example, the ambiguity transport has two meanings: "Biological Transport" assigned the ST Cell Function and "Patient transport" assigned the ST Health Care Activity. A JDI-based methodology can analyze text containing transport and determine which ST receives a higher score for that text, which then returns the associated meaning, presumed to apply to the ambiguity itself. We then present an experiment in which a baseline disambiguation method was compared to four versions of JDI in disambiguating 45 ambiguous strings from NLM's WSD Test Collection. Overall average precision for the highest-scoring JDI version was 0.7873 compared to 0.2492 for the baseline method, and average precision for individual ambiguities was greater than 0.90 for 23 of them (51%), greater than 0.85 for 24 (53%), and greater than 0.65 for 35 (79%). On the basis of these results, we hope to improve performance of JDI and test its use in applications. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. EM humphrey@nlm.nih.gov; wrogers@nlm.nih.gov; halil@nlm.nih.gov; dina_demner@nlm.nih.gov; tcr@nlm.nih.gov FU Intramural NIH HHS [NIH0010104141] NR 46 TC 40 Z9 40 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1532-2882 EI 1532-2890 J9 J AM SOC INF SCI TEC JI J. Am. Soc. Inf. Sci. Technol. PD JAN 1 PY 2006 VL 57 IS 1 BP 96 EP 113 DI 10.1002/asi.20257 PG 18 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 998MZ UT WOS:000234324300010 PM 19890434 ER PT J AU Sachdev, V Aletras, AH Padmanabhan, S Sidenko, S Rao, YN Brenneman, CL Shizukuda, Y Lie, GR Vincent, PS Waclaviw, MA Arai, AE AF Sachdev, Vandana Aletras, Anthony H. Padmanabhan, Sriram Sidenko, Stanislav Rao, Yesoda N. Brenneman, Cynthia L. Shizukuda, Yukitaka Lie, Glenn R. Vincent, Pamela S. Waclaviw, Myron A. Arai, Andrew E. TI Myocardial strain decreases with increasing transmurality of infarction: A Doppler echocardiographic and magnetic resonance correlation study SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID CORONARY-ARTERY-DISEASE; CONTRACTILE FUNCTION; STUNNED MYOCARDIUM; SYSTOLIC FUNCTION; QUANTIFICATION; ISCHEMIA; EXTENT; DEFORMATION; VIABILITY AB Background: Regional abnormalities in myocardial systolic function can be detected with myocardial strain measurements derived from Doppler tissue echocardiography. We studied longitudinal strain measurements in patients with evidence of myocardial infarction by cardiac magnetic resonance imaging to determine whether end-systolic strain could identify the severity of the infarction. Methods: A total of 20 patients with chronic myocardial infarctions and 10 healthy volunteers underwent 2-dimensional echocardiography and cardiac magnetic resonance with delayed gadolinium (Gd) gadopentetate dimeglumine (DTPA) contrast hyperenhancement. Delayed Gd hyperenhancement was graded using the following scale: 0 = none, 1 = less than 25%, 2 = 26% to 50%, 3 = 51% to 75%, and 4 greater than 75%. Results: There was a progressive decrease in peak systolic strain in the infarct segments as the transmural extent of infarction increased. When compared with the peak systolic strain in remote segments without evidence of infarction (- 19.7 +/- 0.9), the strain was significantly lower in segments with greater than 25% Gd hyperenhancement (grade 2, -14.8 +/- 1.1, P =.001; grade 3, -12.9 +/- 2.1, P =.001; grade 4, -9.1 +/- 2.0, P <.001). Conclusions: In patients with chronic myocardial infarctions, strain measurements with echocardiography show a graded response of decreasing regional strain in segments with increasing transmural extent of infarction defined by Gd hyperenhancement. C1 NHLBI, Echocardiog Lab, Cardiovasc Branch, Lab Cardiac Energet,NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. GE Healthcare, Milwaukee, WI USA. RP Sachdev, V (reprint author), NHLBI, Echocardiog Lab, Cardiovasc Branch, Lab Cardiac Energet,NIH, 10 Ctr Dr,MSC-1454, Bethesda, MD 20892 USA. EM sachdevv@nhlbi.nih.gov OI Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS NR 21 TC 19 Z9 19 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JAN PY 2006 VL 19 IS 1 BP 34 EP 39 DI 10.1016/j.echo.2005.07.013 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 138AD UT WOS:000244333900007 PM 16423667 ER PT J AU Shlipak, MG Fyr, CLW Chertow, GM Harris, TB Kritchevsky, SB Tylavsky, FA Satterfield, S Cummings, SR Newman, AB Fried, LF AF Shlipak, Michael G. Fyr, Christina L. Wassel Chertow, Glenn M. Harris, Tamara B. Kritchevsky, Stephen B. Tylavsky, Frances A. Satterfield, Suzanne Cummings, Steven R. Newman, Anne B. Fried, Linda F. TI Cystatin C and mortality risk in the elderly: The health, aging, and body composition study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CORONARY-HEART-DISEASE; EARLY RENAL IMPAIRMENT; OLDER-ADULTS; KIDNEY-FUNCTION; CARDIOVASCULAR EVENTS; CLINICAL EVALUATION; MARKER; INSUFFICIENCY; CREATININE AB Kidney dysfunction is known to decrease life expectancy in the elderly. Cystatin C is a novel biomarker of kidney function that may have prognostic utility in older adults. The association of cystatin C with mortality was evaluated in a biracial cohort of black and white ambulatory elderly and compared with that of serum creatinine concentrations. The Health, Aging and Body Composition study is a cohort of well-functioning elderly that was designed to evaluate longitudinal changes in weight, body composition, and function. A total of 3075 participants who were aged 70 to 79 yr and had no disability were recruited at sites in Memphis, TN, and Pittsburgh, PA, between April 1997 and June 1998 with a follow-up of 6 yr. At entry, the mean cystatin C was 1.05 mg/L and the mean creatinine was 1.06 mg/dl. After 6 yr of follow-up, 557 participants had died. The mortality rates in each ascending cystatin C quintile were 1.7, 2.7, 2.9, 3.1, and 5.4%/yr. After adjustment for demographic risk factors, comorbid health conditions, and inflammatory biomarkers (C-reactive protein, IL-6. and TNF-alpha), each quintile of cystatin C was significantly associated with increased mortality risk compared with the lowest: Hazard ratios (HR; 95% confidence intervals) quintile 1, -1.0 (referent); quintile 2, -1.74 (1.21 to 2.50); quintile 3, -1.51 (1.05 to 2.18); quintile 4, -1.49 (1.04 to 2.13); and quintile 5, -2.18 (1.53 to 3.10). These associations did not differ by gender or race. Results were consistent for cardiovascular and other-cause mortality, but not cancer mortality. Creatinine quintiles were not associated with mortality after multivariate adjustment (HR: 1.0 [referent], 1.00 [0.72 to 1.39], 0.95 [0.68 to 1.32], 1.11 [0.79 to 1.57], 1.16 [0.86 to 1.58]). Cystatin C is a strong, independent risk factor for mortality in the elderly. Future studies should investigate whether cystatin C has a role in clinical medicine. C1 Univ Calif San Francisco, Gen Internal Med Sect, VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. Wake Forest Bowman Gray Sch Med, J Paul Sticht Ctr Aging & Rehabil, Winston Salem, NC USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. Calif Pacific Med Ctr, Inst Res, San Francisco, CA USA. Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, Gen Internal Med Sect, VA Med Ctr, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NHLBI NIH HHS [R01 HL073208-01]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 27 TC 137 Z9 141 U1 0 U2 4 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2006 VL 17 IS 1 BP 254 EP 261 DI 10.1681/ASN.2005050545 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 106SB UT WOS:000242120000032 PM 16267155 ER PT J AU Marill, JL Miller, N Kitendaugh, P AF Marill, JL Miller, N Kitendaugh, P TI The MedlinePlus public user interface: studies of design challenges and opportunities SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Question: What are the challenges involved in designing, modifying, and improving a major health information portal that serves over sixty million page views a month? Setting: MedlinePlus, the National Library of Medicine's (NLM's) consumer health Website, is examined. Method: Challenges are presented as six "studies," which describe selected design issues and how NLM staff resolved them. Main Result: Improving MedlinePlus is an iterative process. Changes in the public user interface are ongoing, reflecting Web design trends, usability testing recommendations, user survey results, new technical requirements, and the need to grow the site in an orderly way. Conclusion: Testing and analysis should accompany Website design modifications. New technologies may enhance a site but also introduce problems. Further modifications to MedlinePlus will be informed by the experiences described here. C1 Natl Lib Med, Publ Serv Div, Bethesda, MD 20894 USA. EM jmarill@loc.gov; naomi_miller@nlm.nih.gov; paula_kitendaugh@nlm.nih.gov NR 18 TC 9 Z9 9 U1 1 U2 3 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2006 VL 94 IS 1 BP 30 EP 40 PG 11 WC Information Science & Library Science SC Information Science & Library Science GA 005PS UT WOS:000234836900005 PM 16404467 ER PT J AU Fay, MP Lee, JH AF Fay, MP Lee, JH TI Measuring agreement between two statistics with applications to age standardization SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Article DE concordance correlation coefficient; mean-median correlation; random marginal agreement coefficient; rater comparison; standardization; vital rates ID RATES AB We detail a general method for measuring agreement between two statistics. An application is two ratios of directly standardized rates which differ only by the choice of the standard. If the statistics have a high value for the coefficient of agreement then the expected squared difference between the statistics is small relative to the variance of the average of the two statistics, and inferences vary little by changing statistics. The estimation of a coefficient of agreement between two statistics is not straightforward because there is only one pair of observed values, each statistic calculated from the data. We introduce estimators of the coefficient of agreement for two statistics and discuss their use, especially as applied to functions of standardized rates. C1 NIAID, Bethesda, MD 20892 USA. Univ S Florida, Tampa, FL USA. RP Fay, MP (reprint author), NIAID, 6700B Rockledge Dr,MSC 7609, Bethesda, MD 20892 USA. EM mfay@niaid.nih.gov RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 14 TC 2 Z9 2 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0964-1998 J9 J ROY STAT SOC A STA JI J. R. Stat. Soc. Ser. A-Stat. Soc. PY 2006 VL 169 BP 81 EP 96 DI 10.1111/j.1467-985X.2005.00379.x PN 1 PG 16 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 010CM UT WOS:000235164500006 ER PT J AU Leung, DHY Qin, J AF Leung, DHY Qin, J TI Analysing survey data with incomplete responses by using a method based on empirical likelihood SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE auxiliary information; empirical likelihood; missing values; surrogate; survey ID PARENT-CHILD AGREEMENT; AUXILIARY INFORMATION; REGRESSION-MODELS; LOGISTIC-MODELS; RELIABILITY; DISORDERS; INTERVIEW AB In many surveys, missing response is a common problem. As an example, Zahner, Jacobs, Freeman and Trainor analysed data from a study of child psychopathology in the State of Connecticut, USA. In that study, the response variable, psychopathology, was inferred from questions that were addressed to teachers of the children and was subject to a high level of missingness. However, the missing responses were supplemented by surrogate information that was provided by the parents and/or the primary care providers of the children. In such a situation, it is conceivable that the supplemental information can be used to recover some of the information that has been lost in the cases with missing response. This paper considers a method using empirical likelihood. Empirical likelihood is well known in providing nonparametric inference. But its application has largely been confined to complete-data situations. The method proposed exploits the semiparametric nature of empirical likelihood. The method gives consistent estimates if the cases with non-missing responses form a random sample of the population. In large samples, the method behaves similarly to a regression estimate that is applied to estimating equations. The method is easy to implement with standard statistical packages. In a small sample study, the method was found to give favourable results, when compared with existing methods. C1 Singapore Management Univ, Sch Econ & Social Sci, Singapore, Singapore. NIAID, Bethesda, MD 20892 USA. RP Leung, DHY (reprint author), Singapore Management Univ, Sch Econ & Social Sci, Singapore, Singapore. EM denisleung@smu.edu.sg RI LEUNG, Denis Heng Yan/D-1439-2009 NR 27 TC 2 Z9 2 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2006 VL 55 BP 379 EP 396 DI 10.1111/j.1467-9876.2006.00542.x PN 3 PG 18 WC Statistics & Probability SC Mathematics GA 043UC UT WOS:000237626700006 ER PT J AU Peddada, SD Haseman, JK Tan, XF Travlos, G AF Peddada, Shyamal D. Haseman, Joseph K. Tan, Xiaofeng Travlos, Greg TI Tests for a simple tree order restriction with application to dose-response studies SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Dunnett's test; isotonic regression; order restrictions; Williams's test AB We propose 'Dunnett-type' test procedures to test for simple tree order restrictions on the means of p independent normal populations. The new tests are based on the estimation procedures that were introduced by Hwang and Peddada and later by Dunbar, Conaway and Peddada. The procedures proposed are also extended to test for 'two-sided' simple tree order restrictions. For non-normal data, nonparametric versions based on ranked data are also suggested. Using computer simulations, we compare the proposed test procedures with some existing test procedures in terms of size and power. Our simulation study suggests that the procedures compete well with the existing procedures for both one-sided and two-sided simple tree alternatives. In some instances, especially in the case of two-sided alternatives or for non-normally distributed data, the gains in power due to the procedures proposed can be substantial. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. PICC Life Insurance Co Ltd, Beijing, Peoples R China. RP Peddada, SD (reprint author), NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 NR 14 TC 6 Z9 6 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2006 VL 55 BP 493 EP 506 DI 10.1111/j.1467-9876.2006.00549.x PN 4 PG 14 WC Statistics & Probability SC Mathematics GA 075OP UT WOS:000239895400005 ER PT J AU Susil, RC Menard, C Krieger, A Coleman, JA Camphausen, K Choyke, P Fichtinger, G Whitcomb, LL Coleman, CN Atalar, E AF Susil, RC Menard, C Krieger, A Coleman, JA Camphausen, K Choyke, P Fichtinger, G Whitcomb, LL Coleman, CN Atalar, E TI Transrectal prostate biopsy and fiducial marker placement in a standard 1.5T magnetic resonance imaging scanner SO JOURNAL OF UROLOGY LA English DT Article DE magnetic resonance imaging; prostate; prostatic neoplasms; biopsy; radiology; interventional ID CANCER; REGISTRATION; BRACHYTHERAPY; INTERVENTIONS; RADIATION; GUIDANCE; SYSTEM AB Purpose: We investigated the accuracy and feasibility of a system that provides transrectal needle access to the prostate concurrent with 1.5 Tesla MRI which previously has not been possible. Materials and Methods: In 5 patients with previously diagnosed prostate cancer, MRI guided intraprostatic placement of gold fiducial markers (4 procedures) and/or prostate biopsy (3 procedures) was performed using local anesthesia. Results: Mean procedure duration was 76 minutes and all patients tolerated the intervention well. Procedure related adverse events included self-limited hematuria and hematochezia following 3 of 8 procedures (all resolved in less than 1 week). Mean needle placement accuracy was 1.9 mm for the fiducial marker placement studies and 1.8 mm for the biopsy procedures. Mean fiducial marker placement accuracy was 4.8 mm and the mean fiducial marker placement accuracy transverse to the needle direction was 2.6 mm. All patients who underwent the procedure were able to complete their course of radiotherapy without delay or complication. Conclusions: While studies of clinical usefulness are warranted, transrectal 1.5 T MRI guided prostate biopsy and fiducial marker placement is feasible using this system, providing new opportunities for image guided diagnostic and therapeutic prostate interventions. C1 Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Comp Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mech Engn, Baltimore, MD 21205 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, DHHS, Bethesda, MD USA. Bilkent Univ, Dept Elect & Elect Engn, Ankara, Turkey. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. RP Atalar, E (reprint author), Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Traylor Bldg Room 330,720 Rutland Ave, Baltimore, MD 21205 USA. EM eatalar@jhu.edu RI Atalar, Ergin/D-3184-2012; OI Atalar, Ergin/0000-0002-6874-6103; Coleman, Jonathan/0000-0002-6428-7835 FU NIBIB NIH HHS [R01 EB002963, R01 EB002963-05] NR 13 TC 52 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2006 VL 175 IS 1 BP 113 EP 120 DI 10.1016/S0022-5347(05)00065-0 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 994AD UT WOS:000234001100028 PM 16406885 ER PT J AU Kaplan, SA McConnell, JD Roehrborn, CG Meehan, AG Lee, MW Noble, WR Kusek, JW Nyberg, LM AF Kaplan, SA McConnell, JD Roehrborn, CG Meehan, AG Lee, MW Noble, WR Kusek, JW Nyberg, LM CA MTOPS Res Grp TI Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 MI or greater SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic hyperplasia; lower urinary tract symptoms; doxazosin; finasteride; combination therapy AB Purpose: We examined data from the Medical Therapy of Prostatic Symptoms trial to determine the relationship between baseline TPV and the effect of medical therapy in men with LUTS secondary to BPH. Materials and Methods: A total of 3,047 patients with LUTS were randomized to placebo, 4 to 8 mg doxazosin, 5 mg finasteride or the combination of doxazosin and finasteride. Average treatment duration was 4.5 years The primary outcome was time to overall clinical progression of BPH, defined as a confirmed 4 point or greater increase in AUA SS, acute urinary retention, incontinence, renal insufficiency or recurrent urinary tract infection. Secondary outcomes were the need for invasive therapy for BPH, and changes in AUA SS and the maximum urinary flow rate with time. TPV was measured by transrectal ultrasound at baseline and study end. Results: In patients with a small prostate (baseline TPV less than 25 ml) combination therapy was no better than doxazosin alone for decreasing the risk of clinical progression of BPH and need for invasive therapy as well as improving AUA SS and the maximum urinary flow rate. However, in patients with moderate size (25 to less than 40 ml) or enlarged (40 ml or greater) glands combination therapy led to a clinical benefit in these outcomes that was superior to that of doxazosin or finasteride. Conclusions: Combination therapy with doxazosin and finasteride led to a greater decrease in the risk of clinical progression of BPH than either drug alone in patients with LUTS with a baseline TPV of 25 ml or greater. C1 Columbia Univ, Med Ctr, New York, NY 10032 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Merck Res Labs, Rahway, NJ USA. George Washington Univ, Bethesda, MD USA. NIDDKD, Bethesda, MD 20892 USA. RP Kaplan, SA (reprint author), Columbia Univ, Med Ctr, Herbert Irving Pavil,11th Floor,Room 1174,161 Ft, New York, NY 10032 USA. EM sk46@columbia.edu FU NIDDK NIH HHS [U01 DK49961, U01 DK 49912, U01 DK41418, U01 DK46416, U01 DK46429, U01 DK46431, U01 DK46437, U01 DK46468, U01 DK46472, U01 DK49880, U01 DK49921, U01 DK49951, U01 DK49954, U01 DK49960, U01 DK49963, U01 DK49964, U01 DK49971, U01 DK49977, U01 DK49980] NR 3 TC 80 Z9 94 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2006 VL 175 IS 1 BP 217 EP 220 DI 10.1016/S0022-5347(05)00041-8 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 994AD UT WOS:000234001100060 PM 16406915 ER PT J AU Seaman, S Logsdon, D Graff-Cherry, C Croix, BS AF Seaman, S. Logsdon, D. Graff-Cherry, C. Croix, B. St. TI Unraveling the tumor endothelial transcriptome by gene expression profiling SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract CT 24th Conference of the European-Society-for-Microcirculation CY AUG 30-SEP 02, 2006 CL Amsterdam, NETHERLANDS SP European Soc Microcirculat C1 NCI, CCR, Genet Program, Frederick, MD 21701 USA. RI Seaman, Steven/A-2755-2013 OI Seaman, Steven/0000-0003-3349-3334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PY 2006 VL 43 SU 1 BP 10 EP 10 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 087JT UT WOS:000240739400023 ER PT J AU Park, MS Kim, Y Kang, MS Oh, SY Cho, DY Shin, NS Kim, DY AF Park, MS Kim, Y Kang, MS Oh, SY Cho, DY Shin, NS Kim, DY TI Disseminated transmissible venereal tumor in a dog SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article DE cog; LINE; lysozyme; metastasis; PCR; transmissible venereal tumor ID CELLS AB Transmissible venereal tumor (TVT) is a well-documented transplantable tumor in dogs, with no breed or sex predilection and a low metastatic rate. In this report, a 2-year-old intact female Mastiff that had numerous, rapidly growing masses throughout the subcutis mainly at the dorsal body plane, the caudal half of the ventral abdomen, and around the vulva was euthanized due to poor prognosis. Neoplastic nodules similar to those seen in the subcutis were also noted in the lung, anterior mediastinum, liver, spleen, kidney, and superficial and deep lymph nodes in both abdominal and thoracic cavities. The neoplastic nodules from the subcutis as well as metastatic foci revealed similar cytologic and histologic features, which were consistent with canine TVT. By immunohistochemical staining, the neoplastic cells were positive for lysozyme and vimentin but were negative for cytokeratin, desmin, CD3, and CD79a. The diagnosis of the TVT was further supported by the identification and analysis of long interspersed nuclear elements (LINE) from paraffin-embedded tumor tissue. This case is a rare example of TVT with multiorgan metastasis. In this case, the polymerase chain reaction technique was useful in differential diagnosis of canine round cell tumors because this technique can be applied in retrospective as well as future study. C1 Seoul Natl Univ, Coll Vet Med, Dept Vet Pathol, Seoul 151742, South Korea. Seoul Natl Univ, Coll Vet Med, Dept Wildlife Med, Seoul 151742, South Korea. Seoul Natl Univ, Sch Agr Biotechnol, Seoul 151742, South Korea. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Louisiana State Univ, Dept Pathobiol, Baton Rouge, LA 70803 USA. RP Kim, DY (reprint author), Seoul Natl Univ, Coll Vet Med, Dept Vet Pathol, San 56-1, Seoul 151742, South Korea. RI Pepper, John/O-1662-2013 OI Pepper, John/0000-0001-9888-0437 NR 14 TC 20 Z9 23 U1 1 U2 2 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD JAN PY 2006 VL 18 IS 1 BP 130 EP 133 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 006CC UT WOS:000234871700023 PM 16566273 ER PT J AU Ojeda, S Senkevich, TG Moss, B AF Ojeda, S Senkevich, TG Moss, B TI Entry of vaccinia virus and cell-cell fusion require a highly conserved cysteine-rich membrane protein encoded by the A16L gene SO JOURNAL OF VIROLOGY LA English DT Article ID INTRACELLULAR MATURE VIRIONS; POXVIRUSES; IDENTIFICATION; MORPHOGENESIS; COMPONENT; PRODUCT; PATHWAY; MODE AB The vaccinia virus A16L open reading frame encodes a 378-amino-acid protein with a predicted C-terminal transmembrane domain and 20 invariant cysteine residues that is conserved in all sequenced members of the poxvirus family. The A16 protein was expressed late in infection and incorporated into intracellular virus particles with the N-terminal segment of the protein exposed on the surface. The cysteine residues were disulfide bonded via the poxvirus cytoplasmic redox system. Unsuccessful attempts to isolate a mutant virus with the A16L gene deleted suggested that the protein is essential for replication. To study the role of the A16 protein, we made a recombinant vaccinia virus that has the Escherichia coli lac operator system regulating transcription of the A16L gene. In the absence of inducer, A16 synthesis was repressed and plaque size and virus yield were greatly reduced. Nevertheless, virus morphogenesis occurred and normal-looking intracellular and extracellular virus particles formed. Purified virions made in the presence and absence of inducer were indistinguishable, though the latter had 60- to 100-fold-lower specific infectivity. A16-deficient virions bound to cells, but their cores did not penetrate into the cytoplasm. Furthermore, A16-deficient virions were unable to induce low-pH-triggered syncytium formation. The phenotype of the inducible A16L mutant was similar to those of mutants in which synthesis of the A21, A28, 112, or L5 membrane protein was repressed, indicating that at least five conserved viral proteins are required for entry of poxviruses into cells as well as for cell-cell fusion. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 33 TC 61 Z9 64 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2006 VL 80 IS 1 BP 51 EP 61 DI 10.1128/JVI.80.1.51-61.2006 PG 11 WC Virology SC Virology GA 009DO UT WOS:000235091700004 PM 16352530 ER PT J AU Oh, J Chang, KW Hughes, SH AF Oh, J Chang, KW Hughes, SH TI Mutations in the U5 sequences adjacent to the primer binding site do not affect tRNA cleavage by Rous sarcoma virus RNase H but do cause aberrant integrations in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; TYPE-1 POLYPURINE TRACT; STRAND DNA-SYNTHESIS; RETROVIRAL DNA; REVERSE-TRANSCRIPTASE; NUCLEOTIDE-SEQUENCE; CONCERTED INTEGRATION; PROTEIN CLEAVES; CIRCLE JUNCTION; AIDS VIRUS AB In most retroviruses, the first nucleotide added to the tRNA primer becomes the right end of the U5 region in the right long terminal repeat (LTR); the removal of this tRNA primer by RNase H defines the right end of the linear double-stranded DNA. Most retroviruses have two nucleotides between the 5' end of the primer binding site (PBS) and the CA dinucleotide that will become the end of the integrated provirus. However, human immunodeficiency virus type 1 (HIV-1) has only one nucleotide at this position, and HIV-2 has three nucleotides. We changed the two nucleotides (TT) between the PBS and the CA dinucleotide of the Rous sarcoma virus (RSV)-derived vector RSVP(A)Z to match the HIV-1 sequence (G) and the HIV-2 sequence (GGT), and we changed the CA dinucleotide to TC. In all three mutants, RNase H removes the entire tRNA primer. Sequence analysis of RSVP(HIV2) proviruses suggests that RSV integrase can remove three nucleotides from the U5 LTR terminus of the linear viral DNA during integration, although this mutation significantly reduced virus titer, suggesting that removing three nucleotides is inefficient. However, the results obtained with RSVP(HIV1) and RSVP(CATC) show that RSV integrase can process and integrate the normal U3 LTR terminus of a linear DNA independently of an aberrant U5 LTR terminus. The aberrant end can then be joined to the host DNA by unusual processes that do not involve the conserved CA dinucleotide. These unusual events generate either large duplications or, less frequently, deletions in the host genomic DNA instead of the normal 5- to 6-base duplications. C1 NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539,Rm 130A, Ft Detrick, MD 21702 USA. EM Hughes@ncifcrf.gov FU Intramural NIH HHS NR 33 TC 18 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2006 VL 80 IS 1 BP 451 EP 459 DI 10.1128/JVI.80.1.451-459.2006 PG 9 WC Virology SC Virology GA 009DO UT WOS:000235091700043 PM 16352569 ER PT J AU Parrish, S Moss, B AF Parrish, S Moss, B TI Characterization of a vaccinia virus mutant with a deletion of the D10R gene encoding a putative negative regulator of gene expression SO JOURNAL OF VIROLOGY LA English DT Article ID HINDIII-D FRAGMENT; MESSENGER-RNA; MICROARRAY ANALYSIS; TRANSCRIPTION; PROTEIN; IDENTIFICATION; RECOMBINANT; INFECTION; SHUTOFF; CELLS AB The D9 and D10 proteins of vaccinia virus are 25% identical to each other, contain a mutT motif characteristic of nudix hydrolases, and are conserved in all sequenced poxviruses. Previous studies indicated that overexpression of D10 and, to a lesser extent, D9 decreased the levels of capped mRNAs and their translation products. Here, we further characterized the D10 protein and showed that only trace amounts are associated with purified virions and that it is expressed exclusively at late times after vaccinia virus infection. A viable deletion mutant (v Delta D10) produced smaller plaques and lower virus yields than either wild-type virus or a D9R deletion mutant (v Delta D9). Purified v Delta D10 virions appeared normal by microscopic examination and biochemical analysis but produced 6- to 10-fold-fewer plaques at the same concentration as wild-type or v Delta D9 virions. When 4 PFU per cell of wild-type or v Delta D9 virions or equal numbers of v Delta D10 virions were used for inoculation, nearly all cells were infected in each case, but viral early and late transcription was initiated more slowly in v Delta D10-infected cells than in the others. However, viral early transcripts accumulated to higher levels in v Delta D10-infected cells than in cells infected with the wild type or v Delta D9. In addition, viral early and late mRNAs and cellular actin mRNA persisted longer in v Delta D10-infected cells than in others. Furthermore, analysis of pulse-labeled proteins indicated prolonged synthesis of cellular and viral early proteins. These results are consistent with a role for D10 in regulating RNA levels in poxvirus-infected cells. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 37 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2006 VL 80 IS 2 BP 553 EP 561 DI 10.1128/JVI.80.2.553-561.2006 PG 9 WC Virology SC Virology GA 999IL UT WOS:000234382900001 PM 16378957 ER PT J AU Raymond, GJ Olsen, EA Lee, KS Raymond, LD Bryant, PK Baron, GS Caughey, WS Kocisko, DA McHolland, LE Favara, C Langeveld, JPM van Zijderveld, FG Mayer, RT Miller, MW Williams, ES Caughey, B AF Raymond, GJ Olsen, EA Lee, KS Raymond, LD Bryant, PK Baron, GS Caughey, WS Kocisko, DA McHolland, LE Favara, C Langeveld, JPM van Zijderveld, FG Mayer, RT Miller, MW Williams, ES Caughey, B TI Inhibition of protease-resistant prion protein formation in a transformed deer cell line infected with chronic wasting disease SO JOURNAL OF VIROLOGY LA English DT Article ID MULE DEER; CULTURED-CELLS; SPONGIFORM ENCEPHALOPATHY; SCRAPIE AGENT; NEUROBLASTOMA-CELLS; PRP; MOUSE; SHEEP; TRANSMISSION; MICE AB Chronic wasting disease (CWD) is an emerging transmissible spongiform encephalopathy (prion disease) of North American cervids, i.e., mule deer, white-tailed deer, and elk (wapiti). To facilitate in vitro studies of CWD, we have developed a transformed deer cell line that is persistently infected with CWD. Primary cultures derived from uninfected mule deer brain tissue were transformed by transfection with a plasmid containing the simian virus 40 genome. A transformed cell line (MDB) was exposed to microsomes prepared from the brainstem of a CWD-affected mule deer. CWD-associated, protease-resistant prion protein (PrPCWD) was used as an indicator of CWD infection. Although no PrPCWD was detected in any of these cultures after two passes, dilution cloning of cells yielded one PrPCWD-positive clone out of 51. This clone, designated MDBCWD, has maintained stable PrPCWD production through 32 serial passes thus far. A second round of dilution cloning yielded 20 PrPCWD-positive subclones out of 30, one of which was designated MDBCWD2. The MDBCWD2 cell line was positive for fibronectin and negative for microtubule-associated protein 2 (a neuronal marker) and glial fibrillary acidic protein (an activated astrocyte marker), consistent with derivation from brain fibroblasts (e.g., meningeal fibroblasts). Two inhibitors of rodent scrapie protease-resistant PrP accumulation, pentosan polysulfate and a porphyrin compound, indium (III) meso-tetra(4-sulfonatophenyl)porphine chloride, potently blocked PrPCWD accumulation in MDBCWD cells. This demonstrates the utility of these cells in a rapid in vitro screening assay for PrPCWD inhibitors and suggests that these compounds have potential to be active against CVM in vivo. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. USDA ARS, Arthropod Borne Anim Dis Res Lab, Laramie, WY 82071 USA. CIDC Lelystad, Dept Bacteriol & TSEs, NL-8203 AA Lelystad, Netherlands. Wildlife Res Ctr, Colorado Div Wildlife, Ft Collins, CO 80526 USA. Univ Wyoming, Dept Vet Sci, Laramie, WY 82070 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. EM bcaughey@niaid.nih.gov RI Lee, Kil/D-3678-2012 FU Intramural NIH HHS NR 42 TC 35 Z9 41 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2006 VL 80 IS 2 BP 596 EP 604 DI 10.1128/JVI.80.2.596-604.2006 PG 9 WC Virology SC Virology GA 999IL UT WOS:000234382900006 PM 16378962 ER PT J AU Kamper, N Day, PM Nowak, T Selinka, HC Florin, L Bolscher, J Hilbig, L Schiller, JT Sapp, M AF Kamper, N Day, PM Nowak, T Selinka, HC Florin, L Bolscher, J Hilbig, L Schiller, JT Sapp, M TI A membrane-destabilizing peptide in capsid protein L2 is required for egress of papillomavirus genomes from endosomes SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; CELL-SURFACE; MONOCLONAL-ANTIBODIES; LIPID-BILAYERS; ADENOVIRUS; TYPE-33; ENTRY; POLIOVIRUS; NEUTRALIZATION; PSEUDOVIRIONS AB Papillomaviruses are internalized via clathrin-dependent endocytosis. However, the mechanism by which viral genomes pass endosomal membranes has not been elucidated. In this report we show that the minor capsid protein L2 is required for egress of viral genomes from endosomes but not for initial uptake and uncoating and that a 23-amino-acid peptide at the C terminus of L2 is necessary for this function. Pseudogenomes encapsidated by L1 and L2 lacking this peptide accumulated in vesicular compartments similar to that observed with L1-only viral particles, and these mutant pseudoviruses were noninfectious. This L2 peptide displayed strong membrane-disrupting activity, induced cytolysis of bacteria and eukaryotic cells in a pH-dependent manner, and permeabilized cells after exogenous addition. Fusions between green fluorescent protein and the L2 peptide integrated into cellular membranes like the wild type but not like C-terminal mutants of L2. Our data indicate that the L2 C terminus facilitates escape of viral genomes from the endocytic compartment and that this feature is conserved among papillomaviruses. Furthermore, the characteristic of this peptide differs from the classical virus-encoded membrane-penetrating peptides. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Ctr Mol & Tumor Virol, Shreveport, LA 71130 USA. Univ Mainz, Inst Med Microbiol & Hyg, D-55101 Mainz, Germany. NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Acad Ctr Dent Amsterdam, Dept Dent Basic Sci, Amsterdam, Netherlands. RP Sapp, M (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Ctr Mol & Tumor Virol, 1501 Kings Highway, Shreveport, LA 71130 USA. EM msapp1@lsuhsc.edu NR 52 TC 104 Z9 113 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2006 VL 80 IS 2 BP 759 EP 768 DI 10.1128/JVI.80.2.759-768.2006 PG 10 WC Virology SC Virology GA 999IL UT WOS:000234382900022 PM 16378978 ER PT J AU Gondois-Rey, F Biancotto, A Fernandez, MA Bettendroffer, L Blazkova, J Trejbalova, K Pion, M Hirsch, I AF Gondois-Rey, F Biancotto, A Fernandez, MA Bettendroffer, L Blazkova, J Trejbalova, K Pion, M Hirsch, I TI R5 variants of human immunodeficiency virus type 1 preferentially infect CD62L(-) CD4(+) T cells and are potentially resistant to nucleoside reverse transcriptase inhibitors SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN LYMPHOID-TISSUE; BLOOD MONONUCLEAR-CELLS; LYMPHOCYTES IN-VITRO; HIV-1 INFECTION; ANTIRETROVIRAL THERAPY; ACQUIRED-IMMUNODEFICIENCY; CD28 COSTIMULATION; NONDIVIDING CELLS; MOLECULAR CLONE; MEMORY AB The persistence of human immunodeficiency virus type I (HIV-1) in memory CD4(+) T cells is a major obstacle to the eradication of the virus with current antiretroviral therapy. Here, we investigated the effect of the activation status of CD4(+) T cells on the predominance of R5 and X4 HIV-1 variants in different subsets of CD4(+) T cells in ex vivo-infected human lymphoid tissues and peripheral blood mononuclear cells (PBMCs). In these cell systems, we examined the sensitivity of HIV replication to reverse transcriptase inhibitors. We demonstrate that R5 HIV-1 variants preferentially produced productive infection in HLA-DR- CD62L(-) CD4(+) T cells. These cells were mostly in the G(1)b phase of the cell cycle, divided slowly, and expressed high levels of CCR5. In contrast, X4 HIV-1 variants preferentially produced productive infection in activated HLA-DR+ CD62L(+) CD4(+) T cells, which expressed high levels of CXCR4. The abilities of the nucleoside reverse transcriptase inhibitors (NRTI) zidovudine and lamivudine to stop HIV-1 replication were 20 times greater in activated T cells than in slowly dividing HLA-DR- CD62L(-) CD4(+) T cells. This result, demonstrated both in a highly physiologically relevant ex vivo lymphoid tissue model and in PBMCs, correlated with higher levels of thymidine kinase mRNA in activated than in slowly dividing HLA-DR- CD62L(-) CD4(+) T cells. The non-NRTI nevirapine was equally efficient in both cell subsets. The lymphoid tissue and PBMC-derived cell systems represent well-defined models which could be used as new tools for the study of the mechanism of resistance to HIV-1 inhibitors in HLA-DR- CD62L(-) CD4(+) T cells. C1 INSERM, U372, F-13009 Marseille, France. INSERM, IFR 137, F-13009 Marseille, France. INSERM, UMR 599, F-13009 Marseille, France. NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. RP Hirsch, I (reprint author), INSERM, UMR 599, Inst Paoli Calmettes, 27 Blvd Lei Roure, F-13009 Marseille, France. EM ihirsch@marseille.inserm.fr RI Pion, Marjorie/D-8139-2012; Trejbalova, Katerina/G-4394-2014; Hirsch, Ivan/J-7726-2015 OI Pion, Marjorie/0000-0002-6406-747X; NR 72 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2006 VL 80 IS 2 BP 854 EP 865 DI 10.1128/JVI.80.2.854-865.2006 PG 12 WC Virology SC Virology GA 999IL UT WOS:000234382900031 PM 16378987 ER PT J AU Zhu, ZY Dimitrov, AS Bossart, KN Crameri, G Bishop, KA Choudhry, V Mungall, BA Feng, YR Choudhary, A Zhang, MY Feng, Y Wang, LF Xiao, XD Eaton, BT Broder, CC Dimitrov, DS AF Zhu, ZY Dimitrov, AS Bossart, KN Crameri, G Bishop, KA Choudhry, V Mungall, BA Feng, YR Choudhary, A Zhang, MY Feng, Y Wang, LF Xiao, XD Eaton, BT Broder, CC Dimitrov, DS TI Potent neutralization of Hendra and Nipah viruses by human monoclonal antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID EMERGENT DEADLY PARAMYXOVIRUS; MEMBRANE-FUSION TROPISM; ENVELOPE GLYCOPROTEINS; PIG-FARMERS; ENCEPHALITIS; RECEPTOR; MECHANISMS; DISEASES; MALAYSIA; BINDING AB Hendra virus (HeV) and Nipah virus (NiV) are closely related emerging viruses comprising the Henipavirus genus of the Paramyxovirinae. Each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. These viruses infect cells by a pH-independent membrane fusion event mediated by their attachment (G) and fusion (F) envelope glycoproteins (Envs). Seven Fabs, m101 to -7, were selected for their significant binding to a soluble form of Hendra G (sG) which was used as the antigen for panning of a large naive human antibody library. The selected Fabs inhibited, to various degrees, cell fusion mediated by the HeV or NiV Envs and virus infection. The conversion of the most potent neutralizer of infectious HeV, Fab m101, to immunoglobulin G1 (IgG1) significantly increased its cell fusion inhibitory activity: the 50% inhibitory concentration was decreased more than 10-fold to approximately 1 mu g/ml. The IgG1 m101 was also exceptionally potent in neutralizing infectious HeV; complete (100%) neutralization was achieved with 12.5 mu g/ml, and 8% neutralization required only 1.6 mu g/ml. The inhibition of fusion and infection correlated with binding of the Fabs to full-length G as measured by immunoprecipitation and less with binding to sG as measured by enzyme-linked immunosorbent assay and Biacore. m101 and m102 competed with the ephrin-B2, which we recently identified as a functional receptor for both HeV and NiV, indicating a possible mechanism of neutralization by these antibodies. The m101, m102, and m103 antibodies competed with each other, suggesting that they bind to overlapping epitopes which are distinct from the epitopes of m106 and m107. In an initial attempt to localize the epitopes of m101 and m102, we measured their binding to a panel of 11 G alanine-scanning mutants and identified two mutants, P185A and Q 191 K192A, which significantly decreased binding to m101 and one, G183, which decreased binding of m102 to G. These results suggest that m101 to -7 are specific for HeV or NiV or both and exhibit various neutralizing activities; they are the first human monoclonal antibodies identified against these viruses and could be used for treatment, prophylaxis, and diagnosis and as research reagents and could aid in the development of vaccines. C1 NCI, CCRNP, CCR,Prot Interact Grp, NIH, Frederick, MD 21702 USA. SAIC Frederick Inc, BRP, NCI, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. CSIRO, Livestock Ind, Australian Anim Hlth Lab, Geelong, Vic 3220, Australia. RP Broder, CC (reprint author), NCI, CCRNP, CCR,Prot Interact Grp, NIH, Bldg 469,Rm 105, Frederick, MD 21702 USA. EM cbroder@usuhs.mil; dimitrov@ncifcrf.gov RI Crameri, Gary/H-8441-2013; OI Bossart, Katharine/0000-0001-6886-6896 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [AI057168, U54 AI057168] NR 37 TC 67 Z9 78 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2006 VL 80 IS 2 BP 891 EP 899 DI 10.1128/JVI.80.2.891-899.2006 PG 9 WC Virology SC Virology GA 999IL UT WOS:000234382900035 PM 16378991 ER PT J AU Kocisko, DA Caughey, B AF Kocisko, DA Caughey, B TI Mefloquine, an antimalaria drug with antiprion activity in vitro, lacks activity in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; RESISTANT PRION PROTEIN; CULTURED-CELLS; SCRAPIE; QUINACRINE; INHIBITION; THERAPY; MICE; ACCUMULATION; DERIVATIVES AB In view of the effectiveness of antimalaria drugs inhibiting abnormal protease-resistant prion protein (PrP-res) formation in scrapie agent-infected cells, we tested other antimalarial compounds for similar activity. Mefloquine (MF), a quinoline antimalaria drug, was the most active compound tested against RML and 22L mouse scrapie agent-infected cells, with 50% inhibitory concentrations of similar to 0.5 and similar to 1.2 mu M, respectively. However, MF administered to mice did not delay the onset of intraperitoneally inoculated scrapie agent, the result previously observed with quinacrine. While most anti-scrapie agent compounds inhibit PrP-res formation in vitro, many PrP-res inhibitors have no activity in vivo. This underscores the importance of testing promising candidates in vivo. C1 Rocky Mt Labs, Hamilton, MT 59840 USA. NIAID, NIH, Hamilton, MT 59840 USA. RP Kocisko, DA (reprint author), Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM dkocisko@niaid.nih.gov FU Intramural NIH HHS NR 25 TC 24 Z9 30 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2006 VL 80 IS 2 BP 1044 EP 1046 DI 10.1128/JVI.80.2.1044-1046.2006 PG 3 WC Virology SC Virology GA 999IL UT WOS:000234382900050 PM 16379006 ER PT J AU Read, JCA Cumming, BG AF Read, Jenny C. A. Cumming, Bruce G. TI Does depth perception require vertical-disparity detectors? SO JOURNAL OF VISION LA English DT Article DE binocular vision; vertical disparity; induced effect ID RANDOM-DOT STEREOGRAMS; PRIMARY VISUAL-CORTEX; HORIZONTAL DISPARITY; STEREOSCOPIC DEPTH; EYE-MOVEMENTS; BINOCULAR DISPARITY; SHEAR DISPARITY; SIZE DISPARITY; SURFACE SLANT; AREAS V1 AB Stereo depth perception depends on the fact that objects project to different positions in the two eyes. Because our eyes are offset horizontally, these retinal disparities are mainly horizontal, and horizontal disparity surfaces to give an impression of depth. However, depending on eye position, there may also be small vertical disparities. These are significant because, given both vertical and horizontal disparities, the brain can deduce eye position from purely retinal information and, hence, derive the position of objects in space. However, we show here that, to achieve this, the brain need measure only the magnitude of vertical disparity; for physically possible stimuli, the sign then follows from the stereo geometry. The magnitude of vertical disparity-and hence eye position-can be deduced from the response of purely horizontal-disparity sensors because vertical disparity moves corresponding features off the receptive fields, reducing the effective binocular correlation. As proof, we demonstrate an algorithm that can accurately reconstruct gaze and vergence angles from the population activity of pure horizontal-disparity sensors and show that it is subject to the induced effect. Given that disparities experienced during natural viewing are overwhelmingly horizontal and that eye position measures require only horizontal-disparity sensors, this work raises two questions: Does the brain in fact contain sensors tuned to nonzero vertical disparities, and if so, why?. C1 Univ Newcastle, Sch Biol & Psychol, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA. RP Read, JCA (reprint author), Univ Newcastle, Sch Biol & Psychol, Henry Wellcome Bldg Neuroecol, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM j.c.a.read@ncl.ac.uk RI Read, Jenny/A-7493-2013 OI Read, Jenny/0000-0002-9029-5185 FU Intramural NIH HHS NR 75 TC 23 Z9 23 U1 2 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2006 VL 6 IS 12 BP 1323 EP 1355 DI 10.1167/6.12.1 PG 33 WC Ophthalmology SC Ophthalmology GA 141UF UT WOS:000244603600001 PM 17209738 ER PT J AU Janiszewski, R Heath-Watson, SL Semidey, AY Rosenthal, AM Do, Q AF Janiszewski, Rosemary Heath-Watson, Shelly L. Semidey, Adrienne Y. Rosenthal, Arlen M. Do, Quynh TI The low visibility of low vision: Increasing awareness through public health education SO JOURNAL OF VISUAL IMPAIRMENT & BLINDNESS LA English DT Article ID ADULTS AB The importance of an informational outreach program focused on eye health and visual impairment is underscored by surveys showing that the vast majority of Americans have misperceptions about or have never heard of low vision. This article uses the National Eye Institute's Low Vision Education Program as a model for the development, implementation, and evaluation of a public health education initiative. The components of an effective public education program are outlined in the context of what people know, don't know, and want to know about vision loss. C1 NEI, Off Commun Hlth Educ & Publ Liaison, Bethesda, MD 20892 USA. ORC Macro, Calverton, MD 20852 USA. RP Janiszewski, R (reprint author), NEI, Off Commun Hlth Educ & Publ Liaison, Bldg 31,Room 6A32,31 Ctr Dr MSC2510, Bethesda, MD 20892 USA. EM rjaniszewski@nei.nih.gov; shelly.l.heath-watson@orcmacro.com; asemidey@shs.net; arlen.m.rosenthal@orcmacro.com; qdo@shs.net NR 17 TC 5 Z9 5 U1 0 U2 4 PU AMER FOUNDATION BLIND PI NEW YORK PA J VISUAL IMPAIRMENT BLINDNESS 11 PENN PLAZA SUITE 300, NEW YORK, NY 10001 USA SN 0145-482X J9 J VISUAL IMPAIR BLIN JI J. Vis. Impair. Blind. PY 2006 VL 100 SI SI BP 849 EP 861 PG 13 WC Rehabilitation SC Rehabilitation GA 136NF UT WOS:000244230700008 ER PT J AU Vogel, A Gandjbakhche, A Gannot, I AF Vogel, Abby Gandjbakhche, Amir Gannot, Israel TI Demystifying optical diagnostics SO JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY LA English DT Review DE optical imaging; optical coherence tomography; X-ray imaging; computed tomography; functional imaging ID COHERENCE TOMOGRAPHY; MAGNETIC-RESONANCE; ATHEROSCLEROTIC PLAQUES; CONTRAST AGENTS; BREAST; MAMMOGRAPHY; TUMORS; QUANTIFICATION; COREGISTRATION; VISUALIZATION AB This paper describes a few optical imaging methods in their translational stage to the clinical phase. The methods are compared to well-established X-ray imaging methods such as computed tomography and mammography. The drawback of the diffuse paths of laser photons compared to the ballistic paths of the X-ray is compensated by coherence methods for tissue characterization adjacent to the surface, and acoustic wave enhanced imaging and fluorescent markers that follow functional changes when deeper tissue is analyzed. This paper presents some of the latest developments in this field as presented in a Bench to Bedside workshop on optical imaging held at the National Institutes of Health. C1 NICHHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Univ Maryland, Dept Biol Resources Engn, College Pk, MD USA. Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. RP Vogel, A (reprint author), NICHHD, NIH, Lab Integrat & Med Biophys, 9000 Rockville Pike,Bldg 9 Room B 1E05, Bethesda, MD 20892 USA. EM vogelab@mail.nih.gov NR 47 TC 1 Z9 1 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0895-3996 J9 J X-RAY SCI TECHNOL JI J. X-Ray Sci. Technol. PY 2006 VL 14 IS 1 BP 55 EP 72 PG 18 WC Instruments & Instrumentation; Optics; Physics, Applied SC Instruments & Instrumentation; Optics; Physics GA 168KT UT WOS:000246524200006 ER PT J AU Newman, AB Kupelian, V Visser, M Simonsick, EM Goodpaster, BH Kritchevsky, SB Tylavsky, FA Rubin, SM Harris, TB AF Newman, AB Kupelian, V Visser, M Simonsick, EM Goodpaster, BH Kritchevsky, SB Tylavsky, FA Rubin, SM Harris, TB CA Hlth Aging Body Composition Study TI Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LOWER-EXTREMITY PERFORMANCE; SKELETAL-MUSCLE; PHYSICAL FUNCTION; OLDER WOMEN; MEN; MOBILITY; AGE; INTERLEUKIN-6; PREDICTORS; QUALITY AB Background. Although muscle strength and mass are highly correlated, the relationship between direct measures of low muscle mass (sareopenia) and strength in association with mortality has not been examined. Methods. Total mortality rates were examined in the Health, Aging and Body Composition (Health ABC) Study in 2292 participants (aged 70-79 years, 51.6% women, and 38.8% black). Knee extension strength was measured with isokinetic dynamometry, grip strength with isometric dynamometry. Thigh muscle area was measured by computed tomography (CT) scan, and leg and arm lean soft tissue mass were determined by dual energy x-ray absorptiometry (DXA). Both strength and muscle size were assessed as in gender-specific Cox proportional hazards models, with age, race, comorbidities, smoking status, level of physical activity, fat area by CT or fat mass by DXA, height, and markers of inflammation, including interleukin-6, C-reactive protein, and tumor necrosis factor-a considered as potential confounders. Results. There were 286 deaths over an average of 4.9 (standard deviation = 0.9) years of follow-up. Both quadriceps and grip strength were strongly related to mortality. For quadriceps strength (per standard deviation of 38 Nm), the crude hazard ratio for men was 1.51 (95% confidence interval, 1.28-1.79) and 1.65 (95% confidence interval, 1.19-2.30) for women. Muscle size, determined by either CT area or DXA regional lean mass, was not strongly related to mortality. In the models of quadriceps strength and mortality, adjustment for muscle area or regional lean mass only slightly attenuated the associations. Further adjustment for other factors also had minimal effect on the association of quadriceps strength with mortality. Associations of grip strength with mortality were similar. Conclusion. Low muscle mass did not explain the strong association of strength with mortality, demonstrating that muscle strength as a marker of muscle quality is more important than quantity in estimating mortality risk. Grip strength provided risk estimates similar to those of quadriceps strength. C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. New England Res Inst, Watertown, MA 02172 USA. Vrije Univ Amsterdam, VU Med Ctr, Inst Res Extramural Med, Amsterdam, Netherlands. Vrije Univ Amsterdam, Inst Hlth Sci, Amsterdam, Netherlands. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA USA. RP Newman, AB (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 N Bellefield Ave,Room 532, Pittsburgh, PA 15213 USA. EM newmana@edc.pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 27 TC 465 Z9 474 U1 14 U2 48 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2006 VL 61 IS 1 BP 72 EP 77 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 010VR UT WOS:000235226500008 PM 16456196 ER PT J AU Coppin, AK Ferrucci, L Lauretani, F Phillips, C Chang, M Bandinelli, S Guralnik, JM AF Coppin, AK Ferrucci, L Lauretani, F Phillips, C Chang, M Bandinelli, S Guralnik, JM TI Low socioeconomic status and disability in old age: Evidence from the InChianti study for the mediating role of physiological impairments SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LOWER-EXTREMITY FUNCTION; DEMOGRAPHIC CHARACTERISTICS; SUBSEQUENT DISABILITY; PHYSICAL PERFORMANCE; ARTERIAL-DISEASE; MORTALITY; MACARTHUR; EDUCATION; MOBILITY; DECLINE AB Background. Low socioeconomic status (SES) has been associated with increased risk of disability in later life. The Purpose of this study was to determine if SES has an impact on mobility functioning and to explore which physiological impairments are also associated with SES and may explain its relationship with mobility. Methods. The study sample consisted of 1025 individuals aged 65 years or older residing in the Chianti area (Italy). Number of years of education was used as an indicator of SES. Mobility functioning was assessed using gait speed (400 m) and the Short Physical Performance Battery (SPPB). Mobility-related physiological impairments were assessed with tests of executive functioning, nerve conduction velocity, muscle power, hip-ankle range of motion, Ankle-Brachial Index, and visual acuity. Linear regression models were used to study the association between number of years of education and mobility and to estimate the contribution of each of the selected physiological impairments to this association. Results. Adjusting for age and sex, slower gait speed (1.16 vs 1.26 m/s, p <.0001) and lower SPPB scores (9.55 vs 10.11, p=.006) were seen in persons with <= 5 years of total education compared with those persons with >= 5 years of total education. Leg power and executive function decreased the strength of the association between educational level and gait speed by more than 15%. Controlling for all selected impairments (full model) decreased the education-gait speed association by 49%. Low education continued to be significantly associated with gait speed (p <.01). Adjusting for all physiological impairments substantially reduced the low education-SPPB score association by 100%, and this association was no longer significant. Conclusions. Low SES is related to multiple physiological impairments, which explain a large amount of the association between education and gait limitations. Further work must be done to understand the mechanisms whereby low SES translates into the impairments that play an important role in mobility. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Ctr Gerontol Res, Baltimore, MD USA. Italian Natl Res Council Aging, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. RP Coppin, AK (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. EM coppina@mail.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS NR 36 TC 49 Z9 49 U1 1 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2006 VL 61 IS 1 BP 86 EP 91 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 010VR UT WOS:000235226500010 PM 16456198 ER PT J AU Lange-Sperandio, B Schimpgen, K Rodenbeck, B Chavakis, T Bierhaus, A Nawroth, P Thornhill, B Schaefer, F Chevalier, RL AF Lange-Sperandio, B Schimpgen, K Rodenbeck, B Chavakis, T Bierhaus, A Nawroth, P Thornhill, B Schaefer, F Chevalier, RL TI Distinct roles of Mac-1 and its counter-receptors in neonatal obstructive nephropathy SO KIDNEY INTERNATIONAL LA English DT Article DE integrins; Mac-1; unilateral ureteral obstruction; macrophages; RAGE; JAM ID UNILATERAL URETERAL OBSTRUCTION; JUNCTIONAL ADHESION MOLECULES; RENAL INTERSTITIAL FIBROSIS; GLYCATION END-PRODUCTS; EXPERIMENTAL HYDRONEPHROSIS; TRANSENDOTHELIAL MIGRATION; TUBULOINTERSTITIAL INJURY; INTEGRIN ALPHA(M)BETA(2); NEUTROPHIL ADHESION; LEUKOCYTE INTEGRINS AB Urinary tract obstruction during renal development leads to tubular atrophy and interstitial fibrosis. Inflammatory macrophages are crucial in this process, and beta(2)-integrins play a major role in leukocyte recruitment. We investigated the role of beta(2)-integrins and their major counter-receptors ( intercellular adhesion molecule-1 (ICAM-1), receptor for advanced glycation endproducts ( RAGE), junctional adhesion molecule ( JAM)-C) in obstructive nephropathy in neonatal mice. Two-day-old beta(2)-integrin-deficient mice ( Mac-1(-/-) and LFA-1(-/-)( deficient for leukocyte function-associated antigen-1)) and wild-type mice ( C57BL/6) underwent unilateral ureteral obstruction ( UUO) or sham operation. After 1, 5 or 12 days of obstruction, renal macrophage infiltration and tubulointerstitial damage were quantitated. Tissue abundance of Mac- 1 and its ligands ICAM-1, RAGE and JAM-C was examined by Western blot and immunoprecipitation. Deficiency of either integrin was associated with reduced early macrophage invasion into the obstructed kidney. After 12 days of UUO, macrophage infiltration and tubulointerstitial injury were reduced only in Mac-1(-/-) but not in LFA-1(-/-) mice. Besides ICAM-1, an upregulation of two novel Mac- 1 ligands, RAGE and JAM-C were observed, however, with distinct time courses. We conclude that beta(2)-integrins mediate macrophage infiltration in UUO. Mac- 1 is the predominant leukocyte integrin involved in leukocyte recruitment after obstruction. ICAM-1 and its new ligands RAGE and JAM-C are sequentially activated in UUO. Blocking of Mac- 1 and its ligands may confer synergistic renoprotective effects in neonatal obstructive nephropathy. C1 Univ Heidelberg, Dept Pediat, D-69120 Heidelberg, Germany. Univ Heidelberg, Dept Internal Med 1, Heidelberg, Germany. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Pediat, Charlottesville, VA USA. RP Lange-Sperandio, B (reprint author), Univ Heidelberg, Dept Pediat, INF 150, D-69120 Heidelberg, Germany. EM baerbel.lange-sperandio@med.uni-heidelberg.de RI Schaefer, Franz/G-4365-2010 FU NIDDK NIH HHS [DK52612] NR 51 TC 18 Z9 20 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2006 VL 69 IS 1 BP 81 EP 88 DI 10.1038/sj.ki.5000017 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 999JX UT WOS:000234386700022 PM 16374427 ER PT J AU Kim, SW Wang, W Sassen, MC Choi, KC Han, JS Knepper, MA Jonassen, TEN Frokiaer, J Nielsen, S AF Kim, SW Wang, W Sassen, MC Choi, KC Han, JS Knepper, MA Jonassen, TEN Frokiaer, J Nielsen, S TI Biphasic changes of epithelial sodium channel abundance and trafficking in common bile duct ligation-induced liver cirrhosis SO KIDNEY INTERNATIONAL LA English DT Article DE liver cirrhosis; epithelial sodium channel; 11 beta-hydroxy steroid dehydrogenase; collecting duct; edema ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE; SYSTEMIC HEMODYNAMICS; MEDIATED REGULATION; RAT-KIDNEY; ALDOSTERONE; RECEPTOR; RETENTION; ASCITES; ENAC; REABSORPTION AB We hypothesize that dysregulation of the epithelial sodium channel ( ENaC) may be responsible for the increased sodium retention in liver cirrhosis. Liver cirrhosis was induced by common bile duct ligation (CBDL). We examined the abundance of ENaC subunits and type 2 isoform of 11 beta-hydroxysteroid dehydrogenase ( 11 beta HSD2) in the kidney by immunoblotting and immunohistochemistry at 6 or 8 weeks after operation. At 6 weeks, cirrhotic rats had developed ascites and displayed a positive sodium balance. The urinary sodium excretion and fractional excretion of sodium were decreased, while plasma aldosterone was unchanged. The abundance of ENaC subunits was not changed in the cortex and outer stripe of the outer medulla ( OSOM). In contrast, immunoperoxidase microscopy revealed an increased apical targeting of alpha-, beta- and gamma ENaC in late distal convoluted tubule, connecting tubule and collecting duct. Moreover, 11 beta HSD2 abundance was decreased in the cortex/OSOM and inner stripe of the outer medulla. At 8 weeks, urinary sodium excretion and fractional excretion of sodium were not changed, while the plasma aldosterone level was decreased. The expression of ENaC subunits was decreased in the cortex/OSOM. Immunoperoxidase microscopy confirmed decreased expression of ENaC subunits, whereas subcellular localization was not changed. These results suggest that increased apical targeting of ENaC subunits and diminished abundance of 11 beta HSD2 may contribute to promote sodium retention in the sodium-retaining stage of liver cirrhosis ( at 6 weeks). The subsequent decreased expression and reduced targeting of ENaC subunits may play a role in promoting sodium excretion in the later stage of liver cirrhosis ( at 8 weeks). C1 Univ Arkansas, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Chonnam Natl Univ, Sch Med, Dept Internal Med, Kwangju, South Korea. Seoul Natl Univ Hosp, Clin Res Inst, Dept Internal Med, Seoul 110744, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Copenhagen, Panum Inst, Dept Pharmacol, Copenhagen N, Denmark. RP Nielsen, S (reprint author), Univ Arkansas, Water & Salt Res Ctr, Bldg 233-234, DK-8000 Aarhus C, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 29 TC 17 Z9 17 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2006 VL 69 IS 1 BP 89 EP 98 DI 10.1038/sj.ki.5000018 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 999JX UT WOS:000234386700023 PM 16374428 ER PT J AU Eddy, EM AF Eddy, E. M. BE Neill, JD TI The Spermatozoon SO KNOBIL AND NEILL'S PHYSIOLOGY OF REPRODUCTION, VOLS 1 AND 2, 3RD EDITON LA English DT Article; Book Chapter ID GUINEA-PIG SPERM; OUTER DENSE FIBERS; PROTEIN-KINASE-A; SOLUBLE ADENYLYL-CYCLASE; MALE GERM-CELLS; MOUSE SPERMATOGENIC CELLS; FIBROUS SHEATH PROTEIN; TESTIS-SPECIFIC GENE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE-S; ADENOSINE TRIPHOSPHATASE ACTIVITY AB This chapter examines the novel structural features of the spermatozoon, their composition and assembly, and the mechanisms regulating their function. The spermatozoon is a highly specialized cell with an array of novel structural features and functional characteristics which provide it with the singular capability of delivering the male genome to the egg. The head of a spermatozoon contains a highly condensed nucleus and the acrosome, an enzyme-filled vesicle whose contents are released as the sperm approaches or reaches the egg surface to facilitate fertilization. The flagellum is a highly novel feature that provides the spermatozoon with the ability to propel itself through liquid medium. Substantial advances have occurred within the last decade in identifying the genes responsible for many of these novel structural features and functional characteristics. Many of the genes are expressed only in spermatids and encode novel proteins that are unique to spermatozoa. They include proteins that package the DNA, form the sperm head cytoskeleton, constitute the enzymes and matrix components of the acrosome, assemble into the novel structural components of the flagellum, become ion channels involved in regulating motility, and are the adenylyl cyclase that produces cyclic adenosine monophosphate (cAMP) to trigger the signaling cascades that regulate spermatozoon functions. Because such proteins are essential to spermatozoa, mutations that disrupt their synthesis or function can result in male infertility. The gene knockout approach has identified many proteins required for normal sperm functions in mice that are likely to be required in humans as well. However, many critical questions remain to be answered about the composition, organization, and function of spermatozoa. C1 NIEHS, Gamete Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Gamete Biol Sect, Lab Reprod & Dev Toxicol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 579 TC 28 Z9 28 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-053527-2 PY 2006 BP 3 EP 54 PG 52 WC Reproductive Biology SC Reproductive Biology GA BCW96 UT WOS:000311804000006 ER PT B AU Bondy, CA Zhou, J Arraztoa, JA AF Bondy, Carolyn A. Zhou, Jian Arraztoa, Jose A. BE Neill, JD TI Growth Hormone, Insulin-Like Growth Factors, and the Ovary SO KNOBIL AND NEILL'S PHYSIOLOGY OF REPRODUCTION, VOLS 1 AND 2, 3RD EDITON LA English DT Article; Book Chapter ID I IGF-I; MESSENGER-RIBONUCLEIC-ACID; PLASMA-PROTEIN-A; FOLLICLE-STIMULATING-HORMONE; HUMAN GRANULOSA-CELLS; RECEPTOR GENE-EXPRESSION; FACTOR-BINDING PROTEIN-1; BOVINE CORPUS-LUTEUM; FEMALE REPRODUCTIVE FUNCTION; LONGITUDINAL BONE-GROWTH C1 [Bondy, Carolyn A.; Zhou, Jian] NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 206 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-053527-2; 978-0-12-515400-0 PY 2006 BP 527 EP 546 PG 20 WC Reproductive Biology SC Reproductive Biology GA BCW96 UT WOS:000311804000018 ER PT B AU Couse, JF Hewitt, SC Korach, KS AF Couse, John F. Hewitt, Sylvia C. Korach, Kenneth S. BE Neill, JD TI Steroid Receptors in the Ovary and Uterus SO KNOBIL AND NEILL'S PHYSIOLOGY OF REPRODUCTION, VOLS 1 AND 2, 3RD EDITON LA English DT Article; Book Chapter ID FOLLICLE-STIMULATING-HORMONE; RAT GRANULOSA-CELLS; MESSENGER-RIBONUCLEIC-ACID; HUMAN ESTROGEN-RECEPTOR; GONADOTROPIN-RELEASING-HORMONE; HUMAN PROGESTERONE-RECEPTOR; EPIDERMAL-GROWTH-FACTOR; BETA ER-BETA; ELEVATED LUTEINIZING-HORMONE; HUMAN ANDROGEN RECEPTOR C1 [Couse, John F.] NIEHS, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. [Korach, Kenneth S.] NIEHS, NIH, Environ Dis Med Program, Res Triangle Pk, NC 27709 USA. RP Couse, JF (reprint author), NIEHS, Lab Reprod & Dev Toxicol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 693 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-053527-2; 978-0-12-515400-0 PY 2006 BP 593 EP 678 PG 86 WC Reproductive Biology SC Reproductive Biology GA BCW96 UT WOS:000311804000020 ER PT S AU Islamaj, R Getoor, L Wilbur, WJ AF Islamaj, Rezarta Getoor, Lise Wilbur, W. John BE Furnkranz, J Scheffer, T Spiliopoulou, M TI A feature generation algorithm for sequences with application to splice-site prediction SO KNOWLEDGE DISCOVERY IN DATABASES: PKDD 2006, PROCEEDINGS SE LECTURE NOTES IN ARTIFICIAL INTELLIGENCE LA English DT Article; Proceedings Paper CT 10th European Conference on Principle and Practice of Knowledge Discovery in Databases CY SEP 18-22, 2006 CL Berlin, GERMANY SP Google, Humboldt Univ Berlin, KD ubiq, STRATO AG, IBM, Deutsch Forsch Gemeinsch, PASCAL, Mach Learning, AFOSR, EOARD ID CLASSIFICATION AB In this paper we present a new approach to feature selection for sequence data. We identify general feature categories and give Construction algorithms for each of them. We show how they can be integrated in a system that tightly couples feature construction and feature selection. This integrated process, which we refer to as feature generation, allows us to systematically search a large space of potential features. We demonstrate the effectiveness of our approach for an important component of the gene finding problem, splice-site prediction. We show that predictive models built using our feature generation algorithm achieve a significant improvement in accuracy over existing, state-of-the-art approaches. C1 Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. RP Islamaj, R (reprint author), Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. EM rezarta@cs.umd.edu; getoor@cs.umd.edu; wilbur@ncbi.nlm.nih.gov OI Islamaj Dogan, Rezarta/0000-0001-5651-1860 NR 14 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-45374-1 J9 LECT NOTES ARTIF INT PY 2006 VL 4213 BP 553 EP 560 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems SC Computer Science GA BFD12 UT WOS:000241104900050 ER PT J AU Wigglesworth, C AF Wigglesworth, Carol TI A word from OLAW SO LAB ANIMAL LA English DT Editorial Material C1 NIH, Off Lab Anim Welf, OER, OD,HHS, Bethesda, MD 20892 USA. RP Wigglesworth, C (reprint author), NIH, Off Lab Anim Welf, OER, OD,HHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JAN PY 2006 VL 35 IS 1 BP 16 EP 16 DI 10.1038/laban0106-16b PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 070SY UT WOS:000239545600004 ER PT J AU Rapkiewicz, AV Lowenthal, M Kleiner, DE Liotta, LA AF Rapkiewicz, AV Lowenthal, M Kleiner, DE Liotta, LA TI The vitreous proteome: An autopsy study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. George Mason Univ, Manassas, VA USA. Univ Colorado, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 15 BP 7A EP 7A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207600016 ER PT J AU Ning, EMLL Palau, MA Garcia-Macias, C Allende, D Silva, A Merino, MJ AF Ning, EMLL Palau, MA Garcia-Macias, C Allende, D Silva, A Merino, MJ TI CISH (TM) is a good technique to determine HER2 gene amplification in cytologic preparations from breast carcinomas: Excellent correlation with FFPE tissue analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Hosp Univ Salamanca, Salamanca, Spain. RI FELIPE-SILVA, ALOISIO/J-9295-2012 OI FELIPE-SILVA, ALOISIO/0000-0001-6668-7907 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 277 BP 63A EP 63A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207600277 ER PT J AU Manosca, F Schinstine, M Fetsch, P Brosky, K Erickson, D Wilder, A Sorbara, L Raffeld, M Filie, A Abati, A AF Manosca, F Schinstine, M Fetsch, P Brosky, K Erickson, D Wilder, A Sorbara, L Raffeld, M Filie, A Abati, A TI The diagnostic effects of prolonged storage on fresh effusion samples SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 288 BP 65A EP 66A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207600288 ER PT J AU Merino, MJ Toro, JR Palau, MA Linehan, WM Torres-Cabala, CA AF Merino, MJ Toro, JR Palau, MA Linehan, WM Torres-Cabala, CA TI The spectrum of morphologic features of renal tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome: Our experience with 34 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 691 BP 150A EP 150A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601125 ER PT J AU Palau, MA Torres-Cabala, C Ning, EL Linehan, WM Merino, MJ AF Palau, MA Torres-Cabala, C Ning, EL Linehan, WM Merino, MJ TI Determination of EGFR status in sporadic and hereditary renal tumors. correlation between CISH and immunohistochemistry SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 707 BP 153A EP 153A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601141 ER PT J AU Torres-Cabala, CA Ning, EL Palau, MA Linehan, WM Merino, MJ AF Torres-Cabala, CA Ning, EL Palau, MA Linehan, WM Merino, MJ TI Are some collecting duct carcinomas indeed HLRCC tumors? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 760 BP 165A EP 165A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601194 ER PT J AU Jiang, L Malpica, A Deavers, A Nuovo, G Merino, M Silva, EG AF Jiang, L Malpica, A Deavers, A Nuovo, G Merino, M Silva, EG TI Endometrioid adenocarcinoma involving the endometrium and the cervix: One tumor or two independent tumors? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 MD Anderson Canc Ctr, Houston, TX USA. Ohio Univ, Columbus, OH USA. Natl Canc Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 845 BP 183A EP 183A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601279 ER PT J AU Ning, EMLL Teller, LS Ricketts, RSJ Otis, C Sobel, M Merino, MJ AF Ning, EMLL Teller, LS Ricketts, RSJ Otis, C Sobel, M Merino, MJ TI Clonality of borderline and serous carcinoma of the ovary: Molecular studies identify a monoclonal origin for primary tumors and their implants SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Baystate Med Ctr, Springfield, MA 01199 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 867 BP 187A EP 187A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601301 ER PT J AU Tilara, A Henson, DE Schwartz, A Grimley, P Anderson, WF AF Tilara, A Henson, DE Schwartz, A Grimley, P Anderson, WF TI Population based epidemiology complements pathological data in gynecological cancers SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 George Washington Univ, Washington, DC USA. George Washington Univ, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 924 BP 199A EP 199A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601358 ER PT J AU Feldman, AL Espina, V Gulmann, C Winters, M Liotta, LA Jaffe, ES AF Feldman, AL Espina, V Gulmann, C Winters, M Liotta, LA Jaffe, ES TI Tissue proteomics, the Bcl-2/Bax switch, and the role of the pathologist SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. George Mason Univ, Fairfax, VA 22030 USA. RI Feldman, Andrew/D-5028-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1044 BP 225A EP 225A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601478 ER PT J AU Maric, I Siddon, A Fu, W Stoddard, J Robyn, J Metcalfe, D Noel, P AF Maric, I Siddon, A Fu, W Stoddard, J Robyn, J Metcalfe, D Noel, P TI Correlation of KIT D816V mutation analysis and immunophenotypic analysis of bone marrow aspirates in patients evaluated for systemic mastocytosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NIH, CC, Bethesda, MD 20892 USA. NIAD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1095 BP 236A EP 236A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601529 ER PT J AU Quintanilla-Martinez, L Pittaluga, S Davies-Hill, T Miething, C Anastosov, N Rudelius, M Duyster, J Jaffe, ES Fend, F Raffeld, M AF Quintanilla-Martinez, L Pittaluga, S Davies-Hill, T Miething, C Anastosov, N Rudelius, M Duyster, J Jaffe, ES Fend, F Raffeld, M TI The transcription factor CCAAT/enhancer binding protein (C/EBP)beta is constitutively expressed in ALK-positive anaplastic large cell lymphomas (ALCL), and is dependent upon NPM-ALK kinase activity SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 GSF, Res Ctr Hlth & Environm, Neuherberg, Germany. NCI, NIH, Bethesda, MD 20892 USA. Tech Univ Munich, D-8000 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1123 BP 242A EP 242A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601557 ER PT J AU Rizzo, KA Streubel, B Chott, A Sorbara, L Kumar, S Pittaluga, S Raffeld, M Jaffe, ES AF Rizzo, KA Streubel, B Chott, A Sorbara, L Kumar, S Pittaluga, S Raffeld, M Jaffe, ES TI MALT lymphoma of the dura: Analysis of clinical, histological and genetic features SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Med Univ Vienna, Vienna Gen Hosp, Vienna, Austria. VA Med Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1130 BP 244A EP 244A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601564 ER PT J AU Salaverria, I Bea, S Zettl, A Valls, J Moreno, V Ott, G Muller-Hermelink, HK Staudt, LM Campo, E Rosenwald, A AF Salaverria, I Bea, S Zettl, A Valls, J Moreno, V Ott, G Muller-Hermelink, HK Staudt, LM Campo, E Rosenwald, A TI Secondary genetic alterations in mantle cell lymphoma influence gene expression and improve the proliferation-based prognostic model SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Hosp Clin Barcelona, Barcelona, Spain. Univ Wurzburg, Wurzburg, Germany. IDIBELL Catalan Inst Oncol, Barcelona, Spain. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1135 BP 245A EP 245A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207601569 ER PT J AU Joshi, S Guindi, M Feld, JJ Diennes, HP Lohse, A Heatchote, EJ AF Joshi, S Guindi, M Feld, JJ Diennes, HP Lohse, A Heatchote, EJ TI Longterm histological and clinical follow-up of anti-mitochondrial antibody (AMA) positive autoimmune hepatitis (AIH): Another variant of autoimmune hepatitis or a well controlled overlap syndrome? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Credit Valley Hosp, Mississauga, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. NIH, Bethesda, MD 20892 USA. Univ Cologne, Cologne, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1269 BP 273A EP 273A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207602117 ER PT J AU Begnami, MD Palau, M Rushing, E Santi, M Quezado, M AF Begnami, MD Palau, M Rushing, E Santi, M Quezado, M TI Evaluation of NF2 gene deletion in sporadic schwannomas, meningiomas and ependymomas by chromogenic in situ hydridization SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Childrens Hosp, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1319 BP 284A EP 284A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207602167 ER PT J AU Shilo, K Fukuoka, J Mani, H Sesterhenn, IA Jen, J Travis, WD Franks, TJ AF Shilo, K Fukuoka, J Mani, H Sesterhenn, IA Jen, J Travis, WD Franks, TJ TI Alpha-methylacyl CoA racemase (AMACR) expression in pulmonary carcinomas: A study of 406 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. Toyama Med & Pharmaceut Univ, Toyama, Japan. NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1473 BP 316A EP 316A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207602321 ER PT J AU Fountaine, T Wincovitch, S Geho, D Garfield, S Pittaluga, S AF Fountaine, T Wincovitch, S Geho, D Garfield, S Pittaluga, S TI Multispectral imaging of cellular targets using semiconductor quantum dots SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, CCR Confocal Microscopy Core Facil, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1529 BP 328A EP 328A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207602377 ER PT J AU Patel, AA Gupta, D Seligson, D Hattab, EM Balis, U Ulbright, TM Berman, JJ Gilbertson Jr Becich, MJ Parwani, AV AF Patel, AA Gupta, D Seligson, D Hattab, EM Balis, U Ulbright, TM Berman, JJ Gilbertson, JR Becich, MJ Parwani, AV TI Availability and quality of paraffin blocks identified by the shared pathology informatics network (SPIN): A multi-institutional study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Shared Pathol Informat Network, Pittsburgh, PA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Indiana Univ, Indianapolis, IN 46204 USA. Harvard Univ, Boston, MA 02115 USA. NCI, DCTD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1549 BP 332A EP 332A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207602397 ER PT J AU Patel, AA Gilbertson Jr Parwani, AV Dhir, R Datta, MW Gupta, R Berman, JJ Becich, MJ AF Patel, AA Gilbertson, JR Parwani, AV Dhir, R Datta, MW Gupta, R Berman, JJ Becich, MJ TI The NCI cooperative prostate cancer tissue resource: Informatics support for a multi-institute biorepository SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Cooperat Prostate Canc Tissue Resource, Pittsburgh, PA USA. Emory Univ, Atlanta, GA 30322 USA. NCI, DCTD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1550 BP 332A EP 333A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207602398 ER PT J AU Silva, AS Palau, M Merino, MJ AF Silva, AS Palau, M Merino, MJ TI Utilization of chromosome Y chromogenic in situ hybridization (CISH (TM)) to detect male cells in surgical pathology specimens SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. RI FELIPE-SILVA, ALOISIO/J-9295-2012 OI FELIPE-SILVA, ALOISIO/0000-0001-6668-7907 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1558 BP 334A EP 334A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207602406 ER PT J AU Riley, CR Vortmeyer, A Oldfield, EH Lonser, R Salah, B Abu-Asab, M Tsokos, M AF Riley, CR Vortmeyer, A Oldfield, EH Lonser, R Salah, B Abu-Asab, M Tsokos, M TI Endolymphatic sac tumorigenesis; Ultrastructural characteristics SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1587 BP 340A EP 340A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207602435 ER PT B AU Lewis, SM Ullrey, DE Barnard, DE Knapka, JJ AF Lewis, Sherry M. Ullrey, Duane E. Barnard, Dennis E. Knapka, Joseph J. BE Suckow, MA Weisbroth, SH Franklin, CL TI Nutrition SO LABORATORY RAT, 2ND EDITION SE American College of Laboratory Animal Medicine Series LA English DT Article; Book Chapter ID COPPER-DEFICIENT RATS; SPONTANEOUSLY HYPERTENSIVE-RATS; FATTY-ACID COMPOSITION; VITAMIN-E REQUIREMENT; DIETARY ZINC-DEFICIENCY; CENTRAL-NERVOUS-SYSTEM; THYROID-HORMONE METABOLISM; CARBOHYDRATE-FREE DIETS; SPRAGUE-DAWLEY RATS; FED VARYING LEVELS C1 [Lewis, Sherry M.] Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. [Barnard, Dennis E.] NIH, ORS, DIRS, VRP, Bethesda, MD 20892 USA. RP Lewis, SM (reprint author), Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. NR 1099 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045432-0; 978-0-12-074903-4 J9 AM COLL LAB PY 2006 BP 219 EP 301 DI 10.1016/B978-012074903-4/50012-1 PG 83 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA BCT73 UT WOS:000311378400011 ER PT B AU Boorman, GA Everitt, JI AF Boorman, Gary A. Everitt, Jeffrey I. BE Suckow, MA Weisbroth, SH Franklin, CL TI Neoplastic Disease SO LABORATORY RAT, 2ND EDITION SE American College of Laboratory Animal Medicine Series LA English DT Article; Book Chapter ID SPRAGUE-DAWLEY RATS; NATIONAL-TOXICOLOGY-PROGRAM; MONONUCLEAR-CELL LEUKEMIA; PATHOLOGY WORKING GROUP; INDUCED MAMMARY CARCINOGENESIS; GRANULAR LYMPHOCYTE LEUKEMIA; MODERATE DIETARY RESTRICTION; SPONTANEOUS URINARY-BLADDER; SPONTANEOUS TUMOR-INCIDENCE; SPONTANEOUS SKIN NEOPLASMS C1 [Boorman, Gary A.] NIEHS, NCT, Tox Path Working Grp, Res Triangle Pk, NC 27709 USA. [Everitt, Jeffrey I.] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. RP Boorman, GA (reprint author), NIEHS, NCT, Tox Path Working Grp, POB 12233, Res Triangle Pk, NC 27709 USA. NR 222 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045432-0; 978-0-12-074903-4 J9 AM COLL LAB PY 2006 BP 479 EP 511 DI 10.1016/B978-012074903-4/50017-0 PG 33 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA BCT73 UT WOS:000311378400016 ER PT J AU Nadon, NL AF Nadon, Nancy L. BE Suckow, MA Weisbroth, SH Franklin, CL TI Gerontology and Age-Associated Lesions SO LABORATORY RAT, 2ND EDITION SE American College of Laboratory Animal Medicine Series LA English DT Article; Book Chapter ID SPRAGUE-DAWLEY RATS; MODERATE DIETARY RESTRICTION; BROWN-NORWAY RATS; OVARIECTOMIZED OSTEOPENIC RATS; MUSCLE GLUCOSE-TRANSPORT; 14-UNIT T-MAZE; FISCHER-344 RATS; CALORIC RESTRICTION; SKELETAL-MUSCLE; BODY-WEIGHT C1 NIA, Off Biol Resources & Resource Dev, Bethesda, MD 20892 USA. RP Nadon, NL (reprint author), NIA, Off Biol Resources & Resource Dev, 7201 Wisconsin Ave,GW 2C231, Bethesda, MD 20892 USA. NR 92 TC 8 Z9 9 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045432-0 J9 AM COLL LAB PY 2006 BP 761 EP 772 DI 10.1016/B978-012074903-4/50028-5 PG 12 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA BCT73 UT WOS:000311378400027 ER PT J AU Hamm, TE King-Herbert, A Vasbinder, MA AF Hamm, Thomas E., Jr. King-Herbert, Angela Vasbinder, Mary Ann BE Suckow, MA Weisbroth, SH Franklin, CL TI Toxicology SO LABORATORY RAT, 2ND EDITION SE American College of Laboratory Animal Medicine Series LA English DT Article; Book Chapter ID AIN-93 PURIFIED DIETS; REPRODUCTIVE TOXICOLOGY; FISCHER-344 RATS; DRUG-METABOLISM; IN-VIVO; RODENT; TOXICITY; MUTAGENICITY; MUTAGENESIS; SUBSTANCES C1 [King-Herbert, Angela] NIEHS, Lab Expt Pathol, NTP, Res Triangle Pk, NC 27709 USA. [Vasbinder, Mary Ann] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. RP Hamm, TE (reprint author), 105 Martinique Pl, Cary, NC 27511 USA. NR 91 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045432-0 J9 AM COLL LAB PY 2006 BP 803 EP 816 DI 10.1016/B978-012074903-4/50030-3 PG 14 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA BCT73 UT WOS:000311378400029 ER PT J AU Colebunders, R Moses, KR Laurence, J Shihab, HM Semitala, F Lutwama, F Bakeera-Kitaka, S Lynen, L Spacek, L Reynolds, SJ Quinn, TC Viner, B Mayanja-Kizza, H AF Colebunders, R Moses, KR Laurence, J Shihab, HM Semitala, F Lutwama, F Bakeera-Kitaka, S Lynen, L Spacek, L Reynolds, SJ Quinn, TC Viner, B Mayanja-Kizza, H TI A new model to monitor the virological efficacy of antiretroviral treatment in resource-poor countries SO LANCET INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOTAL LYMPHOCYTE COUNT; HIV-1 P24 ANTIGEN; LIMITED SETTINGS; DRUG-RESISTANCE; VIRAL LOAD; HIV-1-INFECTED PATIENTS; REVERSE-TRANSCRIPTASE; SOUTH-AFRICA; IMMUNE RECONSTITUTION AB Monitoring the efficacy of antiretroviral treatment in developing countries is difficult because these countries have few laboratory facilities to test viral load and drug resistance. Those that exist are faced with a shortage of trained staff, unreliable electricity supply, and costly reagents. Not only that, but most HIV patients in resource-poor countries do not have access to such testing. We propose a new model for monitoring antiretroviral treatment in resource-limited settings that uses patients' clinical and treatment history, adherence to treatment, and laboratory indices such as haemoglobin level and total lymphocyte count to identify virological treatment failure, and offers patients future treatment options. We believe that this model can make an accurate diagnosis of treatment failure in most patients. However, operational research is needed to assess whether this strategy works in practice. C1 Inst Trop Med Prince Leopold, B-2000 Antwerp, Belgium. Univ Antwerp, B-2020 Antwerp, Belgium. Makerere Univ, Fac Med, Infect Dis Inst, Kampala, Uganda. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Colebunders, R (reprint author), Inst Trop Med Prince Leopold, B-2000 Antwerp, Belgium. EM bcoleb@itg.be RI Lynen, Lutgarde/A-1212-2014 OI Lynen, Lutgarde/0000-0001-7183-4895 NR 76 TC 46 Z9 46 U1 3 U2 5 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JAN PY 2006 VL 6 IS 1 BP 53 EP 59 DI 10.1016/S1473-3099(05)70327-3 PG 7 WC Infectious Diseases SC Infectious Diseases GA 999ZL UT WOS:000234430600023 PM 16377535 ER PT J AU Rothman, N Skibola, CF Wang, SS Morgan, G Lon, Q Smith, MT Spinelli, JJ Willett, E De Sanjose, S Cocco, P Berndt, SI Brennan, P Brooks-Wilson, A Wacholder, S Becker, N Hartge, P Zheng, TZ Roman, E Holly, EA Boffetta, P Armstrong, B Cozen, W Linet, M Bosch, FX Ennas, MG Holford, TR Gallagher, RP Rollinson, S Bracci, PM Cerhan, JR Whitby, D Moore, PS Leaderer, B Lai, A Spink, C Davis, S Bosch, R Scarpa, A Zhang, YW Severson, RK Yeager, M Chanock, S Nieters, A AF Rothman, N Skibola, CF Wang, SS Morgan, G Lon, Q Smith, MT Spinelli, JJ Willett, E De Sanjose, S Cocco, P Berndt, SI Brennan, P Brooks-Wilson, A Wacholder, S Becker, N Hartge, P Zheng, TZ Roman, E Holly, EA Boffetta, P Armstrong, B Cozen, W Linet, M Bosch, FX Ennas, MG Holford, TR Gallagher, RP Rollinson, S Bracci, PM Cerhan, JR Whitby, D Moore, PS Leaderer, B Lai, A Spink, C Davis, S Bosch, R Scarpa, A Zhang, YW Severson, RK Yeager, M Chanock, S Nieters, A TI Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium SO LANCET ONCOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; B-CELL LYMPHOMA; FACTOR-ALPHA; BIOLOGICAL IMPLICATIONS; PROMOTER POLYMORPHISMS; ALCOHOL-CONSUMPTION; POOLED ANALYSIS; ASSOCIATION; POPULATION; INTERLEUKIN-10 AB Background Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph). Methods We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model. Findings The tumour necrosis factor (TNF) -308G -> A polymorphism was associated with increased risk of nonHodgkin lymphoma (p for trend=0 . 005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1 . 29 [95% CI 1 . 10-1 . 51] for GA and 1.65 [1 . 16-2 . 34] for AA, p for trend < 0 . 0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T -> A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0 . 02), again particularly for diffuse large B-cell lymphoma (p for trend=0 . 006). For individuals homozygous for the TNF -308A allele and carrying at least one IL 10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2 . 13 [1 . 37-3 . 32], p=0 . 00083). Interpretation Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England. British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. Univ York, Epidemiol & Genet Unit, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. Catalan Inst Oncol, Epidemiol & Canc Registry Unit, Barcelona, Spain. Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. Univ Cagliari, Dept Cytomorphol, Cagliari, Italy. Int Agcy Res Canc, Unit Environm Canc, F-69372 Lyon, France. German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94143 USA. Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Dept Hlth & Human Serv, Frederick, MD 21701 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Dept Hlth & Human Serv, Frederick, MD 21701 USA. Univ Verona, Dept Pathol, I-37100 Verona, Italy. Univ Bristol, Dept Pathol & Microbiol, Sch Med Sci, Bristol, Avon, England. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Hosp Verge Cinta, Dept Pathol, Tortosa, Spain. Wayne State Univ, Dept Family Med, Detroit, MI USA. Wayne State Univ, Kamanos Canc Inst, Detroit, MI USA. RP Rothman, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS8116, Bethesda, MD 20892 USA. EM rothmann@mail.nih.gov RI Kane, Eleanor/B-4349-2009; Spinelli, John/B-6210-2013; Tang, Macy/B-9798-2014; Brooks-Wilson, Angela/E-9399-2012; de Sanjose Llongueras, Silvia/H-6339-2014; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012; Armstrong, Bruce/K-9464-2015; scarpa, aldo/K-6832-2016; OI Brooks-Wilson, Angela/0000-0003-1009-6408; BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Armstrong, Bruce/0000-0001-8940-7525; scarpa, aldo/0000-0003-1678-739X; Cerhan, James/0000-0002-7482-178X; Ennas, Maria Grazia/0000-0002-9448-715X FU Intramural NIH HHS; NCI NIH HHS [CA104862, CA45614, CA87014, CA89745, N01-CO-12400] NR 52 TC 260 Z9 268 U1 0 U2 13 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2006 VL 7 IS 1 BP 27 EP 38 DI 10.1016/S1470-2045(05)70434-4 PG 12 WC Oncology SC Oncology GA 001XI UT WOS:000234575600022 PM 16389181 ER PT J AU Goldman, J Gordon, M AF Goldman, J Gordon, M TI Why do chronic myelogenous leukemia stem cells survive allogeneic stem cell transplantation or imatinib: does it really matter? SO LEUKEMIA & LYMPHOMA LA English DT Review DE CML; stem cells; SCT; imatinib; mutations ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; GRANULOCYTE-MACROPHAGE PROGENITORS; COMPLETE CYTOGENETIC REMISSION; KINASE INHIBITOR STI571; VERSUS-HOST-DISEASE; CHRONIC-PHASE; RESIDUAL DISEASE; ABL GENE; CLINICAL RESISTANCE AB It is generally accepted that allogeneic stem cell transplantation can 'cure chronic myelogenous leukemia (CML), although occasional patients relapse more than 10 years after the transplant procedure. Such cures presumably result from the combined effects of leukemia stem cells (LSCs) of the conditioning regimen and the graft-vs.-leukemia (GvL) effect mediated by donor-derived T lymphocytes. The advent of imatinib has revolutionized the management of patients with CML, but much evidence suggests that it does not eradicate all LSCs, which theoretically remain a potential source of relapse to chronic phase or advanced phase disease. Moreover, sub-clones of Philadelphia-positive cells bearing mutations that code for amino-acid substitutions in the Bcr-Abl kinase domain can be identified in patients receiving treatment with imatinib and are associated with varying degrees of resistance to this agent. In the present review, we postulate that LSCs, similar to their normal counterparts, may alternate between cycling and quiescent modes. In the cycling mode, they may express Bcr-Abl protein and be susceptible to the acquisition of additional mutations, whereas, in the quiescent mode, they may express little or no Bcr-Abl oncoprotein, cannot acquire additional mutations and are unaffected by imatinib. Thus, a patient who starts treatment early in the natural history of CML, and who responds to imatinib clinically, may not have had the opportunity to acquire additional mutations in LSCs. In this case, the persistence long-term of quiescent 'non-mutated LSCs despite imatinib treatment might be consistent with freedom from relapse to chronic or advanced phase disease, provided that they remain vulnerable to imatinib when they are recruited into cycle. Conversely, when imatinib resistant Philadelphia-positive sub-clones predominate, this is likely to be due to the recruitment to hematopoiesis of quiescent stem cells that had been in cycle before administration of imatinib and that had acquired additional mutations; in such cases, the best approach to eradication of residual LSCs might be to target expressed proteins thought to be targets for the GvL effect. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci & Technol, Dept Haematol, London, England. RP Goldman, J (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM goldmanj2@nhlbi.nih.gov NR 61 TC 63 Z9 70 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2006 VL 47 IS 1 BP 1 EP 7 DI 10.1080/10428190500407996 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 988YY UT WOS:000233641300001 PM 16321820 ER PT J AU Farma, JM Pingpank, JF Alexander, HR AF Farma, Jeffrey M. Pingpank, James F. Alexander, H. Richard TI Isolated hepatic perfusion: Treating unresectable liver metastases SO LIVER AND PANCREATIC DISEASES MANAGEMENT SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HIGH-DOSE MELPHALAN; COLORECTAL-CANCER; UVEAL MELANOMA; OCULAR MELANOMA; FACTOR-ALPHA; INTERFERON-GAMMA; TNF-ALPHA; IRINOTECAN; SURVIVAL C1 NCI, Surg Metab Sect, Surg Branch, CRC, Bethesda, MD 20892 USA. RP Farma, JM (reprint author), NCI, Surg Metab Sect, Surg Branch, CRC, Rm 4W 5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. NR 45 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 574 BP 1 EP 16 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BER76 UT WOS:000239121900001 PM 16836234 ER PT S AU Hoppin, JA Umbach, DM London, SJ Lynch, CF Alavanja, MCR Sandler, DP AF Hoppin, Jane A. Umbach, David M. London, Stephanie J. Lynch, Charles F. Alavanja, Michael C. R. Sandler, Dale P. BE Mehlman, MA Soffritti, M Landrigan, P Bingham, E Belpoggi, F TI Pesticides and adult respiratory outcomes in the agricultural health study SO LIVING IN A CHEMICAL WORLD: FRAMING THE FUTURE IN LIGHT OF THE PAST SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Framing the Future in Light of the Past - Living in a Chemical World CY SEP 18-21, 2005 CL Bologna, ITALY SP Comuni Carpi, European Ramazzini Fdn, Natl Ramazzini Inst, Collegium Ramazzini DE farmers; occupational exposure; organophosphates; pesticide applicators ID AIRWAY HYPERREACTIVITY; APPLICATORS; INHIBITION; MECHANISMS; SELECTION; FARMERS; WORKERS; WHEEZE; ASTHMA AB In the 1700s, Bernardino Ramazzini was among the first to describe respiratory disease among agricultural workers. Since then, farmers continue to have higher rates of respiratory illnesses, even as changes occur in occupational and environmental exposures on farms. While grain and animal exposures have been well studied for their role in agricultural lung diseases, pesticide exposures have not. Using the Agricultural Health Study, a prospective cohort study of 89,000 licensed pesticide applicators and their spouses in Iowa and North Carolina, we are currently assessing the association of pesticides with respiratory outcomes, including wheeze, adult asthma, farmer's lung, and chronic bronchitis. At enrollment (1993-1997),19% of farmers and 22% of commercial pesticide applicators reported wheeze in the previous year. Using logistic regression models adjusted for age, state, smoking status, and body mass index, we evaluated the association of 40 individual pesticides with wheeze within these two groups separately. In both groups, we observed strong evidence of an association of organophosphates with wheeze. For farmers, the organophosphates chlorpyrifos, malathion, and parathion were positively associated with wheeze; for the commercial applicators, the organophosphates chlorpyrifos, dichlorvos, and phorate were positively associated with wheeze. Chlorpyrifos was strongly associated with wheeze in a dose-dependent manner in both groups; use of chlorpyrifos for at least 20 days per year had an odds ratio of 1.48 (95% confidence interval [CI] = 1.00-2.19) for farmers and 1.96 (95% CI =1.05-3.66) for commercial applicators. Our wheeze results are consistent with recent animal models that support a role for organophosphates and respiratory outcomes. C1 NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. NCI, NIH, DHHS, Occupat Epidemiol Branch, Rockville, MD 20852 USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, NIH, DHHS, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018; London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS NR 14 TC 28 Z9 29 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-653-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1076 BP 343 EP 354 DI 10.1196/annals.1371.044 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Multidisciplinary Sciences; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Science & Technology - Other Topics; Toxicology GA BFH91 UT WOS:000241943500025 PM 17119214 ER PT S AU Olden, K AF Olden, Kenneth BE Mehlman, MA Soffritti, M Landrigan, P Bingham, E Belpoggi, F TI Toxicogenomics - A new systems toxicology approach to understanding of gene-environment interactions SO LIVING IN A CHEMICAL WORLD: FRAMING THE FUTURE IN LIGHT OF THE PAST SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Framing the Future in Light of the Past - Living in a Chemical World CY SEP 18-21, 2005 CL Bologna, ITALY SP Comuni Carpi, European Ramazzini Fdn, Natl Ramazzini Inst, Collegium Ramazzini DE gene-gene interactions; gene-environment interactions; environmental response machinery; susceptibility; genomics; proteomics; metabolomics; toxicogenomics; biomarkers ID FINLAND; CANCER; TWINS AB Toxicogenomics is a new interdisciplinary area of research being developed to monitor the expression of multiple genes, proteins, and metabolites simultaneously. It combines new technologies in genomics, proteomics, and metabolomics with traditional tools of pathology and toxicology to study biological response to drugs and other environmental xenobiotics. The biological response to environmental exposure is so complex and involves so many interactive factors that the use of a systems biology analytical approach is required. In my opinion, the development of the field of toxicogenomics will provide powerful and relatively inexpensive tools to identify biomarkers and to relate exposure and biological events during disease progression. C1 NIEHS, Cell Adhesion & Metastasis Sect, Mol Carcinogenesis Lab, NIH,US Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Olden, K (reprint author), NIEHS, Cell Adhesion & Metastasis Sect, Mol Carcinogenesis Lab, NIH,US Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM olden@niehs.nih.gov NR 8 TC 12 Z9 12 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 1-57331-653-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1076 BP 703 EP 706 DI 10.1196/annals.1371.026 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Multidisciplinary Sciences; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Science & Technology - Other Topics; Toxicology GA BFH91 UT WOS:000241943500058 PM 17119247 ER PT S AU Merrick, BA AF Merrick, B. Alex BE Mehlman, MA Soffritti, M Landrigan, P Bingham, E Belpoggi, F TI Toxicoproteomics in liver injury and inflammation SO LIVING IN A CHEMICAL WORLD: FRAMING THE FUTURE IN LIGHT OF THE PAST SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Framing the Future in Light of the Past - Living in a Chemical World CY SEP 18-21, 2005 CL Bologna, ITALY SP Comuni Carpi, European Ramazzini Fdn, Natl Ramazzini Inst, Collegium Ramazzini DE proteomics; toxicoproteomics; biomarkers; tissue injury; liver; environmental toxicity ID PROTEOMICS; EXPRESSION; GENE; BIOINFORMATICS; INTEGRATION; BIOMARKERS; DISEASE AB Toxicoproteomics, in applying proteomics to toxicology, seeks to identify critical proteins and pathways in biological systems responding to adverse chemical exposures and environmental stressors using global protein expression technologies. Toxicoproteomics is being exploited for the discovery of new biomarkers and toxicity signatures in target organs, such as liver, in major biological processes, such as inflammation, in mapping serum, plasma, and other biofluid proteomes, and in parallel proteomic and transcriptomic studies. The new field of toxicoproteomics is uniquely positioned toward discovery of new biomarkers and signatures of tissue injury and a better understanding of protein expression responses during toxicity and environmental disease. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Merrick, BA (reprint author), NIEHS, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM merrick@niehs.nih.gov FU Intramural NIH HHS NR 23 TC 14 Z9 15 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-653-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1076 BP 707 EP 717 DI 10.1196/annals.1371.017 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Multidisciplinary Sciences; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Science & Technology - Other Topics; Toxicology GA BFH91 UT WOS:000241943500059 PM 17119248 ER PT S AU Patterson, RM Germolec, DR AF Patterson, Rachel M. Germolec, Dori R. BE Mehlman, MA Soffritti, M Landrigan, P Bingham, E Belpoggi, F TI Gene expression alterations in immune system pathways following exposure to immunosuppressive chemicals SO LIVING IN A CHEMICAL WORLD: FRAMING THE FUTURE IN LIGHT OF THE PAST SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Framing the Future in Light of the Past - Living in a Chemical World CY SEP 18-21, 2005 CL Bologna, ITALY SP Comuni Carpi, European Ramazzini Fdn, Natl Ramazzini Inst, Collegium Ramazzini DE gene expression; spleen; thymus; immunosuppression; microarray; genomics ID MICE; SUBPOPULATIONS; SENSITIVITY; RESISTANCE; MICROARRAY; APOPTOSIS; GENOMICS; TARGETS; THYMUS; POINTS AB Exposure to environmental agents can affect a number of adverse immunological outcomes, including changes in the incidence of infectious disease. Diethylstilbestrol (DES), dexamethasone (DEX), cyclophosphamide, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are immunosuppressive chemicals that can induce similar pathophysiological end points in the thymus; however, the mechanism of toxicity is different for each compound. We examined differential gene expression in the spleen and thymus following chemical exposure and correlated these changes with alterations in functional immune end points and our knowledge of the known mechanisms of action. RNA from the spleen and thymus has been analyzed using Illumina Sentrix arrays and BeadStudio software. Preliminary data suggest that DES induced the greatest number of gene changes in the spleen, while DEX induced the most changes in the thymus. In both spleen and thymus, genomic analysis revealed gene expression changes that were common to multiple chemicals and that may be associated with xenobiotic-induced immune system perturbations, including alterations in genes associated with apoptosis, antigen processing and presentation, and response to biotic stimulus. This was particularly evident in the thymus, where there were many similarities in the expression profiles, as well as gene alterations unique to a single compound. In contrast, expression profiles in spleen were more distinct. The category of genes most profoundly affected by all four chemicals was response to biotic stimulus: there were both clusters of genes modulated by multiple chemicals and genes altered by a single chemical. The distinct gene profiles may specifically relate to cellular targets and mechanism of action. C1 NIEHS, Res Triangle Pk, NC 27719 USA. RP Germolec, DR (reprint author), 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27719 USA. EM germolec@niehs.nih.gov FU Intramural NIH HHS NR 18 TC 9 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-653-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1076 BP 718 EP 727 DI 10.1196/annals.1371.023 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Multidisciplinary Sciences; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Science & Technology - Other Topics; Toxicology GA BFH91 UT WOS:000241943500060 PM 17119249 ER PT S AU Li, GL Yin, SN AF Li, Guilan Yin, Songnian BE Mehlman, MA Soffritti, M Landrigan, P Bingham, E Belpoggi, F TI Progress of epidemiological and molecular epidemiological studies on benzene in China SO LIVING IN A CHEMICAL WORLD: FRAMING THE FUTURE IN LIGHT OF THE PAST SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Framing the Future in Light of the Past - Living in a Chemical World CY SEP 18-21, 2005 CL Bologna, ITALY SP Comuni Carpi, European Ramazzini Fdn, Natl Ramazzini Inst, Collegium Ramazzini DE benzene; epidemiology; poisoning; hematotoxicity; genomics; molecular aspects; individual susceptibility; adducts ID EXPOSED WORKERS; COHORT; HEMATOTOXICITY; MALIGNANCIES; BIOMARKERS; ADDUCTS; HUMANS; BLOOD AB Benzene is an organic solvent that has been used in industry for about 100 years throughout the world. Since 1973, a series of toxicological and molecular epidemiological studies on benzene were conducted by researchers at the Chinese Academy of Preventive Medicine (CAPM) (1973-1986) and subsequently by a collaboration between the CAPM and the National Cancer Institute (NCI) in the United States that began in 1986, which was joined by investigators from the University of California at Berkeley, the University of North Carolina at Chapel Hill, and New York University. The findings demonstrated that the risk of leukemia and lymphoma among benzene-exposed workers was significantly increased, with elevated risks for leukemia present not only at higher exposure but also among workers exposed to under 10 ppm. Therefore, the benzene permissible level was decreased to 1.8 ppm (6 mg/m(3)) and benzene-induced leukemia is treated as an occupational cancer in China. The benzene permissible level is 1.0 in the United States and in several other developed countries and it has been suggested to be decreased to 0.5 ppm (ACGIH). A number of potential biomarkers are related to benzene exposure and poisoning. Some of these are benzene oxide-protein adducts, chromosome aberration of lymphocytes, and GPA mutations in erythrocytes, a decrease in B cell and CD4(-)T cell counts in peripheral blood, and altered expression of CXCL16, ZNF331, JUN, and PF4 in lymphocytes. Variation in multiple benzene metabolizing genes may be associated with risk of benzene hematotoxicity, including CYP2E1, MPO, NQO1, and GSTT1. C1 China CDC, Natl Inst Occupat Hlth & Poison Control, Natl Chem Assessment Ctr, Beijing 100050, Peoples R China. NCI, Bethesda, MD 20892 USA. China CDC, Int Benzene Res Team, Beijing 100050, Peoples R China. RP Li, GL (reprint author), China CDC, Natl Inst Occupat Hlth & Poison Control, Natl Chem Assessment Ctr, 29 Nan Wei Rd, Beijing 100050, Peoples R China. EM guilanli@263.net.cn NR 30 TC 11 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-653-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1076 BP 800 EP 809 DI 10.1196/annals.1371.035 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Multidisciplinary Sciences; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Science & Technology - Other Topics; Toxicology GA BFH91 UT WOS:000241943500068 PM 17119257 ER PT J AU Spencer, RG Fishbein, KW Cheng, AW Mattson, MP AF Spencer, RG Fishbein, KW Cheng, AW Mattson, MP TI Compatibility of Gd-DTPA perfusion and histologic studies of the brain SO MAGNETIC RESONANCE IMAGING LA English DT Article DE Gd-DTPA; brain imaging; MR microscopy; histology; immunohistochemistry ID MAGNETIC-RESONANCE MICROSCOPY AB Histology, including immunohistochemistry, and magnetic resonance imaging microscopy (mu MRI) are complementary techniques for the analysis of brain structure. Therefore, mu MRI analysis, often of formalin-fixed tissue, precedes histologic evaluation of the same experimental animal in many studies. However, the application of gadopentetate dimeglumine (Gd-DTPA), while of value for MRI studies, has an unknown effect on subsequent histology. We demonstrate here that for the mouse brain, histology with Nissl staining and immunostaining for microtubule-associated protein 2, using standard techniques for tissue preparation, are unaffected by prior perfusion of the tissue with Gd-DTPA. This conclusion was based on qualitative morphologic comparisons of stained sections, as well as quantification of mean immunofluorescence pixel intensities from Gd-treated (mean +/- S.D. = 131.2 +/- 28.4; n = 3) as compared to nontreated specimens (116.2 +/- 34.7; n = 3, P = .7). Therefore, Gd-DTPA may be applied as a mu MRI contrast agent in formalin-fixed brain tissue prior to histologic studies. (c) 2006 Elsevier Inc. All rights reserved. C1 NIA, Nucl Magnet Resonance Unit, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Spencer, RG (reprint author), NIA, Nucl Magnet Resonance Unit, Intramural Res Program, Baltimore, MD 21224 USA. EM spencer@helix.nih.gov RI Mattson, Mark/F-6038-2012; OI Fishbein, Kenneth/0000-0002-6353-4603 NR 10 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JAN PY 2006 VL 24 IS 1 BP 27 EP 31 DI 10.1016/j.mri.2005.10.017 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 006SH UT WOS:000234916800004 PM 16410175 ER PT J AU Centeno, JA Tchounwou, PB Patlolla, AK Mullick, FG Murakata, L Meza, E Todorov, T Longfellow, D Yedjou, CG AF Centeno, Jose A. Tchounwou, Paul B. Patlolla, Anita K. Mullick, Florabel G. Murakata, Linda Meza, Elizabeth Todorov, Todor Longfellow, David Yedjou, Clement G. BE Naidu, R Smith, E Owens, G Bhattacharya, P Nadebaum, P TI Environmental pathology and health effects of arsenic poisoning A critical review SO MANAGING ARSENIC IN THE ENVIRONMENT: FROM SOIL TO HUMAN HEALTH LA English DT Review; Book Chapter ID INDUCED CELL-TRANSFORMATION; DRINKING-WATER; LUNG-CANCER; DOSE-RESPONSE; WEST-BENGAL; SODIUM ARSENITE; NORTHERN SWEDEN; BLADDER-CANCER; MORTALITY; EXPOSURE C1 [Centeno, Jose A.; Mullick, Florabel G.; Murakata, Linda; Meza, Elizabeth; Todorov, Todor] Armed Forces Inst Pathol, Dept Environm & Toxicol Pathol, Div Biophys Toxicol, Washington, DC 20306 USA. [Tchounwou, Paul B.; Patlolla, Anita K.; Yedjou, Clement G.] Jackson State Univ, NIH RCMI Ctr Environm Hlth, Environm Toxicol Program, Jackson, MS USA. [Longfellow, David] NCI, Div Canc Biol, Bethesda, MD 20892 USA. [Longfellow, David] NCI, Canc Etiol Branch, Bethesda, MD 20892 USA. RP Centeno, JA (reprint author), Armed Forces Inst Pathol, Dept Environm & Toxicol Pathol, Div Biophys Toxicol, Washington, DC 20306 USA. NR 87 TC 5 Z9 5 U1 0 U2 1 PU CSIRO PUBLISHING PI COLLINGWOOD PA 150 OXFORD STREET, PO BOX 1139, COLLINGWOOD, VIC 3066, AUSTRALIA BN 978-0-643-09351-5 PY 2006 BP 311 EP 327 PG 17 WC Engineering, Environmental; Environmental Sciences; Toxicology SC Engineering; Environmental Sciences & Ecology; Toxicology GA BVM06 UT WOS:000291852600018 ER PT J AU Fleisher, TA AF Fleisher, Thomas A. BE Detrick, B Hamilton, RG Folds, JD TI Proteomics and Genomics Methodology in the Clinical Immunology Laboratory SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Editorial Material; Book Chapter C1 NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 3 EP 3 PG 1 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100002 ER PT J AU Hortin, GL Remaley, AT AF Hortin, Glen L. Remaley, Alan T. BE Detrick, B Hamilton, RG Folds, JD TI Introduction to Protein Analysis SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Editorial Material; Book Chapter ID HUMAN PLASMA PROTEOME; POSTTRANSLATIONAL MODIFICATIONS; CLASS-I; ANTIGEN C1 [Hortin, Glen L.; Remaley, Alan T.] NIH, Dept Lab Med, Warren G Magnusson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Warren G Magnusson Clin Ctr, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 4 EP 6 PG 3 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100003 ER PT J AU Remaley, AT Hortin, GL AF Remaley, Alan T. Hortin, Glen L. BE Detrick, B Hamilton, RG Folds, JD TI Protein Analysis for Diagnostic Applications SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID LASER-DESORPTION/IONIZATION-TIME; FLIGHT-MASS-SPECTROMETRY; HUMAN PLASMA PROTEOME; BLOOD COLLECTION TUBES; 2-DIMENSIONAL ELECTROPHORESIS; CLINICAL PROTEOMICS; SERUM PROTEOMICS; OVARIAN-CANCER; IMMUNOASSAY; ANTIBODY C1 [Remaley, Alan T.; Hortin, Glen L.] NIH, Dept Lab Med, Warren G Magnusson Clin Ctr, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NIH, Dept Lab Med, Warren G Magnusson Clin Ctr, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. NR 79 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 7 EP 21 PG 15 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100004 ER PT J AU Chanock, SJ AF Chanock, Stephen J. BE Detrick, B Hamilton, RG Folds, JD TI Genomics and Chip Technology SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID GENE; PREDICTION; CANCER; ASSAY; CLASSIFICATION; AMPLIFICATION; FUTURE C1 [Chanock, Stephen J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Chanock, Stephen J.] NCI, Adv Technol Ctr, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Pediat Oncol Branch, 8717 Grovemont Circle, Bethesda, MD 20892 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 22 EP 25 PG 4 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100005 ER PT J AU Hooks, JJ AF Hooks, John J. BE Detrick, B Hamilton, RG Folds, JD TI MANUAL OF Molecular AND Clinical Laboratory Immunology 7TH EDITION Introduction SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Editorial Material; Book Chapter C1 NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bldg 10,Room 10N248, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 339 EP 339 PG 1 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100039 ER PT J AU Nutman, TB AF Nutman, Thomas B. BE Detrick, B Hamilton, RG Folds, JD TI MANUAL OF Molecular AND Clinical Laboratory Immunology 7TH EDITION Introduction SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter C1 [Nutman, Thomas B.] NIH, Helminth Immunol Sect, Bethesda, MD 20892 USA. [Nutman, Thomas B.] NIH, Clin Parasitol Unit, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Nutman, TB (reprint author), NIH, Helminth Immunol Sect, Bldg 4,Rm B1-03, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 555 EP 556 PG 2 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100065 ER PT J AU Wilson, M Schantz, PM Nutman, T AF Wilson, Marianna Schantz, Peter M. Nutman, Thomas BE Detrick, B Hamilton, RG Folds, JD TI Molecular and Immunological Approaches to the Diagnosis of Parasitic Infections SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID POLYMERASE CHAIN-REACTION; ALVEOLAR ECHINOCOCCOSIS; LABORATORY DIAGNOSIS; WUCHERERIA-BANCROFTI; TRYPANOSOMA-CRUZI; MALARIA PARASITES; FECAL SPECIMENS; GIARDIA-LAMBLIA; ANTIGEN; ASSAY C1 [Wilson, Marianna; Schantz, Peter M.] Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30341 USA. [Nutman, Thomas] NIH, Helminth Immunol Sect, Bethesda, MD 20892 USA. [Nutman, Thomas] NIH, Clin Parasitol Unit, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Wilson, M (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, MS F-36,4770 Buford Hwy, Atlanta, GA 30341 USA. NR 38 TC 6 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 557 EP 568 PG 12 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100066 ER PT J AU Shah, KV Major, EO AF Shah, Keerti V. Major, Eugene O. BE Detrick, B Hamilton, RG Folds, JD TI Papillomaviruses and Polyomaviruses SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; JC VIRUS; HUMAN-BRAIN; BK VIRUS; CAUSAL ASSOCIATION; SERUM ANTIBODIES; CERVICAL-CANCER; SIMIAN-VIRUS-40; CELLS; PATHOGENESIS C1 [Shah, Keerti V.] Johns Hopkins Univ, Blooomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. [Major, Eugene O.] NINDS, Mol Med & Virol Sect, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Shah, KV (reprint author), Johns Hopkins Univ, Blooomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St, Baltimore, MD 21205 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 669 EP 676 PG 8 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100076 ER PT J AU Baseler, MW AF Baseler, Michael W. BE Detrick, B Hamilton, RG Folds, JD TI MANUAL OF Molecular AND Clinical Laboratory Immunology 7TH EDITION Introduction SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Editorial Material; Book Chapter C1 NCI FCRDC, Appl & Dev Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Baseler, MW (reprint author), NCI FCRDC, Appl & Dev Res Program, SAIC Frederick Inc, POB B,Bldg 469-6, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 833 EP 833 PG 1 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100094 ER PT J AU Dewar, R Highbarger, H Davey, R Metcalf, J AF Dewar, Robin Highbarger, Helene Davey, Richard Metcalf, Julia BE Detrick, B Hamilton, RG Folds, JD TI Principles and Procedures of Human Immunodeficiency Virus Serodiagnosis SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID GROUP-O INFECTIONS; HIV-ANTIBODY; IMMUNOBLOT ASSAY; IMMUNE-COMPLEXES; UNITED-STATES; WESTERN-BLOT; P24 ANTIGEN; TESTS; INDIVIDUALS; IMMUNOASSAY C1 [Dewar, Robin; Highbarger, Helene] NCI Frederick, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Davey, Richard; Metcalf, Julia] NIAID, Off Clin Res, NIH, Bethesda, MD 20892 USA. RP Dewar, R (reprint author), NCI Frederick, Clin Serv Program, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. NR 47 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 834 EP 846 PG 13 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100095 ER PT J AU Stevens, RA Lempicki, RA Natarajan, V Higgins, J Adelsberger, JW Metcalf, JA AF Stevens, Randy A. Lempicki, Richard A. Natarajan, Ven Higgins, Jeanette Adelsberger, Joseph W. Metcalf, Julia A. BE Detrick, B Hamilton, RG Folds, JD TI General Immunologic Evaluation of Patients with Human Immunodeficiency Virus Infection SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID HIV-1 INFECTION; T-LYMPHOCYTES; IN-VIVO; CELLS; KI-67; ANTIGEN; SUBPOPULATIONS; IDENTIFICATION; PROLIFERATION; EXPRESSION C1 [Stevens, Randy A.; Lempicki, Richard A.; Natarajan, Ven; Higgins, Jeanette; Adelsberger, Joseph W.] NCI Frederick, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Metcalf, Julia A.] NIAID, Off Clin Res, NIH, Bethesda, MD 20892 USA. RP Stevens, RA (reprint author), NCI Frederick, Clin Serv Program, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 847 EP 861 PG 15 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100096 ER PT J AU Elbeik, T Highbarger, H Dewar, R Natarajan, V Imamichi, H Imamichi, T AF Elbeik, Tarek Highbarger, Helene Dewar, Robin Natarajan, Ven Imamichi, Hiromi Imamichi, Tomozumi BE Detrick, B Hamilton, RG Folds, JD TI Quantitation of Viremia and Determination of Drug Resistance in Patients with Human Immunodeficiency Virus Infection SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID ACTIVE ANTIRETROVIRAL THERAPY; POLYMERASE-CHAIN-REACTION; HIV-1 GENOTYPING SYSTEM; GROUP-M SUBTYPES; REVERSE-TRANSCRIPTASE; CLEAVAGE SITES; PLASMA SAMPLES; VIRAL FITNESS; CULTURE ASSAY; TYPE-1 RNA C1 [Elbeik, Tarek] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94110 USA. [Elbeik, Tarek] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Highbarger, Helene; Dewar, Robin; Natarajan, Ven; Imamichi, Hiromi; Imamichi, Tomozumi] NCI Frederick, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Elbeik, T (reprint author), Univ Calif San Francisco, Dept Lab Med, Bldg NH,Room 2M35,1001 Potrero Ave, San Francisco, CA 94110 USA. NR 57 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 862 EP 877 PG 16 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100097 ER PT J AU Hengel, RL Imamichi, T Migueles, SA AF Hengel, Richard L. Imamichi, Tomozumi Migueles, Stephen A. BE Detrick, B Hamilton, RG Folds, JD TI Measurement of T-Cell-Specific Immunity in Patients with Human Immunodeficiency Virus Infection SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID FLOW-CYTOMETRY; ANTIRETROVIRAL THERAPY; HIV-INFECTION; RECEPTOR; RECOGNITION; PHENOTYPE C1 [Hengel, Richard L.] Infect Dis Solut, Atlanta, GA 30309 USA. [Imamichi, Tomozumi] NCI Frederick, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Migueles, Stephen A.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Hengel, RL (reprint author), Infect Dis Solut, 35 Collier Rd,Suite M245, Atlanta, GA 30309 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 878 EP + PG 15 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100098 ER PT J AU Holland, SM AF Holland, Steven M. BE Detrick, B Hamilton, RG Folds, JD TI Neutropenia and Neutrophil Defects SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID CHRONIC GRANULOMATOUS-DISEASE C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bldg 10,CRC B3-4141,MSC 1684,10 Ctr Dr, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 924 EP 932 PG 9 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100104 ER PT J AU Klion, AD AF Klion, Amy D. BE Detrick, B Hamilton, RG Folds, JD TI Diagnosis of Hypereosinophilic Syndromes SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID IMATINIB-MESYLATE; MYELOPROLIFERATIVE VARIANT; FAMILIAL EOSINOPHILIA; FIP1L1-PDGFRA FUSION; EPISODIC ANGIOEDEMA; T-CELLS; ACTIVATION; TH2; INTERLEUKIN-5; MASTOCYTOSIS C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Klion, AD (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr, Bethesda, MD 20892 USA. NR 42 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 984 EP 990 PG 7 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100111 ER PT J AU Hooks, JJ Chin, MS Chan, CC Detrick, B AF Hooks, John J. Chin, Marian S. Chan, Chi-Chao Detrick, Barbara BE Detrick, B Hamilton, RG Folds, JD TI Monitoring Autoimmune Reactivity within the Retina SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID NERVOUS-SYSTEM LYMPHOMA; MELANOMA-ASSOCIATED RETINOPATHY; SYMPATHETIC OPHTHALMIA; ONCHOCERCA-VOLVULUS; BIPOLAR CELLS; IN-VIVO; ANTIBODIES; INTERLEUKIN-10; AUTOANTIBODIES; PHOTORECEPTOR C1 [Hooks, John J.; Chin, Marian S.] NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Detrick, Barbara] Johns Hopkins Univ, Sch Med, Dept Pathol Meyer B125, Immunol Lab, Baltimore, MD 21205 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bldg 10,Room 10N248, Bethesda, MD 20892 USA. NR 24 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 1136 EP 1140 PG 5 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100130 ER PT J AU Raffeld, M Jaffe, ES AF Raffeld, Mark Jaffe, Elaine S. BE Detrick, B Hamilton, RG Folds, JD TI Malignancies of the Immune System: Use of Immunologic and Molecular Tumor Markers in Classification and Diagnostics SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID B-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; NON-HODGKINS-LYMPHOMA; REED-STERNBERG CELLS; DISTINCT CLINICOPATHOLOGICAL ENTITY; POLYMERASE CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; T-CELL; GENE-EXPRESSION C1 [Raffeld, Mark; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Raffeld, M (reprint author), NCI, Hematopathol Sect, Pathol Lab, 10 Ctr Dr,Bldg 10,Room 2N110,MSC-1500, Bethesda, MD 20892 USA. NR 114 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 1152 EP 1170 PG 19 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100133 ER PT J AU Winters, ME Lowenthal, M Feldman, AL Liotta, LA AF Winters, Mary E. Lowenthal, Mark Feldman, Andrew L. Liotta, Lance A. BE Detrick, B Hamilton, RG Folds, JD TI The Future of Cancer Diagnostics: Proteomics, Immunoproteomics, and Beyond SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID CATALYZED REPORTER DEPOSITION; RESONANCE MASS-SPECTROMETRY; SIGNAL AMPLIFICATION; CLINICAL PROTEOMICS; PROTEIN MICROARRAYS; MARKERS; ELECTROPHORESIS; TECHNOLOGY; GEL C1 [Winters, Mary E.; Lowenthal, Mark; Feldman, Andrew L.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Winters, Mary E.; Lowenthal, Mark; Feldman, Andrew L.] NCI, US FDA, Clin Prote Program, Bethesda, MD 20892 USA. [Liotta, Lance A.] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA. RP Winters, ME (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 1183 EP 1192 PG 10 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100135 ER PT J AU Tyan, DB Carrington, M AF Tyan, Dolly B. Carrington, Mary BE Detrick, B Hamilton, RG Folds, JD TI Human Natural Killer Cell Receptors SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID MHC CLASS-I; KIR HAPLOTYPES CONTAIN; HUMAN NK CELLS; INHIBITORY RECEPTORS; GENE CONTENT; HLA-G; CYTOMEGALOVIRUS-INFECTION; HEMATOPOIETIC TRANSPLANTS; T-CELLS; NKG2D C1 [Tyan, Dolly B.] Cedars Sinai Med Ctr, Inst Med Genet, HLA, Los Angeles, CA 90048 USA. [Tyan, Dolly B.] Cedars Sinai Med Ctr, Inst Med Genet, Immunogenet Lab, Los Angeles, CA 90048 USA. [Carrington, Mary] NCI, Lab Genom Div, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Tyan, DB (reprint author), Cedars Sinai Med Ctr, Inst Med Genet, HLA, SSB-197,8723 Alden Dr, Los Angeles, CA 90048 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 1260 EP 1268 PG 9 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100141 ER PT J AU Di Giulio, R Billiard, S Meyer, J Wassenberg, D Hodson, P AF Di Giulio, Richard Billiard, Sonya Meyer, Joel Wassenberg, Deena Hodson, Peter TI Synergistic developmental toxicity of polycyclic aromatic hydrocarbons: Towards a mechanistic understanding SO MARINE ENVIRONMENTAL RESEARCH LA English DT Meeting Abstract C1 Duke Univ, Durham, NC 27706 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Queens Univ, Kingston, ON K7L 3N6, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0141-1136 J9 MAR ENVIRON RES JI Mar. Environ. Res. PY 2006 VL 62 SU S BP S45 EP S46 PG 2 WC Environmental Sciences; Marine & Freshwater Biology; Toxicology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Toxicology GA 062PU UT WOS:000238957800021 ER PT J AU Fleming, LE Broad, K Clement, A Dewailly, E Elmir, S Knap, A Pomponi, SA Smith, S Gabriele, HS Walsh, P AF Fleming, L. E. Broad, K. Clement, A. Dewailly, E. Elmir, S. Knap, A. Pomponi, S. A. Smith, S. Gabriele, H. Solo Walsh, P. TI Oceans and human health: Emerging public health risks in the marine environment SO MARINE POLLUTION BULLETIN LA English DT Article; Proceedings Paper CT International Workshop on Marine-based Public Health Risk CY JUL, 2003 CL Sardinia, ITALY DE harmful algal bloom (HAB); microbial pollution; global climate change; anthropogenic pollution; natural products; marine models ID FLORIDA RED TIDE; NATURAL-PRODUCTS; UNITED-STATES; AEROSOLIZED BREVETOXINS; SUBTROPICAL ENVIRONMENT; MULTISTATE OUTBREAK; RECREATIONAL WATER; ESCHERICHIA-COLI; ATLANTIC COAST; SEAFOOD TOXINS AB There has been an increasing recognition of the inter-relationship between human health and the oceans. Traditionally, the focus of research and concern has been on the impact of human activities on the oceans, particularly through anthropogenic pollution and the exploitation of marine resources. More recently, there has been recognition of the potential direct impact of the oceans on human health, both detrimental and beneficial. Areas identified include: global change, harmful algal blooms (HABs), microbial and chemical contamination of marine waters and seafood, and marine models and natural products from the seas. It is hoped that through the recognition of the inter-dependence of the health of both humans and the oceans, efforts will be made to restore and preserve the oceans. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF NIEHS Oceans & Human Hlth Ctr, Miami, FL 33149 USA. Univ Miami, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Univ Laval, Publ Hlth Res Unit, CHUQ, Quebec City, PQ, Canada. Miami Dade Cty Hlth Dept, Miami, FL USA. Univ Miami, Ctr Ecosyst Sci & Policy, Miami, FL USA. Columbia Univ, Ctr Res Environm Decis, New York, NY USA. RP Fleming, LE (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF NIEHS Oceans & Human Hlth Ctr, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. EM lfleming@med.miami.edu FU NIEHS NIH HHS [P01 ES010594, P01 ES010594-06A1, P30 ES005705, P30 ES05705, P50 ES012736, P50 ES012736-03, P50ES12736] NR 147 TC 78 Z9 84 U1 7 U2 40 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0025-326X EI 1879-3363 J9 MAR POLLUT BULL JI Mar. Pollut. Bull. PY 2006 VL 53 IS 10-12 BP 545 EP 560 DI 10.1016/j.marpolbul.2006.08.012 PG 16 WC Environmental Sciences; Marine & Freshwater Biology SC Environmental Sciences & Ecology; Marine & Freshwater Biology GA 115GO UT WOS:000242723000003 PM 16996542 ER PT S AU Martinez, ED Dull, AB Beutler, JA Hager, GL AF Martinez, Elisabeth D. Dull, Angie B. Beutler, John A. Hager, Gordon L. BE Inglese, J TI High-content fluorescence-based screening for epigenetic-modulators SO MEASURING BIOLOGICAL RESPONSES WITH AUTOMATED MICROSCOPY SE Methods in Enzymology LA English DT Review; Book Chapter ID HISTONE-DEACETYLASE INHIBITORS; PHASE-I; DNA METHYLTRANSFERASES; BINDING-PROTEIN; LEUKEMIA; CANCER; GENES; EXPRESSION; HYPERMETHYLATION; TRANSLOCATION AB Epigenetic processes have gained a great amount of attention in recent years, particularly due to the influence they exert on gene transcription. Several human diseases, including cancer, have been linked to aberrant epigenetic pathways. Consequently, the cellular enzymes that mediate epigenetic events, including histone deacetylases and DNA methyltransferases, have become prime molecular targets for therapeutic intervention. The effective and specific chemical inhibition of these activities is a top priority in cancer research and appears to have therapeutic potential. This chapter describes the development of mammalian cell-based fluorescent assays to screen for epigenetic modulators using an innovative combination of approaches. Detailed protocols for the use of the assays in drug screens, as well as for the initial characterization of hits, are provided. Furthermore, options for evaluating the mechanism of action of these compounds are presented and principles to govern the choice of hit compounds for the development of leads are discussed. C1 NCI, Lab Receptor Biol & Gene Express, Hormone Act & Oncogenesis Sect, NIH, Bethesda, MD 20892 USA. SAIC Frederic INc, Basic Res Program, Mol Targets Dev Program, NCI,NIH, Frederick, MD 21701 USA. RP Martinez, ED (reprint author), NCI, Lab Receptor Biol & Gene Express, Hormone Act & Oncogenesis Sect, NIH, Bethesda, MD 20892 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 30 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182819-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 414 BP 21 EP 36 DI 10.1016/S0076-6879(06)14002-1 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFN15 UT WOS:000243221500002 PM 17110184 ER PT S AU Martinez, ED Hager, GL AF Martinez, Elisabeth D. Hager, Gordon L. BE Inglese, J TI Development of assays for nuclear receptor modulators using fluorescently tagged proteins SO MEASURING BIOLOGICAL RESPONSES WITH AUTOMATED MICROSCOPY SE Methods in Enzymology LA English DT Review; Book Chapter ID GLUCOCORTICOID-RECEPTOR; PROGESTERONE-RECEPTOR; GENE; TRANSLOCATION; LOCALIZATION; EXPRESSION; MUTATIONS; LIGANDS; CHIMERA; BINDING AB This chapter describes a method for designing cell-based assays to screen for nuclear receptor modulators. The basic strategy consists in following the movement of the receptors from the cytoplasm into the nucleus in response to ligand binding or analogous activating events. The receptors are tagged with green fluorescent protein for automated, fluorescent detection. In the case of constitutively nuclear receptors, they are engineered for cytoplasmic retention in the absence of an activating signal by fusing them to specific regions of the glucocorticoid receptor, which is found predominantly in the cytoplasm of cultured cells. The resulting chimeras respond to ligands or receptor modulators by translocating into the nucleus. This movement is monitored easily by automated fluorescent microscopy and serves as the basis for screening libraries. Finally, secondary assays built into the cell system can differentiate between modulators that stimulate, inhibit, or do not affect the transcriptional activity of the receptor under study. This approach has been validated for both the estrogen receptor and the retinoic acid receptor and should be applicable to any member of the superfamily, facilitating the identification of new ligands and selective receptor modulators. C1 NCI, Lab Receptor Biol & Gene Express, Hormone Act & Oncogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Martinez, ED (reprint author), NCI, Lab Receptor Biol & Gene Express, Hormone Act & Oncogenesis Sect, NIH, Bethesda, MD 20892 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182819-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 414 BP 37 EP 50 DI 10.1016/S0076-6879(06)14003-3 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFN15 UT WOS:000243221500003 PM 17110185 ER PT S AU Oakley, RH Hudson, CC Sjaastad, MD Loomis, CR AF Oakley, Robert H. Hudson, Christine C. Sjaastad, Michael D. Loomis, Carson R. BE Inglese, J TI The ligand-independent translocation assay: An enabling technology for screening orphan G protein-coupled receptors by arrestin recruitment SO MEASURING BIOLOGICAL RESPONSES WITH AUTOMATED MICROSCOPY SE Methods in Enzymology LA English DT Review; Book Chapter ID BETA-ARRESTIN; ENDOCYTOSIS; KINASES AB Finding natural and/or synthetic ligands that activate orphan G protein-coupled receptors (oGPCRs) is a major focus in current drug discovery efforts. Transfluor (R) is a cell-based GPCR screening platform that utilizes an arrestin-green fluorescent protein conjugate (arrestin-GFP) to detect ligand interactions with GPCRs. The assay is ideally suited for oGPCRs because binding of arrestin-GFP to activated receptors is independent of the interacting G protein. Before embarking on a high-throughput screen, it is important to know that the target oGPCR can actually bind arrestin-GFP. This information was thought to be inaccessible, however, as arrestin-GFP recruitment is an agonist-driven process. This chapter describes an assay that enables GPCRs to be validated in Transfluor in the absence of ligand. This assay, termed the ligand-independent translocation (LITe) assay, utilizes a modified G protein-coupled receptor kinase to bypass the requirement of ligand for initiating arrestin-GFP translocation. Using the LITe assay, one can determine if an oGPCR binds arrestin-GFP and if the response is quantifiable by high-content screening instruments. In addition, the assay expedites the development and identification of oGPCR stable cell lines with the best Transfluor properties. In this way, the assay provides criteria for selecting the best oGPCRs to move forward for a Transfluor screening campaign. Moreover, the assay can be used for quality control purposes during the orphan receptor screen itself by providing positive translocation responses for calculation of Z prime values. In summary, the LITe assay is a powerful new technology that enables a faster and more reliable path forward in the deorphanization of GPCRs with Transfluor. C1 Xsira Pharmaceut, Res Triangle Pk, NC USA. Natl Human Genome Res Inst, Bethesda, MD USA. RP Oakley, RH (reprint author), Xsira Pharmaceut, Res Triangle Pk, NC USA. NR 19 TC 15 Z9 17 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182819-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 414 BP 50 EP 63 DI 10.1016/S0076-6879(06)14004-5 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFN15 UT WOS:000243221500004 PM 17110186 ER PT S AU Hudson, CC Oakley, RH Sjaastad, MD Loomis, CR AF Hudson, Christine C. Oakley, Robert H. Sjaastad, Michael D. Loomis, Carson R. BE Inglese, J TI High-content screening of known G protein-coupled receptors by arrestin translocation SO MEASURING BIOLOGICAL RESPONSES WITH AUTOMATED MICROSCOPY SE Methods in Enzymology LA English DT Review; Book Chapter ID BETA-ARRESTIN; BETA(2)-ADRENERGIC RECEPTOR; ENDOCYTOSIS; ADAPTER AB G protein-coupled receptors (GPCRs) have proven to be one of the most successful target classes for drug discovery. Accordingly, many assays are available to screen GPCRs, including radioactive-binding assays, second messenger signaling assays, and downstream reporter assays. One of the more novel approaches is the Transfluor technology, a cell-based assay that uses a detectable tag on a cytosolic protein, called arrestin, that is involved in the desensitization or inactivation of GPCRs. Monitoring the translocation of GFP-tagged arrestin from the cytosol to activated GPCRs at the plasma membrane measures the pharmacological effect of test compounds that bind the receptor target. Moreover, the Transfluor assay provides further, high-content information on the test compound itself and its effects on cell processes due to the fluorescent imaging of whole cells used in this screen. Screening known GPCRs with Transfluor against large compound libraries is best accomplished in cell lines stably expressing an optimum level of the target receptor. This chapter describes how to generate a clonal cell line stably expressing the known GPCR with suitable Transfluor properties. It then describes the steps involved in performing a Transfluor screen and discusses high content data resulting from the screen. C1 Xsira Pharmaceut, Res Triangle Pk, NC USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Hudson, CC (reprint author), Xsira Pharmaceut, Res Triangle Pk, NC USA. NR 13 TC 18 Z9 19 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182819-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 414 BP 63 EP 78 DI 10.1016/S0076-6879(06)14005-7 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFN15 UT WOS:000243221500005 PM 17110187 ER PT S AU Auld, DS Johnson, RL Zhang, YQ Veith, H Jadhav, A Yasgar, A Simeonov, A Zheng, W Martinez, ED Westwick, JK Austin, CP Inglese, J AF Auld, Douglas S. Johnson, Ronald L. Zhang, Ya-qin Veith, Henrike Jadhav, Ajit Yasgar, Adam Simeonov, Anton Zheng, Wei Martinez, Elisabeth D. Westwick, John K. Austin, Christopher P. Inglese, James BE Inglese, J TI Fluorescent protein-based cellular assays analyzed by laser-scanning microplate cytometry in 1536-well plate format SO MEASURING BIOLOGICAL RESPONSES WITH AUTOMATED MICROSCOPY SE Methods in Enzymology LA English Estonian DT Review; Book Chapter ID GLUCOCORTICOID-RECEPTOR; GENE; VISUALIZATION; TRANSLOCATION; CHIMERA; CELLS AB Microtiter plate readers have evolved from photomultiplier and charged-coupled device-based readers, where a population-averaged signal is detected from each well, to microscope-based imaging systems, where cellular characteristics from individual cells are measured. For these systems, speed and ease of data analysis are inversely proportional to the amount of data collected from each well. Microplate laser cytometry is a technology compatible with a 1536-well plate format and capable of population distribution analysis. Microplate cytometers such as the Acumen Explorer can monitor up to four fluorescent signals from single objects in microtiter plates with densities as high as 1536 wells. These instruments can measure changes in fluorescent protein expression, cell shape, or simple cellular redistribution events such as cytoplasmic to nuclear translocation. To develop high-throughput screening applications using laser-scanning microplate cytometry, we used green fluorescent protein- and yellow fluorescent protein-expressing cell lines designed to measure diverse biological functions such as nuclear translocation, epigenetic signaling, and G protein-coupled receptor activation. This chapter illustrates the application of microplate laser cytometry to these assays in a manner that is suitable for screening large compound collections in high throughput. C1 NIH, Chem Genom Ctr, Bethesda, MD USA. RP Auld, DS (reprint author), NIH, Chem Genom Ctr, Bethesda, MD USA. RI Zheng, Wei/J-8889-2014 OI Zheng, Wei/0000-0003-1034-0757 FU Intramural NIH HHS NR 25 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182819-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 414 BP 566 EP 589 DI 10.1016/S0076-6879(06)14029-X PG 24 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFN15 UT WOS:000243221500029 PM 17110211 ER PT J AU Ferraris, JD Burg, MB AF Ferraris, Joan D. Burg, Maurice B. TI Tonicity-dependent regulation of osmoprotective genes in mammalian cells SO MECHANISMS AND SIGNIFICANCE OF CELL VOLUME REGULATION SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Article AB Cells in the renal medulla are normally exposed to levels of NaCl that are extremely high and that vary with concentration of the urine. Such high levels of NaCl cause cellular perturbations, including increased DNA double-strand breaks, increased oxidation of DNA and proteins, and cytoskeletal alterations. Despite these perturbations the cells are able to survive and function because of osmoprotective responses that include accumulation of compatible organic osmolytes and increased abundance of heat shock proteins and water channels. Many of the responses are initiated by increased gene transcription, directed by the transcription factor TonEBP/OREBP. Here, we review the sensors of hypertonicity, the signaling pathways to TonEBP/OREBP, and the ways in which it is activated to increase transcription. Multiple signals are involved, including some that arise directly from the cellular perturbations caused by hypertonicity. Although the combination of these signals is necessary for full osmotic activation of TonEBP/OREBP, no one of them, alone, is sufficient. We conclude that hypertonicity profoundly alters the state of cells, providing numerous interrelated inputs to the osmoregulatory network. C1 NHLBI, Kidney & Electrolyte Metab Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), 9000 Rockville Pike,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM maurice_burg@nih.gov NR 95 TC 22 Z9 23 U1 1 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2006 VL 152 BP 125 EP 141 PG 17 WC Cell Biology; Urology & Nephrology SC Cell Biology; Urology & Nephrology GA BFL45 UT WOS:000242826000006 PM 17065809 ER PT J AU Cao, Y Knochel, S Oswald, F Donow, C Zhao, H Knochel, W AF Cao, Y Knochel, S Oswald, F Donow, C Zhao, H Knochel, W TI XBP1 forms a regulatory loop with BMP-4 and suppresses mesodermal and neural differentiation in Xenopus embryos SO MECHANISMS OF DEVELOPMENT LA English DT Article DE X. laevis; embryogenesis; XBP1; mesoderm; BMP-4; Smads; unfolded protein response (UPR) ID UNFOLDED PROTEIN RESPONSE; TGF-BETA SUPERFAMILY; TRANSCRIPTION FACTOR XBP-1; MORPHOGENETIC PROTEIN; HOMEOBOX GENE; VERTEBRATE DEVELOPMENT; ENDOPLASMIC-RETICULUM; SIGNALING PATHWAYS; SPEMANN ORGANIZER; FAMILY-MEMBERS AB The active form of the Xenopus X-box binding protein 1 (xXBP1) partially synergizes and partially antagonizes with BMP-4 signaling. xXBP1 overexpression inhibits mesoderm differentiation and formation of neural tissues. A functional knockdown promotes differentiation of lateral and dorsal mesoderm but not of ventral mesoderm and of neuroectoderm. We show that the active form of xXBP1 in gastrula and early neurula stage embryos is generated by removal of exon 4 and not by an endoribonuclease activity in the endoplasmic reticulum. The N-terminal region of xXBP1 which contains the basic leucine-zipper also contains a nuclear localization signal and both, the N-terminal as well as the C-terminal regions are required for xXBP1 function. The effects of xXBP1 are in part correlated to a regulatory loop between xXBP1 and BMP-4. xXBP1 and BMP-4 stimulate mutually the transcription of each other, but xXBP1 inhibits the BMP-4 target gene, Xvent-2. Both, in vitro and in vivo assays demonstrate that xXBP1 interacts with BMP-4 and Xvent-2B promoters. GST-pulldown assays reveal that xXBP1 can interact with c-Jun, the transcriptional co-activator p300 and with the BMP-4 responsive Smad1. On the other hand, xXBP1 also binds to the inhibitory Smads, Smad6 and Smad7, that can act as transcriptional co-repressors. Based on these data, we conclude that xXBP1 might function as an inhibitor of mesodermal and neural tissue formation by acting either as transcriptional activator or as repressor. This dual activity depends upon binding of cofactors being involved in the formation of distinct transcription complexes. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Ulm, Biochem Abt, D-89081 Ulm, Germany. Univ Ulm, Innere Med Abt 1, D-89081 Ulm, Germany. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Knochel, W (reprint author), Univ Ulm, Biochem Abt, Albert Einstein Allee 11, D-89081 Ulm, Germany. EM walter.knoechel@medizin.uni-ulm.de RI Zhao, Hui/B-8429-2016 NR 56 TC 19 Z9 21 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JAN PY 2006 VL 123 IS 1 BP 84 EP 96 DI 10.1016/j.mod.2005.09.003 PG 13 WC Developmental Biology SC Developmental Biology GA 007ES UT WOS:000234952000009 PM 16278078 ER PT J AU Cizza, G AF Cizza, Giovanni BE Eaton, WW TI Depression A Major, Unrecognized Risk Factor for Osteoporosis? SO MEDICAL AND PSYCHIATRIC COMORBIDITY OVER THE COURSE OF LIFE LA English DT Article; Book Chapter ID BONE-MINERAL DENSITY; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; POSTMENOPAUSAL WOMEN; OLDER-PEOPLE; PREMENOPAUSAL WOMEN; BIPOLAR DISORDER; CUSHINGS-DISEASE; LITHIUM-THERAPY; NERVOUS-SYSTEM; METABOLISM C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Cizza, G (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 71 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-231-3 PY 2006 BP 129 EP 153 PG 25 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA BWM12 UT WOS:000294221100008 ER PT J AU George, DT Phillips, MJ Doty, L Umhau, JC Rawlings, RR AF George, DT Phillips, MJ Doty, L Umhau, JC Rawlings, RR TI A model linking biology, behavior and psychiatric diagnoses in perpetrators of domestic violence SO MEDICAL HYPOTHESES LA English DT Article ID MEDIAL PREFRONTAL CORTEX; DEFENSIVE RAGE BEHAVIOR; NATIONAL EPIDEMIOLOGIC SURVEY; EMOTIONAL FACIAL EXPRESSION; BASOLATERAL AMYGDALA; CONDITIONED FEAR; ORBITOFRONTAL CORTEX; BRAIN STRUCTURES; USE DISORDERS; SELECT GROUP AB Research indicates that perpetrators of domestic violence have abnormalities in central serotonin and testosterone metabolism, an increased sensitivity to anxiogenic stimuli, and an impaired neuro-connection between their cortex and the amygdala. Clinical evaluations show that perpetrators of domestic violence also have a distinguishing set of behaviors and diagnoses related to anxiety, depression, intermittent explosive disorder, and borderline personality disorder. In this paper we propose a model to understand how the biological abnormalities can potentially explain the behaviors and diagnoses exhibited by the perpetrators. Changes in the perpetrator's neurotransmitters lead to a heightened sensitivity to environmental stimuli, anxiety, and conditioned fear. Lack of cortical input to the amygdala impairs the perpetrator's ability to extinguish anxiety and/or conditioned fear and gives rise to either innate behaviors (e.g., fight, flight, and shut down) or learned fear avoidant behaviors designed to avoid anxiety (e.g., alcohol consumption, self-injurious acts, and obsessive behaviors). Linking conditioned fear and fear avoidance to the behaviors and psychiatric diagnoses will serve to change the way the medical community perceives and treats perpetrators of domestic violence. Published by Elsevier Ltd. C1 NIAAA, Lab Clin & Translat Studies, DICBR, NIH, Bethesda, MD 20892 USA. RP George, DT (reprint author), NIAAA, Lab Clin & Translat Studies, DICBR, NIH, 10 Ctr Dr MSC-1540,Bldg 10,Hatfield CRC Room 2-23, Bethesda, MD 20892 USA. EM tedg@mail.nih.gov NR 60 TC 15 Z9 17 U1 3 U2 13 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PY 2006 VL 67 IS 2 BP 345 EP 353 DI 10.1016/j.mehy.2006.01.049 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 057WD UT WOS:000238625000027 PM 16580153 ER PT J AU Sharifi, N Farrar, WL AF Sharifi, N Farrar, WL TI Perturbations in hypoxia detection: A shared link between hereditary and sporadic tumor formation? SO MEDICAL HYPOTHESES LA English DT Article ID RENAL-CELL CARCINOMA; KIDNEY CANCER; GENE; MUTATIONS; PARAGANGLIOMA; MECHANISMS AB The discovery and characterization of the von Hippel Lindau (VHL) syndrome has brought about tremendous advances in understanding the molecular mechanisms of renal cell carcinoma. VHL mutations are known to act through hypoxia inducible factor, which has a physiologic role in detecting hypoxia. Recent investigations into other hereditary forms of kidney cancer with mutations in genes involving energy metabolism and oxidative changes, such as fumarate hydratase, suggest that metabolic changes related to hypoxia detection may be a common mechanism of tumorigenesis. This implicates aberrations in the kidney's physiologic rote in detection of hypoxia in tumor formation. Germline mutations of genes involved in energy metabolism and oxidative perturbations lead to tumors in other tissues that detect hypoxia, such as head and neck paragangliomas that occur in the area of the carotid body. Therefore, aberrations in physiologic detection of hypoxia that predispose to tumor formation may not be a mechanism unique to the kidney. Furthermore, inducers of hypoxic perturbations other than germline mutations in metabolic genes may predispose to cancers in organs that have a physiologic role in detecting hypoxia. Conditions that effectively lead to tissue hypoxia in hypoxia detecting tissues is one such mechanism. We propose that some of the common molecular and physiologic mechanisms in heritable forms of kidney cancer, namely detection of hypoxia, may play a rote in the genesis of sporadic kidney cancer. We survey evidence suggesting that the mechanism of some recognized risk factors of kidney cancer, such as smoking and obesity, may be due in part to tissue hypoxia, reflecting physiologic detection of hypoxia gone awry. Published by Elsevier Ltd. C1 Natl Canc Inst, Cytokine Mol Mech Sect, Mol Immunoregulat Lab, Canc Res Ctr, Ft Detrick, MD 21702 USA. NCI, Med Oncol Branch, Bethesda, MD USA. RP Sharifi, N (reprint author), Natl Canc Inst, Cytokine Mol Mech Sect, Mol Immunoregulat Lab, Canc Res Ctr, Bldg 560,Room 21-81, Ft Detrick, MD 21702 USA. EM nima.sharifi@nih.gov FU Intramural NIH HHS NR 20 TC 14 Z9 15 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PY 2006 VL 66 IS 4 BP 732 EP 735 DI 10.1016/j.mehy.2005.11.003 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 024KS UT WOS:000236194500008 PM 16364563 ER PT S AU Peyrat, JM Sermesant, M Pennec, X Delingette, H Xu, CY AF Peyrat, Jean-Marc Sermesant, Maxime Pennec, Xavier Delingette, Herve Xu, Chenyang BE Larsen, R Nielsen, M Sporring, J TI Towards a statistical atlas of cardiac fiber structure SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2006, PT 1 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 9th International Conference on Computing and Computer-Assisted Intervention CY OCT 01-06, 2006 CL Copenhagen, DENMARK SP AstraZeneca, Ctr Clin & Basic Res, Claron, Elsevier, GE, Medtronic, No Digital Inc, Siemens Corp Res, Springer, Visiopharm AB We propose here a framework to build a statistical atlas of diffusion tensors of canine hearts. The anatomical images of seven hearts are first non-rigidly registered in the same reference frame and their associated diffusion tensors are then transformed with a method that preserves the cardiac laminar sheets. In this referential frame, the mean tensor and its covariance matrix are computed based on the Log-Euclidean framework. With this method, we can produce a smooth mean tensor field that is suited for fiber tracking algorithms or the electromechanical modeling of the heart. In addition, by examining the covariance matrix at each voxel it is possible to assess the variability of the cardiac fiber directions and of the orientations of laminar sheets. The results show a strong coherence of the diffusion tensors and the fiber orientations among a population of seven normal canine hearts. C1 INRIA, Asclepios Res Project, Sophia Antipolis, France. Siemens Corp Res, Princeton, NJ USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Peyrat, JM (reprint author), INRIA, Asclepios Res Project, Sophia Antipolis, France. EM jean-marc.peyrat@sophia.inria.fr RI Pennec, Xavier/L-2537-2013; OI Pennec, Xavier/0000-0002-6617-7664; Sermesant, Maxime/0000-0002-6256-8350 NR 17 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-44707-5 J9 LECT NOTES COMPUT SC PY 2006 VL 4190 BP 297 EP 304 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BFF18 UT WOS:000241556300037 ER PT S AU Seshamani, S Lau, W Hager, G AF Seshamani, Sharmishtaa Lau, William Hager, Gregory BE Larsen, R Nielsen, M Sporring, J TI Real-time endoscopic mosaicking SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2006, PT 1 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 9th International Conference on Computing and Computer-Assisted Intervention CY OCT 01-06, 2006 CL Copenhagen, DENMARK SP AstraZeneca, Ctr Clin & Basic Res, Claron, Elsevier, GE, Medtronic, No Digital Inc, Siemens Corp Res, Springer, Visiopharm ID IMAGES AB With the advancement of minimally invasive techniques for surgical and diagnostic procedures, there is a growing need for the development of methods for improved visualization of internal body structures. Video mosaicking is one method for doing this. This approach provides a broader field of view of the scene by stitching together images in a video sequence. Of particular importance is the need for online processing to provide real-time feedback and visualization for image-guided surgery and diagnosis. We propose a method for online video mosaicking applied to endoscopic imagery, with examples in microscopic retinal imaging and catadioptric endometrial imaging. C1 Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. NIH, Bethesda, MD 20892 USA. RP Seshamani, S (reprint author), Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. EM sharmi@.jhu.edu; william.lau@nih.gov; hager@cs.jhu.edu NR 8 TC 21 Z9 22 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-44707-5 J9 LECT NOTES COMPUT SC PY 2006 VL 4190 BP 355 EP 363 PG 9 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BFF18 UT WOS:000241556300044 ER PT S AU Park, S Clarkson, E Barrett, HH Kupinski, MA Myers, KJ AF Park, Subok Clarkson, Eric Barrett, Harrison H. Kupinski, Matthew A. Myers, Kyle J. BA Eckstein, MP BF Eckstein, MP BE Jiang, Y TI Performance of a channelized-ideal observer using Laguerre-Gauss channels for detecting a Gaussian signal at a known location in different lumpy backgrounds - art. no. 61460P SO Medical Imaging 2006: Image Perception, Observer Performance and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE nonlinear ideal observers; channelized nonlinear-ideal observers; Laguerre-Gauss channels; non-Gaussian distributed lumpy backgrounds AB The Bayesian ideal observer gives a measure for image quality since it uses all available statistical information for a given image data. A channelized-ideal observer (CIO), which reduces the dimensionality of integrals that need to be calculated for the ideal observer, has been introduced in the past. The goal of the CIO is to approximate the performance of the ideal observer in certain detection tasks. In this work, a CIO using Laguerre-Gauss (LG) channels is employed for detecting a rotationally symmetric Gaussian signal at a known location in the non-Gaussian distributed lumpy background. The mean number of lumps in the lumpy background is varied to see the impact of image statistics on the performance of this CIO and a channelized-Hotelling observer (CHO) using the same channels. The width parameter of LG channels is also varied to see its impact on observer performance. A Markov-chain Monte Carlo (MCMC) method is employed to determine the performance of the CIO using large numbers of LG channels. Simulation results show that the CIO is a better observer than the CHO for the task. The results also indicate that the performance of the CIO approaches that of the ideal observer as the mean number of lumps in the lumpy background decreases. This implies that LG channels may be efficient for the CIO to approximate the performance of the ideal observer in tasks using non-Gaussian distributed lumpy backgrounds. C1 US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Park, S (reprint author), US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. NR 7 TC 4 Z9 4 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6425-2 J9 P SOC PHOTO-OPT INS PY 2006 VL 6146 BP P1460 EP P1460 AR 61460P DI 10.1117/12.653931 PG 9 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL81 UT WOS:000238040200022 ER PT S AU Park, S Gallas, B Badano, A Petrick, N Myers, K AF Park, Subok Gallas, Brandon Badano, Aldo Petrick, Nicholas Myers, Kyle BA Eckstein, MP BF Eckstein, MP BE Jiang, Y TI Human efficiency for detecting Gaussian signals in non-Gaussian distributed lumpy backgrounds using different display characteristics and scaling methods. - art. no. 61460Q SO Medical Imaging 2006: Image Perception, Observer Performance and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE human efficiency; Bayesian ideal observer; non-Gaussian distributed lumpy backgrounds ID HUMAN-OBSERVER; DETECTION PERFORMANCE; NOISE; MAMMOGRAMS; MODEL AB A psychophysical study to measure human efficiency relative to the ideal observer for detecting a Gaussian signal at a known location in a non-Gaussian distributed lumpy background was conducted previously by the author. The study found that human efficiency was less than 2.2% while the ideal observer achieved 0.95 in terms of the area under the receiver operating characteristic curve. In this work, a psychophysical study was conducted with a number of changes that substantially improve upon the previous study design. First, a DICOM-calibrated monitor was used in this study for human-observer performance measurements, whereas an uncalibrated LCD monitor was used in the prior study. Second, two scaling methods to display image values were employed to see how scaling affects human performance for the same task. Third, a random order of image pairs was chosen for each observer to reduce any correlations in human performance that is likely caused by the fixed ordering of the image pairs in the prior study. Human efficiency relative to the ideal observer was found to be less than 3.8% at the same performance level of the ideal observer as above. Our variance analysis indicates that neither scaling nor display made a significant difference in human performance on the tasks in the two studies. That is, we cannot say that either of these factors caused low human efficiency in these studies. Therefore, we conclude that using highly non-Gaussian distributed lumpy backgrounds in the tasks may have been the major source of low human efficiency. C1 US FDA, Ctr Devices & Radiol Hlth, NIBIB,Devis Imaging & Appl Math, CDRH,Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Park, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, NIBIB,Devis Imaging & Appl Math, CDRH,Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 19 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 0-8194-6425-2 J9 P SOC PHOTO-OPT INS PY 2006 VL 6146 BP Q1460 EP Q1460 AR 61460Q DI 10.1117/12.653902 PG 9 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL81 UT WOS:000238040200023 ER PT S AU Tan, S Yao, JH Ward, MM Yao, L Summers, RM AF Tan, Sovira Yao, Jianhua Ward, Michael M. Yao, Lawrence Summers, Ronald M. BE Reinhardt, JM Pluim, JPW TI Level set based vertebra segmentation for the evaluation of ankylosing spondylitis - art. no. 614407 SO Medical Imaging 2006: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE segmentation; CT; vertebra; level set; Ankylosing Spondylitis ID ACTIVE CONTOURS AB Ankylosing Spondylitis is a disease of the vertebra where abnormal bone structures (syndesmophytes) grow at intervertebral disk spaces. Because this growth is so slow as to be undetectable on plain radiographs taken over years, it is necessary to resort to computerized techniques to complement qualitative human judgment with precise quantitative measures on 3-D CT images. Very fine segmentation of the vertebral body is required to capture the small structures caused by the pathology. We propose a segmentation algorithm based on a cascade of three level set stages and requiring no training or prior knowledge. First, the noise inside the vertebral body that often blocks the proper evolution of level set surfaces is attenuated by a sigmoid function whose parameters are determined automatically. The 1st level set (geodesic active contour) is designed to roughly segment the interior of the vertebra despite often highly inhomogeneous and even discontinuous boundaries. The result is used as an initial contour for the 2nd level set (Laplacian level set) that closely captures the inner boundary of the cortical bone. The last level set (reversed Laplacian level set) segments the outer boundary of the cortical bone and also corrects small flaws of the previous stage. We carried out extensive tests on 30 vertebrae (5 from each of 6 patients). Two medical experts scored the results at intervertebral disk spaces focusing on end plates and syndesmophytes. Only two minor segmentation errors at vertebral end plates were reported and two syndesmophytes were considered slightly under-segmented. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Tan, S (reprint author), NIH, Ctr Clin, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 9 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 0-8194-6423-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6144 BP 14407 EP 14407 AR 614407 DI 10.1117/12.652399 PN 1-3 PG 10 WC Computer Science, Interdisciplinary Applications; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL75 UT WOS:000238033300007 ER PT S AU Gavrielides, MA Petrick, N Myers, KJ AF Gavrielides, Marios A. Petrick, Nicholas Myers, Kyle J. BE Reinhardt, JM Pluim, JPW TI Alignment of full and partial CT thoracic scans using bony structures - art. no. 61443A SO Medical Imaging 2006: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE AB Diagnostic thoracic procedures using computed tomography (CT) often include comparisons of scans acquired with different slice thicknesses. In this manuscript, we investigated the potential for alignment of different CT scans from the same patient using skeletal knowledge of the thoracic region. Skeletal matching was selected because it is expected to be less susceptible to differences associated with patient breath hold, positioning and cardiac motion. Our method utilized the positioning of the ribs relative to the vertebra for matching. It also included matching the scapula when visible in the scans. Rib positioning was described by the angles formed between the vertebra centroid and combinations of pairs of rib centroids visible on each CT slice; this was used as the primary matching mechanism. Scapula morphology was described using a feature based on the local maxima of the distance transform. Since the scapula is not visible in all slices of a full scan, its description was limited to only defining the potential range of slices. A cost function incorporating the difference of features from rib positioning and scapula morphology between two slices was derived and used to match slices. The method was evaluated on an independent set of 10 pairs of full and partial CT scans. Assessment was based on whether or not slices containing known nodules between each pair of scans were overlapping after the alignment procedure. Results showed that the proposed metric correctly aligned 9 out of 10 scans. The preliminary results are encouraging for using this method as a first step towards temporal analysis of lung nodules. C1 US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst,Div Imaging & App, Rockville, MD 20852 USA. RP Gavrielides, MA (reprint author), 12720 Twinbrook Pkwy,Bldg 1,Rm 128,HFZ 140, Rockville, MD 20852 USA. NR 4 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 0-8194-6423-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6144 BP A1443 EP A1443 AR 61443A DI 10.1117/12.655333 PN 1-3 PG 9 WC Computer Science, Interdisciplinary Applications; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL75 UT WOS:000238033301037 ER PT S AU Li, J Huang, A Yao, J Bitter, I Petrick, N Summers, RM Pickhardt, PJ Choi, JR AF Li, Jiang Huang, Adam Yao, Jianhua Bitter, Ingmar Petrick, Nicholas Summers, Ronald M. Pickhardt, Perry J. Choi, J. Richard BE Reinhardt, JM Pluim, JPW TI Automatic colonic polyp detection using multiobjective evolutionary techniques - art. no. 61445E SO Medical Imaging 2006: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE computer-aided detection; pattern recognition; statistical methods; multiobjective evolution; genetic algorithm ID COMPUTER-AIDED DIAGNOSIS; CT COLONOGRAPHY; OPTIMIZATION AB Colonic polyps appear like elliptical protrusions on the inner wall of the colon. Curvature based features for colonic polyp detection have proved to be successful in several computer-aided diagnostic CT colonography (CTC) systems. Some simple thresholds are set for those features for creating initial polyp candidates. sophisticated classification scheme are then applied on these polyp candidates to reduce false positives. There are two objective functions, the number of missed polyps and false positive rate, that need to be minimized when setting those thresholds. These two objectives conflict and it is usually difficult to optimize them both by a gradient search. In this paper, we utilized a multiobjective evolutionary method, the Strength Pareto Evolutionary Algorithm (SPEA2),(1) to optimize those thresholds. SPEA2 incorporates the concept of Pareto dominance and applies genetic techniques to evolve individual solutions to the Pareto front. The SPEA2 algorithm was applied to colon CT images from 27 patients each having a prone and a supine scan. There are 40 colonoscopically confirmed polyps resulting in 72 positive detections in CTC reading. The results obtained by SPEA2 were compared with those obtained by our old system, where an appropriate value was set for each of those thresholds by a histogram examination method. If we keep the sensitivity the same as that of our old system, the SPEA2 algorithm reduced false positive rate by 76.4% from average false positive 55.6 to 13.3 per data set. If the false positive rate is kept the same for both systems, SPEA2 increased the sensitivity by 13.1% from 53 to 61 among 72 ground truth detections. C1 NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Li, J (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 18 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 0-8194-6423-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6144 BP E1445 EP E1445 AR 61445E DI 10.1117/12.653546 PN 1-3 PG 9 WC Computer Science, Interdisciplinary Applications; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL75 UT WOS:000238033302029 ER PT S AU Paquerault, S Petrick, N Sahiner, B Myers, KJ Chan, HP AF Paquerault, S. Petrick, N. Sahiner, B. Myers, K. J. Chan, H. -P. BE Reinhardt, JM Pluim, JPW TI Potential improvement of computerized mass detection on mammograms using a bilateral pairing technique - art. no. 61445N SO Medical Imaging 2006: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE mammography; computer-aided diagnosis; bilateral detection technique. ID DIGITAL MAMMOGRAMS; SUBTRACTION; SINGLE; IMAGES AB We are developing a bilateral pairing technique to help reduce false-positives identified by a single-view computer-aided detection (CAD) system for breast masses. In this study, we compare the performance of the proposed bilateral CAD to a single-view CAD. A database of 172 right/left breast pairs containing 205 biopsy-proven masses was used. Single-view CAD was run on each image using a lax selection threshold so that 5 objects per image were retained. The automated bilateral pairing algorithm identified all objects in a left breast mammogram '' matching '' a CAD detected object in the corresponding right breast image and visa-versa. Bilateral pairing was based on geometrical correspondence between objects with a matching score derived from a paired right/left object feature set and a linear discriminant analysis classifier. Leave-one out resampling was used to train/test the technique. We compared the FROC performances of the single-view CAD, the proposed bilateral technique and a modified CAD using manual pairing of bilateral structures. At a per-lesion detection sensitivity of 0.7, there were 3.8 FPs/image for the original CAD, 3.3 for the proposed technique, and 2.2 for the modified CAD using manual matching, a 12.6% and 42.1% reduction, respectively. At an FP rate of 1.0 per image, the sensitivities for the original CAD, the proposed technique and the modified CAD using manual matching were 0.47, 0.51 and 0.60, respectively. Preliminary results show that CAD with bilateral pairing did not achieve a significant FP-reduction. C1 NIBIB, CDRH, Joint Lab Assessment Med Imaging Syst, US FDA, Rockville, MD USA. RP Paquerault, S (reprint author), NIBIB, CDRH, Joint Lab Assessment Med Imaging Syst, US FDA, Rockville, MD USA. NR 13 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6423-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6144 BP N1445 EP N1445 AR 61445N DI 10.1117/12.654561 PN 1-3 PG 8 WC Computer Science, Interdisciplinary Applications; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL75 UT WOS:000238033302038 ER PT S AU Yuan, XH Ozturk, C Chi-Fishman, G AF Yuan, Xiaohui Ozturk, Cengizhan Chi-Fishman, Gloria BE Reinhardt, JM Pluim, JPW TI A pseudo wavelet-based method for accurate tagline tracing on tagged MR images of the tongue - art. no. 61440P SO Medical Imaging 2006: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE ID MOTION AB In this paper, we present a pseudo wavelet-based tagline detection method. The tagged MR image is transformed to the wavelet domain, and the prominent tagline coefficients are retained while others are eliminated. Significant stripes are extracted via segmentation, which are mixtures of tags and anatomical boundary that resembles line. A refinement step follows such that broken lines or isolated points are grouped or eliminated. Without assumption on tag models, our method extracts taglines automatically regardless their width and spacing. In addition, founded on the multi-resolution wavelet analysis, our method reconstructs taglines precisely and shows great robustness to various types of taglines. C1 NIH, Dept Rehabil Med, Phys Disabil Branch, Bethesda, MD 20892 USA. RP Yuan, XH (reprint author), NIH, Dept Rehabil Med, Phys Disabil Branch, Bethesda, MD 20892 USA. RI Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 NR 15 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 0-8194-6423-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6144 BP P1440 EP P1440 AR 61440P DI 10.1117/12.653339 PN 1-3 PG 11 WC Computer Science, Interdisciplinary Applications; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL75 UT WOS:000238033300024 ER PT S AU Yuan, X Chi-Fishman, G AF Yuan, Xiaohui Chi-Fishman, Gloria BE Reinhardt, JM Pluim, JPW TI Image registration using shape-constrained mutual information and genetic algorithms - art. no. 61442S SO Medical Imaging 2006: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE AB We present a novel, shape-constrained mutual information-based image registration method using a Genetic Algorithm (GA) for aligning 2D MR images of the in vivo human tongue. By restricting the computation of Mutual Information (MI) using segmented object, we are able to register images in a short time without compromising accuracy. In addition, due to the employment of GA, the robustness of this method is greatly improved such that good registration results can be achieved given large initial transformation difference. Hence, this method eliminates the failure of matching caused by partial object overlap. Our experiments clearly demonstrate the robustness and accuracy of the method. C1 NIH, Dept Rehabil Med, Phys Disabil Branch, Bethesda, MD 20892 USA. RP Yuan, XH (reprint author), NIH, Dept Rehabil Med, Phys Disabil Branch, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 2 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 0-8194-6423-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6144 BP S1442 EP S1442 AR 61442S DI 10.1117/12.653373 PN 1-3 PG 8 WC Computer Science, Interdisciplinary Applications; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL75 UT WOS:000238033301020 ER PT S AU Li, J Yao, JH Petrick, N Summers, RM Hara, AK AF Li, Jiang Yao, Jianhua Petrick, Nicholas Summers, Ronald M. Hara, Amy K. BE Reinhardt, JM Pluim, JPW TI Hybrid committee classifier for a computerized colonic polyp detection system SO MEDICAL IMAGING 2006: IMAGE PROCESSING, PTS 1-3 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE computer-aided detection; pattern recognition; statistical methods; classifier committee; neural network; support vector machine ID CT COLONOGRAPHY; AIDED DIAGNOSIS AB We present a hybrid committee classifier for computer-aided detection (CAD) of colonic polyps in CT colonography (CTC). The classifier involved an ensemble of support vector machines (SVM) and neural networks (NN) for classification, a progressive search algorithm for selecting a set of features used by the SVMs and a floating search algorithm for selecting features used by the NNs. A total of 102 quantitative features were calculated for each polyp candidate found by a prototype CAD system. 3 features were selected for each of 7 SVM classifiers which were then combined to form a committee of SVMs classifier. Similarly, features (numbers varied from 10-20) were selected for 11 NN classifiers which were again combined to form a NN committee classifier. Finally, a hybrid committee classifier was defined by combining the outputs of both the SVM and NN committees. The method was tested on CTC scans (supine and prone views) of 29 patients, in terms of the partial area under a free response receiving operation characteristic (FROC) curve (AUC). Our results showed that the hybrid committee classifier performed the best for the prone scans and was comparable to other classifiers for the supine scans. C1 NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Scottsdale, AZ USA. RP Summers, RM (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Scottsdale, AZ USA. EM rms@nih.gov NR 30 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 0-8194-6423-6 J9 PROC SPIE PY 2006 VL 6144 AR 61445A DI 10.1117/12.652724 PN 1-3 PG 9 WC Computer Science, Interdisciplinary Applications; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL75 UT WOS:000238033302025 ER PT S AU Kyprianou, LS Badano, A D Gallas, B Park, S Myers, KJ AF Kyprianou, Lacovos S. Badano, Aldo D Gallas, Brandon Park, Subok Myers, Kyle J. BE Flynn, MJ Hsieh, J TI A practical method for measuring the H matrix of digital x-ray and cone beam CT imaging systems SO MEDICAL IMAGING 2006: PHYSICS OF MEDICAL IMAGING, PTS 1-3 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE system; matrix; H; cone beam; system evaluation; assessment AB Digital clinical imaging systems designed for radiography or cone-beam computed-tomography are highly shift-variant. The x-ray cone angle of such systems varies between 0 degrees and 15 degrees, resulting in large variations of the focal spot projection across the image field. Additionally, the variable x-ray beam incidence across the detector field creates a location-dependent asymmetric detector response function. In this paper we propose a practical method for the measurement of the angle of incidence dependent two-dimensional presampled detector response function. We also present a method for the measurement of the source radiance at the center of the detector, and provide a geometric transformation for reprojecting given any location in object space. The measurement procedure involves standard, readily available tools such as a focal-spot/pinhole camera, and an edge. Using the measured data and a model based on smooth functions derived from Monte Carlo simulations we obtain the location-dependent detector response function. In this paper we ignore scatter, therefore the resulting location dependent system response is a function of the focal spot and detector response. The system matrix, a representation of the full deterministic point response of the system for all positions in object space, can then be calculated. The eigenvalues and eigenvectors of the system matrix are generated and interpreted. C1 US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP Kyprianou, LS (reprint author), US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, HFZ-140,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM jacovos.kypriwiou@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 11 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6185-7 J9 PROC SPIE PY 2006 VL 6142 AR 61421U DI 10.1117/12.654374 PN 1-3 PG 12 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BEL88 UT WOS:000238049700064 ER PT S AU Huang, A Summers, RM Roy, D AF Huang, Adam Summers, Ronald M. Roy, Dave BE Manduca, A Amini, AA TI Synchronous navigation for CT colonography - art. no. 614315 SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE virtual colonoscopy; virtual navigation; CT colonography; colon flattening; computer-aided diagnosis; polyp detection ID COLON; SUPINE AB We present a synchronous navigation module for CT colonography (CTC) reading. The need for such a system arises because most CTC protocols require a patient to be scanned in both supine and prone positions to increase sensitivity in detecting colonic polyps. However, existing clinical practices are limited to reading one scan at a time. Such limitation is due to the fact that building a reference system between scans for the highly flexible colon is a nontrivial task. The conventional centerline approach, generating only the longitudinal distance along the colon, falls short in providing the necessary orientation information to synchronize the virtual navigation cameras in both scanned positions. In this paper we describe a synchronous navigation system by using the teniae coli as anatomical references. Teniae coli are three parallel bands of longitudinal smooth muscle on the surface of the colon. They are morphologically distinguishable and form a piecewise triple helix structure from the appendix to the sigmoid colon. Because of these characteristics, they are ideal references to synchronize virtual cameras in both scanned positions. Our new navigation system consists of two side-by-side virtual colonoscopic view panels (for the supine and prone data sets respectively) and one single camera control unit (which controls both the supine and prone virtual cameras). The capability to examine the same colonic region simultaneously in both scanned images can raise an observer's confidence in polyp identification and potentially improve the performance of CT colonography. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Huang, A (reprint author), NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP 14315 EP 14315 AR 614315 DI 10.1117/12.653934 PN 1-2 PG 8 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000041 ER PT S AU Franaszek, M Summers, RM Pickhardt, PJ Choi, JR AF Franaszek, Marek Summers, Ronald M. Pickhardt, Perry J. Choi, J. Richard BE Manduca, A Amini, AA TI Automatic procedure to distinguish colonic polyps located on fold vs. not on fold - art. no. 614319 SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE CT colonography; CAD; polyp; haustral fold ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; COLONOGRAPHY; SEGMENTATION AB Performance of Computed Tomographic Colonography (CTC) Computer Aided Detection (CTC CAD) depends sensitively on a set of features chosen to characterize a polyp candidate. Most of the features are derived from some shape related characteristics which are calculated at the points located within the boundaries of a polyp candidate. This approach ignores information from the part of the colonic wall stretching beyond the limits of a polyp candidate. We found that almost 90% of small and medium size polyps missed by our CAD program were located on haustral folds. This suggests that two different classifiers (for detections on a fold and not on a fold) could be used which are better tuned to the local characteristics. Therefore, we developed an automated method to verify independently if a given polyp candidate is located on a fold. This is done by checking the intensity profile along normals originating from the points on the colonic wall which are close to but outside of a patch marking a polyp candidate. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Franaszek, M (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP 14319 EP 14319 AR 614319 DI 10.1117/12.653076 PN 1-2 PG 10 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000045 ER PT S AU Yao, JH Chen, D Lu, WZ Premkumar, A AF Yao, Jianhua Chen, David Lu, Wenzhu Premkumar, Ahalya BE Manduca, A Amini, AA TI Uterine fibroid segmentation and volume measurement on MRI - art. no. 614322 SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE uterine fibroid; level set segmentation; volume measurement; MRI AB Uterine leiomyomas are the most common pelvic tumors in females. The efficacy of medical treatment is gauged by shrinkage of the size of these tumors. In this paper, we present a method to robustly segment the fibroids on MRI and accurately measure the 3D volume. Our method is based on a combination of fast marching level set and Laplacian level set. With a seed point placed inside the fibroid region, a fast marching level set is first employed to obtain a rough segmentation, followed by a Laplacian level set to refine the segmentation. We devised a scheme to automatically determine the parameters for the level set function and the sigmoid function based on pixel statistics around the seed point. The segmentation is conducted on three concurrent views (axial, coronal and sagittal), and a combined volume measurement is computed to obtain a more reliable measurement. We carried out extensive tests on 13 patients, 25 MRI studies and 133 fibroids. The segmentation result was validated against manual segmentation defined by experts. The average segmentation sensitivity (true positive fraction) among all fibroids was 84.6%, and the average segmentation specificity (1-false positive fraction) was 84.3%. C1 NIH, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Bethesda, MD 20892 USA. NR 6 TC 2 Z9 2 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 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP 14322 EP 14322 AR 614322 DI 10.1117/12.653856 PN 1-2 PG 10 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000068 ER PT S AU Pilkinton, D Bitter, I Summers, RM Campbell, S Choi, JR Pickhardt, PJ AF Pilkinton, David Bitter, Ingmar Summers, Ronald M. Campbell, Shannon Choi, J. Richard Pickhardt, Perry J. BE Manduca, A Amini, AA TI The effect of edge-preserving image smoothing on automatic colonic polyp detection for CT colonography - art. no. 614335 SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE CT; colon; 3D reconstruction; colon cancer; image processing; computer-aided detection; colonic polyp detection; anisotropic smoothing; edge-preserving smoothing ID COMPUTER-AIDED DETECTION AB Low radiation dose requirements create relatively noisy images that contribute to high numbers of false positive detections in CAD for CT colonography. Presumably image denoising techniques such as non-linear, edge-preserving smoothing filters can improve automatic colonic polyp detection in CT colonography by reducing overall per patient false positive rates. Here, we have evaluated multiple edge-preserving smoothing filters to determine whether this is so. Prone and supine scans from 81 asymptomatic, average-risk adults with adenomatous polyps were studied with and without smoothing. FROC curves were generated to analyze CAD results. A single, clinically relevant operating point was compared between the best smoothing filter results and the unsmoothed data. Improvement in performance was observed, but the differences were not found to be statistically significant for average dose CT colonography. C1 NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 14 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 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP 14335 EP 14335 AR 614335 DI 10.1117/12.653985 PN 1-2 PG 8 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000106 ER PT S AU Greenblum, S Li, J Huang, A Summers, RM AF Greenblum, Sharon Li, Jiang Huang, Adam Summers, Ronald M. BE Manduca, A Amini, AA TI Wavelet analysis in virtual colonoscopy - art. no. 614336 SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE virtual colonoscopy; wavelet; classifiers; computer aided detection AB The computed tomographic colonography (CTC) computer aided detection (CAD) program is a new method in development to detect colon polyps in virtual colonoscopy. While high sensitivity is consistently achieved, additional features are desired to increase specificity. In this paper, a wavelet analysis was applied to CTCCAD outputs in an attempt to filter out false positive detections. 52 CTCCAD detection images were obtained using a screen capture application. 26 of these images were real polyps, confirmed by optical colonoscopy and 26 were false positive detections. A discrete wavelet transform of each image was computed with the MATLAB wavelet toolbox using the Haar wavelet at levels 1-5 in the horizontal, vertical and diagonal directions. From the resulting wavelet coefficients at levels 1-3 for all directions, a 72 feature vector was obtained for each image, consisting of descriptive statistics such as mean, variance, skew, and kurtosis at each level and orientation, as well as error statistics based on a linear predictor of neighboring wavelet coefficients. The vectors for each of the 52 images were then run through a support vector machine (SVM) classifier using ten-fold cross-validation training to determine its efficiency in distinguishing polyps from false positives. The SVM results showed 100% sensitivity and 51% specificity in correctly identifying the status of detections. If this technique were added to the filtering process of the CTCCAD polyp detection scheme, the number of false positive results could be reduced significantly. C1 NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), Bldg 10 Room 1C660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP 14336 EP 14336 AR 614336 DI 10.1117/12.655680 PN 1-2 PG 8 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000107 ER PT S AU Bitter, I Kelsey, M Summers, RM AF Bitter, Ingmar Kelsey, Matthew Summers, Ronald M. BE Manduca, A Amini, AA TI Performance tuning of candidate determination methods for computer aided detection of colon polyps - art. no. 61431A SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE computed tomography colonoscopy; quantification; performance measurement; automatic segmentation; computer aided detection; colon polyp detection AB We introduce an intuitive measure of computer aided detection (CAD) system performance that can handle simultaneous variation of multiple parameters. On the example of CAD of colon polyps we demonstrate how this measure was used to find the optimal parameters and make improvements to the "water-plane" algorithm that finds initial polyp candidates on the colon wall. In particular, we improved the merging of overlapping clusters to only create fused clusters if they shared at least 50% of their vertices and adjusted size and thickness filter criteria to retain more true positive detections. The system, containing all optimizations, improved significantly over the original system that found initial detections based only on colon surface curvature. This improvement was measured by both free response operating curve (FROC) analysis and our new performance measure. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Bitter, I (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 2 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 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP A1431 EP A1431 AR 61431A DI 10.1117/12.653755 PN 1-2 PG 7 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000046 ER PT S AU Van Uitert, R Bitter, I Summers, RM Choi, JR Pickhardt, PJ AF Van Uitert, Robert Bitter, Ingmar Summers, Ronald M. Choi, J. Richard Pickhardt, Perry J. BE Manduca, A Amini, AA TI Quantitative assessment of colon distention for polyp detection in CT virtual colonoscopy - art. no. 61431B SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE CT; colon; 3D reconstruction; colon cancer; image processing; computer-aided detection AB Virtual colonoscopy is becoming a more prevalent way to diagnose colon cancer. One of the critical elements in detecting cancerous polyps using virtual colonoscopy, especially in conjunction with computer-aided detection of polyps, is that the colon be sufficiently distended. We have developed an automatic method to determine from a CT scan what percentage of the colon is distended by 1 cm or larger and compared our method with a radiologist's assessment of quality of the scan with respect to successful colon polyp detection. A radiologist grouped 41 CT virtual colonoscopy scans into three groups according to the degree of colonic distention, "well", "medium", and "poor". We also employed a subvoxel accurate centerline algorithm and a subvoxel accurate distance transform to each dataset to measure the colon distention along the centerline. To summarize the colonic distention with a single value relevant for polyp detection, the distention score, we recorded the percentage of centerline positions in which the colon distention was 1 cm or larger. We then compared the radiologist's assessment and the computed results. The sorting of all datasets according to the distention score agreed with the radiologist's assessment. The "poor" cases had a mean and standard deviation score of 78.4% +/- 5.2%, the "medium" cases measured 88.7% +/- 1.9%, and the "well" cases 98.8% +/- 1.5%. All categories were shown to be significantly different from each other using impaired two sample t-tests. The presented colonic distention score is an accurate method for assessing the quality of colonic distention for CT colonography. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Van Uitert, R (reprint author), NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP B1431 EP B1431 AR 61431B DI 10.1117/12.653205 PN 1-2 PG 7 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000047 ER PT S AU Kyprianou, IS Thompson, L Banh, DP Pritchard, W Karanian, J Rosen, L Myers, KJ AF Kyprianou, Iacovos S. Thompson, Laura Banh, Diem Phuc Pritchard, William Karanian, John Rosen, Lee Myers, Kyle J. BE Manduca, A Amini, AA TI Gender-specific statistical models of pathological coronary arteries for generating simulated angiograms - art. no. 61432K SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE ID SEX-DIFFERENCES; CAROTID-ARTERY; HEART-DISEASE; ANGIOPLASTY; WOMEN; ATHEROSCLEROSIS; MEN; INTERVENTIONS; PLAQUES; AGE AB Cardiovascular disease is considered the leading cause of death in the US, accounting for 38% of all deaths. There are gender differences in the size of coronary arteries and in the character and location of atherosclerotic lesions that affect the detection of coronary artery disease with the medical imaging modalities currently used (e.g. angiography, computed tomography). These differences also affect the safety and effectiveness of image-guided interventions using therapeutic devices. For the optimization of the medical imaging modalities used for this specific task we require the generation of clinically-realistic, gender-specific images of healthy and pathological coronary angiograms. For this purpose we have created a gender-specific statistical model of a pathological coronary artery tree. Starting from "healthy" heart-phantoms created from high resolution CT scans of cadaver hearts of both genders, the model uses prevalence data obtained from clinical studies of patients with significant (> 50% stenosis) coronary artery disease (CAD). The model determines the plaque deposit locations and character (length, percent stenosis) for each case, based on a flow model. These data are then used to generate artificially diseased artery trees, embedded in a gender-specific torso model. Using an x-ray and optical photon Monte-Carlo simulation program, we then generate simulated angiograms exhibiting realistic disease patterns. The severity of each angiogram. is determined from a set of rules that combines the geometrically increasing severity of lesions, the cumulative effects of multiple obstructions, the significance of their locations, the modifying influence of the collaterals, and the size and quality of the distal vessels. The simulated angiograms will consequently be read by model and human observers. The probability of detection derived in combination with the severity score will be used as a figure of merit for the patient- and gender-specific optimization of the imaging modality under investigation. C1 US FDA, NIBIB, CDRH Joint Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Kyprianou, IS (reprint author), US FDA, NIBIB, CDRH Joint Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP K1432 EP K1432 AR 61432K DI 10.1117/12.654383 PN 1-2 PG 11 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000085 ER PT S AU Van Uitert, R Bitter, I Butman, JA AF Van Uitert, Robert Bitter, Ingmar Butman, John A. BE Manduca, A Amini, AA TI Semi-automatic segmentation and quantification of 3D spinal cord data - art. no. 61430S SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE CT; spinal cord; semi-automatic segmentation; level sets; quantification; length measurement; volume measurement AB Delineation of objects within medical images is often difficult to perform reproducibly when one relies upon hand-segmentation. To avoid inter- and intra-user variability, a semi-automatic segmentation method can more accurately and consistently determine the object boundaries. This paper presents a semi-automatic process for determining the length and volume of the spinal cord between adjacent pairs of intervertebral discs and the total length and volume of the spinal cord. A level set segmentation was performed on MRI data with user selected landmarks in order to obtain a segmentation of the spinal cord. The length and volume measurements were performed on 20 segments from CI to LI with five sets of user selected landmarks. Our results show that the average spinal cord segment length was 21.55 mm with a standard deviation of 25.11% and the average spinal cord segment volume was 2,217.16 mm(3) with a standard deviation of 80.51%. The measurement variability of a single anatomical length across multiple trials of different sets of seed points was three orders of magnitude lower (0.06%) than the variability across different anatomical lengths (25.23%), while the measurement variability of a single anatomical volume across multiple trials of different sets of seed points was two orders of magnitude lower (0.37%) than the variability across different anatomical volumes (79.24%). Our method has been demonstrated to be potentially insensitive to intra- and inter-user variability. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Van Uitert, R (reprint author), NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. OI Butman, John/0000-0002-1547-9195 NR 5 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 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP S1430 EP S1430 AR 61430S DI 10.1117/12.653266 PN 1-2 PG 6 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000028 ER PT S AU Gutierrez, LF de Silva, R McVeigh, ER Ozturk, C Lederman, RJ AF Gutierrez, Luis F. de Silva, Ranil McVeigh, Elliot R. Ozturk, Cengizhan Lederman, Robert J. BE Cleary, KR Galloway, RL TI Targeted endomyocardial injections of therapeutic cells using X-ray fused with MRI guidance SO MEDICAL IMAGING 2006: VISUALIZATION, IMAGE-GUIDED PROCEDURES, AND DISPLAY SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE MRI; X-ray angiography; XMR; image-guided surgery; cardiovascular intervention; cell therapy ID MYOCARDIAL-INFARCTION; ISCHEMIC MYOCARDIUM; TRANSPLANTATION AB The utility of X-ray fused with MRI (XFM) using external fiducial markers to perform targeted endomyocardial injections in infarcted hearts of swine was tested. Endomyocardial injections of feridex-labeled mesenchymal stromal. cells (Fe-MSC) were performed in the previously infarcted hearts of 12 Yucatan miniswine (33-67 kg). Animals had pre-injection cardiac MRI, XFM-guided endomyocardial injection of Fe-MSC suspension spiked with tissue dye, and post-injection MRI. 24 hours later, after euthanasia, the hearts were excised, sliced and stained with TTC. During the injection procedure. operators were provided with 3D surfaces of endocardium, epicardium, myocardial wall thickness and infarct registered with live XF images to facilitate device navigation and choice of injection location. 130 injections were performed in hearts where diastolic wall thickness ranged from 2.6 to 17.7 mm. Visual inspection of the pattern of dye staining on TTC stained heart slices correlated (r=0.98) with XFM-derived injection locations mapped onto delayed hyperenhancement MRI and the susceptibility artifacts seen on the post-injection T-2*-weighted gradient echo MRI. The in vivo target registration error was 3.17 +/- 2.61 mm (n=64) and 75% of injections were within 4 mm of the predicted location. 3D to 2D registration of XF and MR images using external fiducial markers enables accurate targeted endomyocardial injection in a swine model of myocardial infarction. The present data suggest that the safety and efficacy of this approach for performing targeted endomyocardial delivery should be evaluated further clinically. C1 NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Gutierrez, LF (reprint author), NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM luis.gutierrez@philips.com RI Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 NR 12 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 0-8194-6184-9 J9 PROC SPIE PY 2006 VL 6141 AR 614113 DI 10.1117/12.654279 PG 10 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL13 UT WOS:000237688300035 ER PT J AU Gerson, AC Butler, R Moxey-Mims, M Wentz, A Shinnar, S Lande, MB Mendley, SR Warady, BA Furth, SL Hooper, SR AF Gerson, Arlene C. Butler, Robert Moxey-Mims, Marva Wentz, Alicia Shinnar, Shlomo Lande, Marc B. Mendley, Susan R. Warady, Bradley A. Furth, Susan L. Hooper, Stephen R. TI Neurocognitive outcomes in children with chronic kidney disease: Current findings and contemporary endeavors SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE NIH; NIDDK; chronic kidney disease in children prospective cohort study; pediatric chronic illness; neurocognitive outcomes in CKD; chronic renal insufficiency; glomerular filtration rate ID CHRONIC-RENAL-FAILURE; QUALITY-OF-LIFE; COGNITIVE FUNCTION; PLASMA HOMOCYSTEINE; PEDIATRIC DIALYSIS; BLOOD-PRESSURE; UNITED-STATES; HEALTH-STATUS; YOUNG-ADULTS; ADOLESCENTS AB Given the rise in chronic kidney disease (CKD) in both children and adults, CKD has recently been targeted as a public health priority. Childhood onset kidney disease is generally a noncurable and progressive condition that leads to kidney failure by early adulthood. Fortunately, improved identification of kidney problems allows for early intervention, which is thought to slow progression toward end-stage renal disease. In addition, medical interventions for pediatric end-stage renal disease have also improved, allowing children to take advantage of lifesaving renal replacement treatments such as dialysis and kidney transplantation. In spite of improvements in identification and treatment, CKD causes both direct and indirect insults to a variety of organ systems. This paper reviews recently published studies pertaining to the neurocognitive and psychosocial impact of CKD on children of various ages and at various stages of kidney failure. Specific attention is focused on summarizing peer reviewed research that describes associations between kidney functioning and cognitive functioning, language acquisition, visual spatial abilities, memory, and executive functioning. In addition, peer reviewed research describing psychosocial outcomes associated with CKD related to academic achievement, social-behavioral functioning, and quality of life are summarized. The authors also identified disease-specific factors that likely mediate neurocognitive outcomes (e.g., anemia, hypertension, cardiovascular) and endorse the importance of continued interdisciplinary research collaborations that will provide a better understanding of the mechanisms responsible for improved neurocognitive functioning after transplantation. The authors conclude this review by describing a multicenter, prospective, longitudinal, National Institutes of Health funded study that is currently examining the developmental outcomes of children with mild to moderate CKD. The authors speculate that the Chronic Kidney Disease in Children Prospective Cohort Study (CKiD) findings will provide additional evidence-based guidance for clinicians and researchers working with children and adolescents with deteriorating kidney function to improve medical and developmental outcomes. (C) 2006 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Inst Med, Dept Pediat, Baltimore, MD 21218 USA. Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR USA. NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD USA. Johns Hopkins Univ, Sch Publ Hlth, KIDMAC, Baltimore, MD USA. Albert Einstein Coll Med, Dept Neurol & Pediat, New York, NY USA. Univ Rochester, Dept Pediat, Rochester, NY USA. Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. Childrens Mercy Hosp, Dept Pediat, Kansas City, KS USA. Johns Hopkins Univ, Inst Med, Welch Ctr, Baltimore, MD USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Clin Ctr Study Dev & Learning, Chapel Hill, NC USA. RP Gerson, AC (reprint author), Johns Hopkins Univ, Inst Med, Dept Pediat, Baltimore, MD 21218 USA. EM agerson@jhmi.edu FU NIDDK NIH HHS [U01-DK-66116, U01 DK066174, U01-DK-66143, U01-DK-66174] NR 60 TC 48 Z9 48 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2006 VL 12 IS 3 BP 208 EP 215 DI 10.1002/mrdd.20116 PG 8 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 096WE UT WOS:000241406700007 PM 17061289 ER PT J AU Alexander, D Hanson, JW AF Alexander, Duane Hanson, James W. TI NICHD research initiative in newborn screening SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE newborn screening; genetics; technology; therapeutics; public health AB Recent changes In genetics research have created new opportunities to improve the scope and quality of newborn screening services. Changes in newborn screening should be supported and directed by an organized program of research. The NICHD Research Initiative in Newborn Screening includes the development of systematic methods to identify additional conditions appropriate for newborn screening, development and testing innovative interventions and treatments to improve outcomes; education of the provider workforce; development and implementation of appropriate information and communication systems for parents and providers; and, sponsoring an ongoing program of research and research training. Future needs will include the development of a national translational research infrastructure, prevention research and research into behavioral and social sciences Issues. The NICHD Research Initiative in Newborn Screening is expected to be an ongoing and vital initiative that adapts itself to new scientific findings, technological developments, changes in the public and personal health care system, and our evolving understanding of the needs of affected individuals, families and the community. Published 2006 Wiley-Liss, Inc. C1 NICHHD, Bethesda, MD 20892 USA. RP Hanson, JW (reprint author), NICHHD, MSC 7510,6100 Execut Blvd, Bethesda, MD 20892 USA. EM hansonj@mail.nih.gov NR 5 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2006 VL 12 IS 4 BP 301 EP 304 DI 10.1002/mrdd.20131 PG 4 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 122ML UT WOS:000243231000011 PM 17183575 ER PT J AU Fomous, C Miller, N AF Fomous, Cathy Miller, Naomi TI The role of National Library of Medicine (R) web sites in newborn screening education SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE newborn screening; consumer health education; rare diseases; MedlinePlus; National Library of Medicine; Genetics Home Reference ID HUMAN-GENETICS; INFORMATION; INTERNET; DESIGN AB Expanded newborn screening programs and subsequent detection of rare genetic disorders challenge parents and their medical providers to learn about the treatment and management of these disorders. Many people seek medical information on the Internet but may encounter requests for registration or fees, or find that resources are out of date, difficult to understand, or buried in advertisements. The U.S. National Library of Medicine (NLM), a component of the National Institutes of Health, provides web-based resources that address the challenges of newborn screening education. These resources include MedlinePlus (R), Genetics Home Reference (TM), ClinicalTrials.gov, and PubMed (R). NLM websites are riot commercial, do not require registration or fees, and provide varied levels of information for a continuum of audiences from low-literacy consumers to health professionals. Using phenylketonuria as an example, this study describes the information that parents and their medical providers can find through NLM resources. NLM has embraced the digital age and provides the public with reliable, accurate, and up-to-date educational materials. Published 2006 Wiley-Liss, Inc. C1 NIH, Natl Lib Med, Publ Serv Div, Bethesda, MD 20894 USA. Aspens Syst Corp, Rockville, MD USA. RP Miller, N (reprint author), NIH, Natl Lib Med, Publ Serv Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM millern@nlm.nih.gov NR 16 TC 1 Z9 1 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2006 VL 12 IS 4 BP 305 EP 312 DI 10.1002/mrdd.20125 PG 8 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 122ML UT WOS:000243231000012 PM 17183579 ER PT S AU Sutton, DJ Tchounwou, PB AF Sutton, Dwayne J. Tchounwou, Paul B. BE Alpoim, MC Morais, PV TI Mercury induces cytotoxicity and the externalization of phosphaticlylserine HK-2 human renal proximal tubule cells SO Metal Ions in Biology and Medicine, Vol 9 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 9th International Symposium on Metal Ions in Biology and Medicine CY MAY 21-24, 2006 CL Lisbon, PORTUGAL ID CHLORIDE-INDUCED NEPHROTOXICITY; INORGANIC MERCURY; UNILATERAL NEPHRECTOMY; INTRARENAL DISTRIBUTION; LUMINAL TRANSPORT; RABBIT; ACCUMULATION; GLUTATHIONE; KIDNEY; RATS AB Mercury is one of the most environmentally abundant toxic metals, and is known to produce cellular injury in the kidneys. The kidneys serve as a target organ for toxins due to its extremely high blood flow (20 - 25%) of the cardiac output. Hence, heavy metals such as mercury that enter the blood stream will travel to the kidneys. The primary function of the kidneys is to concentrate waste products, including heavy metals such as mercury. Transport and binding sites in the kidneys are present in the proximal tubules, and mercury may alter the structure and function of the proteins and membranes in these cells. These changes may result in long term residual effects. Heavy metals such as mercury elicit adverse effects in the proximal tubule and it is the epithelial cells of the proximal tubule that reabsorbs the mercury that is filtered out of the glomerulus. This research was therefore designed to evaluate the dose response relationship in human renal proximal tubule cells following exposure to mercury. Cytotoxicity was evaluated using the MTT-assay for cell viability. The Annexin-V assay was performed by flow cytometry to determine the extent of phosphatidylserine externalization in HK-2 cells exposed to mercury. Cells were exposed to mercury for 24 hours at doses of 0, 1, 2, 3, 4, 5, and 6 mu g/mL. Cytotoxicity experiments yielded a LD50 value of 4.65 +/- 0.6 mu g/mL upon 24 hours of exposure, indicating that mercury is highly toxic. The percentage of cells undergoing early apoptosis were 0.70 +/- 0.03%, 10.0 +/- 0.02%, 11.70 +/- 0.03%, 15.20 +/- 0.02%, 16.70 +/- 0.03%, 24.20 +/- 0.02%, and 25.60 +/- 0.04% for 0, 1, 2, 3, 4, 5, and 6 mu g/mL of mercury respectively, indicating a dose response relationship with regards to mercury induced cytotoxicity, and early apoptosis in HK-2 cells. C1 Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Sutton, DJ (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Coll Sci Engn & Technol, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0629-X J9 METAL IONS BIOL MED PY 2006 VL 9 BP 277 EP 281 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Toxicology GA BFL30 UT WOS:000242710200050 ER PT S AU Walker, AM Stevens, JJ Tchounwou, PB AF Walker, Alice M. Stevens, Jacqueline J. Tchounwou, Paul B. BE Alpoim, MC Morais, PV TI Arsenic trioxide mediated cytotoxicity and oxidative stress, in breast and lung carcinoma cell lines SO Metal Ions in Biology and Medicine, Vol 9 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 9th International Symposium on Metal Ions in Biology and Medicine CY MAY 21-24, 2006 CL Lisbon, PORTUGAL ID GROWTH AB Arsenic is a metalloid that is commonly found in soil, water and air. It is an element that has no known physiological function but is present in the body as a result of environmental exposure. The primary source of human exposure is through drinking water and food. Arsenic acts on cells through a variety of mechanisms influencing numerous signal transduction pathways resulting in cellular effects such as apoptosis' induction, growth inhibition and angiogenesis inhibition. Although arsenic has been reported to induce reactive oxygen species formation and oxidative stress in liver cells and hematopoetic cells, its effects on breast and lung cells are not well elucidated. The primary objective of this research is to evaluate the effects of arsenic cytotoxcity and to determine whether arsenic induces oxidative stress in breast and lung carcinoma cell lines. To achieve this goal, breast cancer (MCF-7) and lung cancer (A549) cells were cultured following standard protocols, and exposed to various doses of arsenic trioxide for 48 h. The 3-(4, 5 dimethyl-thiazoyl-2-yl) 2,5diphenyl-tetrazolium bromide (MTT) assay was performed to determine the cytotoxicity, and the thiobarbituric acid test was performed to evaluate the degree of lipid peroxidation and oxidative stress. Data obtained from the MTT assay indicated that arsenic significantly reduced the viability of MCF-7 and A549 cells. Upon 48 hr of exposure, the LD50 values from arsenic trioxide treatment were 11.5 and 14.1 mu g/ml for A549 cells and MCF-7 cells, respectively. The result of the thiobarbituric acid test demonstrated that arsenic trioxide treatment resulted in a significant increase (p < 0.05) of malondialdehyde-MDA, indicating that oxidative stress may play a key role in arsenic-induced toxicity in the breast and lung cells. C1 Jackson State Univ, Mol Toxicol Res Lab, Mol & Cellular Biol Res Lab, NIH,Ctr Environm Hlth,Coll Sci Engn & Technol, Jackson, MS USA. RP Walker, AM (reprint author), Jackson State Univ, Mol Toxicol Res Lab, Mol & Cellular Biol Res Lab, NIH,Ctr Environm Hlth,Coll Sci Engn & Technol, 1400 JR Lynch St,Box 18540, Jackson, MS USA. NR 12 TC 3 Z9 3 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0629-X J9 METAL IONS BIOL MED PY 2006 VL 9 BP 287 EP 292 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Toxicology GA BFL30 UT WOS:000242710200052 ER PT S AU Yedjou, C Steverson, M Tchounwou, P AF Yedjou, Clement Steverson, Matthew Tchounwou, Paul BE Alpoim, MC Morais, PV TI Lead nitrate-induced oxidative stress in human liver carcinoma (HepG(2)) cells SO Metal Ions in Biology and Medicine, Vol 9 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 9th International Symposium on Metal Ions in Biology and Medicine CY MAY 21-24, 2006 CL Lisbon, PORTUGAL ID TRANSCRIPTIONAL ACTIVATION; INDUCED HYPERTENSION; ANTIOXIDANT ENZYMES; TOXICITY; EXPRESSION; CADMIUM; GROWTH; GENES AB Most research on lead has focused on its effects on organ systems Such as the nervous system, the red blood cells, and the kidneys which are considered to be the primary targets of lead toxicity. However, its molecular mechanisms of toxicity are still largely unknown. In this research, we used HepG(2) cells as a model to study the cytotoxicity and oxidative stress associated with exposure to lead nitrate. We hypothesized that oxidative stress plays a key role in lead nitrate induced cytotoxicity. To test this hypothesis, we performed the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay for cell viability and the thiobarbituric acid test for lipid peroxidation. Data obtained from the MTT assay indicated that lead nitrate significantly reduced the viability of HepG(2) cells. Data generated from the thiobarbituric acid test showed a significant increase (p <= 0.05) in MDA levels in lead nitrate-treated HepG(2) cells compared to control cells. Lead nitrate treatment significantly increased cellular content of reactive oxygen species (ROS), as evidenced by the increase in MDA, a lipid peroxidation by-product. C1 Jackson State Univ, Coll Sci Engn & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Yedjou, C (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. NR 20 TC 9 Z9 10 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0629-X J9 METAL IONS BIOL MED PY 2006 VL 9 BP 293 EP 297 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Toxicology GA BFL30 UT WOS:000242710200053 ER PT S AU Yedjou, CG Tchounwou, PB AF Yedjou, Clement G. Tchounwou, Paul B. BE Alpoim, MC Morais, PV TI Oxidative stress in human leukemia (HL-60), human liver carcinoma (HepG(2)),and human (Jurkat-T) cells exposed to arsenic trioxide SO Metal Ions in Biology and Medicine, Vol 9 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 9th International Symposium on Metal Ions in Biology and Medicine CY MAY 21-24, 2006 CL Lisbon, PORTUGAL ID APOPTOSIS AB Recent studies have shown that arsenic trioxide (ATO) can induce a clinical remission in patients with acute promyelocytic leukemia. However, the molecular mechanisms of action remain to be elucidated. In this research, we performed the MTT assay to evaluate the cytotoxic effects of ATO to HL-60 cells and to compare their relative sensitivity to that of HepG(2), and Jurkat T cells. We also performed the thiobarbituric acid test to determine the levels of malondialdehyde (MDA) plus 4-hydroxy-2 (E)-nonenal (4-HAE) production in these three cell lines following exposure to ATO. The result of MTT assay clearly demonstrated that ATO has a significant cytotoxic effect on HL-60, Jurkat, and HepG(2) cells; showing 24 hrs LD50 values of 6.4 +/- 0.6 mu g/mL, 15 +/- 3.84 mu g/mL, and 23.2 +/- 6.03 mu g/mL, respectively. These data indicated that HL-60 cells are about twice as sensitive to arsenic toxicity compared to Jurkat T cells and about 3 times more sensitive to arsenic trioxide compared to HepG(2) cells. The result of the thiobarbituric acid test demonstrated that arsenic trioxide treatment resulted in a significant increase (p < 0.05) of MDA and HAE production, indicating that oxidative stress plays a key role in arsenic induced toxicity and cell injury. MDA and HAE levels were significantly higher in ATO-treated HL-60 cells, indicating that these cells appear to be more sensitive to oxidative stress than HepG(2) and Jurkat-T cells. In summary, these results indicate that the pharmacology of ATO as an effective anti-cancer drug is associated with its cytotoxic effects in human promyelocytic leukemic cells. This cytotoxicity is found to be mediated by oxidative stress, a biomarker of cellular injury. C1 Jackson State Univ, Coll Sci Engn & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Yedjou, CG (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. FU NCRR NIH HHS [G12 RR013459, G12 RR013459-02S10007] NR 12 TC 2 Z9 2 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0629-X J9 METAL IONS BIOL MED PY 2006 VL 9 BP 298 EP 303 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Toxicology GA BFL30 UT WOS:000242710200054 PM 26435679 ER PT S AU Patlolla, AK Tchounwou, PB AF Patlolla, Anita K. Tchounwou, Paul B. BE Alpoim, MC Morais, PV TI Arsenic trioxide induced oxidative stress in Sprague-Dawley rats SO Metal Ions in Biology and Medicine, Vol 9 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 9th International Symposium on Metal Ions in Biology and Medicine CY MAY 21-24, 2006 CL Lisbon, PORTUGAL ID DIMETHYLARSINIC ACID; INORGANIC ARSENICS; TOXICITY; CELLS; GENOTOXICITY; ACTIVATION; METABOLITE; APOPTOSIS; RADICALS; EXPOSURE AB Arsenic is a known human carcinogen and induces a variety of human diseases in addition to cancers of the lung, skin, bladder, kidneys and liver. The mechanism, by which arsenic induces cancer, however remains poorly understood. Although multiple pathways such as inhibition of DNA repair, methylation status, and cocarcinogenesis with other environmental toxicants have been proposed, recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which has a role in the pathogenesis of arsenic-induced diseases. The main aim of the present investigation was to determine the concentration of malondialdehyde (MDA), as an indicator of lipid peroxidation in the serum of Sprague-Dawley rats. Four groups of six male rats each weighing approximately 60 +/- 2 g, were injected intraperitoneally, once a day for five days with doses of 5, 10, 15, 20 mg/kg body weight (BW) of arsenic trioxide dissolved in distilled water. A control group was also made of six animals injected with distilled water without chemical. Following anaesthetization, blood specimens were immediately collected in tubes containing EDTA as an anticoagulant, and the concentration of malondialdehyde (MDA), a convenient index of lipid peroxidation in serum samples was determined using by colorimetry (Calbiochem). Arsenic trioxide (As2O3) exposure significantly (p <= 0.05) increased the concentration of MDA in the treated groups [8.0-22.3 mu M] compared to the control group [7.3 mu M], showing a gradual increase in lipid peroxidation with increasing doses of arsenic. These findings indicate that oxidative stress plays a role in arsenic-induced cellular damage in Sprague-Dawley rats. C1 Jackson State Univ, Coll Sci Engn & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Patlolla, AK (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. NR 20 TC 0 Z9 0 U1 1 U2 1 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0629-X J9 METAL IONS BIOL MED PY 2006 VL 9 BP 417 EP 421 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Toxicology GA BFL30 UT WOS:000242710200075 ER PT S AU Patlolla, AK Tchounwou, PB AF Patlolla, Anita K. Tchounwou, Paul B. BE Alpoim, MC Morais, PV TI Serum alkaline phosphatase as a biomarker of arsenic-induced hepatobiliary or cholestatic effect in Sprague-Dawley rats SO Metal Ions in Biology and Medicine, Vol 9 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 9th International Symposium on Metal Ions in Biology and Medicine CY MAY 21-24, 2006 CL Lisbon, PORTUGAL ID TOXICITY; LIVER; MICE AB Recent studies in our laboratory have demonstrated that arsenic trioxide is hepatotoxic and able to biochemically induce a significant increase in the activities of serum aminotransferases in Sprague-Dawley rats [Tchounwou et al., Metal Ions in Biology & Medicine Vol. 8:284-288, 2004]. In humans chemically induced hepatocellular toxicity has also been linked to obstructive cholestasis involving the hepatobiliary system. The mechanisms involved in drug-induced cholestasis are poorly understood. One of the major reasons for this deficiency is a lack of animal model. It is possible, however to produce cholestatic effects in animals with selected bile acids, some steroids and certain chemicals that have no therapeutic utility. The aim of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of alkaline phosphatase (ALP), an important liver enzyme that may be released from hepatocytes as a result of cholestatic injury. Four groups of six male rats each weighing approximately 60 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW), one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthetization, blood specimens were immediately collected using heparinized syringes, alkaline phosphatase identification and quantification was performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly increased the activity of alkaline phosphatase (ALP). Optical density readings of 0.163 +/- 0.014, 0.239 +/- 0.023, 0.242 +/- 0.010, 0.303 +/- 0.024, 0.399 +/- 0.049 (ALP) were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual increase in phosphatase activity with increasing doses of arsenic. Our results indicate that alkaline phosphatase is a candidate biomarker for arsenic-induced hepatobiliary or cholestatic effect in Sprague-Dawley rats. C1 Jackson State Univ, CSET, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Patlolla, AK (reprint author), Jackson State Univ, CSET, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0629-X J9 METAL IONS BIOL MED PY 2006 VL 9 BP 422 EP 425 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Toxicology GA BFL30 UT WOS:000242710200076 ER PT S AU Endo, Y Even-Ram, S Pankov, R Matsumoto, K Yamada, KM AF Endo, Y Even-Ram, S Pankov, R Matsumoto, K Yamada, KM BE Balch, WE Der, CJ Hall, A TI Inhibition of Rho GTPases by RNA interference SO METHODS IN ENZYMOLOGY, VOL 406, REGULATORS AND EFFECTORS OF SMALL GTPASES: RHO FAMILY SE Methods in Enzymology LA English DT Review; Book Chapter ID MAMMALIAN-CELLS; ARGONAUTE2; EXPRESSION; MIGRATION; PATHWAY; RAC AB Selective down-modulation or silencing of individual members of the Rho-GTPase family is now practical using RNA interference. Transfection of mammalian cells with an individual siRNA duplex or siRNA pools can suppress expression of a specific isoform to understand its function. By adjusting the dose of siRNA, intermediate levels of suppression can be attained to test the biological role of different levels of a GTPase such as Rac. Nevertheless, there are significant potential pitfalls, including "off-target" effects of the siRNA on other genes. Besides demonstrating successful, noncytotoxic suppression of protein and activity levels of a specific GTPase, controls are essential to establish specificity. In this chapter, we provide methods for selective knockdown of expression by siRNA and confirmation of the effectiveness of Rho GTPase silencing, as well as descriptions and some examples of controls for specificity that include evaluations of dose-response, negative and positive controls, GTPase specificity, confirmation by using more than one siRNA for the same gene, rescue by a mutated siRNA-resistant cDNA encoding the target gene, and complementary supporting evidence. Selective silencing of specific Rho family GTPases should provide increasing insight into the regulatory and functional roles of each isoform in a wide variety of biological processes. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev biol & Regenerat Branch, NIH, Bethesda, MD USA. Univ Sofia, Dept Cytol Hist & Embryol, Fac Biol, BU-1126 Sofia, Bulgaria. RP Even-Ram, S (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev biol & Regenerat Branch, NIH, Bethesda, MD USA. RI Pankov, Roumen/B-3284-2014; OI Pankov, Roumen/0000-0002-3157-3659; Even-Ram, Sharona/0000-0002-5540-3822; Yamada, Kenneth/0000-0003-1512-6805 FU Intramural NIH HHS NR 19 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182811-5 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 406 BP 345 EP 361 DI 10.1016/S0076-6879(06)06025-3 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDV97 UT WOS:000235750600025 PM 16472669 ER PT S AU Zhou, QF Shung, KK Zhang, Q Djuth, FT AF Zhou, Q. F. Shung, K. K. Zhang, Q. Djuth, F. T. BE George, T Cheng, ZY TI High frequency piezoelectric micromachined ultrasonic transducers for imaging applications - art. no. 62230H SO Micro (MEMS) and Nanotechnologies for Space Applications SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Micro (MEMS) and Nanotechnologies for Space Applications CY APR 19-20, 2006 CL Kissimmee, FL SP SPIE DE high frequency ultrsaound; sol-gel process; ultrasound transducer; MEMS ID FABRICATION AB Methods for fabricating high frequency ultrasound transducer and array based on piezoelectric films and MEMS technology are presented in this paper. Piezoelectric PZT films up to 30 mu m-thick deposited on silicon substrate have been prepared by a modified sol-gel process. The raw materials included lead acetate trihydrate and zirconium n-propoxide and titanate isoproxide. The sol-gel PZT solutions were prepared using above materials and 2-methoxyethanol as the solvent. Spin-coated films were annealed at 750 degrees C by a rapid thermal annealing (RTA) process. Thicker PZT films were fabricated by repeating this process and using a modified PZT composite solution. The high frequency single element transducers actuated by the PZT films were fabricated and pulse-echo measurement results show the transducers had a broad bandwidth and high central frequencies. The beam profile of one 103 MHz transducer was measured using a 8 mu m diameter wire and a lateral resolution of 33 mu m was observed. A micromachined process to fabricate high frequency linear array will be also presented. C1 Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. RP Zhou, QF (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. NR 10 TC 2 Z9 2 U1 2 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 0-8194-6279-9 J9 P SOC PHOTO-OPT INS PY 2006 VL 6223 BP H2230 EP H2230 AR 62230H DI 10.1117/12.667116 PG 7 WC Engineering, Aerospace; Engineering, Electrical & Electronic; Engineering, Mechanical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA BES61 UT WOS:000239303900014 ER PT J AU Provenzano, D Kovac, P Wade, WF AF Provenzano, Daniele Kovac, Pavol Wade, William F. TI The ABCs (Antibody, B cells, and carbohydrate epitopes) of cholera immunity: Considerations for an improved vaccine SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Review DE cholera vaccine; LPS; B cells; antibody; immunity ID SPLENIC MARGINAL ZONE; THYMUS-INDEPENDENT ANTIGENS; TOXIN-COREGULATED PILUS; CONTROLLED FIELD TRIAL; TOLL-LIKE RECEPTORS; SECRETORY IMMUNOGLOBULIN-A; INTESTINAL PLASMA-CELLS; O139 VIBRIO-CHOLERAE; CVD 103-HGR; MONOCLONAL-ANTIBODIES AB Cholera, a diarrheal disease, is known for explosive epidemics that can quickly kill thousands. Endemic cholera is a seasonal torment that also has a significant mortality. Not all nations with extensive rural communities can achieve the required infrastructure or behavioral changes to prevent epidemic or endemic cholera. For some communities, a single-dose cholera vaccine that protects those at risk is the most efficacious means to reduce morbidity and mortality. It is clear that our understanding of what a protective cholera immune response is has not progressed at the rate our understanding of the pathogenesis and molecular biology of cholera infection has. This review addresses V cholerae lipopolysaccharide (LPS)-based immunogens because LPS is the only immunogen proven to induce protective antibody in humans. We discuss the role of anti-LPS antibodies in protection from cholera, the importance and the potential role of B cell subsets in protection that is based on their anatomical location and the intrinsic antigen-receptor specificity of various subsets is introduced. C1 Dartmouth Med Sch, Dept Microbiol & Immunol, Lebanon, NH 03756 USA. Univ Texas, Dept Biol Sci, Brownsville, TX 78520 USA. NIDDK, NIH, LMC, Sect Carbohydrates, Bethesda, MD 20892 USA. RP Wade, WF (reprint author), Dartmouth Med Sch, Dept Microbiol & Immunol, 630W Borwell Bldg, Lebanon, NH 03756 USA. EM william.wade@dartmouth.edu FU Intramural NIH HHS; NIAID NIH HHS [AI064610, AI47373]; NIGMS NIH HHS [GM068855] NR 257 TC 19 Z9 22 U1 2 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PY 2006 VL 50 IS 12 BP 899 EP 927 PG 29 WC Immunology; Microbiology SC Immunology; Microbiology GA 114KV UT WOS:000242666000001 PM 17179659 ER PT J AU Cardones, AR Leitner, WW Fang, L Murakami, T Kapoor, V Udey, MC Hwang, ST AF Cardones, AR Leitner, WW Fang, L Murakami, T Kapoor, V Udey, MC Hwang, ST TI Genetic immunization with LYVE-1 cDNA yields function-blocking antibodies against native protein SO MICROVASCULAR RESEARCH LA English DT Article DE lymphatics; angiogenesis; immunization ID LYMPHATIC ENDOTHELIAL-CELLS; METASTATIC SPREAD; NODE METASTASIS; HYALURONIC-ACID; NUCLEIC-ACID; DNA; LYMPHANGIOGENESIS; EXPRESSION; VACCINES; RECEPTOR AB LYVE-I is a surface bound hyaluronic acid (HA) receptor that is preferentially expressed by lymphatic endothelial cells (LEC). cDNA encoding full-length human LYVE-I was coated onto gold particles that were then delivered via helium-assisted jet propulsion (gene gun) into the skin of Balb/C mice. LY-VE-I antisera, but not control pre-immune sera, recognized LYVE-1-transfected 293T cells by flow cytometry. While 40-70% of cultured human dermal microvascular endothelial cells (HMEC) were positive for LYVE-1 staining, human lung microvascular endothelial cells (LMEC) were negative. LYVE-1 antisera was used to effectively separate HMEC into LYVE-1(hi) and LYVE-1(lo) populations that were enriched or depleted, respectively, for podoplanin, another LEC marker. By immumohistochemistry, LYVE-1 antisera detected CD31(lo) podoplanin hi lymphatic channels in normal and psoriatic human skin as well as in human tonsil. LYVE-1 antisera also blocked binding of FITC-labeled HA to HMEC (but not LMEC), demonstrating that these antibodies recognized regions of LYVE-1 required for HA binding. In summary, gene gun-assisted delivery of cDNA encoding LYVE-1 into skin resulted in reliable production of antisera that specifically and functionally recognized native LYVE-1 protein. Published by Elsevier Inc. C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branches, NIH, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NCI, NIH, 10 Ctr Dr,Room 12N258, Bethesda, MD 20892 USA. EM hwangs@mail.nih.gov RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 FU Intramural NIH HHS NR 31 TC 2 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD JAN PY 2006 VL 71 IS 1 BP 32 EP 39 DI 10.1016/j.mvr.2005.09.002 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 013UQ UT WOS:000235435800004 PM 16257423 ER PT B AU N'Gouemo, P Rogawski, MA AF N'Gouemo, Prosper Rogawski, Michael A. BE Pitkanen, A Schwartzkroin, PA Moshe, SL TI Alcohol Withdrawal Seizures SO MODELS OF SEIZURES AND EPILEPSY LA English DT Article; Book Chapter ID METHYL-D-ASPARTATE; CHRONIC INTERMITTENT ETHANOL; INFERIOR COLLICULUS NEURONS; PONTINE RETICULAR-FORMATION; GAMMA-AMINOBUTYRIC-ACID; ANALOGS DIZOCILPINE MK-801; DOPAMINE TRANSPORTER GENE; QUANTITATIVE-TRAIT-LOCI; SOUND-INDUCED SEIZURES; HIPPOCAMPAL-NEURONS C1 [N'Gouemo, Prosper] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. [Rogawski, Michael A.] NINDS, Epilepsy Res Sect, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP N'Gouemo, P (reprint author), Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. NR 168 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045702-4; 978-0-12-088554-1 PY 2006 BP 161 EP 177 DI 10.1016/B978-012088554-1/50015-3 PG 17 WC Neurosciences SC Neurosciences & Neurology GA BCT46 UT WOS:000311355400015 ER PT J AU Rapkiewicz, AV Lowenthal, M Kleiner, DE Liotta, LA AF Rapkiewicz, AV Lowenthal, M Kleiner, DE Liotta, LA TI The vitreous proteome: An autopsy study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. George Mason Univ, Manassas, VA USA. Univ Colorado, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 15 BP 7A EP 7A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094500016 ER PT J AU Ning, EMLL Palau, MA Garcia-Macias, C Allende, D Silva, A Merino, MJ AF Ning, EMLL Palau, MA Garcia-Macias, C Allende, D Silva, A Merino, MJ TI CISH (TM) is a good technique to determine HER2 gene amplification in cytologic preparations from breast carcinomas: Excellent correlation with FFPE tissue analysis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Hosp Univ Salamanca, Salamanca, Spain. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 277 BP 63A EP 63A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094500277 ER PT J AU Manosca, F Schinstine, M Fetsch, P Brosky, K Erickson, D Wilder, A Sorbara, L Raffeld, M Filie, A Abati, A AF Manosca, F Schinstine, M Fetsch, P Brosky, K Erickson, D Wilder, A Sorbara, L Raffeld, M Filie, A Abati, A TI The diagnostic effects of prolonged storage on fresh effusion samples SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 288 BP 65A EP 66A PG 2 WC Pathology SC Pathology GA 995IR UT WOS:000234094500288 ER PT J AU Merino, MJ Toro, JR Palau, MA Linehan, WM Torres-Cabala, CA AF Merino, MJ Toro, JR Palau, MA Linehan, WM Torres-Cabala, CA TI The spectrum of morphologic features of renal tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome: Our experience with 34 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 691 BP 150A EP 150A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094501130 ER PT J AU Palau, MA Torres-Cabala, C Ning, EL Linehan, WM Merino, MJ AF Palau, MA Torres-Cabala, C Ning, EL Linehan, WM Merino, MJ TI Determination of EGER status in sporadic and hereditary renal tumors. Correlation between CISH and immunohistochemistry SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 707 BP 153A EP 153A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094501146 ER PT J AU Torres-Cabala, CA Ning, EMLL Teller, LS Palau, MA Linehan, WM Merino, MJ AF Torres-Cabala, CA Ning, EMLL Teller, LS Palau, MA Linehan, WM Merino, MJ TI Are some collecting duct carcinomas indeed HLRCC tumors? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 760 BP 165A EP 165A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094501199 ER PT J AU Jiang, L Malpica, A Deavers, M Nuovo, G Merino, M Silva, EG AF Jiang, L Malpica, A Deavers, M Nuovo, G Merino, M Silva, EG TI Endometrioid adenocarcinoma involving the endometrium and the cervix: One tumor or two independent tumors? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Ohio State Univ, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 845 BP 183A EP 183A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094501284 ER PT J AU Ning, EMLL Teller, LS Ricketts, RSJ Otis, C Sobel, M Merino, MJ AF Ning, EMLL Teller, LS Ricketts, RSJ Otis, C Sobel, M Merino, MJ TI Clonality of borderline and serous carcinoma of the ovary: Molecular studies identify a monoclonal origin for primary tumors and their implants SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Baystate Med Ctr, Springfield, MA 01199 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 867 BP 187A EP 187A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094501306 ER PT J AU Tilara, A Henson, DE Schwartz, A Grimley, P Anderson, WF AF Tilara, A Henson, DE Schwartz, A Grimley, P Anderson, WF TI Population based epidemiology complements pathological data in gynecological cancers SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 George Washington Univ, Washington, DC USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 924 BP 199A EP 199A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094501363 ER PT J AU Feldman, AL Espina, V Gulmann, G Winters, M Liotta, LA Jaffe, ES AF Feldman, AL Espina, V Gulmann, G Winters, M Liotta, LA Jaffe, ES TI Tissue proteomics, the Bcl-2/Bax switch, and the role of the pathologist SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. George Mason Univ, Manassas, VA USA. RI Feldman, Andrew/D-5028-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1044 BP 225A EP 225A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094501483 ER PT J AU Maric, I Siddon, A Fu, W Stoddard, J Robyn, J Metcalfe, D Noel, P AF Maric, I Siddon, A Fu, W Stoddard, J Robyn, J Metcalfe, D Noel, P TI Correlation of KIT D816V mutation analysis and immunophenotypic analysis of bone marrow aspirates in patients evaluated for systemic mastocytosis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 CC, NIH, Bethesda, MD USA. NIAD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1095 BP 236A EP 236A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502038 ER PT J AU Quintanilla-Martinez, L Pittaluga, S Davies-Hill, T Miething, C Anastosov, N Rudelius, M Duyster, J Jaffe, ES Fend, F Raffeld, M AF Quintanilla-Martinez, L Pittaluga, S Davies-Hill, T Miething, C Anastosov, N Rudelius, M Duyster, J Jaffe, ES Fend, F Raffeld, M TI The transcription factor CCAAT/enhancer binding protein (C/EBP)beta is constitutively expressed in ALK-positive anaplastic large cell lymphomas (ALCL), and is dependent upon NPM-ALK kinase activity SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 GSF Res Ctr Hlth & Environm, Neuherberg, Germany. NCI, NIH, Bethesda, MD 20892 USA. Tech Univ Munich, D-8000 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1123 BP 242A EP 242A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502066 ER PT J AU Rizzo, KJA Streubel, B Chott, A Sorbara, L Kumar, S Pittaluga, S Raffeld, M Jaffe, ES AF Rizzo, KJA Streubel, B Chott, A Sorbara, L Kumar, S Pittaluga, S Raffeld, M Jaffe, ES TI MALT lymphoma of the dura: Analysis of clinical, histological and genetic features SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Med Univ Vienna, Vienna Gen Hosp, Vienna, Austria. Vet Affairs Med Ctr, Washington, DC 20422 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1130 BP 244A EP 244A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502073 ER PT J AU Salaverria, I Bea, S Zettl, A Valls, J Moreno, V Ott, G Muller-Hermelink, HK Staudt, LM Campo, E Rosenwald, A AF Salaverria, I Bea, S Zettl, A Valls, J Moreno, V Ott, G Muller-Hermelink, HK Staudt, LM Campo, E Rosenwald, A TI Secondary genetic alterations in mantle cell lymphoma influence gene expression and improve the proliferation-based prognostic model SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Hosp Clin Barcelona, Barcelona, Spain. Univ Wurzburg, Wurzburg, Germany. IDIBELL Catalan Inst Oncol, Barcelona, Spain. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1135 BP 245A EP 245A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502078 ER PT J AU Joshi, S Guindi, M Feld, JJ Diennes, HP Lohse, A Heatchote, EJ AF Joshi, S Guindi, M Feld, JJ Diennes, HP Lohse, A Heatchote, EJ TI Long term histological and clinical follow-up of anti-mitochondrial antibody (AMA) positive autoimmune hepatitis (AIH): Another variant of autoimmune hepatitis or a well controlled overlap syndrome? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Credit Valley Hosp, Mississauga, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. NIH, Bethesda, MD 20892 USA. Univ Cologne, D-5000 Cologne 41, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1269 BP 273A EP 273A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502212 ER PT J AU Begnami, MD Palau, M Rushing, E Santi, M Quezado, M AF Begnami, MD Palau, M Rushing, E Santi, M Quezado, M TI Evaluation of NF2 gene deletion in sporadic schwannomas, meningiomas and ependymomas by chromogenic in situ hydridization SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Childrens Hosp, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1319 BP 284A EP 284A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502262 ER PT J AU Shilo, K Fukuoka, J Mani, H Sesterhenn, IA Jen, J Travis, WD Franks, TJ AF Shilo, K Fukuoka, J Mani, H Sesterhenn, IA Jen, J Travis, WD Franks, TJ TI Alpha-methylacyl CoA racemase (AMACR) expression in pulmonary carcinomas: A study of 406 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. Toyama Med & Pharmaceut Univ, Toyama, Japan. NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1473 BP 316A EP 316A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502416 ER PT J AU Fountaine, T Wincovitch, S Geho, D Garfield, S Pittaluga, S AF Fountaine, T Wincovitch, S Geho, D Garfield, S Pittaluga, S TI Multispectral imaging of cellular targets using semiconductor quantum dots SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, CCR Confocal Microscopy Core Facil, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1529 BP 328A EP 328A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502472 ER PT J AU Patel, AA Gupta, D Seligson, D Hattab, EM Balis, U Ulbright, TM Berman, JJ Gilbertson Jr Becich, MJ Parwani, AV AF Patel, AA Gupta, D Seligson, D Hattab, EM Balis, U Ulbright, TM Berman, JJ Gilbertson, JR Becich, MJ Parwani, AV TI Availability and quality of paraffin blocks identified by the Shared Pathology Informatics Network (SPIN): A multi-institutional study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Indiana Univ, Indianapolis, IN 46204 USA. Harvard Univ, Boston, MA 02115 USA. NCI, DCTD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1549 BP 332A EP 332A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502492 ER PT J AU Patel, AA Gilbertson Jr Parwani, AV Dhir, R Datta, MW Gupta, R Berman, JJ Becich, MJ AF Patel, AA Gilbertson, JR Parwani, AV Dhir, R Datta, MW Gupta, R Berman, JJ Becich, MJ TI The NCl cooperative prostate cancer tissue resource: Informatics support for a multi-institute biorepository SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Pittsburgh, PA USA. Emory Univ, Atlanta, GA 30322 USA. NCI, DCTD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1550 BP 332A EP 333A PG 2 WC Pathology SC Pathology GA 995IR UT WOS:000234094502493 ER PT J AU Silva, AS Palau, M Merino, MJ AF Silva, AS Palau, M Merino, MJ TI Utilization of chromosome Y chromogenic in situ hybridization (CISH (TM)) to detect male cells in surgical pathology specimens SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1558 BP 334A EP 334A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502501 ER PT J AU Riley, CR Vortmeyer, A Oldfield, EH Lonser, R Salah, B Abu-Asab, M Tsokos, M AF Riley, CR Vortmeyer, A Oldfield, EH Lonser, R Salah, B Abu-Asab, M Tsokos, M TI Endolymphatic sac tumorigenesis; Ultrastructural characteristics SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1587 BP 340A EP 340A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502530 ER EF