FN Thomson Reuters Web of Science™ VR 1.0 PT B AU Koslow, SH AF Koslow, SH BE Wang, L Rajapakse, JC Fukushima, K Lee, SY Yao, X TI Neuroscience data bases SO ICONIP'02: PROCEEDINGS OF THE 9TH INTERNATIONAL CONFERENCE ON NEURAL INFORMATION PROCESSING: COMPUTATIONAL INTELLIGENCE FOR THE E-AGE LA English DT Proceedings Paper CT 9th International Conference on Neural Information Processing CY NOV 18-22, 2002 CL SINGAPORE, SINGAPORE SP Asia Pacific Neural Network Assembly, Singapore Neurosci Assoc, SEAL & FSKD Conf Steering Comm, Nanyang Technol Univ, Sch Elect & Electr Engn ID SHARING PRIMARY DATA AB The creation of databases for the field of neuroscience research is both a necessary and formidable challenge. It is desirable and necessary to be able to understand and integrate the vast amount of experimentally derived data collected around the globe. This data is growing exponentially, as well as increasing in complexity and sophistication due to the capabilities of the newest technologies that are being applied. We are now beginning to understand the structural, functional and developmental aspects of the nervous system at finer and finer levels of granularity. Creating databases is a formidable challenge because the data are diverse being derived from chemical, biophysical, structural, morphological, physiological or behavioural sources, with each domain having its own characteristic parameters. This presentation will review the important developments that have led to this new field of neuroinformatics and the efforts that are underway in the USA and around the world to make this a true international research effort. C1 NIMH, Off Neuroinformat, NIH, Bethesda, MD 20892 USA. RP Koslow, SH (reprint author), NIMH, Off Neuroinformat, NIH, 6001 Execut Blvd,Room 6167,MSC 9613, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NANYANG TECHNOLOGICAL UNIV PI SINGAPORE PA NANYANG AVENUE, SINGAPORE 639815, SINGAPORE BN 981-04-7524-1 PY 2002 BP 190 EP 192 PG 3 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology SC Computer Science; Engineering; Imaging Science & Photographic Technology GA BW69E UT WOS:000182832400040 ER PT B AU Liu, H Blumenthal, J Clasen, L Lausier, A Giedd, J AF Liu, H Blumenthal, J Clasen, L Lausier, A Giedd, J BE Wang, L Rajapakse, JC Fukushima, K Lee, SY Yao, X TI Using multidimensional scaling to assess shape differences of human corpus callosum SO ICONIP'02: PROCEEDINGS OF THE 9TH INTERNATIONAL CONFERENCE ON NEURAL INFORMATION PROCESSING: COMPUTATIONAL INTELLIGENCE FOR THE E-AGE LA English DT Proceedings Paper CT 9th International Conference on Neural Information Processing CY NOV 18-22, 2002 CL SINGAPORE, SINGAPORE SP Asia Pacific Neural Network Assembly, Singapore Neurosci Assoc, SEAL & FSKD Conf Steering Comm, Nanyang Technol Univ, Sch Elect & Electr Engn ID MRI C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Liu, H (reprint author), NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-2002-8978 NR 8 TC 0 Z9 0 U1 0 U2 0 PU NANYANG TECHNOLOGICAL UNIV PI SINGAPORE PA NANYANG AVENUE, SINGAPORE 639815, SINGAPORE BN 981-04-7524-1 PY 2002 BP 219 EP 221 PG 3 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology SC Computer Science; Engineering; Imaging Science & Photographic Technology GA BW69E UT WOS:000182832400047 ER PT J AU Basser, PJ Pajevic, S Pierpaoli, C Aldroubi, A AF Basser, PJ Pajevic, S Pierpaoli, C Aldroubi, A TI Fiber tract following in the human brain using DT-MRI data SO IEICE TRANSACTIONS ON INFORMATION AND SYSTEMS LA English DT Article DE MRI; DTI; DT; diffusion; tensor; human; brain; white matter; fiber; tract; trajectory; artifact; noise ID DIFFUSION-TENSOR MRI; B-MATRIX; SPECTROSCOPY; ANISOTROPY; ECHO AB In Vivo Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) can now be used to elucidate and investigate major nerve pathways in the brain. Nerve pathways are constructed by a) calculating a continuous diffusion tensor field from the discrete, noisy, measured DT-MRI data and then b) solving an equation describing the evolution of a fiber tract, in which the local direction vector of the trajectory is identified with the direction of maximum apparent diffusivity. This approach has been validated previously using synthesized, noisy DT-MRI data, Presently, it is possible to reconstruct large white matter structures in the brain, such as the corpus callosum and the pyramidal tracts. Several problems, however, still affect the method's reliability. Its accuracy degrades where the fiber-tract directional distribution is non-uniform, and background noise in diffusion weighted MRIs can cause computed trajectories to jump to different tracts. Nonetheless, this method can provide quantitative information with which to visualize and study connectivity and continuity of neural pathways in the central and peripheral nervous systems in vivo, and holds promise for elucidating architectural features in other fibrous tissues and ordered media. C1 NICHHD, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA. NIH, Math Stat & Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Math, Nashville, TN USA. RP Basser, PJ (reprint author), NICHHD, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA. RI Pierpaoli, Carlo/E-1672-2011; Aldroubi, Akram/J-7186-2012; Basser, Peter/H-5477-2011 NR 35 TC 23 Z9 26 U1 0 U2 2 PU IEICE-INST ELECTRONICS INFORMATION COMMUNICATIONS ENG PI TOKYO PA KIKAI-SHINKO-KAIKAN BLDG MINATO-KU SHIBAKOEN 3 CHOME, TOKYO, 105, JAPAN SN 0916-8532 J9 IEICE T INF SYST JI IEICE Trans. Inf. Syst. PD JAN PY 2002 VL E85D IS 1 BP 15 EP 21 PG 7 WC Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA 506TE UT WOS:000172987200004 ER PT J AU Pechhold, K Craighead, N Wesch, D Kabelitz, D AF Pechhold, K Craighead, N Wesch, D Kabelitz, D TI Measurement of cellular proliferation SO IMMUNOLOGY OF INFECTION, SECOND EDITION SE METHODS IN MICROBIOLOGY LA English DT Review ID RAPID COLORIMETRIC ASSAY; MATURE T-LYMPHOCYTES; CELLS; APOPTOSIS; VIABILITY; CYTOMETRY; GROWTH; DEATH C1 NIDDK, Navy Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20889 USA. Univ Kiel, Inst Immunol, D-24105 Kiel, Germany. RP Pechhold, K (reprint author), NIDDK, Navy Transplantat & Autoimmun Branch, NIH, NNMC AFRRI Bldg 46,Room 2417,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 21 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0580-9517 J9 METHOD MICROBIOL PY 2002 VL 32 BP 77 EP 97 PG 21 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA BW02J UT WOS:000180664100004 ER PT J AU De Groot, AS Sbai, H Martin, B Berzofsky, JA AF De Groot, AS Sbai, H Martin, B Berzofsky, JA TI Use of bioinformatics to predict MHC ligands and T-cell epitopes: Application to epitope-driven vaccine design SO IMMUNOLOGY OF INFECTION, SECOND EDITION SE METHODS IN MICROBIOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; CLASS-I MOLECULES; MYCOBACTERIUM-TUBERCULOSIS; CTL EPITOPE; COSTIMULATORY MOLECULES; PEPTIDE VACCINE; TRANSGENIC MICE; DNA VACCINES; HLA-A2.1-TRANSGENIC MICE C1 Brown Univ, TB HIV Res Lab, Ctr Biomed, Providence, RI 02912 USA. EpiVax Inc, Vaccine Design Unit, Providence, RI 02906 USA. NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP De Groot, AS (reprint author), Brown Univ, TB HIV Res Lab, Ctr Biomed, Box B-G 579,Rm 579,85 Brown St, Providence, RI 02912 USA. OI De Groot, Annie/0000-0001-5911-1459 NR 104 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0580-9517 J9 METHOD MICROBIOL PY 2002 VL 32 BP 99 EP 123 PG 25 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA BW02J UT WOS:000180664100005 ER PT B AU Winslow, RL Helm, P Baumgartner, W Peddi, S Ratnanather, T McVeigh, E Miller, MI AF Winslow, RL Helm, P Baumgartner, W Peddi, S Ratnanather, T McVeigh, E Miller, MI BE Bock, G Goode, JA TI Imaging-based integrative models of the heart: closing the loop between experiment and simulation SO IN SILICO SIMULATION OF BIOLOGICAL PROCESSES SE NOVARTIS FOUNDATION SYMPOSIUM LA English DT Article; Proceedings Paper CT Symposium on In Silico Simulation of Biological Processes CY NOV 27-29, 2001 CL NOVARTIS FDN, LONDON, ENGLAND HO NOVARTIS FDN ID COMPUTATIONAL ANATOMY; DIFFUSION TENSOR; BIDOMAIN MODEL; GEOMETRY; FAILURE AB We describe methodologies for: (a) mapping ventricular activation using high-density epicardial electrode arrays; (b) measuring and modelling ventricular geometry and fibre orientation at high spatial resolution using diffusion tensor magnetic resonance imaging (DTMRI); and (c) simulating electrical conduction; using comprehensive data sets collected from individual canine hearts. We demonstrate that computational models based on these experimental data sets yield reasonably accurate reproduction of measured epicardial activation patterns. We believe this ability to electrically map and model individual hearts will lead to enhanced understanding of the relationship between anatomical structure, and electrical conduction in the cardiac ventricles. C1 Johns Hopkins Univ, Whitaker Biomed Engn Inst, Ctr Computat Med & Biol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Ctr Imaging Sci, Baltimore, MD 21218 USA. Johns Hopkins Univ, NIH, Lab Cardiac Energet, Med Imaging Sect 3, Baltimore, MD 21218 USA. RP Winslow, RL (reprint author), Johns Hopkins Univ, Whitaker Biomed Engn Inst, Ctr Computat Med & Biol, Baltimore, MD 21218 USA. RI Miller, Michael I./A-3213-2010 FU NHLBI NIH HHS [P50 HL52307, R01 HL60133] NR 25 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER PO19 1UD, WEST SUSSEX, ENGLAND BN 0-470-84480-9 J9 NOVART FDN SYMP PY 2002 VL 247 BP 129 EP 143 PG 15 WC Biology; Medicine, General & Internal SC Life Sciences & Biomedicine - Other Topics; General & Internal Medicine GA BW40V UT WOS:000181919300011 PM 12539953 ER PT J AU Le, YY Cui, YH Iribarren, P Ying, GG Wang, JM AF Le, YY Cui, YH Iribarren, P Ying, GG Wang, JM TI Manipulating chemoattractant and receptor genes SO IN VIVO LA English DT Review DE chemoattractants; chemokines; receptors; transgene; gene targeting ID PLATELET-ACTIVATING-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CC-CHEMOKINE RECEPTOR-2; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; PULMONARY GRANULOMA-FORMATION; HUMAN INTERLEUKIN-8 RECEPTOR; DENDRITIC CELL LOCALIZATION; LEUKOTRIENE B-4 RECEPTOR; N-FORMYLPEPTIDE RECEPTOR; HIGH ENDOTHELIAL VENULES AB Chemoattractants, including classical chemotactic factors and members of the chemokine superfamily, function as inducers of leukocyte trafficking and activation based on interactions with seven transmembrane (STM), G protein-coupled receptors. These molecules are expressed by many cell types either constitutively or upon stimulation. Considerable knowledge about the pathophysiological role of chemoattractants and their receptors has been accumulated during the past two decades. However; recent studies using transgenic and gene targeting technology have provided a better illustration of the importance and complexity of the involvement of chemoattractants and receptors in leukocyte trafficking, inflammation, infection, immune responses, development, angiogenesis/angiostasis, and malignant tumors. C1 NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. FU NCI NIH HHS [N0 I-CO-56000] NR 137 TC 10 Z9 10 U1 1 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JAN-FEB PY 2002 VL 16 IS 1 BP 1 EP 23 PG 23 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 541QX UT WOS:000174996200001 PM 11985303 ER PT S AU Arking, R Buck, S Hwangbo, DS Lane, M AF Arking, R Buck, S Hwangbo, DS Lane, M BE Harman, D TI Metabolic alterations and shifts in energy allocations are corequisites for the expression of extended longevity genes in Drosophila SO INCREASING HEALTHY LIFE SPAN: CONVENTIONAL MEASURES AND SLOWING THE INNATE AGING PROCESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Congress of the International-Association-of-Biomedical-Gerontology CY JUN 27-30, 2001 CL VANCOUVER, CANADA SP Int Assoc Biomed Gerontol, Now Foods, Glenn Fdn Med Res, Wild Blueberry Assoc N Amer DE extended longevity phenotypes; metabolic alterations; energy allocations; genes; aging; Drosophila; free radicals; ROS; antioxidant defense systems; somatic maintenance; fecundity; mathematical modeling ID LIFE-SPAN; OXIDATIVE DAMAGE; MELANOGASTER; SELECTION; RESTRICTION; PHENOTYPES; HYPOTHESIS; SENESCENCE; RESISTANCE; PATTERNS AB Evolutionary theories suggest that the expression of extended longevity depends on the organism's ability to shift energy from reproduction to somatic maintenance. New data led us to reexamine our older data and integrate the two into a larger picture of the genetic and metabolic alterations required if the animal is to live long. Our Ra normal-lived control strain can express any one of three different extended longevity phenotypes, only one of which involves significant and proportional increases in both mean and maximum longevity and thus a delayed onset of senescence. This phenotype is dependent on the up-regulation of the antioxidant defense system (ADS) genes and enzymes. Animals that express this phenotype typically have a pattern of altered specific activities in metabolically important enzymes, suggesting they are necessary to support the NAD(+)/NADP(+) reducing system required for the continued high ADS enzyme activities. Fecundity data suggests that the energy required for this higher level of somatic maintenance initially came from a reduced egg production. This was only transient, however, for the females significantly increased their fecundity in later generations while still maintaining their longevity. The energy required for this enhanced fecundity was probably obtained from an increased metabolic efficiency, for the mitochondria of the La long-lived strain are metabolically more efficient and have a lower leakage of reactive oxygen species (ROS) to the cytosol. Selection pressures that do not lead to these shifts in energy allocations result in extended longevity phenotypes characterized by increased early survival or increased late survival but not by a delayed onset of senescence. C1 Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Arking, R (reprint author), Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. NR 37 TC 21 Z9 22 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-360-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 959 BP 251 EP 262 PG 12 WC Geriatrics & Gerontology; Multidisciplinary Sciences SC Geriatrics & Gerontology; Science & Technology - Other Topics GA BU36U UT WOS:000175782200021 PM 11976200 ER PT S AU Nelson, JP AF Nelson, JP GP IEEE IEEE TI A better understanding of harmonic distortion in the petrochemical industry SO INDUSTRY APPLICATIONS SOCIETY 49TH ANNUAL PETROLEUM AND CHEMICAL INDUSTRY CONFERENCE SE RECORD OF CONFERENCE PAPERS - PETROLEUM AND CHEMICAL INDUSTRY CONFERENCE LA English DT Proceedings Paper CT 49th Annual Petroleum and Chemical Industry Conference CY SEP 23-25, 2002 CL NEW ORLEANS, LA SP IEEE, Ind Applicat Soc DE converter; distortion factor; exciting current; generator; harmonics; non-linear loads; magnetic circuits power factor; power quality; pitch factor; symmetrical components; total harmonic distortion (THD) and transformer AB This paper provides an in depth discussion on harmonic distortion on power systems in the petrochemical industry. The paper begins with a discussion on harmonics caused by saturable magnetic devices such as generators, transformers and motors. Production and control of harmonic voltages and currents produced in these devices will be covered. Then, a discussion on the production and control of harmonic voltages and currents produced by power electronic devices will be discussed. An example. of power system harmonics and harmonic suppression techniques will be presented. C1 NEI, Elect Power Engn, Arvada, CO USA. RP Nelson, JP (reprint author), NEI, Elect Power Engn, Arvada, CO USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0090-3507 BN 0-7803-7384-7 J9 RECORD CONF PAP PETR PY 2002 BP 237 EP 250 DI 10.1109/PCICON.2002.1045008 PG 14 WC Engineering, Chemical; Engineering, Petroleum; Engineering, Electrical & Electronic SC Engineering GA BV49N UT WOS:000179162900030 ER PT J AU Bornstein, MH DiPietro, JA Hahn, CS Painter, K Haynes, OM Costigan, KA AF Bornstein, Marc H. DiPietro, Janet A. Hahn, Chun-Shin Painter, Kathleen Haynes, O. Maurice Costigan, Kathleen A. TI Prenatal Cardiac Function and Postnatal Cognitive Development: An Exploratory Study SO INFANCY LA English DT Article AB Fetal cardiac function was measured at 24, 30, and 36 weeks gestation and quantified in terms of heart rate, variability, and episodic accelerations. Children's representational capacity was evaluated at 27 months in terms of language and play. Thirty-and 36-week-old fetuses that displayed greater heart-rate variability and more episodic accelerations, and fetuses that exhibited a more precipitous increase in heart-rate variability and acceleration over gestation achieved higher levels of language competence. Thirty-six-week-old fetuses with higher heart-rate variability and accelerations, and steeper growth trajectories over gestation, achieved higher levels of symbolic play. Cardiac patterning during gestation may reflect an underlying neural substrate that persists through early childhood: Individual variation in rate of development could be stable, or efficient cardiac function could positively influence the underlying neural substrate to enhance cognitive performance. C1 [Bornstein, Marc H.; Hahn, Chun-Shin; Painter, Kathleen; Haynes, O. Maurice] NICHHD, Bethesda, MD 20892 USA. [DiPietro, Janet A.; Costigan, Kathleen A.] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Bornstein, MH (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 66 TC 11 Z9 12 U1 4 U2 6 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1525-0008 J9 INFANCY JI Infancy PY 2002 VL 3 IS 4 BP 475 EP 494 DI 10.1207/S15327078IN0304_04 PG 20 WC Psychology, Developmental SC Psychology GA V73VK UT WOS:000204990400004 ER PT J AU Bornstein, MH AF Bornstein, MH TI Measurement variability in infant and maternal behavioral assessment SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE time-sampling; continuous coding; infant-mother interaction ID UNITED-STATES; NATURALISTIC EXCHANGES; JAPAN; MOTHER; FRANCE; RESPONSIVENESS; ARGENTINA; DURATION; SELF; CARE AB Evaluations of methodological assessments sometimes show similar, sometimes different patterns of findings reflective of different approaches to the same problem. In this study, frequencies of behaviors of infants and mothers in two cultures based on continuous coding were compared with frequencies based on time-sampling, and resulting patterns of findings were evaluated. Time-sampling and continuous coding give different estimates of absolute frequency of typical infant and maternal behaviors between individuals and between cultural groups. However, time-sampling adequately preserves the relative ranking of infant and mother behaviors among individuals and between cultural groups. If research is concerned with the relative standing of individuals and/or groups on frequency of infant or maternal behavior, then (under specified circumstances) time-sampling and continuous coding yield comparable results. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, NIH, Rockledge 1,Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM marc_h_bornstein@nih.gov NR 69 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PY 2002 VL 25 IS 4 BP 413 EP 432 AR PII S0163-6383(02)00143-1 DI 10.1016/S0163-6383(02)00143-1 PG 20 WC Psychology, Developmental SC Psychology GA 641WM UT WOS:000180770100005 ER PT J AU Arterberry, ME Bornstein, MH AF Arterberry, ME Bornstein, MH TI Variability and its sources in infant categorization SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE infant categorization; information-processing variables; point-light display ID CROSS-MODAL TRANSFER; INDIVIDUAL-DIFFERENCES; YOUNG INFANTS; VISUAL-ATTENTION; BASIC-LEVEL; HABITUATION; REPRESENTATIONS; COMPETENCE; PERCEPTION AB Variability of infants' categorization performance and potential sources of this variability were investigated. Using data from 13 categorization studies employing a habituation-of-looking paradigm with infants 3, 5, 6, and 9 months of age, a method for establishing a categorization criterion was developed and then used to classify individual infants as "categorizers" for particular tasks. Logistic regression analyses were then used to identify demographic and information-proces sing variables that predicted "categorizer" classification. Variables that increased the odds of being classified as a categorizer were gender, number of habituation trials, and duration of peak look during habituation; total looking time during habituation decreased the odds of categorizer classification. These findings are discussed in the context of individual differences in information processing. Published by Elsevier Science Inc. C1 Gettysburg Coll, Dept Psychol, Gettysburg, PA 17325 USA. NICHHD, Bethesda, MD 20892 USA. RP Arterberry, ME (reprint author), Gettysburg Coll, Dept Psychol, Gettysburg, PA 17325 USA. NR 35 TC 14 Z9 14 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PY 2002 VL 25 IS 4 BP 515 EP 528 AR PII S0163-6383(02)00148-0 DI 10.1016/S0163-6383(02)00148-0 PG 14 WC Psychology, Developmental SC Psychology GA 641WM UT WOS:000180770100010 ER PT J AU Biswas, B Adhya, S Washart, P Paul, B Trostel, AN Powell, B Carlton, R Merril, CR AF Biswas, B Adhya, S Washart, P Paul, B Trostel, AN Powell, B Carlton, R Merril, CR TI Bacteriophage therapy rescues mice bacteremic from a clinical isolate of vancomycin-resistant Enterococcus faecium SO INFECTION AND IMMUNITY LA English DT Article ID PHAGE THERAPY; ANTIBIOTICS; INFECTIONS; AGENTS AB Colonization of the gastrointestinal tract with vancomycin-resistant Enterococcus faecium (VRE) has become endemic in many hospitals and nursing homes in the United States. Such colonization predisposes the individual to VRE bacteremia and/or endocarditis, and immunocompromised patients are at particular risk for these conditions. The emergence of antibiotic-resistant bacterial strains requires the exploration of alternative antibacterial therapies, which led our group to study the ability of bacterial viruses (bacteriophages, or phages) to rescue mice with VRE bacteremia. The phage strain used in this study has lytic activity against a wide range of clinical isolates of VRE. One of these VRE strains was used to induce bacteremia in mice by intraperitoneal (i.p.) injection of 10(9) CFU. The resulting bacteremia was fatal within 48 h. A single i.p. injection of 3 x 10(8) PFU of the phage strain, administered 45 min after the bacterial challenge, was sufficient to rescue 100% of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50% of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue bacteremic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of bacteremic mice could be effected only by, phage strains able to grow in vitro on the bacterial host used to infect the animals, and when such strains are heat inactivated they lose their ability to rescue the infected mice. C1 NIMH, NIH, Bethesda, MD 20892 USA. Exponential Biotherapies Inc, Pt Washington, NY 11050 USA. RP Merril, CR (reprint author), NIMH, NIH, 9000 Rockville Pike,Bldg 10,Room 2D54, Bethesda, MD 20892 USA. NR 19 TC 217 Z9 243 U1 6 U2 58 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 2002 VL 70 IS 1 BP 204 EP 210 DI 10.1128/IAI.70.1.204-210.2002 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 504FX UT WOS:000172847600029 PM 11748184 ER PT J AU Conrads, TP Issaq, HJ Veenstra, TD AF Conrads, TP Issaq, HJ Veenstra, TD TI An accurate mass tag strategy for quantitative and high throughput proteome measurements SO INSTRUMENTATION SCIENCE & TECHNOLOGY LA English DT Article ID YEAST; ELECTROPHORESIS; IDENTIFICATION; SPECTROMETRY; TECHNOLOGY; PROTEINS; DATABASE; GENOME AB We review a global strategy aimed at extending the breadth and throughput of proteomic measurements based on utilizing polypeptide "accurate mass tags" produced by global protein enzymatic digestion. The two-stage strategy described employs conventional mass spectrometric techniques to provide initial putative identifications of peptides based on searching genome databases using the partial sequence information gleaned from tandem mass spectrometric data. The second stage of the strategy utilizes advanced mass spectrometric instrumentation to "validate" those putative identifications initially made using conventional tandem mass spectrometric data. Specifically, the high mass accuracy provided by more advanced instrumentation is utilized and ultimately correlated with the conventional tandem mass spectrometric data (along with each of the peptides' liquid chromatographic elution time) to validate the putative identifications. The strategy described provides greater confidence in the assignment of protein identifications than possible with conventional tandem mass spectrometric data alone. The result is the generation of a database of accurate mass tags whose constituent peptides provide the basis for unambiguous identification of their cognate parent proteins and provide the basis for subsequent high throughput quantitative proteome measurements without the need for repeated tandem mass spectrometry. C1 NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. RP Veenstra, TD (reprint author), NCI, Sci Applicat Int Corp Frederick Inc, POB B, Frederick, MD 21701 USA. NR 15 TC 0 Z9 0 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1073-9149 J9 INSTRUM SCI TECHNOL JI Instrum. Sci. Technol. PY 2002 VL 30 IS 2 BP 211 EP 223 DI 10.1081/CI-120003901 PG 13 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA 557TN UT WOS:000175924400009 ER PT J AU Le, YY Yang, YM Cui, YH Yazawa, H Gong, WH Qiu, CP Wang, JM AF Le, YY Yang, YM Cui, YH Yazawa, H Gong, WH Qiu, CP Wang, JM TI Receptors for chemotactic formyl peptides as pharmacological targets SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE Alzheimer's disease; chemotaxis; formyl peptide receptors; HIV-1; prion diseases ID N-FORMYLPEPTIDE RECEPTOR; METHIONYL-LEUCYL-PHENYLALANINE; C5A CHEMOATTRACTANT RECEPTORS; SIGNAL-TRANSDUCTION PATHWAYS; PRION PROTEIN-FRAGMENT; HIV-1 ENVELOPE GP41; ALZHEIMERS-DISEASE; HUMAN PHAGOCYTES; CYCLOSPORINE-H; PHOSPHOINOSITIDE 3-KINASE-GAMMA AB Leukocytes accumulate at sites of inflammation and immunological reaction in response to locally existing chemotactic mediators. N-formyl peptides, such as fMet-Leu-Phe (fMLF), are some of the first identified and most potent chemoattractants for phagocytic leukocytes. In addition to the bacterial peptide fMLF and the putative endogenously produced formylated peptides, a number of novel peptide agonists have recently been identified that selectively activate the high-affinity fMLF receptor FPR and/or its low-affinity variant FPRLI, both of which belong to the seven-transmembrane (STM), G protein-coupled receptor (GPCR) superfamily. These agonists include peptide domains derived from the envelope proteins of human immunodeficiency virus type 1 (HIV-1) and at least three amyloidogenic polypeptides, the human acute phase protein serum amyloid A, the 42 amino acid form of beta amyloid peptide and a 21 amino acid fragment of human prion. Furthermore, a cleavage fragment of neutrophil granule-derived bactericidal cathelicidin, LL-37, is also a chemotactic agonist for FPRLI. Activation of formyl peptide receptors results in increased cell migration, phagocytosis, release of proinflammatory mediators, and the signaling cascade culminates in heterologous desensitization of other STM receptors including chemokine receptors CCR5 and CXCR4, two coreceptors for HIV-1. Thus, by interacting with a variety of exogenous and host-derived agonists, formyl peptide receptors may play important roles in proinflammatory and immunological diseases and constitute a novel group of pharmacological targets. Published by Elsevier Science B.V. C1 NCI, Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, SAIC, Frederick, MD 21702 USA. RP Le, YY (reprint author), NCI, Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 111 TC 72 Z9 74 U1 0 U2 8 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 2002 VL 2 IS 1 BP 1 EP 13 DI 10.1016/S1567-5769(01)00150-3 PG 13 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 507HA UT WOS:000173019900001 PM 11789660 ER PT J AU Anderson, DE Chesney, MA AF Anderson, DE Chesney, MA TI Gender-specific association of perceived stress and inhibited breathing pattern SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE blood pressure (BP); breathing; end tidal CO(2); gender; stress ID END-TIDAL CO2; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; WOMEN; DEFENSIVENESS; RESPIRATION; POPULATION; DISORDERS; RESPONSES; HEALTH AB Stress can potentiate the development of hypertension via inhibition of renal excretory function. One potential mediating mechanism is an inhibited breathing pattern, because hypoventilation can decrease renal sodium excretion acutely via effects on pCO(2) and acid-base balance. Large individual differences in resting breathing patterns have been well-documented, with some individuals maintaining slow frequency and high pCO(2). Whether this breathing pattern is related to chronic stress has not been investigated. This study reports that high perceived stress over the past month was associated with significantly lower frequency breathing at rest, independently of age, race, or body mass index. This finding was more marked in women than in men. In addition, slow breathing frequency was independently associated with higher resting end tidal CO(2) in both men and women. This is the first known report of an association of sustained stress with an inhibited breathing pattern in humans, and points to a pathway by which chronic stress might contribute to the development of hypertension, especially in women. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Off Res Womens Hlth, Baltimore, MD USA. RP Anderson, DE (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 43 TC 6 Z9 6 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PY 2002 VL 9 IS 3 BP 216 EP 227 DI 10.1207/S15327558IJBM0903_04 PG 12 WC Psychology, Clinical SC Psychology GA 595UJ UT WOS:000178126900004 PM 12360838 ER PT J AU Kelloff, G AF Kelloff, G TI Prevention and treatment of early lesions SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 13 EP 13 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900043 ER PT J AU Thorgeirsson, SS AF Thorgeirsson, SS TI HCC carcinogensis from genes and cellular biology to HCC SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Expt Carcinogenesis Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 45 EP 45 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900145 ER PT J AU Blair, A AF Blair, A TI New understanding of cancer biology through occupational cancer research SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 58 EP 58 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900185 ER PT J AU Hurt, EM Ma, C Rosenwald, A Giltnane, JM Henrickson, SE Staudt, LM AF Hurt, EM Ma, C Rosenwald, A Giltnane, JM Henrickson, SE Staudt, LM TI Gene profiling of hematopoietic cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RI Giltnane, Jennifer/D-2584-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 59 EP 59 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900187 ER PT J AU Boyd, MR Wiltrout, RH Barrett, JC AF Boyd, MR Wiltrout, RH Barrett, JC TI Molecular targets drug discovery program, CCR, NCI SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 61 EP 62 PG 2 WC Oncology SC Oncology GA 565PP UT WOS:000176378900196 ER PT J AU Lee, COL AF Lee, COL TI Supporting potentially promising complementary and alternative medicine (CAM): the national cancer institute's (NCI) best case series (BCS) program SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 72 EP 72 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900229 ER PT J AU Yang, XD Wang, P Fredlin, P Jia, XC Oppenheim, JJ Davis, CG AF Yang, XD Wang, P Fredlin, P Jia, XC Oppenheim, JJ Davis, CG TI Therapeutic potential of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for the treatment of human cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Abgenix Inc, Preclin Biol, Fremont, CA USA. Abgenix Inc, Hybridoma, Fremont, CA USA. Natl Canc Inst, Frederick, MD USA. Abgenix Inc, Res Management, Fremont, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 86 EP 87 PG 2 WC Oncology SC Oncology GA 565PP UT WOS:000176378900278 ER PT J AU Crawford, ED Chia, D Andriole, GL Reding, D Gelman, EP Gohagan, JK Pinsky, P Hayes, RB Levin, DL Fagerstrom, RM Kramer, BS AF Crawford, ED Chia, D Andriole, GL Reding, D Gelman, EP Gohagan, JK Pinsky, P Hayes, RB Levin, DL Fagerstrom, RM Kramer, BS TI PSA testing interval, reduction in screening intervals: data from the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA USA. Washington Univ, Sch Med, St Louis, MO USA. Marshfield Clin & Med Ctr, Marshfield, WI USA. Natl Inst Hlth, Natl Canc Inst, Div Canc Prevent, Bethesda, MD USA. NCI, NIH, Div Canc Prevent, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 97 EP 97 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900309 ER PT J AU Krebs, LU Bradley, A Burhansstipanov, L Gamito, E Osborn, K AF Krebs, LU Bradley, A Burhansstipanov, L Gamito, E Osborn, K TI Developing a culturally competent clinical trials education curriculum: lessons learned SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Sch Nursing, Denver, CO USA. NCI Rocky Mtn Canc Informat Serv, Colorado Springs, CO USA. Nat Amer Canc Res, Pine, MN USA. Univ Colorado, Hlth Sci Ctr, PLCO Canc Screening, Denver, CO USA. Univ Colorado, Ctr Comprehens Canc & Control, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 103 EP 103 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900328 ER PT J AU Terry, MB Gammon, MD Schoenberg, JB Brinton, LA Arber, N Hibshoosh, H AF Terry, MB Gammon, MD Schoenberg, JB Brinton, LA Arber, N Hibshoosh, H TI Oral contraceptive use and Cyclin D1 overexpression in breast cancer among young women SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Columbia Univ, Mailman SPH, New York, NY USA. Univ N Carolina, Chapel Hill, NC USA. New Jersey DOH, Canc Epidemiol, Trenton, NJ USA. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 137 EP 137 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900432 ER PT J AU Toh, U Sayers, TJ Seki, N Shirouzu, K Yamana, H AF Toh, U Sayers, TJ Seki, N Shirouzu, K Yamana, H TI The synergy effects of proteasome inhibitor PS-341 and TRAIL on the apoptosis of human tumor cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Kurume Univ, Sch Med, Kurume, Fukuoka 830, Japan. NCI, Expt Immunol Lab, Frederick, MD USA. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 154 EP 154 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900492 ER PT J AU de Carvalho, M AF de Carvalho, M TI Results of the use of probability models for predicting BRCA1/2 carrier status SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Canc Genet Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 186 EP 186 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900595 ER PT J AU Lee, COL AF Lee, COL TI Complementary and alternative medicine (CAM) in the 21st century in the United States (US): supportive avenues in advanced oractice oncology nursing (APN) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 305 EP 305 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900978 ER PT J AU Bright, MA AF Bright, MA TI Utilization of technology to expand public access to cancer information SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Canc Informat Serv Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 310 EP 311 PG 2 WC Oncology SC Oncology GA 565PP UT WOS:000176378900995 ER PT J AU Thorsen, F Afione, S Tysnes, BB Kotin, R Lonning, E Bjerkvig, R Hoover, F AF Thorsen, F Afione, S Tysnes, BB Kotin, R Lonning, E Bjerkvig, R Hoover, F TI Adeno-associated viral vectors 2, 4 and 5 transduce glioma tissue and breast carcinoma cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Univ Bergen, Haukeland Hosp, Dept Anat & Cell Biol, Dept Radiophys, N-5021 Bergen, Norway. NIH, Lab Biochem Genet, Bethesda, MD 20892 USA. Univ Bergen, Dept Anat & Cell Biol, Bergen, Norway. Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 318 EP 318 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378901021 ER PT J AU Chen, LT Chao, Y Yao, TJ Huang, JD Chang, JY Chin, YH Chuang, TR Reed, E Whang-Peng, J Liu, TW AF Chen, LT Chao, Y Yao, TJ Huang, JD Chang, JY Chin, YH Chuang, TR Reed, E Whang-Peng, J Liu, TW TI Phase I and pharmacokinetic studies of oral thalidomide in advanced hepatocellular carcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Kaohsiung Med Univ Hosp, Dept Internal Med, Div Canc Res, Kaohsiung, Taiwan. Kaohsiung Med Univ Hosp, Dept Internal Med, Div Biostat, Kaohsiung, Taiwan. Kaohsiung Med Univ Hosp, Dept Internal Med, Div Bioinformat, Kaohsiung, Taiwan. Vet Gen Hosp, Canc Treatment Ctr, Taipei, Taiwan. Natl Hlth Res Inst, Div Canc Res, Taipei, Taiwan. Div Biotechnol & Pharmaceut Res, Taipei, Taiwan. Natl Cheng Kong Univ Hosp, Coll Med, Dept Pharmacol, Tainan, Taiwan. NCI, Div Clin Sci, Med Branch, Bethesda, MD 20892 USA. RI Chen, Li-Tzong/D-2071-2010; Chang, Jang-Yang/D-2099-2010; Liu, Tsang-Wu/D-2100-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 336 EP 337 PG 2 WC Oncology SC Oncology GA 565PP UT WOS:000176378901080 ER PT J AU Martinez, G Mishina, Y Bertram, JF AF Martinez, G Mishina, Y Bertram, JF TI BMPs and BMP receptors in mouse metanephric development: in vivo and in vitro studies SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE BMPs; noggin; metanephros; kidney; branching ID KIDNEY; MORPHOGENESIS; EXPRESSION; EMBRYOGENESIS; STEREOLOGY; GLOMERULI; DEFICIENT; APOPTOSIS; ECTODERM; DEFECTS AB BMPs have recently emerged as likely regulators of development of the permanent kidney (metanephros). Transcripts for BMPs and their receptors have been localised in the developing metanephros. In vitro, BMPs 2, 4 and 7 have direct or indirect roles in regulation of ureteric branching morphogenesis and branch formation. In vivo, renal phenotypes have been reported in BMP7 homozygous null mutant mice and BMP4 heterozygous null mutant mice. In the present study, in vivo and in vitro roles of BMPs and BMP receptors in metanephric development were further analysed. Stereology and histology were used to analyse kidneys from mice heterozygous for mutations in either BMP2, BMPR-IA or ActR-IA. Roles of BMPs 2 and 4 in mouse metanephric development in vitro were analysed by culturing whole metanephroi in the presence of BMP2, BMP4, the BMP inhibitor noggin, and BMP4 plus noggin. Ureteric branching morphogenesis and nephrogenesis were analysed. By qualitative histology, kidneys from BMP2, BMPR-IA and ActR-IA heterozygous null mutant mice were found to be the same as those from wild type mice. The kidneys of the heterozygous mice contained the normal complement of nephrons. In vitro, high concentrations of BMP4 inhibited branching of the ureteric epithelium and changed its morphology, while nephrogenesis was inhibited by 50%. A range of concentrations of BMP2 did not alter ureteric or mesenchyme morphology, or the number of glomeruli formed. Noggin did not alter metanephric development in vitro, but did block the effect of BMP4. The experiments described in this study have shown that BMP4 has distinct roles from BMP2 in metanephric development. C1 Monash Univ, Dept Anat & Cell Biol, Clayton, Vic 3800, Australia. Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC USA. RP Martinez, G (reprint author), Monash Univ, Dept Anat & Cell Biol, Clayton, Vic 3800, Australia. RI Bertram, John/I-2588-2014 OI Bertram, John/0000-0001-5863-6464 NR 29 TC 28 Z9 30 U1 0 U2 1 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 2002 VL 46 IS 4 SI SI BP 525 EP 533 PG 9 WC Developmental Biology SC Developmental Biology GA 573HY UT WOS:000176824700025 PM 12141440 ER PT J AU Seghatoleslami, MR Martinez, A Cuttitta, F Kosher, RA AF Seghatoleslami, MR Martinez, A Cuttitta, F Kosher, RA TI Distribution and possible function of an Adrenomedullin-like peptide in the developing chick limb bud SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE adrenomedullin; limb development; AER; limbless mutant chick embryos; proliferation ID APICAL ECTODERMAL RIDGE; HYPOTENSIVE PEPTIDE; GROWTH-FACTOR; EXPRESSION; CELLS; CLONING; MUTANT; MORPHOGENESIS; EMBRYOGENESIS; PRECURSOR AB Adrenomedullin (AM) is a multifunctional peptide that exhibits discrete domains of expression during mouse embryogenesis consistent with a role in regulating growth and differentiation during morphogenesis. Here we report that AM immunoreactivity is present at high levels throughout the apical ectodermal ridge (AER) of the chick limb bud as the AER is directing the outgrowth and patterning of underlying limb mesoderm. Immunostaining is particularly strong along the surfaces of the contiguous cells of the AER. AM immunoreactivity attenuates as the AER regresses and is absent from the distal apical ectoderm of stage 20 limbless mutant limb buds which fail to develop an AER. To explore the possible role of AM in AER activity, we examined the effect of exogenous AM and an AM inhibitor on the in vitro morphogenesis of limb mesoderm, cultured in the presence and absence of the AER. Although exogenous AM cannot substitute for the AER in promoting outgrowth of limb mesoderm in vitro, a specific AM antagonist, AM(22-52), impairs the outgrowth and proliferation of limb mesoderm cultured in the presence of the AER. This is consistent with the possibility that inhibition of endogenous AM activity in the AER impairs the ability of the AER to promote limb morphogenesis. Taken together, these studies suggest that an AM-like molecule may function in an autocrine fashion to regulate some aspect of AER activity. C1 Univ Connecticut, Ctr Hlth, Dept Biostruct & Funct, Farmington, CT 06030 USA. NCI, Cell & Canc Biol Dept, NIH, Rockville, MD USA. RP Kosher, RA (reprint author), Univ Connecticut, Ctr Hlth, Dept Biostruct & Funct, MC3705,263 Farmington Ave, Farmington, CT 06030 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 FU NICHD NIH HHS [HD22610] NR 29 TC 3 Z9 3 U1 0 U2 1 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 2002 VL 46 IS 7 SI SI BP 957 EP 961 PG 5 WC Developmental Biology SC Developmental Biology GA 616BG UT WOS:000179281400018 PM 12455634 ER PT J AU Gobbi, G Sangiorgi, L Lenzi, L Casadei, R Canaider, S Strippoli, P Lucarelli, E Ghedini, I Donati, D Fabbri, N Warzecha, J Yeoung, C Helman, LJ Picci, P Carinci, P AF Gobbi, G Sangiorgi, L Lenzi, L Casadei, R Canaider, S Strippoli, P Lucarelli, E Ghedini, I Donati, D Fabbri, N Warzecha, J Yeoung, C Helman, LJ Picci, P Carinci, P TI Seven BMPs and all their receptors are simultaneously expressed in osteosarcoma cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE bone morphogenetic protein; BMP receptor; activin receptor; osteosarcoma; RT-PCR ID BONE MORPHOGENETIC PROTEINS; GROWTH-FACTOR-BETA; II RECEPTOR; IMMUNOHISTOCHEMICAL DETECTION; VENTRALIZING FACTOR; DIFFERENTIATION; OSTEOBLAST; SKELETAL; TISSUE; ROLES AB Members of the bone morphogenetic protein (BMP) family and their receptors (BMPRs and activin receptors-ActRs) promote the development of bones with a fine regulation of their expression. Mutations in BMPs or BMPRs cause several diseases, as shown in knockout mice, such as skeletal defects, familial primary pulmonary hypertension and neoplasias. Osteosarcoma is the most frequent primary malignant tumor of bone. Due to their importance in bone development, BMPs, BMPRs and ActRs could also play a role in osteosarcoma growth and development. Previous data have shown that the overexpression of the BMPR-II was related to poor prognosis in malignant and metastatic bone tumors. We evaluate by reverse transcription-linked polymerase chain reaction analysis (RT-PCR) the expression pattern of BMPs, BMPRs and ActRs in five different human osteosarcoma cell lines (MG63, G292, HOS, SaOS and U2). Moreover, we performed the mutational screening of the complete BMPR-II mRNA by automated sequencing of the correspondent cDNA to evaluate the presence of point mutations in osteosarcoma cell lines. All the osteosarcoma cell lines studied simultaneously expressed the BMPs, BMPRs and ActRs investigated. No mutations were detected in the BMPR-II cDNA. Our results suggest the presence of a mechanism involving the simultaneous activation of the BMPs and their receptors in osteosarcoma cell lines. C1 Rizzoli Orthopaed Inst, Lab Oncol Res, I-40136 Bologna, Italy. Rizzoli Orthopaed Inst, Orthoped Clin, I-40136 Bologna, Italy. Univ Bologna, Genet Res Ctr, Fdn Carisbo Mol, Bologna, Italy. Univ Bologna, Inst Histol, Bologna, Italy. NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. RP Sangiorgi, L (reprint author), Rizzoli Orthopaed Inst, Lab Oncol Res, Via Barbiano 1-10, I-40136 Bologna, Italy. RI casadei, raffaella/K-1730-2015; Gobbi, Giuliana/O-8735-2015; Picci, Piero/J-5979-2016; Lucarelli, Enrico/G-3588-2015 OI Gobbi, Giuliana/0000-0003-1197-3484; Picci, Piero/0000-0002-8519-4101; Lucarelli, Enrico/0000-0002-6681-6374 NR 42 TC 39 Z9 41 U1 1 U2 4 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 2002 VL 20 IS 1 BP 143 EP 147 PG 5 WC Oncology SC Oncology GA 505ML UT WOS:000172916500020 PM 11743655 ER PT J AU Li, AG Griffin, JD AF Li, AG Griffin, JD TI Cloning and analysis of a mads-box gene expressed in Poa annua md-2 apices during floral meristem formation SO INTERNATIONAL JOURNAL OF PLANT SCIENCES LA English DT Article DE RT-PCR; cDNA library; Poa floral gene; MADS-box gene ID TRANSCRIPTION FACTORS; DNA-BINDING; ARABIDOPSIS; FAMILY; RICE; PROTEINS; GENOTYPES; PLANTS; MAIZE AB Poa annua MD-2 is a day-neutral, annual grass, which flowers 25-35 d after planting under controlled conditions. Although the physiology and anatomy of flowering is fairly well understood, the genetic regulation of flowering in P. annua has not been studied. MADS-box genes regulate reproductive development in other plants and are candidate genes for regulating flowering in P. annua. The purpose of this study was to isolate MADS-box genes expressed in P. annua MD-2 floral meristems. Degenerate primers based on the MADS-box sequences of maize and rice were used to amplify a fragment of ca. 170 bp from MD-2 genomic DNA. Plasmids containing inserts were sequenced and three of them (named PaMADS) were found to be 89%-93% identical to MADS sequences from maize. A cDNA library was constructed from 5 mg of MD-2 floral meristem tissue between the transition and the panicle/branch primordial initiation stages. PaMADS sequence was used to screen the cDNA library and one full-length MADS-box gene named PaMADS1 was isolated. PaMADS1 is 1159 bp in length and encodes a 258 amino acid protein which shares 54.4% identity with AGL6 from Arabidopsis thaliana. The MADS-box motif of PaMADS1 is identical with those of TaMADS#12 from wheat, ZAG3 from maize, and OsMADS6 from rice, and 98% identical with AGL6 and 83.0% with AGL13 from A. thaliana. The K-box of PaMADS1 has 88.1%-94.1% identity with those of ZAG3, ZAG5, TaMADS#12, and OsMADS6, but only 60.4% identity with AGL6 and 53.5% with AGL13. Northern blot analysis indicated that PaMADS1 is a floral-specific gene and is highly expressed at panicle/branch-primordia-initiation and prepollen stages. Southern hybridization indicated that there are ca. 10 copies of MADS-box genes in both P. annua and Poa pratensis. C1 NEI, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Idaho, Dept Plant Soil & Entomol Sci, Moscow, ID 83844 USA. RP Li, AG (reprint author), NEI, Natl Inst Hlth, Bldg 6,Room 313,6 Ctr Dr,MSC 2740, Bethesda, MD 20892 USA. NR 27 TC 2 Z9 2 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-5893 J9 INT J PLANT SCI JI Int. J. Plant Sci. PD JAN PY 2002 VL 163 IS 1 BP 43 EP 50 DI 10.1086/324529 PG 8 WC Plant Sciences SC Plant Sciences GA 498ZA UT WOS:000172542400003 ER PT J AU Cumberlin, RL Deye, J Coleman, CN AF Cumberlin, RL Deye, J Coleman, CN TI In regard to "Research in medical physics," IJROBP 49:891-895; 2001 - Response SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter C1 NCI, Radiat Res Program, Med Phys Sect, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Sci Program, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Cumberlin, RL (reprint author), NCI, Radiat Res Program, Med Phys Sect, NIH, Bethesda, MD 20892 USA. NR 3 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. PD JAN 1 PY 2002 VL 52 IS 1 BP 274 EP 275 DI 10.1016/S0360-3016(01)01817-X PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 508TF UT WOS:000173105100037 ER PT J AU Greig, NH Lahiri, DK Sambamurti, K AF Greig, NH Lahiri, DK Sambamurti, K TI Butyrylcholinesterase: An important new target in Alzheimer's disease therapy SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE acetylcholinesterase; Alzheimer's disease; beta-amyloid; butyrylcholinesterase; cholinesterase inhibitor; cymserine; donepezil; galantamine; rivastigmine; tacrine ID AMYLOID PRECURSOR PROTEIN; MOLECULAR-FORMS; CSF ACETYLCHOLINESTERASE; CELLULAR-DIFFERENTIATION; NONCLASSICAL ACTIONS; DRUG PHENSERINE; BETA-PEPTIDES; K VARIANT; CHOLINESTERASES; PLAQUES AB Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (BuChE) considered to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remains unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral and global functioning characteristic of AD. The two enzymes differ in substrate specificity, kinetics and activity in different brain regions. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine analogues, MF-8622) and the dual inhibitor of both AChE and BuChE, rivastigmine, indicates potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. Recent evidence suggests that both AChE and BuChE may have roles in the aetiology and progression of AD beyond regulation of synaptic ACh levels. The development of specific BuChE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Baltimore, MD 21224 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. Mayo Clin, Dept Pharmacol, Jacksonville, FL 32224 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Baltimore, MD 21224 USA. NR 64 TC 114 Z9 123 U1 2 U2 24 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2002 VL 14 SU 1 BP 77 EP 91 DI 10.1017/S1041610203008676 PG 15 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 647FH UT WOS:000181081800005 PM 12636181 ER PT J AU Baum, BJ Wellner, RB Deng, CY AF Baum, BJ Wellner, RB Deng, CY TI Gene transfer to salivary glands SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 213 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review DE salivary glands; gene transfer; gene therapy; gene therapeutics; adenovirus; biotechnology; exocrine glands ID ADENO-ASSOCIATED VIRUS; HERPES-SIMPLEX VIRUS; PAROTID ACINAR-CELLS; RECOMBINANT ADENOASSOCIATED VIRUS; RAT SUBMANDIBULAR GLANDS; HUMAN TISSUE KALLIKREIN; IN-VIVO; REP PROTEIN; REGULATED EXOCYTOSIS; VIRAL VECTORS C1 NIH, Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NR 231 TC 53 Z9 57 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2002 VL 213 BP 93 EP 146 PG 54 WC Cell Biology SC Cell Biology GA BT76E UT WOS:000173969500003 PM 11837896 ER PT J AU Parsegian, VA AF Parsegian, VA TI Protein-water interactions SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 215 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review DE Gibbs adsorption isotherm; hydration forces; intermolecular interactions; ionic channels; molecular assembly; osmotic stress; surface excess/deficit; water effect ID PROBING ALAMETHICIN CHANNELS; CUBIC INSULIN CRYSTALS; OSMOTIC-STRESS; SOLUBLE POLYMERS; HEMOGLOBIN; HYDRATION; FORCES C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Parsegian, VA (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NR 20 TC 36 Z9 40 U1 2 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2002 VL 215 BP 1 EP 31 PG 31 WC Cell Biology SC Cell Biology GA BU26E UT WOS:000175518600001 PM 11952225 ER PT J AU Oliver, B AF Oliver, B TI Genetic control of germline sexual dimorphism in Drosophila SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 219 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review DE gametogenesis; gonadogenesis; mosaics; sex chromosomes; ovarian tumor; ovo; sex determination; sex differentiation; sex-lethal ID OVARIAN TUMOR GENE; FEMALE-STERILE MUTATIONS; BAG-OF-MARBLES; MELANOGASTER MEIGEN DIPTERA; MATERNAL EFFECT PHENOTYPES; ELEMENT-INDUCED MUTATIONS; RNA-BINDING PROTEINS; MUSCA-DOMESTICA L.; HUMAN Y-CHROMOSOME; DOSAGE COMPENSATION C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Oliver, B (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 245 TC 25 Z9 25 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2002 VL 219 BP 1 EP 60 PG 68 WC Cell Biology SC Cell Biology GA BV10U UT WOS:000177839400001 PM 12211627 ER PT J AU Lopez, J Martinez, A AF Lopez, J Martinez, A TI Cell and molecular biology of the multifunctional peptide, adrenomedullin SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 221 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review DE adrenomedullin; receptors; binding protein; cardiovascular system; cancer; diabetes; knockouts; transgenic models ID GENE-RELATED-PEPTIDE; SMOOTH-MUSCLE CELLS; INCREASED PLASMA ADRENOMEDULLIN; TERMINAL 20 PEPTIDE; PROADRENOMEDULLIN N-TERMINAL-20 PEPTIDE; ACTIVITY-MODIFYING PROTEINS; RECEPTOR-LIKE RECEPTOR; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; CENTRAL-NERVOUS-SYSTEM C1 Univ Autonoma Madrid, Cell Biol Unit, Madrid 28049, Spain. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Lopez, J (reprint author), Univ Autonoma Madrid, Cell Biol Unit, Madrid 28049, Spain. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 666 TC 113 Z9 116 U1 1 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2002 VL 221 BP 1 EP 92 PG 92 WC Cell Biology SC Cell Biology GA BV69M UT WOS:000179786500001 PM 12455746 ER PT J AU Schoenberg, SO Essig, M Hallscheidt, P Sharafuddin, MJ Stolpen, AH Knopp, MV Yuh, WTC AF Schoenberg, SO Essig, M Hallscheidt, P Sharafuddin, MJ Stolpen, AH Knopp, MV Yuh, WTC TI Multiphase magnetic resonance angiography of the abdominal and pelvic arteries - Results of a bicenter multireader analysis SO INVESTIGATIVE RADIOLOGY LA English DT Article DE multiphase magnetic resonance angiography; multicenter study; interobserver variability; abdominal arteries ID ENHANCED MR-ANGIOGRAPHY; BREATH-HOLD; CONVENTIONAL ANGIOGRAPHY; RENAL-ARTERIES; STENOSIS; DISEASE; AORTA AB RATIONALE AND OBJECTIVES The objective is to assess the diagnostic accuracy and interobserver variability of multiphase 3D gadolinium-enhanced magnetic resonance angiography (3D-Gd-MRA) for assessment of abdominal and pelvic vascular disease. METHODS. In 41 patients from two different institutions multiphase 3D-Gd-MRA of the aorta and pelvis was performed using an identical scanning protocol. In a single breath-hold three to four consecutive phases were acquired. Stenoses in the renal arteries, and aorta and pelvic arteries were independently evaluated by three readers and compared with digital subtraction angiography. Interobserver variability was compared by means of a K statistic. RESULTS. Accuracy for stenosis grading consistently ranged between 80% and 90% for all three readers in all vessel segments studied. Good interobserver agreement was found with x values exceeding 0.75. Vessel segments with delayed fill-in could be reliably detected on the multiple successive MRA phases. Overall, MRA was rated slightly superior to Digital Subtraction Angiography in terms of interobserver variability, diagnostic confidence and image quality. CONCLUSIONS. Multiphase MRA is a highly robust technique With reproducible accuracy for different observers and different institutions. It can therefore be recommended for screening of atherosclerotic abdominal and pelvic disease. C1 Deutsch Krebsforschungszentrum, FSP Radiol E0103, Dept Radiol, D-69120 Heidelberg, Germany. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Radiol, Heidelberg, Germany. RP Schoenberg, SO (reprint author), Deutsch Krebsforschungszentrum, FSP Radiol E0103, Dept Radiol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. RI Hallscheidt, Peter/H-4760-2011 NR 24 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JAN PY 2002 VL 37 IS 1 BP 20 EP 28 DI 10.1097/00004424-200201000-00005 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 508XM UT WOS:000173115100004 PM 11753150 ER PT B AU Rhee, S Zhang, SJ Molingou, G Shrout, T Shung, K AF Rhee, S Zhang, SJ Molingou, G Shrout, T Shung, K BE White, G Tsurumi, T TI BSPT- and PZNT-based high frequency single element transducers for medical ultrasonic imaging SO ISAF 2002: PROCEEDINGS OF THE 13TH IEEE INTERNATIONAL SYMPOSIUM ON APPLICATIONS OF FERROELECTRICS LA English DT Proceedings Paper CT 13th IEEE International Symposium on Applications of Ferroelectrics CY MAY 28-JUN 01, 2002 CL NARA, JAPAN SP IEEE ID TEMPERATURE AB Ferroelectric single crystals with tetragonal compositions Pb(Zn1/3Nb2/3)O-3-xPbTiO(3) (PZNT) and high T-C (1-x)BiScO3-xPbTiO(3) (BSPT) were grown by Flux technique, respectively. Dielectric and piezoelectric characterization revealed high thickness coupling coefficients. (kt > 60 %) and relatively low dielectric permittivities (epsilon(S) < 300) qualifying them as candidates for high frequency (> 20 MHz) single element transducers. Modeling based on the KLM equivalent circuit was performed resulting in projected bandwidth > 60 % for BSPT and > 70 % for PZNT and therefore high sensitivity. Single element transducers were fabricated with suitable matching and backing layers. For a PZNT transducer with a 3 5 MHz center frequency, a bandwidth of similar to 80 % was realized. C1 Penn State Univ, NIH, Resource Ctr Med Ultrason Transducer Technol, University Pk, PA 16802 USA. RP Rhee, S (reprint author), Penn State Univ, NIH, Resource Ctr Med Ultrason Transducer Technol, Hallowell Bldg, University Pk, PA 16802 USA. NR 4 TC 0 Z9 0 U1 1 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-7414-2 PY 2002 BP 315 EP 318 PG 4 WC Engineering, Electrical & Electronic; Physics, Applied; Physics, Condensed Matter SC Engineering; Physics GA BW84T UT WOS:000183375500077 ER PT B AU Cannata, JM Shrout, TR Shung, KK AF Cannata, JM Shrout, TR Shung, KK BE White, G Tsurumi, T TI A 35 MHz linear ultrasonic array for medical imaging SO ISAF 2002: PROCEEDINGS OF THE 13TH IEEE INTERNATIONAL SYMPOSIUM ON APPLICATIONS OF FERROELECTRICS LA English DT Proceedings Paper CT 13th IEEE International Symposium on Applications of Ferroelectrics CY MAY 28-JUN 01, 2002 CL NARA, JAPAN SP IEEE ID TRANSDUCERS AB Ultrasound backscatter microscope (UBM) imaging systems operating above 20 MHz are capable of achieving the axial and lateral resolutions needed for applications in ophthalmology and dermatology. Unfortunately these systems rely upon mechanically scanned single element transducers and suffer from a fixed focus, low frame rate and cumbersome scanning hardware. High frequency arrays are therefore desirable for several reasons, including the ability to dynamically focus the sound beam, increase frame rates and clinical convenience. This study investigates the design tradeoffs involved in the development of a high frequency (35 MHz) 64-element linear array. This array was designed primarily for human eye and skin imaging, and features monolithic elements mechanically diced out of a fine grain high density PZT-5H ceramic. Array elements were spaced with a 50 mum pitch, interconnected via a flexible circuit and matched to the 50 0 system electronics via a 85 Omega transmission line coaxial cable. Several prototype arrays were constructed with promising results. An average center frequency of 34 MHz with a -6 dB bandwidth of at least 45% per element was achieved. The maximum combined electrical and acoustical crosstalk for nearest and next nearest elements was less than -29 dB, and the average -40 dB pulse length was 105 ns. C1 Penn State Univ, NIH, Res Ctr Med Ultrason Transducer Technol, University Pk, PA 16802 USA. RP Cannata, JM (reprint author), Penn State Univ, NIH, Res Ctr Med Ultrason Transducer Technol, University Pk, PA 16802 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-7414-2 PY 2002 BP 343 EP 346 PG 4 WC Engineering, Electrical & Electronic; Physics, Applied; Physics, Condensed Matter SC Engineering; Physics GA BW84T UT WOS:000183375500084 ER PT J AU Leshner, AI AF Leshner, AI TI Editorial: Science-based views of drug abuse and addiction SO ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES LA English DT Editorial Material ID COCAINE; BRAIN C1 NIDA, NIH, Washington, DC USA. RP Leshner, AI (reprint author), NIDA, NIH, Washington, DC USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU GEFEN PUBLISHING HOUSE LTD PI JERUSALEM PA PO BOX 36004, JERUSALEM 91360, ISRAEL SN 0333-7308 J9 ISRAEL J PSYCHIAT JI Isr. J. Psychiatr. Relat. Sci. PY 2002 VL 39 IS 2 BP 83 EP 85 PG 3 WC Psychiatry SC Psychiatry GA 613ER UT WOS:000179119600002 PM 12227231 ER PT J AU Sora, I Ide, S Funada, M Shinohara-Tanaka, K Hata, H Kobayashi, H Hall, FS Uhi, GR Ikeda, K AF Sora, I Ide, S Funada, M Shinohara-Tanaka, K Hata, H Kobayashi, H Hall, FS Uhi, GR Ikeda, K TI Different morphine actions in mu opioid receptor gene mutant mice SO JAPANESE JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 Tokyo Inst Psychiat, Dept Mol Psychiat, Tokyo 1568585, Japan. Kyoto Univ, Fac Pharmaceut Sci, Dept Mol Pharmacol, Kyoto 6068501, Japan. NIDA, Mol Neurobiol, NIH, Baltimore, MD 21224 USA. RI Ide, Soichiro/D-5472-2012; Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 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 0021-5198 J9 JPN J PHARMACOL JI Jpn. J. Pharmacol. PY 2002 VL 88 SU 1 MA P93 BP 85P EP 85P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 531ZT UT WOS:000174447700318 ER PT J AU Koshimizu, T Stojilkovic, SS Gozoh, T AF Koshimizu, T Stojilkovic, SS Gozoh, T TI Dependence of calcium influx through purinergic receptor-channels on the structure of extracellular and carboxyl-terminal domains SO JAPANESE JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 Natl Childrens Med Res Ctr, Dept Mol Cell Pharmacol, Tokyo 1548509, Japan. NICHHD, Sect Cellular Signaling, NIH, ERRB, Rockville, MD 20852 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 0021-5198 J9 JPN J PHARMACOL JI Jpn. J. Pharmacol. PY 2002 VL 88 SU 1 MA P600 BP 211P EP 211P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 531ZT UT WOS:000174447700825 ER PT J AU Andohl, T Chock, PB Chiueh, CC AF Andohl, T Chock, PB Chiueh, CC TI Thioredoxin inhibits neuronal cell death induced by serum deprivation SO JAPANESE JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 Toyama Med & Pharmaceut Univ, Dept Appl Pharmacol, Toyama 9300194, Japan. NIMH, NIH, Clin Sci Lab, Bethesda, MD 20892 USA. NHLBI, NIH, Biochem 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 0021-5198 J9 JPN J PHARMACOL JI Jpn. J. Pharmacol. PY 2002 VL 88 SU 1 MA P742 BP 247P EP 247P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 531ZT UT WOS:000174447700968 ER PT J AU VandeWoude, S Hageman, CA O'Brien, SJ Hoover, EA AF VandeWoude, S Hageman, CA O'Brien, SJ Hoover, EA TI Nonpathogenic lion and puma lentiviruses impart resistance to superinfection by virulent feline immunodeficiency virus SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE animal models; pathogenesis; retrovirus; feline; interforence; superinfection ID EXPERIMENTAL VACCINE PROTECTION; CHEMOKINE RECEPTOR CXCR4; LONG-TERM PROTECTION; ENV GENE; ENVELOPE GLYCOPROTEIN; MUCOSAL TRANSMISSION; PHYLOGENETIC ASPECTS; NONDOMESTIC FELIDS; ANTIVIRAL ACTIVITY; SUBUNIT VACCINES AB Lion lentivirus (LLV) and puma lentivirus (PLV) exist as highly divergent virus clades among populations of indigenously infected nondomestic felidae. The feline immunodeficiency virus (FIV) is highly divergent from LLV and PLV and is pathogenic for domestic cats. When domestic cats are infected with LLV or PLV, they have immunologic ally and clinically silent persistent infections. We examined whether LLV or PLV infection might impart resistance to FIV superinfection in vitro by infecting domestic cat lymphoid cells with PLV and assessing resistance of these cells to FIV. We found that infection with FIV was highly restricted by prior established PLV infection. To examine whether this resistance applied in vivo, domestic cats were asymptomatically infected with either LLV or PLV and then challenged with pathogenic FIV. Although all cats became infected with FIV, prior LLV or PLV exposure blunted CD4(+) cell depiction and suppressed plasma and peripheral blood mononuclear cell FIV loads relative to FIV-challenged controls not infected with LLV or PLV, despite the lack of prechallenge neutralizing antibody activity against FIV. Thus, as compared with naive controls, cats previously infected with LLV or PLV were able to more effectively control FIV infection and resist its immunologic effects, despite the substantial genetic divergence between these lentiviruses-raising the possibility that superinfection may impart resistance to lentivirus infection by heightening innate immune mechanisms. C1 Colorado State Univ, Dept Pathol, Ft Collins, CO 80523 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP VandeWoude, S (reprint author), Colorado State Univ, Dept Pathol, Ft Collins, CO 80523 USA. FU NIAID NIH HHS [1 R29AI41871] NR 85 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD JAN 1 PY 2002 VL 29 IS 1 BP 1 EP 10 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 512HG UT WOS:000173318500001 PM 11782584 ER PT J AU Taylor, SL Hefle, SL Bindslev-Jensen, C Bock, SA Burks, AW Christie, L Hill, DJ Host, A Hourihane, JO Lack, G Metcalfe, DD Moneret-Vautrin, DA Vadas, PA Rance, F Skrypec, DJ Trautman, TA Yman, IM Zeiger, RS AF Taylor, SL Hefle, SL Bindslev-Jensen, C Bock, SA Burks, AW Christie, L Hill, DJ Host, A Hourihane, JO Lack, G Metcalfe, DD Moneret-Vautrin, DA Vadas, PA Rance, F Skrypec, DJ Trautman, TA Yman, IM Zeiger, RS TI Factors affecting the determination of threshold doses for allergenic foods: How much is too much? SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergy; food; challenge; threshold dose ID DOUBLE-BLIND; MILK; ANAPHYLAXIS; CHALLENGE; INGESTION; PROTEIN; CHILD AB Background: Ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies. The threshold dose for provocation of such reactions is often considered to be zero. However, because of various practical limitations in food production and processing, foods, may occasionally contain trace residues of the offending food. Are these very low, residual quantities hazardous to allergic consumers? How much of the offending food is too much? Very little quantitative information exists to allow any risk assessments to be conducted by the food industry. Objective: We sought to determine whether the quality and quantity of existing clinical data on threshold doses for commonly allergenic foods were sufficient to allow consensus to be reached on establishment of threshold doses for specific foods. Methods: In September 1999, 12 clinical allergists and other interested parties were invited to participate in a roundtable conference to share existing data on threshold doses and to discuss clinical approaches that would allow the acquisition of that information. Results: Considerable data were identified in clinical files relating to the threshold doses for peanut, cows' milk, and egg; limited data were available for other foods, such as fish and mustard. Conclusions: Because these data were often obtained by means of different protocols, the estimation of a threshold dose was very difficult. Development of a standardized protocol for clinical experiments to allow determination of the threshold dose is needed. C1 Univ Nebraska, Food Allergy Res & Resource Program, Lincoln, NE 68583 USA. Odense Univ Hosp, Dept Dermatol, DK-5000 Odense, Denmark. Boulder Valley Asthma & Allergy Clin, Boulder, CO USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Melbourne Childrens Hosp, Dept Allergy, N Melbourne, Australia. Odense Univ Hosp, Dept Pediat, DK-5000 Odense, Denmark. Southampton Gen Hosp, Allergy & Inflammat Sci Div, Southampton SO9 4XY, Hants, England. St Marys Hosp, Dept Pediat Allergy & Immunol, London, England. NIAID, Allerg Dis Lab, NIH, Bethesda, MD 20892 USA. Hop Cent, Dept Clin Immunol & Allergol, Nancy, France. Univ Toronto, St Michaels Hosp, Div Clin Immunol & Allergy, Toronto, ON M5B 1W8, Canada. Hop Enfants, Dept Allergol, Toulouse, France. Kraft Gen Foods Inc, Glenview, IL 60025 USA. Gen Mills Inc, Minneapolis, MN USA. Natl Food Adm, Res & Dev, Uppsala, Sweden. Kaiser Permanente Med Ctr, San Diego, CA USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. RP Taylor, SL (reprint author), Univ Nebraska, Food Allergy Res & Resource Program, 143 Food Ind Bldg, Lincoln, NE 68583 USA. RI Bindslev-Jensen, Carsten/H-1877-2011; Osborne, Nicholas/N-4915-2015 OI Bindslev-Jensen, Carsten/0000-0002-8940-038X; Osborne, Nicholas/0000-0002-6700-2284 NR 19 TC 225 Z9 232 U1 0 U2 15 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 2002 VL 109 IS 1 BP 24 EP 30 DI 10.1067/mai.2002.120564 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 519RM UT WOS:000173739300004 PM 11799361 ER PT J AU Brockow, K Akin, C Huber, M Scott, LM Schwartz, LB Metcalfe, DD AF Brockow, K Akin, C Huber, M Scott, LM Schwartz, LB Metcalfe, DD TI Levels of mast-cell growth factors in plasma and in suction skin blister fluid in adults with mastocytosis: Correlation with dermal mast-cell numbers and mast-cell tryptase SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE mastocytosis; atopic dermatitis; mast cells; tryptase; stem-cell factor; IL-6 ID BLOOD MONONUCLEAR-CELLS; C-KIT; CUTANEOUS MASTOCYTOSIS; RHEUMATOID-ARTHRITIS; ATOPIC-DERMATITIS; INTERLEUKIN-6; IDENTIFICATION; HYPERPLASIA; URTICARIA; PROTEINS AB Background: Mast-cell accumulation has been observed in the skin and other organs of patients with systemic indolent mastocytosis (SM). The basis for this pathologic increase is not fully understood. Objective: We sought to determine levels of mast-cell growth factors in the skin and plasma of patients with SM, patients with atopic dermatitis (AD), and healthy individuals and to correlate these levels to dermal mast-cell numbers and levels of mast-cell tryptase. Methods: Skin suction blister fluid and plasma levels of stem-cell factor, IL-3, IL-4, IL-6, vascular endothelial growth factor, and total mast-cell tryptase were analyzed by means of ELISA. The number of mast cells wag determined in a biopsy section taken from adjacent skin. Results. Mast-cell numbers in the dermis were higher in patients with SM compared with numbers in patients with AD (P <.001) or in healthy control subjects (P <.0001) and. correlated with tryptase levels in both skin blister fluid (P <.0001) and plasma (P <.0001). Stem-cell factor and vascular endothelial growth factor levels in the skin blister fluid and plasma of patients with SM were not significantly different from those in patients with AD or healthy control subjects. IL-3 and IL-4 levels were below the limit of detection. IL-6 levels were significantly increased in the plasma of patients with SM compared with in plasma of patients with AD (P <.002) and healthy control subjects (P <.0001) and correlated with plasma tryptase levels (P <.05) and dermal mast-cell numbers (P <.02). Conclusion: Because elevated levels of IL-6 could contribute to the fever, fatigue, and osteoporosis observed in patients with SM and because IL-6 is antiapoptotic for mast cells, IL-6 could potentiate the biologic consequences of this disease. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Div Rheumatol Allergy & Immunol, Richmond, VA USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI20487] NR 33 TC 34 Z9 34 U1 1 U2 2 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 2002 VL 109 IS 1 BP 82 EP 88 DI 10.1067/mai.2001.120524 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 519RM UT WOS:000173739300013 PM 11799370 ER PT J AU Cohen, SG AF Cohen, SG TI Francis M. Rackemann, MD - Pioneers and milestones SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Biographical-Item C1 NIAID, Bethesda, MD 20892 USA. Natl Lib Med, NIH, Bethesda, MD USA. RP Cohen, SG (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 BP 179 EP 180 DI 10.1067/mai.2002.120947 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 519RM UT WOS:000173739300032 PM 11799389 ER PT J AU Akin, C Kirshenbaum, AS Metcalfe, DD AF Akin, C Kirshenbaum, AS Metcalfe, DD TI Serum tryptase levels combined with flow cytometric analysis of bone marrow aspirate mast cells differentiate systemic mastocytosis from idiopathic syndromes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 539 BP S182 EP S182 DI 10.1016/S0091-6749(02)81675-X PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800538 ER PT J AU Alston, M Valerio, C Dixon, A Morrow, K Slater, J AF Alston, M Valerio, C Dixon, A Morrow, K Slater, J TI Lyophilization does not affect the activity or secondary structure of cat allergen vaccines SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2002 VL 109 IS 1 SU S MA 387 BP S134 EP S134 DI 10.1016/S0091-6749(02)81523-8 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800386 ER PT J AU Arbes, SJ Muilenberg, M Burge, H Friedman, W Zeldin, D AF Arbes, SJ Muilenberg, M Burge, H Friedman, W Zeldin, D TI The relationship between bed dust mite allergen and asthma in the First National Survey of Lead and Allergens in Housing SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. US Dept Housing & Urban Dev, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 1113 BP S357 EP S357 DI 10.1016/S0091-6749(02)82247-3 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744801109 ER PT J AU Blumenthal, MN Langfeild, CD Bleecker, ER Beaty, TH Ober, C Banks-Schlegel, SP Meyer, DA Rich, SS AF Blumenthal, MN Langfeild, CD Bleecker, ER Beaty, TH Ober, C Banks-Schlegel, SP Meyer, DA Rich, SS CA Collaborat Study Genet Ashma TI Genome screen for susceptibility loci contributing to mite sensitivity in US populations SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Chicago, Chicago, IL 60637 USA. Johns Hopkins Univ, Bethesda, MD USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 515 BP S174 EP S174 DI 10.1016/S0091-6749(02)81651-7 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800514 ER PT J AU Bocek, P Paul, WE AF Bocek, P Paul, WE TI IFN gamma has a potential to enhance IL4 production by CD4+T cells in vitro SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 979 BP S318 EP S318 DI 10.1016/S0091-6749(02)82114-5 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800976 ER PT J AU Borchers, MT Justice, JP Ansay, T Mancino, V McGarry, MP Crosby, JR Simon, MI Lee, NA Lee, JJ AF Borchers, MT Justice, JP Ansay, T Mancino, V McGarry, MP Crosby, JR Simon, MI Lee, NA Lee, JJ TI Gq signaling is required for allergen-induced pulmonary eosinophilia in the mouse SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Mayo Clin, Scottsdale, AZ USA. NIAID, Scottsdale, AZ USA. CALTECH, Pasadena, CA 91125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 17 BP S25 EP S25 DI 10.1016/S0091-6749(02)81154-X PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800018 ER PT J AU Brockow, K Akin, C Huber, MM Metcalfe, DD AF Brockow, K Akin, C Huber, MM Metcalfe, DD TI Plasma IL-6 correlates with disease category and with hematological parameters in patients with mastocytosis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 465 BP S158 EP S158 DI 10.1016/S0091-6749(02)81601-3 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800464 ER PT J AU Chen, LC Lin, J Myers, A Zhang, Z Huang, SK AF Chen, LC Lin, J Myers, A Zhang, Z Huang, SK TI Altered pulmonary allergic responses regulatory in mice deficient for clara cell secretory protein, CC10 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 496 BP S168 EP S168 DI 10.1016/S0091-6749(02)81632-3 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800495 ER PT J AU Hauk, PJ Strickland, I Vottero, A Chrousos, GP Kisich, KO Leung, DYM AF Hauk, PJ Strickland, I Vottero, A Chrousos, GP Kisich, KO Leung, DYM TI Increased glucocorticoid receptor beta expression leads to reduced nuclear translocation of glucocorticoid receptor alpha and impaired steroid responsiveness SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Natl Jewish Med & Res Ctr, Denver, CO USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 795 BP S261 EP S261 DI 10.1016/S0091-6749(02)81930-3 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800792 ER PT J AU Hsieh, LS Moharram, R Akasawa, A Slater, J Martin, BM AF Hsieh, LS Moharram, R Akasawa, A Slater, J Martin, BM TI Banana allergen detection and identification using SELDI technology SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. Natl Childrens Med Res Ctr, Tokyo 154, Japan. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2002 VL 109 IS 1 SU S MA 938 BP S305 EP S305 DI 10.1016/S0091-6749(02)82073-5 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800935 ER PT J AU Hunter, LBC Plainetr, V Foster, B Huber, MM Metcalfe, DD Prussin, C AF Hunter, LBC Plainetr, V Foster, B Huber, MM Metcalfe, DD Prussin, C TI Direct determination of allergen specific T cell cytokine responses during immunotherapy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 1091 BP S350 EP S350 DI 10.1016/S0091-6749(02)82225-4 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744801087 ER PT J AU Jirapongsananuruk, O Kuhns, DB Anderson-Cohen, M Brown, MR Niemela, JE Malech, HL Fleisher, TA AF Jirapongsananuruk, O Kuhns, DB Anderson-Cohen, M Brown, MR Niemela, JE Malech, HL Fleisher, TA TI Detection of X-linked chronic granulomatous disease variants using dihydrorhodamine assay SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 846 BP S277 EP S277 DI 10.1016/S0091-6749(02)81981-9 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800843 ER PT J AU Klion, AD Law, M Noel, P Nutman, TB AF Klion, AD Law, M Noel, P Nutman, TB TI Serum tryptase levels as a possible marker of myeloproliferative disease in a subset of patients with hypereosinophilic syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 692 BP S229 EP S229 DI 10.1016/S0091-6749(02)81828-0 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800690 ER PT J AU Luccioli, S Justice, JP Isenberg-Feig, H Prussin, C Keane-Myers, A AF Luccioli, S Justice, JP Isenberg-Feig, H Prussin, C Keane-Myers, A TI Passive sensitization via IgE leads to immediate AHR and IL-4 production without subsequent Th2-mediated inflammation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Rockville, MD USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 907 BP S296 EP S296 DI 10.1016/S0091-6749(02)82042-5 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800904 ER PT J AU Montgomery, JR Martin, BL Olivos-Glander, I Turner, M Darnell, D Holland, SM AF Montgomery, JR Martin, BL Olivos-Glander, I Turner, M Darnell, D Holland, SM TI Recurrent cutaneous infections, hyperkeratosis, ichthyosis and deafness and a newly identified Connexin 26 gene mutation A40V SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA. GeneDx, Rockville, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 195 BP S78 EP S78 DI 10.1016/S0091-6749(02)81331-8 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800194 ER PT J AU Pawliczak, R Nanavaty, UB Huang, XL Lawrence, MG Copland, JR Eckert, EK Shelhamer, JH AF Pawliczak, R Nanavaty, UB Huang, XL Lawrence, MG Copland, JR Eckert, EK Shelhamer, JH TI Hydrogen peroxide induces arachidonic acid release through increasing cytosolic phospholipase A(2) (cPLA(2)) phosphorylation utilizing an epidermal growth factor receptor (EGFR) mediated pathway in human airway epithelial cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2002 VL 109 IS 1 SU S MA 162 BP S68 EP S68 DI 10.1016/S0091-6749(02)81298-2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800161 ER PT J AU Peebles, S Hashimoto, K Morrow, JD Collins, R Jarzecka, K Furlong, J Mitchell, D Graham, BS Sheller, JR AF Peebles, S Hashimoto, K Morrow, JD Collins, R Jarzecka, K Furlong, J Mitchell, D Graham, BS Sheller, JR TI Augmentation of allergic inflammation by cyclooxygenase inhibition is not dependent on IL-4 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Vanderbilt Univ, Nashville, TN USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 464 BP S158 EP S158 DI 10.1016/S0091-6749(02)81600-1 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800463 ER PT J AU Rabin, RL Alston, M Farber, JM AF Rabin, RL Alston, M Farber, JM TI Dual roles for the chemokine receptor CXCR3 in adaptive immunity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 1109 BP S356 EP S356 DI 10.1016/S0091-6749(02)82243-6 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744801105 ER PT J AU Shen, HHJ Justice, JP Borchers, MT Crosby, JR Hines, E O'Neill, K Ansay, T Lee, NA Lee, JJ AF Shen, HHJ Justice, JP Borchers, MT Crosby, JR Hines, E O'Neill, K Ansay, T Lee, NA Lee, JJ TI A direct causative relationship exists between eosinophils and the development of allergen-mediated pulmonary pathologies, including airway mucus production and the development of AHR SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Mayo Clin, Scottsdale, AZ USA. NIAID, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 682 BP S226 EP S226 DI 10.1016/S0091-6749(02)81818-8 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800680 ER PT J AU Tkaczyk, C Okayama, Y Metcalfe, DD Gilfillan, AM AF Tkaczyk, C Okayama, Y Metcalfe, DD Gilfillan, AM TI Comparison of FceRI and Fc gamma RI-dependent signaling pathways in human mast cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 1124 BP S361 EP S361 DI 10.1016/S0091-6749(02)82259-X PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744801120 ER PT J AU Webb, DC Mahalingam, S Noben-Trauth, N Donaldson, DD Foster, PS AF Webb, DC Mahalingam, S Noben-Trauth, N Donaldson, DD Foster, PS TI Interleukin (IL)-13 regulates pathophysiological features of allergic airways disease independently of the IL-4 receptor alpha chain SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Australian Natl Univ, Canberra, ACT, Australia. NIH, Rockville, MD USA. Genet Inst Inc, Cambridge, MA 02140 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 109 IS 1 SU S MA 1135 BP S364 EP S364 DI 10.1016/S0091-6749(02)82270-9 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744801131 ER PT J AU Perry, T Greig, NH AF Perry, TracyAnn Greig, Nigel H. TI The glucagon-like peptides: a new genre in therapeutic targets for intervention in Alzheimer's disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article AB Glucagon-like peptide-1 (7-36)-amide (GLP-1) is an insulinotropic hormone, secreted from the enteroendocrine L cells of the intestinal tract in response to nutrient ingestion. It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose in patients with type 2 diabetes mellitus. GLP-1 receptors, which are coupled to the cyclic AMP second messenger pathway, are expressed throughout the brains of rodents and humans. The chemoarchitecture of receptor distribution in the brain correlates well with a central role for GLP-1 in the regulation of food intake and response to aversive stress. We have recently reported that GLP-1 and several longer acting analogs that bind at the GLP-1 receptor, possess neurotrophic properties, and offer protection against glutamate-induced apoptosis and oxidative injury in cultured neuronal cells. Furthermore, GLP-1 can modify processing of the amyloid beta- protein precursor in cell culture and dose-dependently reduces amyloid beta-peptide levels in the brain in vivo. As such, this review discusses the known role of GLP-1 within the central nervous system, and considers the potential of GLP-1 and analogs as novel therapeutic targets for intervention in Alzheimer's disease (AD) and potentially other central and peripheral neurodegenerative conditions. C1 [Perry, TracyAnn; Greig, Nigel H.] NIA, Neurosci Lab, Sect Drug Design & Dev, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Perry, T (reprint author), NIA, Neurosci Lab, Sect Drug Design & Dev, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM perryt@grc.nia.nih.gov NR 79 TC 53 Z9 57 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2002 VL 4 IS 6 BP 487 EP 496 PG 10 WC Neurosciences SC Neurosciences & Neurology GA V24ZH UT WOS:000208447800005 PM 12515900 ER PT J AU Bar-Haim, Y Perez-Edgar, K Fox, NA Beck, JM West, GM Bhangoo, RK Myers, FS Leibenluft, E AF Bar-Haim, Y Perez-Edgar, K Fox, NA Beck, JM West, GM Bhangoo, RK Myers, FS Leibenluft, E TI The emergence of childhood bipolar disorder: a prospective study from 4 months to 7 years of age SO JOURNAL OF APPLIED DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE longitudinal research; bipolar mood disorder; ADHD; psychophysiology; temperament; childhood ID DEFICIT HYPERACTIVITY DISORDER; BEHAVIORAL-INHIBITION; YOUNG-CHILDREN; TEMPERAMENT; COMORBIDITY; INFANT; ADHD; ASYMMETRY; CONDUCT; EMOTION AB The present study reviews the development from 4 to 84 months of age of a boy diagnosed with bipolar mood disorder (BPD) and attention deficit hyperactivity disorder (ADHD) at 7 years of age. Extensive data were collected in four central domains: psychophysiology (EEG and ECG), child temperament, mother-child interactions, and peer interactions. The target child's development was traced across time and compared with a cohort of 81 normally developing children. The target child displayed an unusual psychophysiological pattern from early infancy. His highly active central nervous system was coupled with an under-aroused autonomic nervous system. By preschool, his social interactions were marked by inappropriate affect and behavioral disinhibition, along with impulsivity and aggression. Possible links between the child's psychophysiological pattern and his behavior are discussed. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Maryland, Child Dev Lab, College Pk, MD 20742 USA. Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. Reg Int Children & Adolescents, Rockville, MD USA. NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Fox, NA (reprint author), Univ Maryland, Child Dev Lab, 3304 Bejamin Bldg, College Pk, MD 20742 USA. RI Perez-Edgar, Koraly/B-8463-2008; OI Perez-Edgar, Koraly/0000-0003-4051-9563 NR 43 TC 1 Z9 1 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0193-3973 J9 J APPL DEV PSYCHOL JI J. Appl. Dev. Psychol. PY 2002 VL 23 IS 4 BP 431 EP 450 AR PII S0193-3973(02)00127-2 DI 10.1016/S0193-3973(02)00127-2 PG 20 WC Psychology, Developmental SC Psychology GA 638QL UT WOS:000180581700004 ER PT J AU Joe, GO Kovacs, JA Miller, KD Kelly, GG Koziol, DE Jones, EC Mican, JM Masur, H Gerber, L AF Joe, GO Kovacs, JA Miller, KD Kelly, GG Koziol, DE Jones, EC Mican, JM Masur, H Gerber, L TI Diagnosis of avascular necrosis of the hip in asymptomatic HIV-infected patients: Clinical correlation of physical examination with magnetic resonance imaging SO JOURNAL OF BACK AND MUSCULOSKELETAL REHABILITATION LA English DT Article ID FEMORAL-HEAD; OSTEONECROSIS AB Objective: To determine if physical examination can identify avascular necrosis of the hip (AVN) in asymptomatic HIV-infected patients. Design: Prospective, blinded population study Results: Ten of the 176 patients were positive for AVN by MRI. Four subjects had unilateral disease and six had bilateral disease. Five hips (1.4%) in four patients were indeterminate. We evaluated physical examination maneuvers both singly and in combination. Tests done singly generally provided a higher degree of specificity (67-92%) but sensitivities were lower (0-50%) with all p-values greater than or equal to0.08. Positive predictive values based on physical exam, were <17% and negative predictive values were >90% for any single test. Combining all tests gave a high sensitivity (88%) and negative predictive value (98%), but low Specificity (34%) and positive predictive value (6%) with p = 0.10. Only two of 16 hips with positive MRI findings showed no abnormalities when all tests were combined Conclusions: This study establishes the limited usefulness of a detailed physical examination of the hip early in the course of AVN. Patients who test negative on physical exam are unlikely to have AVN positive by MRI. Positive findings on physical examination of the hip may help identify patients who need further evaluation by MRI based on overall clinical suspicion. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Joe, GO (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Rehabil Med, Bldg 10,Room 6S235,MSC-1604, Bethesda, MD 20892 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8127 J9 J BACK MUSCULOSKELET JI J. Back Musculoskelet. Rehabil. PY 2002 VL 16 IS 4 BP 135 EP 139 PG 5 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 733BA UT WOS:000185979000002 PM 22387437 ER PT J AU Ge, RR Tao, LH Kramer, PM Cunningham, ML Pereira, MA AF Ge, RR Tao, LH Kramer, PM Cunningham, ML Pereira, MA TI Effect of peroxisome proliferators on the methylation and protein level of the c-myc protooncogene in B6C3F1 mice liver SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE 2,4-dichlorophenoxyacetic acid; dibutyl phthalate; DNA hypomethylation; gemfibrozil; c-myc; partial hepatectomy; peroxisome Proliferators; Wy-14,643 ID ACTIVATED RECEPTOR-ALPHA; DNA METHYLATION; MOUSE-LIVER; TRICHLOROACETIC-ACID; DICHLOROACETIC ACID; SPECIES-DIFFERENCES; EXPRESSION; CARCINOGENESIS; TRICHLOROETHYLENE; MECHANISMS AB Peroxisome proliferators in general are nongenotoxic mouse liver carcinogens for which DNA hypomethylation and altered gene expression are proposed mechanisms. Therefore, the peroxisome proliferators 2,4-dichlorophenoxyacetic acid (2,4-D), dibutyl phthalate (DBP), gemfibrozil, and Wy-14,643 were evaluated for the ability to alter the methylation and expression of the c-myc protooncogene. Male B6C3F1 mice were administered for 6 days in their diet Wy-14,643 (5-500 ppm), 2,4-D (1,680 ppm), DBP (20,000 ppm), or gemfibrozil (8,000 ppm). All four peroxisome proliferators caused hypomethylation of the c-myc gene in the liver. Wy-14,643 appeared to be the most efficacious with a threshold between 10 and 50 ppm. The level of the c-myc protein was increased by Wy-14,643, but not the other peroxisome proliferators. When female B6C3F1 mice received a two-thirds partially hepatectomy and 16 h later were administered 50 mg/kg Wy-14,643 by gavage, hypomethylation of the gene occurred 24 h later. Hypomethylation was not found in mice that received Wy-14,643 following a sham operation. Hypomethylation of the c-myc gene within 24 h of administering Wy-14,643 after a partial hepatectomy but not after a sham operation supports the hypothesis that the peroxisome proliferators prevent methylation of hemimethylated sites formed by DNA replication. (C) 2002 Wiley Periodicals, Inc. C1 Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Pereira, MA (reprint author), Med Coll Ohio, Dept Pathol, POB 10008, Toledo, OH 43614 USA. FU NIEHS NIH HHS [R03 ES09772] NR 42 TC 12 Z9 13 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2002 VL 16 IS 1 BP 41 EP 47 DI 10.1002/jbt.10019 PG 7 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 526DY UT WOS:000174115100006 PM 11857776 ER PT J AU Miller, DS AF Miller, DS TI Xenobiotic export pumps, endothelin signaling, and tubular nephrotoxicants - A case of molecular hijacking SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Review DE p-glycoprotein; Mrp2; renal transport ID RENAL PROXIMAL TUBULE; NITRIC-OXIDE; MULTIDRUG-RESISTANCE; RECEPTOR SUBTYPES; CYCLOSPORINE-A; P-GLYCOPROTEIN; ORGANIC ANION; RAT-KIDNEY; SECRETION; CELLS AB This article is a review on recent studies in intact renal proximal tubules that link tubular nephrotoxicants with endothelin (ET) regulation of xenobiotic export pump function. The data show that transport on p-glycoprotein and Mrp2 decreases rapidly when ET signals through an ETB receptor, NO synthase (NOS), and protein kinase C (PKC). Surprisingly, nephrotoxicants, such as radiocontrast agents, aminoglycoside antibiotics, and heavy metal salts, "hijack" this signaling pathway, causing ET release from the tubules, hormone binding to its receptor, activation of NOS and PKC, and reduced xenobiotic transport. These findings suggest a new common mechanism by which nephrotoxicants may act to disrupt renal tubular function. (C) 2002 Wiley Periodicals, Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 43 TC 32 Z9 33 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2002 VL 16 IS 3 BP 121 EP 127 DI 10.1002/jbt.10030 PG 7 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 567HU UT WOS:000176480000002 PM 12112711 ER PT J AU Sahlin, M Cho, KB Potsch, S Lytton, SD Huque, Y Gunther, MR Sjoberg, BM Mason, RP Graslund, A AF Sahlin, M Cho, KB Potsch, S Lytton, SD Huque, Y Gunther, MR Sjoberg, BM Mason, RP Graslund, A TI Peroxyl adduct radicals formed in the iron/oxygen reconstitution reaction of mutant ribonucleotide reductase R2 proteins from Escherichia coli SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Article DE peroxyl radical; tryptophan radical; tyrosyl radical; ribonucleotide reductase; radical transfer pathways ID CYTOCHROME-C PEROXIDASE; ELECTRON-PARAMAGNETIC-RESONANCE; TRYPTOPHAN RADICALS; ENDOR SPECTROSCOPY; OXYGEN ACTIVATION; HYDROGEN-PEROXIDE; CRYSTAL-STRUCTURE; COMPOUND-ES; SUBUNIT; EXCHANGE AB Catalytically important free radicals in enzymes are generally formed at highly specific sites, but the specificity is often lost in point mutants where crucial residues have been changed. Among the transient free radicals earlier found in the Y122F mutant of protein R2 in Escherichia coli ribonucleotide reductase after reconstitution with Fe2+ and O-2, two were identified as tryptophan radicals. A third radical has an axially symmetric EPR spectrum, and is shown here using O-17 exchange and simulations of EPR spectra to be a peroxyl adduct radical. Reconstitution of other mutants of protein R2 (i.e. Y122F/W48Y and Y122F/W107Y) implicates W48 as the origin of the peroxyl adduct. The results indicate that peroxyl radicals form on primary transient radicals on surface residues such as W48. which is accessible to oxygen. However, the specificity of the reaction is not absolute since the single mutant W48Y also gives rise to a peroxyl adduct radical. We used density functional calculations to investigate residue-specific effects on hyperfine coupling constants using models of tryptophan, tyrosine, glycine and cysteine. The results indicate that any peroxyl adduct radical attached to the first three amino acid alpha -carbons gives similar O-17 hyperfine coupling constants. Structural arguments and experimental results favor W48 as the major site of peroxyl adducts in the mutant Y122F. Available molecular oxygen can be considered as a spin trap for surface-located protein free radicals. C1 Univ Stockholm, Dept Mol Biol & Funct Genom, S-10691 Stockholm, Sweden. Univ Stockholm, Dept Biochem & Biophys, S-10691 Stockholm, Sweden. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Frankfurt, Dept Biochem 2, D-60590 Frankfurt, Germany. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sahlin, M (reprint author), Univ Stockholm, Dept Mol Biol & Funct Genom, S-10691 Stockholm, Sweden. RI Cho, Kyung-Bin/B-6006-2011; OI Cho, Kyung-Bin/0000-0001-6586-983X; Lytton, Simon/0000-0001-5617-4139 NR 42 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-8257 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD JAN PY 2002 VL 7 IS 1-2 BP 74 EP 82 DI 10.1007/s007750100267 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 507JP UT WOS:000173024100009 PM 11862543 ER PT J AU Gandjbakhche, AH Patterson, M Follen, M AF Gandjbakhche, AH Patterson, M Follen, M TI Optical imaging and spectroscopy: From benchtop to bedside SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada. McMaster Univ, Hamilton, ON L8S 4L8, Canada. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Gandjbakhche, AH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2002 VL 7 IS 1 BP 6 EP 6 DI 10.1117/1.1450595 PG 1 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 522NX UT WOS:000173904400001 ER PT J AU Gannot, I Gannot, G Garashi, A Gandjbakhche, A Buchner, A Keisari, Y AF Gannot, I Gannot, G Garashi, A Gandjbakhche, A Buchner, A Keisari, Y TI Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE lasers; fluorescence; tissues AB Fourteen BALB/c mice were divided into two groups. One group served as the control and the second group was injected with a squamous cell carcinoma cell line to the tongue. After tumor development (1-4 weeks), mice were injected with a FITC conjugated CD3 marker to their tongues. immediately after the marker injection, the clearance of the marker was measured using a laser spectroscopy system. The markers were excited by an argon laser at 488 nm and the fluorescence signal was measured as a function of time. A biopsy was taken from every mouse after the procedure and the excised tissue was histologically evaluated. Analysis of clearance times revealed a second order exponential decay for both groups with a slower pace of signal clearance for the sick mice. (C) 2002 Society of Photo-Optical Instrumentation Engineers. C1 Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sch Dent Med, Dept Oral Pathol, IL-69978 Tel Aviv, Israel. NICHHD, Unit Biomed Stochast Phys, Lab Integrat & Med BIophys, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel. RP Gannot, I (reprint author), Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. NR 10 TC 6 Z9 6 U1 0 U2 0 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2002 VL 7 IS 1 BP 14 EP 19 DI 10.1117/1.142913 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 522NX UT WOS:000173904400003 PM 11818007 ER PT J AU Chernomordik, V Hattery, DW Grosenick, D Wabnitz, H Rinneberg, H Moesta, KT Schlag, PM Gandjbakhche, A AF Chernomordik, V Hattery, DW Grosenick, D Wabnitz, H Rinneberg, H Moesta, KT Schlag, PM Gandjbakhche, A TI Quantification of optical properties of a breast tumor using random walk theory SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE photon migration; time-resolved imaging; light propagation in tissue; differential absorption; optical mammography ID RESOLVED TRANSILLUMINATION EXPERIMENTS; PHOTON MIGRATION; IN-VIVO; TURBID MEDIA; PATH-LENGTH; TISSUE; TOMOGRAPHY; ABNORMALITIES; SCATTERING; RECONSTRUCTION AB For the first time we use a random walk methodology based on time-dependent contrast functions to quantify the optical properties of breast tumors (invasive ductal carcinoma) of two patients. Previously this theoretical approach was successfully applied for analysis of embedded objects in several phantoms. Data analysis was performed on distributions of times of flight for photons transmitted through the breast which were recorded in vivo using a time-domain scanning mammograph at 670 and 785 nm. The size of the tumors, their optical properties, and those of the surrounding tissue were reconstructed at both wavelengths. The tumors showed increased absorption and scattering. From the absorption coefficients at both wavelengths blood oxygen saturation was estimated for the tumors and the surrounding tissue. (C) 2002 Society of Photo-Optical Instrumentation Engineers. C1 Natl Inst Child Hlth & Dev, NIH, Bethesda, MD 20892 USA. Phys Tech Bundesanstalt, D-10587 Berlin, Germany. Humboldt Univ, Robert Roessle Hosp, Charite, D-13125 Berlin, Germany. RP Chernomordik, V (reprint author), Natl Inst Child Hlth & Dev, NIH, Bethesda, MD 20892 USA. NR 46 TC 40 Z9 41 U1 0 U2 3 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2002 VL 7 IS 1 BP 80 EP 87 DI 10.1117/1.1427049 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 522NX UT WOS:000173904400011 PM 11818015 ER PT J AU Grigoryan, AM Dougherty, ER Kononen, J Bubendorf, L Hostetter, G Kallioniemi, O AF Grigoryan, AM Dougherty, ER Kononen, J Bubendorf, L Hostetter, G Kallioniemi, O TI Morphological spot counting from stacked images for automated analysis of gene copy numbers by fluorescence in situ hybridization SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE FISH; fluorescence microscopy; image analysis; mathematical morphology ID INTERPHASE CELL-NUCLEI; INSITU HYBRIDIZATION; FISH AB Fluorescence in situ hybridization (FISH) is a molecular diagnostic technique in which a fluorescent labeled probe hybridizes to a target nucleotide sequence of deoxyribose nucleic acid. Upon excitation, each chromosome containing the target sequence produces a fluorescent signal (spot). Because fluorescent spot counting is tedious and often subjective, automated digital algorithms to count spots are desirable. New technology provides a stack of images on multiple focal planes throughout a tissue sample. Multiple-focal-plane imaging helps overcome the biases and imprecision inherent in single-focal-plane methods. This paper proposes an algorithm for global spot counting in stacked three-dimensional slice FISH images without the necessity of nuclei segmentation. It is designed to work in complex backgrounds, when there are agglomerated nuclei, and in the presence of illumination gradients. It is based on the morphological top-hat transform, which locates intensity spikes on irregular backgrounds. After finding signals in the slice images, the algorithm groups these together 140 form three-dimensional spots. Filters are employed to separate legitimate spots from fluorescent noise. The algorithm is set in a comprehensive toolbox that provides visualization and analytic facilities. It includes simulation software that allows examination of algorithm performance for various image and algorithm parameter settings, including signal size, signal density, and the number of slices. (C) 2002 Society of Photo-Optical Instrumentation Engineers. C1 Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. Univ Texas, Coll Engn, San Antonio, TX 78285 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Dougherty, ER (reprint author), Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. RI Kallioniemi, Olli/H-5111-2011; Bubendorfl, Lukas/H-5880-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 15 TC 13 Z9 13 U1 0 U2 3 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2002 VL 7 IS 1 BP 109 EP 122 DI 10.1117/1.1428292 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 522NX UT WOS:000173904400015 PM 11818019 ER PT J AU Zhang, P Nicholson, DE Bujnicki, JM Su, XZ Brendle, JJ Ferdig, M Kyle, DE Milhous, WK Chiang, PK AF Zhang, P Nicholson, DE Bujnicki, JM Su, XZ Brendle, JJ Ferdig, M Kyle, DE Milhous, WK Chiang, PK TI Angiogenesis inhibitors specific for methionine aminopeptidase 2 as drugs for malaria and leishmaniasis SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE angiogenesis; malaria; leishmaniasis; methionine; aminopeptidase; fumagillin; TNP-470 ID ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; FUMAGILLIN; AGM-1470; TNP-470; GROWTH; PROFILES; ANALOGS; METAP-2; MODEL AB Methionine aminopeptidase 2 (MetAP2) is responsible for the hydrolysis of the initiator methionine molecule from the majority of newly synthesized proteins. We have cloned the MetAP2 gene from the malaria parasite Plasmodium falciparum (PfMetAP2; GenBank accession number AF348320). The cloned PfMetAP2 has no intron, consists of 1,544 bp and encodes a protein of 354 amino acids with a molecular mass of 40,537 D and an overall base composition of 72.54% A + T. PfMetAP2 has 40% sequence identity with human MetAP2 and 45% identity with yeast MetAP2, and is located in chromosome 14 of P. falciparum. The three-dimensional structure of Pf MetAP2 has been modeled based on the crystal structure of human MetAP2, and several amino acid side chains protruding into the binding pocket that differ between the plasmodial and human enzyme have been identified. The specific MetAP2 inhibitors, fumagillin and TNP-470, potently blocked in vitro growth of P. falciparum and Leishmania donavani, with IC50 values similar to the prototype drugs. Furthermore, in the case of P. falciparum, the chloroquine-resistant strains are equally susceptible to these two compounds. Copyright (C) 2002 National Science Council, ROC and S. Karger AG, Basel. C1 Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. NIAID, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Int Inst Mol & Cell Biol, Warsaw, Poland. RP Chiang, PK (reprint author), Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA. RI Ferdig, Michael/C-6627-2016; OI Su, Xinzhuan/0000-0003-3246-3248 NR 27 TC 53 Z9 57 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD JAN-FEB PY 2002 VL 9 IS 1 BP 34 EP 40 DI 10.1007/BF02256576 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 515MX UT WOS:000173500600005 PM 11810023 ER PT J AU Shaheduzzaman, S Krishnan, V Petrovic, A Bittner, M Meltzer, P Trent, J Venkatesan, S Zeichner, S AF Shaheduzzaman, S Krishnan, V Petrovic, A Bittner, M Meltzer, P Trent, J Venkatesan, S Zeichner, S TI Effects of HIV-1 Nef on cellular gene expression profiles SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review DE HIV; Nef; microarray; viral pathogenesis ID HUMAN-IMMUNODEFICIENCY-VIRUS; TISSUE GROWTH-FACTOR; ENVELOPE GLYCOPROTEIN GP160; VASCULAR ENDOTHELIAL-CELLS; CLATHRIN-COATED VESICLES; ACTIN-CAPPING PROTEIN; DNA TOPOISOMERASE-I; HAMSTER OVARY CELLS; RNA-POLYMERASE-II; C-YES GENE AB The early human immunodeficiency virus (HIV) accessory protein Nef makes an important contribution to virulence, but the mechanisms by which Nef influences pathogenesis remain unclear. Many well-studied effects of Nef, like CD4 and class I MHC downregulation, occur posttranslationally. However, Nef has the potential to affect gene expression by interfering with cell signaling pathways and by virtue of structural features such as the Pro-X-X-Pro motif, which may interact with src homology region-3 domains of src-like kinases. We used a cDNA microarray screening strategy to identify cellular genes whose steady state transcriptional levels may be affected by Nef. We generated HeLa cell lines expressing wild-type or mutant HIV-1 nef protein sequences. Using cDNA microarray technology, we compared the patterns of cellular gene expression in the various cell lines to the pattern in non-Nef-expressing HeLa cells. By matching the patterns of cellular gene expression in HeLa cell lines expressing various Nefs with that of parental HeLa cells, we identified several cellular genes whose expression was modulated differentially by Nef and its mutants. We confirmed the differential expression of selected genes by RNA filter blotting. Genes expressed at higher levels included proteases, transcription factors, protein kinases, nuclear import/export proteins, adaptor molecules and cyclins, some of which have previously been implicated as being important for HIV replication and pathogenesis. The results indicate that Nef expression can alter the expression of cellular genes and suggest that this alteration in cellular gene expression may serve to optimize the cell to support the subsequent stages of viral replication. Copyright (C) 2002 National Science Council, ROC and S. Karger AG, Basel. C1 NCI, HAMB, NIH, Bethesda, MD 20892 USA. NIAAA, Mol Microbiol Lab, NIH, Bethesda, MD USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. RP Zeichner, S (reprint author), NCI, HAMB, NIH, 10S255,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. NR 110 TC 24 Z9 24 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD JAN-FEB PY 2002 VL 9 IS 1 BP 82 EP 96 DI 10.1159/000048202 PG 15 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 515MX UT WOS:000173500600010 PM 11810028 ER PT J AU Saksena, R Zhang, J Kovac, P AF Saksena, R Zhang, J Kovac, P TI Synthesis of 2-(trimethylsilyl)ethyl alpha-D-mannopyranosides revisited SO JOURNAL OF CARBOHYDRATE CHEMISTRY LA English DT Article DE 2-(trimethylsilyl)ethyl glycosides; glycosylation; NIS/AgOTf; anomerization ID O-POLYSACCHARIDE; SEROTYPE INABA; GLYCOSIDES; TRANSFORMATION; CHLORIDES; TERMINUS; PROTEINS; LINKING AB Glycosylation of 2-(trimethylsilyl)ethanol with various ethyl 1-thioglycosides, which were activated with N-iodosuccinimide and silver triflate, was studied. The starting thioglycosides, some prepared for the first time, were obtained conventionally from the corresponding alpha-1-acetates. When beta-1-acetates were more readily available, these were converted to the alpha-anomers by anomerization, prior to the glycosylation. Using ethyl 1-thioglycosides as glycosyl donors, especially those bearing a pivaloyl or a nonparticipating group at O-2, the corresponding 2-(trimethylsilyl)ethyl alpha-D-mannopyranosides were obtained in excellent yields. C1 NIDDK, LMC, NIH, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, LMC, NIH, Bethesda, MD 20892 USA. NR 21 TC 5 Z9 5 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0732-8303 J9 J CARBOHYD CHEM JI J. Carbohydr. Chem. PY 2002 VL 21 IS 6 BP 453 EP 470 DI 10.1081/CAR-120016846 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 629NN UT WOS:000180055900001 ER PT J AU Guttman, MA Lederman, RJ Sorger, JM McVeigh, ER AF Guttman, MA Lederman, RJ Sorger, JM McVeigh, ER TI Real-time volume rendered MRI for interventional guidance SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE real-time; volume; 3D; interventional; catheterization; MRI, magnetic resonance imaging ID MAGNETIZATION PREPARATION; ANGIOGRAPHY; VISUALIZATION; ACQUISITION; CATHETERS AB Volume renderings from magnetic resonance imaging data can be created and displayed in real-time with user interactivity. This can provide continuous 3D feedback to assist in guiding an interventional procedure. A system is presented which can produce real-time volume renderings from 2D multi-slice or 3D MR pulse sequences. Imaging frame rates up to 30 per second have been demonstrated with a latency of approximately one-third of a second, depending on the image matrix size. Several interactive capabilities have been implemented to enhance visualization such as cut planes, individual channel scaling and color highlighting, view sharing, saturation preparation, complex subtraction, gating control, and choice of alpha blending or MIP rendering. The system is described and some interventional application examples are shown. To view movies of some of the examples, enter the following address into a web browser: http://nhlbi.nih.gov/labs/papers/lce/guttman/ rtvolmri/index/htm. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Guttman, MA (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. OI lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [Z01 HL005062-05, Z01 HL004608-08] NR 26 TC 32 Z9 32 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2002 VL 4 IS 4 BP 431 EP U1 DI 10.1081/JCMR-120016382 PG 13 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 634HC UT WOS:000180333100002 PM 12549231 ER PT J AU Al-Hasani, H Kunamneni, RK Dawson, K Hinck, CS Muller-Wieland, D Cushman, SW AF Al-Hasani, H Kunamneni, RK Dawson, K Hinck, CS Muller-Wieland, D Cushman, SW TI Roles of the N- and C-termini of GLUT4 in endocytosis SO JOURNAL OF CELL SCIENCE LA English DT Article DE adaptin; adipose cell; glucose transporter ID GLUCOSE-TRANSPORTER GLUT4; RAT ADIPOSE-CELLS; REGULATED MEMBRANE AMINOPEPTIDASE; SUBCELLULAR TRAFFICKING KINETICS; 3T3-L1 ADIPOCYTES; INTERNALIZATION MOTIF; SORTING SIGNALS; INSULIN; TRANSLOCATION; VESICLES AB In insulin target cells, the predominantly expressed glucose transporter isoform GLUT4 recycles between distinct intracellular compartments and the plasma membrane. To characterize putative targeting signals within GLUT4 in a physiologically relevant cell type, we have analyzed the trafficking of hemagglutinin (HA)-epitope-tagged GLUT4 mutants in transiently transfected primary rat adipose cells. Mutation of the C-terminal dileucine motif (LL489/90) did not affect the cell-surface expression of RA-GLUT4. However, mutation of the N-terminal phenylalanine-based targeting sequence (F5) resulted in substantial increases, whereas deletion of 37 or 28 of the 44 C-terminal residues led to substantial decreases in cell-surface HA-GLUT4 in both the basal and insulin-stimulated states. Studies with wortmannin and coexpression of a dominant-negative dynamin GTPase mutant indicate that these effects appear to be primarily due to decreases and increases, respectively, in the rate of endocytosis. Yeast two-hybrid analyses revealed that the N-terminal phenylalanine-based targeting signal in GLUT4 constitutes a binding site for medium chain adaptins mu1,mu2, and mu3A, implicating a role of this motif in the targeting of GLUT4 to clathrin-coated vesicles. C1 Univ Cologne, Inst Biochem, Ctr Mol Med, D-50674 Cologne, Germany. NIDDKD, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Al-Hasani, H (reprint author), Univ Cologne, Inst Biochem, Ctr Mol Med, Otto Fischer Str 12-14, D-50674 Cologne, Germany. NR 31 TC 53 Z9 53 U1 0 U2 0 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 2002 VL 115 IS 1 BP 131 EP 140 PG 10 WC Cell Biology SC Cell Biology GA 515GC UT WOS:000173486200016 PM 11801731 ER PT J AU Gasparian, AV Yao, YJ Kowalczyk, D Lyakh, LA Karseladze, A Slaga, TJ Budunova, IV AF Gasparian, AV Yao, YJ Kowalczyk, D Lyakh, LA Karseladze, A Slaga, TJ Budunova, IV TI The role of IKK in constitutive activation of NF-kappa B transcription factor in prostate carcinoma cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE NF-kappa B; I kappa B alpha phosphorylation; IKK; prostate cancer ID GROWTH-FACTOR ACTIVATION; BREAST-CANCER CELLS; KINASE COMPLEX; ANDROGEN RECEPTOR; STERNBERG CELLS; CYCLIN D1; TNF-ALPHA; IN-VIVO; EXPRESSION; PROTEINS AB Rel/NF-kappaB transcription factors are implicated in the control of cell proliferation, apoptosis and transformation. The key to NF-kappaB regulation is the inhibitory IkappaB proteins. During response to diverse stimuli, IkappaBs are rapidly phosphorylated by IkappaB kinases (IKKs), ubiquitinated and undergo degradation. We have investigated the expression and function of NF-kappaB, IkappaB inhibitors and IKKs in normal prostate epithelial cells and prostate carcinoma (PC) cell lines LNCaP, MDA PCa 2b, DU145, PC3, and JCA1. We found that NF-kappaB was constitutively activated in human androgen-independent PC cell lines DU145, PC3, JCA1 as well as androgen-independent CL2 cells derived from LNCaP. In spite of a strong difference in constitutive kappaB binding, Western blot analysis did not reveal any significant variance in the expression of p50, p65, IkappaBs, IKKalpha, and IKKbeta between primary prostate cells, androgen-dependent and androgen-independent PC cells. However, we found that in androgen-independent PC cells IkappaBalpha was heavily phosphorylated and displayed a faster turnover. Using an in vitro kinase assay we demonstrated constitutive activation of IKK in androgen-independent PC cell lines. Blockage of NF-kappaB activity in PC cells by dominant-negative IkappaBalpha resulted in increased constitutive and TNF-alpha-induced apoptosis. Our data suggest that increased IKK activation leads to the constitutive activation of NF-kappaB 6 survival signaling' pathway in androgen-independent PC cells. This may be important for the support of their androgen-independent status and growth advantage. C1 AMC Canc Res Ctr, Denver, CO 80214 USA. NCI, Regulat Cell Growth Lab, Ctr Canc Res, Frederick, MD 21702 USA. NN Blokhin Canc Res Ctr, Moscow 115478, Russia. RP Budunova, IV (reprint author), AMC Canc Res Ctr, Denver, CO 80214 USA. NR 49 TC 198 Z9 206 U1 3 U2 6 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 2002 VL 115 IS 1 BP 141 EP 151 PG 11 WC Cell Biology SC Cell Biology GA 515GC UT WOS:000173486200017 PM 11801732 ER PT J AU Geiman, TM Robertson, KD AF Geiman, TM Robertson, KD TI Chromatin remodeling, histone modifications, and DNA methylation - How does it all fit together? SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE epigenetics; DNA methylation; histone methylation; chromatin remodeling; gene expression ID MAMMALIAN DEVELOPMENT; CYTOSINE-5 METHYLTRANSFERASES; FAMILY MEMBER; SNF2 FAMILY; LYSINE 9; DNMT3B; H3; LSH; PROLIFERATION; LYMPHOCYTES AB DNA methylation is important in the control of gene transcription and chromatin structure. The complexities of this process are just beginning to be elucidated in relationship to other epigenetic mechanisms. Exciting new research in the areas of histone methylation and chromatin remodeling make it clear just how important the connections between these various mechanisms and DNA methylation are for the control of chromosome structure and gene expression. Emerging evidence suggests that chromatin remodeling enzymes and histone methylation are essential for proper DNA methylation patterns. Other histone modifications, such as acetylation and phosphorylation, in turn, affect histone methylation and histone methylation also appears to be highly reliant on chromatin remodeling enzymes. This review will summarize what is likely only the beginning of a flood of new information that will ultimately link all epigenetic modifications of the mammalian genome. A model will also be put forth to account for how chromatin modifications lead to genomic DNA methylation patterns. C1 NCI, Epigenet Gene Regulat & Canc Sect, NIH, Bethesda, MD 20892 USA. RP Robertson, KD (reprint author), NCI, Epigenet Gene Regulat & Canc Sect, NIH, 41 Lib Dr,Bldg 41,Rm C302, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA84535-01] NR 37 TC 165 Z9 181 U1 2 U2 20 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 87 IS 2 BP 117 EP 125 DI 10.1002/jcb.10286 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 601MX UT WOS:000178451300001 PM 12244565 ER PT J AU DeLise, AM Tuan, RS AF DeLise, AM Tuan, RS TI Alterations in the spatiotemporal expression pattern and function of N-cadherin inhibit cellular condensation and chondrogenesis of limb mesenchymal cells in vitro SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE chondrogenesis; N-cadherin; cell adhesion; condensation; cartilage; limb development; retroviral gene transduction; cell-cell interaction ID DEVELOPING CHICK LIMB; GAP JUNCTIONAL COMMUNICATION; MEMBRANE-PROXIMAL REGION; CYTOPLASMIC DOMAIN; SKELETAL DEVELOPMENT; IN-VITRO; CARTILAGE DIFFERENTIATION; EXTRACELLULAR DOMAIN; PROTEIN INTERACTIONS; COLORIMETRIC ASSAY AB Cartilage formation in the embryonic limb is presaged by a cellular condensation phase that is mediated by both cell-cell and cell-matrix interactions. N-Cadherin, a Ca2+-dependent cell-cell adhesion molecule, is expressed at higher levels in the condensing mesenchyme, followed by down-regulation upon chondrogenic differentiation, strongly suggesting a functional role in the cellular condensation process. To further examine the role of N-cadherin, we have generated expression constructs of wild type and two deletion mutants (extracellular and intracellular) of N-cadherin in the avian replication-competent, RCAS retrovirus, and transfected primary chick limb mesenchymal cell cultures with these constructs. The effects of altered, sustained expression of N-cadherin and its mutant forms on cellular condensation, on the basis of peanut agglutinin (DNA) staining, and chondrogenesis, based on expression of chondrocyte phenotypic markers, were characterized. Cellular condensation was relatively unchanged in cultures overexpressing wild type N-cadherin, compared to controls on all days in culture. However, expression of either of the deletion mutant forms of N-cadherin resulted in decreased condensation, with the extracellular deletion mutant demonstrating the most severe inhibition, suggesting a requirement for N-cadherin mediated cell-cell adhesion and signaling in cellular condensation. Subsequent chondrogenic differentiation was also affected in all cultures overexpressing the N-cadherin constructs, on the basis of metabolic sulfate incorporation, the presence of the cartilage matrix proteins collagen type 11 and cartilage proteoglycan link protein, and alcian blue staining of the matrix. The characteristics of the Cultures suggest that the N-cadherin mutants disrupt proper cellular condensation and subsequent chondrogenesis, while the cultures overexpressing wild type N-cadherin appear to condense normally, but are unable to proceed toward differentiation possibly due to the prolonged maintenance of increased cell-cell adhesiveness. Thus, spatiotemporally regulated N-cadherin expression and function, at the level of both homotypic binding and linkage to the cytoskeleton, is required for chondrogenesis of limb mesenchymal cells. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, 50 S Dr,Bldg 50,Room 1503, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR42887, AR45181]; NIDCR NIH HHS [DE16864]; NIEHS NIH HHS [ES07005, ES07282, T32ES07282] NR 87 TC 65 Z9 66 U1 0 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 87 IS 3 BP 342 EP 359 DI 10.1002/jcb.10308 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 607ZA UT WOS:000178819600010 PM 12397616 ER PT J AU Barnes, GL Della Torre, T Sommer, B Young, MF Gerstenfeld, LC AF Barnes, GL Della Torre, T Sommer, B Young, MF Gerstenfeld, LC TI Transcriptional regulation restricting bone sialoprotein gene expression to both hypertrophic chondrocytes and osteoblasts SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE bone sialoprotein; osteoblast; chondrocyte; Dlx5 ID HOMEODOMAIN PROTEINS; PROMOTER; BINDING; DIFFERENTIATION; IDENTIFICATION; OSTEOPONTIN; MATRIX; MICE; DLX5; MSX2 AB This study identifies a cis-acting element that confers tissue-restricted expression to the bone sialoprotein (BSP) gene. Using both gain of function and loss-of function studies, we demonstrate that this element acts as a tissue specific enhancer of BSP expression in osteoblasts and hypertrophic chondrocytes but does not function in non-hypertrophic chondrocytes or fibroblasts. Furthermore, our data demonstrate that binding of this element occurs in correlation with active BSP expression. While DIx5 has been implicated as the tissue-specific regulator of BSP expression through direct DNA binding at an element with homology to the one under study here, our results demonstrate that DIx5 does not act as a positive regulator of BSP expression. Finally, mutational analyses of this element demonstrate that while there is homology to putative homeodomain binding elements, this site is unlikely to bind homeodomain factors including DIx5. Thus, these studies identify an important cis-acting element in the BSP promoter that acts as a tissue-specific enhancer of BSP expression in both osteoblasts and hypertrophic chondrocytes. As such this is the first demonstration of a common regulatory mechanism utilized by both chondrocytes and osteoblasts for the tissue-restricted expression of the BSP gene. C1 Boston Univ, Med Ctr, Dept Orthopaed Surg, Boston, MA 02118 USA. Boston Univ, Med Ctr, Orthopaed Res Lab, Boston, MA 02118 USA. NIDR, Cranio & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Barnes, GL (reprint author), Boston Univ, Med Ctr, Dept Orthopaed Surg, 715 Albany St,R-205, Boston, MA 02118 USA. OI /0000-0002-0477-1211 FU NIAMS NIH HHS [AR-47045]; NICHD NIH HHS [HD-22400] NR 21 TC 8 Z9 8 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 87 IS 4 BP 458 EP 469 DI 10.1002/jcb.10351 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 608VP UT WOS:000178868200010 PM 12397605 ER PT J AU Otsuki, T Young, DB Sasaki, DT Pando, MP Li, JW Manning, A Hoekstra, M Hoatlin, ME Mercurio, F Liu, JM AF Otsuki, T Young, DB Sasaki, DT Pando, MP Li, JW Manning, A Hoekstra, M Hoatlin, ME Mercurio, F Liu, JM TI Fanconi anemia protein complex is a novel target of the IKK signalsome SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE fanconi anemia; FANCA; IKK signalsome; NF-kappa B ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; LIVER DEGENERATION; MICE LACKING; KINASE IKK; ACTIVATION; GENE; BETA; COMPLEMENTATION; PHOSPHORYLATION AB Fanconi anemia (FA), a genetic disorder predisposing to aplastic anemia and cancer, is characterized by hypersensitivity to DNA-damaging agents and oxidative stress. Five of the cloned FA proteins (FANCA, FANCC, FANCE, FANCF, FANCG) appear to be involved in a common functional pathway that is required for the monoubiquitination of a sixth gene product, FANCD2. Here, we report that FANCA associates with the IkappaB kinase (IKK) signalsome via interaction with IKK2. Components of the FANCA complex undergo rapid, stimulus-dependent changes in phosphorylation, which are blocked by kinase-inactive IKK2 (IKK2 K > M). When exposed to mitomycin C (MMC), cells expressing IKK2 K > M develop a cell cycle abnormality characteristic of FA. Thus, FANCA may function to recruit IKK2, thus providing the cell a means of rapidly responding to stress. (C) 2002 Wiley-Liss, Inc. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Celgene Corp, Signal Res Div, San Diego, CA 92121 USA. Salk Inst Biol Studies, La Jolla, CA 92037 USA. Oregon Hlth Sci Univ, Div Mol Med, Portland, OR 97201 USA. RP Liu, JM (reprint author), NHLBI, Hematol Branch, Bldg 10,Rm 7C103, Bethesda, MD 20892 USA. NR 33 TC 19 Z9 20 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 86 IS 4 BP 613 EP 623 DI 10.1002/jcb.10270 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 581JZ UT WOS:000177289900001 PM 12210728 ER PT J AU Wilson, MA Chrysogelos, SA AF Wilson, MA Chrysogelos, SA TI Identification and characterization of a negative regulatory element within the epidermal growth factor receptor gene first intron in hormone-dependent breast cancer cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE gene expression; transcriptional repression; EGFR overexpression; estrogen-receptor positive; estrogen regulated ID A-CHAIN GENE; ESTROGEN-RECEPTOR; TRANSCRIPTIONAL ACTIVATION; GEL-ELECTROPHORESIS; MOLECULAR-CLONING; ENHANCER ELEMENT; ERBB2 EXPRESSION; FACTOR-BINDING; EGFR GENE; SEQUENCES AB The epidermal growth factor receptor (EGFR) exhibits an inverse correlation with estrogen receptor (ER) expression in the majority of breast cancers, predicting a poor response to endocrine therapy and poor survival rate. Inappropriate overexpression of EGFR in breast cancer is associated with a more aggressive phenotype. Transcriptional regulation is the major regulatory mechanism controlling EGFR overexpression in breast cancer cells. We have identified a region within the first intron of the EGFR gene that mediates transcriptional repression of EGFR gene expression in ER +/low EGFR expressing but not in ER-/high EGFR expressing breast cancer cells. Utilizing transient transfections of homologous and heterologous promoter-reporter constructs, we localized optimal repressive activity to a 96 bp intron domain. The 96 bp fragment displayed differential DNA-protein complex formation with nuclear extracts from ER + vs. ER- breast cancer cells. Moreover, factors interacting with this intron negative regulatory element appear to be estrogen-regulated. Consequently, our results suggest that we have identified a potential mechanism by which maintenance of low levels of EGFR expression and subsequent EGFR upregulation may be attributed to the loss of transcriptional repression of EGFR gene expression in hormone-dependent breast cancer cells. C1 Georgetown Univ, Dept Biochem & Mol Biol, Lombardi Canc Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Oncol, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Wilson, MA (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5002,37 Convent Dr,MCS 4264, Bethesda, MD 20892 USA. OI Wilson, Melissa/0000-0002-5391-7838 FU NCI NIH HHS [CA55677, 2P50-CA58185, 2P30-CA51008] NR 51 TC 26 Z9 29 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 85 IS 3 BP 601 EP 614 DI 10.1002/jcb.10168 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547QD UT WOS:000175342500016 PM 11968000 ER PT J AU Khan, SA Lopez-Chua, CA Zhang, J Fisher, LW Sorensen, ES Denhardt, DT AF Khan, SA Lopez-Chua, CA Zhang, J Fisher, LW Sorensen, ES Denhardt, DT TI Soluble osteopontin inhibits apoptosis of adherent endothelial cells deprived of growth factors SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE BCl-X-L; programmed cell death; DNA fragmentation; integrin-mediated cell death ID NF-KAPPA-B; BONE SIALOPROTEIN; FACTOR WITHDRAWAL; DEFICIENT MICE; SURVIVAL; GENE; BCL-X(L); PROTEIN; RESORPTION; ACTIVATION AB Osteopontin (OPN) is primarily an extracellular glycosylated phosphoprotein capable of stimulating cell migration and cell attachment, predominantly to mineralized surfaces. Found in moderate levels in plasma, it acts as a cytokine able to modify gene expression via integrins and certain CD44 isoforms. In this work we show that soluble OPN inhibits apoptosis of adherent human umbilical vein endothelial cells incubated in medium lacking critical growth factors and cytokines. In a dose-dependent manner OPN reduced the formation of apoptotic bodies and suppressed DNA fragmentation. OPN also caused an increase in Bcl-X-L mRNA levels, suppressed the apparent dispersion of Bcl-X-L throughout the cytoplasm, and slightly enhanced IKB-alpha protein degradation. These data suggest that a function of OPN in homeostatic processes is to facilitate the survival of stressed endothelial cells, possibly by occupying unligated integrins and suppressing integrin-mediated death. C1 Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Univ Aarhus, Prot Chem Lab, DK-8000 Aarhus C, Denmark. RP Denhardt, DT (reprint author), Nelson Labs, 604 Allison Rd, Piscataway, NJ 08854 USA. FU NIAMS NIH HHS [AR44434]; NIEHS NIH HHS [ES06897] NR 48 TC 92 Z9 97 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 85 IS 4 BP 728 EP 736 DI 10.1002/jcb.10170 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 548RX UT WOS:000175404400008 PM 11968013 ER PT J AU Seghatoleslami, MR Tuan, RS AF Seghatoleslami, MR Tuan, RS TI Cell density dependent regulation of AP-1 activity is important for chondrogenic differentiation of C3H10T1/2 mesenchymal cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE AP-1; chondrogenesis; C3H10T1/2 mesenchymal cells; micromass cultures; transcriptional regulation; MAP kinase; bone morphogenetic protein-2 ID LIMB CARTILAGE DIFFERENTIATION; ACTIVATED PROTEIN-KINASE; C-FOS PROTOONCOGENE; IN-VITRO; GLUCOCORTICOID RECEPTOR; MICROMASS CULTURES; RETINOIC ACID; N-CADHERIN; FIBRONECTIN; EXPRESSION AB The multipotential C3H10T1/2 mesenchymal cells undergo chondrogenic differentiation only when seeded as high-density micromass cultures, particularly upon treatment with bone morphogenetic protein-2 (BMP-2). The molecular mechanism(s) responsible for the cell density-dependent onset of cartilage-specific gene expression is presently unknown. Interestingly, a number of recent studies have indicated that activating protein-1 (AP-1), a well known downstream target of the mitogenic activated protein kinase (MAP kinase) signaling pathway, is a target of chondrogenic/osteogenic growth factors such as BMP-2, and plays a role in osteogenic gene regulation as well as in chondrogenic differentiation. The aim of this study is to examine the density-dependent alteration in the level and binding activity of AP-1 and its functional involvement in C3H10T1/2 mesenchymal chondrogenesis. To measure the activity of the AP-I transcription factor, we generated a pool of stable C3H10T1/2 cell lines harboring a luciferase expression vector driven by a concatamer of an efficient AP-1 response element (AP1-10T1/2 cells). Luciferase activity of AP1-10T1/2 cultures was found to decrease sharply with increase in cell density, either as a function of culture time or initial cell seeding densities. In C3H10T1/2 micromass cultures undergoing chondrogenesis, AP-1 activity was further reduced and then maintained at a low, steady level for the entire 3-4 day culture period. AP-1 activity in micromass cultures was not significantly affected by BMP-2 treatment, but chondrogenesis was compromised upon competitive inhibition of AP-1 activity with a double-stranded AP-1 binding oligonucleotide. The level of AP-1 binding correlated with the activity of its response element but not with the levels of its leucine-zipper containing subunits, c-jun and c-Fos. These findings suggest that a cell density-dependent, low but steady level of AP-1 binding and activity is required for promoting the chondrogenic potential of C3H10T1/2 cells. (C) 2001 Wiley-Liss, Inc. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bldg 13,Rm 3W17,MSC5755, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR45181, AR46821, T32AR07583]; NIDCR NIH HHS [DE12864]; NIEHS NIH HHS [ES07005] NR 39 TC 25 Z9 28 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 84 IS 2 BP 237 EP 248 DI 10.1002/jcb.10019 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 505KB UT WOS:000172911000004 PM 11787053 ER PT J AU Li, TK Baksh, S Cristillo, AD Bierer, BE AF Li, TK Baksh, S Cristillo, AD Bierer, BE TI Calcium- and FK506-independent interaction between the immunophilin FKBP51 and calcineurin SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE immunosuppression; transplantation; FKBPs; cyclosporin; rapamycin; calcineurin; immunophilin ID RECEPTOR-MEDIATED TRANSCRIPTION; CIS-TRANS-ISOMERASES; GLUCOCORTICOID RECEPTOR; BINDING-PROTEIN; FK506-BINDING PROTEIN; PROGESTERONE-RECEPTOR; PHOSPHATASE-ACTIVITY; SIGNALING PATHWAYS; HOMOLOGOUS PROTEIN; MOLECULAR-CLONING AB FKBP51 is a member of the immunophilin family having intrinsic peptidyl-prolyl cis-trans-isomerase (PPlase) activity. Its enzymatic activity is inhibited by binding either immunosuppressive agent FK506 or rapamycin. Similar to FKBP12, but at higher concentrations of FK506, FKBP51 has been shown to inhibit the serine/threonine phosphatase activity of calcineurin in the presence of calcium and calmodulin. Here we show that a glutathione S-transferase (GST) fusion protein of FKBP51 on glutathione-Sepharose beads precipitated both purified calcineurin from bovine brain and calcineurin from murine T cell lysates. Surprisingly, the binding of GST-FKBP51 to calcineurin was FK506-independent and independent of a requirement for calcium or exogenous calmodulin. Unlike FKBP12, FKBP51 transiently expressed in COS-7 cells was precipitated by calcineurin bound to calmodulin-Sepharose beads in the absence of either FK506 or rapamycin. Unlike FKBP12, however, overexpression of FKBP51 in Jurkat T cells did not significantly affect the transcriptional activation of nuclear factor of activated T cells (NFAT) upon physiological stimulation, nor did it affect the ability of FK506 to inhibit NFAT-driven transcription. We generated a series of FKBP51 mutations to map the interaction of FKBP51 with calcineurin. Deletion of the aminoterminal, FKBP12-like domain of FKBP51 did not affect the ability of FKBP51 to bind to purified calcineurin, while deletion of the FKBP51 carboxyterminal domain abrogated the ability of FKBP51 to bind to calcineurin. Taken together, these results demonstrate a novel interaction between calcineurin and the immunophilin FKBP51 that is independent of calcium, calmodulin, and drug. The binding site on calcineurin for FKBP51 is separable from the immunophilin PPlase-active and drug-binding site. Published (C) 2001 Wiley-Liss, Inc.(dagger). C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, Lab Lymphocyte Biol, NIH, 10 Ctr Dr,Bldg 10,Room 6C208, Bethesda, MD 20892 USA. NR 60 TC 23 Z9 24 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 84 IS 3 BP 460 EP 471 DI 10.1002/jcb.10026 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 513BP UT WOS:000173358300004 PM 11813252 ER PT J AU Fischer, L Boland, G Tuan, RS AF Fischer, L Boland, G Tuan, RS TI Wnt signaling during BMP-2 stimulation of mesenchymal chondrogenesis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE cartilage development; micromass culture; N-cadherin; Wnt signaling; CSK-3 beta; lithium ID GLYCOGEN-SYNTHASE KINASE-3; N-CADHERIN EXPRESSION; BONE MORPHOGENETIC PROTEIN-2; CELL-CELL ADHESION; BETA-CATENIN; LIMB CHONDROGENESIS; MICROMASS CULTURES; INHIBITION; PHOSPHORYLATION; ACTIVATION AB Members of both the Wnt and bone morphogenetic protein (BMP) families of signaling molecules have been implicated in the regulation of cartilage development. A key component of the Wnt signaling pathway is the cytosolic protein, beta-catenin. We have recently shown that the chondrogenic activity of BMP-2 in vitro involves the action of, the cell-cell adhesion protein, N-cadherin, which functionally complexes with beta-catenin. The aim of this study is to test the hypothesis that Wnts may be involved in BMP-2 induced chondrogenesis, using an in vitro model of high-density micromass cultures of the murine multipotent mesenchymal cell line, C3H10T1/2. Expression of a number of Wnt members was detected in these cultures, including Wnt-3A and Wnt-7A, whose levels were up- and downregulated, respectively, by BMP-2. To assess the functional involvement of Wnt signaling in BMP-2 induced chondrogenesis, cultures were treated with lithium chloride, a Wnt-7A mimetic that acts by inhibiting the serine/threonine phosphorylation activity of glycogen synthase kinase-3beta (GSK-3beta). Lithium treatment significantly inhibited BMP-2 stimulation of chondrogenesis as well as CSK-3beta enzymatic activity, and decreased the levels of N-cadherin protein and mRNA. Furthermore, lithium decreased BMP-2 upregulation of total and nuclear levels of LEF-1 and beta-catenin as well as their interaction during later chondrogenesis; similarly, the interaction of beta-catenin with N-cadherin was also decreased. Interestingly, lithium treatment did not affect the ability of BMP-2 to decrease ubiquitination of beta-catenin, although it did reduce the interaction of beta-catenin with GSK-3beta during late chondrogenesis (days 9-13). We suggest that the chondro-inhibitory effect of lithium on BMP-2 induced chondrogenesis indicates antagonism between lithium-like Wnts and BMP-2 during mesenchymal condensation. (C) 2002 Wiley-Liss, lnc. C1 Natl Inst Hlth, Cartilage Biol & Orthopaed Branch, NIAMSD, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Grad Program Biochem & Mol Biol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Grad Program Cell & Tissue Engn, Philadelphia, PA 19107 USA. RP Tuan, RS (reprint author), Natl Inst Hlth, Cartilage Biol & Orthopaed Branch, NIAMSD, Bldg 13,3W17, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR39740, AR45181]; NIDCR NIH HHS [DE12864]; NIEHS NIH HHS [ES07005] NR 53 TC 76 Z9 81 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 84 IS 4 BP 816 EP 831 DI 10.1002/jcb.10091 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 517PH UT WOS:000173618800016 PM 11835406 ER PT J AU Medin, JA Fowler, DH AF Medin, JA Fowler, DH TI Post-transduction events in retrovirus-mediated gene therapy involving hematopoietic stem cells: Beyond efficiency issues SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE retrovirus; hematopoietic stem cells; immunotherapy; gene therapy; Th1/Th2; preselection ID BONE-MARROW CELLS; T-CELLS; VECTOR; LYMPHOCYTES; DISEASE; EXPANSION; SELECTION; INFECTION; MDR1; MICE AB Numerous incremental technological improvements have occurred recently in the application of therapeutic retrovirus-mediated gene transfer into hematopoietic stem cells (HSCs). Improved transduction efficiencies are now reaching levels that may correct some inherited or acquired disorders. Novel retroviral vector systems likewise offer the possibility for an expanded portfolio of treatment approaches. Most importantly, however, investigators are now also focusing efforts on post-transduction events to fully impact correction. Here we describe recent advances in the field, with a special emphasis on the role of post-transduction processes, for correction of disorders or treatments that involve HSCs or their progeny. C1 Ontario Canc Inst, Div Expt Therapeut, Toronto, ON M5G 2M1, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M1, Canada. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Medin, JA (reprint author), Univ Hlth Network, 67 Coll St,Rm 406, Toronto, ON M5G 2M1, Canada. NR 40 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 SU 38 BP 46 EP 54 DI 10.1002/jcb.10052 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 550EA UT WOS:000175489600008 ER PT J AU Li, KCP Guccione, S Bednarski, MD AF Li, KCP Guccione, S Bednarski, MD TI Combined vascular targeted imaging and therapy: A paradigm for personalized treatment SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE angiogenesis; imaging; diagnosis; treatment ID PARAMAGNETIC POLYMERIZED LIPOSOMES; TUMOR ANGIOGENESIS; ADHESION; INFLAMMATION; EXPRESSION; GROWTH AB In order to be successful in personalizing treatment, methods for selecting patients as well as good surrogate biomarkers for monitoring the effects of treatment are required in addition to development of an efficacious targeted therapy. We have developed a polymerized nanoparticle platform technology that will allow us to put different targeting moieties on the surface of the particles in addition to loading the particles with different contrast and therapeutic agents. We have proven that these nanoparticles can be targeted to endothelial receptors and different payloads of contrast and therapeutic agents have been delivered to target cells with high target to background ratios. Using this combined vascular targeted imaging and therapy approach, we are optimistic that personalized treatment regimens can be developed for different disease processes such as cancer, inflammation, and ischemia. C1 NIH, Radiol & Imaging Sci Program, Ctr Clin, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Radiol, Lucas MRS Res Ctr, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. RP Li, KCP (reprint author), NIH, Radiol & Imaging Sci Program, Ctr Clin, Bldg 10,Room 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 27 TC 8 Z9 8 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 SU 39 BP 65 EP 71 DI 10.1002/jcb.10401 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 641ZU UT WOS:000180777600009 ER PT J AU Costouros, NG Diehn, FE Libutti, SK AF Costouros, NG Diehn, FE Libutti, SK TI Molecular imaging of tumor angiogenesis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE magnetic resonance imaging; optical imaging; intravital videomicroscopy; positron emission tomography; ultrasound ID IN-VIVO; NUDE-MICE; AGENTS AB The emergence of angiogenesis as an important target for cancer therapy has led to Increased research aimed at understanding the mechanisms underlying the development, maintenance, and destruction of tumor vasculature. Concurrently, molecular imaging technologies have been developed and arc, being incorporated as integral components of biomedical research due to their ability to noninvasively monitor in vivo molecular events. With the evaluation of numerous anti-angiogenic agents in clinical trials, the adaptation and validation or molecular Imaging modalities for monitoring angiogenesis is actively being pursued. The importance of selecting appropriate molecular targets in the study of angiogenesis has become increasingly complex due to the pleiotropy of vascular phenotypes. Furthermore, due to both the relatively low abundance of endothelial cells in tumor tissue and the inherent difficulties of detecting molecular events, molecular imaging of vasculature necessitates continued improvements in achieving higher sensitivity. While several studies have been published that set the groundwork for imaging angiogenesis, much has yet to be accomplished. Various tumor models and transgenic mice provide an excellent resource for developing molecular imaging technologies for the understanding of angiogenesis, This research may play a particularly crucial role in evaluating mechanism and efficacy during pre-clinical testing of anti-angiogenic drugs. Due to practical limitations, however, the implementation of angiogenesis-directed molecular imaging may not extend beyond highly specialized clinical trials. That is, imaging modalities that evaluate angiogenesis at a functional level may prove more appropriate, Despite future technical challenges, molecular imaging will become an important research and clinical tool in evaluating tumor angiogenesis. C1 NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, HHMI, Res Scholars Program, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NIH, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. NR 27 TC 31 Z9 32 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 SU 39 BP 72 EP 78 DI 10.1002/jcb.10426 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 641ZU UT WOS:000180777600010 ER PT J AU Dong, F Wu, HB Hong, J Rechler, MM AF Dong, F Wu, HB Hong, J Rechler, MM TI Insulin-like growth factor binding protein-2 mediates the inhibition of DNA synthesis by transforming growth factor-beta in mink lung epithelial cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the Endocrine-Society CY JUN 21-24, 2000 CL TORONTO, CANADA SP Endocrine Soc ID BREAST-CANCER CELLS; I IGF-I; RETINOIC ACID; RAT-LIVER; RECEPTOR; FIBROBLASTS; LINE; MECHANISM; MEMBRANE; GENE AB Insulin-like growth factor binding protein-3 (IGFBP-3) has been proposed to mediate the growth inhibitory effects of transforming growth factor (TGF)-beta in breast and prostate cancer cells. Both TGF-beta and exogenous IGFBP-3 inhibit DNA synthesis in Mv1 mink lung epithelial cells (CCL64). The present study asks whether IGFBPs synthesized by CCL64 cells mediate growth inhibition by TGF-beta. CCL64 cells synthesize and secrete a single 34-kDa IGFBP that was identified as IGFBP-2 by immunoprecipitation and immunodepletion. Recombinant bovine IGFBP-2 inhibited CCL64 DNA synthesis in serum-free media in an IGF-independent manner. Coincubation with Leu(60)-IGF-I, an IGF-I analog that binds to IGFBPs with higher affinity than to IGF-I receptors, decreased the inhibition by bIGFBP-2. Leu(60)-IGF-I also decreased the inhibition of CCL64 DNA synthesis by TGF-beta by up to 70%, whereas Long-R3-IGF-I, an IGF-I analog with higher affinity for IGF-I receptors than for IGFBPs, did not decrease inhibition, suggesting that the effect of Leu(60)-IGF-I resulted from its forming complexes with endogenous IGFBPs. Leu(60)-IGF-I did not decrease TGF-beta stimulation of a Smad3-dependent reporter gene. Following incubation of intact CCL64 cells with bIGFBP-2 at 0 degreesC, bIGFBP-2 was recovered in membrane fractions; membrane association was abolished by coincubation with Leu(60)-IGF-I. If exogenous and secreted IGFBP-2 must bind to CCL64 cells to inhibit DNA synthesis, Leu(60)-IGF-I might reduce the inhibition of DNA synthesis by bIGFBP-2 or TGF-beta by inhibiting the association of IGFBP-2 in the media with CCL64 cells. Since TGF-beta does not increase IGFBP-2 abundance, we propose that TGF-beta sensitizes CCL64 cells to the latent growth inhibitory activity of endogenous IGFBP-2 by potentiating an intracellular IGFBP-2 signaling pathway or by promoting the association of secreted IGFBP-2 with the plasma membrane. Published 2002 Wiley-Liss, Inc.(dagger) C1 NIDDKD, Growth & Dev Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Rechler, MM (reprint author), NIDDKD, Growth & Dev Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 48 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2002 VL 190 IS 1 BP 63 EP 73 DI 10.1002/jcp.10034 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 499GU UT WOS:000172563800008 PM 11807812 ER PT J AU Bianco, C Normanno, N De Luca, A Maiello, MR Wechselberger, C Sun, Y Khan, N Adkins, H Sanicola, M Vonderhaar, B Cohen, B Seno, M Salomon, D AF Bianco, C Normanno, N De Luca, A Maiello, MR Wechselberger, C Sun, Y Khan, N Adkins, H Sanicola, M Vonderhaar, B Cohen, B Seno, M Salomon, D TI Detection and localization of Cripto-1 binding in mouse mammary epithelial cells and in the mouse mammary gland using an immunoglobulin-Cripto-1 fusion protein SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; VERTEBRATE DEVELOPMENT; TRANSGENIC MICE; BREAST-CANCER; GENE FAMILY; GROWTH; EXPRESSION; AMPHIREGULIN; RECEPTOR; GASTRULATION AB Human Cripto-1 (CR-1), a member of the epidermal growth factor-CFC (EGF-CFC) family of peptides, is expressed in the developing mouse mammary gland and can modulate mammary epithelial cell migration, branching morphogenesis and milk protein expression in vitro. In order to screen for a CR-1 receptor and to identify potential CR-1 target tissues, we constructed a fusion protein comprising the EGF-like domain of CR-1 and the Fc domain of a human IgG1. The recombinant CR-1 fusion protein (CR-1-Fc) was biologically active as it was able to activate the ras/raf/mitogen activated protein kinase (MAPK) pathway and to inhibit transcription of the milk protein P-casein in NMuMG and HC-11 mouse mammary epithelial cells. By using immunocytochemistry and by an in situ enzyme-linked immunosorbent assay (ELISA), CR-1-Fc was found to specifically bind to NMuMG and HC-11 cells. Finally, immunohistochemical analysis using CR-1-Fc showed a specific localization of CR-1 binding to tissue sections from mouse mammary gland. In particular, more than 60% of the epithelial cells were intensely stained with the CR-1-Fc fusion protein in the lactating mouse mammary gland, whereas approximately 25% of the mammary epithelial cells were stained in the gland from pregnant mouse. Since expression of mouse cripto-1 (Cr-1) in the pregnant and lactating mouse mammary gland as well as its presence in milk has been previously demonstrated, these data strongly suggest that an autocrine pathway involving Cr-1 and its putative receptor is operating in the mouse mammary gland during pregnancy and lactation. Published 2002 Wiley-Liss, Inc.(dagger) C1 NCI, TGFS, BRI, NIH, Bethesda, MD 20892 USA. ITN Fdn Pascale, Oncol Sperimentale D, Naples, Italy. NCI, Mol Endocrinol Sect, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Pfizer Cent Res Div, Groton, CT USA. Okayama Univ, Fac Engn, Dept Biosci & Biotechnol, Okayama, Japan. Biogen Inc, Cambridge, MA 02142 USA. RP Salomon, D (reprint author), NCI, TGFS, BRI, NIH, Bldg 10,Rm 5B39,9000 Rockville Pike, Bethesda, MD 20892 USA. RI SENO, Masaharu /B-2092-2011; De Luca, Antonella/J-8737-2016; OI SENO, Masaharu /0000-0001-8547-6259; De Luca, Antonella/0000-0001-5762-447X; Normanno, Nicola/0000-0002-7158-2605 NR 41 TC 18 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2002 VL 190 IS 1 BP 74 EP 82 DI 10.1002/jcp.10037 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 499GU UT WOS:000172563800009 PM 11807813 ER PT J AU Ihlenfeldt, WD Voigt, JH Bienfait, B Oellien, F Nicklaus, MC AF Ihlenfeldt, WD Voigt, JH Bienfait, B Oellien, F Nicklaus, MC TI Enhanced CACTVS browser of the open NCI database SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID DRUG INFORMATION-SYSTEM; GENERATION; MODULE; SMILES AB A Web-based, graphical user interface has been developed to conduct rapid searches by numerous criteria in the more than 250 000 structures of the Open NCI Database. It is based oil the chemistry information toolkit CACTVS. Nearly all structures and anticancer and anti-HIV screening data provided by NCI's Developmental Therapeutics Program have been included. This data set has been augmented by a large amount of additional. mostly computed, data, such as calculated log P values, predicted biological activities, systematically determined names, and others. Complex boolean searches are possible. Flexible substructure searches have been implemented. The user call conduct 3D pharmacophore queries in up to 25 conformations precalculated for each compound. Numerous output formats as well as 2D and 3D visualization options are provided. It is possible to export search results in various forms and with choices for data contents in the exported files, for structure sets ranging in size from a single compound to the entire database. Only a Web browser is needed to use this service, with a few plug-ins being useful but optional. C1 NCI Frederick, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. Univ Erlangen Nurnberg, Inst Organ Chem, D-91052 Erlangen, Germany. Univ Erlangen Nurnberg, Comp Chem Ctr, D-91052 Erlangen, Germany. RP Nicklaus, MC (reprint author), NCI Frederick, Med Chem Lab, Ctr Canc Res, NIH, 376 Boyles St, Frederick, MD 21702 USA. RI Nicklaus, Marc/N-4183-2014; OI Nicklaus, Marc/0000-0002-4775-7030 NR 16 TC 66 Z9 69 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JAN-FEB PY 2002 VL 42 IS 1 BP 46 EP 57 DI 10.1021/ci010056s PG 12 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 519MX UT WOS:000173731000006 PM 11855965 ER PT J AU Moolchan, ET Ruckel, SJ AF Moolchan, ET Ruckel, SJ TI Tobacco cessation for adolescents: Developing a group therapy approach SO JOURNAL OF CHILD & ADOLESCENT SUBSTANCE ABUSE LA English DT Article DE group therapy; adolescent; tobacco; cessation ID TRANSDERMAL NICOTINE PATCH; ILLICIT DRUG-USE; SMOKING CESSATION; SUBSTANCE-ABUSERS; BEHAVIORAL CHANGE; FOLLOW-UP; INTERVENTION; HEALTH; INITIATION; PREDICTORS AB Evidence indicates the importance of cognitive-behavioral approaches for the treatment of tobacco dependence among adults, used either alone or in combination with pharmacotherapy. However, there are few reports of behavioral approaches for teenage tobacco cessation. The objective of the clinic-based predominantly cognitive-behavioral therapeutic approach described herein is to help teenagers better manage life stressors by using effective and adaptive coping skills, while identifying and addressing specific factors that lead either to smoking or maintaining abstinence from smoking behavior. Multidimensional heterogeneity and high level of clinical challenge presented by teenage smokers favor the development of a novel approach. Adolescents' orientation to peers suggests that group participation might enhance adherence to the treatment process. The clinic environment and specific group exercises that empower teens to take control of multiple dimensions of cessation are discussed along with suggested session goals and content. (C) 2002 by The Haworth Press, Inc. All rights reserved. C1 NIDA, IRP, Teen Tobacco Addict Treatment Res Ctr, Clin Pharmacol & Therapeut Branch,NIH, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, IRP, Teen Tobacco Addict Treatment Res Ctr, Clin Pharmacol & Therapeut Branch,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 60 TC 7 Z9 7 U1 4 U2 6 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1067-828X J9 J CHILD ADOLES SUBST JI J. Child Adolesc. Subst. Abus. PY 2002 VL 12 IS 1 BP 65 EP 92 DI 10.1300/J029v12n01_04 PG 28 WC Substance Abuse SC Substance Abuse GA 633CP UT WOS:000180261900004 ER PT J AU Desper, R Vingron, M AF Desper, R Vingron, M TI Tree fitting: Topological recognition from ordinary least-squares edge length estimates SO JOURNAL OF CLASSIFICATION LA English DT Article DE estimates of branch lengths; least-squares methods; phylogenetic inference; test of topological difference ID MULTIPLE SEQUENCE ALIGNMENT; MINIMUM-EVOLUTION TREES; PHYLOGENETIC TREES; MICROCOMPUTER; CLUSTAL AB Distance methods play a central role in the field of phylogeny reconstruction, providing fast, efficient algorithms which yield reliable trees. A leading method in this field is the minimum evolution (ME) method, which selects the topology whose size is minimized when edge lengths have been selected for each topology via an ordinary least-squares (OLS) criterion. Vach and Degens (1991) have demonstrated that this OLS solution can be found by constraining edge lengths for a given topology such that average distances across each split in the tree metric equal those of the input metric. In this work we consider the vector space of tree metrics with regard to a basis generated by split average distances. This algebraic structure leads us to a conjecture regarding the edge weights of OLS tree fitting. We conjecture that if we fit a tree metric to an incorrect topology, the incorrectness will he detectable via a negative length assignment to one of the edges corresponding to a split in the test topology which is not shared by the true topology. This conjecture is proven for topologies sufficiently close to the true topology, and simulations suggest that it may be true in a more general case. We consider the durability of this topological signal in the presence of noisy sampling. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Max Planck Inst Mol Genet, D-14195 Berlin, Germany. RP Desper, R (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 45,Room 6AN-16D-31,8600 Rockville Pl, Bethesda, MD 20894 USA. NR 34 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0176-4268 EI 1432-1343 J9 J CLASSIF JI J. Classif. PY 2002 VL 19 IS 1 BP 87 EP 112 DI 10.1007/s00357-001-0034-x PG 26 WC Mathematics, Interdisciplinary Applications; Psychology, Mathematical SC Mathematics; Psychology GA 556UE UT WOS:000175866700004 ER PT J AU Jurado, MA Junque, C Vallejo, J Salgado, P Grafman, J AF Jurado, MA Junque, C Vallejo, J Salgado, P Grafman, J TI Obsessive-compulsive disorder (OCD) patients are impaired in remembering temporal order and in judging their own performance SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID FRONTAL-LOBE LESIONS; CEREBRAL BLOOD-FLOW; GLUCOSE METABOLIC-RATE; BASAL GANGLIA; COMPUTERIZED-TOMOGRAPHY; AMNESIC PATIENTS; MEMORY; DYSFUNCTION; BEHAVIOR; ABNORMALITIES AB Obsessive-compulsive disorder (OCD) has been related to frontostriatal dysfunction, but some inconsistencies between studies and a relative paucity of neuropsychological research still characterizes the study of OCD. We compared 28 patients with OCD and matched healthy controls on two neuropsychological tests sensitive to frontal dysfunction: temporal ordering and a "feeling-of-doing'' (FOD) judgment about ordering. The OCD group performed significantly worse than controls in the temporal ordering task despite showing normal recognition memory. Patients were also impaired in "feeling-of-doing'' judgments suggesting they have a lack of self-awareness of their performance. Thus, the results of the current study reinforces previous research that indicates that OCD patients fail on tasks that require adequate functioning of the frontal-striatal pathways. C1 Univ Barcelona, Dept Psiquiatria & Psicobiol Clin, Barcelona 08035, Spain. Hosp Princeps Espanya, Barcelona, Spain. NINCDS, Cognit Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Jurado, MA (reprint author), Univ Barcelona, Dept Psiquiatria & Psicobiol Clin, Passeig Vall Dhebron 171, Barcelona 08035, Spain. RI Junque, Carme/B-4400-2011; JURADO, MARIA ANGELES/E-1745-2011; OI Junque, Carme/0000-0002-6381-3063; JURADO, MARIA ANGELES/0000-0002-9403-1670; Grafman, Jordan H./0000-0001-8645-4457 NR 51 TC 8 Z9 8 U1 11 U2 13 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2002 VL 24 IS 3 BP 261 EP 269 DI 10.1076/jcen.24.3.261.986 PG 9 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 549MR UT WOS:000175448400001 PM 11992208 ER PT J AU Levav, M Mirsky, AF Herault, J Xiong, L Amir, N Andermann, E AF Levav, M Mirsky, AF Herault, J Xiong, L Amir, N Andermann, E TI Familial association of neuropsychological traits in patients with generalized and partial seizure disorders SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID JUVENILE MYOCLONIC EPILEPSY; AUTOSOMAL RECESSIVE DISEASE; SUSCEPTIBILITY GENE; CHILDREN; CHROMOSOME-6; PERFORMANCE; MEMORY; RISK AB To investigate familial effects of neuropsychological deficits associated with seizure disorders, we studied 65 families, in which 1 member had epilepsy. The disorders included childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME) and temporal lobe epilepsy (TLE). Age-appropriate tests were administered to assess sustained attention, encoding and verbal memory, executive and focused attention and attentional flexibility/impulsivity. CAE probands attained lower scores than other probands in visual sustained attention and the ability to focus on and execute a visual-motor task. Scores of the unaffected relatives tended to fall between those of the probands and the controls. JME relatives had lower scores than other relatives in tests of visual and auditory sustained attention and attentional flexibility, and showed greater variability in response time. Behavioral information of this type may aid in the specification and differentiation of genetic linkages in affected families. C1 NIMH, Sect Clin & Expt Neuropsychol, NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. Shaare Tzedek Med Ctr, Jerusalem, Israel. RP Mirsky, AF (reprint author), NIMH, Sect Clin & Expt Neuropsychol, NIH, Lab Brain & Cognit, 5415 W Cedar Lane,Suite 203-B,MSC 2615, Bethesda, MD 20892 USA. NR 48 TC 38 Z9 40 U1 0 U2 3 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2002 VL 24 IS 3 BP 311 EP 326 DI 10.1076/jcen.24.3.311.985 PG 16 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 549MR UT WOS:000175448400007 PM 11992214 ER PT J AU Bolan, C Oral, EA Gorden, P Taylor, S Leitman, SF AF Bolan, C Oral, EA Gorden, P Taylor, S Leitman, SF TI Intensive, long-term plasma exchange therapy for severe hypertriglyceridemia in acquired generalized lipoatrophy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PANCREATITIS AB We report dramatic improvement in clinical and laboratory parameters after intensive plasma exchange therapy in a 15-yr-old girl with acquired generalized lipoatrophy and refractory hypertriglyceridemia. One hundred and twenty-five procedures were performed over 720 d. Two or three plasma volumes were exchanged per procedure, using peripheral venous access and albumin as replacement solution. Regression of painful cutaneous xanthomata and reduction in massive hepatomegaly were noted within the first two procedures. Triglyceride levels started at 109 mmol/liter (9670 mg/dl) and decreased acutely by 60-85%/procedure. Lipid removal averaged 83 g/procedure and was highly correlated with preexchange lipid levels. Lipid levels rebounded to baseline values within 7 d after exchange and appeared to rebound more rapidly after larger exchanges. Maximum benefit was achieved with weekly 1.5- to 2.0-volume exchanges. No significant decrease in apolipoprotein CII levels was detected after plasma exchange regardless of the volume of exchange; however, other plasma factors regulating triglyceride synthesis or clearance may have been removed during the procedures. Plasma exchange was well tolerated, without clinical, immunological, or hormonal deterioration. These data indicate that intensive plasma exchange therapy over a protracted time may produce sustained benefit in patients with severe, symptomatic hypertriglyceridemia refractory to standard medical therapy. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Warren Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. RP Oral, EA (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 8D20,10 Ctr Dr,MSC 1770, Bethesda, MD 20892 USA. EM elif_arioglu@nih.gov OI Oral, Elif/0000-0002-9171-1144 NR 13 TC 18 Z9 19 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 2002 VL 87 IS 1 BP 380 EP 384 DI 10.1210/jc.87.1.380 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 514PR UT WOS:000173450700059 PM 11788680 ER PT J AU Castle, PE Hildesheim, A Bowman, FP Strickler, HD Walker, JL Pustilnik, T Edwards, RP Crowley-Nowick, PA AF Castle, PE Hildesheim, A Bowman, FP Strickler, HD Walker, JL Pustilnik, T Edwards, RP Crowley-Nowick, PA TI Cervical concentrations of interleukin-10 and interleukin-12 do not correlate with plasma levels SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE IL-10; IL-12; cervix; plasma; HPV ID HUMAN-PAPILLOMAVIRUS; CANCER; INFERTILITY; PREVALENCE; WORLDWIDE; FERTILE; DISEASE; MUCUS; WOMEN; SERUM AB Human papillomavirus (HPV) infects the transformation zone of the cervix and is the primary cause of cervical cancer. The infection is localized to the cervix and mucosal immunity is likely to be an important determinant for viral clearance. Previous studies of immunity to HPV have measured immune markers in the blood, but the relationship of systemic immunity to cervical immunity is poorly understood. In this study of 70 women enrolled in the ASCUS-LSIL Triage Study (ALTS), a clinical trial for management of low-grade cytologic abnormalities of the cervix, we collected paired plasma and cervical secretions to investigate the relationship between cervical concentrations of interleukin-10 (IL-10) and interleukin-12 (IL-12) and plasma levels. Neither IL-10 (p = 0.11), or IL-12 (p = -0.04) nor the ratio of IL-12 to IL-10 (p = 0.06) were correlated between blood and cervical secretions. Except for weak correlations of IL-10 among nonsmokers (p = 0.35, P = 0.019) and those in day 18-27 of their menstrual cycle (p = 0.51, P = 0.015), this lack of correlation persisted in all subgroups defined by genital inflammation or infection, current oral contraceptive use, heme contamination and volume of collected secretions, HPV16 seropositivity, and repeat HPV infection and/or cytologic abnormalities. The lack of correlation and high concentrations in cervical secretions indicate that the cervical IL-10 and IL-12 concentrations exceed what could be expected from blood as a principle source of IL-10 and IL-12 and suggest that cytokine concentrations in cervical secretions are predominantly the result of local cytokine production. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Fearing Res Lab,Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. Univ Oklahoma, Coll Med, Dept Obstet & Gynecol, Oklahoma City, OK USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL USA. Univ Pittsburgh, Med Ctr, Dept Obstet & Gynecol, Pittsburgh, PA USA. Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7074,MSC 7234, Bethesda, MD 20892 USA. FU NCI NIH HHS [CN55159, CN55153, CN55156, CN55105, CN55154, CN55155, CN55158, CN55157] NR 14 TC 33 Z9 34 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JAN PY 2002 VL 22 IS 1 BP 23 EP 27 DI 10.1023/A:1014252402630 PG 5 WC Immunology SC Immunology GA 539RT UT WOS:000174884800004 PM 11958590 ER PT J AU Barker, PE Watson, MS Ticehurst, JR Colbert, JC O'Connell, CD AF Barker, PE Watson, MS Ticehurst, JR Colbert, JC O'Connell, CD TI NIST physical standards for DNA-based medical testing SO JOURNAL OF CLINICAL LABORATORY ANALYSIS LA English DT Article DE DNA; standard; diagnostics ID TECHNOLOGY NAT ASSAYS; PROFILING MEASUREMENTS; INTERNATIONAL STANDARD; POLYMORPHISM; DIAGNOSIS; SIZE AB As DNA and RNA become major targets for clinical laboratory analysis, benchmark reagents will play an increasingly important role in standardization. Reliable national and international nucleic acid standards promote automation and third-party reimbursement for clinical testing. Furthermore, nucleic acid standards provide materials for quality assurance and quality control (QA/QC), and proficiency testing. Standard methods and training initially evolved from consensus guidelines endorsed by professional societies and governmental agencies. The National Institute of Standards and Technology (NIST), a nonregulatory agency of the U.S. Department of Commerce, develops and certifies physical and chemical standards in support of national commerce, manufacturing, and science. In its role supporting U.S. science and industry, the NIST responds to specific standards needs, most recently for medically and biologically important analytes. Broad-based consensus developed through interdisciplinary NIST workshops initiated development of NIST-certified DNA standards. Such materials serve the diagnostic community and help manufacturers benchmark a variety of DNA diagnostic testing platforms. Here we summarize the NIST experience and programs for development of national standards for DNA-based medical diagnostic testing. (C) 2002 Wiley-Liss, Inc. C1 NIST, Biomarkers Validat lab, NCI, Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Amer Coll Med Genet, Bethesda, MD USA. US FDA, Ctr Devices & Radiol Hlth, DCLD, ODE,Microbiol Branch, Rockville, MD 20857 USA. Johns Hopkins Med Inst, Dept Pathol, Div Microbiol, Baltimore, MD 21205 USA. Natl Inst Stand & Technol, Off Measurement Serv, NIST, SRM Program, Gaithersburg, MD 20899 USA. RP Barker, PE (reprint author), NIST, Biomarkers Validat lab, NCI, Natl Inst Stand & Technol, Room B248,Bldg 227,100 Bur Dr, Gaithersburg, MD 20899 USA. RI Ticehurst, John/I-7532-2012 FU NCI NIH HHS [Y1-CN-0103-1] NR 36 TC 2 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-8013 J9 J CLIN LAB ANAL JI J. Clin. Lab. Anal. PY 2002 VL 16 IS 1 BP 5 EP 10 DI 10.1002/jcla.2062 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 514TF UT WOS:000173456600002 PM 11835524 ER PT J AU Meng, XJ Wiseman, B Elvinger, F Guenette, DK Toth, TE Engle, RE Emerson, SU Purcell, RH AF Meng, XJ Wiseman, B Elvinger, F Guenette, DK Toth, TE Engle, RE Emerson, SU Purcell, RH TI Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID OPEN-READING FRAME-2; E INFECTION; INSECT CELLS; HEV; IDENTIFICATION; SEROREACTIVITY; SEQUENCE; VARIANT; FAILURE; STRAINS AB Hepatitis E virus (HEV) is endemic in many developing and some industrialized countries. It has been hypothesized that animals may be the source of infection. The recent identification of swine HEV in U.S. pigs and the demonstration of its ability to infect across species have lent credence to this hypothesis. To assess the potential risk of zoonotic HEV infection, we tested a total of 468 veterinarians working with swine (including 389 U.S. swine veterinarians) and 400 normal U.S. blood donors for immunoglobulin G anti-HEV. Recombinant capsid antigens from a U.S. strain of swine HEV and from a human HEV strain (Sar-55) were each used in an enzyme-linked immunosorbent assay. The anti-HEV prevalence assayed with the swine HEV antigen showed 97% concordance with that obtained with the human HEV antigen (kappa = 92%). Among the 295 swine veterinarians tested from the eight U.S. states (Minnesota, Indiana, Nebraska, Iowa, Illinois, Missouri, North Carolina, and Alabama) from which normal blood donor samples were available, 26% were positive with Sar-55 antigen and 23% were positive with swine HEV antigen. In contrast, 18% of the blood donors from the same eight U.S. states were positive with Sar-55 antigen and 17% were positive with swine HEV antigen. Swine veterinarians in the eight states were 1.51 times more likely when tested with swine HEV antigen (95% confidence interval, 1.03 to 2.20) and 1.46 times more likely when tested with Sar-55 antigen (95% confidence interval, 0.99 to 2.17) to be anti-HEV positive than normal blood donors. We did not find a difference in anti-HEV prevalence between veterinarians who reported having had a needle stick or cut and those who had not or between those who spent more time (greater than or equal to80% of the time) and those who spent less time (less than or equal to20% of the time) working with pigs. Similarly, we did not find a difference in anti-HEV prevalence according to four job categories (academic, practicing, student, and industry veterinarians). There was a difference in anti-HEV prevalence in both swine veterinarians and blood donors among the eight selected states, with subjects from Minnesota six times more likely to be anti-HEV positive than those from Alabama. Age was not a factor in the observed differences from state to state. Anti-HEV prevalence in swine veterinarians and normal blood donors was age specific and paralleled increasing age. The results suggest that swine veterinarians may be at somewhat higher risk of HEV infection than are normal blood donors. C1 Virginia Polytech Inst & State Univ, Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. Virginia Polytech Inst & State Univ, Coll Vet Med, Dept Large Anim Clin Sci, Blacksburg, VA 24061 USA. Nextran Inc, Princeton, NJ 08540 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Meng, XJ (reprint author), Virginia Polytech Inst & State Univ, Coll Vet Med, Ctr Mol Med & Infect Dis, 1410 Prices Fork Rd, Blacksburg, VA 24601 USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 FU NIAID NIH HHS [AI46505, AI01653] NR 49 TC 303 Z9 319 U1 3 U2 9 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 2002 VL 40 IS 1 BP 117 EP 122 DI 10.1128/JCM.40.1.117-122.2002 PG 6 WC Microbiology SC Microbiology GA 509AK UT WOS:000173121800021 PM 11773103 ER PT J AU Toso, JF Gill, VJ Hwu, P Marincola, FM Restifo, NP Schwartzentruber, DJ Sherry, RM Topalian, SL Yang, JC Stock, F Freezer, LJ Morton, KE Seipp, C Haworth, L Mavroukakis, S White, D MacDonald, S Mao, J Sznol, M Rosenberg, SA AF Toso, JF Gill, VJ Hwu, P Marincola, FM Restifo, NP Schwartzentruber, DJ Sherry, RM Topalian, SL Yang, JC Stock, F Freezer, LJ Morton, KE Seipp, C Haworth, L Mavroukakis, S White, D MacDonald, S Mao, J Sznol, M Rosenberg, SA TI Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANTITUMOR AGENT; LIPID-A; MACROPHAGES; INFECTIONS; INDUCTION AB Purpose: A strain of Salmonella typhimurium (VNP20009), attenuated by chromosomal deletion of the purl and msbB genes, was found to target to tumor and inhibit tumor growth in mice. These findings led to the present phase 1 study of the intravenous infusion of VNP20009 to patients with metastatic cancer. Patients and Methods: In cohorts consisting of three to six patients, 24 patients with metastatic melanoma and one patient with metastatic renal cell carcinoma received 30-minute intravenous bolus infusions containing 10(6) to 10(9) cfu/m(2) of VNP20009. Patients were evaluated for dose-related toxicities, selective replication within tumors, and antitumor effects. Results: The maximum-tolerated dose was 3 x 10(8) cfu/m(2). Dose-limiting toxicity was observed in patients receiving 1 x 109 cfu/m(2), which included thrombocytopenia, anemia, persistent bacteremia, hyperbilirubinemia, diarrhea, vomiting, nausea, elevated alkaline phosphatase, and hypophosphatemia. VNP20009 induced a dose-related increase in the circulation of proinflammatory cytokines, such as interleukin (IL)-1beta, tumor necrosis factor alpha, IL-6, and IL-12. Focal tumor colonization was observed in two patients receiving 1 x 10(9) cfu/m(2) and in one patient receiving 3 x 10(8) cfu/m(2). None of the patients experienced objective tumor regression, including those patients with colonized tumors. Conclusion: The VNP20009 strain of Salmonella typhimurium can be safely administered to patients, and at the highest tolerated dose, some tumor colonization was observed. No antitumor effects were seen, and additional studies are required to reduce dose-related toxicity and improve tumor localization. (C) 2001 by American Society of Clinical Oncology. C1 NCI, Canc Res Ctr, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Microbiol Serv, Bethesda, MD 20892 USA. Vion Pharmaceut, New Haven, CT USA. RP Rosenberg, SA (reprint author), NCI, Canc Res Ctr, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 21 TC 259 Z9 270 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2002 VL 20 IS 1 BP 142 EP 152 DI 10.1200/JCO.20.1.142 PG 11 WC Oncology SC Oncology GA 510XE UT WOS:000173231900019 PM 11773163 ER PT J AU Cianfrocca, M Cooley, TP Lee, JY Rudek, MA Scadden, DT Ratner, L Pluda, JM Figg, WD Krown, SE Dezube, BJ AF Cianfrocca, M Cooley, TP Lee, JY Rudek, MA Scadden, DT Ratner, L Pluda, JM Figg, WD Krown, SE Dezube, BJ TI Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: A phase I AIDS malignancy consortium study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TISSUE INHIBITOR; METASTATIC PHENOTYPE; GELATINASE-A; TUMOR-GROWTH; CELLS; DOXYCYCLINE; EXPRESSION; MELANOMA; MICE; PHARMACOKINETICS AB Purpose: Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis and are over-expressed in Kaposi's sarcoma (KS) cells. The primary aim was to define the safety and toxicity of the MMP inhibitor COL-3 in patients with AIDS-related KS. Secondary aims were to evaluate tumor response, pharmacokinetics, and changes in blood levels of MMP-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). Patients and Methods: COL-3 was administered orally once daily, and doses were escalated in cohorts of three to six subjects. Patients with symptomatic visceral KS or severe tumor-associated edema were excluded. Antiretroviral therapy was permitted but not required. Study end points were grade 3 or 4 toxicity or progressive KS. Serial blood specimens were obtained for pharmacokinetics and levels of MMP-2, MMP-9, VEGF, and bFGF. Results: Eighteen patients received COL-3 in dosing cohorts of 25, 50, and 70 mg/m(2)/d. Prior KS therapy was reported by 17 patients (94%). COL-3-related grade 3 or 4 adverse events were reported by six patients and included photosensitivity, rash, and headache. There was one complete response and seven partial responses, for an overall response rate of 44%, with a median response duration of 25+ weeks. The median COL-3 half-life was 39.3 hours (range, 4.1 to 251.1 hours). There was a significant difference between responders and nonresponders with respect to the change in MMP-2 serum levels from baseline to minimum value on treatment (P = .037). Conclusion: COL-3 administered orally once daily to patients with AIDS-related KS is reasonably well tolerated. The most common adverse event was dose-related photosensitivity. Antitumor activity was noted. Further evaluation of COL-3 for the treatment of KS is warranted. (C) 2001 by American Society of Clinical Oncology. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Boston Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Chicago, IL 60611 USA. Washington Univ, St Louis, MO USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Clin Pharmacokinet Sect, Bethesda, MD USA. NCI, Canc Therapy Evaluat Program, Investigat Drug Branch, Bethesda, MD USA. Univ Alabama, AIDS Malignancy Consortium Operat Ctr, Birmingham, AL USA. RP Dezube, BJ (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,CC-913, Boston, MA 02215 USA. RI Figg Sr, William/M-2411-2016 FU NCI NIH HHS [U01 CA 70019, U01 CA 70047, U01 CA 70054, U01 CA 70062, U01 CA 70072, U01 CA 70080, U01 CA 71375, U01 CA 83035]; NCRR NIH HHS [RR 00036, RR 00533, RR 01032] NR 33 TC 113 Z9 117 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2002 VL 20 IS 1 BP 153 EP 159 DI 10.1200/JCO.20.1.153 PG 7 WC Oncology SC Oncology GA 510XE UT WOS:000173231900020 PM 11773164 ER PT J AU Warren, JL Brown, ML Fay, MP Schussler, N Potosky, AL Riley, GF AF Warren, JL Brown, ML Fay, MP Schussler, N Potosky, AL Riley, GF TI Costs of treatment for elderly women with early-stage breast cancer in fee-for-service settings SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; OLDER WOMEN; CONSERVING SURGERY; CARE; AGE; COMORBIDITY; MASTECTOMY; DIAGNOSIS; CARCINOMA; PATTERNS AB Purpose: This study provides population-based estimates of the treatment costs for elderly women with early-stage breast cancer, with emphasis on costs of modified radical mastectomy (MRM) compared with breast-conserving surgery (BCS) and radiation therapy (RT). Patients and Methods: Women with breast cancer from the Surveillance, Epidemiology, and End Results cancer registries were linked with their Medicare claims, 1990 through 1998. Each claim was assigned to an initial, continuing, or terminal care phase after a cancer diagnosis. Mean monthly phase-specific costs were determined for all health care and for treatment related only to cancer. Cumulative long-term costs of care that accrue during a women's remaining lifetime were calculated by treatment group. Results: Initial care costs for the 6 months after diagnosis for women who underwent BCS with RT were approximately $450 per month higher than for women with MRM. During the continuing-care phase, costs for women undergoing BCS with RT were significantly less expensive than for MRM cases. The two groups had similar costs in the terminal-care phase. Assuming the same survival distributions, long-term costs for women undergoing BCS with RT were not statistically different than for women undergoing MRM. Conclusion: Although mastectomy was less costly in the initial phase, the lifetime costs of BCS with RT and mastectomy were equivalent. Thus, women's preferences, resources to cover out-of-pocket costs, and life situations should be the major factors addressed in shared decision making about treatment options. (C) 2001 by American Society of Clinical Oncology. C1 NCI, Appl Res Program, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Warren, JL (reprint author), NCI, Appl Res Program, Execut Plaza N,Rm 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 45 TC 72 Z9 72 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2002 VL 20 IS 1 BP 307 EP 316 DI 10.1200/JCO.20.1.307 PG 10 WC Oncology SC Oncology GA 510XE UT WOS:000173231900040 PM 11773184 ER PT J AU Rajasekaran, S Jin, X Spouge, JL AF Rajasekaran, S Jin, X Spouge, JL TI The efficient computation of position-specific match scores with the fast Fourier transform SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE position-specific scoring matrices; fast Fourier transform; algorithm ID HIDDEN MARKOV-MODELS; ACID SUBSTITUTION MATRICES; PROTEIN SEQUENCES; PROFILE ANALYSIS; DNA-SEQUENCES; PSI-BLAST; SEARCH; SIMILARITIES; PERIODICITY; DATABASES AB Historically, in computational biology the fast Fourier transform (FFT) has been used almost exclusively to count the number of exact letter matches between two biosequences. This paper presents an FFT algorithm that can compute the match score of a sequence against a position-specific scoring matrix (PSSM). Our algorithm finds the PSSM score simultaneously over all offsets of the PSSM with the sequence, although like all previous FFT algorithms, it still disallows gaps. Although our algorithm is presented in the context of global matching, it can be adapted to local matching without gaps. As a benchmark, our PSSM-modified FFT algorithm computed pairwise match scores. In timing experiments, our most efficient FFT implementation for pairwise scoring appeared to be 10 to 26 times faster than a traditional FFT implementation, with only a factor of 2 in the acceleration attributable to a previously known compression scheme. Many import-ant algorithms for detecting biosequence similarities, e.g., gapped BLAST or PSIBLAST, have a heuristic screening phase that disallows gaps. This paper demonstrates that FFT algorithms merit reconsideration in these screening applications. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Florida, Dept Comp & Informat Sci & Engn, Gainesville, FL 32611 USA. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM spouge@nih.gov NR 33 TC 15 Z9 15 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 EI 1557-8666 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2002 VL 9 IS 1 BP 23 EP 33 DI 10.1089/10665270252833172 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 531QL UT WOS:000174426900002 PM 11911793 ER PT J AU Dougherty, ER Barrera, J Brun, M Kim, S Cesar, RM Chen, YD Bittner, M Trent, JM AF Dougherty, ER Barrera, J Brun, M Kim, S Cesar, RM Chen, YD Bittner, M Trent, JM TI Inference from clustering with application to gene-expression microarrays SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE clustering; gene expression; microarray ID CLASSIFICATION; PATTERNS AB There are many algorithms to cluster sample data points based on nearness or a similarity measure. Often the implication is that points in different clusters come from different underlying classes, whereas those in the same cluster come from the same class. Stochastically, the underlying classes represent different random processes. The inference is that clusters represent a partition of the sample points according to which process they belong. This paper discusses a model-based clustering toolbox that evaluates cluster accuracy. Each random process is modeled as its mean plus independent noise, sample points are generated, the points are clustered, and the clustering error is the number of points clustered incorrectly according to the generating random processes. Various clustering algorithms are evaluated based on process variance and the key issue of the rate at which algorithmic performance improves with increasing numbers of experimental replications. The model means can be selected by hand to test the separability of expected types of biological expression patterns. Alternatively, the model can be seeded by real data to test the expected precision of that output or the extent of improvement in precision that replication could provide. In the latter case, a clustering algorithm is used to form clusters, and the model is seeded with the means and variances of these clusters. Other algorithms are then tested relative to the seeding algorithm. Results are averaged over various seeds. Output includes error tables and graphs, confusion matrices, principal-component plots, and validation measures. Five algorithms are studied in detail: K-means, fuzzy C-means, self-organizing maps, hierarchical Euclidean-distance-based and correlation-based clustering. The toolbox is applied to gene-expression clustering based on cDNA microarrays using real data. Expression profile graphics are generated and error analysis is displayed within the context of these profile graphics. A large amount of generated output is available over the web. C1 Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. Univ Sao Paulo, Dept Ciencia Comp, Sao Paulo, Brazil. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Dougherty, ER (reprint author), Texas A&M Univ, Dept Elect Engn, 3128 TAMU, College Stn, TX 77843 USA. RI Cesar, Roberto/C-4120-2012 OI Cesar, Roberto/0000-0003-2701-4288 NR 12 TC 105 Z9 109 U1 1 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2002 VL 9 IS 1 BP 105 EP 126 DI 10.1089/10665270252833217 PG 22 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 531QL UT WOS:000174426900006 PM 11911797 ER PT J AU Kim, S Dougherty, ER Barrera, J Chen, YD Bittner, ML Trent, JM AF Kim, S Dougherty, ER Barrera, J Chen, YD Bittner, ML Trent, JM TI Strong feature sets from small samples SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE perceptron; gene expression; classification; cancer ID CONTROLLED RANDOM SEARCH; GENE-EXPRESSION; GLOBAL OPTIMIZATION; MOLECULAR CLASSIFICATION; CDNA MICROARRAYS; BREAST-CANCER; ALGORITHMS; PATTERNS; NETWORKS; TISSUES AB For small samples, classifier design algorithms typically suffer from overfitting. Given a set of features, a classifier must be designed and its error estimated. For small samples, an error estimator may be unbiased but, owing to a large variance, often give very optimistic estimates. This paper proposes mitigating the small-sample problem by designing classifiers from a probability distribution resulting from spreading the mass of the sample points to make classification more difficult, while maintaining sample geometry. The algorithm is parameterized by the variance of the spreading distribution. By increasing the spread, the algorithm finds gene sets whose classification accuracy remains strong relative to greater spreading of the sample. The error gives a measure of the strength of the feature set as a function of the spread. The algorithm yields feature sets that can distinguish the two classes, not only for the sample data, but for distributions spread beyond the sample data. For linear classifiers, the topic of the present paper, the classifiers are derived analytically from the model, thereby providing an enormous savings in computation time. The algorithm is applied to cancer classification via cDNA microarrays. In particular, the genes BRCA1 and BRCA2 are associated with a hereditary disposition to breast cancer, and the algorithm is used to find gene sets whose expressions can be used to classify BRCA1 and BRCA2 tumors. C1 Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. Univ Sao Paulo, Dept Ciencia Comp, Sao Paulo, Brazil. NIH, Natl Human Genome Res Inst, Canc Genet Branch, Bethesda, MD 20892 USA. RP Dougherty, ER (reprint author), Texas A&M Univ, Dept Elect Engn, 3128 TAMU, College Stn, TX 77843 USA. NR 39 TC 54 Z9 56 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2002 VL 9 IS 1 BP 127 EP 146 DI 10.1089/10665270252833226 PG 20 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 531QL UT WOS:000174426900007 PM 11911798 ER PT J AU Radmacher, MD McShane, LM Simon, R AF Radmacher, MD McShane, LM Simon, R TI A paradigm for class prediction using gene expression profiles SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE gene expression profiles; class prediction; permutation test ID CLASSIFICATION; CANCER; VALIDATION AB We propose a general framework for prediction of predefined tumor classes using gene expression profiles from microarray experiments. The framework consists of 1) evaluating the appropriateness of class prediction for the given data set, 2) selecting the prediction method, 3) performing cross-validated class prediction, and 4) assessing the significance of prediction results by permutation testing. We describe an application of the prediction paradigm to gene expression profiles from human breast cancers, with specimens classified as positive or negative for BRCA1 mutations and also for BRCA2 mutations. In both cases, the accuracy of class prediction was statistically significant when compared to the accuracy of prediction expected by chance. The framework proposed here for the application of class prediction is designed to reduce the occurrence of spurious findings, a legitimate concern for high-dimensional microarray data. The prediction paradigm will serve as a good framework for comparing different prediction methods and may accelerate the development of molecular classifiers that are clinically useful. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Radmacher, MD (reprint author), NCI, Biometr Res Branch, 6130 Execut Blvd, Bethesda, MD 20892 USA. NR 12 TC 175 Z9 180 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2002 VL 9 IS 3 BP 505 EP 511 DI 10.1089/106652702760138592 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 570VG UT WOS:000176679000004 PM 12162889 ER PT J AU Sung, MH Zhao, YD Martin, R Simon, R AF Sung, MH Zhao, YD Martin, R Simon, R TI T-cell epitope prediction with combinatorial peptide libraries SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE epitope prediction; cell-mediated immunity; combinatorial peptide library; autoimmunity; TCR ligand identification; MHC class II binding ID MYELIN BASIC-PROTEIN; ARTIFICIAL NEURAL-NETWORK; INDIVIDUAL AMINO-ACIDS; MULTIPLE-SCLEROSIS; BINDING PEPTIDES; MHC-BINDING; QUANTITATIVE-ANALYSIS; ANTIGEN RECOGNITION; MOLECULAR MIMICRY; LYME-DISEASE AB T cell receptors (TCR) recognize antigenic peptides in complex with the major histocompatibility complex (MHC) molecules and this trimolecular interaction initiates antigen-specific signaling pathways in the responding T lymphocytes. For the study of autoimmune diseases and vaccine development, it is important to identify peptides (epitopes) that can stimulate a given TCR. The use of combinatorial peptide libraries has recently been introduced as a powerful tool for this purpose. A combinatorial library of n-mer peptides is a set of complex mixtures each characterized by one position fixed to be a specified amino acid and all other positions randomized. A given TCR can be fingerprinted by screening a variety of combinatorial libraries using a proliferation assay. Here, we present statistical models for elucidating the recognition profile of a TCR using combinatorial library proliferation assay data and known MHC binding data. C1 NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. American Univ, Dept Math & Stat, Washington, DC 20016 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, NIH, 6130 Execut Blvd,EPN 8146,MSC 7434, Bethesda, MD 20892 USA. NR 49 TC 10 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2002 VL 9 IS 3 BP 527 EP 539 DI 10.1089/106652702760138619 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 570VG UT WOS:000176679000006 PM 12162891 ER PT J AU Desper, R Gascuel, O AF Desper, R Gascuel, O TI Fast and accurate phylogeny reconstruction algorithms based on the minimum-evolution principle SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE phylogenetic inference; distance methods; minimum evolution; topological accuracy; computational speed ID LEAST-SQUARES; SEQUENCE DATA; TREES; SUBSTITUTIONS; SIMULATION; MODELS; RATES AB The Minimum Evolution (ME) approach to phylogeny estimation has been shown to be statistically consistent when it is used in conjunction with ordinary least-squares (OLS) fitting of a metric to a tree structure. The traditional approach to using ME has been to start with the Neighbor Joining (NJ) topology for a given matrix and then do a topological search from that starting point. The first stage requires O (n(3)) time, where n is the number of taxa, while the current implementations of the second are in O (pn(3)) or more, where P is the number of swaps performed by the program. In this paper, we examine a greedy approach to minimum evolution which produces a starting topology in O (n(2)) time. Moreover, we provide an algorithm that searches for the best topology using nearest neighbor interchanges (NNIs), where the cost of doing p NNIs is O(n(2) + pn), i.e., O(n(2)) in practice because p is always much smaller than n. The Greedy Minimum Evolution (GME) algorithm, when used in combination with NNIs, produces trees which are fairly close to NJ trees in terms of topological accuracy. We also examine ME under a balanced weighting scheme, where sibling subtrees have equal weight, as opposed to the standard "unweighted" OLS, where all taxa have the same weight so that the weight of a-subtree is equal to the number of its taxa. The balanced minimum evolution scheme (BME) runs slower than the OLS version, requiring O (n(2) x diam(T)) operations to build the starting tree and O(pn x diam(T)) to perform the NNIs, where diam(T) is the topological diameter of the output tree. In the usual Yule-Harding distribution on phylogenetic trees, the diameter expectation is in log(n), so our algorithms are in practice faster that NJ. Moreover, this BME scheme yields a very significant improvement over NJ and other distance-based algorithms, especially with large trees, in terms of topological accuracy. C1 LIRMM, Dept Informat Fondamentale & Applicat, F-34392 Montpellier, France. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP LIRMM, Dept Informat Fondamentale & Applicat, 161,Rue Ada, F-34392 Montpellier, France. EM gascuel@lirmm.fr NR 33 TC 210 Z9 214 U1 0 U2 12 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 EI 1557-8666 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2002 VL 9 IS 5 BP 687 EP 705 DI 10.1089/106652702761034136 PG 19 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 618CU UT WOS:000179401200001 PM 12487758 ER PT J AU McVeigh, E Faris, O Ennis, D Helm, P Evans, F AF McVeigh, E Faris, O Ennis, D Helm, P Evans, F TI Electromechanical mapping with MRI tagging and epicardial sock electrodes SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 27th Annual ISCE Conference on Research and Technology Transfer in Computerized Electrocardiology CY APR 20-25, 2002 CL DOORWERTH, NETHERLANDS SP ISCE ID MECHANICAL ACTIVATION; PACED HEART; MOTION; IMAGES; ARRHYTHMIAS; STRETCH AB Methods currently exist for the precise measurement of local three-dimensional myocardial motion noninvasivly with magnetic resonace imaging tagging. From these motion estimates, strain images representing the local deformation of the myocardium can be formed to show local myocardial contraction. These images clearly show the sequence of mechanical events during the activation and relaxation of the heart, making them ideal to visualize abnormalities caused by asynchronous electrical activation or ischemia. Coupled with the near simultaneous mapping of electrical depolarization with a sock electrode array, we can investigate the relationship between electical activity and mechanical function on a local level in the in vivo heart. Registered fiber angle maps can be also be obtained in the same heart with diffusion magnetic resonance imaging to assist in the construction of the electromechanical model of the whole heart. C1 NHLBI, Cardiac Energet Lab, DHHS, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. RP McVeigh, E (reprint author), NHLBI, Cardiac Energet Lab, DHHS, NIH, Bldg 10,Room B1D416, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL004609-08] NR 20 TC 7 Z9 7 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 2002 VL 35 SU S BP 61 EP 64 DI 10.1054/jelc.2002.37156 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DD UT WOS:000180263200009 PM 12539100 ER PT J AU Church, TR Hodges, M Bailey, JJ Mongin, SJ AF Church, TR Hodges, M Bailey, JJ Mongin, SJ TI Risk stratification applied to CAST registry data: Combining 9 predictors SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 27th Annual ISCE Conference on Research and Technology Transfer in Computerized Electrocardiology CY APR 20-25, 2002 CL DOORWERTH, NETHERLANDS SP ISCE DE risk stratification; sudden cardiac death; ejection fraction; multivariate methods ID SUDDEN CARDIAC DEATH; MYOCARDIAL-INFARCTION; RANDOMIZED TRIALS; DEFIBRILLATOR; PREVENTION; ARRHYTHMIA; MORTALITY AB Over 200,000 people in the United States die of sudden cardiac death (SCD) every year. Although many of these deaths occur in asymptomatic individuals, the vast majority of deaths occur in people who are under care for existing coronary heart disease. Implantable cardioverter/defibrillators (ICDs) have been shown in several randomized trials to be effective in prolonging lives of those at high risk for sudden cardiac death, but the criteria used in these trials and the ACC/AHA consensus guidelines would cover only a minority of patients. Developing methods to assign risk to individual patients without prior SCD events could promote the use of this life-saving therapy in those with especially high risk. Given sufficient physiologically relevant measurements from electrocardiogram analysis, clinical assessment, and demographic status, multivariate statistical methods for predicting survival can be used to combine many predictors of risk and calculate the risk for an individual patient. A survival analysis using Cox regression on data from the Cardiac Arrhythmia Suppression Trial (CAST) illustrates this concept. Patient age, sex, ejection fraction, smoking history, and prior myocardial infarction history, along with the frequency of premature beats and the presence of runs of ventricular tachycardia on Holter monitoring and the time from the index myocardial infarction to the baseline Holter and to recruitment into CAST were combined in a multivariate predictor derived from the Cox regression; this predictor significantly outperforms the individual predictors. A proposed test based on this predictor would identify as positive 7% of the CAST registry, with an average, risk of death among the positives of 47%; 20% of those dead at 2 years would be positive. With improved component measurements, this approach has the potential for significantly improving risk stratification for the prevention of SCD. C1 Univ Minnesota, Sch Publ Hlth, Div Environm & Occupat Med, Minneapolis, MN 55455 USA. Minneapolis Heart Inst Fdn, Res Grp, Minneapolis, MN USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Church, TR (reprint author), Univ Minnesota, Sch Publ Hlth, Div Environm & Occupat Med, MMC 807,420 Delaware St SE, Minneapolis, MN 55455 USA. OI Church, Timothy R./0000-0003-3292-5035 NR 24 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 2002 VL 35 SU S BP 117 EP 122 DI 10.1054/jelc.2002.37168 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DD UT WOS:000180263200017 PM 12539108 ER PT J AU Faris, O Leclercq, C Kato, R Evans, F Halperin, H Kass, D McVeigh, EV AF Faris, O Leclercq, C Kato, R Evans, F Halperin, H Kass, D McVeigh, EV TI Assessment of electrical and mechanical function in the paced LBBB failing heart using tagged MRI and epicardial mapping SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 27th Annual ISCE Conference on Research and Technology Transfer in Computerized Electrocardiology CY APR 20-25, 2002 CL DOORWERTH, NETHERLANDS SP ISCE C1 Johns Hopkins Univ, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. RP Faris, O (reprint author), Johns Hopkins Univ, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 2002 VL 35 SU S BP 205 EP 205 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DD UT WOS:000180263200030 ER PT J AU Tokumasu, F Jin, AJ Dvorak, JA AF Tokumasu, F Jin, AJ Dvorak, JA TI Lipid membrane phase behaviour elucidated in real time by controlled environment atomic force microscopy SO JOURNAL OF ELECTRON MICROSCOPY LA English DT Article DE atomic force microscopy; membrane; phase transition; mean-field theory; 1,2-dimyristoyl-sn-glycero-3-phosphocholine; thermodynamics ID MODEL; TRANSITION; SURFACE; RAFTS; PHOSPHOLIPIDS; POLYMORPHISM; ERYTHROCYTES; BILAYER AB Lipids are integral components of all biological membranes. Understanding the physical and chemical properties of these lipids is critical to our understanding of membrane functions. We developed a new atomic force microscope (AFM) approach to visualize in real time the temperature-induced lipid phase transition and domain separation processes in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membranes and estimate the thermodynamics of the phase transition process. The gel and liquid crystalline phases of DMPC coexisted over a broad temperature range (similar to10degreesC). Equal partitioning into two phases occurred at a transition temperature (T,) of 28.5degreesC. We developed a mathematical model to analyse AFM-derived DMPC membrane height changes as multi-peak Gaussian distributions. This approach allowed us to estimate the DMPC domain size, N, as 18-75 molecules per leaflet corresponding to a similar to4.2 nm diameter circular nano-domain. Lipid nanodomains may organize into microdomains or rafts which, in concert with proteins and other lipid components, play an important dynamic role in many biomedically important processes. C1 NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. Natl Inst Hlth, ORS OD, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Dvorak, JA (reprint author), NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. OI Tokumasu, Fuyuki/0000-0003-2790-1071; Jin, Albert/0000-0003-3826-1081 NR 35 TC 71 Z9 72 U1 0 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-0744 J9 J ELECTRON MICROSC JI J. Electron Microsc. PY 2002 VL 51 IS 1 BP 1 EP 9 DI 10.1093/jmicro/51.1.1 PG 9 WC Microscopy SC Microscopy GA 532RM UT WOS:000174488900001 PM 12003236 ER PT J AU Burroughs, KD Howe, SR Okubo, Y Fuchs-Young, R LeRoith, D Walker, CL AF Burroughs, KD Howe, SR Okubo, Y Fuchs-Young, R LeRoith, D Walker, CL TI Dysregulation of IGF-I signaling in uterine leiomyoma SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; ESTROGEN-RECEPTOR MODULATORS; AGING FEMALE RATS; INSULIN-LIKE; GENE-EXPRESSION; HUMAN MYOMETRIUM; RIBONUCLEIC-ACID; HORMONE AGONIST; MENSTRUAL-CYCLE; GONADOTROPIN AB IGF-I expression has been observed in human uterine leiomyomas. To examine whether autocrine IGF-I signaling plays a role in the growth of these tumors, we used an animal model of uterine leiomyonia (the Eker rat) to investigate regulation of IGF-I and the IGF-I receptor (IGF-IR) expression in tumors and normal myometrium. During the normal estrous cycle, myometrial IGF-I expression peaked on the day of proestrus when the rate of proliferation in this tissue is, greatest. In leiomyomas, the expression of IGF-I was increased 7.5-fold compared with the age-matched normal tissue. The level of IGF-IR mRNA in both tumor and non-tumor tissues was found to inversely correlate with that of IGF-I. Changes observed in IGF-I signaling components correlated with the activation state of the signal-transducing protein insulin receptor substrate-1 (IRS-1). During diestrus and proestrus when IGF-I levels were increasing, tyrosine phosphorylation of IRS-1 was increased Lip to 5-7-fold in the normal myometrium relative to estrus, when IGF-I levels were the lowest. Additionally, IRS-1 phosphorylation was 4-fold greater in leiomyomas relative to age- matched normal myometrium. Autocrine stimulation of the IGF-IR may, therefore, play a role in regulating the normal growth of the myometrium, and dysregulation of IGF-I signaling could contribute to the neoplastic growth of uterine leiomyomas. C1 Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Sci Pk Res, Smithville, TX 78957 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Walker, CL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Sci Pk Res, POB 389, Smithville, TX 78957 USA. FU NCI NIH HHS [CA16672, CA72253]; NIEHS NIH HHS [ES07784, ES08263] NR 34 TC 34 Z9 38 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JAN PY 2002 VL 172 IS 1 BP 83 EP 93 DI 10.1677/joe.0.1720083 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 514ZP UT WOS:000173471200007 PM 11786376 ER PT J AU Reynolds, K Novosad, B Hoffhines, A Gipson, J Johnson, J Peters, J Gonzalez, F Gimble, J Hill, M AF Reynolds, K Novosad, B Hoffhines, A Gipson, J Johnson, J Peters, J Gonzalez, F Gimble, J Hill, M TI Pretreatment with troglitazone decreases lethality during endotoxemia in mice SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACTIVATED RECEPTOR-GAMMA; NITRIC-OXIDE SYNTHASE; FACTOR-ALPHA; SEPTIC SHOCK; MONOCLONAL-ANTIBODIES; PPAR-GAMMA; PHOSPHOENOLPYRUVATE CARBOXYKINASE; INSULIN-RESISTANCE; LIPID-METABOLISM AB Troglitazone is an oral antidiabetic drug that is a ligand for peroxisome proliferator activated receptor gamma (PPARgamma). Based on other studies that have implicated an immunosuppressive role for PPARgamma during inflammatory responses, we hypothesized that troglitazone treatment would improve survival in a murine model of endotoxemia and that the protective effect would be mediated by decreased expression of inflammatory mediators. C57B1/6N x Sv/129 (wild-type [WT]) or PPARalpha null mice treated for 2 weeks with dietary troglitazone (0.1%) had significantly fewer deaths and a higher LD50 value compared to control-fed mice when challenged with lipopolysaccharide (LPS). PPARalpha null mice were more sensitive to the lethal effects of LPS as evidenced by a 2-fold lower LD50 (6.6 mg/kg) compared to WT mice (14.6 mg/kg). Troglitazone treatment had no significant effect on LPS-induced plasma TNF, glucose, or nitric oxide levels in WT or PPARalpha null mice at any of the time points examined. However, troglitazone treatment significantly reduced LPS-induced plasma IL-6 levels in both WT and PPARalpha null mice. The results of these studies suggest that troglitazone treatment protects mice against a lethal challenge of LPS, but whether or not this effect is mediated through decreased expression of inflammatory mediators remains unclear. C1 Oklahoma Christian Univ, Dept Nat Sci, Oklahoma City, OK 73190 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Radiol Technol, Oklahoma City, OK USA. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Artecell Inc, Tissue Engn Program, Durham, NC USA. RP Hill, M (reprint author), Oklahoma Christian Univ, Dept Nat Sci, Oklahoma City, OK 73190 USA. RI Peters, Jeffrey/D-8847-2011 NR 46 TC 15 Z9 16 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 2002 VL 8 IS 4 BP 307 EP 314 DI 10.1179/096805102125000515 PG 8 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 598UF UT WOS:000178294300007 PM 12230920 ER PT J AU Simon, SL Graham, JC Terp, SD AF Simon, SL Graham, JC Terp, SD TI Uptake of K-40 and Cs-137 in native plants of the Marshall Islands SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY LA English DT Article DE cesium-137; soil; vegetation; K-40; concentration ratio ID SOIL CHARACTERISTICS; CONCENTRATION RATIOS; RADIOCESIUM; LINEARITY; SYSTEMS AB Uptake of Cs-137 and K-40 was studied in seven native plant species of the Marshall Islands. Plant and soil samples were obtained across a broad range of Soil Cs-137 concentrations (0.083900 Bq/kg) and a narrower range of K-40 soil concentrations (2.3-55 Bq/kg). but with no systematic variation of K-40 relative to Cs-137. Potassium-40 concentrations in plants varied little within the range of K-40 soil concentrations observed. Unlike the case for K-40, Cs-137 concentrations increased in plants with increasing Cs-137 Soil concentrations though not precisely in a proportionate manner. The best-fit relationship between soil and plant concentrations was P = aS(b) where a and b are regression coefficients and P and S are plant and soil concentrations, respectively. The exponent b for K-40 was zero, implying plant concentrations were a single value, while b for Cs-137 varied between 0.51 and 0.82, depending on the species. For both K-40 and Cs-137, we observed a decreasing concentration ratio (where concentration ratio = plant concentration/soil concentration) with increasing soil concentrations. For the CR values, the best-fit relationship was of the form CR = aS(b)/S = aS(b-1). For the K-40 CR functions, the exponent b - 1 was close to -1 for all species. For the Cs-137 CR functions, the exponent b - 1 varied from -0.19 to -0.48. The findings presented here, as well as those by other investigators, collectively argue against the usefulness of simplistic ratio models to accurately predict uptake of either K-40 or Cs-137 in plants over wide ranges of soil concentration. Published by Elsevier Science Ltd. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Colorado State Univ, Environm Hlth Serv, Ft Collins, CO 80523 USA. Los Alamos Natl Lab, Air Qual Grp, Los Alamos, NM USA. Marshall Isl Nationwide Radiol Study, Majuro, Marshall Island. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC-7238,Execut Plaza S, Bethesda, MD 20892 USA. NR 35 TC 11 Z9 13 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0265-931X J9 J ENVIRON RADIOACTIV JI J. Environ. Radioact. PY 2002 VL 59 IS 2 BP 223 EP 243 AR PII S0265-931X(01)00138-2 DI 10.1016/S0265-931X(01)00138-2 PG 21 WC Environmental Sciences SC Environmental Sciences & Ecology GA 522NF UT WOS:000173902900008 PM 11900208 ER PT J AU Makhnovskii, YA Berezhkovskii, AM Grigor'ev, IV AF Makhnovskii, YA Berezhkovskii, AM Grigor'ev, IV TI Kinetics of Brownian particle trapping by randomly distributed traps of various sizes SO JOURNAL OF EXPERIMENTAL AND THEORETICAL PHYSICS LA English DT Article ID DIFFUSION-CONTROLLED REACTIONS; WIENER SAUSAGE; SINKS AB Diffusion of a particle in a medium in the presence of absorbing traps of various size is considered. A theory describing the kinetics of particle trapping in the entire interval of time is suggested. Analytical relations for the probability of a particle survival in situations when many-body effects are weak and when they dominate are obtained. It is shown that polydispersity of traps leads to the slowdown of particle trapping and to attenuation of many-body effects inherent in the problem. (C) 2002 MAIK "Nauka / Interperiodica". C1 Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Moscow 117912, Russia. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Makhnovskii, YA (reprint author), Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Leninskii Pr 29, Moscow 117912, Russia. RI Makhnovskii, Yurii/B-1223-2014 OI Makhnovskii, Yurii/0000-0002-1517-536X NR 31 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1063-7761 J9 J EXP THEOR PHYS+ JI J. Exp. Theor. Phys. PY 2002 VL 94 IS 2 BP 403 EP 410 DI 10.1134/1.1458491 PG 8 WC Physics, Multidisciplinary SC Physics GA 528DR UT WOS:000174229600023 ER PT J AU Toso, JF Lapointe, R Hwu, P AF Toso, JF Lapointe, R Hwu, P TI CD40 ligand and lipopolysaccharide enhance the in vitro generation of melanoma-reactive T-cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE melanoma-reactive T cells; CD40 ligand; lipopolysaccharide ID IN-VITRO; DENDRITIC CELLS; CANCER VACCINES; PEPTIDE; LYMPHOCYTES; IMMUNITY; BLOOD; FREQUENCIES; INDIVIDUALS; REGRESSION AB Cancer vaccine trials require sensitive assays for evaluating T-cell responses in immunized patients. In addition, these methods are used for identifying novel tumor-associated antigens (TAA). Therefore, our aim was to improve the methods for evaluating patients receiving the cancer vaccines by enhancing the in vitro detection of tumor-specific T cells from the peripheral blood. We have developed an efficient and reproducible method for detecting tumor-specific T cells by optimizing the activation of antigen presenting cells (APC) in peripheral blood mononuclear cells (PBMC) of metastatic melanoma patients with soluble trimeric CD40-ligand (CD40L) or lipopolysaccharide (LPS). This method significantly improved the,generation of Melan-A/MART-1:27-35 and Melan-A/MART-1:26-35(27L) peptide/tumor-specific cells as well as lower frequency tyrosinase:368-376(370D) specific T cells from the PBMC of melanoma patients. T-cell enhancement from activated PBMC cultures was found to be reproducible within individual patients and was observed after the addition of either CD40L or LPS to PBMC cultures. Additionally, PBMC activation improved the detection of tumor-specific precursors from melanoma patients previously immunized with peptides derived from Melan-A/MART-1, tyrosinase and gp100. Collectively, these findings describe a novel approach for evaluating patients receiving the cancer vaccines and may provide a useful method for the characterization of novel tumor-associated antigens. Published by Elsevier Science B.V. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Hwu, P (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. NR 24 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 1 PY 2002 VL 259 IS 1-2 BP 181 EP 190 DI 10.1016/S0022-1759(01)00513-0 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 507XT UT WOS:000173057100018 PM 11730853 ER PT J AU Segal, BM Glass, DD Shevach, EM AF Segal, BM Glass, DD Shevach, EM TI Cutting edge: IL-10-producing CD4(+) T cells mediate tumor rejection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-I; IMMUNE-RESPONSES; KILLER-CELL; IFN-GAMMA; INTERLEUKIN-10; IL-10; MICE; METASTASIS; ANTIGEN; PROLIFERATION AB IL-10 has potent immunosuppressive properties, and IL-10-producing CD4(+) Tr1 cells have been characterized as regulators of Th1-mediated immunity. In this study, using a s.c. model of glioma cell growth in mice, we demonstrate that CD4(+), but not CD8(+), T cells play a critical role in tumor rejection following vaccination with irradiated glioma cells. Surprisingly, glioma-specific CD4(+) T cells produce IL-10 but neither IL-4 nor IFN-gamma, and glioma rejection is compromised in IL-10(-/-) hosts. Hence, our findings demonstrate that IL-10-producing CD4(+) T cells can manifest antitumor functions and suggest that IL-10 may have proinflammatory effects in disease states. C1 Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Ctr Canc, Rochester, NY 14642 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Segal, BM (reprint author), Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. OI Segal, Benjamin/0000-0002-0906-6319 NR 33 TC 72 Z9 77 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 2002 VL 168 IS 1 BP 1 EP 4 PG 4 WC Immunology SC Immunology GA 505UM UT WOS:000172934000001 PM 11751938 ER PT J AU Uehara, S Song, KM Farber, JM Love, PE AF Uehara, S Song, KM Farber, JM Love, PE TI Characterization of CCR9 expression and CCL25/thymus-expressed chemokine responsiveness during T cell development: CD3(high) CD69(+) thymocytes and gamma delta TCR+ thymocytes preferentially respond to CCL25 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTESTINAL-MUCOSA; RECEPTOR CCR9; CUTTING EDGE; THYMUS; LYMPHOCYTES; TECK; MICE; DIFFERENTIATION; IDENTIFICATION; MATURATION AB CCR9 mediates chemotaxis of thymocytes in response to CCL25/thymus-expressed chemokine, and its mRNA is selectively expressed in thymus and small intestine, the two known sites of T lymphopoiesis. To examine the expression of CCR9 during lymphocyte development, we generated polyclonal Ab that recognizes murine CCR9. CCR9 was expressed on the majority of immature CD4(+)CD8(+) (double-positive) thymocytes, but not on immature CD4(-)CD8(-) (double-negative) thymocytes. CCR9 was down-regulated during the transition of double-positive thymocytes to the CD4(+) or CD8(+) (single-positive) stage, and only a minor subset of CD8(+) lymph node T cells expressed CCR9. All CCR9(+) thymocyte subsets migrated in response to CCL25; however, CD69(+) thymocytes demonstrated enhanced CCL25-induced migration compared with CD69- thymocytes. Ab-mediated TCR stimulation also enhanced CCL25 responsiveness, indicating that CCL25-induced thymocyte migration is augmented by TCR signaling. Approximately one-half or all gamma delta TCR+ thymocytes and peripheral gamma delta TCR+ T cells expressed CCR9 on their surface, and these cells migrated in response to CCL25. These findings suggest that CCR9 may play an important role in the development and trafficking of both alpha beta TCR+ and gamma delta TCR+ T cells. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, 9000 Rockville Pike,Bldg 6B,Room 2B210,MSC 2780, Bethesda, MD 20892 USA. NR 32 TC 66 Z9 70 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2002 VL 168 IS 1 BP 134 EP 142 PG 9 WC Immunology SC Immunology GA 505UM UT WOS:000172934000019 PM 11751956 ER PT J AU Perez-Diez, A Spiess, PJ Restifo, NP Matzinger, P Marincola, FM AF Perez-Diez, A Spiess, PJ Restifo, NP Matzinger, P Marincola, FM TI Intensity of the vaccine-elicited immune response determines tumor clearance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IFN-GAMMA; METASTATIC MELANOMA; T-CELLS; INFILTRATING LYMPHOCYTES; PEPTIDE VACCINE; IN-VITRO; CANCER; ANTIGEN; EXPRESSION; REACTIVITY AB Tumor Ag-specific vaccines used for cancer immunotherapy can generate specific CD8 responses detectable in PBMCs and in tumor-infiltrating lymphocytes. However, human studies have shown that detection of a systemic vaccine-induced response does not necessarily correlate with the occasional instances of tumor rejection. Because this discrepancy might partially be attributable to the genetic heterogeneity of human cancers, as well as to the immunosuppressive effects of previous treatments, we turned to a mouse model in which these variables could be controlled to determine whether a relationship exists between the strength of vaccine-induced immune responses and tumor rejection. We challenged mice with the beta -galactosidase (beta -gal)-expressing tumor cells, C25.F6, vaccinated them with beta -gal-carrying viral vectors, and used quantitative RT-PCR to measure the vaccine-induced immune response of splenocytes directly ex vivo. We found that the strength of the response increased with increasing doses of beta -gal-carrying vector and/or upon boosting with a heterologous beta -gal-carrying virus. Most importantly, we found that the strength of the detected immune response against this foreign Ag strongly correlated with reduction in the number of lung metastases. The results from this mouse model have major implications for the implementation of tumor vaccines in humans. C1 NIAID, Cellular & Mol Immunol Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Room 2B42 10,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 39 TC 64 Z9 65 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 2002 VL 168 IS 1 BP 338 EP 347 PG 10 WC Immunology SC Immunology GA 505UM UT WOS:000172934000042 PM 11751979 ER PT J AU Cui, YH Le, YY Gong, WH Proost, P Van Damme, J Murphy, WJ Wang, JM AF Cui, YH Le, YY Gong, WH Proost, P Van Damme, J Murphy, WJ Wang, JM TI Bacterial lipopolysaccharide selectively up-regulates the function of the chemotactic peptide receptor formyl peptide receptor 2 in murine microglial cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID N-FORMYLPEPTIDE RECEPTOR; SERUM AMYLOID-A; CHEMOKINE RECEPTORS; HUMAN MONOCYTES; G-PROTEIN; EXPRESSION; ACTIVATION; ENDOTOXIN; NEUTROPHILS; CCR2 AB Receptors for the bacterial chemotactic peptide fMLP are implicated in inflammation and host defense against microbial infection. We investigated the expression and function of fMLPR in microglial cells, which share characteristics of mononuclear phagocytes and play an important role in proinflammatory responses in the CNS. The expression of the genes encoding formyl peptide receptor (FPR)1 and FPR2, the high- and low-affinity fMLPR, was detected in a murine microglial cell line N9, but these cells did not respond to chemotactic agonists known for these receptors. N9 cells incubated with bacterial LPS increased the expression of fMLPR genes and developed a species of specific, but low-affinity, binding sites for fMLP, in association with marked calcium mobilization and chemotaxis responses to fMLP in a concentration range that typically activated the low-affinity receptor FPR2. In addition, LPS-treated N9 cells were chemoattracted by two FPR2-specific agonists, the HIV-1 envelope-derived V3 peptide, and the 42 aa form of the amyloid beta peptide which is a pathogenic agent in Alzheimer's disease. Primary murine microglial cells also expressed FPR1 and FPR2 genes, but similar to N9 cells, exhibited FPR2-mediated activation only after LPS treatment. In contrast to its effect on the function of FPR2, LPS reduced N9 cell binding and biological responses to the chemokine stromal cell-derived factor-1 alpha. Thus. LPS selectively modulates the function of chemoattractant receptors in microglia and may promote host response in inflammatory diseases in the CNS. C1 NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. Univ Louvain, Rega Inst, Louvain, Belgium. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Div Basic Sci, Bldg 560,Room 31-40, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 42 TC 66 Z9 70 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2002 VL 168 IS 1 BP 434 EP 442 PG 9 WC Immunology SC Immunology GA 505UM UT WOS:000172934000053 PM 11751990 ER PT J AU Thurber, SE Khong, HT Kammula, US Rosenberg, SA AF Thurber, SE Khong, HT Kammula, US Rosenberg, SA TI Identification of endogenous HLA-A2-restricted reactivity against shared melanoma antigens in patients using the quantitative real-time polymerase chain reaction SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma antigens; histocompability leukocyte antigen immunotherapy; quantitativereal-time polymerase chain reaction ID METASTATIC MELANOMA; PERIPHERAL-BLOOD; CANCER; CELLS; INTERLEUKIN-2 AB This study was conducted to determine whether reactivity to melanoma cells of pretreatment peripheral blood mononuclear cells (PBMCs) from patients with metastatic melanoma correlated with subsequent response to treatment with interleukin-2 (IL-2). The sensitivity of the quantitative real-time polymerase chain reaction (PCR) assay was optimized, including the total number of cells used (3 x 10(6) in 1 mL), the responder-to-stimulator cell ratio (5:1), the optimal time to incubate PBMCs with tumor (2 h), the appropriate tumor stimulators (melanoma cell lines differing only in the expression of histocompatibility leukocyte antigen [HLA-A2]), the duration of recovery in the culture of PBMCs after cryopreservation (18-24 h), and the medium used (Iscove, 10% human AB serum). Using this optimized assay to detect HLA-A2-restricted antitumor reactivity in the pretreatment PBMCs from patients with melanoma, positive reactive responses were detected in 7 of 28 patients with an objective clinical response to IL-2 therapy compared with 6 of 21 positive reactive responses in nonresponding patients. None of 12 healthy donors were positive in this study. Thus, there was no significant difference in the reactivity of pretreatment PBMCs When responders were compared with nonresponders, although the melanoma patients had an increased incidence of response compared with healthy donors (p = 0.05). The PBMCs from I I of the 13 melanoma patients with pretreatment HLA-A2-restricted antimelanoma reactivity were tested against a panel of transfectants expressing known shared melanoma antigens. Anti-MART-1 reactivity was detected in the pretreatment PBMCs of three patients. It thus appears that some melanoma patients are immunologically primed to antigens expressed on the tumor surface, although the HLA-A2-restricted antimelanoma activity detected in this real-time PCR assay was not predictive of patients' responses to IL-2 therapy. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Thurber, SE (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 12 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN-FEB PY 2002 VL 25 IS 1 BP 63 EP 71 DI 10.1097/00002371-200201000-00007 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 509KK UT WOS:000173146800008 PM 11924911 ER PT J AU Guirguis, LM Yang, JC White, DE Steinberg, TM Liewehr, TJ Rosenberg, SA Schwartzentruber, DJ AF Guirguis, LM Yang, JC White, DE Steinberg, TM Liewehr, TJ Rosenberg, SA Schwartzentruber, DJ TI Safety and efficacy of high-dose interleukin-2 therapy in patients with brain metastases SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE interleukin-2; melanoma; brain metastases; safety ID RENAL-CELL CANCER; PROSPECTIVE RANDOMIZED TRIAL; CONSECUTIVE PATIENTS; BOLUS INTERLEUKIN-2; MELANOMA; IMMUNOTHERAPY AB The authors determined the safety and efficacy of recombinant high-dose interleukin-2 administration in patients with brain metastases. This retrospective review included 1,069 patients with metastatic melanoma or renal cell carcinoma who received high-dose interleukin-2 alone or in combination with other immunotherapy or chemotherapy from July 1985-July 2000. All patients were evaluated for both toxicity and response. Only the first exposure to interleukin-2 was considered. Parameters evaluated among the groups included toxicity profiles, reasons for stopping treatment, number of interleukin-2 doses per cycle, and response to therapy. Three patient groups were compared. Group I (n = 27) comprised patients with previously treated brain metastases (surgery or radiation), group 2 (n = 37) comprised patients with untreated brain metastases, and group 3 (n = 1,005) comprised patients without brain metastases. For most comparisons between patients with brain metastases and those without, no significant differences were noted in toxicity profiles or reasons for stopping interleukin-2 therapy. Patients with previously treated brain metastases received fewer interleukin-2 doses per cycle (median, 6.5) than patients with previously untreated brain metastases (median, 7.5) or patients without brain metastases (median, 7.5). Patients with previously treated brain metastases demonstrated an 18.5% overall clinical response to interleukin-2 treatment. However, patients with evaluable (previously untreated) brain metastases had an overall 5.6% response rate, which was less than the 19.8% response rate of patients without brain metastases. Two of thirty-six patients with evaluable brain metastases demonstrated objective regression of intracranial and extracranial disease after receiving interleukin-2. Carefully selected patients with brain metastases can safely receive high-dose interleukin-2, and some can experience a response to treatment at intracranial and extracranial disease sites. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Schwartzentruber, DJ (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B06,10 Ctr Dr, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 14 TC 48 Z9 51 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN-FEB PY 2002 VL 25 IS 1 BP 82 EP 87 DI 10.1097/00002371-200201000-00009 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 509KK UT WOS:000173146800010 PM 11924913 ER PT J AU Dybul, M Hidalgo, B Chun, TW Belson, M Migueles, SA Justement, JS Herpin, B Perry, C Hallahan, CW Davey, RT Metcalf, JA Connors, M Fauci, AS AF Dybul, M Hidalgo, B Chun, TW Belson, M Migueles, SA Justement, JS Herpin, B Perry, C Hallahan, CW Davey, RT Metcalf, JA Connors, M Fauci, AS TI Pilot study of the effects of intermittent interleukin-2 on human immunodeficiency virus (HIV)-specific immune responses in patients treated during recently acquired HIV infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; PNEUMOCYSTIS-CARINII PNEUMONIA; CYTOTOXIC T-LYMPHOCYTE; ANTICYTOMEGALOVIRUS THERAPY; INTRAVENOUS INTERLEUKIN-2; PROLIFERATIVE RESPONSES; CELL RECONSTITUTION; INTERFERON-GAMMA; VIRAL-LOAD; CD4 CELLS AB Highly active antiretroviral therapy (HAART) initiated during acute human immunodeficiency virus (HIV) infection may preserve HIV-specific CD4(+) T cell responses that are thought to enhance HIV-specific CD8(+) T cell function. The present pilot study was designed to determine whether preserved HIV-specific immune responses are augmented by the administration of the immunomodulatory agent interleukin (IL)-2. Nine persons recently (<6 months) infected with HIV were randomized to receive HAART alone or HAART plus 3 cycles of intermittent IL-2 during a 12-month period. Although HAART plus IL-2 significantly increased counts of total and naive CD4(+) T cells, compared with HAART alone, there was no increase in CD4(+) or CD8(+) HIV-specific immune responses. In addition, adjuvant IL-2 therapy did not reduce the pool of HIV-infected resting CD4(+) T cells. Thus, although intermittent IL-2 plus HAART quantitatively increased CD4(+) T cells, this increase was not selective for HIV-specific CD4(+) or CD8(+) T cell responses in recently infected persons. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Dybul, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,room 11N204, Bethesda, MD 20892 USA. NR 41 TC 58 Z9 59 U1 3 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 2002 VL 185 IS 1 BP 61 EP 68 DI 10.1086/338123 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 502AZ UT WOS:000172722600008 PM 11756982 ER PT J AU Tamura, T Ozato, K AF Tamura, T Ozato, K TI ICSBP/IRF-8: Its regulatory roles in the development of myeloid cells SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Review ID SEQUENCE-BINDING-PROTEIN; MURINE PERITONEAL-MACROPHAGES; TRANSCRIPTION FACTOR; FACTOR FAMILY; IFN-GAMMA; GP91(PHOX) EXPRESSION; CHICKEN INTERFERON; IMMUNE-RESPONSES; ICSBP GENE; IN-VIVO AB Interferon (IFN) consensus sequence binding protein (ICSBP)/IFN regulatory factor (IRF)-8 is an IFNgamma-inducible transcription factor of the IRF family and regulates transcription through multiple target DNA elements, such as IFN-stimulated response element (ISRE), Ets/IRF composite element, and IFN-gamma activation site (GAS). ICSBP-/- mice are immunodeficient and susceptible to various pathogens. They have defects in the macrophage function, including the ability to induce interleukin-12 (IL-12) p40 and some IFN-gamma-responsible genes. In addition, ICSBP-/- mice develop a chronic myelogenous leukemia (CML)-like syndrome, where a systemic expansion of granulocytes is followed by a fatal blast crisis. ICSBP-/- mice harbor an increased number of myeloid progenitor cells, and the -/- progenitors preferentially give rise to granulocytes, although they cannot efficiently generate another descendant of the myeloid lineage, macrophages. Studies with myeloid progenitor cells have shown that ICSBP drives their differentiation toward macrophage, whereas it inhibits granulocyte differentiation. Furthermore, myeloid cells from ICSBP-/- mice are resistant to apoptosis. These results illustrate the mechanism by which the loss of ICSBP leads to immunodeficiency and CML-like syndrome and suggest ICSBP's critical role in the development of myeloid cells. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Tamura, T (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Room 416,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 65 TC 126 Z9 129 U1 0 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JAN PY 2002 VL 22 IS 1 BP 145 EP 152 DI 10.1089/107999002753452755 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 521CP UT WOS:000173821500017 PM 11846985 ER PT J AU Jarnik, M de Viragh, PA Scharer, E Bundman, D Simon, MN Roop, DR Steven, AC AF Jarnik, M de Viragh, PA Scharer, E Bundman, D Simon, MN Roop, DR Steven, AC TI Quasi-normal cornified cell envelopes in loricrin knockout mice imply the existence of a loricrin backup system SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE epidermal keratinocytes; immunoelectron microscopy; scanning transmission electron microscopy; small proline-rich proteins; terminal differentiation ID CROSS-LINKED ENVELOPE; TRANSMISSION ELECTRON-MICROSCOPY; HUMAN EPIDERMAL-KERATINOCYTES; PROLINE-RICH PROTEIN-1; DIFFERENTIAL EXPRESSION; INVOLUCRIN GENE; EPITHELIA; BARRIER; PRECURSOR; TISSUES AB The cornified cell envelope, a lipoprotein layer that assembles at the surface of terminally differentiated keratinocytes, is a resilient structure on account of covalent crosslinking of its constituent proteins, principally loricrin, which accounts for up to 60%-80% of total protein. Despite the importance of the cell envelope as a protective barrier, knocking out the loricrin gene in mice results in only mild syndromes. We have investigated the epidermis and forestomach epithelium of these mice by electron microscopy. In both tissues, corneocytes have normal-looking cell envelopes, despite the absence of loricrin, which was confirmed by immunolabeling, and the absence of the distinctive loricrin-containing keratohyalin granules (L-granules). Isolated cell envelopes were normal in thickness (approximate to15 nm) and mass per unit area (approximate to7.3 kDa per nm(2)); however, metal shadowing revealed ail altered substructure on their cytoplasmic surface. Their amino acid compositions indicate altered protein compositions. Analysis of these data implies that the epidermal cell envelopes have elevated levels of the small proline-rich proteins, and cell envelopes of both kinds contain other protein(s) that, like loricrin, are rich in glycine and serine. These observations imply that, in the absence of loricrin, the mechanisms that govern cell envelope assembly function normally but employ different building-blocks. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bldg 50,Room 1517, Bethesda, MD 20892 USA. FU NCRR NIH HHS [P41-RR01777]; NIAMS NIH HHS [AR40240] NR 54 TC 26 Z9 28 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2002 VL 118 IS 1 BP 102 EP 109 DI 10.1046/j.0022-202x.2001.01661.x PG 8 WC Dermatology SC Dermatology GA 517BV UT WOS:000173592000014 PM 11851882 ER PT J AU McKee, MD Cecco, SA Niemela, JE Cormier, J Kim, CJ Steinberg, SM Rehak, NN Elin, RJ Rosenberg, SA AF McKee, MD Cecco, SA Niemela, JE Cormier, J Kim, CJ Steinberg, SM Rehak, NN Elin, RJ Rosenberg, SA TI Effects of interleukin 2 therapy on lymphocyte magnesium levels SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID RENAL-CELL CARCINOMA; ACTIVATED KILLER CELLS; RECOMBINANT INTERLEUKIN-2; MEDIATES ADHESION; DIVALENT-CATIONS; ADVANCED CANCER; IMMUNOTHERAPY; INTEGRIN; NEUTROPHILS; DEFICIENCY AB Interleukin 2 (IL-2) can cause partial or complete tumor regression in approximately 20% of patients with renal cell carcinoma. Among the many physiologic effects of IL-2, decreased serum levels of the divalent cations magnesium (Mg) and calcium have been demonstrated, with corresponding decreases in their urinary excretion. We investigated the effect of IL-2 on lymphocyte Mg levels among patients receiving three different dosing regimens. Twenty-eight patients with metastatic renal cell carcinoma were treated with high-dose intravenous, low-dose intravenous, or subcutaneous IL-2 therapy. Serum ionized Mg, urinary Mg, and peripheral blood mononuclear cell Mg levels were measured in samples from patients during treatment and compared with pretreatment levels. Serum Mg and ionized Mg levels decreased for all patients within 12 hours of treatment (P <.005) and remained low for the duration of therapy. Urinary Mg decreased in parallel with serum levels in all patients (P <.005). The peripheral blood mononuclear cell Mg content per cell increased within 24 hours of treatment (P <.005). The magnitude of these changes was similar during the first week of treatment for patients receiving intravenous or subcutaneous administration of IL-2. During IL-2 therapy, lymphocyte Mg increases coincident with serum Mg depletion. Mg availability may have functional implications for lymphocyte proliferation and integrin function. C1 NCI, Surg Branch, Clin Pathol & Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP McKee, MD (reprint author), Univ Chicago, Div Biol Sci, 5841 S Maryland Ave,MC 5094, Chicago, IL 60637 USA. OI Niemela, Julie/0000-0003-4197-3792 NR 47 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JAN PY 2002 VL 139 IS 1 BP 5 EP 12 DI 10.1067/mlc.2002.120361 PG 8 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 530ZE UT WOS:000174389100001 PM 11873239 ER PT J AU Yao, L Pike, SE Tosato, G AF Yao, L Pike, SE Tosato, G TI Laminin binding to the calreticulin fragment vasostatin regulates endothelial cell function SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE angiogenesis; extracellular matrix; laminin ID EXTRACELLULAR-MATRIX; GROWTH-FACTOR; MOLECULAR-BASIS; TUMOR-GROWTH; RECEPTOR; ANGIOGENESIS; EXPRESSION; ADHESION; INHIBITION; MODULATION AB Vasostatin, the 1-180 amino acids NH2 domain of calreticulin, inhibits endothelial cell proliferation, angiogenesis, and tumor growth, but the, mechanisms underlying these effects are unclear. We show that endothelial cells express the extracellular matrix protein laminin, including chains alpha5 and gamma1 and that vasostatin specifically binds to laminin. When added to endothelial cell cultures, vasostatin specifically inhibits endothelial cell attachment to laminin and by this mechanism, can reduce subsequent endothelial cell growth induced by basic fibroblast growth factor. As an angiogenesis inhibitor that specifically disrupts endothelial cell attachment to components of the extracellular matrix, vasostatin has a unique potential as a cancer therapeutic. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Yao, L (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 12N226,MSC 1907, Bethesda, MD 20892 USA. NR 41 TC 44 Z9 53 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2002 VL 71 IS 1 BP 47 EP 53 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 510CR UT WOS:000173191600005 PM 11781379 ER PT J AU Rosenberger, TA Oki, J Purdon, AD Rapoport, SI Murphy, EJ AF Rosenberger, TA Oki, J Purdon, AD Rapoport, SI Murphy, EJ TI Rapid synthesis and turnover of brain microsomal ether phospholipids in the adult rat SO JOURNAL OF LIPID RESEARCH LA English DT Article DE brain; plasmalogen; hexadecanol; autoradiography; myelin; half-life; synapses; synaptosome; peroxisome; microsome ID FATTY-ACID INCORPORATION; SIGNAL-TRANSDUCTION; PLASMALOGENS; METABOLISM; LIPIDS; ACYLTRANSFERASES; BIOSYNTHESIS; MECHANISM; SYNTHASE; ANALOG AB The rates of synthesis, turnover, and half-lives were determined for brain microsomal ether phospholipids in the awake adult unanesthetized rat. A multicompartmental kinetic model of phospholipid metabolism, based on known pathways of synthesis, was applied to data generated by a 5 min intravenous infusion of [1,1-H-3]hexadecanol. At 2 It post-infusion, 29%, 33%, and 31% of the total labeled brain phospholipid was found in the 1-O-alkyl-2-acyl-sn-glycero-3-phosphate, ethanolamine, and choline ether phospholipid fractions, respectively. Autoradiography and membrane fractionation showed that 3% of the net incorporated radiotracer was in myelin at 2 It, compared to 97% in gray matter microsomal and synaptosomal fractions. Based on evidence that ether phospholipid synthesis occurs in the microsomal membrane fraction, we calculated the synthesis rates of plasmanylcholine, plasmanylethanolamine, plasmenylethanolamine, and plasmenylcholine equal to 1.2, 9.3, 27.6, and 21.5 nmol . g(-1) . min(-1), respectively. Therefore, 8% of the total brain ether phospholipids have half-lives of about 36.5, 26.7, 23.1, and 15.1 min, respectively. Furthermore, we clearly demonstrate that there are at least two pools of ether phospholipids in the adult rat brain. One is the static myelin pool with a slow rate of tracer incorporation and the other is a dynamic pool found in gray matter. The short half-lives of microsomal ether phospholipids and the rapid transfer to synaptosomes are consistent with evidence of the marked involvement of these lipids in brain signal transduction and synaptic function. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rosenberger, TA (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Room 6N202, Bethesda, MD 20892 USA. NR 58 TC 41 Z9 44 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2002 VL 43 IS 1 BP 59 EP 68 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 516RY UT WOS:000173571600008 PM 11792723 ER PT J AU Boyer, JD Chattergoon, M Muthumani, K Kudchodkar, S Kim, J Bagarazzi, M Pavlakis, G Sekaly, R Weiner, DB AF Boyer, JD Chattergoon, M Muthumani, K Kudchodkar, S Kim, J Bagarazzi, M Pavlakis, G Sekaly, R Weiner, DB TI Next generation DNA vaccines for HIV-1 SO JOURNAL OF LIPOSOME RESEARCH LA English DT Article; Proceedings Paper CT 5th International Conference on Liposome Advances CY DEC 17-21, 2001 CL UNIV LONDON, SCH PHARMACY, LONDON, ENGLAND HO UNIV LONDON, SCH PHARMACY DE DNA vaccine; HIV-1; Cytokines; immune responses ID MEDIATED PROTECTIVE IMMUNITY; HERPES-SIMPLEX VIRUS-2; RHESUS-MONKEYS; IN-VIVO; VACCINATION; EXPRESSION; RESPONSES; PLASMID; GAG; IMMUNOGENICITY AB We studied the effects of first generation HIV-1 plasmid vaccines in 167 individuals. The vaccines were very well tolerated and induced helper T cell responses in most vaccine recipients. However, the CTL responses were below a 20% response rate. Improvement in vaccine potency is an important goal of this technology and a central focus of our laboratory. To improve on these response rates, we used RNA optimized constructs pGag and pEnv). These vaccines express 20-100 fold better than first generation vectors. However, our studies support that additional enhancements are needed to further boost the immune response. We report that we can significantly enhance the induced CD8 effector cell response by including engineered 137 costimulatory molecules. We observed that B7.2 was more effective at driving cellular immune responses than B7.1 as a plasmid vaccine. We developed gene swaps and deletions between these two molecules. This manipulation resulted in a dramatically enhanced cellular immune response as measured by CTL, or ICC or Elispot. We have also explored the use of cytokines as plasmid vaccine adjuvants. We observed that IL-12 and IL-15 were effective as plasmid vaccine adjuvants. Interestingly, IL-15 appeared to allow T cell expansion in the absence of significant T cell help. Improvement of the immune response induced by plasmid vaccines can be engineered in multiple ways. Our studies show that both costimulation as well as cytokine signals can be harnessed for more potent vaccine development. These results have important implications for the design of vaccines for prophylaxis and therapy. C1 Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Merck Vaccines, W Point, PA USA. Viral Genomix, Philadelphia, PA USA. NCI, Frederick, MD USA. Univ Montreal, Montreal, PQ, Canada. CANVAC, Montreal, PQ, Canada. RP Weiner, DB (reprint author), Univ Penn, Dept Pathol & Lab Med, 505 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA. RI Muthumani, Karuppiah/D-1092-2009; Weiner, David/H-8579-2014 NR 19 TC 12 Z9 16 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0898-2104 J9 J LIPOSOME RES JI J. Liposome Res. PY 2002 VL 12 IS 1-2 BP 137 EP 142 DI 10.1081/LPR-120004786 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 582NA UT WOS:000177357000017 PM 12604047 ER PT J AU Issaq, HJ AF Issaq, HJ TI Thirty-five years of capillary electrophoresis: Advances and perspectives SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID MICELLAR ELECTROKINETIC CHROMATOGRAPHY; PERFORMANCE LIQUID-CHROMATOGRAPHY; ELECTROOSMOTIC FLOW ENVIRONMENT; INDUCED FLUORESCENCE DETECTION; POLYMERASE-CHAIN-REACTION; DYNAMIC PH GRADIENT; ZONE-ELECTROPHORESIS; INFLUENCE MOBILITY; AMINO-ACIDS; MASS-SPECTROMETRY AB Since the publication by Hjerten of his study on free zone electrophoresis thirty-five years ago and the publication by Jorgenson and Lukacs of their study in 1981, CE instrumentation and applications have become widespread. CE today includes capillary zone electrophoresis, micellar electrokinetic chromatography, capillary gel electrophoresis, capillary isoelectric focusing, isotacophoresis, and capillary electrochromatography. Array capillary electrophoresis and array microchip separations are also important aspects of modem CE instrumentation. CE has become a versatile analytical technique, which is successfully used for the separation of small ions, neutral molecules, and large biomolecules and for the study of physicochemical parameters. It is being utilized in widely different fields, such as analytical, forensic, clinical, and organic chemistry, in addition to natural products, the pharmaceutical industry, chiral separations, molecular biology, and other fields. C1 NCI, Analyt Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, Analyt Chem Lab, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. NR 96 TC 23 Z9 25 U1 2 U2 12 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2002 VL 25 IS 8 BP 1153 EP 1170 DI 10.1081/JLC-120004015 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 568MR UT WOS:000176546500001 ER PT J AU Matsuda, K Matsuda, S Saito, M Ito, Y AF Matsuda, K Matsuda, S Saito, M Ito, Y TI Separation of phospholipids and glycolipids using analytical toroidal-coil countercurrent chromatography. I. Separation of human brain lipids SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID SIGNAL-TRANSDUCTION; GLYCOSPHINGOLIPIDS; MICRODOMAINS; ADHESION; SPEED AB We demonstrated the separation of human brain lipids using the toroidal-coil countercurrent chromatography (TC-CCC). It became possible to select the suitable two-phase solvent systems, because retention of a stationary phase is much more stable in the TC-CCC than in high-speed countercurrent chromatography (HS-CCC). Optimizing the solvent systems, we succeeded in separating major brain lipids. The two-phase solvent of chloroform: methanol: water (5: 4: 3) was suitable for the separation of acidic phospholipids (phosphatidic acid, phosphatidylserine, phosphatidylinositol, lysophosphatidylinositol, and lysophosphatidylserine). Using hexane: ethylacetate: ethanol: 0.1% aqueous ammonia (5: 5: 5:4), neutral phospholipids (phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine) were separated. Non-polar lipids (cholesterol, alkali-labile glycoglycerolipids and cerebrosides) were separated using the solvent of hexane: ethanol: water (10 : 15: 4). Sphingomyelin (SPM), cerebrosides, and phosphatidylcholine are each reported to have more than 100 molecular species, which are derived from variations of the hydrophobic tail group in mammalian. For this reason, SPM was further separated into two groups (SPM-I and SPM-II). Cerebrosides were separated into several groups using hexane: ethanol: water (5: 4: 3). It was clearly shown that synthesized PC (distearoyl phosphatidylglycerol and dipalmitoyl phosphatidylglycerol) was completely separated. Phosphatidylserine and phosphatidic acid were also separated in some groups. Because the partition behavior of molecules in the two-phase solvent system can be measured, the TC-CCC could be useful not only for the separation but also for the biological analysis of mammalian cell-membrane lipids. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Natl Canc Ctr, Res Inst, Virol & Glycobiol Div, Chuo Ku, Tokyo 1040045, Japan. Kosei Gen Hosp, Dept Dermatol, Nakano Ku, Tokyo 1648617, Japan. RP Matsuda, K (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 27 TC 4 Z9 4 U1 0 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2002 VL 25 IS 8 BP 1255 EP 1269 DI 10.1081/JLC-120004023 PG 15 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 568MR UT WOS:000176546500008 ER PT J AU Ito, Y AF Ito, Y TI Centrifugal precipitation chromatography: Novel fractionation method for biopolymers, based on their solubility SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE centrifugal precipitation chromatography; solubility; purification; biopolymers; protein; recombinant enzyme; monoclonal antibody; polysaccharide; dextran ID AMMONIUM-SULFATE; PROTEINS; SEPARATION AB A recently developed chromatographic system called centrifugal precipitation chromatography is reviewed. The system internally generates a concentration gradient of precipitant, such as ammonium sulfate for protein separation, through a long separation channel under a centrifugal force field. Chromatographic elution is performed by gradually lowering the concentration of the precipitant in the gradient, so that the samples are subjected to a repetitive process of dissolution and precipitation along the channel, until they are finally eluted from the column according to their solubility. The separation column consists of a pair of disks equipped with mutually mirror-imaged spiral grooves. A dialysis membrane is sandwiched between these disks to form two identical channels partitioned by the membrane. The disk assembly is mounted on a seal-less continuous flow centrifuge. When a concentrated ammonium sulfate solution is eluted through one channel and water through the other channel in an opposite direction, an exponential gradient of ammonium sulfate is formed through the channel. A series of basic studies was conducted to measure mass transfer of ammonium sulfate and osmosis through the membrane, and the effects of various parameters on separation were investigated using a set of standard protein samples. Using an optimized set of conditions, various protein samples were separated, including serum proteins, monoclonal antibodies, recombinant enzyme, and PEG-protein conjugates. The method is extended to the separation of other biopolymers such as polysaccharides and polycatechin using a suitable organic solvent as a precipitant. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP NHLBI, Biophys Chem Lab, NIH, Bldg 10,Rm 3334,50 S Dr MSC 8014, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 18 TC 9 Z9 9 U1 2 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6076 EI 1520-572X J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2002 VL 25 IS 13-15 BP 2039 EP 2064 DI 10.1081/JLC-120013994 PG 26 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 596KE UT WOS:000178163400007 ER PT J AU Du, QZ Cai, WJ Ito, Y AF Du, QZ Cai, WJ Ito, Y TI Preparative separation of fruit extract of Silybum marianum using a high-speed countercurrent chromatograph with scale-up columns SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID SILYMARIN AB A crude extract (12 g) of fruits of Silybum marianum was separated with a two-phase solvent system composed of water/ methanol/ethyl acetate/n-hexane (4:3:4: 1, v/v/v/v) by high speed countercurrent chromatography. Using a set of three large multilayer coil separation columns with a total capacity of 2460 mL, the separation yielded 1.37 g of silycristin at 93.1% purity, 3.47 g of silybin at 95.7% purity, and 0.93 g of isosilybin at 89.7% purity. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Rm 3334,50 South Dr MSC 8014, Bethesda, MD 20892 USA. NR 9 TC 14 Z9 16 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2002 VL 25 IS 16 BP 2515 EP 2520 DI 10.1081/JLC-120014271 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 601XT UT WOS:000178474900009 ER PT J AU Shinomiya, K Kabasawa, Y Ito, Y AF Shinomiya, K Kabasawa, Y Ito, Y TI Protein separation by cross-axis coil planet centrifuge with spiral column assemblies SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID PERFORMING COUNTERCURRENT CHROMATOGRAPHY; PHASE DISTRIBUTION; STATIONARY-PHASE; ROTARY SEALS; ACCELERATION; EFFICIENCY; APPARATUS; RETENTION; SYSTEMS AB A newly fabricated spiral column assembly was first applied to the countercurrent chromatographic separation of proteins using the cross-axis coil planet centrifuge (cross-axis CPC). The separation was performed by a set of stable proteins such as cytochrome C, myoglobin, and lysozyme with an aqueous-aqueous polymer phase solvent system composed of 12.5% (w/w) polyethylene glycol (PEG) 1000-12.5% (w/w) dibasic potassium phosphate. Three sets of left-handed single-layer spiral columns with different IDs (1.0, 1.5, and 2.0 mm) were employed to investigate the effect of column ID on partition efficiency at four different elution modes. The elution modes consisted of the combinations of the direction of revolution (P-I = counterclockwise; P-II = clockwise), the head-tail elution mode (H = head to tail; T = tail to head), and the inward-outward elution mode (I inward; O = outward). Among these experiments, the best separation of proteins was attained using a 1.5 mm-ID column assembly with the P-I-H-O elution mode of the lower phase mobile. The resolution between cytochrome C and myoglobin peaks was 0.9 and between myoglobin and lysozyme peaks was 1.0, while the retention of the stationary phase was 32.7%. In order to improve the partition efficiency, the four-layer spiral column assembly with 1.0 mm-ID column tubing was applied to the protein separation. The resolution between these peaks was improved to 1.1 and 1.2, respectively, while the stationary phase retention decreased to 20.9%. Further studies using a single-layer spiral coiled column also revealed the effective peak resolution of proteins, but with lower stationary phase retention. The overall results demonstrated the spiral column assembly was useful for the protein separation using the cross-axis CPC with the aqueous-aqueous polymer phase system. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. NR 15 TC 13 Z9 15 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2002 VL 25 IS 17 BP 2665 EP 2678 DI 10.1081/JLC-120014383 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 601XV UT WOS:000178475200007 ER PT J AU Gosse, B Anatole, G Amissa, AA Ito, Y AF Gosse, B Anatole, G Amissa, AA Ito, Y TI Chemical analysis of the seed of the ripe fruit of Tieghemella heckelii SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB The seed of Tieghemella heckelii was analyzed by various chromatographic methods. The hexane extracts yielded nine fatty acids and sixteen steroid alcohols resolved by GC. These compounds are the main constituents of the solid substance of the hexane extract of the seed used in traditional environment for food and skin disorders. The water extract usually discarded in traditional use of the seed, was found to contain two triterpoid saponins with antiviral activity. Here, we report the isolation and chemical analysis of the hexane extract and water extract. C1 NIH, Biophys Chem Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Inst Natl Polytech, Dept Chim, Yamoussokro, Cote Ivoire. RP Ito, Y (reprint author), NIH, Biophys Chem Lab, Bldg 50,Room 3334,50 South Dr, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2002 VL 25 IS 18 BP 2873 EP 2882 DI 10.1081/JLC-120014956 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 608MF UT WOS:000178849600012 ER PT J AU Phillips, TM Smith, PD AF Phillips, TM Smith, PD TI Immunoaffinity analysis of substance P in complex biological fluids: Analysis of sub-microliter samples SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID ELECTROPHORESIS; CHROMATOGRAPHY; CYTOKINES; SYSTEMS AB There is a growing need for systems capable of measuring specific analytes in biological samples, especially complex biological fluids. Additionally, this need extends to applying such analyses to precious clinical or research samples, for many of which only micro quantities are still in existence. Immunoaffinity separations provide a useful approach to isolating specific analytes from complex matrices, as well as being capable of miniaturization. In the present communication, we have designed an immunoaffinity system capable of measuring a single analyte in 50 nL samples. We have chosen the clinically important neuropeptide, substance P (SP), as our model analyte and applied it to studying the ability of a micro-chromatography system to measure SP in a number of different biological matrices. The system capable of isolating SP from biological fluids, including cell cytosols, with reasonable efficiency anti reproducibility. The incorporation of laser induced fluorescence detection enabled the system to achieve a lower limit of detection around 500 femtograms/mL and could isolate the specific analyte in under 5 min, thus, making it potentially used for high throughput clinical series. C1 NIH, Div Bioengn & Phys Sci, Off Res Serv, Off Director, Bethesda, MD 20892 USA. RP Phillips, TM (reprint author), NIH, Div Bioengn & Phys Sci, Off Res Serv, Off Director, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 10 Z9 10 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2002 VL 25 IS 19 BP 2889 EP 2900 DI 10.1081/JLC-120015881 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 625JU UT WOS:000179814000001 ER PT J AU Pajevic, S Aldroubi, A Basser, PJ AF Pajevic, S Aldroubi, A Basser, PJ TI A continuous tensor field approximation of discrete DT-MRI data for extracting microstructural and architectural features of tissue SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE MRI; MR; diffusion; DTI; DT-MRI; in vivo; tensor; field; interpolation; anisotropy; fiber; tractography; curvature ID DIFFUSION-TENSOR; HUMAN BRAIN; B-MATRIX; IMAGES; SPECTROSCOPY; PROJECTIONS; TRACKING; NOISE; ECHO AB The effective diffusion tensor of water, (D) under bar, measured by diffusion tensor MRI (DT-MRI), is inherently a discrete, noisy, voxel-averaged sample of an underlying macroscopic effective diffusion tensor field, (D) under bar (x). Within fibrous tissues this field is presumed to be continuous and smooth at a gross anatomical length scale. Here a new, general mathematical framework is proposed that uses measured DT-MRI data to produce a continuous approximation to (D) under bar (x). One essential finding is that the continuous tensor field representation can be constructed by repeatedly performing one-dimensional B-spline transforms of the DT-MRI data. The fidelity and noise-immunity of this approximation are tested using a set of synthetically generated tensor fields to which background noise is added via Monte Carlo methods. Generally, these tensor field templates are reproduced faithfully except at boundaries where diffusion properties change discontinuously or where the tensor field is not microscopically homogeneous. Away from such regions, the tensor field approximation does not introduce bias in useful DT-MRI parameters, such as Trace((D) under bar (x)). It also facilitates the calculation of several new parameters, particularly differential quantities obtained from the tensor of spatial gradients of (D) under bar (x). As an example, we show that they can identify tissue boundaries across which diffusion properties change rapidly using in vivo human brain data. One important application of this methodology is to improve the reliability and robustness of DT-MRI fiber tractography. (C) 2002 Elsevier Science. C1 NICHHD, STBB, NIH, Bethesda, MD 20892 USA. NICHHD, MSCL, CIT, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Math, Nashville, TN 37203 USA. RP Basser, PJ (reprint author), NICHHD, STBB, NIH, Bldg 13,Room 3W16,13 South Dr, Bethesda, MD 20892 USA. RI Aldroubi, Akram/J-7186-2012; Basser, Peter/H-5477-2011 NR 40 TC 106 Z9 113 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2002 VL 154 IS 1 BP 85 EP 100 DI 10.1006/jmre.2001.2452 PG 16 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 518JH UT WOS:000173663900011 PM 11820830 ER PT J AU Ostuni, JL Richert, N Wisniewski, R Lewis, BK Howard, T Patel, J Frank, JA AF Ostuni, JL Richert, N Wisniewski, R Lewis, BK Howard, T Patel, J Frank, JA TI Comparison of methods for obtaining longitudinal whole-brain magnetization transfer measurements SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetization transfer ratio; multiple sclerosis; registration; interpolation; image mask; MTR histogram ID MULTIPLE-SCLEROSIS; TRANSFER RATIO; IMAGE REGISTRATION; DISEASE BURDEN; RESONANCE; MRI; MS AB Purpose: To investigate whether the method of applying image masks can alter quantifiable measures determined from whole-brain MTR calculations. Materials and Methods: Thirty-five T1/MT image pairs were obtained from five normal volunteers. For each pair a mask was used to specify the regions to be analyzed. Using these regions, a histogram was used to calculate seven global MTR metrics. This process was performed three ways: 1) using a unique mask for each T1/MT pair, 2) sharing a single mask for each subject and registering all intrasubject images to the image corresponding to their mask, and 3) sharing a single mask for each subject and transforming that mask into alignment with each of their original T1/MT image pairs, Results: With respect to the first method, the latter two methods caused small but significant differences in several parameters. Conclusion: The method of applying image masks can affect whole-brain MTR values. C1 NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Ostuni, JL (reprint author), NIH, Lab Diagnost Radiol Res, Room B1N256,Bldg 10,10 Ctr Dr MSC 1074, Bethesda, MD 20892 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JAN PY 2002 VL 15 IS 1 BP 8 EP 15 DI 10.1002/jmri.10040 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 537LF UT WOS:000174759400002 PM 11793451 ER PT J AU Hovey, RC Trott, JF Vonderhaar, BK AF Hovey, RC Trott, JF Vonderhaar, BK TI Establishing a framework for the functional mammary gland: From endocrinology to morphology SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Review DE ductal; hormones; growth factors; epithelial-stromal; morphogenesis ID EPIDERMAL GROWTH-FACTOR; NORMAL HUMAN-BREAST; HORMONE-RELATED PROTEIN; ATHYMIC NUDE-MICE; DEOXYRIBONUCLEIC-ACID SYNTHESIS; ESTROGEN-RECEPTOR-ALPHA; PROGESTERONE-RECEPTOR; MENSTRUAL-CYCLE; FAT PAD; DUCTAL MORPHOGENESIS AB From its embryonic origins, the mammary gland in females undergoes a course of ductal development that supports the establishment of alveolar structures during pregnancy prior to the onset of lactogenesis. This development includes multiple stages of proliferation and morphogenesis that are largely directed by concurrent alterations in key hormones and growth factors across various reproductive states. Ductal elongation is directed by estrogen, growth hormone, insulin-like growth factor-I, and epidermal growth factor, whereas ductal branching and alveolar budding is influenced by additional factors such as progesterone, prolactin, and thyroid hormone. The response by the ductal epithelium to various hormones and growth factors is influenced by epithelial-stromal interactions that differ between species, possibly directing species-specific morphogenesis. Evolving technologies continue to provide the opportunity to further delineate the regulation of ductal development. Defining the hormonal control of ductal development should facilitate a better understanding of the mechanisms underlying mammary gland tumorigenesis. C1 NCI, Mol & Cellular Endocrinol Sect, Basic Res Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Vonderhaar, BK (reprint author), NCI, Mol & Cellular Endocrinol Sect, Basic Res Lab, Ctr Canc Res,NIH, Bldg 10,Room 5B47,10 Ctr Dr, Bethesda, MD 20892 USA. NR 184 TC 164 Z9 166 U1 2 U2 14 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JAN PY 2002 VL 7 IS 1 BP 17 EP 38 AR UNSP PP475-372732 DI 10.1023/A:1015766322258 PG 22 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 557TL UT WOS:000175924200003 PM 12160083 ER PT J AU Haslam, SZ Osuch, JR Raafat, AM Hofseth, LJ AF Haslam, SZ Osuch, JR Raafat, AM Hofseth, LJ TI Postmenopausal hormone replacement therapy: Effects on normal mammary gland in humans and in a mouse postmenopausal model SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE menopause; hormone replacement therapy; estrogen; progestin; breast cancer ID BREAST-CANCER RISK; MAMMOGRAPHIC PARENCHYMAL PATTERNS; ESTROGEN-PROGESTIN-REPLACEMENT; ENDOMETRIAL CANCER; PLUS PROGESTIN; EPITHELIAL PROLIFERATION; MENOPAUSAL ESTROGEN; MENSTRUAL-CYCLE; WOMEN; DENSITY AB Endogenous estrogen exposure has long been implicated in the causation of breast cancer through a mechanism of epithelial cell proliferation. Whether estrogen, progesterone, or both exhibit mitogenic activity and promote carcinogenesis in the human breast has been the subject of considerable debate. The purpose of this review article is to examine the evidence for the effects of hormone replacement therapy in its various forms on the biology of the postmenopausal breast both in humans and in an animal model, and to identify the gaps in knowledge that research will need to address to further understand this complex issue. C1 Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Surg, E Lansing, MI 48824 USA. NCI, Lab Pathophysiol, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Haslam, SZ (reprint author), Michigan State Univ, Dept Physiol, 108 Giltner Hall, E Lansing, MI 48824 USA. FU NIA NIH HHS [AG13059] NR 78 TC 32 Z9 33 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JAN PY 2002 VL 7 IS 1 BP 93 EP 105 AR UNSP PP475-372737 DI 10.1023/A:1015726608146 PG 13 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 557TL UT WOS:000175924200008 PM 12160089 ER PT J AU Shinar, Y Ben-Zeev, B Brand, N Lahat, H Gross-Zur, V MacGregor, D Bahan, T Kastner, DL Pras, E AF Shinar, Y Ben-Zeev, B Brand, N Lahat, H Gross-Zur, V MacGregor, D Bahan, T Kastner, DL Pras, E TI A common ancestral haplotype in carrier chromosomes from different ethnic backgrounds in vacuolating megalencephalic leucoencephalopathy with subcortical cysts SO JOURNAL OF MEDICAL GENETICS LA English DT Letter ID MILD CLINICAL COURSE; LEUKOENCEPHALOPATHY; LEUKODYSTROPHY C1 Chaim Sheba Med Ctr, Danek Gartner Inst Human Genet, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Heller Inst Med Sci, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Paediat Neurol Unit, IL-52621 Tel Hashomer, Israel. Shearey Zedek Med Ctr, Paediat Neurol Unit, IL-81031 Jerusalem, Israel. Hosp Sick Children, Div Neurol, Toronto, ON M5G 1X8, Canada. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Pras, E (reprint author), Chaim Sheba Med Ctr, Danek Gartner Inst Human Genet, IL-52621 Tel Hashomer, Israel. NR 8 TC 3 Z9 3 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL 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 2002 VL 39 IS 1 BP 54 EP 57 DI 10.1136/jmg.39.1.54 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 511PG UT WOS:000173274300012 PM 11826027 ER PT J AU Christensen, PB Engle, RE Jacobsen, SEH Krarup, HB Georgsen, J Purcell, RH AF Christensen, PB Engle, RE Jacobsen, SEH Krarup, HB Georgsen, J Purcell, RH TI High prevalence of hepatitis E antibodies among Danish prisoners and drug users SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE hepatitis E antibodies; Danish; prisoners; injecting drug users ID E VIRUS; HEV INFECTION; SEROREACTIVITY; IDENTIFICATION; TRANSMISSION; CALIFORNIA; BIOLOGY; VARIANT; SWINE AB Injecting drug users and prisoners have high prevalences of antibodies to hepatitis A-C. The aim of this study was to determine the prevalence of antibodies to hepatitis E virus (anti-HEV) in two Danish high-risk populations and correlate anti-HEV with risk factors for transmission. Three hundred thirty male prisoners and 137 patients at a drug treatment center were tested for anti-HEV with an in-house enzyme-linked immunoassay (EIA) utilizing antigens derived from open reading frame 2 (ORF2). This was compared with a commercial test with antigens derived from ORF2 and ORF3 (Abbott HEV EIA). In addition the samples were tested for antibodies against hepatitis A-C viruses, human immunodeficiency virus (HIV) 1 and 2, human T lymphotropic virus (HTLV) I and II and herpes simplex virus type 2 (HSV2). The participants were interviewed about risk factors for transmission. The anti-HEV prevalence was 16.9% (95% Cl 14-21) for the inhouse assay compared to 4.1% (95% Cl 2.5-6.3) with the commercial assay. The correlation between the two assays was low (87% overall agreement; kappa value 0.32). One sample was strongly anti-HEV IgM positive, suggesting recent HEV infection inside Denmark. The presence of anti-HEV was associated significantly with anti-HAV among prisoners and increased with age in both groups. In contrast, associations were not found with injecting drug use or sexual risk factors. With the commercial assay an increased prevalence of anti-HEV was found among participants who had spent more than 5 years outside Northern Europe. In conclusion, anti-HEV was highly prevalent among Danish prisoners and drug users but not related to risk factors for blood-borne or sexual transmission. (C) 2002 Wiley-Liss, Inc. C1 Odense Univ Hosp, Dept Clin Immunol, DK-5000 Odense C, Denmark. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Sonderborg Sygehus, Dept Clin Immunol, Sonderborg, Denmark. Aalborg Hosp, Dept Clin Chem, Aalborg, Denmark. RP Christensen, PB (reprint author), Odense Univ Hosp, Dept Clin Immunol, Sdr Blvd 29, DK-5000 Odense C, Denmark. RI Christensen, Peer/B-8042-2015 NR 30 TC 34 Z9 34 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JAN PY 2002 VL 66 IS 1 BP 49 EP 55 DI 10.1002/jmv.2110 PG 7 WC Virology SC Virology GA 499FJ UT WOS:000172560100008 PM 11748658 ER PT J AU Zaharevitz, DW Holbeck, SL Bowerman, C Svetlik, PA AF Zaharevitz, DW Holbeck, SL Bowerman, C Svetlik, PA TI COMPARE: a web accessible tool for investigating mechanisms of cell growth inhibition SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE cell-based screening; correlation analysis; COMPARE; drug discovery; antitumor drugs ID GENE-EXPRESSION PATTERNS; ANTICANCER DRUG SCREEN; TOPOISOMERASE-II; LINES; IDENTIFICATION; CYTOTOXICITY; AZATOXIN; DEHYDROGENASE; KINASE AB For more than 10 years the National Cancer Institute (NCI) has tested compounds for their ability to inhibit the growth of human tumor cell lines in culture (NCI screen). Work of Ken Paull [J. Natl. Cancer Inst. 81 (1989) 1088] demonstrated that compounds with similar mechanism of cell growth inhibition show similar patterns of activity in the NCI screen. This observation was developed into an algorithm called COMPARE and has been successfully used to predict mechanisms for a wide variety of compounds. More recently, this method has been extended to associate patterns of cell growth inhibition by compounds with measurements of molecular entities (such as gene expression) in the cell lines in the NCI screen. The COMPARE method and associated data are freely available on the Developmental Therapeutics Program (DTP) web site (http://dtp.nei.nih.gov/). Examples of the use of COMPARE on these web pages will be explained and demonstrated. Published by Elsevier Science Inc. C1 NCI, Informat Technol Branch, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Zaharevitz, DW (reprint author), NCI, Informat Technol Branch, Dev Therapeut Program, EPN Room 811,6130 Execut Blvd, Bethesda, MD 20892 USA. EM zaharevitz@dtpax2.nciferf.gov NR 22 TC 66 Z9 69 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD JAN PY 2002 VL 20 IS 4 BP 297 EP 303 DI 10.1016/S1093-3263(01)00126-7 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 518HP UT WOS:000173662100006 PM 11858638 ER PT J AU Anantharaman, V Koonin, EV Aravind, L AF Anantharaman, V Koonin, EV Aravind, L TI SPOUT: a class of methyltransferases that includes spoU and trmD RNA methylase superfamilies, and novel superfamilies of predicted prokaryotic RNA methylases SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID ESCHERICHIA-COLI; DATABASE; PROTEIN; ALIGNMENT; GM18 C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 17 TC 90 Z9 91 U1 1 U2 9 PU HORIZON SCIENTIFIC PRESS PI WYMONDHAM PA PO BOX 1, NORFOLK, WYMONDHAM NR18 0JA, ENGLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PD JAN PY 2002 VL 4 IS 1 BP 71 EP 75 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 497PW UT WOS:000172465500006 PM 11763972 ER PT J AU Lipschultz, CA Yee, A Mohan, S Li, YL Smith-Gill, SJ AF Lipschultz, CA Yee, A Mohan, S Li, YL Smith-Gill, SJ TI Temperature differentially affects encounter and docking thermodynamics of antibody-antigen association SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Article DE antigen-antibody association; protein-protein complexes; binding kinetics; temperature; thermodynamics; biosensor; BIACORE, rate constants ID SURFACE-PLASMON RESONANCE; MONOCLONAL-ANTIBODIES; PROTEIN INTERACTIONS; EXPERIMENTAL-DESIGN; AVIAN LYSOZYME; BINDING; SITE; RECOGNITION; EQUILIBRIUM; SPECIFICITY AB Using BIACORE SPR, we have examined the mechanism of temperature effects on the binding kinetics of two closely related antibody Fabs (H10 and H26) which recognize coincident epitopes on lien egg-white lysozyme (HEL), and whose association and dissociation kinetics are best described by the two-step conformational change model which we interpret as molecular encounter and docking. Time-course series data obtained at a series of six temperatures (6, 10, 15, 25, 30 and 37 degreesC) showed that temperature differentially affects the rate constants of the encounter and docking steps. Docking is more temperature-sensitive than the encounter step, and energetically less favorable at higher temperatures. At elevated temperatures, the time required for docking is longer and the apparent increase in off-rate reflects the greater proportion of the molecules failing to dock and remaining in the less stable encounter state. As a consequence, distribution of free energy change between the encounter and docking steps is altered. At physiological temperature (37 degreesC) the docking step of the H26 complex is energetically unfavorable and most complexes essentially do not dock. There is a significant decrease in total free energy change of the H26 complex at higher temperatures. Elevated temperature changes the rate-limiting step of H26-HEL association from the encounter to the docking step, but not that of H10-HEL. Our results indicate that the mechanism by which elevated temperature reduces the affinities of antigen-antibody complexes is to decrease the net docking rate, and/or stability of the docked complex; at higher temperatures, a smaller proportion of the complexes actually anneal to a more stable docked state. This mechanism may have broad applicability to other receptor-ligand complexes. Published in 2002 by John Wiley Sons, Ltd. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. RP Smith-Gill, SJ (reprint author), NCI, Basic Res Lab, POB B,Bldg 469,Room 206, Frederick, MD 21702 USA. NR 28 TC 23 Z9 24 U1 1 U2 10 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD JAN-FEB PY 2002 VL 15 IS 1 BP 44 EP 52 DI 10.1002/jmr.559 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 527NF UT WOS:000174191600007 PM 11870921 ER PT J AU Kudryashov, DS Vorotnikov, AV Dudnakova, TV Stepanova, OV Lukas, TJ Sellers, JR Watterson, DM Shirinsky, VP AF Kudryashov, DS Vorotnikov, AV Dudnakova, TV Stepanova, OV Lukas, TJ Sellers, JR Watterson, DM Shirinsky, VP TI Smooth muscle myosin filament assembly under control of a kinase-related protein (KRP) and caldesmon SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID LIGHT-CHAIN KINASE; CROSS-LINKING; BINDING; CONFORMATION; GIZZARD; SITES; PHOSPHORYLATION; EXPRESSION; CELLS; ACTIN AB Kinase-related protein (KRP) and caldesmon are abundant myosin-binding proteins of smooth muscle. KRP induces the assembly of unphosphorylated smooth muscle myosin filaments in the presence of ATP by promoting the unfolded state of myosin. Based upon electron microscopy data, it was suggested that caldesmon also possessed a KRP-like activity (Katayama et al., 1995, J Biol Chem 270: 3919-3925). However, the nature of its activity remains obscure since caldesmon does not affect the equilibrium between the folded and unfolded state of myosin. Therefore, to gain some insight into this problem we compared the effects of KRP and caldesmon, separately, and together on myosin filaments using turbidity measurements, protein sedimentation and electron microscopy. Turbidity assays demonstrated that KRP reduced myosin filament aggregation, while caldesmon had no effect. Additionally, neither caldesmon nor its N-terminal myosin binding domain (N152) induced myosin polymerization at subthreshold Mg2+ concentrations in the presence of ATP, whereas the filament promoting action of KRP was enhanced by Mg2+. Moreover, the amino-terminal myosin binding fragment of caldesmon, like the whole protein, antagonizes Mg2+-induced myosin filament formation. In electron microscopy experiments, caldesmon shortened myosin filaments in the presence of Mg2+ and KRP, but N152 failed to change their appearance from control. Therefore, the primary distinction between caldesmon and KRP appears to be that caldesmon interacts with myosin to limit filament extension, while KRP induces filament propagation into defined polymers. Transfection of tagged-KRP into fibroblasts and overlay of fibroblast cytoskeletons with Cy3KRP demonstrated that KRP colocalizes with myosin structures in vivo. We propose a new model that through their independent binding to myosin and differential effects on myosin dynamics, caldesmon and KRP can, in concert, control the length and polymerization state of myosin filaments. C1 Cardiol Res Ctr, Lab Cell Motil, Moscow 121552, Russia. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Drug Discovery Program, Chicago, IL 60611 USA. Northwestern Univ, Dept Biol Chem & Mol Pharmacol, Chicago, IL 60611 USA. RP Shirinsky, VP (reprint author), Cardiol Res Ctr, Lab Cell Motil, 3rd Cherepkovskaya St 15A, Moscow 121552, Russia. RI Vorotnikov, Alexander/A-8392-2014; Kudryashov, Dmitri/P-9004-2014; OI Vorotnikov, Alexander/0000-0002-1460-971X; Watterson, Daniel/0000-0001-7605-5866 NR 51 TC 10 Z9 10 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PY 2002 VL 23 IS 4 BP 341 EP 351 DI 10.1023/A:1022086228770 PG 11 WC Cell Biology SC Cell Biology GA 636KJ UT WOS:000180454400011 PM 12630709 ER PT J AU Hampel, H Teipel, SJ Alexander, GE Pogarell, O Rapoport, SI Moller, HJ AF Hampel, H Teipel, SJ Alexander, GE Pogarell, O Rapoport, SI Moller, HJ TI In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease - Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE corpus callosum; neocortex; hippocampus; dementia; mild cognitive impairment; Alzheimer's disease; progression; neurodegeneration; brain atrophy; therapy; prevention; neuroimaging; MRI; PET; EEG ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL METABOLIC ASYMMETRIES; ENTORHINAL CORTEX ATROPHY; MILD COGNITIVE IMPAIRMENT; WHITE-MATTER PATHOLOGY; IN-VIVO; GLUCOSE-METABOLISM; FRONTOTEMPORAL DEMENTIA; HIPPOCAMPAL ATROPHY; ANTERIOR-POSTERIOR AB Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, (18)FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with (18)FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression. C1 Univ Munich, Dept Psychiat, Alzheimer Mem Ctr, D-80336 Munich, Germany. Univ Munich, Geriatr Psychiat Branch, Dementia & Neuroimaging Sect, D-80336 Munich, Germany. Univ Munich, Dept Psychiat, Electrophysiol Sect, D-80336 Munich, Germany. Arizona State Univ, Arizona Alzheimers Dis Res Ctr, MRI Morphol Core, Tempe, AZ USA. Arizona State Univ, Dept Psychol, Tempe, AZ USA. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Hampel, H (reprint author), Univ Munich, Dept Psychiat, Alzheimer Mem Ctr, Nussbaumstr 7, D-80336 Munich, Germany. NR 90 TC 54 Z9 61 U1 1 U2 6 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PY 2002 VL 109 IS 5-6 SI SI BP 837 EP 855 DI 10.1007/s007020200069 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 561MZ UT WOS:000176145900026 PM 12111472 ER PT J AU Duan, W Ladenheim, B Cutler, RG Kruman, II Cadet, JL Mattson, MP AF Duan, W Ladenheim, B Cutler, RG Kruman, II Cadet, JL Mattson, MP TI Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic, neurons in models of Parkinson's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; dopamine; folic acid; 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine; rotenone; substantia nigra ID PLASMA HOMOCYSTEINE; SYNTHASE DEFICIENCY; RISK-FACTORS; APOPTOSIS; MPTP; ACID; AGE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; ANTIOXIDANTS; DEGENERATION AB Although the cause of Parkinson's disease (PD) is unknown, data suggest roles for environmental factors that may sensitize dopaminergic neurons to age-related dysfunction and death. Based upon epidemiological data suggesting roles for dietary factors in PD and other age-related neurodegenerative disorders, we tested the hypothesis that dietary folate can modify vulnerability of dopaminergic neurons to dysfunction and death in a mouse model of PD. We report that dietary folate deficiency sensitizes mice to MPTP-induced PD-like pathology and motor dysfunction. Mice on a folate-deficient diet exhibit elevated levels of plasma homocysteine. When infused directly into either the substantia nigra or striatum, homocysteine exacerbates MPTP-induced dopamine depletion, neuronal degeneration and motor dysfunction. Homocysteine exacerbates oxidative stress, mitochondrial dysfunction and apoptosis in human dopaminergic cells exposed to the pesticide rotenone or the pro-oxidant Fe2+. The adverse effects of homocysteine on dopaminergic cells is ameliorated by administration of the antioxidant uric acid and by an inhibitor of poly (ADP-ribose) polymerase. The ability of folate deficiency and elevated homocysteine levels to sensitize dopaminergic neurons to environmental toxins suggests a mechanism whereby dietary folate may influence risk for PD. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. NIDA, Intramural Res Program, Mol Neuropsychiat Sect, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 49 TC 228 Z9 245 U1 0 U2 20 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2002 VL 80 IS 1 BP 101 EP 110 DI 10.1046/j.0022-3042.2001.00676.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 507YV UT WOS:000173059900011 PM 11796748 ER PT J AU Igbavboa, U Hamilton, J Kim, HY Sun, GY Wood, WG AF Igbavboa, U Hamilton, J Kim, HY Sun, GY Wood, WG TI A new role for apolipoprotein E: modulating transport of polyunsaturated phospholipid molecular species in synaptic plasma membranes SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; apolipoprotein E; cholesterol; docosahexaenoic acid; neurons; phospholipid molecular species ID DENSITY-LIPOPROTEIN RECEPTOR; CENTRAL-NERVOUS-SYSTEM; GUINEA-PIG BRAIN; ALZHEIMERS-DISEASE; TRANSBILAYER DISTRIBUTION; DEFICIENT MICE; CHOLESTEROL; PHOSPHATIDYLSERINE; MICROSOMES; FLUIDITY AB Phospholipids and their acyl group composition are important in providing the proper membrane environment for membrane protein structure and function. In particular, the highly unsaturated phospholipids in synaptic plasma membranes in the CNS are known to play an important role in modulating receptor function and neurotransmitter release processes. Apolipoprotein E (apoE) is a major apolipoprotein in the CNS, mediating the transport of cholesterol, phospholipids and their fatty acids, particularly in reparative mechanisms during neuronal injury. This study was performed to determine whether deficiency in the apoE gene contributes to an alteration of the phospholipids in synaptic plasma membranes. Phospholipid molecular species were identified and quantitated by HPLC/electrospray ionization-mass spectrometry. Analysis of the different phospholipid classes in membranes of apoE-deficient and C57BL/6 J mice indicated no obvious differences in the distribution of different phospholipid classes but substantial differences in composition of phospholipid molecular species. Of special interest was the prevalence of phospholipids (phosphatidylcholine, diacyl-phosphatidylethanolamine, and phosphaticlylserine) with 22:6n-3 in both the sn-1 and sn-2 positions of SPM and these phospholipid species were significantly higher in apoE-deficient mice as compared to control mice. Since polyunsaturated fatty acids in neurons are mainly supplied by astrocytes, these results revealed a new role for apoE in regulating polyunsaturated phospholipid molecular species in neuronal membranes. C1 Univ Minnesota, Sch Med, VA Med Ctr, Ctr Geriatr Res Educ & Clin, Minneapolis, MN 55417 USA. Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55417 USA. NIAAA, LMBB, Sect Mass Spectrometry, NIH, Bethesda, MD USA. Univ Missouri, Dept Biochem, Columbia, MO USA. RP Wood, WG (reprint author), Univ Minnesota, Sch Med, VA Med Ctr, Ctr Geriatr Res Educ & Clin, GRECC 11G,1 Vet Dr, Minneapolis, MN 55417 USA. FU NIA NIH HHS [1P0AG-18357, AG-11056]; NIAAA NIH HHS [AA-10806] NR 35 TC 45 Z9 48 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2002 VL 80 IS 2 BP 255 EP 261 DI 10.1046/j.0022-3042.2001.00688.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 512YX UT WOS:000173352100005 PM 11902115 ER PT J AU Luo, YQ Long, JM Lu, CB Chan, SL Spangler, EL Mascarucci, P Raz, A Longo, DL Mattson, MP Ingram, DK Weng, NP AF Luo, YQ Long, JM Lu, CB Chan, SL Spangler, EL Mascarucci, P Raz, A Longo, DL Mattson, MP Ingram, DK Weng, NP TI A link between maze learning and hippocampal expression of neuroleukin and its receptor gp78 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE aging; gp78; hippocampus; learning and memory; neuroleukin; 14-unit Stone T-maze ID AUTOCRINE MOTILITY FACTOR; ISOMERASE GPI DEFICIENCY; LONG-TERM POTENTIATION; GLUCOSE-6-PHOSPHATE ISOMERASE; PHOSPHOHEXOSE ISOMERASE; NEUROTROPHIC FACTOR; MOLECULAR-CLONING; HEMOLYTIC-ANEMIA; SPATIAL MEMORY; MELANOMA-CELLS AB Neuroleukin (NLK) is a multifunctional protein involved in neuronal growth and survival, cell motility and differentiation, and glucose metabolism. We report herein that hippocampal expression of NLK and its receptor gp78 is associated with maze learning in rats. First, mRNA levels of NLK and gp78 were significantly increased in hippocampi of male Fischer-344 rats following training in the Stone T-maze and the Morris water maze. Second, a parallel increase was found in hippocampal NLK and gp78 proteins after maze learning. Third, NLK and gp78 mRNA and protein expression in hippocampus was reduced in a group of aged rats that showed more errors during the acquisition of the Stone maze task as compared with young rats. Finally, application of recombinant NLK to hippocampal neurons significantly enhanced glutamate-induced ion currents, functional molecular changes that have been correlated with learning in vivo. Taken together, our results identify a novel association of hippocampal expression of NLK and its receptor gp78 with rat maze learning. Interaction of NLK with gp78 and subsequent signaling may strengthen synaptic mechanisms underlying learning and memory formation. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. Karamanos Canc Inst, Detroit, MI USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, 4C16,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 FU NCI NIH HHS [R01-CA51714] NR 43 TC 25 Z9 33 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2002 VL 80 IS 2 BP 354 EP 361 DI 10.1046/j.0022-3042.2001.00707.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 512YX UT WOS:000173352100016 PM 11902125 ER PT J AU Mendel, I Shevach, EM AF Mendel, I Shevach, EM TI Differentiated Th1 autoreactive effector cells can induce experimental autoimmune encephalomyelitis in the absence of IL-12 and CD40/CD40L interactions SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE EAE/MS; autoimmunity; Th1/Th2; cytokines; in vivo animal models ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TYPE-1 CYTOKINE RESPONSES; IFN-GAMMA PRODUCTION; T-CELLS; MULTIPLE-SCLEROSIS; INTERLEUKIN-12 PRODUCTION; ENDOGENOUS IL-12; CD40 LIGAND; IN-VIVO; MICE AB IL-12 plays a critical role in the priming of Th1 responses to bacterial/parasitic antigens and autoantigens. Several studies have demonstrated a dependency on CD40/CD40L interactions and IL-12 for maintenance of both antibacterial/parasitic and autoreactive Th1 cells in vivo. However, it is still unclear if fully differentiated Th1 effectors require continued stimulation by IL-12. We demonstrate that the proliferative response and IFN-gamma production by a fully differentiated T cell line specific for myelin oligodendrocyte glycoprotein are completely independent of IL-12 and CD40/CD40L interactions. The capacity of this line to adoptively transfer experimental autoimmune encephalomyelitis is also independent of IL-12 and CD40/CD40L. These results have important implications regarding the therapeutic usefulness of blockade of IL-12 or the CD40/CD40L pathway for treatment of autoimmune disease. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIH, NIAID, Immunol Lab, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIH, NIAID, Immunol Lab, 10-11N307,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 34 TC 9 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN PY 2002 VL 122 IS 1-2 BP 65 EP 73 DI 10.1016/S0165-5728(01)00465-9 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 516UQ UT WOS:000173575500007 PM 11777544 ER PT J AU Sawaki, L Boroojerdi, B Kaelin-Lang, A Burstein, AH Butefisch, CM Kopylev, L Davis, B Cohen, LG AF Sawaki, L Boroojerdi, B Kaelin-Lang, A Burstein, AH Butefisch, CM Kopylev, L Davis, B Cohen, LG TI Cholinergic influences on use-dependent plasticity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ADULT SQUIRREL-MONKEYS; HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; MOVEMENT REPRESENTATIONS; MUSCARINIC RECEPTORS; HUMAN BRAIN; MEMORY; REORGANIZATION AB Motor practice elicits use-dependent plasticity in humans as well as in animals. Given the influence of cholinergic neurotransmission on learning and memory processes, we evaluated the effects of scopolamine (a muscarinic receptor antagonist) on use-dependent plasticity and corticomotor excitability in a double-blind placebo-controlled randomized design study. Use-dependent plasticity was substantially attenuated by scopolamine in the absence of global changes in corticomotor excitability. These results identify a facilitatory role for cholinergic influences in use-dependent plasticity in the human motor system. C1 NINCDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINCDS, Human Cort Physiol Sect, NIH, Bldg 10,Rm 5N 234,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 53 TC 67 Z9 67 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2002 VL 87 IS 1 BP 166 EP 171 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 509PD UT WOS:000173155700015 PM 11784739 ER PT J AU Brasted, PJ Bussey, TJ Murray, EA Wise, SP AF Brasted, PJ Bussey, TJ Murray, EA Wise, SP TI Fornix transection impairs conditional visuomotor learning in tasks involving nonspatially differentiated responses SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID STIMULUS-STIMULUS ASSOCIATION; RHESUS-MONKEYS; MEMORY IMPAIRMENT; HIPPOCAMPUS; LESIONS; ABLATION; AMYGDALA; LOCATION; OBJECTS AB Rhesus monkeys learned a series of conditional visuomotor associations involving two-dimensional "objects" that instructed one of three responses: tapping a touch screen, steady contact with the screen for a brief period, or steady contact for a longer period. Relative to controls, fornix-transected monkeys were impaired in the acquisition of new associations and in the retention of preoperatively learned ones. These findings challenge the view that the hippocampal system participates in associative learning only when spatial information is relevant to either the stimulus or the response. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Brasted, PJ (reprint author), NIMH, Lab Syst Neurosci, Bldg 49,Rm B1EE17,49 Convent Dr,MSC 4401, Bethesda, MD 20892 USA. RI Bussey, Timothy/M-2758-2016; OI Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642 NR 23 TC 18 Z9 18 U1 0 U2 0 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 2002 VL 87 IS 1 BP 631 EP 633 PG 3 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 509PD UT WOS:000173155700054 PM 11784778 ER PT J AU Hampson, AJ Grimaldi, M AF Hampson, AJ Grimaldi, M TI 12-Hydroxyeicosatetrenoate (12-HETE) attenuates AMPA receptor-mediated neurotoxicity: Evidence for a G-protein-coupled HETE receptor SO JOURNAL OF NEUROSCIENCE LA English DT Article DE HETE; hydroxyeicosatetraenoic acid; lipoxygenase; ischemia; AMPA; eicosanoid; G-protein; VSCCs; glutamate; excitotoxicity ID FIBER NERVE-ENDINGS; ARACHIDONIC-ACID; CEREBRAL-ISCHEMIA; GLUTAMATE RELEASE; CALCIUM CHANNELS; CA2+ CHANNELS; DEPENDENT MODULATION; CANINE BRAIN; NEURONS; RAT AB 12-Hydroxyeicosatetraenoic acid (12-HETE) is a neuromodulator that is synthesized during ischemia. Its neuronal effects include attenuation of calcium influx and glutamate release as well as inhibition of AMPA receptor (AMPA-R) activation. Because 12-HETE reduces ischemic injury in the heart, we examined whether it can also reduce neuronal excitotoxicity. When treated with 12-(S)HETE, cortical neuron cultures subjected to AMPA-R-mediated glutamate toxicity suffered up to 40% less damage than untreated cultures. The protective effect of 12-(S)HETE was concentration-dependent (EC50 = 88 nM) and stereostructurally selective. Maximal protection was conferred by 300 nM 12-(S) HETE; 300 nM 15-(S)HETE was similarly protective, but 300 nM 5-(S) HETE was less effective. The chiral isomer 12-(R)HETE offered no protection; neither did arachidonic acid or 12-(S)hydroperoxyeicosatetraenoic acid. Excitotoxicity was calcium-dependent, and 12-(S)HETE was demonstrated to protect by inactivating N and L (but not P) calcium channels via a pertussis toxin-sensitive mechanism. Calcium imaging demonstrated that 12-(S) HETE also attenuates glutamate-induced calcium influx into neurons via a pertussis toxin-sensitive mechanism, suggesting that it acts via a G-protein-coupled receptor. In addition, 12-(S) HETE stimulates GTP gammaS binding (indicating G-protein activation) and inhibits adenylate cyclase in forskolin-stimulated cultures over the same concentration range as it exerts its anti-excitotoxic and calcium-influx attenuating effects. These studies demonstrate that 12-(S) HETE can protect neurons from excitotoxicity by activating a G(i/o)-protein-coupled receptor, which limits calcium influx through voltage-gated channels. C1 NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. NINCDS, Lab Adapt Syst, Bethesda, MD 20892 USA. RP Hampson, AJ (reprint author), Cortex Pharmaceut, 15231 Barranca Pkwy, Irvine, CA 92618 USA. OI Grimaldi, Maurizio/0000-0002-7331-7055 NR 49 TC 30 Z9 30 U1 2 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN PY 2002 VL 22 IS 1 BP 257 EP 264 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 505GU UT WOS:000172905700034 PM 11756509 ER PT J AU Xie, T Tong, LQ Barrett, T Yuan, J Hatzidimitriou, G McCann, UD Becker, KG Donovan, DM Ricaurte, GA AF Xie, T Tong, LQ Barrett, T Yuan, J Hatzidimitriou, G McCann, UD Becker, KG Donovan, DM Ricaurte, GA TI Changes in gene expression linked to methamphetamine-induced dopaminergic neurotoxicity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amphetamines; neurotoxicity; dopamine; neurodegeneration; cytochrome c oxidase; microarray ID MESSENGER-RNA EXPRESSION; RAT STRIATUM; ENVIRONMENTAL-TEMPERATURE; TERMINAL DEGENERATION; INDUCED HYPERTHERMIA; UPTAKE INHIBITORS; SUBSTANTIA-NIGRA; MICE; AMPHETAMINE; NEURONS AB The purpose of these studies was to examine the role of gene expression in methamphetamine (METH)-induced dopamine (DA) neurotoxicity. First, the effects of the mRNA synthesis inhibitor, actinomycin-D, and the protein synthesis inhibitor, cycloheximide, were examined. Both agents afforded complete protection against METH-induced DA neurotoxicity and did so independently of effects on core temperature, DA transporter function, or METH brain levels, suggesting that gene transcription and mRNA translation play a role in METH neurotoxicity. Next, microarray technology, in combination with an experimental approach designed to facilitate recognition of relevant gene expression patterns, was used to identify gene products linked to METH-induced DA neurotoxicity. This led to the identification of several genes in the ventral midbrain associated with the neurotoxic process, including genes for energy metabolism [cytochrome c oxidase subunit 1 (COX1), reduced nicotinamide adenine dinucleotide ubiquinone oxidoreductase chain 2, and phosphoglycerate mutase B], ion regulation (members of sodium/hydrogen exchanger and sodium/bile acid cotransporter family), signal transduction (adenylyl cyclase III), and cell differentiation and degeneration (N-myc downstream-regulated gene 3 and tau protein). Of these differentially expressed genes, we elected to further examine the increase in COX1 expression, because of data implicating energy utilization in METH neurotoxicity and the known role of COX1 in energy metabolism. On the basis of time course studies, Northern blot analyses, in situ hybridization results, and temperature studies, we now report that increased COX1 expression in the ventral midbrain is linked to METH-induced DA neuronal injury. The precise role of COX1 and other genes in METH neurotoxicity remains to be elucidated. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ricaurte, GA (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Dept Neurol, 5501 Hopkins Bayview Circle,Room 5B-71E, Baltimore, MD 21224 USA. OI Becker, Kevin/0000-0002-6794-6656 FU NIDA NIH HHS [DA10217, DA13790, DA00206, DA09487] NR 52 TC 48 Z9 50 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN PY 2002 VL 22 IS 1 BP 274 EP 283 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 505GU UT WOS:000172905700036 PM 11756511 ER PT J AU Dodgson, JE Duckett, L Garwick, A Graham, BL AF Dodgson, JE Duckett, L Garwick, A Graham, BL TI An ecological perspective of breastfeeding in an indigenous community SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE breastfeeding; American Indian; ecological approach; ethnography ID HEALTH PROMOTION; QUALITATIVE RESEARCH; SOCIAL ECOLOGY; NAVAJO; BEHAVIOR; MODEL; RIGOR AB Purpose: To describe the sociocultural patterns that promote breastfeeding or weaning in the Ojibwe community, which has very low breastfeeding rates compared to the general population. Design: A focused ethnographic approach with an ecological framework provided community level data. Semi-structured interviews (N = 52) were conducted in an urban Ojibwe community and with three groups of women: health or social service providers, women currently breastfeeding, or people who acted as resources. Methods: Data were analyzed using an ethnographic approach. Group summaries were compiled and community-level patterns were identified. Findings: Four patterns were identified that encompassed the influences of (a) Ojibwe and mainstream cultures (traditions), (b) communication-related barriers from a variety of sources (mixed messages), (c) socioeconomic issues (life circumstances) and (d) social support (nurturing and supporting). Conclusions: The values and practices of the studied group were not always congruent with those of the larger mainstream culture. Successful breastfeeding promotion and intervention programs based on culturally relevant perspectives are needed. C1 Univ Hong Kong, Dept Nursing Studies, Hong Kong, Hong Kong, Peoples R China. Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. NINR, Minneapolis, MN USA. RP Dodgson, JE (reprint author), Duke Univ, Sch Nursing, Med Ctr, Box 3322, Durham, NC 27710 USA. FU NINR NIH HHS [1F31-NR07211-01] NR 32 TC 18 Z9 18 U1 0 U2 7 PU SIGMA THETA TAU INT PI INDIANAPOLIS PA 550 W NORTH STREET, INDIANAPOLIS, IN 46202 USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2002 VL 34 IS 3 BP 235 EP 241 DI 10.1111/j.1547-5069.2002.00235.x PG 7 WC Nursing SC Nursing GA 636FX UT WOS:000180444900015 PM 12237985 ER PT J AU Pennington, JAT Hubbard, VS AF Pennington, JAT Hubbard, VS TI Nutrition education materials from the National Institutes of Health: Development, review, and availability SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article AB Many of the institutes, centers, and offices (ICOs) within the National Institutes of Health (NIH) develop and disseminate nutrition education materials for the general public. These materials provide information about the relationship of diet to health and about associations between diet and specific diseases. The materials, which are drafted by the NIH or contract science writers, go through pretesting (for literacy level and appropriateness for target audiences) and ICO clearance (for scientific accuracy). To further ensure scientific and technical accuracy and consistency with the Dietary Guidelines for Americans, the materials then go through a two-tiered governmental review system. The first review is through the Nutrition Education Subcommittee (NES) of the NIH Nutrition Coordinating Committee. The second review, which is required for federal nutrition education materials, is conducted jointly by the Department of Health and Human Services (DHHS) Nutrition Policy Board Committee on Dietary Guidance and by the US Department of Agriculture (USDA) Dietary Guidance Working Group. The review process helps ensure consistency in nutrition messages within the NIH ICOs and among government agencies. The pretesting, ICO clearance, NES review, and joint DHHS/USDA review result in materials for nutrition educators that are high in quality, low in cost or free, easily accessible, appropriate for the intended target audience, and consistent with the Dietary Guidelines for Americans. C1 NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. RP Pennington, JAT (reprint author), NIH, Div Nutr Res Coordinat, 6707 Democracy Blvd,Room 629, Bethesda, MD 20892 USA. NR 1 TC 3 Z9 3 U1 1 U2 2 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 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD JAN-FEB PY 2002 VL 34 IS 1 BP 53 EP 58 DI 10.1016/S1499-4046(06)60224-8 PG 6 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 539LK UT WOS:000174871400007 PM 11917672 ER PT J AU McNeil, DE Langer, JC Choyke, P DeBaun, MR AF McNeil, DE Langer, JC Choyke, P DeBaun, MR TI Feasibility of partial nephrectomy for Wilms' tumor in children with Beckwith-Wiedemann syndrome who have been screened with abdominal ultrasonography SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Beckwith-Wiedemann syndrome; Wilms' tumor; partial nephrectomy ID RISK AB Background: Children with Beckwith-Wiedemann syndrome (BWS), a congenital syndrome associated with Wilms' tumor commonly are screened with abdominal sonography resulting in detection of tumor at a lower stage. Wilms' tumors have been traditionally treated with complete nephrectomy; however, smaller tumors are amenable to nephron-sparing surgery, Because Wilms' tumors may be metachronous and nonmalignant disease may compromise renal function in BWS, nephron-sparing approaches may be desirable as the first option, Methods: Seven patients with BWS and Wilms' tumor underwent nephrectomy. The preoperative computed tomography (CT) or ultrasound scan were evaluated by a pediatric surgeon to assess whether partial nephrectomy would have been feasible. The determining criteria included tumor involving one third or less of the kidney and no involvement of either hilar or vascular structures. Results:Seven patients underwent complete nephrectomies. The remaining patient, who had undergone a left nephrectomy before the initiation of screening had salvage chemotherapy after biopsy results showed right kidney involvement with Wilms' tumor. Conclusions: Nephron-sparing surgery is reasonable to consider in children with Beckwith-Wiedemann syndrome who are screened at intervals of 4 months or less. The relative benefits of partial nephrectomy for children with Wilms' tumor-predisposing conditions only can be assessed in the setting of a cooperative clinical trial. J Pediatr Surg 37:57-60. Copyright (C) 2002 by WB. Saunders Company. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,EPS, Bethesda, MD 20892 USA. NCI, Dept Radiol, Ctr Clin, NIH, Bethesda, MD 20892 USA. Univ Toronto, Dept Surg, Toronto, ON, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP DeBaun, MR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,EPS, Room 7125,6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. NR 10 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 2002 VL 37 IS 1 BP 57 EP 60 DI 10.1053/jpsu.2002.29427 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 507WK UT WOS:000173054100011 PM 11781987 ER PT J AU Liu, J Saavedra, JE Lu, T Song, JG Clark, J Waalkes, MP Keefer, LK AF Liu, J Saavedra, JE Lu, T Song, JG Clark, J Waalkes, MP Keefer, LK TI O-2-Vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate protection against D-galactosamine/endotoxin-induced hepatotoxicity in mice: Genomic analysis using microarrays SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ALPHA-INDUCED APOPTOSIS; NITRIC-OXIDE; LIVER-INJURY; DNA-BINDING; IN-VIVO; NECROSIS; INHIBITION; ENDOTOXEMIA; EXPRESSION; RAT AB O-2-Vinyl 1-(pyrrolidin-1-yl)diazen-1-lum-1,2-diolate(V-PYRRO/NO), a liver-selective nitric oxide (NO)-donating prodrug, is metabolized by hepatic enzymes to release NO within the liver. This study was undertaken to examine the effects of V-PYRRO/NO on D-galactosamine/lipopolysaccharide (GlaN/LPS)-induced liver injury in mice. Mice were given injections of V-PYRRO/NO (10 mg/kg, s.c. at 2-h intervals) before and after GIaN/LPS (700 mg/30 mug/kg, i.p.). V-PYRRO/NO administration dramatically reduced GlaN/LPS-induced hepatotoxicity, as evidenced by reduced serum alanine aminotransferase activity and improved pathology. To examine the mechanisms of the protection, cDNA microarray was performed to profile the gene expression pattern in livers of mice treated with GlaN/LPS, GIaN/LPS plus V-PYRRO/NO, or controls. V-PYRRO/NO administration greatly ameliorated GlaN/LPS-induced alterations in the expression of genes encoding the stress response, DNA damage/repair response, and drug-metabolizing enzymes in accordance with hepatoprotection. Gel shift assay and Western blot analysis supported microarray results, showing that V-PYRRO/NO suppressed GlaN/LPS-induced activation of nuclear factor-kappaB and GlaN/LPS-induced increases in caspase-1, caspase-8, tumor necrosis factor receptor 1 (TNFR1)-associated death domain, and TNF-related apoptosis-inducing ligand. Immunohistochemical analysis further revealed that GlaN/LPS-induced activation of TNFR1, caspase-3, and hepatocellular apoptosis was ameliorated by V-PYRRO/NO treatment. GlaN/LPS-induced elevation of hepatic caspase-3 activity was diminished by V-PYRRO/NO treatment. In addition, V-PYRRO/NO alone suppressed the basal expression of genes encoding inducible NO synthase and TNF-alpha-related components, as revealed by mouse 1.2 array. In summary, this study demonstrates that the liver-selective NO donor, V-PYRRO/NO, is effective in blocking GlaN/LPS-induced hepatotoxicity in mice, and that this protection appears to involve, at least in part, the suppression of the TNF-alpha-mediated cell death pathways. C1 NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Res Triangle Pk, NC 27709 USA. NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. Acad Sinica, Inst Biochem, Shanghai, Peoples R China. Sci Applicat Int Corp, Frederick, MD USA. NCI, Chem Sect, Lab Comparat Carcinogenesis, Frederick, MD USA. RP Liu, J (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Mail Drop FO-09, Res Triangle Pk, NC 27709 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000] NR 36 TC 39 Z9 43 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2002 VL 300 IS 1 BP 18 EP 25 DI 10.1124/jpet.300.1.18 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509GB UT WOS:000173137000003 PM 11752092 ER PT J AU Schindler, CW Gilman, JP Bergman, J Mello, NK Woosley, RL Goldberg, SR AF Schindler, CW Gilman, JP Bergman, J Mello, NK Woosley, RL Goldberg, SR TI Interactions between cocaine and dopamine agonists on cardiovascular function in squirrel monkeys SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CONSCIOUS RATS; BLOOD-PRESSURE; MECHANISMS; RESPONSES; ANTAGONISTS; (+)-UH-232; ADDICTION; SYSTEM; DOGS AB Conscious squirrel monkeys were treated i.v. with cocaine and various dopamine agonist drugs. Cocaine produced a dose-dependent increase in blood pressure, heart rate, and the rate-pressure product (RPP). The dopamine D1 receptor agonist (+/-)-6-chloro-3-allyl-1 -phenyl-2,3,4,5-tetrahydro-1 H3-benzazepine hydrobromide (SKF 82958) produced effects comparable to cocaine. The D1 agonist (+/-)-6-chloro-7, 8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) also produced increases in blood pressure and heart rate but was much less potent than either cocaine or SKF 82958. The partial D1 agonist (+/-)-7,8-dihydroxy-3-allyl-1 -phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride (SKF 77434) did not significantly affect any cardiovascular parameters. The D2 agonist quinpirole slightly decreased blood pressure and increased heart rate. As such, the RPP only slightly increased. The selective dopamine uptake inhibitor 1-[2-[bis-(4-fluorphenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909) produced increases in blood pressure, heart rate, and RPP, but again these effects were smaller and only seen at doses higher than cocaine. Effects similar to those with GBR 12909 were seen with the dopamine autoreceptor antagonist cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin (UH 232). The combination of GBR 12909, SKF 82958, or SKF 77434 with cocaine produced effects that were clearly subadditive. The effects of quinpirole in combination with cocaine were comparable to, or lower than, those of cocaine alone on blood pressure and RPP. The effects on heart rate were additive. Only UH 232 produced additive effects with cocaine for all three measures. As dopamine agonists have been proposed as potential treatments for cocaine abuse, these results suggest that dopamine D1 agonists and uptake inhibitors can be used safely in combination with cocaine. Caution may be warranted, however, with the use of dopamine autoreceptor antagonists in the treatment of cocaine abuse. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02178 USA. Univ Arizona, Arizona Hlth Sci Ctr, Tucson, AZ USA. RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, NIH,Intramural Res Program, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA11007, K05-DA00101] NR 39 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2002 VL 300 IS 1 BP 180 EP 187 DI 10.1124/jpet.300.1.180 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509GB UT WOS:000173137000025 PM 11752114 ER PT J AU Russo, P Ottoboni, C Malacarne, D Crippa, A Riou, JF O'Connor, PM AF Russo, P Ottoboni, C Malacarne, D Crippa, A Riou, JF O'Connor, PM TI Nonpeptidomimetic farnesyltransferase inhibitor RPR-115135 increases cytotoxicity of 5-fluorouracil: Role of p53 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID COLORECTAL-CANCER; CELL-LINES; MICHAELIS-MENTEN; KINETIC SYSTEMS; SENSITIVITY; DISRUPTION; APOPTOSIS; P14(ARF); PATHWAY; AGENTS AB A new nonpeptidic farnesyltransferase inhibitor, RPR-115135, in combination with 5-fluorouracil (5-FU) was studied in an isogenic cell line model system consisting of human colon cancer HCT-116 cells. HCT-116 cells were transfected with an empty control pCMV vector and with a dominant-negative mutated p53 transgene (248R/W). We found that, relative to control transfectants, there was a slight tendency for the p53 inactivated cells to be less sensitive to 5-FU after 6 days of continuous treatment. Simultaneous administration of RPR-115135 and 5-FU, at equitoxic concentrations, resulted in an enhancement of 5-FU cytotoxicity, especially in the CMV-2 clone. Growth inhibition could be accounted for on the basis of a specific cell cycle arrest phenotype (G(2)-M arrest in CMV-2 and S arrest in mutated clones), as assayed by flow cytometry. The combination RPR-115135 + 5-FU increases apoptotic events only in the CMV-2 clone. C1 Ist Nazl Ric Canc, Mol Pathol Sect, Expt Oncol Lab, I-16132 Genoa, Italy. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Ctr Rech Rhone Poulenc Rorer Aventis Pharma, Anticanc Res Program, Vitry Sur Seine, France. RP Russo, P (reprint author), Ist Nazl Ric Canc, Mol Pathol Sect, Expt Oncol Lab, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 36 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2002 VL 300 IS 1 BP 220 EP 226 DI 10.1124/jpet.300.1.220 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509GB UT WOS:000173137000031 PM 11752120 ER PT J AU McNulty, PA Macefield, VG Taylor, JL Hallett, M AF McNulty, PA Macefield, VG Taylor, JL Hallett, M TI Cortically evoked neural volleys to the human hand are increased during ischaemic block of the forearm SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; REORGANIZATION FOLLOWING MOTOR; UPPER-LIMB AMPUTATION; ISCHEMIC NERVE BLOCK; DYNAMIC ORGANIZATION; TARGET MUSCLES; ADULT-RATS; PLASTICITY; OUTPUTS AB Reorganisation of the motor cortex may occur after limb amputation or spinal cord injury. In humans, transcranial magnetic stimulation (TMS) shows expansion of motor cortical representations of muscles proximal to the injury. Similarly, ischaemic block of the hand can increase acutely the representation of the biceps muscle, measured by increased biceps motor potentials evoked by TMS. It is thought that this increase occurs at the expense of the cortical representation of the paralysed and deafferented hand muscles but this has never been investigated. To study what changes occur in the cortical representation of the hand muscles during ischaemic block, a tungsten microelectrode was inserted into the ulnar or median nerve above the elbow and the size of the neural potential elicited by TMS in fascicles supplying the hand was measured in seven subjects. Prior to ischaemia, TMS evoked EMG responses in the intrinsic hand muscles. In the nerve, a brief motor potential preceded the response in the muscle and was followed by a contraction-induced sensory potential. During 40 min of ischaemia produced by a blood pressure cuff inflated around the forearm to 210 mmHg, the EMG response to TMS and the sensory potential from the hand were progressively blocked. However, the motor neural evoked potential showed a significant increase in amplitude during the ischaemic period (30.5%, P = 0.005). The increase in the neural potential suggests that output to the hand evoked from the cortex by TMS was not decreased by ischaemic block. Thus, we conclude that the increased response of biceps to TMS during distal ischaemia is not accompanied by a corresponding decrease in the motor cortical representation of the hand. C1 Univ New S Wales, Sydney, NSW, Australia. NINCDS, Human Motor Contol Sect, NIH, Bethesda, MD USA. RP McNulty, PA (reprint author), Prince Wales Med Res Inst, Barker St, Randwick, NSW 2031, Australia. RI Taylor, Janet/C-9667-2011; McNulty, Penelope/D-7765-2011 OI Taylor, Janet/0000-0001-8976-5162; NR 30 TC 33 Z9 33 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2002 VL 538 IS 1 BP 279 EP 288 DI 10.1113/jphysiol.2001.013200 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 517XT UT WOS:000173636300026 PM 11773335 ER PT J AU Weiner, MF Tractenberg, RE Jin, S Gamst, A Thomas, RG Koss, E Thal, LJ AF Weiner, MF Tractenberg, RE Jin, S Gamst, A Thomas, RG Koss, E Thal, LJ TI Assessing Alzheimer's disease patients with the Cohen-Mansfield Agitation Inventory: scoring and clinical implications SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Cohen-Mansfield Agitation Inventory; Alzheimer's disease; assessment ID BEHAVIOR RATING-SCALE; DEMENTIA AB We explored the applicability of the standard scoring of the Cohen-Mansfield Agitation Inventory (CMAI), a widely used nursing-home derived instrument, to community-dwelling persons with Alzheimer's disease (AD). Item responses to the CMAI were Gathered from participants in two large clinical Studies, one of which specifically included patients with behavioral disturbances. Confirmatory factor analysis in these two groups of well-characterized AD patients suggested that conventional CMAI subscoring did not adequately describe the responses of these two groups. Exploratory factor analysis indicated that the four CMAI subscores, based on a verbal-physical and aggressive-non-aggressive conceptualization of behavioral disturbance, did not fit community dwelling persons with AD. Based on cross-sectional and longitudinal analyses, there was suggestive evidence for three behavioral clusters, but these clusters did not achieve statistical significance Overall, the CMAI seemed best suited to describe the overall level rather than the specific subtypes of behavioral dyscontrol in community-dwelling persons with AD. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75390 USA. Univ Calif San Diego, Dept Neurosci, Alzheimers Dis Cooperat Study, San Diego, CA 92103 USA. NIA, Bethesda, MD 20892 USA. RP Weiner, MF (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. OI Weiner, Myron/0000-0001-5682-4410 FU NIA NIH HHS [AG 10483] NR 20 TC 14 Z9 16 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JAN-FEB PY 2002 VL 36 IS 1 BP 19 EP 25 DI 10.1016/S0022-3956(01)00047-4 PG 7 WC Psychiatry SC Psychiatry GA 514TN UT WOS:000173457300003 PM 11755457 ER PT J AU Dean, J AF Dean, J TI Oocyte-specific genes regulate follicle formation, fertility and early mouse development SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT International Congress on Fertilization, Embryo Development and Implantation CY NOV, 2000 CL NEW DELHI, INDIA DE oocyte-specific gone expression; Zona pellucida; folliculogenesis; fertilization; maternal effect genes; bHLH transcription factors ID EARLY EMBRYONIC-DEVELOPMENT; PELLUCIDA GLYCOPROTEIN ZP3; O-LINKED OLIGOSACCHARIDES; SPERM RECEPTOR ACTIVITY; ZONA-PELLUCIDA; EGG INTERACTION; FIG-ALPHA; MICE; EXPRESSION; PROTEINS AB Gene products expressed in oocytes play important roles in folliculogenesis, fertilization and pre-implantation development. Factor in the Germline, alpha (FIG alpha) is a basic helix-loop-helix (bHLH) transcription factor first detected in oocytes at E13.5 that persists in adults. Female mice lacking FlG alpha are unable to form primordial follicles which results in massive depletion of oocytes and sterility. FlGa is also required for expression of the zona pellucida genes that encode ZP1, ZP2, and ZP3. Mice lacking ZP1 form structurally abnormal zonae and have decreased fecundity. Mice lacking ZP3 have no zona matrix despite the presence of the other two zona proteins. Although, folliculogenesis occurs in Zp3 null mice, few eggs are ovulated and females are sterile. Transgenic mice expressing human ZP3 have been crossed with Zp3 null mice and reconstitute a chimeric zona pellucida matrix (moZP1, moZP2, moZP3). Unexpectedly, human sperm do not bind to 'humanized' zonae pellucidae in vitro, but mouse sperm do. Although, late in oogenesis, oocytes becomes transcriptionally inactive and maternal RNA is degraded, the activation of early development requires pre-existing maternal products from the egg. Maternal antigen that embryos require (Mater) is a single-copy gene that is transcribed in growing oocytes and, although its transcripts are degraded during meiotic maturation, MATER protein persists into the blastocyst. Female mice lacking this 125 kDa cytoplasmic protein produce no off-spring because of an embryonic block at the early cleavage stage. Thus, Hater represents one of the few documented maternal effect genes in mammalian development, Published by Elsevier Science Ireland Ltd. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Room 3134,50 S DR MSC 8028, Bethesda, MD 20892 USA. NR 47 TC 80 Z9 89 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD JAN PY 2002 VL 53 IS 1-2 SI SI BP 171 EP 180 DI 10.1016/S0165-0378(01)00100-0 PG 10 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 504UB UT WOS:000172873300016 PM 11730914 ER PT J AU Hitchon, CA Danning, CL Illei, GG El-Gabalawy, HS Boumpas, DT AF Hitchon, CA Danning, CL Illei, GG El-Gabalawy, HS Boumpas, DT TI Gelatinase expression and activity in the synovium and skin of patients with erosive psoriatic arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE arthritis; psoriatic; metalloendopeptidases; gelatinases; tissue inhibitor of metalloproteinase; skin ID RHEUMATOID-ARTHRITIS; MATRIX METALLOPROTEINASES; TISSUE INHIBITOR; BONE-RESORPTION; 92-KDA GELATINASES; GENE-EXPRESSION; IV COLLAGENASE; CATHEPSIN-B; IN-VITRO; MEMBRANE AB Objective. Matrix metalloproteinases (MMP), especially the gelatinases (MMP2, MMP9), have been implicated in several features of inflammatory arthritis including angiogenesis and bone erosions. We examined the expression and activity of the gelatinases and their regulators in psoriatic skin and synovium using tissue immunohistochemistry and a sensitive tissue based zymographic technique. Methods. Lesional and perilesional skin biopsies and synovial samples obtained by closed needle biopsy from 15 patients with erosive psoriatic arthritis (PsA) were analyzed by immunohistochemistry for the expression of the gelatinases and their regulators, tissue inhibitor of metalloproteinase I and 2 (TIMP-1, TIMP-2) and membrane type metalloproteinases (MT1-MMP, MT2-MMP), using immunohistochemistry. Synovial tissue from 8 patients with erosive rheumatoid arthritis (RA) was used as a comparison. MMP tissue expression was quantified by 2 blinded independent observers. Immunohistochemical data are reported as the mean percentage positive cells per total nucleated cells in 10 high power fields +/- SD. Functional activity of the gelatinases was measured using a sensitive tissue based zymography technique and corrected for protein content. Zymography data are presented as ng/mg +/- SE. Results. MMP expression was greater in the synovial lining layer (LL) than in the synovial sublining layer (SL) in both PsA and RA tissue for most MMP except collagenase I (MMPI), which was equally distributed between the LL and SL. Expression of MMP or their regulators did not differ between PsA synovial membrane (SM) and RA SM in LL. Moreover, although latent gelatinase A (MMP2) staining in PsA SM was equivalent to RA SM, increased gelatinase A activity was found in PsA SM over RA SM using zymography [82.4 (SD 62.8) vs 10.1 (SD 1.7); p = 0.02]. Compared to PsA SM, lesional skin had lower levels of MT1-MMP (MMP 14) (1.4 +/- 1.7 vs 15.7 +/- 8.4; p = 0.009) and MT2-MMP (MMP 15) (12.1 +/- 8.7 vs 21.6 +/- 9.9; p = 0.001). Conclusion. We characterized the expression and activity of gelatinases in PsA and demonstrate that gelatinase activity in SM of PsA patients with erosive disease is comparable to if not greater than that in RA synovium. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Hitchon, CA (reprint author), Univ Manitoba, RR 149,800 Sherbrook St, Winnipeg, MB R3A 1M4, Canada. NR 65 TC 23 Z9 23 U1 0 U2 0 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 2002 VL 29 IS 1 BP 107 EP 117 PG 11 WC Rheumatology SC Rheumatology GA 509KH UT WOS:000173146600018 PM 11824946 ER PT J AU Lyon, GR AF Lyon, GR TI Reading development, reading difficulties, and reading instruction educational and public health issues SO JOURNAL OF SCHOOL PSYCHOLOGY LA English DT Article ID KNOWLEDGE; LANGUAGE C1 NICHHD, Child Dev & Behav Branch, NIH, Bethesda, MD 20892 USA. RP Lyon, GR (reprint author), NICHHD, Child Dev & Behav Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 11 TC 11 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-4405 J9 J SCHOOL PSYCHOL JI J. Sch. Psychol. PD JAN-FEB PY 2002 VL 40 IS 1 BP 3 EP 6 AR PII S0022-4405(01)00091-7 DI 10.1016/S0022-4405(01)00091-7 PG 4 WC Psychology, Educational SC Psychology GA 524YJ UT WOS:000174040200002 ER PT J AU Parry, DAD Marekov, LN Steinert, PM Smith, TA AF Parry, DAD Marekov, LN Steinert, PM Smith, TA TI A role for the 1A and L1 rod domain segments in head domain organization and function of intermediate filaments: Structural analysis of trichocyte keratin SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on Coiled-Coils, Collagen, and Co-Proteins CY SEP 16-21, 2001 CL ALPBACH, AUSTRIA DE disulfide bonds; head domain structure; intermediate filaments; trichocyte keratins ID AMINO-ACID-SEQUENCE; HUMAN TYPE-I; HYDROGEN-BONDED CRYSTALS; CONSISTENT FORCE-FIELD; INTER-MOLECULAR FORCES; PROTEIN FOLD RECOGNITION; HUMAN HAIR KERATINS; ALPHA-KERATIN; WOOL KERATIN; DIFFERENTIAL EXPRESSION AB A dynamic model is proposed to explain how the 1A and linker L1 segments of the rod domain in intermediate filament (IF) proteins affect the head domain organization and vice versa. We have shown in oxidized trichocyte IF that the head domain sequences fold back over and interact with the rod domain. This phenomenon may occur widely in reduced IF as well. Its function may be to stabilize the 1A segments into a parallel two-stranded coiled coil or something closely similar. Under differing reversible conditions, such as altered states of IF assembly, or posttranslational modifications, such as phosphorylation etc., the head domains may no longer associate with the 1A segment. This could destabilize segment 1A and cause the two a-helical strands to separate. Linker L1 would thus act as a hinge and allow the heads to function over a wide lateral range. This model has been explored using the amino acid sequences of the head (N-terminal) domains of Type I and Type II trichocyte keratin intermediate filament chains. This has allowed several quasi-repeats to be identified. The secondary structure corresponding to these repeats has been predicted and a model has been produced for key elements of the Type II head domain. Extant disulfide cross-link data have been used as structural constraints. A model for the head domain structure predicts that a twisted beta-sheet region may wrap around the 1A segment and this may reversibly stabilize a coiled-coil conformation for 1A. The evidence in favor of the swinging head model for IF is discussed. (C) 2002 Elsevier Science (USA). C1 Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Parry, DAD (reprint author), Massey Univ, Inst Fundamental Sci, Private Bag 11-22, Palmerston North, New Zealand. NR 94 TC 22 Z9 24 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN-FEB PY 2002 VL 137 IS 1-2 BP 97 EP 108 DI 10.1006/jsbi.2002.4437 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 566XL UT WOS:000176453500012 PM 12064937 ER PT J AU Watts, NR Jones, LN Cheng, NQ Wall, JS Parry, DAD Steven, AC AF Watts, NR Jones, LN Cheng, NQ Wall, JS Parry, DAD Steven, AC TI Cryo-electron microscopy of trichocyte (hard alpha-keratin) intermediate filaments reveals a low-density core SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on Coiled-Coils, Collagen, and Co-Proteins CY SEP 16-21, 2001 CL ALPBACH, AUSTRIA DE hair; image reconstruction; keratin filaments; polymorphism; scanning transmission electron microscope ID TOBACCO MOSAIC-VIRUS; EPIDERMAL KERATIN; MACROMOLECULAR COMPLEXES; ASSEMBLED INVITRO; MASS; MICROGRAPHS; VIMENTIN; STEM; NEUROFILAMENTS; VISUALIZATION AB Trichocyte intermediate filaments (IF) are the principal components of epidermal appendages such as hair and nail. Based on studies by a variety of techniques, it has been inferred that trichocyte IF are structurally similar to other kinds of IF. However, some basic structural attributes have yet to be established: in particular, it has remained unclear whether IF are hollow. We have examined trichocyte IF isolated from rat vibrissae and human hair follicles by electron microscopy. Scanning transmission electron microscopy of freeze-dried specimens yielded mass-per-unit-length values of similar to32 kDa/nm, with the human preparations also containing filaments at half this density, corresponding to two rather than four protofibrils. Radial density profiles calculated from cryo-electron micrographs of vitrified specimens preserved in a near-native state revealed a low-density region of similar to3 nm diameter around the filament axis. A minor species of filament with the same internal structure was surface-decorated with material arranged with a helical pitch length of 9.3 nm. These filaments appear to represent IF coated with associated proteins-perhaps, "high-sulfur" proteins-readied for incorporation into the filament-matrix biocomposite of the mature hair. (C) 2002 Elsevier Science (USA). C1 NIH, Struct Biol Res Lab, Bethesda, MD 20892 USA. CSIRO, Div Wool Technol, Belmont, Vic 3216, Australia. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. RP Steven, AC (reprint author), NIH, Struct Biol Res Lab, 50 South Dr,Room 1517, Bethesda, MD 20892 USA. FU NCRR NIH HHS [P41-RR01777] NR 41 TC 30 Z9 30 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN-FEB PY 2002 VL 137 IS 1-2 BP 109 EP 118 DI 10.1006/jsbi.2002.4469 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 566XL UT WOS:000176453500013 PM 12064938 ER PT J AU Lenczowski, JM Cronquist, SD Turner, ML AF Lenczowski, JM Cronquist, SD Turner, ML TI Mucocutaneous pustules and erosions associated with ulcerative colitis, sclerosing cholangitis, and peripheral blood eosinophilia SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PYODERMATITIS-PYOSTOMATITIS VEGETANS; INFLAMMATORY DISEASE; BOWEL-DISEASE; CELLS C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Dept Dermatol, Washington, DC USA. RP Turner, ML (reprint author), NCI, Dermatol Branch, Bldg 10,Rm 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM mlturner@mail.nih.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2002 VL 46 IS 1 BP 107 EP 110 DI 10.1067/mjd.2002.118346 PG 4 WC Dermatology SC Dermatology GA 511YR UT WOS:000173294800014 PM 11756954 ER PT J AU Baum, BJ Kok, M Tram, SD Yamano, S AF Baum, BJ Kok, M Tram, SD Yamano, S TI The impact of gene therapy on dentistry - A revisiting after six years SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID GLANDS IN-VIVO; SALIVARY-GLANDS; MEDIATED TRANSFER; AQUAPORIN-1 CDNA; GROWTH-HORMONE; NECK-CANCER; ADENOVIRUS; DELIVERY; SECRETION; CELLS AB Background. Gene therapy is an emerging field of biomedicine. that has commanded considerable scientific and popular attention. The procedure involves the transfer of genes to patients for clinical benefit. Transferred genes can be used for either reparative or pharmacological purposes. Overview. In 1995, the first author and a.-colleague described the potential impact of gene therapy on dentistry, on the basis of initial studies of gene transfer applications to salivary glands, keratinocytes and cancer cells. Their conclusion was that gene therapy would have a significant impact on the nature of dental practice within 20 years. In this article, the authors consider research progress since 1995 and re-examine the earlier conclusion. Practice Implications. In the past six years, remarkable progress has been made in the field of gene therapy, including seven areas relevant to dental practice: bone repair, salivary glands, autoimmune disease, pain, DNA vaccinations, keratinocytes and cancer. While considerable problems remain, thus impeding the routine clinical use of gene transfer, gene therapy will have a pervasive and significant impact on areas of dental practice that are based in biological science. By 2015, this will translate into practitioners' having a wide range of novel biological treatment options for their patients. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1N113, Bethesda, MD 20892 USA. NR 56 TC 25 Z9 27 U1 0 U2 2 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JAN PY 2002 VL 133 IS 1 BP 35 EP 44 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 513VZ UT WOS:000173402100016 PM 11811741 ER PT J AU Blank, PS Sjomeling, CM Backlund, PS Yergey, AL AF Blank, PS Sjomeling, CM Backlund, PS Yergey, AL TI Use of cumulative distribution functions to characterize mass spectra of intact proteins SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID IDENTIFICATION; SPECTROMETRY; PEPTIDES AB The MH+ ions of matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) spectra for a series of closely related but otherwise indistinguishable proteins were analyzed for singularity using a distribution free statistic, the Kolmogorov-Smirnov non-parametric statistic, K-S. The approach allows spectra which might otherwise be taken as identical, to be distinguished. Such analysis of the spectra may lead to a greater understanding of the chemistry of the proteins under investigation. The analysis requires only standard instrumentation. A standard data analysis protocol was developed and applied to generate a normalized cumulative distribution function (NCDF) for each spectrum. Differences in the NCDF for two different spectra were calculated and the maximum difference, Delta (max) compared to critical values of K-S. Values of Delta (max) exceeding the critical value of K-S are taken as the basis for rejecting the statistical null-hypothesis and assigning statistical significance to the differences in the two spectra. We have shown that this approach allows spectra of 1:1 mixtures of closely related recombinant proteins to be distinguished from either protein alone, and that mixtures of a 45 kDa protein and a labeled version of that protein can be distinguished from the pure material and from one another at the level of about 25%. In addition, we are able to use this approach to characterize the extent to which a synthetic glyococonjugation reaction has proceeded under circumstances of differing reaction times. (J Am Soc Mass Spectrom 2002, 13, 40-46) (C) 2002 American Society for Mass Spectrometry. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Yergey, AL (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Room 9D52,MSC 1580, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JAN PY 2002 VL 13 IS 1 BP 40 EP 46 DI 10.1016/S1044-0305(01)00338-5 PG 7 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 504QX UT WOS:000172868300005 PM 11777198 ER PT J AU Rusk, RA Li, XN Mori, Y Irvine, T Jones, M Zetts, AD Kenny, A Sahn, DJ AF Rusk, RA Li, XN Mori, Y Irvine, T Jones, M Zetts, AD Kenny, A Sahn, DJ TI Direct quantification of transmitral flow volume with dynamic 3-dimensional digital color Doppler: A validation study in an animal model SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID CARDIAC-OUTPUT MEASUREMENT; VELOCITY PROFILES; AORTIC REGURGITATION; MITRAL REGURGITATION; CLINICAL VALIDATION; ORIFICE METHOD; CANINE MODEL; IN-VITRO; ECHOCARDIOGRAPHY; AREA AB Accurately quantifying transmitral flow volume is clinically important not only as a measure of cardiac output, but also as a value from which to subtract aortic flow, for determining the severity of mitral regurgitation. However, controversy exists over the accuracy of pulsed Doppler for mitral flow quantification because of the complexity of mitral flow geometry and dynamic changes in flow profile and flow area. To explore the feasibility of directly quantifying transmitral flow volume with a newly developed dynamic 3-dimensional digital color Doppler technique, this in vivo experimental study was conducted to validate the method. Eight open chest sheep were imaged with a multiplane transesophageal (TEE) probe placed on the heart for digital 3-dimensional gated acquisition of mitral inflow over a 180-degree acquisition. The digital velocity data were contour detected for flow area after computing the velocity vectors and flow profile perpendicular to a spherical 3-dimensional surface across the mitral annulus. Flow areas and actual velocities were then integrated in time and space and the resulting flow volumes were compared with those obtained by a reference electromagnetic flowmeter on the aorta for 26 steady hemodynamic states. The flow volumes correlated closely to the electromagnetic references (y = 0.87x + 2.49, r = 0.92, SEE = 1.9 mL per beat). Our study shows that transmitral flow volume can be accurately determined in vivo by this dynamic 3-dimensional digital color Doppler flow quantification method. C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. ATL Ultrasound, Bothell, WA USA. NHLBI, Lab Anim Med & Surg, Bethesda, MD 20892 USA. Freeman Rd Hosp, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England. RP Jones, M (reprint author), NIH, Room 107A,Bldg 14E, Bethesda, MD 20892 USA. NR 27 TC 22 Z9 24 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JAN PY 2002 VL 15 IS 1 BP 55 EP 62 DI 10.1067/mje.2002.116716 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 512HW UT WOS:000173319800009 PM 11781555 ER PT J AU Fettes, KJ Howard, N Hickman, DT Adah, S Player, MR Torrence, PF Micklefield, J AF Fettes, KJ Howard, N Hickman, DT Adah, S Player, MR Torrence, PF Micklefield, J TI Synthesis and nucleic-acid-binding properties of sulfamide- and 3 '-N-sulfamate-modified DNA SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID CONFORMATIONAL-ANALYSIS; PHOSPHODIESTER LINKAGE; DUPLEX STABILITY; IN-VITRO; RNA; OLIGONUCLEOTIDE; AMINOLYSIS; MONOPHOSPHATES; THERAPEUTICS; REPLACEMENT AB A novel synthetic route for the preparation of sulfamide- and 3'-N-sulfamate-modified dinucleosides has been developed. The synthesis utilises 4-nitrophenyl chlorosulfate to prepare 4-nitrophenyl 3'- or 5'-sulfamates (e.g., 18 and 27), which couple smoothly with the alcohol or amine functionalities of other nucleosides. The conformational properties of the sulfamide- and 3'-N-sulfamate-modified dinucleosides d(TnsnT) and d(TnsoT) were compared with the native dinucleotide d(TpT) using NMR and CD spectroscopy. Whilst both modi cations result in a shift in the conformational equilibrium of the 5'-terminal ribose rings from C2'-endo to a preferred C3'-endo conformation, only the 3'-N-sulfamate-modified dimer exhibits an increased propensity to adopt a base-stacked helical conformation. Incorporation of the sulfamide- and 3'-N-sulfamate modi cations into the DNA sequence d(GCGT(10)GCG) allowed the duplex melting temperature to be determined using UV thermal denaturation experiments. This reveals that the sulfamide modi cation significantly destabilises duplexes with both complementary DNA and RNA. However, the 3'-N-sulfamate modi cation has little effect on duplex stability and even stabilises DNA duplexes at low salt concentration. These results indicate that the 3'-N-sulfamate group is one of the most promising neutral replacements of the phosphodiester group in nucleic acids, that have been developed to date, for therapeutic and other important applications. C1 Univ Manchester, Inst Sci & Technol, Dept Chem, Manchester M60 1QD, Lancs, England. Univ London Birkbeck Coll, Dept Chem, London WC1H 0PP, England. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. No Arizona Univ, Dept Chem, Flagstaff, AZ 86011 USA. RP Micklefield, J (reprint author), Univ Manchester, Inst Sci & Technol, Dept Chem, Faraday Bldg,POB 88, Manchester M60 1QD, Lancs, England. RI Micklefield, Jason/I-8502-2016 OI Micklefield, Jason/0000-0001-8951-4873 NR 45 TC 18 Z9 18 U1 1 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1472-7781 J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PY 2002 IS 4 BP 485 EP 495 DI 10.1039/b110603c PG 11 WC Chemistry, Organic SC Chemistry GA 521DF UT WOS:000173823000006 ER PT J AU Chong, HS Ganguly, B Broker, GA Rogers, RD Brechbiel, MW AF Chong, HS Ganguly, B Broker, GA Rogers, RD Brechbiel, MW TI Stereoselective and regioselective synthesis of azepane and azepine derivatives via piperidine ring expansion SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID EFFICIENT SYNTHESIS; BALANOL; AGENTS; ACID AB Diastereomerically pure azepane derivatives 5, 13 were prepared by piperidine ring expansion with exclusive stereoselectivity and regioselectivity and in excellent yield. The structure and stereochemistry of 5 were confirmed via X-ray crystallographic analysis. The ring expansion strategy was applied to the construction of an azepine backbone 22 of a potential biologically active compound. The regiochemistry and stereochemistry of the piperidine ring expansion process were investigated by semiempirical molecular orbital calculations. C1 NCI, Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Cent Salt & Marine Chem Res Inst, Bhavnagar 364002, Gujarat, India. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. RP Brechbiel, MW (reprint author), NCI, Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Rm B3B69, Bethesda, MD 20892 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 20 TC 17 Z9 17 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1472-7781 J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PY 2002 IS 18 BP 2080 EP 2086 DI 10.1039/b204677f PG 7 WC Chemistry, Organic SC Chemistry GA 592HL UT WOS:000177931600010 ER PT J AU Mennemeier, M Vezey, E Lamar, M Jewell, G AF Mennemeier, M Vezey, E Lamar, M Jewell, G TI Crossover is not a consequence of neglect: A test of the orientation/estimation hypothesis SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE neglect; orientation; magnitude estimation; line bisection; attention; confabulation ID UNILATERAL SPATIAL NEGLECT; LINE BISECTION; VISUAL NEGLECT; ATTENTION; STIMULUS; PSEUDONEGLECT; ASYMMETRIES; LAW AB Most patients with neglect demonstrate a crossover effect on line bisection. Crossover refers to a pattern of performance in which long lines (>10 cm) are bisected ipsilateral to brain injury and short lines (<2 cm) are bisected contralateral to brain injury. Crossover bisections on short lines are of interest because they are not predicted by contemporary theories concerning neglect. However, we propose that the effect depends on two independent factors that normally influence bisection performance but are merely exaggerated in neglect-a tendency to overestimate the length of short lines and underestimate long lines and a tendency to orient attention preferentially in one spatial direction. We predicted that both patients with unilateral left and right hemisphere injury would demonstrate crossover on line bisection and that they would overestimate short lines and underestimate Iona lines upon direct visual inspection. Further, the 2 groups were predicted to demonstrate crossover in opposite directions owing to different lesion-induced biases in attentional orientation. Testing 5 patients with right hemisphere injury and 7 patients with left hemisphere injury confirmed each prediction. Additionally, errors in length estimation were exaggerated among patients with right hemisphere injury, most of whom had neglect. It is concluded that while crossover is accentuated in cases of neglect, it is not a consequence of neglect per se. As such, crossover bisections are not at odds with contemporary neglect theory. C1 UAB, Spain Rehabil Ctr, Dept Phys Med & Rehabil, Birmingham, AL 35249 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. Natl Inst Aging, Baltimore, MD USA. Univ Alabama, Dept Psychol, Birmingham, AL USA. RP Mennemeier, M (reprint author), UAB, Spain Rehabil Ctr, Dept Phys Med & Rehabil, Rm 530 1717 6th Ave South, Birmingham, AL 35249 USA. FU NINDS NIH HHS [NS31815] NR 33 TC 9 Z9 11 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JAN PY 2002 VL 8 IS 1 BP 107 EP 114 DI 10.1017/S1355617701020100 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 535TT UT WOS:000174663000010 PM 11843067 ER PT J AU Humphreys, BL AF Humphreys, BL TI Adjusting to progress: interactions between the National Library of Medicine and health sciences librarians, 1961-2001 SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the Medical-Library-Association CY MAY 25-30, 2001 CL ORLANDO, FLORIDA SP Med Lib Assoc AB Most health sciences librarians would agree that the National Library of Medicine's (NLM's) leadership and its services have been highly beneficial to the field, but this does not prevent specific NLM actions or lack of action-from being perceived as annoying or infuriating. Over the past forty years, NLM's interactions with health sciences librarians have been affected by significant additions to NLM's mission and services, the expansion of NLM's direct user groups, and the growing range of possible relationships between health sciences librarians and NLM. The greatest friction between NLM and health services librarians occurs when there is a fundamental change in the way NLM carries out its mission-a change that adds to the web of relationships that link librarians and NLM and prompts corresponding changes in the way other libraries do business. Between 1961 and 2001, there were two such fundamental changes: the implementation of the National Network of Libraries of Medicine and the development and promotion of services targeted toward individual health professionals. On a lesser scale, each new service that connects NLM and health sciences librarians is another potential source of irritation, ready to flare up when the service is interrupted, changed, or eliminated. Other factors-including strong personalities, mistakes, and poor communication-add to, but do not cause, the intermittent problems between NLM and its most longstanding and engaged user group. These problems are in essence the price we pay for the leadership and vision of NLM's directors and for NLM's success in developing excellent services and in enhancing them based on advice from librarians and other users. C1 Natl Lib Med, Lib Operat, Bethesda, MD 20894 USA. RP Humphreys, BL (reprint author), Natl Lib Med, Lib Operat, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 42 TC 7 Z9 7 U1 0 U2 0 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 2002 VL 90 IS 1 BP 4 EP 20 PG 17 WC Information Science & Library Science SC Information Science & Library Science GA 563HR UT WOS:000176250700002 PM 11838459 ER PT J AU Florance, V Giuse, NB Ketchell, DS AF Florance, V Giuse, NB Ketchell, DS TI Information in context: integrating information specialists into practice settings SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID HEALTH-SCIENCES LIBRARIANS; EDUCATION; GRANT AB An information need (the problem) cannot be divorced from its context. The problem context determines the urgency, granularity of detail, authority, and level of certainty required for an acceptable answer and dictates the expertise and resources that can be brought to bear. The size and diversity of the sources that can be marshaled during clinical problem solving is cognitively unmanageable-too large and too complex for a single person to process effectively in a constrained timeframe. Can the clinical team, as currently constituted, collectively handle this information-processing task, or is there a need for special information expertise on the team? If there is such a need, what is the best way to prepare information specialists to participate in context-based problem solving? This article explores preparation for work in information-rich, problem-solving environments. The authors provide two case studies, one clinical and one bioscientific, that elucidate knowledge and training requirements for information specialists who work as peers in patient care and research settings. C1 Natl Lib Med, Bethesda, MD 20892 USA. Vanderbilt Univ, Ctr Med, Eskind Biomed Lib, Nashville, TN 37232 USA. Univ Washington, Hlth Sci Lib, Seattle, WA 98195 USA. RP Florance, V (reprint author), Natl Lib Med, Rockledge 1,Suite 301,6705 Rockledge Dr, Bethesda, MD 20892 USA. RI Giuse, Nunzia/N-2032-2016; OI Giuse, Nunzia/0000-0002-7644-9803; Florance, Valerie/0000-0001-9135-3562 NR 36 TC 24 Z9 24 U1 1 U2 2 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 2002 VL 90 IS 1 BP 49 EP 58 PG 10 WC Information Science & Library Science SC Information Science & Library Science GA 563HR UT WOS:000176250700006 PM 11838460 ER PT J AU Wexler, P Phillips, S AF Wexler, P Phillips, S TI Tools for clinical toxicology on the World Wide Web: Review and scenario SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Article DE information; computers; Web; toxicology ID INFORMATION; RESOURCES AB Clinical toxicologists are entrusted with the health and safety of humans and animals exposed to toxic substances. To do their jobs well they need a solid knowledge of toxicological principles, an ability to handle emergent situations, a "bedside" manner that results in a good rapport with patients, and the ability to access current and accurate information in order to properly care for the afflicted. An information armamentarium that is increasingly digital and Web-based is becoming a necessity. This article reviews Web resources that can assist the toxicologist. A case scenario is presented to provide a practical perspective to the information tools outlined. C1 Natl Lib Med, Toxicol & Environm Hlth Informat Program, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Toxicol Associates, Denver, CO 80262 USA. RP Wexler, P (reprint author), Natl Lib Med, Toxicol & Environm Hlth Informat Program, 2 Democracy Plaza,Suite 510,6707 Democracy Blvd, Bethesda, MD 20892 USA. NR 12 TC 1 Z9 1 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 2002 VL 40 IS 7 BP 893 EP 902 DI 10.1081/CLT-120016961 PG 10 WC Toxicology SC Toxicology GA 629LC UT WOS:000180050300010 PM 12507059 ER PT J AU Dylewski, ML Picciano, MF AF Dylewski, ML Picciano, MF TI Milk selenium content is enhanced by modest selenium supplementation in extended lactation SO JOURNAL OF TRACE ELEMENTS IN EXPERIMENTAL MEDICINE LA English DT Article DE selenium; lactation; dietary supplement; human milk; dietary reference intakes ID BREAST-FED INFANTS; GLUTATHIONE-PEROXIDASE ACTIVITY; STABLE-ISOTOPE TRACERS; DIETARY SELENIUM; WOMEN; BLOOD; DEFICIENCY; NUTRITION; MOTHERS; FORMULA AB Supplemental selenium (Se) as selenate, selenomethionine, or Se-enriched yeast at 100-200 mug Se/day causes an increase or prevents a decline in human milk selenium content during the first 6 months of lactation. In this study, we evaluated the impact of supplemental Se as sodium selenate at 20 mug/day, an amount that closely approximates the quantity of selenium lost daily via milk secretion. Lactating women (n = 23) provided dietary data and milk and plasma samples at 3 and 6 months postpartum. At 3 months postpartum, all women received a daily vitamin/mineral supplement that furnished 20 mug of Se as sodium selenate for 3 months. Mean Se intake from self-selected diets was 111 +/- 40 mug/day and did not differ between 3 and 6 months. Selenium supplementation increased milk Se from 3 (295 +/- 18 nmol/L; 23 +/- 7 ng/ mL) to 6 months (417 +/- 39 nmol/L; 32 +/- 14 ng/mL) postpartum (P less than or equal to 0.01) and corresponding infant Se intakes from 12 mug/day to 20 mug/day. Maternal plasma Se concentration was 1.46 +/- 0.42 mumol/L (115 +/- 33 ng/mL) at 3 months and 1.76 +/- 0.20 mumol/L (155 +/- 16 ng/mL) at 6 months postpartum, but this apparent difference was not significantly different. Maternal supplemental Se at 20 mug/day caused a 41% increase in human milk Se and a corresponding 67% increase in infant Se intake. Data show that supplemental Se at or near the quantity secreted daily is sufficient to prevent a decline in human milk Se with advancing lactation. C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Penn State Univ, Grad Program Nutr, University Pk, PA 16802 USA. RP Picciano, MF (reprint author), NIH, Off Dietary Supplements, 31 Ctr Dr,11-329, Bethesda, MD 20892 USA. NR 40 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0896-548X J9 J TRACE ELEM EXP MED JI J. Trace Elem. Exp. Med. PY 2002 VL 15 IS 4 BP 191 EP 199 DI 10.1002/jtra.10016 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 608BV UT WOS:000178826000002 ER PT J AU Cermelli, C Vinceti, M Scaltriti, E Bazzani, E Beretti, F Vivoli, G Portotani, M AF Cermelli, C Vinceti, M Scaltriti, E Bazzani, E Beretti, F Vivoli, G Portotani, M TI Selenite inhibition of Coxsackie virus B5 replication: implications on the etiology of Keshan disease SO JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY LA English DT Article DE Keshan disease; Coxsackie virus; selenite inhibition ID SODIUM SELENITE; SULFHYDRYL COMPOUNDS; INDUCED MYOCARDITIS; OXIDATIVE STRESS; CELL-GROWTH; APOPTOSIS; MICE; RNA; EPIDEMIOLOGY; GLUTATHIONE AB Keshan disease is a cardiomyopathy of unknown origin reported in some areas of China. Because of epidemiologic features, this disease was ascribed to an infectious agent, likely a Coxsackie virus, but it has also been thought to depend on selenium deficiency, mainly because selenite is effective in its prophylaxis. We examined the hypothesis that pharmacological activity of selenite on Coxsackie virus growth was associated with prevention of Keshan disease. We studied the antiviral effects of three selenium compounds on Coxsackie virus B5 replication: five muM selenite reduced viral replication, whilst 10 muM selenate and selenomethionine did not exhibit any antiviral activity. The inhibitory activity of selenite on viral replication was due to its toxicity following its interaction with thiols, as that activity could be blocked by dithiothreitol, a sulfhydryl-protecting agent known to reverse several toxic effect of selenite. Zinc, another inhibitor of selenite toxicity, also counteracted the antiviral effect of selenite. The selenium compounds showed only limited activity against herpes simplex 1 virus and IHD strain of vaccinia virus. A direct inhibitory effect of selenite on Coxsackie virus replication might explain the efficacy demonstrated by this compound in the prophylaxis of Keshan disease. C1 Univ Modena, Dipartimento Sci Igienist Microbiol & Biostat, I-41100 Modena, Italy. RP Cermelli, C (reprint author), NINCDS, Neuroimmunol Branch, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. RI Cermelli, Claudio/L-1501-2016; Vinceti, Marco/O-2509-2015 OI Cermelli, Claudio/0000-0003-3396-0000; Vinceti, Marco/0000-0002-0551-2473 NR 44 TC 17 Z9 18 U1 1 U2 3 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0946-672X J9 J TRACE ELEM MED BIO JI J. Trace Elem. Med. Biol. PY 2002 VL 16 IS 1 BP 41 EP 46 DI 10.1016/S0946-672X(02)80007-4 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 526WG UT WOS:000174152200006 PM 11878751 ER PT J AU DeVore, GR Romero, R AF DeVore, GR Romero, R TI Genetic sonography - A cost-effective method for evaluating women 35 years and older who decline genetic amniocentesis SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE genetic sonography; amniocentesis; tisomy 21; cost-effectiveness ID 2ND-TRIMESTER AMNIOCENTESIS; RISK ASSESSMENT; DOWNS-SYNDROME; MATERNAL AGE; FETAL LOSS; TRISOMY-21; ULTRASOUND; FETUSES; PREGNANCY; MARKERS AB Objective. To determine whether offering genetic sonography to patients who decline invasive testing can increase the detection rate of trisomy 21 and is cost-effective. Methods. The detection rate of trisomy 21, the number of pregnancy losses after amniocentesis, and the cost of detecting a single fetus with trisomy 21 were determined in women 35 years and older managed according to the following 3 policies: (1) universal amniocentesis, (2) genetic counseling for maternal age-associated risks for trisomy 21 followed by amniocentesis in patients who elected it, and (3) genetic counseling followed by genetic sonography in patients who originally declined genetic amniocentesis. Results. From a population of 40,143 women 35 years and older, the expected number of trisomy 21 fetuses was 349. After genetic counseling, 32% of patients declined invasive testing, resulting in detection of 70% of fetuses with trisomy 21. For universal amniocentesis, the cost to detect I fetus with trisomy 21 was $138,036. For the 32% who declined invasive testing after genetic counseling and underwent genetic sonography, the cost to detect a single fetus with trisomy 21 was a function of sensitivity and the screen-positive rate. For screen-positive rates between 5% and 25%, genetic sonography resulted in a cost savings between 14.3% and 18.8% when compared with universal invasive testing and resulted in a considerable increase in detection of fetuses with trisomy 21 (77% to 97%). Conclusions. A policy of offering genetic sonography followed by amniocentesis to patients 35 years and older who originally decline invasive testing for the diagnosis of trisomy 21 is cost-effective and results in a higher overall detection rate for trisomy 21 without an increased risk of pregnancy loss. C1 NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. RP DeVore, GR (reprint author), Suite 206,301 S Fair Oaks Ave, Pasadena, CA 91105 USA. NR 22 TC 11 Z9 12 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JAN PY 2002 VL 21 IS 1 BP 5 EP 13 PG 9 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 509AE UT WOS:000173121300002 PM 11794403 ER PT J AU Pavlovich, CP Walther, MM Choyke, PL Pautler, SE Chang, R Linehan, WM Wood, BJ AF Pavlovich, CP Walther, MM Choyke, PL Pautler, SE Chang, R Linehan, WM Wood, BJ TI Percutaneous radio frequency ablation of small renal tumors: Initial results SO JOURNAL OF UROLOGY LA English DT Article DE kidney neoplasms; carcinoma, renal cell; surgical procedures, minimally invasive ID PARENCHYMAL SPARING SURGERY; RADIOFREQUENCY ABLATION; CELL CARCINOMA; NATURAL-HISTORY; LINDAU DISEASE; IN-VIVO; CANCER; SIZE; EXPERIENCE; HEREDITARY AB Purpose: Thermal tissue ablation with radio frequency energy is an experimental treatment of renal tumor. We report early results of an ongoing trial of percutaneous radio frequency ablation for small renal tumors. Materials and Methods: Patients with percutaneously accessible renal tumors were evaluated for radio frequency ablation. Tumors were solid on computerized tomography (CT), 3 cm. or less in diameter and enlarging during at least 1 year. Ablation was performed at the Interventional Radiology suite under ultrasound and/or CT guidance. A 50 W., 460 kHz. electrosurgical generator delivered radio frequency energy via a percutaneously placed 15 gauge coaxial probe. At least 2, 10 to 12-minute ablation cycles were applied to each lesion. Patients were observed overnight before discharge from hospital and reevaluated 2 months later. Results: A total of 24 ablations were performed in 21 patients with renal tumor, including solid von Hippel-Lindau clear cell tumor in 19 and hereditary papillary renal cancer 2. Most (22 of 24) procedures were performed with patients under conscious sedation. At 2 months postoperatively mean tumor diameter plus or minus standard deviation decreased from 2.4 +/- 0.4 to 2.0 +/- 0.5 cm. (p = 0.001), and a majority of tumors (19 of 24, 79%) ceased to be enhanced on contrast CT. Mean serum creatinine plus or minus standard deviation was unchanged during this interval (1.0 +/- 0.2 mg./dl.). No major and 4 minor complications were encountered, including 2 episodes each of transient psoas pain and flank skin numbness. Conclusions: Percutaneous radio frequency ablation of small renal tumor is well tolerated and minimally invasive. It will remain experimental until procedural and imaging parameters that correlate with tumor destruction are validated. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Div Radiol, Bethesda, MD 20892 USA. RP Pavlovich, CP (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 22 TC 209 Z9 222 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2002 VL 167 IS 1 BP 10 EP 15 DI 10.1016/S0022-5347(05)65371-2 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 502CM UT WOS:000172726200002 PM 11743264 ER PT J AU Pautler, SE Richards, C Libutti, SK Linehan, WM Walther, MM AF Pautler, SE Richards, C Libutti, SK Linehan, WM Walther, MM TI Intentional resection of the diaphragm during cytoreductive laparoscopic radical nephrectomy SO JOURNAL OF UROLOGY LA English DT Article DE kidney; laparoscopy; nephrectomy; diaphragm ID RENAL-CELL CARCINOMA; EXPERIENCE AB Purpose: Laparoscopic radical nephrectomy is being performed more commonly. To our knowledge intentional resection of the diaphragm during laparoscopic radical nephrectomy for large renal tumors has not yet been described. We detail the laparoscopic management of diaphragmatic resection. Materials and Methods: From March 1996 to February 2001, 36 patients underwent cytoreductive laparoscopic radical nephrectomy at our institution in preparation for systemic immunotherapy. Charts and operative tapes were reviewed and cases were identified in which diaphragmatic resection was performed for locally invasive tumors. Results: In 3 patients a portion of the diaphragm was dissected via laparoscopy during debulking nephrectomy. All patients had renal cell carcinoma with documented metastatic disease. The diaphragm was repaired laparoscopically using intracorporeal suturing techniques in 2 of the 3 patients and a chest tube was placed in all 3. Transient systolic hypotension and hypercarbia in 1 case resolved with manual ventilation. The chest tube was removed on postoperative days 2 to 4. There were no complications and no ipsilateral pleural metastasis was identified at an average of 6 weeks (range 2 to 23) of followup. Conclusions: A portion of the diaphragm may be intentionally resected during laparoscopic radical nephrectomy. This maneuver may be successfully managed without conversion to an open procedure. In cases of a large diaphragmatic defect or the potential for coagulopathy postoperatively a chest tube should be inserted. Potential invasion of the diaphragm by large tumors should not be considered a contraindication to cytoreductive laparoscopic radical nephrectomy. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Anesthesiol, Bethesda, MD 20892 USA. RP Pautler, SE (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 11 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2002 VL 167 IS 1 BP 48 EP 50 DI 10.1016/S0022-5347(05)65380-3 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 502CM UT WOS:000172726200014 PM 11743273 ER PT J AU Coady, SA Sharrett, AR Zheng, ZJ Evans, GW Heiss, G AF Coady, SA Sharrett, AR Zheng, ZJ Evans, GW Heiss, G TI Vasectomy, inflammation, atherosclerosis and long-term follow-up for cardiovascular diseases: No associations in the atherosclerosis risk in communities study SO JOURNAL OF UROLOGY LA English DT Article DE testis; vasectomy; cardiovascular diseases; atherosclerosis ID CORONARY-HEART-DISEASE; MEN; INFARCTION; STROKE AB Purpose: Although human studies have failed to reveal an increased risk of clinical cardiovascular disease in men who undergo vasectomy, the possibility exists that an association may be detectable only after a long followup, or it may be more evident for subclinical than clinical disease. We assessed the association of vasectomy with inflammation and coagulation factors, carotid intimal-medial thickness, carotid plaque, prevalent peripheral arterial disease, and incident coronary heart disease and stroke in the Atherosclerosis Risk in Communities cohort. Materials and Methods: Included in the study were 3,957 white men 45 to 64 years old who were free of coronary heart disease at the Atherosclerosis Risk in Communities (ARIC) baseline examination in 1987 to 1989. Data on vasectomy was collected at baseline by self-reporting. High resolution B-mode ultrasound was done to assess carotid intimal-medial thickness and carotid plaque. The cohort was followed an average of 9 years for incident cardiovascular events. Results: Average time since vasectomy was 16 years. Approximately 20% of the population had undergone vasectomy 20 years or more ago at baseline. Multivariate analysis showed no association of vasectomy status with inflammation or coagulation factors, peripheral arterial disease, carotid plaque, carotid far wall thickness, incident coronary heart disease or stroke. Associations were unaffected by the time since vasectomy. Conclusions: There is no evidence in this population based sample of men indicating that vasectomy is related to atherosclerosis even after more than 20 years of followup. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Cardiovasc Hlth Branch, Atlanta, GA USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. RP Coady, SA (reprint author), NHLBI, Div Epidemiol & Clin Applicat, Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2002 VL 167 IS 1 BP 204 EP 207 DI 10.1016/S0022-5347(05)65413-4 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 502CM UT WOS:000172726200054 PM 11743306 ER PT J AU Chen, KJ Keshner, EA Peterson, BW Hain, TC AF Chen, KJ Keshner, EA Peterson, BW Hain, TC TI Modeling head tracking of visual targets SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article DE mathematical model; head control; vision; gaze ID PURSUIT EYE-MOVEMENTS; HUMAN SMOOTH PURSUIT; RANDOM ROTATIONS; HORIZONTAL PLANE; POSTURAL CONTROL; VERTICAL PLANE; MAIN-SEQUENCE; STABILIZATION; MECHANISMS; BALANCE AB Control of the head involves somatosensory, vestibular, and visual feedback. The dynamics of these three feedback systems must be identified in order to gain a greater understanding of the head control system. We have completed one step in the development of a head control model by identifying the dynamics of the visual feedback system. A mathematical model of human head tracking of visual targets in the horizontal plane was fit to experimental data from seven subjects performing a visual head tracking task. The model incorporates components based on the underlying physiology of the head control system. Using optimization methods, we were able to identify neural processing delay, visual control gain, and neck viscosity parameters in each experimental subject. C1 Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. Rehabil Inst Chicago, Sensory Motor Performance Program, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Physiol, Chicago, IL 60610 USA. Northwestern Mem Hosp, Dept Otolaryngol, Chicago, IL 60611 USA. RP Chen, KJ (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [DC01125, DC02072]; NINDS NIH HHS [NS22490] NR 43 TC 4 Z9 4 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2002 VL 12 IS 1 BP 25 EP 33 PG 9 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 633NA UT WOS:000180288300003 PM 12515889 ER PT J AU Stevceva, L Kelsall, B Nacsa, J Moniuszko, M Hel, Z Tryniszewska, E Franchini, G AF Stevceva, L Kelsall, B Nacsa, J Moniuszko, M Hel, Z Tryniszewska, E Franchini, G TI Cervicovaginal lamina propria lymphocytes: Phenotypic characterization and their importance in cytotoxic T-lymphocyte responses to simian immunodeficiency virus SIVmac251 SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTED RHESUS-MONKEYS; ALPHA(E) (CD103)-DEFICIENT MICE; CELL DEPLETION; E-CADHERIN; INTRAEPITHELIAL LYMPHOCYTES; EPITHELIAL-CELLS; IMMUNE-RESPONSES; INTEGRIN CD103; VAGINAL MUCOSA; SIV INFECTION AB Most human immunodeficiency virus (HIV) type I infections occur by the mucosal route. Thus, it is important to assess the immune responses to HIV in the vaginal, cervical, and rectal compartments. Here we quantitated the virus-specific CD8(+) T-cell response and characterized the phenotype of lymphocytes in the genital tracts of naive macaques, macaques acutely or chronically infected with simian immunodeficiency virus SIVmac251, and macaques chronically infected with chimeric simian/human immunodeficiency virus SHIVKU2. Vaginal biopsy samples or samples obtained at the time of euthanasia were used in this analysis. The percentage of Gag-specific, tetramer-positive T cells was as high as 13 to 14% of the CD3(+) CD8(+) T-cell population in the vaginal and cervical laminae propriae of both SIVmac251 and SHIVKU2 chronically infected macaques. In most cases, the frequency of this response in the cervicovaginal compartment far exceeded the frequency in the blood or the draining iliac lymph node. Vaginal laminae propriae of naive macaques contained 55 to 65% CD3(+) CD8(+) cells and 28 to 34% CD3(+) CD4(+) cells, while the majority of intraepithelial cells were CD8(+) T cells (75 to 85%). For the same cells, the surface expression of CD62L was low whereas that of alphaE beta7 was high. No difference in the expression of CD45RA on CD8(+) T cells was observed in the chronic stage of SIVmac251 infection. Although no decrease in the percentage of CD4(+) cells in the genital tract was observed within the first 12 days of infection, by 6 weeks from SIVmac251 infection and thereafter the percentage of CD4(+) T cells was decreased in the laminae propriae of the vagina and cervix. Expression of CD45RA did not differ in naive and acutely SIVmac251 infected macaques. Information on the quality and quantity of local immune responses may help in the design of vaccine strategies aimed at containing viral replication at the site of viral encounter. C1 NCI, Anim Models & Retroviral Vaccines Sect, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NIAID, Muscosal Immun Sect, Lab Clin Invest, NIH, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Basic Res Lab, NIH, 41-D804, Bethesda, MD 20892 USA. OI Hel, Zdenek/0000-0002-4923-4794 NR 62 TC 41 Z9 41 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 2002 VL 76 IS 1 BP 9 EP 18 DI 10.1128/JVI.76.1.9-18.2002 PG 10 WC Virology SC Virology GA 500UJ UT WOS:000172644900002 PM 11739667 ER PT J AU DiFronzo, NL Leung, CT Mammel, MK Georgopoulos, K Taylor, BJ Pham, QN AF DiFronzo, NL Leung, CT Mammel, MK Georgopoulos, K Taylor, BJ Pham, QN TI Ikaros, a lymphoid-cell-specific transcription factor, contributes to the leukemogenic phenotype of a mink cell focus-inducing murine leukemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; DNA-BINDING PROTEINS; DISEASE SPECIFICITY; HEMATOPOIETIC PROGENITORS; ENHANCER SEQUENCES; VIRAL SEQUENCES; GENE ENCODES; AKR MICE; IN-VIVO; 3' END AB Mink cell focus-inducing (MCF) viruses induce T-cell lymphomas in AKR/J strain mice. MCF 247, the prototype of this group of nonacute murine leukemia viruses, transforms thymocytes, in part, by insertional mutagenesis and enhancer-mediated dysregulation of cellular proto-oncogenes. The unique 3' (U3) regions in the long terminal repeats of other murine leukemia viruses contain transcription factor binding sites known to be important for enhancer function and for the induction of T-cell lymphomas. Although transcription factor binding sites important for the biological properties of MCF 247 have not been identified, pathogenesis studies from our laboratory suggested to us that binding sites for Ikaros, a lymphoid-cell-restricted transcriptional regulator, affect the biological properties of MCF 247. In this report, we demonstrate that Ikaros binds to predicted sites in U3 sequences of MCF 247 and that site-directed mutations in these sites greatly diminish this binding in vitro. Consistent with these findings, ectopic expression of Ikaros in murine cells that do not normally express this protein significantly increases transcription from the viral promoter in transient gene expression assays. Moreover, site-directed mutations in specific Ikaros-binding sites reduce this activity in T-cell lines that express Ikaros endogenously. To determine whether the Ikaros-binding sites are functional in vivo, we inoculated newborn mice with a variant MCF virus containing a mutant Ikaros-binding site. The variant virus replicated in thymocytes less efficiently and induced lymphomas with a delayed onset compared to the wild-type virus. These data are consistent with the hypothesis that the Ikaros-binding sites in the U3 region of MCF 247 are functional and cooperate with other DNA elements for optimal enhancer function in vivo. C1 George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Ctr Virol Immunol & Infect Dis Res, Washington, DC 20010 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02138 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP DiFronzo, NL (reprint author), George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Ctr Virol Immunol & Infect Dis Res, Washington, DC 20010 USA. NR 51 TC 9 Z9 10 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 2002 VL 76 IS 1 BP 78 EP 87 DI 10.1128/JVI.76.1.78-87.2002 PG 10 WC Virology SC Virology GA 500UJ UT WOS:000172644900008 PM 11739673 ER PT J AU von Gegerfelt, AS Liska, V Li, PL McClure, HM Horie, K Nappi, F Montefiori, DC Pavlakis, GN Marthas, ML Ruprecht, RM Felber, BK AF von Gegerfelt, AS Liska, V Li, PL McClure, HM Horie, K Nappi, F Montefiori, DC Pavlakis, GN Marthas, ML Ruprecht, RM Felber, BK TI Rev-independent simian immunodeficiency virus strains are nonpathogenic in neonatal macaques SO JOURNAL OF VIROLOGY LA English DT Article ID ATTENUATED VACCINE STRAINS; MESSENGER-RNA EXPORT; RHESUS MACAQUES; POSTTRANSCRIPTIONAL REGULATION; RETROVIRUS TYPE-1; MOLECULAR CLONES; VIRAL LOAD; ELEMENT; LIVE; SIV AB The viral protein Rev is essential for the export of the subset of unspliced and partially spliced lentiviral mRNAs and the production of structural proteins. Rev and its RNA binding site RRE can be replaced in both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) by the constitutive RNA transport element CTE of the simian type D retroviruses. We used neonatal macaques as a sensitive animal model to evaluate the pathogenicity of a pair of SIV mutant strains generated from Rev-independent molecular clones of SIVmac239 which differ only in the presence of the nef open reading frame. After high primary viremia, all animals remained persistently infected at levels below the threshold of detection. All macaques infected as neonates developed normally, and none showed any signs of immune dysfunction or disease during follow-up ranging from 2.3 to 4 years. Therefore, the Rev-RRE regulatory mechanism plays a key role in the maintenance of high levels of virus propagation, which is independent of the presence of nef. These data demonstrate that Rev regulation plays an important role in the pathogenicity of SIV. Replacement of Rev-RRE by the CTE provides a novel approach to dramatically lower the virulence of a pathogenic lentivirus. These data further suggest that antiretroviral strategies leading to even a partial block of Rev function may modulate disease progression in HIV-infected individuals. C1 NCI, Frederick Canc Res & Dev Ctr, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Human Retrovirus Sect, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA. Univ Calif Davis, Dept Vet Pathol Microbiol & Immunol, Davis, CA 95616 USA. RP Felber, BK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Human Retrovirus Pathogenesis Sect, Bldg 535,Rm 110, Frederick, MD 21702 USA. FU NCIRD CDC HHS [IP3028691-01]; NCRR NIH HHS [P51 RR000169, R01 RR014180, P51 RR000165, R01 RR14180, RR-00165, RR00169]; PHS HHS [R01 A135533-S1] NR 39 TC 12 Z9 12 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 2002 VL 76 IS 1 BP 96 EP 104 DI 10.1128/JVI.76.1.96-104.2002 PG 9 WC Virology SC Virology GA 500UJ UT WOS:000172644900010 PM 11739675 ER PT J AU Demirov, DG Orenstein, JM Freed, EO AF Demirov, DG Orenstein, JM Freed, EO TI The late domain of human immunodeficiency virus type 1 p6 promotes virus release in a cell type-dependent manner SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; MURINE LEUKEMIA-VIRUS; LATE ASSEMBLY DOMAIN; ROUS-SARCOMA VIRUS; GP41 CYTOPLASMIC TAIL; PROLINE-RICH MOTIF; GAG PROTEIN; PARTICLE-PRODUCTION; MATRIX PROTEIN; SH3 DOMAINS AB The p6 domain of human immunodeficiency virus type I (HIV-1) is located at the C terminus of the Gag precursor protein Pr55(Gag). Previous studies indicated that p6 plays a critical role in HIV-1 particle budding from virus-expressing HeLa cells. In this study, we performed a detailed mutational analysis of the N terminus of p6 to map the sequences required for efficient virus release. We observed that the highly conserved P-T/S-A-P motif located near the N terminus of p6 is remarkably sensitive to change; even conservative mutations in this sequence imposed profound virus release defects in HeLa cells. In contrast, single and double amino acid substitutions outside the P-T/S-A-P motif had no significant effect on particle release. The introduction of stop codons one or two residues beyond the P-T/S-A-P motif markedly impaired virion release, whereas truncation four residues beyond P-T/S-A-P had no effect on particle production in HeLa cells. By examining the effects of p6 mutation in biological and biochemical analyses and by electron microscopy, we defined the role of p6 in particle release and virus replication in a panel of T-cell and adherent cell lines and in primary lymphocytes and monocyte-derived macrophages. We demonstrated that the effects of p6 mutation on virus replication are markedly cell type dependent. Intriguingly, even in T-cell lines and primary lymphocytes in which p6 mutations block virus replication, these changes had little or no effect on particle release. However, p6-mutant particles produced in T-cell lines and primary lymphocytes exhibited a defect in virion-virion detachment, resulting in the production of tethered chains of virions. Virus release in monocyte-derived macrophages was markedly inhibited by p6 mutation. To examine further the cell type-specific virus release defect in HeLa versus T cells, transient heterokaryons were produced between HeLa cells and the Jurkat T-cell line. These heterokaryons display a T-cell-like phenotype with respect to the requirement for p6 in particle release. The results described here define the role of p6 in virus replication in a wide range of cell types and reveal a strong cell type-dependent requirement for p6 in virus particle budding. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. RP Freed, EO (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 307, Bethesda, MD 20892 USA. NR 68 TC 146 Z9 147 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 2002 VL 76 IS 1 BP 105 EP 117 DI 10.1128/JVI.76.1.105-117.2002 PG 13 WC Virology SC Virology GA 500UJ UT WOS:000172644900011 PM 11739676 ER PT J AU Moore, AC Kong, WP Chakrabarti, BK Nabel, GJ AF Moore, AC Kong, WP Chakrabarti, BK Nabel, GJ TI Effects of antigen and genetic adjuvants on immune responses to human immunodeficiency virus DNA vaccines in mice SO JOURNAL OF VIROLOGY LA English DT Article ID FLT3 LIGAND; IN-VIVO; DENDRITIC CELLS; HIV-1; IMMUNIZATION; INFECTION; CYTOKINE; AUGMENTATION; CODELIVERY; EXPRESSION AB The effects of genetic adjuvants on Immoral and cell-mediated immunity to two human immunodeficiency virus antigens, Env and Nef, have been examined in mice. Despite similar levels of gene expression and the same gene delivery vector, the immune responses to these two gene products differed following DNA immunization. Intramuscular immunization with a Nef expression vector plasmid generated a humoral response and antigen-specific gamma interferon (IFN-gamma) production but little cytotoxic-T-lymphocyte (CTL) immunity. In contrast, immunization with an Env vector stimulated CTL activity but did not induce a high-titer antibody response. The ability to modify these antigen-specific immune responses was investigated by coinjection of DNA plasmids encoding cytokine and/or hematopoietic growth factors, interleukin-2 (IL-2), IL-12, IL-15, FIt3 ligand (FL), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Coadministration of these genes largely altered the immune responses quantitatively but not qualitatively. IL-12 induced the greatest increase in IFN-gamma and immunoglobulin G responses to Nef, and GM-CSF induced the strongest IFN-gamma and CTL responses to Env. A dual approach of expanding innate immunity by administering the FL gene, together with a cytokine that enhances adaptive immune responses, IL-2, IL-12, or IL-15, generated the most potent immune response at the lowest doses of Nef antigen. These findings suggest that intrinsic properties of the antigen determine the character of immune reactivity for this method of immunization and that specific combination of innate and adaptive immune cytokine genes can increase the magnitude of the response to DNA vaccines. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. NR 34 TC 84 Z9 101 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2002 VL 76 IS 1 BP 243 EP 250 DI 10.1128/JVI.76.1.243-250.2002 PG 8 WC Virology SC Virology GA 500UJ UT WOS:000172644900024 PM 11739689 ER PT J AU Pal, R Venzon, D Letvin, NL Santra, S Montefiori, DC Miller, NR Tryniszewska, E Lewis, MG VanCott, TC Hirsch, V Woodward, R Gibson, A Grace, M Dobratz, E Markham, PD Hel, Z Nacsa, J Klein, M Tartaglia, J Franchini, G AF Pal, R Venzon, D Letvin, NL Santra, S Montefiori, DC Miller, NR Tryniszewska, E Lewis, MG VanCott, TC Hirsch, V Woodward, R Gibson, A Grace, M Dobratz, E Markham, PD Hel, Z Nacsa, J Klein, M Tartaglia, J Franchini, G TI ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; CELLULAR IMMUNE-RESPONSES; LONG-TERM NONPROGRESSORS; INFECTED RHESUS-MONKEYS; VACCINIA VIRUS; ANTIRETROVIRAL TREATMENT; NEUTRALIZING ANTIBODIES; UNINFECTED VOLUNTEERS; RECOMBINANT VACCINE; SERONEGATIVE ADULTS AB T-cell-mediated immune effector mechanisms play an important role in the containment of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication after infection. Both vaccination- and infection-induced T-cell responses are dependent on the host major histocompatibility complex classes I and II (MHC-I and MHC-II) antigens. Here we report that both inherent, host-dependent immune responses to SIVmac251 infection and vaccination-induced immune responses to viral antigens were able to reduce virus replication and/or CD4(+) T-cell loss. Both the presence of the MHC-I Mamu-A*01 genotype and vaccination of rhesus macaques with ALVAC-SIV-gag-pol-env (ALVAC-SIV-gpe) contributed to the restriction of SIVmac251 replication during primary infection, preservation of CD4(+) T cells, and delayed disease progression following ;intrarectal challenge exposure of the animals to SIVmac251 ((561)). ALVAC-SIV-gpe immunization induced cytotoxic T-lymphocyte (CTL) responses cumulatively in 67% of the immunized animals. Following viral challenge, a significant secondary virus-specific CD8(+) T-cell response was observed in the vaccinated macaques. In the same immunized macaques, a decrease in virus load during primary infection (P = 0.0078) and protection from CD4 loss during both acute and chronic phases of infection (P = 0.0099 and P = 0.03, respectively) were observed. A trend for enhanced survival of the vaccinated macaques was also observed. Neither boosting the ALVAC-SIV-gpe with gp120 immunizations nor administering the vaccine by the combination of mucosal and systemic immunization routes increased significantly the protective effect of the ALVAC-SIV-gpe vaccine. While assessing the role of MHC-I Mamu-A*01 alone in the restriction of viremia following challenge of nonvaccinated animals with other SIV isolates, we observed that the virus load was not significantly lower in MamuA*01-positive macaques following intravenous challenge with either SIVmac251 (561) or SIVSME660. However, a significant delay in CD4(+) T-cell loss was observed in Mamu-A*01-positive macaques in each group. Of interest, in the case of intravenous or intrarectal challenge with the chimeric SIV/HIV strains SHIV89.6P or SHIVKU2, respectively, MHC-I Mamu-A*01-positive macaques did not significantly restrict primary viremia. The finding of the protective effect of the Mamu-A*01 molecule parallels the protective effect of the B*5701 HLA allele in HIV-1-infected humans and needs to be accounted for in the evaluation of vaccine efficacy against SIV challenge models. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Adv BioSci Labs Inc, Kensington, MD 20895 USA. NIAID, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Duke Univ, Med Ctr, Ctr AIDS Res, Dept Surg, Durham, NC 27710 USA. Med Acad Bialystok, Dept Pediat 3, Bialystok, Poland. So Res Inst, Frederick, MD 21701 USA. Walter Reed Army Inst Res, Rockville, MD 20852 USA. Henry M Jackson Fdn, Rockville, MD 20852 USA. NIAID, Rockville, MD 20852 USA. Aventis Pasteur Ltd, F-69280 Marcy Letoile, France. Aventis Pasteur Ltd, Toronto, ON M2R 3T4, Canada. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; OI Hel, Zdenek/0000-0002-4923-4794 FU NIAID NIH HHS [AI-65312, AI-85343, N01-AI55260, N01-AI55271, R21 AI065312] NR 56 TC 186 Z9 187 U1 3 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2002 VL 76 IS 1 BP 292 EP 302 DI 10.1128/JVI.76.1.292-302.2002 PG 11 WC Virology SC Virology GA 500UJ UT WOS:000172644900029 PM 11739694 ER PT J AU Ding, C Urabe, M Bergoin, M Kotin, RM AF Ding, C Urabe, M Bergoin, M Kotin, RM TI Biochemical characterization of Junonia coenia densovirus nonstructural protein NS-1 SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-DNA REPLICATION; ADENOASSOCIATED VIRUS; SEQUENCE REQUIREMENTS; NUCLEOTIDE-SEQUENCE; TERMINAL REPEATS; MINUTE VIRUS; BINDING; PARVOVIRUS; HELICASE; STRANDS AB Junonia coenia densovirus (JcDNV) is an autonomous parvovirus that infects the larvae of the common buckeye butterfly, Junonia coenia. Unlike vertebrate parvoviruses, the genes encoding the structural protein and nonstructural (NS) proteins of JcDNV are in opposite orientations; thus, each strand contains a sense and antisense open reading frame (ORF). The promoter at map position 93 controls expression of NS ORFs 2, 3, and 4, which encode three NS proteins, NS-1, NS-2, and NS-3. These proteins are likely to be involved in viral DNA replication, among other functions. In contrast to the nonstructural proteins of the vertebrate parvoviruses, the NS proteins of the Densovirinae have not been characterized. Here, we describe biochemical properties of the NS-1 protein of JcDNV. The NS-1 ORF was cloned in frame with the Escherichia coli malE gene, which encodes the bacterial maltose binding protein (MBP). Using electrophoretic mobility shift and DNase I protection assays, we identified the region of the JcDNV terminal sequence that is recognized specifically by the MBP-NS-1 fusion protein. The site consists of (GAC)4 and is located on the A-A' region of the terminal palindrome. In addition, the MBP-NS-1 fusion protein catalyzes the cleavage of single-stranded DNA (ssDNA) substrates derived from the JcDNV putative origin of replication, primarily at two sites in the motif 5'-G*TAT*TG-3'. One cleavage site is between the thymidine dinucleotide at positions 92 and 93 and the other site corresponds to thymidine at nucleotide 95; both sites are on the complementary strand of the sequence assigned GenBank accession number A12984. Cleavage of ssDNA is dependent on the presence of a divalent metal cofactor but does not require nucleoside triphosphate hydrolysis. Parvovirus NS proteins contain the phylogenically conserved Walker A- and B-site ATPase motifs. These sites in JcDNV NS-I diverge from the consensus, yet despite these atypical motifs our analyses support that MBP-NS-1 has ATP-dependent helicase activity. These results indicate that JcDNV NS-1 possesses activities common to the superfamily of rolling-circle replication initiator proteins in general and the parvovirus replication proteins in particular, and they provide a basis for comparative analyses of the structure and function relationships among the parvovirus NS-1 equivalents. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. Univ Montpellier 2, Lab Pathol Comparee, Montpellier, France. RP Kotin, RM (reprint author), NHLBI, Lab Biochem Genet, NIH, 10 Ctr Bldg,10 Rm 7D18, Bethesda, MD 20892 USA. RI kotin, robert/B-8954-2008 NR 34 TC 23 Z9 26 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 2002 VL 76 IS 1 BP 338 EP 345 DI 10.1128/JVI.76.1.338-345.2002 PG 8 WC Virology SC Virology GA 500UJ UT WOS:000172644900033 PM 11739698 ER PT J AU Igarashi, T Brown, CR Byrum, RA Nishimura, Y Endo, Y Plishka, RJ Buckler, C Buckler-White, A Miller, G Hirsch, VM Martin, MA AF Igarashi, T Brown, CR Byrum, RA Nishimura, Y Endo, Y Plishka, RJ Buckler, C Buckler-White, A Miller, G Hirsch, VM Martin, MA TI Rapid and irreversible CD4(+) T-cell depletion induced by the highly pathogenic simian/human immunodeficiency virus SHIVDH12R is systemic and synchronous SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS-MONKEYS; IN-VIVO; THYMOCYTE DEPLETION; HIV-1 INFECTION; LYMPH-NODES; TYPE-1; AIDS; EXPRESSION; THYMUS; MECHANISM AB Highly pathogenic simian/human immunodeficiency virus chimeric viruses are known to induce a rapid, irreversible depletion of CD4(+) T lymphocytes in the peripheral blood of acutely infected macaque monkeys. To more fully assess the systemic effects of this primary virus infection, specimens were collected serially between days 3 and 21 postinfection from variety of lymphoid tissues (lymph nodes, thymus, and spleen) and gastrointestinal tract and examined by DNA and RNA PCR, in situ hybridization, and immunohistochemical assays. In addition, the lymphoid tissues were evaluated by fluorescence-activated cell sorting. Virus infection was initially detected by DNA PCR on day 3 postinfection in lymph node samples and peaked on day 10 in the T-lymphocyte-rich areas of this tissue. CD4(+) T-cell levels remained stable through day 10 in several lymphoid tissue specimens examined but fell precipitously between days 10 and 21. In situ terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) assays revealed the accumulation of apoptotic cells during the second week of infection in both lymph nodes and thymus, which colocalized, to a large extent, to sites of both virus replication and CD4(+) T-lymphocyte loss. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIH, Off Res Serv, Vet Resources Program, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. NR 48 TC 45 Z9 45 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 2002 VL 76 IS 1 BP 379 EP 391 DI 10.1128/JVI.76.1.379-391.2002 PG 13 WC Virology SC Virology GA 500UJ UT WOS:000172644900037 PM 11739702 ER PT J AU Dittmer, U Race, B Peterson, KE Stromnes, IM Messer, RJ Hasenkrug, KJ AF Dittmer, U Race, B Peterson, KE Stromnes, IM Messer, RJ Hasenkrug, KJ TI Essential roles for CD8(+) T cells and gamma interferon in protection of mice against retrovirus-induced immunosuppression SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; MONOCLONAL-ANTIBODIES; IN-VIVO; DENDRITIC CELLS; ERYTHROLEUKEMIA; AIDS; REQUIREMENTS; SUPPRESSION; ACTIVATION; RESISTANCE AB It is known that both animal and human retroviruses typically cause immunosuppression in their respective hosts, but the mechanisms by which this occurs are poorly understood. The present study uses Friend virus (FV) infections of mice as a model to determine how major histocompatibility complex (MHC) genes influence immunosuppression. Previously, MHC-I genes were shown to influence antibody responses to potent antigenic challenges given during acute FY infection. The mapping of an immune response to an MHC-I gene implicated CD8(+) T cells in the mechanism, so we directly tested for their role by using in vivo CD8(+) T-cell depletions. Mice resistant to FV-induced immunosuppression became susceptible when they were depleted of CD8+ T cells. Resistance also required gamma interferon (IFN-gamma), as in vivo neutralization of IFN-gamma converted mice from a resistant to susceptible phenotype. On the other hand, susceptibility to FV-induced immunosuppression was dependent on the immunosuppressive cytokine, interleukin-10 (IL-10), as antibody responses were restored in susceptible mice when IL-10 function was blocked in vivo. Thus, FV-induced immunosuppression of antibody responses involves complex mechanisms controlled at least in part by CD8(+) T cells. C1 NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. Univ Wurzburg, Inst Virol, Wurzburg, Germany. RP Hasenkrug, KJ (reprint author), NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 NR 33 TC 31 Z9 31 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 2002 VL 76 IS 1 BP 450 EP 454 DI 10.1128/JVI.76.1.450-454.2002 PG 5 WC Virology SC Virology GA 500UJ UT WOS:000172644900048 PM 11739713 ER PT J AU White, CL Senkevich, TG Moss, B AF White, CL Senkevich, TG Moss, B TI Vaccinia virus G4L glutaredoxin is an essential intermediate of a cytoplasmic disulfide bond pathway required for virion assembly SO JOURNAL OF VIROLOGY LA English DT Article ID ESCHERICHIA-COLI; GENE ENCODES; MORPHOGENESIS; REDUCTASE; SYSTEM; STATES; DSBA AB Our previous studies provided evidence that E10R, a vaccinia virus protein belonging to the ERV1/ALR family, has a redox function and is required for virion assembly. Repression of E10R prevented the formation of intramolecular disulfide bonds of the G4L glutaredoxin, the: UR membrane protein, and the structurally related F9L protein. Here, we demonstrate an oxidation pathway (E10R(ss) --> G4L(ss) --> L1R(ss), F9L(ss)) in which G4L occupies an intermediate position. By, reacting free thiols with 4-acetamido-4'-malemideyistilbene-2,2'-disulfonic acid, alkylated and nonalkylated disulfide-bonded forms of G4L could be resolved from each other by polyacrylamide gel electrophoresis. The cysteines of intracellular G4L were in both disulfide and reduced forms, whereas those of E10R, L1R, and F9L and virion-associated G4L were mostly disulfide bonded. Repression of G4L expression prevented the formation of disulfide bonds in both L1R and F9L but not E10R. Both cysteines of G4L were required for L1R and F9L disulfide! bond formation or for trans-complementation of virus infectivity when G4L expression was repressed. No role in the E10R-G4L redox pathway was found for O2L, a nonessential glutaredoxin encoded by vaccinia virus. We suggest that cytoplasmic G4L is a redox shuttle between membrane-associated E10R and UR or F9L. 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. NR 24 TC 36 Z9 37 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2002 VL 76 IS 2 BP 467 EP 472 DI 10.1128/JVI.76.8.467-472.2002 PG 6 WC Virology SC Virology GA 506HZ UT WOS:000172965300001 PM 11752136 ER PT J AU Hanley, KA Lee, JJ Blaney, JE Murphy, BR Whitehead, SS AF Hanley, KA Lee, JJ Blaney, JE Murphy, BR Whitehead, SS TI Paired charge-to-alanine mutagenesis of dengue virus type 4 NS5 generates mutants with temperature-sensitive, host range, and mouse attenuation phenotypes SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN; VACCINE; SITE; IDENTIFICATION; DIMERIZATION; SELECTION; MUTATION; VIREMIA; FEVER AB Charge-to-alanine mutagenesis of dengue virus type 4 (DEN4) NS5 gene generated a collection of attenuating mutations for potential use in, a recombinant live, attenuated DEN vaccine. Codons for 80 contiguous pairs of charged amino acids in NS5 were individually mutagenized to create uncharged pairs of alanine residues, and 32 recombinant mutant viruses were recovered from the 80 full-length mutant DEN4 cDNA constructs. These mutant viruses were tested for temperature-sensitive (ts) replication in both Vero cells and HuH-7 human hepatoma cells. Of the 32 mutants, 13 were temperature sensitive (ts) in both cell lines, 11 were not ts in either cell line, and 8 exhibited a host range (tshr) phenotype. One tshr mutant was ts only in Vero cells, and seven were ts only in HuH-7 cells. Nineteen of the 32 mutants were 10-fold or more restricted in replication in the brains of suckling mice compared to that of wild-type DEN4, and three mutants were approximately 10,000-fold restricted in replication. The level, of temperature sensitivity of replication in vitro did not correlate with attenuation in vivo. A virus bearing two pairs of charge-to-alanine mutations was constructed and demonstrated increased temperature sensitivity and attenuation relative, to either parent virus. This large set of charge-to-alanine mutations specifying a wide range of attenuation for mouse brain should prove useful in fine-tuning recombinant live attenuated DEN vaccines. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hanley, KA (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Room 100,7 Ctr Dr, Bethesda, MD 20892 USA. NR 40 TC 60 Z9 64 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 2002 VL 76 IS 2 BP 525 EP 531 DI 10.1128/JVI.76.2.525-531.2002 PG 7 WC Virology SC Virology GA 506HZ UT WOS:000172965300008 PM 11752143 ER PT J AU Tang, JM Shelton, B Makhatadze, NJ Zhang, Y Schaen, M Louie, LG Goedert, JJ Seaberg, EC Margolick, JB Mellors, J Kaslow, RA AF Tang, JM Shelton, B Makhatadze, NJ Zhang, Y Schaen, M Louie, LG Goedert, JJ Seaberg, EC Margolick, JB Mellors, J Kaslow, RA TI Distribution of chemokine receptor CCR2 and CCR5 genotypes and their relative contribution to human immunodeficiency virus type 1 (HIV-1) seroconversion, early HIV-1 RNA concentration in plasma, and later disease progression SO JOURNAL OF VIROLOGY LA English DT Article ID HLA CLASS-I; VIRAL LOAD; AIDS PROGRESSION; HOMOSEXUAL-MEN; HETEROSEXUAL TRANSMISSION; ANTIRETROVIRAL THERAPY; GENETIC RESTRICTION; VIRUS-1-INFECTED INDIVIDUALS; PERINATAL TRANSMISSION; INFECTED INDIVIDUALS AB At the CC (beta) chemokine receptor 2 (CCR2) and CCR5 loci, combinations of common single-nucleotide polymorphisms (SNPs) and a 32-bp deletion (Delta 32) form nine stable haplotypes (designated A through G*2). The distribution of these CCR2-CCR5 haplotypes was examined among 703 participants in the Multicenter AIDS Cohort Study (MACS), the District of Columbia Gay (DCG) Study, and the San Francisco Men's Health Study (SFMHS). Highly exposed and persistently seronegative (HEPS; n = 90) Caucasian men from MACS more frequently carried heterozygous G*2 (Delta 32) genotypes (especially A/G*2) and less frequently carried the homozygous E/E genotype compared with 469 Caucasian seroconverters (SCs) from the same cohort (P = 0.004 to 0.042). Among 341 MACS Caucasian SCs with 6- to 12-month human immunodeficiency virus type I (HIV-1) seroconversion intervals and no potent antiretroviral therapy, mean plasma HIV-1 RNA level during the initial 42 months after seroconversion was higher in carriers of the E/E genotype and lower in those with the 64I-bearing haplotype F*2 or the Delta 32-bearing haplotype G*2 (and especially genotypes A/G*2 and F*2/G*2). A multivariable model containing these CCR markers showed significant composite effects on HIV-1 RNA at each of four postconversion intervals (P = 0.0004 to 0.050). In other models using time to AIDS as the endpoint, the same markers showed more modest contributions (P = 0.08 to 0.24) to differential outcome during 11.5 years of follow-up. Broadly consistent findings in the larger MACS Caucasian SCs and the smaller groups of MACS African-American SCs and the DCG and SFMHS Caucasian SCs indicate that specific CCR2-CCR5 haplotypes or genotypes mediate initial acquisition of HIV-1 infection, early host-virus equilibration, and subsequent pathogenesis. C1 Univ Alabama Birmingham, Sch Publ Hlth, Program Epidemiol Infect & Immun, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Sch Med, Dept Med, Div Geog Med, Birmingham, AL 35294 USA. Childrens Hosp Oakland Res Inst, Oakland, CA 94609 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21218 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. RP Univ Alabama Birmingham, Sch Publ Hlth, Program Epidemiol Infect & Immun, 220A Ryals Bldg,1665 Univ Blvd, Birmingham, AL 35294 USA. EM rkaslow@uab.edu OI Tang, Jianming/0000-0003-0137-7486 FU NIAID NIH HHS [R01 AI041951, R01 AI36661, R01 AI41951] NR 77 TC 71 Z9 72 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2002 VL 76 IS 2 BP 662 EP 672 DI 10.1128/JVI.76.2.662-672.2002 PG 11 WC Virology SC Virology GA 506HZ UT WOS:000172965300022 PM 11752157 ER PT J AU Garvey, TL Bertin, J Siegel, RM Wang, GH Lenardo, MJ Cohen, JI AF Garvey, TL Bertin, J Siegel, RM Wang, GH Lenardo, MJ Cohen, JI TI Binding of FADD and caspase-8 to molluscum contagiosum virus MC159 Ni-FLIP is not sufficient for its antiapoptotic function SO JOURNAL OF VIROLOGY LA English DT Article ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; DEATH-EFFECTOR DOMAIN; FACTOR RECEPTOR-1-INDUCED APOPTOSIS; FAS-MEDIATED APOPTOSIS; SIGNAL-TRANSDUCTION; TRAIL RECEPTOR-2; TNF RECEPTOR; MUTATIONS; COMPLEX; CD95 AB Molluscum contagiosum virus (MCV), a member of the human poxvirus family, encodes the MC159 protein that inhibits Fas-, tumor necrosis factor (TNF)-, and TNF-related apoptosis-inducing ligant (TRAIL)-induced apoptosis. We used site-directed mutagenesis to change charged or hydrophobic amino acid residues to alanines to identify regions of MC159 that are critical for protection from apoptosis and for protein-protein interactions. Surprisingly, while MC159: is thought to block apoptosis, by binding to Fas-associated death domain (FADD) or caspase-8, several mutants that lost apoptosis blocking activity still bound to both FADD and caspase-8. Mutations in the predicted hydrophobic patch I and alpha2 regions of both death effector domains (DEDs) within MC159 resulted in loss of the ability to bind to,FADD or caspase-8 and to block apoptosis. Amino acid substitutions in the RXDL motif located in the alpha6 region of either DED resulted in loss of protection from apoptosis induced by Fas, TNF, and TRAIL and abolished the ability of MC159 to block death effector filament formation. Thus, charged or hydrophobic amino acids in three regions of the MC159 DEDs (hydrophobic patch 1, alpha2, and alpha6) are critical for the protein's ability to interact with cellular proteins and to block apoptosis. C1 NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Dev Immune Syst Sect, Immunol Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bldg 10,Rm 11N228, Bethesda, MD 20892 USA. RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 30 TC 54 Z9 55 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 2002 VL 76 IS 2 BP 697 EP 706 DI 10.1128/JVI.76.2.697-706.2002 PG 10 WC Virology SC Virology GA 506HZ UT WOS:000172965300025 PM 11752160 ER PT J AU Mothe, BR Horton, H Carter, DK Allen, TM Liebl, ME Skinner, P Vogel, TU Fuenger, S Vielhuber, K Rehrauer, W Wilson, N Franchini, G Altman, JD Haase, A Picker, LJ Allison, DB Watkins, DI AF Mothe, BR Horton, H Carter, DK Allen, TM Liebl, ME Skinner, P Vogel, TU Fuenger, S Vielhuber, K Rehrauer, W Wilson, N Franchini, G Altman, JD Haase, A Picker, LJ Allison, DB Watkins, DI TI Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; MHC-CLASS-I; RHESUS-MONKEYS; LYMPHOCYTE-RESPONSE; SIV VACCINE; VIREMIA; PROTECTION; MACAQUES; ESCAPE; HIV-1 AB Cytotoxic T-lymphocyte (CTL) responses are thought to control human immunodeficiency virus replication during the acute phase of infection. Understanding the CD8(+) T-cell immune responses early after infection may, therefore, be important to vaccine design. Analyzing these responses in humans is difficult since few patients are diagnosed during early infection. Additionally, patients are infected by a variety of viral subtypes, making it hard to design reagents to measure their acute-phase immune responses. Given the complexities in evaluating acute-phase CD8(+) responses in humans, Nye analyzed these important immune responses in rhesus macaques expressing a common rhesus macaque major histocompatibility complex class I molecule (Mamu-A*01) for which we had developed a variety of immunological assays. We infected eight Mamu-A*01-positive macaques and five Mamu-A*01-negative macaques with the molecularly cloned virus SIV(mac)23 and determined all of the simian immunodeficiency virus-specific CD8(+) T-cell responses against overlapping peptides spanning the entire virus. We also monitored the evolution of particular CD8(+) T-cell responses by tetramer staining of peripheral lymphocytes as well as lymph node cells in situ. In this first analysis of the entire CD8(+) immune response to autologous virus we, show that between 2 and 12 responses are detected during the acute phase in each animal. CTL against the early proteins (Tat, Rev, and Nef) and against regulatory proteins Vif and Vpr dominated the acute phase. Interestingly, CD8(+) responses against Mamu-A*01-restriced epitopes Tat(28-35)SL8 and Gag(181-189)CM9 were immunodominant in the acute phase. After the acute phase, however, this pattern of reactivity changed, and the Mamu-A*01-restricted response against the Gag(181-189)CM9 epitope became dominant. In most of the Mamu-A*01-positive macaques tested, CTL responses against epitopes bound by Mamu-A*01 dominated the CD8(+) cellular immune response. C1 Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Emory Vaccine Ctr, Atlanta, GA 30329 USA. Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53792 USA. RP Watkins, DI (reprint author), Univ Wisconsin, Wisconsin Reg Primate Res Ctr, 1220 Capitol Ct, Madison, WI 53715 USA. RI Allen, Todd/F-5473-2011; OI Allison, David/0000-0003-3566-9399; Skinner, Pamela/0000-0003-3388-1687 FU NCRR NIH HHS [P51 RR000167, R24 RR015371, RR00167, RR15371]; NIAID NIH HHS [AI45461, AI46366, R01 AI046366]; PHS HHS [A149120] NR 40 TC 105 Z9 110 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 2002 VL 76 IS 2 BP 875 EP 884 DI 10.1128/JVI.76.2.875-884.2002 PG 10 WC Virology SC Virology GA 506HZ UT WOS:000172965300041 PM 11752176 ER PT J AU Rotstein, DS Taylor, SK Birkenhauer, A Roelke-Parker, M Homer, BL AF Rotstein, DS Taylor, SK Birkenhauer, A Roelke-Parker, M Homer, BL TI Retrospective study of proliferative papillary vulvitis in Florida panthers SO JOURNAL OF WILDLIFE DISEASES LA English DT Article DE Florida panther; cougar; Pumas concolor coryi; proliferative vulvitis; vestibulum vaginae; pathology; reproduction AB Proliferative, papillary vulvitis was identified in 16 of 34 (47%) free-ranging and captive female Florida panthers (Puma concolor coryi) monitored over a period from 1983-98. Gross lesions were characterized by extensive papilliferous proliferation in the mucosa of the vestibulum vaginae. Within lesions, the mean length and width of vestibular papillae were 1.07 +/- 0.39 mm (CV = 36%) and 0.55 +/- 0.11 mm (CV = 20%) respectively. Histologically, three to 12 layers of non-cornified stratified squamous epithelium with various degrees of basal cell spongiosis and rete ridge formation covered fibrous papillae. Mixed leukocytic mucosal inflammation also was observed. Infectious organisms were not observed, and immunohistochemical testing for the presence of papillomavirus antigens in specimens from seven panthers was negative. Lesions in nearly all of the panthers were first observed during a six-year period (1986-92), with one each in 1983, 1996 and 1998. There were no significant differences between the number of females having litters, the number of litters between age-matched and interval-matched females, and the interval between litters among lesion positive and lesion negative females over the 15 yr period. The severity of lesions did not appear to differ between parous and nulliparous free-ranging lesion-positive females. The cause of proliferative vulvitis remains unknown. However, the lesion did not appear to have a significant effect on reproduction. C1 Univ Florida, Coll Vet Med, Dept Pathobiol, Gainesville, FL 32611 USA. Univ Florida, Coll Vet Med, Dept Physiol, Gainesville, FL 32611 USA. Florida Fish & Wildlife Conservat Commiss, Gainesville, FL 32601 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Univ Florida, Coll Vet Med, Dept Pathobiol, Gainesville, FL 32611 USA. RP Homer, BL (reprint author), Univ Florida, Coll Vet Med, Dept Pathobiol, POB 110880, Gainesville, FL 32611 USA. NR 16 TC 0 Z9 0 U1 0 U2 1 PU WILDLIFE DISEASE ASSN, INC PI LAWRENCE PA 810 EAST 10TH ST, LAWRENCE, KS 66044-8897 USA SN 0090-3558 J9 J WILDLIFE DIS JI J. Wildl. Dis. PD JAN PY 2002 VL 38 IS 1 BP 115 EP 123 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 518VT UT WOS:000173689100015 PM 11838202 ER PT J AU Christmas, C O'Connor, KG Harman, SM Tobin, JD Munzer, T Bellantoni, MF Clair, CS Pabst, KM Sorkin, JD Blackman, MR AF Christmas, C O'Connor, KG Harman, SM Tobin, JD Munzer, T Bellantoni, MF Clair, CS Pabst, KM Sorkin, JD Blackman, MR TI Growth hormone and sex steroid effects on bone metabolism and bone mineral density in healthy aged women and men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID ADOLESCENT MALE HYPOGONADISM; RANDOMIZED CONTROLLED TRIAL; LEAN BODY-MASS; GH DEFICIENCY; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; FACTOR-I; TESTOSTERONE REPLACEMENT; TRANSDERMAL ESTROGEN; SUBSTITUTION THERAPY AB Background. Aging is associated with concomitant declines in activity of the growth hormone (GH) and gonadal steroid axes, and in bone mineral density (BMD). in both sexes. Long-term estrogen replacement slows bone loss and prevents fractures in postmenopausal women, whereas the effects of supplementation of GH or testosterone on bone metabolism and BMD in aged individuals remains uncertain. Methods. Using a randomized, placebo-controlled, double-blind study design, we investigated the separate and interactive effects of 6 months of administration of recombinant human GH and/or gonadal steroids on bone biochemical markers and BMD in 125 healthy, older (>65 years) women (n = 53) and men (n = 72) with age-related reductions in GH and gonadal steroids. Results. In women. administration of GH. but not GH + hormone replacement therapy (HRT). increased serum levels of osteocalcin and procollagen peptide (PICP) and increased urinary excretion of deoxypyridinoline (DPD) crosslinks. Urinary calcium excretion decreased after HRT. In men. GH, and to a greater extent GH + T. increased osteocalcin. GH increased serum PICP. and GH + T increased urinary DPD. Urinary calcium excretion was unaffected by hormone treatment in men. In women. administration of HRT and GH + HRT, but not GH. increased BMD at the lumbar spine. femoral neck. and distal radius. In men, GH + T led to a small decrease in BMD at the proximal radius: there were no other significant effects of hormone administration on BMD. Conclusions. These data suggest that short-term administration of HRT exerts beneficial effects on bone metabolism and BMD in post menopausal women, which are not significantly altered by the coadministration of GH. In andropausal men, T administration to achieve physiologic levels did not result in significant effects on bone metabolism or BMD, whereas GH + T increased one marker of bone formation and decreased one marker of bone resorption. Given the known biphasic actions of GH on bone and the apparent favorable biochemical effects of GH + T in men. the longer-term effects of GH + T on BMD in aged men remain to be clarified. C1 NIA, Endocrine Sect, Clin Invest Lab, Intramural Res Program,NIH, Bethesda, MD 20892 USA. NIA, Appl Physiol Sect, Clin Invest Lab, Intramural Res Program,NIH, Bethesda, MD 20892 USA. NIA, Metab Sect, Clin Invest Lab, Intramural Res Program,NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. NIA, Lab Clin Invest, Natl Ctr Complementary & Alternat Med, Endocrine Sect,Intramural Res Program,NIH, Bethesda, MD 20892 USA. RP Blackman, MR (reprint author), NIA, Lab Clin Invest, Natl Ctr Complementary & Alternat Med, Endocrine Sect,Intramural Res Program,NIH, Bldg 10,8 West Dr,QRTRS 15 B-1, Bethesda, MD 20892 USA. FU NCRR NIH HHS [M0-1-RR-02719]; NIA NIH HHS [R0-1 AG11005] NR 56 TC 61 Z9 65 U1 1 U2 3 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 2002 VL 57 IS 1 BP M12 EP M18 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 509RQ UT WOS:000173163800008 PM 11773207 ER PT J AU Leypoldt, JK Cheung, AK Delmez, JA Jennifer, JJ Levin, NW Lewis, JAB Lewis, JL Rocco, MV AF Leypoldt, JK Cheung, AK Delmez, JA Jennifer, JJ Levin, NW Lewis, JAB Lewis, JL Rocco, MV CA HEMO Study Grp TI Relationship between volume status and blood pressure during chronic hemodialysis SO KIDNEY INTERNATIONAL LA English DT Article DE body weight; dry weight; fluid removal; hypertension; plasma volume; postdialysis volume overload ID INTERDIALYTIC WEIGHT-GAIN; MAINTENANCE HEMODIALYSIS; PLASMA-VOLUME; DIALYSIS PATIENTS; HYDRATION STATE; DRY-WEIGHT; HYPERTENSION; ULTRAFILTRATION; MORTALITY; HYPOTENSION AB Background. The relationship between volume status and blood pressure (BP) in chronic hemodialysis (HD) patients remains incompletely understood. Specifically, the effect of interdialytic fluid accumulation (or intradialytic fluid removal) on BP is controversial. Methods. We determined the association of the intradialytic decrease in body weight (as an indicator of interdialytic fluid gain) and the intradialytic decrease in plasma volume (as an indicator of postdialysis volume status) with predialysis and postdialysis BP in a cross-sectional analysis of a subset of patients (N = 468) from the Hemodialysis (HEMO) Study. Fifty-five percent of patients were female, 62% were black, 43% were diabetic and 72% were prescribed antihypertensive medications. Dry weight was defined as the postdialysis body weight below, which the patient developed symptomatic hypotension or muscle cramps in the absence of edema. The intradialytic decrease in plasma volume was calculated from predialysis and postdialysis total plasma protein concentrations and was expressed as a percentage of the plasma volume at the beginning of HD. Results. Predialysis systolic and diastolic BP values were 153.1 +/- 24.7 (mean +/- SD) and 81.7 +/- 14.8 mm Hg. respectively postdialysis systolic and diastolic BP values were 136.6 +/- 22.7 and 73.4 +/- 13.6 mm Hg. respectively. As a result of HD, body weight was reduced by 3.1 +/- 1.3 kg and plasma volume was contracted by 10.1 +/- 9.5%. Multiple linear regression analyses showed that each kg reduction in body weight during HD was associated with a 2.95 mm Hg (P = 0.004) and a 1.65 mm Hg (P = NS) higher predialysis and postdialysis systolic BP, respectively. In contrast, each 5% greater contraction of plasma volume during HD was associated with a 1.50 mm Hg (P = 0.026) and a 2.56 mm Hg (P < 0.001) lower predialysis and postdialysis systolic BP, respectively. The effects of intradialytic decreases in body weight and plasma volume were greater on systolic BP than on diastolic BP. Conclusions. HD treatment generally reduces BP, and these reductions in BP are associated with intradialytic decreases in both body weight and plasma volume, The absolute predialysis and postdialysis BP levels are influenced differently by acute intradialytic decreases in body weight and acute intradialytic decreases in plasma volume: these parameters provide different information regarding volume status and may be dissociated from each other. Therefore, evaluation of volume status in chronic HD patients requires, at minimum, assessments of both interdialytic fluid accumulation (or the intradialytic decrease in body weight) and postdialysis volume overload. C1 Univ Utah, Dialysis Program, Salt Lake City, UT 84112 USA. Washington Univ, St Louis, MO USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Vanderbilt Univ, Nashville, TN USA. Univ Alabama, Birmingham, AL USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NIDDK, NIH, Bethesda, MD USA. RP Leypoldt, JK (reprint author), Univ Utah, Dialysis Program, 85 N Med Dr E, Salt Lake City, UT 84112 USA. NR 49 TC 78 Z9 89 U1 0 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2002 VL 61 IS 1 BP 266 EP 275 DI 10.1046/j.1523-1755.2002.00099.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 505GK UT WOS:000172904900031 PM 11786109 ER PT J AU Kopp, JB AF Kopp, JB TI BMP-7 and the proximal tubule SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID INJURY; RAT C1 NIH, Kidney Dis Sect, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIH, Kidney Dis Sect, Bldg 10,Room 3N116, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 9 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2002 VL 61 IS 1 BP 351 EP 352 DI 10.1046/j.1523-1755.2002.00126.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 505GK UT WOS:000172904900041 PM 11786119 ER PT J AU Kearney, DL Perez-Atayde, AR AF Kearney, DL Perez-Atayde, AR CA P2C2 HIV Study Grp TI Postmortem cardiomegaly and its clinicopathologic significance in HIV-infected children. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 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 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 20 BP 4P EP 4P PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701491 ER PT J AU Romero, ME Wexler, LH Harrison-Shahan, Y Helman, L Tsokos, M AF Romero, ME Wexler, LH Harrison-Shahan, Y Helman, L Tsokos, M TI Survivin inhibits drug-induced apoptosis and correlates with prognosis in Ewing's sarcoma family tumors (ESFT). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 28 BP 5P EP 5P PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701499 ER PT J AU Feldman, AL Bartlett, DL Libutti, SK Alexander, HR Kleiner, DE AF Feldman, AL Bartlett, DL Libutti, SK Alexander, HR Kleiner, DE TI Relationship between histologic grade and outcome in patients with peritoneal mesothelioma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 43 BP 14A EP 14A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700057 ER PT J AU Palacios, J Garcia-Macias, MC Bryant, B Sobel, ME Merino, MJ AF Palacios, J Garcia-Macias, MC Bryant, B Sobel, ME Merino, MJ TI E-cadherin (ECD) gene inactivation in pleomorphic lobular carcinoma (PLC) of the breast SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Ctr Nacl Invest Oncol, Madrid, Spain. Univ Hosp, Salamanca, Spain. NCI, Bethesda, MD 20892 USA. RI Hardisson, David/E-2832-2010 OI Hardisson, David/0000-0002-2183-3699 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 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 177 BP 45A EP 45A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700190 ER PT J AU Palacios, J Bryant, B Hardisson, D Sobel, ME Merino, MJ AF Palacios, J Bryant, B Hardisson, D Sobel, ME Merino, MJ TI cDNA microarray gene expression analysis of microdissected frozen ductal breast carcinomas after linear RNA amplification SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Hosp La Paz, Madrid, Spain. Ctr Nacl Invest Incol, Madrid, Spain. NIH, Bethesda, MD 20892 USA. RI Hardisson, David/E-2832-2010 OI Hardisson, David/0000-0002-2183-3699 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 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 176 BP 45A EP 45A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700189 ER PT J AU van de Rijn, M Perou, C Tibshirani, R Kallioniemi, O Kononen, J Sauter, G Botstein, D Brown, P AF van de Rijn, M Perou, C Tibshirani, R Kallioniemi, O Kononen, J Sauter, G Botstein, D Brown, P TI Tissue microarray analysis of cytokeratin 17 and 5 expression shows association with poor clinical outcome in breast carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Stanford Univ, Stanford, CA 94305 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Basel, CH-4003 Basel, Switzerland. NIH, Bethesda, MD 20892 USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 218 BP 55A EP 55A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700232 ER PT J AU Auerbach, A Filie, AC Copeland, C Sorbara, L Raffeld, M Stetler-Stevenson, M Barnes, E Abati, A AF Auerbach, A Filie, AC Copeland, C Sorbara, L Raffeld, M Stetler-Stevenson, M Barnes, E Abati, A TI Cerebrospinal fluid specimens for diagnosing lymphomas and lymphoproliferative disorders: A comparison of diagnosis by cytology, flow cytometry and molecular diagnostics SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 264 BP 66A EP 66A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700278 ER PT J AU Bryant-Greenwood, PK Filie, AC Little, R Yarchoan, R Raffeld, M Sorbara, L Abati, A AF Bryant-Greenwood, PK Filie, AC Little, R Yarchoan, R Raffeld, M Sorbara, L Abati, A TI Morphologic and molecular camparison of recurrent effusions in HIV plus patients with and without documented HHV8 disease manifestations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 267 BP 66A EP 67A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700281 ER PT J AU Clark, BD Filie, AC Sorbara, L Stetler-Stevenson, M Raffeld, M Abati, A AF Clark, BD Filie, AC Sorbara, L Stetler-Stevenson, M Raffeld, M Abati, A TI Diagnosis of lymphomatoid granulomatosis by cytology: A comparison of conventional cytology, flow cytometry, and polymerase chain reaction (PCR) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NIH, Cytopathol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 273 BP 68A EP 68A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700287 ER PT J AU Rosenblatt, KP Cassarino, DS Auerbach, A Duray, PH AF Rosenblatt, KP Cassarino, DS Auerbach, A Duray, PH TI Pathology and immunophenotype of 10 cases of aggressive melanoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 440 BP 107A EP 107A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700453 ER PT J AU De la Cruz, A Fojo, A Merino, MJ AF De la Cruz, A Fojo, A Merino, MJ TI Expression of the ACTH-receptor in normal and neoplastic adrenal issues SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 469 BP 113A EP 114A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700482 ER PT J AU Merino, MJ Roberts, DD Bryant, B Krutzsch, HC AlBarazi, H Libutti, SK Sarlis, NJ Panizo, A AF Merino, MJ Roberts, DD Bryant, B Krutzsch, HC AlBarazi, H Libutti, SK Sarlis, NJ Panizo, A TI Differences of protein expression in benign and malignant microdissected thyroid tissues SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 487 BP 117A EP 118A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700500 ER PT J AU Luo, J Gage, WR Hick, JL Wanders, RJ Trent, JM Isaacs, WB De Marzo, AM AF Luo, J Gage, WR Hick, JL Wanders, RJ Trent, JM Isaacs, WB De Marzo, AM TI Overexpression of alpha methyl acyl-CoA racemase (AMACR) in prostate cancer analyzed by cDNA microarrays and high density tissue microarrays SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Amsterdam, Amsterdam, Netherlands. NHGRI, Bethesda, MD 20892 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 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 712 BP 171A EP 171A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700725 ER PT J AU Ronchetti, R Auerbach, A Harris, CA Linehan, M Zbar, B Quezado, M Merino, MJ AF Ronchetti, R Auerbach, A Harris, CA Linehan, M Zbar, B Quezado, M Merino, MJ TI Type I papillary renal cell carcinoma, correlation between morphology, immunophenotype, genetic changes and outcome SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 743 BP 178A EP 178A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700756 ER PT J AU Barry, TS Taddesse-Heath, L Raffeld, M Sorbara, L Pittaluga, S Jaffe, ES AF Barry, TS Taddesse-Heath, L Raffeld, M Sorbara, L Pittaluga, S Jaffe, ES TI Hodgkin's transformation of marginal zone B-cell lymphoma (MZBCL): Evidence for clonal evolution SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 969 BP 231A EP 231A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700982 ER PT J AU Barry, TS Jaffe, ES Raffeld, M Pittaluga, S AF Barry, TS Jaffe, ES Raffeld, M Pittaluga, S TI Peripheral T-cell lymphomas simulating classical Hodgkin's lymphoma with Reed-Sternberg-like giant cells of T-cell phenotype SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 968 BP 231A EP 231A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700981 ER PT J AU Barry, TS Pittaluga, S Raffeld, M Jaffe, ES AF Barry, TS Pittaluga, S Raffeld, M Jaffe, ES TI Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) and T-cell rich/histiocyte rich large B-cell lymphoma (T/HCRLBCL): Evidence for a biological overlap SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 970 BP 231A EP 232A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700983 ER PT J AU Greiner, TC Farrell, BT Weisenburger, DD Hoeck, L Armitage, JO Staudt, L Chan, WC AF Greiner, TC Farrell, BT Weisenburger, DD Hoeck, L Armitage, JO Staudt, L Chan, WC TI P53 mutations may explain the decreased survival in the activated B-like subgroup of diffuse large B-cell lymphomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1011 BP 242A EP 242A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701024 ER PT J AU Hans, CP Weisenburger, DD Gascoyne, RD Greiner, TC Cochran, GT Pan, X Gao, Z Farinha, P Hock, L Lynch, JC Rosenwald, A Staudt, LM Connors, J Armitage, JO Chan, WC AF Hans, CP Weisenburger, DD Gascoyne, RD Greiner, TC Cochran, GT Pan, X Gao, Z Farinha, P Hock, L Lynch, JC Rosenwald, A Staudt, LM Connors, J Armitage, JO Chan, WC TI Classification of diffuse large B-cell lymphoma into prognostically significant subgroups by immunohistochemistry using a tissue microarray SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Peking Univ, Hlth Sci Ctr, Beijing 100871, Peoples R China. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1015 BP 243A EP 243A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701028 ER PT J AU Taddesse-Heath, L Pittaluga, S Sorbara, L Raffeld, M Hedge, U Wilson, W Jaffe, ES AF Taddesse-Heath, L Pittaluga, S Sorbara, L Raffeld, M Hedge, U Wilson, W Jaffe, ES TI Incidence and clinical significance of clonal/oligoclonal T cell expansions in patients with lymphomatoid granulomatosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1104 BP 265A EP 266A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701117 ER PT J AU Kleiner, DE Hewitt, SM Hale, DA Mannon, RB Swanson, SJ Kirk, AD AF Kleiner, DE Hewitt, SM Hale, DA Mannon, RB Swanson, SJ Kirk, AD TI Unusual immunologic response to renal allografts in patients receiving CAMPATH-1H as a sole immunosuppressant SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NIDDK, Transplantat & Autoimmun Branch, Bethesda, 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 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1154 BP 278A EP 278A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701167 ER PT J AU Coleman, KE Kelavkar, UP Lawson, D Haseman, J Cohen, C AF Coleman, KE Kelavkar, UP Lawson, D Haseman, J Cohen, C TI 15-lipoxygenase-1 (15-LO-1) as a molecular marker in cancer: An immunohistochemical study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Div Renal, Atlanta, GA 30322 USA. NIEHS, Res Triangle Pk, NC 27709 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 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1264 BP 304A EP 304A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701277 ER PT J AU Fujii, T Gillespie, JW Jen, J Travis, WD AF Fujii, T Gillespie, JW Jen, J Travis, WD TI Mitochondrial D-loop mutation and AAAG microsatellite instability as molecular markers for clonality analysis: An application to sclerosing hemangioma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. NCI, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 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 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1327 BP 319A EP 319A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701340 ER PT J AU He, P Miura, K Bowman, ED Welsh, JA Travis, WD Harris, CC AF He, P Miura, K Bowman, ED Welsh, JA Travis, WD Harris, CC TI Molecular profiling of pulmonary neuroendocrine tumors with laser capture microdissection and cDNA microarray SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Washington, DC 20306 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1336 BP 321A EP 321A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701349 ER PT J AU Valencia, JC Blankinship, GL Yu, ZX Moss, J Ferrans, VJ AF Valencia, JC Blankinship, GL Yu, ZX Moss, J Ferrans, VJ TI Expression of microphthalmia-asscociated transcription factor (MITF) and CD63 melanoma antigen in pulmonary lymphangioleiomyomatosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NHLBI, 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1374 BP 330A EP 330A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701387 ER PT S AU Ye, HQQ Chan, CC Smith, JA AF Ye, HQQ Chan, CC Smith, JA BE Sullivan, DA Stern, ME Tsubota, K Dartt, DA Sullivan, RM Bromberg, BB TI Immunopathogenesis of conjunctival histopathologic alteration in non-Sjogren's keratoconjunctivitis sicca SO LACRIMAL GLAND, TEAR FILM, AND DRY EYE SYNDROMES 3: BASIC SCIENCE AND CLINICAL RELEVANCE, PTS A & B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Lacrimal Gland, Tear Film and Dry Eye Syndromes CY NOV 15-18, 2000 CL MAUI, HAWAII SP Alcon Lab, Minamiaoyama Eye Clin, Inspire Pharmaceut Inc, Bausch & Lomb ID EXPRESSION; CYTOKINE C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Ye, HQQ (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47282-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 506 BP 801 EP 803 PG 5 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BW22U UT WOS:000181264100113 PM 12613995 ER PT J AU Spring, KR AF Spring, KR TI Acousto-optic tunable filters improve optical microscopy SO LASER FOCUS WORLD LA English DT Article ID FLUORESCENCE AB Used with a laser-scanning confocal microscope, an acousto-optic tunable filter selects wavelengths and specific field regions for illumination. C1 NHLBI, Sect Transport Physiol, NIH, Bethesda, MD 20892 USA. RP Spring, KR (reprint author), NHLBI, Sect Transport Physiol, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU PENNWELL PUBL CO PI NASHUA PA 98 SPIT BROOK RD, NASHUA, NH 03062-2801 USA SN 0740-2511 J9 LASER FOCUS WORLD JI Laser Focus World PD JAN PY 2002 VL 38 IS 1 BP 123 EP + PG 4 WC Optics SC Optics GA 514AY UT WOS:000173415000035 ER PT J AU Snyder, SK Byrnes, KR Borke, RC Sanchez, A Anders, JJ AF Snyder, SK Byrnes, KR Borke, RC Sanchez, A Anders, JJ TI Quantitation of calcitonin gene-related peptide mRNA and neuronal cell death in facial motor nuclei following axotomy and 633 nm low power laser treatment SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE 633 nm; biostimulation; CGRP; facial nerve transection; light therapy; LLLT; low level laser therapy; PCR quantitation ID MESSENGER-RNA EXPRESSION; HE-NE-LASER; CENTRAL-NERVOUS-SYSTEM; DORSAL-ROOT GANGLION; LOW-DOSE LASER; ALPHA-CGRP; PERIPHERAL-NERVE; RAT MOTONEURONS; SPINAL-CORD; DIFFERENTIAL REGULATION AB Background and Objectives: A persistent increase in calcitonin gene-related peptide (CGRP) immunoreactivity in motoneurons may serve as an indicator for regeneration after peripheral nerve injury [Borke et al., J Neurocytol 1993;22:141-153]. Study Design/Materials and Methods: We examined the effects of low power laser treatment (633 nm) on axotomy-induced changes in alpha-CGRP mRNA and long-term neuronal survival in facial motoneurons. A quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay for alpha-CGRP mRNA was used to detect changes in the response to axotomy and laser irradiation. Cell counts of neurons in injured and non-injured facial motor nuclei of laser-treated and non-treated rats were done to estimate neuronal survival. Results: A 10-fold increase (P<0.0001) in mRNA for α-CGRP at 11 days post-transection and an almost threefold increase (P < 0.0001) in neuronal survival at 6-9 months post-transection were found in 633 nm light treated rats. Discussion: These findings demonstrate that 633 nm laser light upregulates CGRP mRNA and support the theory that laser irradiation increases the rate of regeneration, target reinnervation, and neuronal survival of the axotomized neuron. C1 Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Neurosci Program, Bethesda, MD 20814 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Byrnes, KR (reprint author), Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Neurosci Program, Room B2047,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. OI Byrnes, Kimberly/0000-0002-7501-7734 NR 45 TC 46 Z9 57 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 VL 31 IS 3 BP 216 EP 222 DI 10.1002/lsm.10098 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 598EQ UT WOS:000178262800011 PM 12224097 ER PT J AU Ma, D McDevitt, MR Barendswaard, E Lai, L Curcio, MJ Pellegrini, V Brechbiel, MW Scheinberg, DA AF Ma, D McDevitt, MR Barendswaard, E Lai, L Curcio, MJ Pellegrini, V Brechbiel, MW Scheinberg, DA TI Radioimmunotherapy for model B cell malignancies using Y-90-labeled anti-CD19 and anti-CD20 monoclonal antibodies SO LEUKEMIA LA English DT Article DE monoclonal antibody; anti-CD19; anti-CD20; Y-90; radioimmunotherapy; non-Hodgkins' lymphoma ID NON-HODGKINS-LYMPHOMA; NUDE-MICE; THERAPY; ANTIGEN; CD22; LEUKEMIA; CANCER; LIGAND; TRIAL; Y-90 AB In recent years, radioimmunotherapy (RIT) with beta-particle emitting radionuclides targeting the CD20 antigen on B cells in the treatment of non-Hodgkin's lymphoma has provided the most compelling human clinical data for the success of RIT. CD19, like CD20, is an antigen expressed on the surface of cells of the B lineage, and CD19 may provide an alternative target for radioimmunotherapy of B cell neoplasms. CD19 has been largely overlooked as a target for conventional I-131 RIT, because the antigen rapidly internalizes upon binding of antibody, resulting in catabolism and significant release of I-131. Such modulation may be an advantage to RIT with radiometals such as Y-90, Lu-177, Bi-213 and Ac-225. Herein, we have compared beta particle RIT with antibodies targeting either CD19 or CD20. The anti-CD19 and anti-CD20 antibodies, B4 or C2B8, respectively, were appended with the SCN-CHX-A"-DTPA bifunctional chelating agent and labeled with Y-90. In the tumor model used, there were three times as many CD20 target sites on lymphoma cells as compared to CD19 sites (62000 vs 20000 binding sites, respectively). We compared the efficacy of the Y-90-labeled antibodies to reduce lymphoma in a nude mouse xenograft solid tumor model, after measurable lymphoma appeared. Reduction in tumor size began at day 3 in all three Y-90-treated groups, but tumor began to recur in many animals 9 days after the treatments. There was one cure in each specific treatment group. In contrast, the tumor in the two control groups showed no regression. There was a significant prolongation of median survival time from xenograft (P < 0.0001) in all the Y-90-labeled antibody construct-treated groups (32 days for 0.15 mCi Y-90-B4; 26 days for 0.20 mCi Y-90-C2B8, and 23 days for 0.15 mCi 90Y-C2B8) in comparison to the two control groups (11 days for 0.02 mg of C2B8 and 9 days for untreated growth controls). Specificity of the radioimmunotherapy was also shown. In conclusion, Y-90-labeled anti-CD19 antibody has efficacy comparable to Y-90-lab-labeled anti-CD20 antibody in the treatment of mice bearing human lymphoma xenografts. These data suggest that CD19-targeted RIT merits further study. C1 Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Therapeut, New York, NY 10021 USA. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Scheinberg, DA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Therapeut, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [P01 CA33049] NR 31 TC 40 Z9 42 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2002 VL 16 IS 1 BP 60 EP 66 DI 10.1038/sj.leu.2402320 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 514PW UT WOS:000173451100009 PM 11840264 ER PT J AU Kulkarni, MS Daggett, JL Bender, TP Kuehl, WM Bergsagel, PL Williams, ME AF Kulkarni, MS Daggett, JL Bender, TP Kuehl, WM Bergsagel, PL Williams, ME TI Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: ectopic p18 expression inhibits growth and induces apoptosis SO LEUKEMIA LA English DT Article DE multiple myeloma; cyclin D1; apoptosis; cell cycle; p18; mantle cell lymphoma ID MOLECULAR ANALYSIS; P18(INK4C); GENES; CANCER; CDK6; DIFFERENTIATION; LYMPHOMA; FAMILY; D1; SUPPRESSION AB Multiple myeloma (MM) is a clonal neoplasm of plasma cells which offers an excellent model to study multistep molecular oncogenesis. In 20-25% of primary tumors and cell lines examined, cyclin D1 is overexpressed due to the translocation t(11;14)(q13;q32). We have characterized cyclin-dependent kinase inhibitor p15 (CDKN2B), p16 (CDKN2A) and p18 (CDKN2C) deletions in cyclin D1-expressing and non-expressing MM cell lines. p18 was found to be frequently deleted (38%); in some cases p18 deletions coexisted with hemizygous p16 deletion. To examine the function of p18 as a putative tumor suppressor in myeloma cells, a zinc-inducible p18 construct was stably transfected into KMS12, a MM cell line with biallelic p18 and monoallelic p16 deletions as well as cyclin D1 overexpression. Ectopic expression of p18 caused 40-45% growth suppression as determined by trypan blue exclusion and MTS assays. p18 induction also resulted in apoptosis, suggesting that inhibition of the cyclin D1/CDK/pRb pathway in these tumor cells could be a crucial step toward the induction of tumor regression via apoptotic cell death. This cell cycle pathway is thus frequently mutated and provides a potentially novel target for gene therapeutic or pharmacologic approaches to human myeloma. C1 Univ Virginia, Sch Med, Div Hematol Oncol, Dept Internal Med, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Microbiol, Charlottesville, VA 22908 USA. NCI, USN, Med Oncol Branch, Bethesda, MD USA. Cornell Univ, Med Ctr, New York Hosp, Dept Internal Med, New York, NY 10021 USA. RP Kulkarni, MS (reprint author), Univ Virginia, Sch Med, Div Hematol Oncol, Dept Internal Med, Box 800716,Jefferson Pk Ave, Charlottesville, VA 22908 USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU FIC NIH HHS [TW02297]; NIGMS NIH HHS [R01-GM55985] NR 33 TC 43 Z9 46 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2002 VL 16 IS 1 BP 127 EP 134 DI 10.1038/sj.leu.2402328 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 514PW UT WOS:000173451100017 PM 11840272 ER PT S AU Bogardus, C Baier, L Permana, P Prochazka, M Wolford, J Hanson, R AF Bogardus, C Baier, L Permana, P Prochazka, M Wolford, J Hanson, R BE Klimes, I Sebokova, E Howard, BV Ravussin, E TI Identification of susceptibility genes for complex metabolic diseases SO LIPIDS AND INSULIN RESISTANCE: THE ROLE OF FATTY ACID METABOLISM AND FUEL PARTITIONING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Meeting on Lipids and Insulin Resistance CY AUG 29-SEP 02, 2001 CL SMOLENICE CASTLE, SLOVAKIA SP Astra Zeneca, European Commiss, Berlin Chemie, Coca Cola Beverages, Eli Lilly, Fournier Labs, GlaxoSmithKline, Lipha Merck, NY Acad Sci, Novo Nordisk, Pfizer, Roche Diagnost Syst, Servier, Slovak Diabetes Soc DE Mendelian/non-Mendelian disease; susceptibility genes; genetic; linkage; positional cloning; allele; subphenotype ID GENOME AB There are few successful attempts to identify genes for common, non-Mendelian diseases such as diabetes, hyperlipidemia, hypertension, etc. Such common disorders are typically both metabolically and genetically complex and the genetic technologies to identify their underlying susceptibility genes are still in their infancy. Nonetheless, genetic strategies have emerged that, when the technologies are fully developed, should allow similar success rates as for Mendelian diseases. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Bogardus, C (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16Th St,Room 541, Phoenix, AZ 85016 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 8 TC 6 Z9 6 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-368-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 967 BP 1 EP 6 PG 6 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BU83P UT WOS:000177158000001 PM 12079829 ER PT S AU Baier, L Kovacs, P Wiedrich, C Cray, K Schemidt, A Shen, GQ Sutherland, J Thuillez, P Muller, YL Traurig, M Bogardus, C AF Baier, L Kovacs, P Wiedrich, C Cray, K Schemidt, A Shen, GQ Sutherland, J Thuillez, P Muller, YL Traurig, M Bogardus, C BE Klimes, I Sebokova, E Howard, BV Ravussin, E TI Positional cloning of an obesity/diabetes susceptibility gene(s) on chromosome 11 in Pima Indians SO LIPIDS AND INSULIN RESISTANCE: THE ROLE OF FATTY ACID METABOLISM AND FUEL PARTITIONING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Meeting on Lipids and Insulin Resistance CY AUG 29-SEP 02, 2001 CL SMOLENICE CASTLE, SLOVAKIA SP Astra Zeneca, European Commiss, Berlin Chemie, Coca Cola Beverages, Eli Lilly, Fournier Labs, GlaxoSmithKline, Lipha Merck, NY Acad Sci, Novo Nordisk, Pfizer, Roche Diagnost Syst, Servier, Slovak Diabetes Soc DE type 2 diabetes; obesity; linkage disequilibrium mapping; single nucleotide polymorphisms ID TYPE-2 DIABETES-MELLITUS; BODY-MASS INDEX; INSULIN-RESISTANCE; OBESITY; ASSOCIATION; CALPAIN-10 AB Prior results from our genomic scan in Pima Indians indicated an obesity locus in a region on chromosome 11q23-24 that was also linked to diabetes. Bivariate linkage analysis for the combined phenotype "diabesity" gave the strongest evidence for linkage (LOD = 5.2). Our aim is to positionally clone the gene(s) responsible for the linkage. Linkage disequilibrium mapping is being used to narrow the chromosomal region. Single nucleotide polymorphisms (SNPs) are being systematically identified and genotyped at 50-kb intervals across the region of linkage. To date, 455 SNPs have been genotyped in 1229 Pimas. A region containing a cluster of SNPs strongly associated with BMI and a second region, approximately 2 Mb telomeric, containing a cluster of SNPs associated with diabetes have been preliminarily identified. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Baier, L (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 15 TC 8 Z9 9 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-368-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 967 BP 258 EP 264 PG 7 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BU83P UT WOS:000177158000025 PM 12079853 ER PT S AU Del Parigi, A Gautier, JF Chen, KW Salbe, AD Ravussin, E Reiman, E Tataranni, PA AF Del Parigi, A Gautier, JF Chen, KW Salbe, AD Ravussin, E Reiman, E Tataranni, PA BE Klimes, I Sebokova, E Howard, BV Ravussin, E TI Neuroimaging and obesity - Mapping the brain responses to hunger and satiation in humans using positron emission tomography SO LIPIDS AND INSULIN RESISTANCE: THE ROLE OF FATTY ACID METABOLISM AND FUEL PARTITIONING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Meeting on Lipids and Insulin Resistance CY AUG 29-SEP 02, 2001 CL SMOLENICE CASTLE, SLOVAKIA SP Astra Zeneca, European Commiss, Berlin Chemie, Coca Cola Beverages, Eli Lilly, Fournier Labs, GlaxoSmithKline, Lipha Merck, NY Acad Sci, Novo Nordisk, Pfizer, Roche Diagnost Syst, Servier, Slovak Diabetes Soc DE brain; humans; hunger; hypothalamus; mapping; neuroimaging; obesity; positron emission tomography (PET); satiation ID CLONING; PET AB The hypothalamus has a major role in the control of food intake. However, neurotracing studies have shown that the hypothalamus receives input from several other regions of the brain that are likely to modulate its activity. Of particular interest to the understanding of human eating behavior is the possible involvement of the cortex. Using positron emission tomography (PET), we generated functional brain maps of the neuroanatomical correlates of hunger (after a 36-h fast) and satiation (after oral administration of a liquid formula meal) in lean and obese subjects. Results in lean individuals indicate that the neuroanatomical correlates of hunger form a complex network of brain regions including the hypothalamus, thalamus, and several limbic/paralimbic areas such as the insula, hippocampal/parahippocampal formation, and the orbitofrontal cortex. Satiation was associated with preferentially increased neuronal activity in the prefrontal cortex. Our studies also indicate that the brain responses to hunger/satiation in the hypothalamus, limbic/paralimbic areas (commonly associated with the regulation of emotion), and prefrontal cortex (thought to be involved in the inhibition of inappropriate response tendencies) might be different in obese and lean individuals. In conclusion, neuroimaging of the human brain is proving to be an important tool for understanding the complexity of brain involvement in the regulation of eating behavior. PET studies might help to unravel the neuropathophysiology underlying human obesity. C1 NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Good Samaritan Reg Med Ctr, Phoenix, AZ 85012 USA. RP Tataranni, PA (reprint author), NIDDK, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 541, Phoenix, AZ 85016 USA. RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 NR 26 TC 134 Z9 137 U1 2 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-368-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 967 BP 389 EP 397 PG 9 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BU83P UT WOS:000177158000038 PM 12079866 ER PT S AU Koska, J Ksinantova, L Sebokova, E Kvetnansky, R Klimes, I Chrousos, G Pacak, K AF Koska, J Ksinantova, L Sebokova, E Kvetnansky, R Klimes, I Chrousos, G Pacak, K BE Klimes, I Sebokova, E Howard, BV Ravussin, E TI Endocrine regulation of subcutaneous fat metabolism during cold exposure in humans SO LIPIDS AND INSULIN RESISTANCE: THE ROLE OF FATTY ACID METABOLISM AND FUEL PARTITIONING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Meeting on Lipids and Insulin Resistance CY AUG 29-SEP 02, 2001 CL SMOLENICE CASTLE, SLOVAKIA SP Astra Zeneca, European Commiss, Berlin Chemie, Coca Cola Beverages, Eli Lilly, Fournier Labs, GlaxoSmithKline, Lipha Merck, NY Acad Sci, Novo Nordisk, Pfizer, Roche Diagnost Syst, Servier, Slovak Diabetes Soc DE lipolysis; glycerol; glucose; catecholamines; cold; stress ID HUMAN ADIPOSE-TISSUE; ADRENERGIC REGULATION; GLYCEROL LEVELS; BLOOD-FLOW; LIPOLYSIS; DIALYSATE; DOPAMINE; INSITU; STRESS AB Increased oxidation of carbohydrates and free fatty acids is a well-known phenomenon during cold stress. Nevertheless, sources of the fuels used have not been fully clarified as yet. Thus, the aim of our study was to evaluate the effect of acute cold exposure on lipid and carbohydrate metabolism in human subcutaneous adipose tissue and to identify the possible regulatory mechanisms involved. Ten volunteers were exposed for 30 min to an ambient temperature of 4degreesC. Interstitial metabolism was assessed with the aid of the microdialysis technique. Lipolysis intensity was evaluated from changes of glycerol concentration in plasma and in dialysate. Cold exposure induced a significant increase of glycerol concentration both in plasma (by 199 +/- 16%, p < 0.01) and in dialysate (by 308 +/- 58%, p < 0.001). No changes in glucose concentration were found whether in plasma or in the dialysate. Ethanol concentration in dialysate increased (148 +/- 15%, p < 0.01), indicating a slower blood flow in the subcutaneous region. Plasma concentrations of various gluco- and/or lipid-regulatory hormones remained unaffected by the cold exposure, except for norepinephrine, which rose about threefold (309 +/- 41%, p < 0.001). The data indicate an important role for subcutaneous adipose tissue in mobilization of free fatty acids during cold exposure. This process seems to be regulated by the sympathetic nervous system, whereas hormones involved in the regulation of lipid metabolism, such as epinephrine, insulin, cortisol, and growth hormone, may play a less significant role-at least under the conditions studied. C1 Slovak Acad Sci, Inst Expt Endocrinol, Bratislava 83306, Slovakia. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. RP Koska, J (reprint author), Slovak Acad Sci, Inst Expt Endocrinol, Vlarska 3, Bratislava 83306, Slovakia. NR 19 TC 11 Z9 12 U1 1 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-368-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 967 BP 500 EP 505 PG 6 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BU83P UT WOS:000177158000052 PM 12079880 ER PT S AU Vozarova, B Weyer, C Bogardus, C Ravussin, E Tataranni, PA AF Vozarova, B Weyer, C Bogardus, C Ravussin, E Tataranni, PA BE Klimes, I Sebokova, E Howard, BV Ravussin, E TI Differences in oral temperature and body shape in two populations with different propensities for obesity SO LIPIDS AND INSULIN RESISTANCE: THE ROLE OF FATTY ACID METABOLISM AND FUEL PARTITIONING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Meeting on Lipids and Insulin Resistance CY AUG 29-SEP 02, 2001 CL SMOLENICE CASTLE, SLOVAKIA SP Astra Zeneca, European Commiss, Berlin Chemie, Coca Cola Beverages, Eli Lilly, Fournier Labs, GlaxoSmithKline, Lipha Merck, NY Acad Sci, Novo Nordisk, Pfizer, Roche Diagnost Syst, Servier, Slovak Diabetes Soc DE thermogenesis; ethnicity; surface area; insulin sensitivity ID PIMA-INDIANS; DIABETES-MELLITUS; INSULIN AB Objective-Body temperature is a function of heat production and heat dissipation. Substantial interindividual variability has been reported in healthy humans. We hypothesized that Pima Indians, a population with a high prevalence of abdominal obesity, may have a lower surface area relative to volume, that is, lower radiating area, and therefore a higher body temperature compared to Caucasians. Methods-Body composition, including volume (hydrodensitometry), and oral temperature were assessed in 69 nondiabetic Caucasian [age, 30 +/- 7 years; body fat, 21 +/- 8% (mean +/- SD)] and 115 Pima Indian males [age, 27 +/- 6 years; body fat, 28 +/- 6%]. Surface area was estimated from height, weight, and waist circumference (Bouchard's equation). In 47 Pima Indians, measures of insulin sensitivity (M, hyperinsulinemic euglycemic clamp) were available. Results-Compared to Caucasians, Pima Indians had a higher oral temperature [36.4 +/- 0.3degreesC vs. 36.3 +/- 0.3degreesC (mean SD), p < 0.04] and lower surface area relative to volume (2.19 +/- 0.05 vs. 2.23 +/- 0.26 m(2), p < 0.0001). Surface area relative to volume was negatively correlated with oral temperature (r = -0.14, p < 0.05), but in a multiple linear regression model it did not entirely explain the ethnic difference in oral temperature. Oral temperature was inversely correlated with M (r = -0.28, p < 0.05). Conclusions-Pima Indians have higher oral temperature and lower surface area relative to volume than Caucasians. The ethnic difference in temperature does not seem to be entirely explained by differences in body composition and body shape. Interestingly, higher oral temperature was associated with insulin resistance, a risk factor for type 2 diabetes. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Vozarova, B (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 541-a, Phoenix, AZ 85016 USA. OI de Courten, Barbora/0000-0001-8760-2511 NR 8 TC 3 Z9 3 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-368-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 967 BP 516 EP 521 PG 6 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BU83P UT WOS:000177158000054 PM 12079882 ER PT J AU Cooper, GS Parks, CG Treadwell, EL St Clair, EW Gilkeson, GS Cohen, PL Roubey, RAS Dooley, MA AF Cooper, GS Parks, CG Treadwell, EL St Clair, EW Gilkeson, GS Cohen, PL Roubey, RAS Dooley, MA TI Differences by race, sex and age in the clinical and immunologic features of recently diagnosed systemic lupus erythematosus patients in the southeastern United States SO LUPUS LA English DT Article DE lupus; demographics; age; sex; race; autoantibodies ID GENDER DIFFERENCES; REVISED CRITERIA; MANIFESTATIONS; ONSET; CLASSIFICATION; EXPRESSION; PROGNOSIS; CHINESE; COHORT; MALES AB We examined the prevalence of clinical and immunologic features of systemic lupus erythematosus (SLE) by race, sex and age in a population-based study of 265 SLE patients. Patients fulfilled the American College of Rheumatology classification criteria. The median time between diagnosis and study enrollment was 13 months. The clinical and hematologic data were limited to occurrences up to 6 months after the diagnosis date, as documented in medical records. We used sera collected at study enrollment from 244 (92%) patients for serologic testing of autoantibodies. The associations between clinical and immunological features of SLE and age, sex and race were examined using logistic regression. The effect of each of these variables was examined adjusting for the other two demographic factors, Mean age at diagnosis was 6 years younger among African-Americans and other minorities compared with white patients (P < 0.01). Discoid lupus, proteinuria, anti-Sm and anti-RNP autoantibodies were more commonly seen in African-American patients, with odds ratios higher than 3.0. Photosensitivity and mucosal ulcers were noted less often in African-American patients. Proteinuria, leukopenia, lymphopenia and thrombocytopenia were approximately three times more common in men compared with women. The prevalence of oral or nasal ulcers and anti-DNA autoantibodies declined with age. The extent to which the differences we observed reflect genetic or environmental influences on the disease process should be investigated. C1 NIEHS, Epidemiol Branch, Durham, NC 27709 USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC USA. Duke Univ, Med Ctr, Div Rheumatol Allergy & Clin Immunol, Durham, NC USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. Univ N Carolina, Div Rheumatol & Immunol, Thurston Arthritis Res Ctr, Chapel Hill, NC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Durham, NC 27709 USA. OI Parks, Christine/0000-0002-5734-3456 NR 25 TC 114 Z9 115 U1 0 U2 3 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2002 VL 11 IS 3 BP 161 EP 167 DI 10.1191/0961203302lu161oa PG 7 WC Rheumatology SC Rheumatology GA 541DW UT WOS:000174970800005 PM 11999880 ER PT S AU Hayward, AR AF Hayward, AR BE Rockson, SG TI The role of the National Center for Research Resources at the National Institutes of Health - Infrastructure to forge a new road for lymphatic biology and therapeutics SO LYMPHATIC CONTINUUM: LYMPHATIC BIOLOGY AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Lymphatic Continuum CY MAY 03-04, 2002 CL NIH NATCHER CTR, BETHESDA, MARYLAND HO NIH NATCHER CTR DE lymphatic diseases; research careers; NIH infrastructure; Florence Sabin AB Lymphatic research has infrastructure needs ranging from the nursing support provided by General Clinical Research Centers to training grants for future clinician investigators. Both have high priority in the activities currently funded by the Division of Clinical Research at NCRR. Further into the future, the therapeutic development networks and embryonic stem cells resources that are currently being developed should seem equally to have been essential resources. C1 NIH, Div Clin Res, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Hayward, AR (reprint author), NIH, Div Clin Res, Natl Ctr Res Resources, 6705 Rockledge Dr,Suite 6030, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-414-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 979 BP 5 EP 9 PG 5 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BW05J UT WOS:000180751900002 PM 12543711 ER PT S AU Leak, LV Petricoin, EF Jones, M Paweletz, CP Ardekani, AM Fusaro, VA Ross, S Liotta, LA AF Leak, LV Petricoin, EF Jones, M Paweletz, CP Ardekani, AM Fusaro, VA Ross, S Liotta, LA BE Rockson, SG TI Proteomic technologies to study diseases of the lymphatic vascular system SO LYMPHATIC CONTINUUM: LYMPHATIC BIOLOGY AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Lymphatic Continuum CY MAY 03-04, 2002 CL NIH NATCHER CTR, BETHESDA, MARYLAND HO NIH NATCHER CTR DE proteomics; cancer; lymph; lymphatic endothelium; lymphedema; laser capture microdissection; protein microarrays; SELDI-TOF-mass spectroscopy ID LASER CAPTURE MICRODISSECTION; IMMOBILIZED PH GRADIENTS; MASS-SPECTROMETRY; 2-DIMENSIONAL ELECTROPHORESIS; HUMAN GENOME; VEGF-C; PROTEINS; CANCER; PROSTATE; CELLS AB Now that the human genome has been mapped, a new challenge has emerged: deciphering the various products of individual genes. Consequently, new proteomic technologies are being developed to monitor and identify protein function and interactions responsible for the total activities of the cell. The application of these new proteomic technologies to study cellular activities, will lead to a faster sample throughput and increased sensitivity for the detection of individual proteins, thus providing major opportunities for the discovery of new biomarkers for the early detection of protein alterations associated with the progression of the disease state. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Clin Proteom Program Therapeut Prot, CBER, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Anat, Washington, DC 20059 USA. NHLBI, Lab Anim Surg & Med, NIH, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 61 TC 6 Z9 8 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-414-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 979 BP 211 EP 228 PG 18 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BW05J UT WOS:000180751900021 PM 12543730 ER PT S AU Okamoto, Y Douek, DC McFarland, RD Koup, RA AF Okamoto, Y Douek, DC McFarland, RD Koup, RA BE Gupta, S Butcher, E Paul, W TI Il-7, the thymus, and naive T cells SO LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION IX: HOMEOSTASIS AND LYMPHOCYTE TRAFFIC SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 9th International Conference on Lymphocyte Activation and Immune Regulation CY FEB 08-12, 2002 CL NEWPORT BEACH, CALIFORNIA ID BONE-MARROW TRANSPLANTATION; RECEPTOR-GAMMA-CHAIN; SEVERE COMBINED IMMUNODEFICIENCY; NATURAL-KILLER-CELLS; INTERLEUKIN-7 RECEPTOR; IMMUNE RECONSTITUTION; DENDRITIC CELLS; DEFICIENT MICE; GROWTH-FACTOR; ALPHA-BETA C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Douek, DC (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 66 TC 5 Z9 6 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47395-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 512 BP 81 EP 90 PG 10 WC Cell Biology; Immunology; Medicine, Research & Experimental SC Cell Biology; Immunology; Research & Experimental Medicine GA BV49H UT WOS:000179161600011 PM 12405190 ER PT S AU Min, B Sempowski, GD Paul, WE AF Min, B Sempowski, GD Paul, WE BE Gupta, S Butcher, E Paul, W TI Neonates support "homeostatic" proliferation SO LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION IX: HOMEOSTASIS AND LYMPHOCYTE TRAFFIC SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 9th International Conference on Lymphocyte Activation and Immune Regulation CY FEB 08-12, 2002 CL NEWPORT BEACH, CALIFORNIA ID T-CELL HOMEOSTASIS; THYMIC EMIGRANTS; NAIVE; SURVIVAL; SELECTION C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Min, B (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 14 TC 6 Z9 6 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47395-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 512 BP 91 EP 95 PG 5 WC Cell Biology; Immunology; Medicine, Research & Experimental SC Cell Biology; Immunology; Research & Experimental Medicine GA BV49H UT WOS:000179161600012 PM 12405191 ER PT S AU Germain, RN Stefanova, I Dorfman, J AF Germain, RN Stefanova, I Dorfman, J BE Gupta, S Butcher, E Paul, W TI Self-recognition and the regulation of CD4+T cell survival SO LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION IX: HOMEOSTASIS AND LYMPHOCYTE TRAFFIC SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 9th International Conference on Lymphocyte Activation and Immune Regulation CY FEB 08-12, 2002 CL NEWPORT BEACH, CALIFORNIA ID CD4(+) T-CELLS; MHC CLASS-I; HOMEOSTATIC PROLIFERATION; TCR-ZETA; COMPLEX; NAIVE; RECEPTOR; LINEAGE; MEMORY; SELECTION C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Dorfman, Jeffrey/B-4854-2011 OI Dorfman, Jeffrey/0000-0001-9938-8911 NR 40 TC 18 Z9 18 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47395-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 512 BP 97 EP 105 PG 9 WC Cell Biology; Immunology; Medicine, Research & Experimental SC Cell Biology; Immunology; Research & Experimental Medicine GA BV49H UT WOS:000179161600013 PM 12405192 ER PT S AU Ben-Sasson, SZ Zukovsky, I Biton, A Vogel, R Foucras, G Hayashi, N Paul, WE AF Ben-Sasson, SZ Zukovsky, I Biton, A Vogel, R Foucras, G Hayashi, N Paul, WE BE Gupta, S Butcher, E Paul, W TI Generation and characterization of memory CD4 T cells SO LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION IX: HOMEOSTASIS AND LYMPHOCYTE TRAFFIC SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 9th International Conference on Lymphocyte Activation and Immune Regulation CY FEB 08-12, 2002 CL NEWPORT BEACH, CALIFORNIA ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IL-6-DEFICIENT MICE; INNATE IMMUNITY; DIFFERENTIATION; IL-6; INTERLEUKIN-6; INDUCTION; STIMULATION; MACROPHAGES; ACTIVATION C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-91010 Jerusalem, Israel. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Ben-Sasson, SZ (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-91010 Jerusalem, Israel. NR 17 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47395-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 512 BP 129 EP 134 PG 6 WC Cell Biology; Immunology; Medicine, Research & Experimental SC Cell Biology; Immunology; Research & Experimental Medicine GA BV49H UT WOS:000179161600017 PM 12405196 ER PT J AU Baruch, DI Rogerson, SJ Cooke, BM AF Baruch, DI Rogerson, SJ Cooke, BM TI Asexual blood stages of malaria antigens: Cytoadherence SO MALARIA IMMUNOLOGY, 2ND EDITION SE CHEMICAL IMMUNOLOGY LA English DT Review ID FALCIPARUM-INFECTED ERYTHROCYTES; CHONDROITIN SULFATE-A; INTERCELLULAR-ADHESION MOLECULE-1; MICROVASCULAR ENDOTHELIAL-CELLS; MEMBRANE PROTEIN-1 PFEMP1; HISTIDINE-RICH PROTEIN; PLASMODIUM-FALCIPARUM; CEREBRAL MALARIA; FLOW CONDITIONS; RED-CELLS C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Melbourne, Dept Med, Parkville, Vic 3052, Australia. Monash Univ, Dept Microbiol, Melbourne, Vic 3004, Australia. RP Baruch, DI (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room Bl-37,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. OI Rogerson, Stephen/0000-0003-4287-1982 NR 106 TC 29 Z9 30 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem.Immunol. PY 2002 VL 80 BP 144 EP 162 PG 19 WC Immunology SC Immunology GA BU66Z UT WOS:000176677300007 PM 12058637 ER PT S AU Lahiri, DK Utsuki, T Shaw, KTY Ge, YW Sambamurti, K Eder, PS Rogers, JT Farlow, MR Giordino, T Greig, NH AF Lahiri, DK Utsuki, T Shaw, KTY Ge, YW Sambamurti, K Eder, PS Rogers, JT Farlow, MR Giordino, T Greig, NH BE Mizuno, Y Fisher, A Hanin, I TI Phenserine regulates translation of vamyloid precursor protein message - A novel drug target for Alzheimer's disease SO MAPPING THE PROGRESS OF ALZHEIMER'S AND PARKINSON'S DISEASE SE ADVANCES IN BEHAVIORAL BIOLOGY LA English DT Proceedings Paper CT 5th International Conference on the Progress in Alzheimers and Parkinsons Disease/9th International Catecholamine Symposium CY MAR 31-APR 05, 2001 CL KYOTO, JAPAN ID MESSENGER-RNA; INTERLEUKIN-1; RATS C1 Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Mayo Clin, Jacksonville, FL 32224 USA. Harvard Univ, Sch Med, Genet & Aging Unit, Boston, MA 02115 USA. Message Pharmaceut, Malvern, PA USA. NIA, NIH, Baltimore, MD USA. RP Lahiri, DK (reprint author), Indiana Univ, Sch Med, 791 Union Dr, Indianapolis, IN 46202 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0099-9962 BN 0-306-46763-1 J9 ADV BEHAV BIOL PY 2002 VL 51 BP 211 EP 215 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA BV16K UT WOS:000178038700035 ER PT S AU Chiueh, CC Andoh, T AF Chiueh, CC Andoh, T BE Mizuno, Y Fisher, A Hanin, I TI Cyclic GMP-mediated preconditioning gene induction as a treatment of Alzheimer's dementia and Parkinson's disease SO MAPPING THE PROGRESS OF ALZHEIMER'S AND PARKINSON'S DISEASE SE ADVANCES IN BEHAVIORAL BIOLOGY LA English DT Proceedings Paper CT 5th International Conference on the Progress in Alzheimers and Parkinsons Disease/9th International Catecholamine Symposium CY MAR 31-APR 05, 2001 CL KYOTO, JAPAN ID NITRIC-OXIDE SYNTHASE; ISCHEMIC TOLERANCE; CEREBRAL-ISCHEMIA; RAT-BRAIN; IN-VIVO; NEUROPROTECTION; HIPPOCAMPUS; ESTROGEN; STRESS; BCL-2 AB With advancements in molecular biology and genetics it is now feasible to employ gene technology as a treatment of diseases including some of the neurodegenerative brain disorders. Currently, gene transfer and multipurpose stem cells have been targeted for their future use in the management of Alzheimer's dementia and Parkinson's disease. We are investigating whether gene induction evoked by either sublethal stress or subtoxic chemicals, can induce adaptation or compensatory protection through a polygenic induction of cytoprotective genes and proteins. We have developed a human brain cell model for investigating hormesis or preconditioning neuroprotective mechanism mediated by multiple gene induction and new protein synthesis (Andoh, Lee and Chiueh, 2000; http://fasebj.org/cgi/doi/10.1096/fj.00-0151fje). Preconditioning induction of neuronal nitric oxide synthase and associated nitric oxide-cGMP-PKG pathway increases antioxidative (thioredoxin and MnSOD), anti-apoptotic (Bcl-2 and Ref-1), and cell-repairing proteins (BDNF) for protecting human brain cells against oxidative stress caused by serum deprivation and 1-methyl-4-phenylpyridinium (MPP+). This nitric oxide-cGMP mediated gene induction and cytoprotection is likely to becoming the mechanism in common in some of the atypical neuroprotective agents such as 17beta-estradiol and statins since both of them induce NOS I or NOS3 and nitric oxide. Without complications of brain surgery and intracerebral injection of viral vectors, gene induction may be more practically than gene therapy as a non-invasive treatment in Parkinson's disease and Alzheimer's dementia, especially for slowing progression in neurodegeneration and clinical deterioration. C1 NIMH, Clin Sci Lab, Unit Neurodegenerat & Neuroprotect, NIH, Bethesda, MD 20892 USA. RP Chiueh, CC (reprint author), NIMH, Clin Sci Lab, Unit Neurodegenerat & Neuroprotect, NIH, Bldg 10,Rm 3D-41, Bethesda, MD 20892 USA. NR 19 TC 1 Z9 1 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0099-9962 BN 0-306-46763-1 J9 ADV BEHAV BIOL PY 2002 VL 51 BP 447 EP 454 PG 8 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA BV16K UT WOS:000178038700076 ER PT B AU Leshner, AI AF Leshner, AI BE Crano, WD Burgoon, M TI Mass media and drug prevention: Classic and contemporary theories and research - Foreword SO MASS MEDIA AND DRUG PREVENTION: CLASSIC AND CONTEMPORARY THEORIES AND RESEARCH SE Claremont Symposium on Applied Social Psychology Series LA English DT Proceedings Paper CT 17th Claremont Symposium on Applied Social Psychology CY FEB 26, 2000 CL CLAREMONT GRAD UNIV, CLAREMONT, CA HO CLAREMONT GRAD UNIV C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-3478-8; 0-8058-3477-X J9 CLAR SYMP PY 2002 BP IX EP X PG 2 WC Communication; Psychology, Social SC Communication; Psychology GA BT92P UT WOS:000174462700001 ER PT J AU D'Souza, UM Lammers, CH Hwang, CK Yajima, S Mouradian, MM AF D'Souza, UM Lammers, CH Hwang, CK Yajima, S Mouradian, MM TI Developmental expression of the zinc finger transcription factor DRRF (dopamine receptor regulating factor) SO MECHANISMS OF DEVELOPMENT LA English DT Article DE embryogenesis; dopamine receptor regulating factor; dopaminergic neurotransmission ID GENE-EXPRESSION; INSITU HYBRIDIZATION; RAT STRIATUM; ONTOGENY; D1 AB Dopamine receptor regulating factor (DRRF) is a novel transcription factor with unique anatomical distribution and functional properties, suggesting its importance in regulating dopaminergic neurotransmission. To gain insight into the in vivo function of this factor during embryogenesis, we studied its distribution at embryonic days E8-E16 in the mouse using in situ hybridization. DRRF mRNA is expressed uniquely during development at all time points tested with high levels observed at E12, E14 and E16 in various tissues. DRRF expression is also found in particular brain regions, such as the neopallial cortex, olfactory lobe and corpus striatum. This pattern of DRRF distribution during embryogenesis overlaps with that found in the adult brain, and with the expression profile of dopamine receptors both in the adult and during development. Crown Copyright (C) 2002 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 NINCDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), Bldg 10,Room 5C116,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. NR 11 TC 12 Z9 12 U1 0 U2 0 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 2002 VL 110 IS 1-2 BP 197 EP 201 DI 10.1016/S0925-4773(01)00564-0 PG 5 WC Developmental Biology SC Developmental Biology GA 513JP UT WOS:000173375000020 PM 11744383 ER PT S AU Cannata, JM Ritter, TA Shung, KK AF Cannata, JM Ritter, TA Shung, KK BE Insana, MF Walker, WF TI A 35 MHz linear array for medical imaging SO MEDICAL IMAGE 2002: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE ultrasound; array; high frequency; medical imaging; transducer; transmission line AB This paper discusses the design, fabrication and testing of a 35 MHz linear ultrasonic array. The array features monolithic piezoelectric elements diced out of TRS 600FGHD fine grain high-density ceramic. A lossy urethane doped with gas filled microspheres; is used as a kerf-filler to dampen inter-element acoustic propagation and reduce pulse length. The array incorporates a slotted single matching layer made from an unloaded epoxy. This matching layer also contributes to the reduction of pulse length and an increase in sensitivity. Array elements are spaced by a 50 mum pitch and interconnected via a flexible circuit. An 85 Omega transmission line coaxial cable is used to electrically match the array elements to the 50 Omega system electronics. The final 64-element array design is based on experimental results obtained from several four-element prototype arrays. An average center frequency of 34 MHz with a -6 dB bandwidth of at least 45% is achieved with the final prototype array. The maximum combined electrical and acoustical cross-talk for nearest and next nearest elements is less than -29 dB. The average -40 dB pulse length is 105 ns. The simple design and satisfactory performance of this array make it suitable for large-scale production. C1 Penn State Univ, NIH, Resource Ctr Med Ultrason Transducer Technol, Dept Bioengn, University Pk, PA 16802 USA. RP Cannata, JM (reprint author), Penn State Univ, NIH, Resource Ctr Med Ultrason Transducer Technol, Dept Bioengn, 205 Hallowell Bldg, University Pk, PA 16802 USA. NR 6 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 0-8194-4432-4 J9 P SOC PHOTO-OPT INS PY 2002 VL 4687 BP 120 EP 126 DI 10.1117/12.462145 PG 7 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BU54Z UT WOS:000176292800012 ER PT S AU Pham, DL Han, X Rettmann, ME Xu, CY Tosun, D Resnick, SM Prince, JL AF Pham, DL Han, X Rettmann, ME Xu, CY Tosun, D Resnick, SM Prince, JL BE Sonka, M Fitzpatrick, JM TI New approaches for measuring changes in the cortical surface using an automatic reconstruction algorithm SO MEDICAL IMAGING 2002: IMAGE PROCESSING, VOL 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE image segmentation; cerebral cortex; magnetic resonance imaging; deformable models; fuzzy clustering ID MAGNETIC-RESONANCE IMAGES; HUMAN CEREBRAL-CORTEX; FUZZY SEGMENTATION; MRI AB In previous work, the authors presented a multi-stage procedure for the semi-automatic reconstruction of the cerebral cortex from magnetic resonance images. This method suffered from several disadvantages. First, the tissue classification algorithm used can be sensitive to noise within the image. Second, manual interaction was required for masking out undesired regions of the brain image, such as the ventricles and putamen. Third, iterated median filters were used to perform a topology correction on the initial cortical surface, resulting in an overly smoothed initial surface. Finally, the deformable surface used to converge to the cortex had difficulty capturing narrow gyri. In this work, all four disadvantages of the procedure have been addressed. A more robust tissue classification algorithm is employed and the manual masking step is replaced by an automatic method involving level set deformable models. Instead of iterated median filters, an algorithm developed specifically for topology correction is used. The last disadvantage is addressed using an algorithm that artificially separates adjacent sulcal banks. The new procedure is more automated but also more accurate than the previous one. Its utility is demonstrated by performing a preliminary study on data from the Baltimore Longitudinal Study of Aging. C1 NIA, Lab Personality & Cognit, Baltimore, MD 21224 USA. RP Pham, DL (reprint author), 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 25 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 0-8194-4429-4 J9 P SOC PHOTO-OPT INS PY 2002 VL 4684 BP 191 EP 200 DI 10.1117/12.467145 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BU94Y UT WOS:000177471900019 ER PT S AU Long, LR Krainak, DM Thoma, GR AF Long, LR Krainak, DM Thoma, GR BE Sonka, M Fitzpatrick, JM TI Identifying image structures for content-based retrieval of digitized spine x-rays SO MEDICAL IMAGING 2002: IMAGE PROCESSING, VOL 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE digitized x-rays; content-based image retrieval; spine; image segmentation ID VERTEBRAE AB We present ongoing work for the computer-assisted indexing of biomedical images at the Lister Hill National Center for Biomedical Communications, a research and development division of the National Library of Medicine (NLM). For any class of biomedical images, a problem confronting the researcher in image indexing is developing robust algorithms for localizing and identifying anatomy relevant for that image class and relevant to the indexing goals. This problem is particularly acute in the case of digitized spine x-rays, due to the projective nature of the data, which results in overlapping boundaries with possibly ambiguous interpretations; the highly irregular shapes of the vertebral bodies, sometimes additionally distorted by pathology; and possible occlusions of the vertebral anatomy due to subject positioning. We present algorithms that we have developed for the localization and identification of vertebral structure and show how these algorithms fit into the family of algorithms that we continue to develop for our general indexing problem. We also review the indexing goals for this particular collection of digitized spine x-rays and discuss the use of the indexed images in a content-based image retrieval system. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Long, LR (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 5 TC 0 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 0-8194-4429-4 J9 P SOC PHOTO-OPT INS PY 2002 VL 4684 BP 1204 EP 1214 DI 10.1117/12.467079 PG 11 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BU94Y UT WOS:000177471900128 ER PT S AU Yim, PJ Vasbinder, B Ho, VB Choyke, PL AF Yim, PJ Vasbinder, B Ho, VB Choyke, PL BE Sonka, M Fitzpatrick, JM TI A deforrnable isosurface and vascular applications SO MEDICAL IMAGING 2002: IMAGE PROCESSING, VOL 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE deformable model; magnetic resonance angiography; carotid artery; renal artery ID IMAGES AB Vascular disease produces changes in lumenal shape evident in magnetic resonance angiography (MRA). However, quantification of vascular shape from MRA is problematic due to image artifacts. Prior deformable models for vascular surface reconstruction primarily resolve problems of initialization of the surface mesh. However, initialization can be obtained in a trivial manner for MRA using isosurfaces. We propose a methodology for deforming the isosurface to conform to the boundaries of objects in the image with minimal a priori assumptions of object shape. As in conventional methods, external forces attract the surface towards edges in the image. However, smoothing is produced by torsional forces that align the normals of adjacent surface triangles. The torsional forces are unbiased with regard to determination of object size. The deformable isosurface was applied to MRA of carotid and renal arteries with moderate stenosis and to a digital phantom of an artery with high-grade stenosis (6-voxel normal diameter). The reconstruction of the carotid and renal arteries from MRA was entirely consistent with expert interpretation of the MRA. The deformable isosurface determined the degree of stenosis of the digital phantom to within 10.0% accuracy. The deformable isosurface is an excellent method for analysis of vascular shape C1 NIH, Imaging Sci Program, Bethesda, MD 20892 USA. RP Yim, PJ (reprint author), NIH, Imaging Sci Program, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 21 Z9 21 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 0-8194-4429-4 J9 P SOC PHOTO-OPT INS PY 2002 VL 4684 BP 1390 EP 1397 DI 10.1117/12.467104 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BU94Y UT WOS:000177471900149 ER PT S AU Suh, EB Warach, S Cheung, H Wang, SA Tangiral, P Luby, M Martino, RL AF Suh, EB Warach, S Cheung, H Wang, SA Tangiral, P Luby, M Martino, RL BE Siegel, EL Huang, HK TI A web-based medical image archive system SO MEDICAL IMAGING 2002: PACS AND INTEGRATED MEDICAL INFORMATION SYSTEMS: DESIGN AND EVALUATION SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE medical image archive; web-based image archive; image database; image storage and retrieval AB This paper presents a Web-based medical image archive system that has a three-tier, client-server architecture for the storage and retrieval of medical image data, as well as patient information and clinical data. The Web-based medical image archive system was designed to meet the need of the National Institute of Neurological Disorders and Stroke for a central image repository to address questions of stroke pathophysiology and imaging biomarkers in stroke clinical trials by analyzing images obtained from a large number of clinical trials conducted by government, academic and pharmaceutical industry researchers. In the database management-tier, we designed the image storage hierarchy to accommodate large binary image data files that the database software can access in parallel. In the middle-tier, a commercial Enterprise Java Bean server and secure Web server manages user access to the image database system. User-friendly Web-interfaces and applet tools are provided in the client-tier for easy access to the image archive system over the Internet. Benchmark test results show that our three-tier image archive system yields fast system response time for uploading, downloading, and querying the image database. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Suh, EB (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 3 Z9 3 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 0-8194-4430-8 J9 P SOC PHOTO-OPT INS PY 2002 VL 4685 BP 31 EP 41 DI 10.1117/12.467027 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BU70D UT WOS:000176734200005 ER PT S AU Petridou, N Loew, M Bandettini, PA AF Petridou, N Loew, M Bandettini, PA BE Antonuk, LE Yaffe, MJ TI S/N and fMRI sensitivity SO MEDICAL IMAGING 2002: PHYSICS OF MEDICAL IMAGING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE signal to noise; physiological noise; field strength; surface coil ID RETROSPECTIVE ESTIMATION; PHYSIOLOGICAL ARTIFACTS; FUNCTIONAL MRI; NOISE; SIGNAL; IMAGES; FLUCTUATIONS; REDUCTION; EPI AB it is commonly thought that improvements in image SIN translate directly to improvements in fMRI sensitivity. This study demonstrates that improvements in image SIN by means of increased field strength, and the use of surface coils, does not translate to similar gains in temporal SIN, due to physiological noise. An analysis of the SIN dependence on signal strength for both the imaginary and real noise components is presented. The real noise component, which is lower than the imaginary component, is a significant contributor to temporal variations in single-shot fMRI procedures. The imaginary component becomes an important contributor to time series fluctuations in multi-shot or 3D techniques. In the experiments presented here, the relationship between image and temporal SIN is examined by modulating the signal strength by means of echo time stepping, field strength modulation, and RF coil comparison. The spatial and temporal noise contributions of the resting brain are characterized by comparing phantom, subject, and thermal noise measurements. The sensitivity of both spiral and EPI single-shot acquisition methods to physiologic and systematic noise is characterized. The results suggest that the fMRI sensitivity plateaus as image SIN is increased unless physiological noise is filtered out. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Petridou, N (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. NR 29 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 0-8194-4427-8 J9 P SOC PHOTO-OPT INS PY 2002 VL 4682 BP 746 EP 754 DI 10.1117/12.465623 PG 3 WC Engineering, Biomedical; Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BU70C UT WOS:000176734000079 ER PT S AU Jerebko, AK Malley, JD Franaszek, M Summers, RM AF Jerebko, AK Malley, JD Franaszek, M Summers, RM BE Clough, AN Chen, CT TI Multi network classification scheme for detection of colonic polyps in CT colonography data sets SO MEDICAL IMAGING 2002: PHYSIOLOGY AND FUNCTION FROM MULTIDIMENSIONAL IMAGES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE virtual colonoscopy; colon cancer; classification; neural network AB A multi-network decision classification scheme for colonic polyp detection is presented. The approach is based on the results of voting over several neural networks using different variable sets of size N which are selected randomly or by an expert from a general variable set of size M. Detection of colonic polyps is complicated by a large variety of polypoid looking shapes (haustral folds, leftover stool) on the colon surface. Using various shape and curvature characteristics, intensity, size measurements and texture features to distinguish real polyps from false positives leads to an intricate classification problem. We used 17 features including region density, Gaussian and average curvature and sphericity, lesion size, colon wall thickness, and their means and standard deviations in the vicinity of the prospective polyp. Selection of the most important parameters to reduce a feature set to acceptable size is a generally unsolved problem. The method suggested in this paper uses a collection of subsets of variables. These sets of variables are weighted by their effectiveness. The effectiveness cost function is calculated on the basis of the training and test sample misclassification rates obtained by the training neural net with the given variable set. The final decision is based on the majority vote across the networks generated using the variable subsets, and takes into account the weighted votes of all nets. This method reduces the false positive rate by a factor of 1.7 compared to single net decisions. The overall sensitivity and specificity rates reached are 100% and 95% correspondingly. Best specificity and sensitivity rates were reached using back propagation neural nets with one hidden layer trained with the Levenberg-Marquardt algorithm. Ten-fold cross-validation is used to better estimate the true error rates. C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Jerebko, AK (reprint author), NIH, Dept Radiol, Bldg 10, Bethesda, MD 20892 USA. NR 6 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 0-8194-4428-6 J9 P SOC PHOTO-OPT INS PY 2002 VL 4683 BP 207 EP 212 DI 10.1117/12.463584 PG 6 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BU67T UT WOS:000176683700021 ER PT J AU Simonds, WF James-Newton, LA Agarwal, SK Yang, B Skarulis, MC Hendy, GN Marx, SJ AF Simonds, WF James-Newton, LA Agarwal, SK Yang, B Skarulis, MC Hendy, GN Marx, SJ TI Familial isolated hyperparathyroidism - Clinical and genetic characteristics of 36 kindreds SO MEDICINE LA English DT Review ID MULTIPLE ENDOCRINE NEOPLASIA; JAW TUMOR SYNDROME; NEONATAL SEVERE HYPERPARATHYROIDISM; CALCIUM-SENSING RECEPTOR; BENIGN HYPOCALCIURIC HYPERCALCEMIA; PRIMARY PARATHYROID HYPERPLASIA; TYPE-1 MEN1 GENE; MUTATION ANALYSIS; HEREDITARY HYPERPARATHYROIDISM; GERMLINE MUTATIONS C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Physiol, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. RP Simonds, WF (reprint author), Bldg 10,Room 8C-101,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 113 TC 145 Z9 149 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2002 VL 81 IS 1 BP 1 EP 26 DI 10.1097/00005792-200201000-00001 PG 26 WC Medicine, General & Internal SC General & Internal Medicine GA 513AF UT WOS:000173355200001 PM 11807402 ER PT S AU Yoo, TS Ackerman, MJ Lorensen, WE Schroeder, W Chalana, V Aylward, S Metaxas, D Whitaker, R AF Yoo, TS Ackerman, MJ Lorensen, WE Schroeder, W Chalana, V Aylward, S Metaxas, D Whitaker, R BE Westwood, JD Hoffman, HM Robb, RA Stredney, D TI Engineering and algorithm design for an image processing API: A technical report on ITK - the insight toolkit SO MEDICINE MEETS VIRTUAL REALITY 02/10: DIGITAL UPGRADES: APPLYING MOORES LAW TO HEALTH SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 10th Annual Medicine Meets Virtual Reality Conference CY JAN 23, 2002 CL NEWPORT BEACH, CA AB We present the detailed planning and execution of the Insight Toolkit (ITK), an application programmers interface (API) for the segmentation and registration of medical image data. This public resource has been developed through the NLM Visible Human Project, and is in beta test as an open-source software offering under cost-free licensing. The toolkit concentrates on 3D medical data segmentation and registration algorithms, multimodal and multiresolution capabilities, and portable platform independent support for Windows, Linuix/Unix systems. This toolkit was built using current practices in software engineering. Specifically, we embraced the concept of generic programming during the development of these tools, working extensively with C++ templates and the freedom and flexibility they allow. Software development tools for distributed consortium-based code development have been created and are also publicly available. Vie discuss our assumptions, design decisions, and some lessons learned. C1 Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Natl Lib Med, NIH, Bethesda, MD 20894 USA. NR 4 TC 173 Z9 173 U1 0 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-203-8 J9 STUD HEALTH TECHNOL PY 2002 VL 85 BP 586 EP 592 PG 7 WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BU64M UT WOS:000176591900107 PM 15458157 ER PT J AU Royak-Schaler, R Klabunde, CN Greene, WF Lannin, DR DeVellis, B Wilson, KR Cheuvront, B AF Royak-Schaler, R Klabunde, CN Greene, WF Lannin, DR DeVellis, B Wilson, KR Cheuvront, B TI Communicating breast cancer risk: Patient perceptions of provider discussions SO MEDSCAPE WOMENS HEALTH LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; INFORMED DECISION-MAKING; FAMILY HISTORY; PSYCHOLOGICAL DISTRESS; SCREENING MAMMOGRAPHY; CARE PROVIDERS; WOMEN; POPULATION; PHYSICIAN; TAMOXIFEN AB This study investigated the relationship between breast cancer risk communication delivered by providers and patient knowledge, perceptions, and screening practices. Telephone interviews were conducted with 141 African American (n = 71) and white (n = 70) first-degree relatives of breast cancer patients who received medical services at 2 university medical centers in North Carolina during 1994-95. Multiple items assessed subjects' reports of discussions with providers about family history and personal risk, knowledge of breast cancer risk factors, risk perceptions, breast cancer concerns, and screening practices. African American (AA) women were less likely than white women to report being informed of their increased personal risk of breast cancer because of family history. After controlling for education level, AA women aged >/= 50 years were less likely than white women to have ever had a mammogram. Both AA and white women who discussed family history and risk with their providers were significantly more likely to have had a mammogram within the past 2 years. Although these discussions seemed to increase participants' perceived risk of developing breast cancer, they did not promote knowledge of risk factors or increase levels of cancer concern. Study results indicate that provider discussions about family history and personal risk, accompanied by increases in risk perception, promote patient compliance with screening goals. Findings suggest that accurate knowledge about specific breast cancer risk factors may not be necessary to achieve screening compliance. However, additional studies are needed to investigate the relationship between knowledge of breast cancer risk factors and the adoption of behaviors associated with reducing breast cancer risk. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. E Carolina Univ, Sch Med, Greenville, NC USA. E Carolina Univ, Dept Sociol, Greenville, NC USA. Boston Univ, Boston, MA 02215 USA. RP Royak-Schaler, R (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 47 TC 0 Z9 0 U1 3 U2 3 PU MEDSCAPE INC PI NEW YORK PA 134 WEST 29TH ST, NEW YORK, NY 10001 USA SN 1521-2076 J9 MEDSCAPE WOMENS HEAL JI Medscape Womens Health PY 2002 VL 7 IS 2 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 549UQ UT WOS:000175465500003 ER PT J AU de Morais, CNL de Souza, JR de Melo, WG Aroucha, ML Domingues, ALC Wynn, T Abath, FGC Montenegro, SML AF de Morais, CNL de Souza, JR de Melo, WG Aroucha, ML Domingues, ALC Wynn, T Abath, FGC Montenegro, SML TI Studies on the production and regulation of interleukin, IL-13, IL-4 and interferon-gamma in human schistosomiasis mansoni SO MEMORIAS DO INSTITUTO OSWALDO CRUZ LA English DT Article; Proceedings Paper CT 8th International Symposium on Schistosomiasis CY DEC 02-05, 2001 CL RECIFE, BRAZIL DE Schistosoma mansoni; cytokines; human schistosomiasis ID GRANULOMA-FORMATION; IFN-GAMMA; CYTOKINE; MICE; EGGS AB The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma was evaluated in different clinical forms of human schistosomiasis. The mechanisms of immune regulation are apparently different in the various clinical stages of the disease, some of them being antigen specific. C1 Ctr Pesquisas Aggeu Magalhaes Fiocruz, BR-50670420 Recife, PE, Brazil. Univ Fed Pernambuco, Recife, PE, Brazil. NIH, Bethesda, MD 20892 USA. RP Montenegro, SML (reprint author), Ctr Pesquisas Aggeu Magalhaes Fiocruz, Av Morais Rego S-N,Cidade Univ, BR-50670420 Recife, PE, Brazil. NR 12 TC 1 Z9 1 U1 0 U2 0 PU FUNDACO OSWALDO CRUZ PI RIO DE JANEIRO, RJ PA AV BRASIL 4365, 21045-900 RIO DE JANEIRO, RJ, BRAZIL SN 0074-0276 J9 MEM I OSWALDO CRUZ JI Mem. Inst. Oswaldo Cruz PY 2002 VL 97 SU 1 BP 113 EP 114 PG 2 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA 607VH UT WOS:000178811100023 PM 12426605 ER PT J AU Nelson, KB Willoughby, RE AF Nelson, KB Willoughby, RE TI Overview: Infection during pregnancy and neurologic outcome in the child SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Editorial Material C1 NINCDS, Ctr Clin, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Nelson, KB (reprint author), NINCDS, Ctr Clin, Neuroepidemiol Branch, NIH, Room 5S221, Bethesda, MD 20892 USA. NR 7 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2002 VL 8 IS 1 BP 1 EP 2 DI 10.1002/mrdd.10010 PG 2 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 527NY UT WOS:000174193200001 PM 11921379 ER PT J AU Goncalves, LF Chaiworapongsa, T Romero, R AF Goncalves, LF Chaiworapongsa, T Romero, R TI Intrauterine infection and prematurity SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE preterm labor; interauterine infection; fetal infection; PCR; prenatal diagnosis; treatment; antibiotics ID AMNIOTIC-FLUID INTERLEUKIN-6; POLYMERASE-CHAIN-REACTION; LOW-BIRTH-WEIGHT; BLOOD-CELL COUNT; PLACEBO-CONTROLLED TRIAL; ACUTE INFLAMMATORY LESIONS; COLONY-STIMULATING FACTOR; RAPID DIAGNOSTIC-TESTS; GROUP-B STREPTOCOCCI; PRETERM LABOR AB Intrauterine infection is a major cause of premature labor with and without intact membranes. Intrauterine infection is present In approximately 25% of all preterm births and the earlier the gestational age at delivery, the higher the frequency of intra-amniotic infection. Microorganisms may also gain access to the fetus before delivery. A fetal inflammatory response syndrome elicited in response to microbial products is associated with the impending onset of preterm labor and also with multi-systemic organ involvement in the human fetus and a higher rate of perinatal morbidity. The most common microorganisms involved in intrauterine Infections are Ureaplasma urealyticum, Fusobacterium species and Mycoplasma hominis. The role of Chlamydia trachomatis and viruses in preterm labor remain to be determined. Use of molecular microbiology techniques to diagnose intrauterine infection may uncover the role of fastidious microorganisms that have not yet been discovered. Antibiotic administration to patients with asymptomatic bacteriuria is associated with a significant reduction in the rate of preterm birth. However, such benefit has not been demonstrated for patients with bacterial vaginosis, or women who carry Streptococcus agalactia, Ureaplasma urealyticum or Trichomonas vaginalis. Antibiotic administration to patients with preterm premature rupture of membranes is associated with prolongation of pregnancy and a reduction in the rate of clinical chorioamnionitis and neonatal sepsis. The benefit has not been demonstrated in patients with preterm labor and intact membranes. Major efforts are required to determine why some women develop an ascending intrauterine infection and others do not and also what interventions may reduce the deleterious effect of systemic fetal inflammation. (C) 2002 Wiley-Liss, Inc. C1 Hutzel Hosp, Perinatol Res Branch, NICHD, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Hutzel Hosp, Perinatol Res Branch, NICHD, Dept Obstet & Gynecol, 4707 St Antoine Blvd, Detroit, MI 48201 USA. NR 150 TC 280 Z9 286 U1 1 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2002 VL 8 IS 1 BP 3 EP 13 DI 10.1002/mrdd.10008 PG 11 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 527NY UT WOS:000174193200002 PM 11921380 ER PT J AU Nelson, KB AF Nelson, KB TI The epidemiology of cerebral palsy interm infants SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE cerebral palsy; prematurity; chorioamnionitis; coagulation disorders ID NORTHERN CALIFORNIA COUNTIES; NORMAL BIRTH-WEIGHT; FULL-TERM INFANTS; RISK-FACTORS; NEWBORN ENCEPHALOPATHY; CHILDREN; INFARCTION; STROKE; PREGNANCY; INFECTION AB Half of cerebral palsy (CP) arises in infants of normal birthweight yet, many fewer studies seek to identify risk factors for CP in term and near-term infants than in those born very prematurely. There has been no net decrease in the prevalence of CP in term and near-term infants over recent decades. Potentially asphyxiating birth complications account for a small minority of CP cases. Recent studies suggest that disorders of coagulation and intrauterine exposure to infection or inflammation are associated with risk of CP, and that both can be accompanied by signs of neonatal encephalopathy, the best available predictor of CP in term neonates, Therapeutic interventions directed at preventing interruption of oxygen supply have not been shown to reduce the occurrence of CP. There have not yet been studies examining whether medical interventions directed at infection or coagulation disorder can reduce the frequency of CP. (C) 2002 Wiley-Liss, Inc. C1 NINDS, Ctr Clin, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Nelson, KB (reprint author), NINDS, Ctr Clin, Neuroepidemiol Branch, NIH, Room 5S221, Bethesda, MD 20892 USA. NR 60 TC 81 Z9 87 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2002 VL 8 IS 3 BP 146 EP 150 DI 10.1002/mrdd.10037 PG 5 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 588ZQ UT WOS:000177733100004 PM 12216058 ER PT S AU Tchounwou, PB Ishaque, AB Sutton, D Ninashvili, N Shen, E AF Tchounwou, PB Ishaque, AB Sutton, D Ninashvili, N Shen, E BE Khassanova, L Collery, P Maymard, I Khassanova, Z Etienne, JC TI Biomarkers of sensitivity and effect associated with cadmium and mercury toxicity in human liver carcinoma (HepG(2)) cells SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 7 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 7th International Symposium on Metal Ions in Biology and Medicine CY MAY 05-09, 2002 CL ST PETERSBURG UNIV, ST PETERSBURG, RUSSIA SP Bashkir State Pedag Univ, Publishing House, Alpha Color, Publishing House, Belaya Reka HO ST PETERSBURG UNIV ID TRANSCRIPTION AB In the past, demonstrating the biologic significance of chemical exposure has relied significantly on assessing and identifying the pathology induced by xenobiotic compounds. However, biomarkers of sensitivity have in recent years, increasingly being used in toxicology for detecting and predicting the harmful effects of chemical agents on the health and well being of humans and other life forms. This research was therefore designed to assess the cellular and molecular responses of human liver carcinoma cells following exposure to cadmium, and mercury; and to subsequently identify the potential biomarkers of sensitivity and effect associated with exposure to these metal compounds. Cytotoxicity was evaluated using the MTT-assay for cell viability, while. the gene profile (CAT-Tox) assay was performed to measure the transcriptional activation of stress genes in thirteen different recombinant cell lines generated from HepG(2) cells. Cyctotoxicity experiments yielded LD50 values of 3.5+/-0.6, and 6.1+/-0.8 ug/mL upon 48 hrs of exposure to mercury, and cadmium, respectively; indicating that mercury was more toxic than cadmium to HepG(2) cells. A dose-response relationship was recorded with respect to both cytotoxicity and gene expression. Overall, nine (GSTYa, HMTIIA, c-fos, HSP70, CRE, p53RE, GADD153, GADD45, and GRP78) out of the thirteen recombinant cell lines tested for mercury showed inductions to statistically significant levels (p<0.05). Following exposure to cadmium, four of these stress genes (HMTIIA, HSP70, CRE, and XRE) were significantly induced and seven were marginally induced. No significant inductions (p>0.05) were observed for CYP1A1, and RARE. As expected, these results indicate that metallothioneins and heat shock proteins appear to be excellent candidates for biomarkers for detecting metal-induced proteotoxic effects at the molecular and cellular levels. C1 Jackson State Univ, Mol Toxicol Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Mol Toxicol Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, Jackson, MS 39217 USA. NR 11 TC 5 Z9 5 U1 1 U2 1 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0429-7 J9 METAL IONS BIOL MED PY 2002 VL 7 BP 132 EP 137 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA BW97U UT WOS:000183835700029 ER PT S AU Tchounwou, PB AF Tchounwou, PB BE Khassanova, L Collery, P Maymard, I Khassanova, Z Etienne, JC TI Health risk assessment and management of arsenic toxicity and carcinogenesis SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 7 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 7th International Symposium on Metal Ions in Biology and Medicine CY MAY 05-09, 2002 CL ST PETERSBURG UNIV, ST PETERSBURG, RUSSIA SP Bashkir State Pedag Univ, Publishing House, Alpha Color, Publishing House, Belaya Reka HO ST PETERSBURG UNIV ID DRINKING-WATER; CANCER AB Acute and chronic exposure to arsenic has been reported in several countries of the world, with major outbreaks of arsenosis occurring in Argentina, Bangladesh, India, Mexico, Thailand, and Taiwan, where a large proportion of drinking water (groundwater) is contaminated with high concentrations of arsenic. Hence, arsenic poisoning appears to be one of the major public health problems of pandemic nature. A comprehensive analysis of published data indicates that arsenic exposure induces cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, heamatologic disorders, and various types of cancer, including skin, and lung neoplasms. Recent epidemiologic studies have demonstrated a strong correlation between arsenic exposure and the increase in incidence of human cancers. Research has also pointed out significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution. There is therefore a great need for developing a comprehensive risk assessment (RA) model, to be used in the management of health risks associated with arsenic exposure. The development of such model requires a thorough understanding of the physical and chemical properties of arsenic, its production and use, fate and transport, toxicokinetics, systemic and carcinogenic health effects, regulatory and health guidelines, analytical methods, and treatment technologies. This paper aims at using the National Academy of Science's RA paradigm as a guide; to present a conceptual RA framework for managing the potential risks of toxicity and carcinogenesis associated with arsenic exposure. C1 Jackson State Univ, Sch Sci & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Sch Sci & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. NR 21 TC 0 Z9 0 U1 1 U2 3 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0429-7 J9 METAL IONS BIOL MED PY 2002 VL 7 BP 365 EP 370 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA BW97U UT WOS:000183835700076 ER PT J AU Pile, LA Wassarman, DA AF Pile, LA Wassarman, DA TI Localizing transcription factors on chromatin by immunofluorescence SO METHODS LA English DT Article DE Drosophila; polytene chromosomes; immunofluorescence; chromatin; euchromatin; heterochromatin; salivary glands; transcription; transcription factor; antibody ID HEAT-SHOCK; DROSOPHILA-MELANOGASTER; X-CHROMOSOME; IN-VIVO; PROMOTER; COMPLEX; PHOSPHORYLATION; LOCALIZATION; ELEMENTS; DOMAINS AB This article contains a detailed protocol for localizing transcription factors on Drosophila melanogaster polytene chromosomes by immunofluorescence. The large polytene chromosomes from third-instar larval salivary gland cells allow mapping of chromosome-associated proteins at high resolution. Thus, this method has been used to investigate how broadly transcription factors function and to identify and characterize cis-acting protein domains, trans-acting proteins, and trans-acting DNA elements that are necessary for chromosomal association of transcription factors. The ability to directly visualize transcription factors bound to chromosomes during a transcriptionally active stage of the cell cycle has greatly enhanced our understanding of how transcription factors function in vivo. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Wassarman, DA (reprint author), Univ Wisconsin, Sch Med, Dept Pharmacol, 1300 Univ Ave, Madison, WI 53706 USA. NR 27 TC 16 Z9 16 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JAN PY 2002 VL 26 IS 1 BP 3 EP 9 AR PII S1046-2023(02)00002-6 DI 10.1016/S1046-2023(02)00002-6 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 551QM UT WOS:000175572600002 PM 12054899 ER PT J AU Akiyama, SK AF Akiyama, SK TI Functional analysis of cell adhesion: Quantitation of cell-matrix attachment SO METHODS IN CELL-MATRIX ADHESION SE METHODS IN CELL BIOLOGY LA English DT Review ID SITE-DIRECTED MUTAGENESIS; AMINO-ACID-SEQUENCE; BINDING DOMAIN; PLASMA FIBRONECTIN; FIBROBLASTIC CELLS; INTEGRIN; MIGRATION; RECEPTOR; LAMININ; IDENTIFICATION C1 Natl Inst Environm Hlth Sci, Lab Mol Carcinogensis, NIH, Res Triangle Pk, NC 27709 USA. RP Akiyama, SK (reprint author), Natl Inst Environm Hlth Sci, Lab Mol Carcinogensis, NIH, Res Triangle Pk, NC 27709 USA. NR 53 TC 6 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2002 VL 69 BP 281 EP 296 DI 10.1016/S0091-679X(02)69018-1 PG 16 WC Cell Biology SC Cell Biology GA BU68R UT WOS:000176706600017 PM 12070999 ER PT J AU Lindberg, DAB AF Lindberg, DAB TI Medicine in the 21st century: Global problems, global solutions SO METHODS OF INFORMATION IN MEDICINE LA English DT Editorial Material DE medical informatics; health informatics AB Objectives: To discuss application areas of information technology in medicine and health care on the occasion of the opening of the Private Universitat fur Medizinische Informatik und Technik Tirol/University for Health Informatics and Technology Tyrol (UMIT) at Innsbruck, Tyrol, Austria. Results and Conclusions: Important application areas of information technology in medicine and health are appropriate individual access to medical knowledge, new engineering developments such as new radiant imaging methods and the implantable pacemaker/defibrillator devices, mathematical modeling for understanding the workings of the human body, the computer-based patient record, as well as new knowledge in molecular biology, human genetics, and biotechnology. Challenges and responsibilities for medical informatics research include medical data privacy and intellectual property rights inherent in the content of the information systems. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Lindberg, DAB (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2002 VL 41 IS 3 BP 235 EP 236 PG 2 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 577YA UT WOS:000177089600011 PM 12162150 ER PT J AU McCray, AT Haux, R AF McCray, AT Haux, R TI Supporting open access to scientific information SO METHODS OF INFORMATION IN MEDICINE LA English DT Editorial Material C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. Univ Hlth Informat & Technol Tyrol, Inst Hlth Informat Syst, A-6020 Innsbruck, Austria. RP McCray, AT (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 8 TC 4 Z9 4 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2002 VL 41 IS 4 BP 243 EP 244 PG 2 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 607GL UT WOS:000178783700001 PM 12425234 ER PT S AU Weng, NP Liu, KB Catalfamo, M Li, Y Henkart, PA AF Weng, NP Liu, KB Catalfamo, M Li, Y Henkart, PA BE Aujame, L Burdin, N Dodet, B Vicari, M TI IL-15 is a growth factor and an activator of CD8 memory T cells SO MICROARRAYS, IMMUNE RESPONSES AND VACCINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Microarrays, Immune Responses and Vaccines CY MAY 26-29, 2002 CL VEYRIER DU LAC, FRANCE SP Fdn Merieux DE IL-15; memory CD8 T cells; TCR; microarray; cytotoxicity ID IN-VIVO; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; DENDRITIC CELLS; HUMAN MONOCYTES; NATURAL-KILLER; MESSENGER-RNA; STAT PROTEINS; RECEPTOR; NAIVE AB Memory lymphocytes, arising from naive lymphocytes after antigenic stimulation and being long-lived, are the cellular basis for immunological memory. Recent studies of CD8 T cells suggest that generation of CD8 memory T cells requires the engagement of T cell antigen receptors (TCR) with antigen, yet the maintenance of CD8 memory T cells appears to be dependent on cytokines, such as IL-15, independent of TCR. Although considerable progress has been made in understanding the molecular and cellular events of TCR-induced differentiation and proliferation in the past decade, less is known about the mechanisms of IL-15 action. From a kinetic and comparative analysis of the responses of memory phenotype CD8 T cells to IL-15 and TCR stimulation in vitro, we found that IL-15 and anti-CD3 induce highly similar responses in memory phenotype CD8 T cells as measured by general gene expression profiles, synthesis of effector molecules (IFNgamma, TNFbeta, granzyme B and perforin), induction of cytotoxicity, and cellular proliferation. These findings indicate that IL-15 is not only a growth factor but also an antigen-independent activator for CD8 memory T cells. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM wengn@grc.nia.nih.gov OI Liu, Kebin/0000-0003-1965-7240 NR 40 TC 52 Z9 60 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-446-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 975 BP 46 EP 56 PG 11 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BW05G UT WOS:000180751500004 PM 12538153 ER PT J AU Knight, SAB Lesuisse, E Stearman, R Klausner, RD Dancis, A AF Knight, SAB Lesuisse, E Stearman, R Klausner, RD Dancis, A TI Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator SO MICROBIOLOGY-SGM LA English DT Article DE iron regulation; ferric reductase; multicopper oxidase; ferrous permease; siderophores ID SACCHAROMYCES-CEREVISIAE; FERRIC REDUCTASE; FUNGAL-INFECTIONS; ESCHERICHIA-COLI; NADPH OXIDASE; YEAST; GENE; TRANSPORT; VIRULENCE; ENCODES AB High-affinity iron uptake by a ferrous permease in the opportunistic pathogen Candida albicans is required for virulence. Here this iron uptake system has been characterized by investigating three distinct activities: an externally directed surface ferric reductase, a membrane-associated PPD (p-phenylenediamine) oxidase and a cellular ferrous iron transport activity. Copper was required for the PPD oxidase and ferrous transport activities. In contrast, copper was not required for iron uptake from siderophores. Addition of iron to the growth medium repressed ferric reductase and ferrous transport, indicating homeostatic regulation. To identify the genes involved, orthologous mutants of Saccharomyces cerevisiae were transformed with a genomic library of C. albicans. CFL95, a gene with sequence similarity to ferric reductases, restored reductase activity to the orthologous S. cerevisiae mutant. CaFTR2 and CaFTR1, genes with homology to ferrous permeases, conferred ferrous transport activity to the orthologous S. cerevisiae mutant. However, neither a genomic library nor CaFET99, a multicopper oxidase homologue and candidate gene for the PPD oxidase, complemented the S. cerevisiae mutant, possibly because of problems with targeting or assembly. Transcripts for CF195, CaFTR1 and CaFET99 were strongly repressed by iron, whereas the CaFTR2 transcript was induced by iron. Deletion of the TUP1 regulator perturbed the homeostatic control of reductive iron uptake. Incidentally, iron starvation was noted to induce flavin production and this was misregulated in the absence of TUP1 control. The opposite regulation of two iron permease genes and the role of TUP1 indicate that the process of iron acquisition by C. albicans may be more complex and potentially more adaptable than by S. cerevisiae. C1 Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. Univ Paris 07, Inst Jacques Monod, Lab Ingeniere Prot & Controle Metab, F-75251 Paris 05, France. Univ Paris 06, Inst Jacques Monod, Lab Ingeniere Prot & Controle Metab, F-75251 Paris 05, France. NCI, Off Director, NIH, Bethesda, MD 20892 USA. RP Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. EM adancis@mail.med.upenn.edu NR 43 TC 85 Z9 94 U1 1 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JAN PY 2002 VL 148 BP 29 EP 40 PN 1 PG 12 WC Microbiology SC Microbiology GA 513AE UT WOS:000173355100005 PM 11782496 ER PT J AU Laquerriere, P Michel, J Balossier, G Chenais, B AF Laquerriere, P Michel, J Balossier, G Chenais, B TI Light elements quantification in stimulated cells cryosections studied by electron probe microanalysis SO MICRON LA English DT Review DE X-ray microanalysis; electron energy loss spectroscopy; cells cryosection; light elements ID NITRIC-OXIDE SYNTHASE; ENERGY LOSS SPECTROSCOPY; X-RAY-MICROANALYSIS; DIGITAL-FILTERS; TRACE-ELEMENTS; OPTIMIZATION; OXYGEN AB The quantification of intracellular light elements such as carbon, nitrogen and oxygen may be useful in understanding the biological mechanisms, for example the generation of nitric oxide which is involved in apoptosis and inflammatory reaction. Electron energy loss spectroscopy (EELS) coupled with scanning transmission electron microscopy is a useful method to detect light elements in thin cryosections. Recent developments of X-ray detectors with ultra-thin protection windows allows the detection of such elements by energy dispersive X-ray spectroscopy, In the present study. we have demonstrated using both methods that the stimulation of BV-2 murine microglial cell line by gamma-interferon and lipopolysaccharide leads to the increase of intracellular oxygen concentration and no change in the intracellular nitrogen concentration. This indicates the use of exogeneous molecular oxygen in response to the stimulation. But the increase of oxygen concentration detected could not be only due to NO expression because the NO production was 1000 times less than the oxygen concentration increase observed. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 UFR Sci, IFR 53, EA 2068, Lab Micoscopie Elect, F-51685 Reims 2, France. Fac Pharm Reims, IFR 53, Unite MeDIAN, CNRS,UMR 6142, F-51096 Reims, France. RP Laquerriere, P (reprint author), NIH, Div Bioengn & Phys Sci, Bldg 13,Room 3E73,13 South Dr, Bethesda, MD 20892 USA. RI Chenais, Benoit/C-6465-2009; Laquerriere, Patrice/P-1025-2016 OI Chenais, Benoit/0000-0003-2441-1966; Laquerriere, Patrice/0000-0001-7637-9094 NR 21 TC 5 Z9 5 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-4328 J9 MICRON JI Micron PY 2002 VL 33 IS 7-8 BP 597 EP 603 AR PII S0968-4328(02)00032-X DI 10.1016/S0968-4328(02)00032-X PG 7 WC Microscopy SC Microscopy GA 632AK UT WOS:000180200600002 PM 12475556 ER PT J AU Mattson, MP AF Mattson, MP TI Contributions of mitochondrial alterations, resulting from bad genes and a hostile environment, to the pathogenesis of Alzheimer's disease SO MITOCHONDRIAL FUNCTION AND DYSFUNCTION SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID AMYLOID-PRECURSOR PROTEIN; NF-KAPPA-B; MANGANESE SUPEROXIDE-DISMUTASE; PERTURBED CALCIUM HOMEOSTASIS; CORTICAL SYNAPTIC TERMINALS; NEURONAL CA2+ HOMEOSTASIS; AMPA RECEPTOR SUBUNITS; TRANSGENIC MOUSE MODEL; BETA-PEPTIDE TOXICITY; ISCHEMIC BRAIN-DAMAGE C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr 4F01, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 132 TC 23 Z9 24 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2002 VL 53 BP 387 EP 409 PG 23 WC Neurosciences SC Neurosciences & Neurology GA BV91Y UT WOS:000180386700013 PM 12512347 ER PT J AU de Souza-Pinto, NC Bohr, VA AF de Souza-Pinto, NC Bohr, VA TI The mitochondrial theory of aging: Involvement of mitochondrial DNA damage and repair SO MITOCHONDRIAL FUNCTION AND DYSFUNCTION SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID BASE EXCISION-REPAIR; HYDROGEN-PEROXIDE TREATMENT; FREE-RADICAL PRODUCTION; AGE-ASSOCIATED DAMAGE; OXIDATIVE DAMAGE; DIETARY RESTRICTION; MAMMALIAN-CELLS; NUCLEAR-DNA; LIFE-SPAN; PROTEIN OXIDATION C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 83 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2002 VL 53 BP 519 EP 534 PG 16 WC Neurosciences SC Neurosciences & Neurology GA BV91Y UT WOS:000180386700017 PM 12512351 ER PT J AU Kearney, DL Perez-Atayde, AR AF Kearney, DL Perez-Atayde, AR CA HIV Study Grp TI Postmortem cardiomegaly and its clinico-pathologic significance in HIV-infected children. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 20 BP 4P EP 4P PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901498 ER PT J AU Romero, ME Wexler, LH Harrison-Shahan, Y Helman, L Tsokos, M AF Romero, ME Wexler, LH Harrison-Shahan, Y Helman, L Tsokos, M TI Survivin inhibits drug-induced apoptosis and correlates with prognosis in Ewing's sarcoma family tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NCI, 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 28 BP 5P EP 5P PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901506 ER PT J AU Feldman, AL Bartlett, DL Libutti, SK Alexander, HR Kleiner, DE AF Feldman, AL Bartlett, DL Libutti, SK Alexander, HR Kleiner, DE TI Relationship between histologic grade and outcome in patients with peritoneal mesothelioma SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 43 BP 14A EP 14A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900060 ER PT J AU Palacios, J Garcia-Macias, MC Bryant, B Sobel, ME Merino, MJ AF Palacios, J Garcia-Macias, MC Bryant, B Sobel, ME Merino, MJ TI E-cadherin (ECD) gene inactivation in pleomorphic lobular carcinoma (PLC) of the breast SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Ctr Nacl Invest Oncol, Madrid, Spain. Univ Hosp, Salamanca, Spain. RI Hardisson, David/E-2832-2010 OI Hardisson, David/0000-0002-2183-3699 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 177 BP 45A EP 45A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900194 ER PT J AU Palacios, J Bryant, B Hardisson, D Sobel, ME Merino, MJ AF Palacios, J Bryant, B Hardisson, D Sobel, ME Merino, MJ TI cDNA microarray gene expression analysis of microdissected frozen ductal breast carcinomas after linear RNA amplification SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Ctr Nacl Invest Oncol, Madrid, Spain. Hosp La Paz, Madrid, Spain. RI Hardisson, David/E-2832-2010 OI Hardisson, David/0000-0002-2183-3699 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 176 BP 45A EP 45A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900193 ER PT J AU van de Rijn, M Perou, C Tibshirani, R Kallioniemi, O Kononen, J Sauter, G Botstein, D Brown, P AF van de Rijn, M Perou, C Tibshirani, R Kallioniemi, O Kononen, J Sauter, G Botstein, D Brown, P TI Tissue microarray analysis of cytokeratin 17 and 5 expression shows association with poor clinical outcome in breast carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Stanford Univ, Stanford, CA 94305 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Basel, Basel, Switzerland. NIH, Bethesda, MD 20892 USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 218 BP 55A EP 55A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900235 ER PT J AU Auerbach, A Filie, AC Copeland, C Sorbara, L Raffeld, M Stetler-Stevenson, M Barnes, E Abati, A AF Auerbach, A Filie, AC Copeland, C Sorbara, L Raffeld, M Stetler-Stevenson, M Barnes, E Abati, A TI Cerebrospinal fluid specimens for diagnosing lymphomas and lymphoproliferative disorders: A comparison of diagnosis by cytology, flow cytometry and molecular diagnostics SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 264 BP 66A EP 66A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900281 ER PT J AU Bryant-Greenwood, PK Filie, AC Little, R Yarchoan, R Raffeld, M Sorbara, L Abati, A AF Bryant-Greenwood, PK Filie, AC Little, R Yarchoan, R Raffeld, M Sorbara, L Abati, A TI Morphologic and molecular camparison of recurrent effusions in HIV plus patients with and without documented HHV8 disease manifestations SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 267 BP 66A EP 67A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900284 ER PT J AU Clark, BD Filie, AC Sorbara, L Stetler-Stevenson, M Raffeld, M Abati, A AF Clark, BD Filie, AC Sorbara, L Stetler-Stevenson, M Raffeld, M Abati, A TI Diagnosis of lymphomatoid granulomatosis by cytology: A comparison of conventional cytology, flow cytometry, and polymerase chain reaction (PCR) SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NIH, Cytopathol Sect, Bethesda, 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 273 BP 68A EP 68A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900290 ER PT J AU Mason, D Andre, P Bensussan, A Buckley, C Civin, C Clark, E de Haas, M Goyert, S Hadam, M Hart, D Horejsi, V Meuer, S Morrissey, J Schwartz-Albiez, R Shaw, S Simmons, D Uguccioni, M van der Schoot, E Vivier, E Zola, H AF Mason, D Andre, P Bensussan, A Buckley, C Civin, C Clark, E de Haas, M Goyert, S Hadam, M Hart, D Horejsi, V Meuer, S Morrissey, J Schwartz-Albiez, R Shaw, S Simmons, D Uguccioni, M van der Schoot, E Vivier, E Zola, H TI CD antigens 2001 SO MODERN PATHOLOGY LA English DT Article ID HUMAN DENDRITIC CELLS; MONOCLONAL-ANTIBODY; MOLECULAR CHARACTERIZATION; SURFACE-MOLECULE; PERIPHERAL-BLOOD; RECEPTOR; MEMBER; CLONING; FAMILY; MACROPHAGES C1 John Radcliffe Hosp, Dept Haematol, Oxford OX3 9DU, England. INSERM CNRS Marseille Luminy, Ctr Immunol, Marseille, France. INSERM, Creteil, France. MRC, Ctr Immune Regulat, Div Immun & Infect, Birmingham, W Midlands, England. Johns Hopkins Comprehens Canc Ctr, Baltimore, MD USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Dept Expt Immunohematol, CLB, Amsterdam, Netherlands. Cornell Univ Med Coll, Div Mol Med, Lab Mol Hematol, Manhasset, NY 11030 USA. Hannover Med Sch, Kinderklin, Hannover, Germany. Mater Hosp, Mater Med Res Inst, Brisbane, Australia. Acad Sci Czech Republ, Inst Mol Genet, Prague, Czech Republic. Univ Heidelberg, Inst Immunol, D-6900 Heidelberg, Germany. Univ Illinois, Coll Med, Urbana, IL 61801 USA. German Canc Res Ctr, D-6900 Heidelberg, Germany. NIH, Bethesda, MD 20892 USA. Celltech R&D Ltd, Cambridge, England. Inst Res Biomed, Bellinzona, Switzerland. Womens & Childrens Hosp, Child Hlth Res Inst, Adelaide, SA, Australia. RP Mason, D (reprint author), John Radcliffe Hosp, Dept Haematol, Oxford OX3 9DU, England. EM david.mason@ndcls.ox.ac.uk RI Horejsi, Vaclav/G-3113-2014; Bensussan, Armand/E-5434-2017; OI Uguccioni, Mariagrazia/0000-0002-9570-7011 NR 32 TC 3 Z9 3 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 BP 71 EP 76 DI 10.1038/modpathol.3880492 PG 6 WC Pathology SC Pathology GA 513QD UT WOS:000173388900011 PM 11796844 ER PT J AU Rosenblatt, KP Cassarino, DS Auerbach, A Duray, PH AF Rosenblatt, KP Cassarino, DS Auerbach, A Duray, PH TI Pathology and immunophenotype of 10 cases of aggressive melanoma SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 440 BP 107A EP 107A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900457 ER PT J AU De la Cruz, A Fojo, A Merino, MJ AF De la Cruz, A Fojo, A Merino, MJ TI Expression of the ACTH-receptor in normal and neoplastic adrenal tissues SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 469 BP 113A EP 114A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900486 ER PT J AU Merino, MJ Roberts, DD Bryant, B Krutzsch, HC AlBarazi, H Libutti, SK Sarlis, NJ Panizo, A AF Merino, MJ Roberts, DD Bryant, B Krutzsch, HC AlBarazi, H Libutti, SK Sarlis, NJ Panizo, A TI Differences of protein expression in benign and malignant microdissected thyroid tissues SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 487 BP 117A EP 118A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900504 ER PT J AU Luo, J Gage, WR Hick, JL Wanders, RJ Trent, JM Isaacs, WB De Marzo, AM AF Luo, J Gage, WR Hick, JL Wanders, RJ Trent, JM Isaacs, WB De Marzo, AM TI Overexpression of alpha methyl acyl-Coa racemase (AMACR) in prostate cancer analyzed by cDNA microarrays and high density tissue microarrays SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Amsterdam, Amsterdam, Netherlands. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 712 BP 171A EP 171A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900729 ER PT J AU Ronchetti, R Auerbach, A Harris, CA Linehan, M Zbar, B Quezado, M Merino, MJ AF Ronchetti, R Auerbach, A Harris, CA Linehan, M Zbar, B Quezado, M Merino, MJ TI Type I Papillary Renal Cell Carcinoma, correlation between morphology, immunophenotype, genetic changes and outcome SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 743 BP 178A EP 178A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900760 ER PT J AU Barry, TS Pittaluga, S Raffeld, M Jaffe, ES AF Barry, TS Pittaluga, S Raffeld, M Jaffe, ES TI Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) and T-cell rich/histiocyte rich large B-cell lymphoma (T/HCRLBCL): Evidence for a biological overlap SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 970 BP 231A EP 232A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900993 ER PT J AU Barry, TS Taddesse-Heath, L Raffeld, M Sorbara, L Pittaluga, S Jaffe, ES AF Barry, TS Taddesse-Heath, L Raffeld, M Sorbara, L Pittaluga, S Jaffe, ES TI Hodgkin's transformation of marginal zone B-cell lymphoma (MZBCL): Evidence for clonal evolution SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 969 BP 231A EP 231A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900992 ER PT J AU Barry, TS Jaffe, ES Raffeld, M Pittaluga, S AF Barry, TS Jaffe, ES Raffeld, M Pittaluga, S TI Peripheral T-cell lymphomas simulating classical Hodgkin's lymphoma with Reed-Sternberg-like giant cells of T-cell phenotype SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 968 BP 231A EP 231A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900991 ER PT J AU Greiner, TC Farrell, BT Weisenburger, DD Hoeck, L Armitage, JO Staudt, L Chan, WC AF Greiner, TC Farrell, BT Weisenburger, DD Hoeck, L Armitage, JO Staudt, L Chan, WC TI P53 mutations may explain the decreased survival in the activated B-like subgroup of diffuse large B-cell lymphomas SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1011 BP 242A EP 242A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901034 ER PT J AU Hans, CP Weisenburger, DD Gascoyne, RD Greiner, TC Cochran, GT Pan, X Gao, Z Farinha, P Hock, L Lynch, JC Rosenwald, A Staudt, LM Connors, J Armitage, JO Chan, WC AF Hans, CP Weisenburger, DD Gascoyne, RD Greiner, TC Cochran, GT Pan, X Gao, Z Farinha, P Hock, L Lynch, JC Rosenwald, A Staudt, LM Connors, J Armitage, JO Chan, WC TI Classification of diffuse large B-cell lymphoma into prognostically significant subgroups by immunohistochemistry using a tissue microarray SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Peking Univ, Hlth Sci Ctr, Beijing 100871, Peoples R China. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1015 BP 243A EP 243A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901038 ER PT J AU Taddesse-Heath, L Pittaluga, S Sorbara, L Raffeld, M Hedge, U Wilson, W Jaffe, WS AF Taddesse-Heath, L Pittaluga, S Sorbara, L Raffeld, M Hedge, U Wilson, W Jaffe, WS TI Incidence and clinical significance of clonal/oligoclonal T cell expansions in patients with lymphomatoid granulomatosis SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1104 BP 265A EP 266A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388901127 ER PT J AU Kleiner, DE Hewitt, SM Hale, DA Mannon, RB Swanson, SJ Kirk, AD AF Kleiner, DE Hewitt, SM Hale, DA Mannon, RB Swanson, SJ Kirk, AD TI Unusual immunologic response to renal allografts in patients receiving CAMPATH-1H as a sole immunosuppressant SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NIDDK, Transplantat & Autoimmun Branch, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1154 BP 278A EP 278A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901177 ER PT J AU Coleman, KE Kelavkar, UP Lawson, D Haseman, J Cohen, C AF Coleman, KE Kelavkar, UP Lawson, D Haseman, J Cohen, C TI 15-lipoxygenase-1 (15-LO-1) as a molecular marker in cancer: An immunohistochemical study SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Div Renal, Atlanta, GA 30322 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 2 Z9 2 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1264 BP 304A EP 304A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901287 ER PT J AU Fujii, T Gillespie, JW Jen, J Travis, WD AF Fujii, T Gillespie, JW Jen, J Travis, WD TI Mitochondrial D-loop mutation and AAAG microsatellite instability as molecular markers for clonality analysis: An application to sclerosing hemangioma SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1327 BP 319A EP 319A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901349 ER PT J AU He, P Miura, K Bowman, ED Welsh, JA Travis, WD Harris, CC AF He, P Miura, K Bowman, ED Welsh, JA Travis, WD Harris, CC TI Molecular profiling of pulmonary neuroendocrine tumors with laser capture microdissection and cDNA microarray SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Washington, DC 20306 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1336 BP 321A EP 321A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901358 ER PT J AU Valencia, JC Blankinship, GL Yu, ZX Moss, J Ferrans, VJ AF Valencia, JC Blankinship, GL Yu, ZX Moss, J Ferrans, VJ TI Expression of microphthalmia-asscociated transcription factor (MITF) and CD63 melanoma antigen in pulmonary lymphangioleiomyomatosis SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NHLBI, 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1374 BP 330A EP 330A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901396 ER PT J AU Merante, F Altamentova, SM Mickle, DAG Weisel, RD Thatcher, BJ Martin, BM Marshall, JG Tumiati, LC Cowan, DB Li, RK AF Merante, F Altamentova, SM Mickle, DAG Weisel, RD Thatcher, BJ Martin, BM Marshall, JG Tumiati, LC Cowan, DB Li, RK TI The characterization and purification of a human transcription factor modulating the glutathione peroxidase gene in response to oxygen tension SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE DNA binding proteins; glutathione peroxidase; hypoxia; Ku-antigen; protein purification; transcription factors ID HYPOXIA-INDUCIBLE FACTOR-1; DEPENDENT PROTEIN-KINASE; MOBILITY SHIFT ASSAYS; DNA HELICASE-II; KU AUTOANTIGEN; CATALYTIC SUBUNIT; BINDING PROTEIN; NUCLEIC-ACIDS; SEQUENCE; ANTIGEN AB An oxygen responsive transcription factor regulating human glutathione peroxidase gene (GPx) through two oxygen responsive elements (ORE1 and ORE2) has been purified and characterized by sequence-specific DNA affinity chromatography. The DNA binding activity, termed Oxygen Responsive Element Binding Protein (OREBP), was partially represented by a 77 kD polypeptide (p70) possessing a blocked N-terminus. The p70 subunit co-eluted with an 86 kD subunit (p80) from affinity columns. N-terminal sequencing analysis of the 86 kD component revealed that this protein represented the larger member of the Ku antigen complex. The identity of the purified 77 kD subunit was determined by Western blot analysis using an antibody directed against the p70 protein. In addition to binding the GPx-ORE, the OREBP was itself regulated by oxygen tension. It was found that the abundance of the ORE binding activity was decreased in cells maintained at low oxygen tension (40 mm Hg). Anti-Ku-antibodies specifically supershifted the OREBP-ORE DNA complex. These observations further add to the numerous nuclear roles of the Ku-transcription factor. C1 Univ Toronto, Toronto Hosp, Cardiovasc Res Ctr, Dept Clin Biochem, Toronto, ON M5G 2C4, Canada. Univ Toronto, Toronto Hosp, Div Cardiovasc Surg, Toronto, ON M5G 2C4, Canada. Tm Biosci Corp, Toronto, ON, Canada. NIMH, NIH, Bethesda, MD 20892 USA. RP Mickle, DAG (reprint author), Univ Toronto, Toronto Hosp, Cardiovasc Res Ctr, Dept Clin Biochem, EC 3-306,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. RI Marshall, John /E-8974-2012 OI Marshall, John /0000-0002-7124-1448 NR 41 TC 14 Z9 19 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 2002 VL 229 IS 1-2 BP 73 EP 83 DI 10.1023/A:1017921110363 PG 11 WC Cell Biology SC Cell Biology GA 521WZ UT WOS:000173865500009 PM 11936849 ER PT J AU Schaber, M Lindgren, A Schindler, K Bungard, D Kaldis, P Winter, E AF Schaber, M Lindgren, A Schindler, K Bungard, D Kaldis, P Winter, E TI CAK1 promotes meiosis and spore formation in Saccharomyces cerevisiae in a CDC28-independent fashion SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CDK-ACTIVATING KINASE; SPORULATION-SPECIFIC GENES; CYCLIN-DEPENDENT KINASE; COLI SHUTTLE VECTORS; PROTEIN-KINASE; BUDDING YEAST; MAP KINASE; TRANSCRIPTIONAL REGULATION; PACHYTENE CHECKPOINT; RESTRICTION SITES AB CAK1 encodes a protein kinase in Saccharomyces cerevisiae whose sole essential mitotic role is to activate the Cdc28p cyclin-dependent kinase by phosphorylation of threonine-169 in its activation loop. SMK1 encodes a sporulation-specific mitogen-activated protein (MAP) kinase homolog that is required to regulate the postmeiotic events of spore wall assembly. CAK1 was previously identified as a multicopy suppressor of a weakened smk1 mutant and shown to be required for spore wall assembly. Here we show that Smk1p, like other MAP kinases, is phosphorylated in its activation loop and that Smk1p is not activated in a cak1 missense mutant. Strains harboring a hyperactivated allele of CDC28 that is CAK1 independent and that lacks threonine-169 still require CAK1 to activate Smk1p. The data indicate that Cak1p functions upstream of Smk1p by activating a protein kinase other than Cdc28p. We also found that mutants lacking CAK1 are blocked early in meiotic development, as they show substantial delays in premeiotic DNA synthesis and defects in the expression of sporulation-specific genes, including IME1. The early meiotic role of Cak1p, like the postmeiotic role in the Smk1p pathway, is CDC28 independent. The data indicate that Cak1p activates multiple steps in meiotic development through multiple protein kinase targets. C1 Thomas Jefferson Univ, Dept Mol Pharmacol & Biochem, Philadelphia, PA 19107 USA. NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Winter, E (reprint author), Thomas Jefferson Univ, Dept Mol Pharmacol & Biochem, Philadelphia, PA 19107 USA. RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU NIGMS NIH HHS [R01 GM061817, R01 GM61817] NR 47 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 1 BP 57 EP 68 DI 10.1128/MCB.22.1.57-68.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 501LK UT WOS:000172686000006 PM 11739722 ER PT J AU Li, CJ DePamphilis, ML AF Li, CJ DePamphilis, ML TI Mammalian Orc1 protein is selectively released from chromatin and ubiquitinated during the S-to-M transition in the cell division cycle SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ORIGIN RECOGNITION COMPLEX; MINICHROMOSOME MAINTENANCE PROTEINS; EUKARYOTIC DNA-REPLICATION; XENOPUS EGG EXTRACT; CHROMOSOME-REPLICATION; INITIATION; CDC6; GENE; ASSOCIATION; YEAST AB Previous studies have shown that changes in the affinity of the hamster Orc1 protein for chromatin during the M-to-G, transition correlate with the activity of hamster origin recognition complexes (ORCs) and the appearance of prereplication complexes at specific sites. Here we show that Orc1 is selectively released from chromatin as cells enter S phase, converted into a mono- or diubiquitinated form, and then deubiquitinated and re-bound to chromatin during the M-to-G, transition. Orc1 is degraded by the 26S proteasome only when released into the cytosol, and peptide additions to Orc1 make it hypersensitive to polyubiquitination. In contrast, Orc2 remains tightly bound to chromatin throughout the cell cycle and is not a substrate for ubiquitination. Since the concentration of Orc1 remains constant throughout the cell cycle, and its half-life in vivo is the same as that of Orc2, ubiquitination of non-chromatin-bound Orc1 presumably facilitates the inactivation of ORCs by sequestering Orc1 during S phase. Thus, in contrast to yeast (Saccharomyces cerevisiae and Schizosaccharomyces pombe), mammalian ORC activity appears to be regulated during each cell cycle through selective dissociation and reassociation of Orc1 from chromatin-bound ORCs. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bldg 6,Room 416, Bethesda, MD 20892 USA. NR 59 TC 96 Z9 98 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 1 BP 105 EP 116 DI 10.1128/MCB.22.1.105-116.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 501LK UT WOS:000172686000010 PM 11739726 ER PT J AU Blass, M Kronfeld, I Kazimirsky, G Blumberg, PM Brodie, C AF Blass, M Kronfeld, I Kazimirsky, G Blumberg, PM Brodie, C TI Tyrosine phosphorylation of protein kinase C delta is essential for its apoptotic effect in response to etoposide SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PKC-DELTA; SIGNAL-TRANSDUCTION; PROTEOLYTIC ACTIVATION; GLUTAMINE-SYNTHETASE; GROWTH-FACTOR; CANCER CELLS; GLIAL-CELLS; U937 CELLS; EXPRESSION; CLEAVAGE AB Protein kinase C delta (PKC delta) is involved in the apoptosis of various cells in response to diverse stimuli. In this study, we characterized the role of PKC delta in the apoptosis of C6 glioma cells in response to etoposide. We found that etoposide induced apoptosis in the C6 cells within 24 to 48 h and arrested the cells in the G(1)/S phase of the cell cycle. Overexpression of PKC delta increased the apoptotic effect induced by etoposide, whereas the PKC delta selective inhibitor rottlerin and the PKC delta dominant-negative mutant K376R reduced this effect compared to control cells. Etoposide-induced tyrosine phosphorylation of PKC delta and its translocation to the nucleus within 3 h was followed by caspase-dependent cleavage of the enzyme. Using PKC chimeras, we found that both the regulatory and catalytic domains of PKC delta were necessary for its apoptotic effect. The role of tyrosine phosphorylation of PKC delta in the effects of etoposide was examined using cells overexpressing a PKC delta mutant in which five tyrosine residues were mutated to phenylalanine (PKC delta5). These cells exhibited decreased apoptosis in response to etoposide compared to cells overexpressing PKC delta. Likewise, activation of caspase 3 and the cleavage of the PKC delta5 mutant were significantly lower in cells overexpressing PKC delta5. Using mutants of PKC delta altered at individual tyrosine residues, we identified tyrosine 64 and tyrosine 187 as important phosphorylation sites in the apoptotic effect induced by etoposide. Our results suggest a role of PKC delta in the apoptosis induced by etoposide and implicate tyrosine phosphorylation of PKC delta as an important regulator of this effect. C1 Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diag Res Ctr, IL-52900 Ramat Gan, Israel. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Brodie, C (reprint author), Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diag Res Ctr, IL-52900 Ramat Gan, Israel. NR 59 TC 166 Z9 169 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 1 BP 182 EP 195 DI 10.1128/MCB.22.1.182-195.2002 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 501LK UT WOS:000172686000017 PM 11739733 ER PT J AU Aladjem, MI Rodewald, LW Lin, CM Bowman, S Cimbora, DA Brody, LL Epner, EM Groudine, M Wahl, GM AF Aladjem, MI Rodewald, LW Lin, CM Bowman, S Cimbora, DA Brody, LL Epner, EM Groudine, M Wahl, GM TI Replication initiation patterns in the beta-globin loci of totipotent and differentiated murine cells: Evidence for multiple initiation regions SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BIDIRECTIONAL DNA-REPLICATION; CHROMATIN STRUCTURE; ACTIVATION REGION; ORIGIN; GENE; SITES; MOUSE; IDENTIFICATION; SEQUENCE; TRANSCRIPTION AB The replication initiation pattern of the murine beta -globin locus was analyzed in totipotent embryonic stem cells and in differentiated cell lines. Initiation events in the murine beta -globin locus were detected in a region extending from the embryonic Ey gene to the adult beta minor gene, unlike the restricted initiation observed in the human locus. Totipotent and differentiated cells exhibited similar initiation patterns. Deletion of the region between the adult globin genes did not prevent initiation in the remainder of the locus, suggesting that the potential to initiate DNA replication was not contained exclusively within the primary sequence of the deleted region. In addition, a deletion encompassing the six identified 5' hypersensitive sites in the mouse locus control region had no effect on initiation from within the locus. As this deletion also did not affect the chromatin structure of the locus, we propose that the sequences determining both chromatin structure and replication initiation lie outside the hypersensitive sites removed by the deletion. C1 NCI, Mol Pharmacol Lab, DBS, NIH, Bethesda, MD 20892 USA. Salk Inst, Gene Express Lab, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Arizona Canc Ctr, BMT, Tucson, AZ 85724 USA. RP Aladjem, MI (reprint author), NCI, Mol Pharmacol Lab, DBS, NIH, Bldg 37,Rm 5056D,37 Convent Dr, Bethesda, MD 20892 USA. RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU NCI NIH HHS [CA48405, R01 CA048405]; NIDDK NIH HHS [DK44746, R37 DK044746]; NIGMS NIH HHS [GM51104] NR 38 TC 49 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 2 BP 442 EP 452 DI 10.1128/MCB.22.2.442-452.2002 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506QU UT WOS:000172983900006 PM 11756541 ER PT J AU Young, MR Nair, R Bucheimer, N Tulsian, P Brown, N Chapp, C Hsu, TC Colburn, NH AF Young, MR Nair, R Bucheimer, N Tulsian, P Brown, N Chapp, C Hsu, TC Colburn, NH TI Transactivation of Fra-1 and consequent activation of AP-1 occur extracellular signal-regulated kinase dependently SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-FOS PROMOTER; PROTEIN-KINASE; NEOPLASTIC TRANSFORMATION; DNA-BINDING; JB6 CELLS; TRANSCRIPTIONAL ACTIVATION; RESPONSE ELEMENT; TUMOR PROMOTION; DELETION MUTANT; MAP KINASES AB Mitogen-activated protein (MAP) kinase, extracellular-signal-regulated kinases (ERKs) play an important role in activating AP-1-dependent transcription. Studies using the JB6 mouse epidermal model and a transgenic mouse model have established a requirement for AP-1-dependent transcription in tumor promotion. Tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor induce activator protein 1 (AP-1) activity and neoplastic transformation in JB6 transformation-sensitive (P+) cells, but not in transformation-resistant (P-) variants. The resistance in one of the P- variants can be attributed to the low levels of the MAP kinases, ERKs 1 and 2, and consequent nonresponsiveness to AP-1 activation. The resistant variant is not deficient in c-fos transcription. The purpose of these studies was to define the targets of activated ERK that lead to AP-1 transactivation. The results establish that the transactivation domain of Fra-1 can be activated, that activation of Fra-1 is ERK dependent, and that a putative ERK phosphorylation site must be intact for activation to occur. Fra-1 was activated by TPA in ERK-sufficient P+ cells but not in ERK-deficient P- cells. A similar activation pattern was seen for c-Fos but not for Fra-2. Gel shift analysis identified Fra-1 as distinguishing mitogen-activated (P+) from nonactivated (P-) AP-1 complexes. A second AP-1-nonresponsive P- variant that underexpresses Fra-1 gained AP-1 response upon introduction of a Fra-1 expression construct. These observations suggest that ERK-dependent activation of Fra-1 is required for AP-1 transactivation in JB6 cells. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. RP Young, MR (reprint author), NCI, Basic Res Lab, POB B,Bldg 560,Rm 21-27, Frederick, MD 21702 USA. NR 71 TC 94 Z9 94 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 2 BP 587 EP 598 DI 10.1128/MCB.22.2.587-598.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506QU UT WOS:000172983900019 PM 11756554 ER PT J AU Bardeesy, N Morgan, J Sinha, M Signoretti, S Srivastava, S Loda, M Merlino, G DePinho, RA AF Bardeesy, N Morgan, J Sinha, M Signoretti, S Srivastava, S Loda, M Merlino, G DePinho, RA TI Obligate roles for p16(Ink4a) and p19(Arf)-p53 in the suppression of murine pancreatic neoplasia SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; ARF TUMOR-SUPPRESSOR; TRANSGENIC MICE; FACTOR-ALPHA; P53-DEPENDENT APOPTOSIS; INK4A LOCUS; PLASMACYTOMA SUSCEPTIBILITY; CELL-PROLIFERATION; CYSTIC TUMORS; TGF-ALPHA AB Epithelial tumors of the pancreas exhibit a wide spectrum of histologies with varying propensities for metastasis and tissue invasion. The histogenic relationship among these tumor types is not well established; moreover, the specific role of genetic lesions in the progression of these malignancies is largely undefined. Transgenic mice with ectopic expression of transforming growth factor alpha (TGF-alpha) in the pancreatic acinar cells develop tubular metaplasia, a potential premalignant lesion of the pancreatic ductal epithelium. To evaluate the cooperative interactions between TGF-ci and signature mutations in pancreatic tumor genesis and progression, TGF alpha transgenic mice were crossed onto Ink4a/Arf and/or p53 mutant backgrounds. These compound mutant mice developed a novel pancreatic neoplasm, serous cystadenoma (SCA), presenting as large epithelial tumors bearing conspicuous gross and histological resemblances to their human counterpart. TGF alpha animals heterozygous for both the Ink4a/Arf and the p53 mutation showed a dramatically increased incidence of SCA, indicating synergistic interaction of these alleles. Inactivation of p16(Ink4a) by loss of heterozygosity, intragenic mutation, or promoter hypermethylation was a common feature in these SCAs, and correspondingly, none of the tumors expressed wild-type p16(Ink4a). kll tumors sustained loss of p53 or Arf, generally in a mutually exclusive fashion. The tumor incidence data and molecular profiles establish a pathogenic role for the dual inactivation of p16(Ink4a) and p19(Arf)-p53 in the development of SCA in mice, demonstrating that p16(Ink4a) is a murine tumor suppressor. This genetically defined model provides insights into the molecular pathogenesis of SCA and serves as a platform for dissection of cell-specific programs of epithelial tumor suppression. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NCI, Mol Biol Lab, Mol Genet Sect, Bethesda, MD 20892 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St M413, Boston, MA 02115 USA. FU NCI NIH HHS [5R01-CA81755, 5K08CA72744-05] NR 61 TC 48 Z9 51 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 2 BP 635 EP 643 DI 10.1128/MCB.22.2.635-643.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506QU UT WOS:000172983900023 PM 11756558 ER PT J AU Rane, SG Cosenza, SC Mettus, RV Reddy, EP AF Rane, SG Cosenza, SC Mettus, RV Reddy, EP TI Germ line transmission of the Cdk4(R24C) mutation facilitates tumorigenesis and escape from cellular senescence SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ONCOGENIC RAS; MICE LACKING; TUMOR SUPPRESSION; CDK INHIBITORS; RETINOBLASTOMA PROTEIN; TARGETED DISRUPTION; G(1) CONTROL; INK4A LOCUS; IN-VIVO; GENE AB Mutations in CDK4 and its key kinase inhibitor p16(INK4a) have been implicated in the genesis and progression of familial human melanoma. The importance of the CDK4 locus in human cancer first became evident following the identification of a germ line CDK4-Arg24Cys (R24C) mutation, which abolishes the ability of CDK4 to bind to p16(INK4a). To determine the role of the Cdk4(R24C) germ line mutation in the genesis of other cancer types, we introduced the R24C mutation in the Cdk4 locus of mice by using Cre-loxP-mediated "knock-in" technology. Cdk4(R24C/R24C) mouse embryo fibroblasts (MEFs) displayed increased Cdk4 kinase activity resulting in hyperphosphorylation of all three members of the Rb family, pRb, p107, and p130. MEFs derived from Cdk4(R24C/R24C) mice displayed decreased doubling times, escape from replicative senescence, and escape sensitivity to contact-induced growth arrest. These MEFs also exhibited a high degree of susceptibility to oncogene-induced transformation, suggesting that the Cdk4(R24C) mutation can serve as a primary event in the progression towards a fully transformed phenotype. In agreement with the in vitro data, homozygous Cdk(4R24C/R24C) mice developed tumors of various etiology within 8 to 10 months of their life span. The majority of these tumors were found in the pancreas, pituitary, brain, mammary tissue, and skin. In addition, Cdk4(R24C/R24C) mice showed extraordinary susceptibility to carcinogens and developed papillomas within the first 8 to 10 weeks following cutaneous application of the carcinogens 9,10-di-methyl-1,2-benz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). This report formally establishes that the activation of Cdk4 is sufficient to promote cancer in many tissues. The observation that a wide variety of tumors develop in mice harboring the Cdk4(R24C) mutation offers a genetic proof that Cdk4 activation may constitute a central event in the genesis of many types of cancers in addition to melanoma. C1 Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. RP Rane, SG (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,41 Lib Dr, Bethesda, MD 20892 USA. RI Reddy, E. Premkumar/F-6233-2011 FU NCI NIH HHS [R24 CA088261, R24CA088261] NR 53 TC 101 Z9 101 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 2 BP 644 EP 656 DI 10.1128/MCB.22.2.644-656.2002 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506QU UT WOS:000172983900024 PM 11756559 ER PT J AU Kraakman-van der Zwet, M Overkamp, WJI van Lange, REE Essers, J van Duijn-Goedhart, A Wiggers, I Swaminathan, S van Buul, PPW Errami, A Tan, RTL Jaspers, NGJ Sharan, SK Kanaar, R Zdzienicka, MZ AF Kraakman-van der Zwet, M Overkamp, WJI van Lange, REE Essers, J van Duijn-Goedhart, A Wiggers, I Swaminathan, S van Buul, PPW Errami, A Tan, RTL Jaspers, NGJ Sharan, SK Kanaar, R Zdzienicka, MZ TI Brca2 (XRCC11) deficiency results in radioresistant DNA synthesis and a higher frequency of spontaneous deletions SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STRAND BREAK REPAIR; CANCER SUSCEPTIBILITY GENE; ATAXIA-TELANGIECTASIA CELLS; RAY-SENSITIVE MUTANTS; CHINESE-HAMSTER CELLS; IONIZING-RADIATION; CENTROSOME AMPLIFICATION; CHROMOSOMAL INSTABILITY; OCCURRING MUTATIONS; VERTEBRATE CELLS AB We show here that the radiosensitive Chinese hamster cell mutant (V-C8) of group XRCC11 is defective in the breast cancer susceptibility gene Brca2. The very complex phenotype of V-C8 cells is complemented by a single human chromosome 13 providing the BRCA2 gene, as well as by the murine Brca2 gene. The Brca2 deficiency in V-C8 cells causes hypersensitivity to various DNA-damaging agents with an extreme sensitivity toward interstrand DNA cross-linking agents. Furthermore, V-C8 cells show radioresistant DNA synthesis after ionizing radiation, suggesting that Brca2 deficiency affects cell cycle checkpoint regulation. In addition, V-C8 cells display tremendous chromosomal instability and a high frequency of abnormal centrosomes. The mutation spectrum at the hprt locus showed that the majority of spontaneous mutations in V-C8 cells are deletions, in contrast to wild-type V79 cells. A mechanistic explanation for the genome instability phenotype of Brca2-deficient cells is provided by the observation that the nuclear localization of the central DNA repair protein in homologous recombination, Rad51, is reduced in V-C8 cells. C1 Leiden State Univ, Med Ctr, Dept Radiat Genet & Chem Mutagenesis MGC, NL-2333 AL Leiden, Netherlands. JA Cohen Inst, Interuniv Res Inst Radiopathol & Radiat Protect, Leiden, Netherlands. Erasmus Univ, Dept Cell Biol & Genet MGC, Rotterdam, Netherlands. Univ Rotterdam Hosp Daniel, Dept Radiat Oncol, Rotterdam, Netherlands. NCI, Mouse Canc Genet Program, FCRDC, Frederick, MD USA. RP Zdzienicka, MZ (reprint author), Leiden State Univ, Med Ctr, Dept Radiat Genet & Chem Mutagenesis MGC, Wassenaarseweg 72, NL-2333 AL Leiden, Netherlands. NR 50 TC 180 Z9 181 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 2 BP 669 EP 679 DI 10.1128/MCB.22.2.669-679.2002 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506QU UT WOS:000172983900026 PM 11756561 ER PT J AU Parker, CE Tomer, KB AF Parker, CE Tomer, KB TI MALDI/MS-based epitope mapping of antigens bound to immobilized antibodies SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE proteolytic footprinting; mass spectrometry; epitope mapping; MALDI/MS; HIV p26 ID IONIZATION MASS-SPECTROMETRY; MONOCLONAL-ANTIBODY; DISCONTINUOUS EPITOPE; CHEMICAL MODIFICATION; LIMITED PROTEOLYSIS; ESCHERICHIA-COLI; PROTEIN ANTIGEN; CORE PROTEIN; VIRUS; GAG AB Proteolytic digestion of proteins bound to immobilized antibodies, combined with matrix assisted laser desorption (MALDI) mass spectrometric identification of the affinity-bound peptides, can be a powerful technique for epitope determination. Binding of the protein to the antibody is done while the protein is in its native, folded state. A purified protein is not required for this procedure, because only proteins containing the antigenic determinant will bind to the antibody in the initial step. The method makes use of the resistance of the antibody to enzymatic digestion. Enzymatic cleavage products of the antigenic protein not containing the epitope are washed off the beads, leaving the epitope-containing fragments affinity bound to the immobilized antibody. Dissociation of the antigen-antibody complex prior to mass spectrometric analysis is unnecessary because the affinity-bound peptides are released by the MALDI matrix crystallization process, although the antibody remains covalently attached to the sepharose beads. This epitope-mapping protocol has been used in the determination of both continuous and discontinuous epitopes on both glycosylated and unglycosylated proteins. C1 Natl Inst Environm Hlth Sci, Lab Mol Biophys, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 27 TC 17 Z9 17 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JAN PY 2002 VL 20 IS 1 BP 49 EP 62 DI 10.1385/MB:20:1:049 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 516WB UT WOS:000173578800005 PM 11876299 ER PT J AU Newton, DL Rybak, SM AF Newton, DL Rybak, SM TI Preparation of recombinant RNase single-chain antibody fusion proteins SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE RNase; single chain antibody; RNase chimeras; RNase sFv; RNase fusion proteins; RNase immunofusion proteins ID GROWTH-FACTOR; MONOCLONAL-ANTIBODIES; IMMUNOTOXINS; ANGIOGENIN; RIBONUCLEASE; CYTOTOXICITY; POLYMERASE; EXPRESSION; RESPONSES; SEQUENCE AB This article describes the construction, expression, and purification of RNase single-chain antibody fusion proteins. To construct a fusion protein, the gene for each moiety, the RNase and the binding ligand, is modified separately to contain complementary DNA encoding a 13 amino acid spacer that separates the RNase from the binding moiety. Appropriate restriction enzyme sites for cloning into the vector are also added. The modified DNA is combined and fused using the PCR technique of splicing by overlap extension (1). The resulting DNA construct is expressed in inclusion bodies in BL21(DE3) bacteria that are specifically engineered for the expression of toxic proteins (2). After isolation and purification of the inclusion bodies, the fusion protein is solubilized, denatured, and renatured. The renatured RNase fusion protein mixture is purified to homogeneity by two chromatography steps. The first column, a CM-Sephadex C-50 or a heparin Sepharose column, eliminates the majority of contaminating proteins while the second column, an affinity column (Ni2+-NTA agarose), results in the final purification of the RNase fusion protein. C1 FCRDC, NCI, Ft Detrick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Ft Detrick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Frederick, MD 21702 USA. EM rybak@ncifcrf.gov NR 45 TC 3 Z9 4 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 EI 1559-0305 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JAN PY 2002 VL 20 IS 1 BP 63 EP 76 DI 10.1385/MB:20:1:063 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 516WB UT WOS:000173578800006 PM 11876300 ER PT J AU Sale, S Sung, R Shen, PD Yu, K Wang, Y Duran, GE Kim, JH Fojo, T Oefner, PJ Sikic, BI AF Sale, S Sung, R Shen, PD Yu, K Wang, Y Duran, GE Kim, JH Fojo, T Oefner, PJ Sikic, BI TI Conservation of the class I beta-tubulin gene in human populations and lack of mutations in lung cancers and paclitaxel-resistant ovarian cancers SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TAXOL-INDUCED APOPTOSIS; MITOTIC BLOCK; ALTERED EXPRESSION; SEQUENCE VARIATION; COLORECTAL-CANCER; DNA POLYMORPHISM; HMSH2 GENE; CELL-LINE; MICROTUBULE; MUTANT AB The goal of this study was to determine the prevalence of sequence variants in the class I beta-tubulin (clone m40) gene and their occurrence in human tumors and cancer cell lines. DNA was isolated from 93 control individuals representing a wide variety of ethnicities, 49 paclitaxel-naive specimens (16 ovarian cancers, 17 non-small cell lung cancers, and 16 ovarian cancer cell lines), and 30 paclitaxel-resistant specimens (9 ovarian cancers, 9 ovarian cancer cell lines, and 12 ovarian cancer xenografts in nude mice). Denaturing high-performance liquid chromatography and direct sequence analysis detected two silent polymorphisms in exon 4, Leu217Leu (CTG/CTA) and Gly400Gly (GGC/ GGT), with minor allele frequencies of 17 and 0.5%, respectively. Five nucleotide substitutions and one single-base deletion were detected in introns 1, 2, and 3 and in the 3' untranslated region. Analysis of 49 paclitaxel-naive and 30 paclitaxel-resistant specimens revealed no additional polymorphisms in the coding region. In addition, no amino acid replacements were found in chimpanzee, gorilla, and orangutan in comparison to human. Our data demonstrate a very high degree of sequence conservation in class I beta-tubulin, suggesting that all residues are important in tubulin structure and function. Individual variation in response to treatment with paclitaxel is not likely to be caused by genetic variations in the beta-tubulin drug target. Moreover, acquired mutations in class I beta-tubulin are unlikely to be a clinically relevant cause of drug resistance. C1 Stanford Univ, Sch Med, Div Oncol, Stanford, CA 94305 USA. Stanford Genome Technol Ctr, Palo Alto, CA 94306 USA. NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Sikic, BI (reprint author), Stanford Univ, Sch Med, Div Oncol, 269 Campus Dr,CCSR-1105, Stanford, CA 94305 USA. RI Oefner, Peter/K-1116-2016 OI Oefner, Peter/0000-0002-1499-3977 FU NCI NIH HHS [R01 CA 68217]; NHGRI NIH HHS [R01 HG01932] NR 56 TC 70 Z9 75 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2002 VL 1 IS 3 BP 215 EP 225 PG 11 WC Oncology SC Oncology GA 606MA UT WOS:000178736700007 PM 12467216 ER PT J AU Khan, QA Dipple, A Anderson, LM AF Khan, QA Dipple, A Anderson, LM TI Protease inhibitor-induced stabilization of p21(waf1/cip1) and cell-cycle arrest in chemical carcinogen-exposed mammary and lung cells SO MOLECULAR CARCINOGENESIS LA English DT Article DE mammary cells; type II lung cells; benzo[a]pyrene; p53; p21(waf1/cip1); G(1) arrest; actinomycin D; protease inhibitor ID AROMATIC HYDROCARBON CARCINOGENS; HAMSTER OVARY CELLS; S-PHASE CHECKPOINTS; DNA-DAMAGE; DIHYDRODIOL EPOXIDE; DEPENDENT KINASES; GENE-PRODUCT; MCF-7 CELLS; P53; P21 AB In previous studies, we have shown that human breast and lung carcinoma cells and mouse nontransformed type II lung cells fail to undergo cell-cycle arrest in G(1) phase in response to treatment with hydrocarbon carcinogens but rather accumulate in the S phase with damaged DNA. This situation may lead to replication of DNA on a damaged template and enhance frequency of mutations. The mechanism of this G(1) arrest failure was examined. Western immunoblot analyses of MCF7 human mammary cancer cells exposed to actinomycin D (used as a positive control for G(1) cell-cycle arrest) or hydrocarbon carcinogens revealed that while all of these chemicals caused an increase in p53, only trace levels of p21(waf1/cip1) protein were observed in the hydrocarbon carcinogen-treated samples. Similarly, in murine lung E10 type 11 cells, p53 but not p21(waf1/cip1) protein increased in response to benzo[a]pyrene dihydrodiol epoxide. Treatment of either MCF7 mammary or E10 lung cells with the protease inhibitor calpain I resulted in increased levels of p21(waf1/cip1) protein and enhancement of arrest of the cells in early phases of the cell cycle (G(1) and early S phase). The results suggest that failure of cell-cycle arrest in carcinogen-treated mammary and lung cells is related to increased protease-mediated degradation of p21(waf1/cip1) and/or related regulatory proteins. Published 2002 Wiley-Liss, Inc.(dagger). C1 NCI, Cellular Pathogenesis Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. Adv Biosci Labs, Basic Res Program, Frederick, MD USA. RP Khan, QA (reprint author), NCI, Mol Pharmacol Lab, Bldg 37, Bethesda, MD 20892 USA. NR 52 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2002 VL 33 IS 1 BP 1 EP 8 DI 10.1002/mc.10013 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 511QK UT WOS:000173276900001 PM 11807952 ER PT J AU Ahram, M Best, CJM Flaig, MJ Gillespie, JW Leiva, IM Chuaqui, RF Zhou, G Shu, HJ Duray, PH Linehan, WM Raffeld, M Ornstein, DK Zhao, YM Petricoin, EF Emmert-Buck, MR AF Ahram, M Best, CJM Flaig, MJ Gillespie, JW Leiva, IM Chuaqui, RF Zhou, G Shu, HJ Duray, PH Linehan, WM Raffeld, M Ornstein, DK Zhao, YM Petricoin, EF Emmert-Buck, MR TI Proteomic analysis of human prostate cancer SO MOLECULAR CARCINOGENESIS LA English DT Article DE prostate cancer; proteomics; microarray; microdissection; heterogeneity ID GENE-EXPRESSION; MICROARRAYS; RESOURCES; CARCINOMA; TUMORS; MODEL AB Proteomics is a promising approach in the identification of proteins and biochemical pathways involved in tumorigenesis. In an effort to discover such proteins and pathways that are deregulated in prostate tumorigenesis, cellular proteomes of matched normal prostate epithelial cells and high-grade prostate cancer cells were analyzed by tissue microdissection, two-dimensional electrophoresis, and mass spectrometry. Forty protein alterations were detected in the tumors; however, the majority of these charges were not shared among the 12 neoplasms. In contrast, parallel cDNA microarray analysis identified a number of common gene expression changes. The marked heterogeneity of the observed protein alterations may have significance with regard to tumor biology and research strategies for molecular profiling analyses of human prostate cancer. Published 2002 Wiley-Liss, Inc.(dagger) C1 NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Urol, Chapel Hill, NC USA. US FDA, Ctr Biol Evaluat & Res, Tissue Proteom Unit, Bethesda, MD USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, NIH, Room 2A33,10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 104 Z9 108 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2002 VL 33 IS 1 BP 9 EP 15 DI 10.1002/mc.10019 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 511QK UT WOS:000173276900002 PM 11807953 ER PT J AU Hursting, SD Shen, JC Sun, XY Wang, TTY Phang, JM Perkins, SN AF Hursting, SD Shen, JC Sun, XY Wang, TTY Phang, JM Perkins, SN TI Modulation of cyclophilin gene expression by N-4-(hydroxyphenyl)retinamide: Association with reactive oxygen species generation and apoptosis SO MOLECULAR CARCINOGENESIS LA English DT Article DE differential display; LNCaP; MCF-7; mitochondrial permeability transition pore ID SYNTHETIC RETINOID FENRETINIDE; PROSTATE-CANCER; N-(4-HYDROXYPHENYL) RETINAMIDE; CARCINOMA-CELLS; GROWTH; CHEMOPREVENTION; INVOLVEMENT; STRESS; PORE AB To explore the mechanisms underlying the pro-apoptotic effects of the synthetic retinoid N-4-(hydroxyphenyl)retinamide (4-HPR) on LNCaP human prostate cancer cells, we used the differential display-polymerase chain reaction (DD-PCR) technique to identify 4-HPR-responsive genes. RNA extracted from LNCaP cells that had been treated for 24 h with 4-HPR at a dose (2.5 muM) optimal for apoptosis induction was used for DD-PCR analysis using random primers. A differentially expressed 115 bp fragment was cloned and sequenced and then identified in GenBank as having a high degree of homology with several members of the cyclophilin gene family. Northern blot analyses using specific probes for cyclophilin A, cyclophilin D, and the cloned 115-bp fragment were performed on RNA extracted from LNCaP cells and MCF-7 human breast cancer cells treated with 4-HPR, N-acetylcysteine (NAC, an anti-oxidant), 4-HPR plus NAC, cyclosporin A, R-1881 (a synthetic androgen), dehydroepiandrosterone, all-trans retinoic acid, or prednisone. 4-HPR downregulated the transcript detected by the 115-bp fragment. Expression patterns detected by the 115-bp fragment and cyclophilin D probes were identical in response to each treatment; none of these treatments affected cyclophilin A expression. Furthermore, expression of mRNA transcripts detected by the 115-bp fragment and cyclophilin D probes correlated with the generation of reactive oxygen species (ROS), as detected by measurement of 2,7-dichlorofluorescein oxidation. Therefore, members of the cyclophilin gene family, such as cyclophilin D (a component of the mitochondrial permeability transition pore previously linked with oxidative stress and apoptosis), may play a role in the ROS-mediated apoptotic effects of 4-HPR, Published 2002 Wiley-Liss, Inc.(dagger). C1 NCI, Off Prevent Oncol, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Frederick, MD 21701 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Houston, TX 77030 USA. NCI, Basic Res Lab, Frederick, MD 21701 USA. USDA, Phytonutrients Lab, Beltsville, MD 20705 USA. RP Hursting, SD (reprint author), NCI, Off Prevent Oncol, Div Canc Prevent, 6130 Execut Blvd,MSC 7105, Bethesda, MD 20892 USA. NR 26 TC 20 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2002 VL 33 IS 1 BP 16 EP 24 DI 10.1002/mc.10020 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 511QK UT WOS:000173276900003 PM 11807954 ER PT J AU Dundr, M Misteli, T AF Dundr, M Misteli, T TI Nucleolomics: An inventory of the nucleolus SO MOLECULAR CELL LA English DT Editorial Material ID PROTEIN AB In the January 8 issue of Current Biology, two papers from the Lamond and Mann laboratories describe the largest proteomics analysis to date of a cellular compartment, the nucleolus. As a byproduct of this tour de force, a novel nuclear compartment, the paraspeckles, was identified. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Dundr, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 11 TC 29 Z9 30 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN PY 2002 VL 9 IS 1 BP 5 EP 7 DI 10.1016/S1097-2765(02)00433-1 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 513PP UT WOS:000173387300003 PM 11804579 ER PT J AU Zhang, AX Wassarman, KM Ortega, J Steven, AC Storz, G AF Zhang, AX Wassarman, KM Ortega, J Steven, AC Storz, G TI The Sm-like Hfq protein increases OxyS RNA interaction with target mRNAs SO MOLECULAR CELL LA English DT Article ID PHAGE Q-BETA; OMPA MESSENGER-RNA; HOST FACTOR-I; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; RIBOSOME BINDING; SIGMA(S) SUBUNIT; RPOS TRANSLATION; QBETA-REPLICASE; GENE AB The Escherichia coli host factor I, Hfq, binds to many small regulatory RNAs and is required for OxyS RNA repression of fhIA and rpoS mRNA translation. Here we report that Hfq is a bacterial homolog of the Sm and Sm-like proteins integral to RNA processing and mRNA degradation complexes in eukaryotic cells. Hfq exhibits the hallmark features of Sm and Sm-like proteins: the Sm1 sequence motif, a multisubunit ring structure (in this case a homomeric hexamer), and preferential binding to polyU. We also show that Hfq increases the OxyS RNA interaction with its target messages and propose that the enhancement of RNA-RNA pairing may be a general function of Hfq, Sm, and Sm-like proteins. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 53 TC 329 Z9 336 U1 4 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN PY 2002 VL 9 IS 1 BP 11 EP 22 DI 10.1016/S1097-2765(01)00437-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 513PP UT WOS:000173387300006 PM 11804582 ER PT J AU Miura, K Jacques, KM Stauffer, S Kubosaki, A Zhu, KJ Hirsch, DS Resau, J Zheng, Y Randazzo, PA AF Miura, K Jacques, KM Stauffer, S Kubosaki, A Zhu, KJ Hirsch, DS Resau, J Zheng, Y Randazzo, PA TI ARAP1: A point of convergence for Arf and Rho signaling SO MOLECULAR CELL LA English DT Article ID GTPASE-ACTIVATING PROTEIN; PLECKSTRIN-HOMOLOGY DOMAINS; SWISS 3T3 FIBROBLASTS; ACTIN STRESS FIBERS; BINDING PROTEIN; FOCAL ADHESIONS; PAXILLIN RECRUITMENT; STRUCTURAL BASIS; CELL-MIGRATION; ANKYRIN REPEAT AB We have identified ARAP1 and ARAP2 and examined ARAP1 as a possible link between phosphoinositide-, Arf-, and Rho-mediated cell signaling. ARAP1 contains Arf GAP, Rho GAP, Ankyrin repeat, Ras-associating, and five PH domains. In vitro, ARAP1 had Rho GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent Arf GAP activity. ARAP1 associated with the Golgi. The Rho GAP activity mediated cell rounding and loss of stress fibers when ARAP1 was overexpressed. The Arf GAP activity mediated changes in the Golgi apparatus and the formation of filopodia, the latter a consequence of increased cellular activity of Cdc42. The Arf GAP and Rho GAP activities both contributed to inhibiting cell spreading. Thus, ARAP1 is a PIP3-dependent Arf GAP that regulates Arf-, Rho-, and Cdc42-dependent cell activities. C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Van Andel Res Inst, Grand Rapids, MI 49503 USA. RP Randazzo, PA (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RI Zheng, Yi/J-7235-2015 OI Zheng, Yi/0000-0001-7089-6074 NR 48 TC 117 Z9 119 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN PY 2002 VL 9 IS 1 BP 109 EP 119 DI 10.1016/S1097-2765(02)00428-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 513PP UT WOS:000173387300014 PM 11804590 ER PT J AU Costanzo, A Merlo, P Pediconi, N Fulco, M Sartorelli, V Cole, PA Fontemaggi, G Fanciulli, M Schiltz, L Blandino, G Balsano, C Levrero, M AF Costanzo, A Merlo, P Pediconi, N Fulco, M Sartorelli, V Cole, PA Fontemaggi, G Fanciulli, M Schiltz, L Blandino, G Balsano, C Levrero, M TI DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes SO MOLECULAR CELL LA English DT Article ID KINASE C-ABL; HISTONE ACETYLTRANSFERASES; P53-INDUCED APOPTOSIS; TRANSCRIPTION FACTORS; INDUCE APOPTOSIS; GENOTOXIC STRESS; TERMINAL DOMAIN; HUMAN CANCERS; P53 MUTANTS; P300 AB The tumor suppressor p53 and its close relative p73 are activated in response to DNA damage resulting in either cell cycle arrest or apoptosis. Here, we show that DNA damage induces the acetylation of p73 by the acetyltransferase p300. Inhibiting the enzymatic activity of p300 hampers apoptosis in a p53(-/-) background. Furthermore, a nonacetylatable p73 is defective in activating transcription of the proapoptotic p53AIP1 gene but retains an intact ability to regulate other targets such as p21. Finally, p300-mediated acetylation of p73 requires the protooncogene c-abl. Our results suggest that DNA damage-induced acetylation potentiates the apoptotic function of p73 by enhancing the ability of p73 to selectively activate the transcription of proapoptotic target genes. C1 Univ Roma La Sapienza, Fdn Andrea Cesalpino, Gene Express Lab, I-00161 Rome, Italy. Univ Roma Tor Vergata, Dept Dermatol, I-00161 Rome, Italy. NIAMS, Muscle Biol Lab, Muscle Gene Express Grp, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Regina Elena Canc Ctr, Dept Expt Oncol, I-00158 Rome, Italy. Univ Aquila, Dept Internal Med, I-67100 Laquila, Italy. Univ Cagliari, Dept Internal Med, I-09124 Cagliari, Italy. RP Levrero, M (reprint author), Univ Roma La Sapienza, Fdn Andrea Cesalpino, Gene Express Lab, Piazzale Aldo Moro 5, I-00161 Rome, Italy. RI Costanzo, Antonio/D-3896-2012; Blandino, Giovanni/B-1137-2013; Merlo, Paola/K-5330-2014; OI Blandino, Giovanni/0000-0002-6970-2241; Merlo, Paola/0000-0003-0105-7044; Fontemaggi, Giulia/0000-0001-8332-8842 NR 39 TC 241 Z9 246 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN PY 2002 VL 9 IS 1 BP 175 EP 186 DI 10.1016/S1097-2765(02)00431-8 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 513PP UT WOS:000173387300020 PM 11804596 ER PT S AU Weiss, J DeLeo, F Nauseef, WM AF Weiss, J DeLeo, F Nauseef, WM BE Sansonetti, P Zychlinsky, A TI Antimicrobial activity of host cells SO MOLECULAR CELLULAR MICROBIOLOGY SE Methods in Microbiology LA English DT Review ID FLOW CYTOMETRIC ANALYSIS; PERITONEAL INFLAMMATORY EXUDATE; ESCHERICHIA-COLI; NADPH OXIDASE; RESPIRATORY BURST; BACTERIAL LIPOPOLYSACCHARIDES; POLYMORPHONUCLEAR LEUKOCYTES; EXTRACELLULAR COMPONENTS; STAPHYLOCOCCUS-AUREUS; HUMAN NEUTROPHILS C1 Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Inflammat Program, Iowa City, IA 52242 USA. Iowa City Vet Adm Med Ctr, Iowa City, IA 52246 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. NR 57 TC 2 Z9 2 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 0580-9517 BN 0-12-521531-2 J9 METHOD MICROBIOL JI Methods Microbiol. PY 2002 VL 31 BP 477 EP 505 DI 10.1016/S0580-9517(02)31027-4 PG 29 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA BT76G UT WOS:000173973000026 ER PT J AU Teng, CT Gladwell, W Beard, C Walmer, D Teng, CS Brenner, R AF Teng, CT Gladwell, W Beard, C Walmer, D Teng, CS Brenner, R TI Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE endometrium; estrogen response element; human and monkey; lactoferrin; lactoferrin gene promoter ID EPIDERMAL GROWTH-FACTOR; REPRODUCTIVE-TRACT; MOLECULAR MECHANISM; MILK LACTOFERRIN; MOUSE; PROMOTER; BINDING; RECEPTOR; PROTEIN; ELEMENTS AB We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 by upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding, from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed, that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium. C1 NIEHS, Reprod & Dev Toxicol Lab, Gene Regulat Grp, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Durham, NC 27710 USA. N Carolina State Univ, Sch Vet Med, Dept APR, Raleigh, NC 27695 USA. Oregon Reg Primate Res Ctr, Div Reprod Sci, Beaverton, OR 97006 USA. RP Teng, CT (reprint author), POB 12233,MD E2-01, Res Triangle Pk, NC 27709 USA. NR 37 TC 36 Z9 37 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD JAN PY 2002 VL 8 IS 1 BP 58 EP 67 DI 10.1093/molehr/8.1.58 PG 10 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 516FW UT WOS:000173544100008 PM 11756570 ER PT J AU Tarazona, R Borrego, F Galiani, MD Aguado, E Pena, J Coligan, JE Solana, R AF Tarazona, R Borrego, F Galiani, MD Aguado, E Pena, J Coligan, JE Solana, R TI Inhibition of CD28-mediated natural cytotoxicity by KIR2DL2 does not require p56(lck) in the NK cell line YT-Indy SO MOLECULAR IMMUNOLOGY LA English DT Article DE HLA recognition; killer immunoglobulin-like receptor; PLC-gamma 1; Src kinases ID CLASS-I MOLECULES; MHC-RECOGNIZING RECEPTORS; TYROSINE KINASE LCK; KILLER-CELL; HLA-E; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; CONFERS PROTECTION; T-LYMPHOCYTES; ACTIVATION AB CD28 functions as a cytotoxicity activation receptor in the NK cell line YT-Indy. To analyze the requirement of p56(lck) kinase in the function of killer inhibitory receptors, we transfected the p56(lck) negative YT-Indy cell line with the c143 gene encoding for KIR2DL2. Pervanadate treatment revealed KIR2DL2 phosphorylation in YT-Indy-cl43, as well as SHP1/SHP2 recruitment. YT-Indy-cl43 cells were inhibited in their ability to lyse target cells expressing HLA-Cw3, a ligand for KIR2DL2. This inhibition was blocked by anti-KIR2DL2 or anti-HLA class I mAb. CD28 crosslinking on YT-Indy-cl43 enhanced tyrosine phosphorylation of PLC-gamma1. The simultaneous ligation of KIR2DL2 with mAb resulted in a decrease in CD28-induced tyrosine phosphorylation of PLC-gamma1 confirming that dephosphorylation of this protein is involved in the KIR2DL2-induced inhibition of CD28-mediated cytotoxicity. As YT-Indy-cl43 did not express detectable levels of p56(lck), these results indicate that this kinase is not required for transmitting the negative signals generated by KIR2DL2 ligation. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Cordoba, Reina Sofia Hosp, Fac Med, Dept Immunol, E-14004 Cordoba, Spain. NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Solana, R (reprint author), Univ Cordoba, Reina Sofia Hosp, Fac Med, Dept Immunol, Avda Menendez Pidal S-N, E-14004 Cordoba, Spain. RI Aguado, Enrique/L-4908-2014 OI Aguado, Enrique/0000-0002-7232-2661 NR 60 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2002 VL 38 IS 7 BP 495 EP 503 DI 10.1016/S0161-5890(01)00092-X PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 511EN UT WOS:000173251800001 PM 11750651 ER PT J AU Ploug, T Ralston, E AF Ploug, T Ralston, E TI Exploring the whereabouts of GLUT4 in skeletal muscle (Review) SO MOLECULAR MEMBRANE BIOLOGY LA English DT Review DE subcellular organization; trafficking; metabolism; transporters ID GLUCOSE-TRANSPORTER GLUT4; INSULIN-RESPONSIVE GLUCOSE-TRANSPORTER-4; REGULATED MEMBRANE AMINOPEPTIDASE; BROWN ADIPOSE-TISSUE; 3T3-L1 ADIPOCYTES; TRANSVERSE TUBULES; PLASMA-MEMBRANE; TRANSFERRIN RECEPTOR; GOLGI-APPARATUS; T-TUBULES AB The glucose transporter GLUT4 is expressed in muscle, fat cells, brain and kidney. In contrast to other glucose transporters, GLUT4 in unstimulated cells is mostly intracellular. Stimuli such as insulin and muscle contractions then cause the translocation of GLUT4 to the cell surface. Questions related to GLUT4 storage compartments, trafficking to the surface membrane, and nature of the intracellular pools, have kept many groups busy for the past 20 years. Yet, one of the main questions in the field remains the universality of GLUT4 features. Can one extrapolate work done on fat cells to muscle or brain? Or vice-versa? Can one use cultures to predict GLUT4 behaviour in fully differentiated tissues? This review summarizes the authors' knowledge of GLUT4 biology in skeletal muscle, which is the predominant tissue for glucose homeostasis. The results are compared to those obtained with the fat cell system, and an attempt is made to assess the universality principle. C1 Univ Copenhagen, Panum Inst, Dept Med Physiol, Copenhagen Muscle Res Ctr, DK-2200 Copenhagen N, Denmark. NIAMS, Light Imaging Sect, NIH, Bethesda, MD USA. RP Ploug, T (reprint author), Univ Copenhagen, Panum Inst, Dept Med Physiol, Copenhagen Muscle Res Ctr, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. NR 120 TC 19 Z9 21 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PD JAN-MAR PY 2002 VL 19 IS 1 BP 39 EP 49 DI 10.1080/09687680110119229 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 533UA UT WOS:000174547700004 PM 11989821 ER PT J AU Martin, RG Gillette, WK Martin, NI Rosner, JL AF Martin, RG Gillette, WK Martin, NI Rosner, JL TI Complex formation between activator and RNA polymerase as the basis for transcriptional activation by MarA and SoxS in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID MULTIPLE ANTIBIOTIC-RESISTANCE; SUPEROXIDE-INDUCIBLE GENES; DNA-BINDING SITE; PROTEIN; PROMOTERS; ROB; PURIFICATION; SEQUENCE; OPERON; REINITIATION AB Transcriptional activation in Escherichia coli is generally considered to proceed via the formation of an activator-DNA-RNA polymerase (RNP) ternary complex. Although the order of assembly of the three elements is thermodynamically irrelevant, a prevalent idea is that the activator-DNA complex is formed first, and recruitment of RNP to the binary complex occurs subsequently. We show here that the closely related activators, MarA, SoxS and Rob, which activate the same family of genes, are capable of forming complexes with RNP core or holoenzyme in the absence of DNA. In addition, we find that the ternary MarA-DNA-RNP and SoxS-DNA-RNP complexes are more stable than the corresponding Rob-DNA-RNP complex, although the binary Rob-DNA complex is often more stable than the corresponding MarA- or SoxS-DNA complexes. These results may help to explain certain puzzling aspects of the MarA/SoxS/Rob system. We suggest that activator-RNP complexes scan the chromosome and bind promoters of the regulon more efficiently than either RNP or the activators alone. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, RG (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 333, Bethesda, MD 20892 USA. NR 49 TC 57 Z9 58 U1 1 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2002 VL 43 IS 2 BP 355 EP 370 DI 10.1046/j.1365-2958.2002.02748.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 521XD UT WOS:000173865900007 PM 11985714 ER PT J AU Ueda, A Hamadeh, HK Webb, HK Yamamoto, Y Sueyoshi, T Afshari, CA Lehmann, JM Negishi, M AF Ueda, A Hamadeh, HK Webb, HK Yamamoto, Y Sueyoshi, T Afshari, CA Lehmann, JM Negishi, M TI Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital SO MOLECULAR PHARMACOLOGY LA English DT Article ID RAT CYP2B2 GENE; 5'-FLANKING REGION; INDUCTION; EXPRESSION; LIVER; CLUSTER; DISPLAY; MOUSE; CYP4A AB Phenobarbital (PB) induces various gene encoding drug/ steroid-metabolizing enzymes such as cytochromes P450 (P450s) and transferases. Although the nuclear orphan constitutive active receptor (CAR) has been identified as a key transcription factor that regulates the induction of CYP2B, the full scope of CAR-regulated genes still remains a major question. To this end, reverse transcriptase-polymerase chain reaction and cDNA microarray techniques were employed to examine gene expression in wild-type and CAR-null mice. The results show that a total of 138 genes were detected to be either induced or repressed in response to PB treatment, of which about half were under CAR regulation. including CYP2B10, CYP3A11, and NADPH-CYP reductase, CAR regulated a group of the PB-induced drug/steroid-metabolizing enzymes. Enzymes such as amino levulinate synthase I and squalene epoxidase displayed CAR-independent induction by PB. Cyp4a10 and Cyp4a14 represented the group of genes induced by PB only in CAR-null mice, indicating that CAR may be a transcription blocker that prevents these genes from being induced by PB. Additionally, the group of genes encoding enzymes and proteins involved in basic biological processes such as energy metabolism underwent the CAR-dependent repression by PB. Thus, CAR seems to have diverse roles, both as a positive and negative regulator, in the regulation of hepatic genes in response to PB beyond drug/steroid metabolism. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Microarray Ctr, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Tularik, San Francisco, CA USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 27 TC 312 Z9 325 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2002 VL 61 IS 1 BP 1 EP 6 DI 10.1124/mol.61.1.1 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509FE UT WOS:000173135000001 PM 11752199 ER PT J AU Loaiza-Perez, AI Trapani, V Hose, C Singh, SS Trepel, JB Stevens, MFG Bradshaw, TD Sausville, EA AF Loaiza-Perez, AI Trapani, V Hose, C Singh, SS Trepel, JB Stevens, MFG Bradshaw, TD Sausville, EA TI Aryl hydrocarbon receptor mediates sensitivity of MCF-7 breast cancer cells to antitumor agent 2-(4-amino-3-methylphenyl) benzothiazole SO MOLECULAR PHARMACOLOGY LA English DT Article ID IN-VITRO; DNA-BINDING; AH RECEPTOR; 2-(4-AMINOPHENYL)BENZOTHIAZOLES; EXPRESSION; TOXICITY; PROTEIN; INDUCTION; MECHANISM; OXIDATION AB 2-(4-Amino-3-methylphenyl) benzothiazole (NSC 674495; DF 203) demonstrates drug uptake and metabolism by tumor cells sensitive to the antiproliferative activity of the drug [J Med Chem 1999;42:4172-4184]. In insensitive cells, little metabolism occurs. Because CYP1A1 can metabolize DF 203, the aryl hydrocarbon receptor (AhR) may mediate drug action. We demonstrate here that DF 203 increases CYP1A1 and CYP1B1 transcription in sensitive MCF-7 cells, accompanied by AhR translocation to the nucleus, increase in xenobiotic-responsive element (XRE)-driven luciferase activity, and induction of protein/DNA complexes on the XRE sequence of the CYP1A1 promoter. MDA-MB-435 and PC3 cells, resistant to DF 203, did not show drug-induced CYP1A1 and CYP1B1 gene expression. AhR was observed to be constitutively localized in the nucleus, with no induction of XRE-driven luciferase activity in transiently transfected cells and weak or no induction of protein/DNA complexes on the XRE sequence of CYP1A1. Taken together, these data elucidate a novel basis for antitumor drug action: induction in sensitive cells of a metabolizing system for the drug itself. These results suggest that clarification of the basis for differential engagement of AhR-related signaling in different tumor cell types may aid in further preclinical development and perhaps early clinical studies. C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Frederick, MD 20892 USA. Univ Nottingham, Sch Pharmaceut Sci, Canc Res Labs, Nottingham, England. RP Loaiza-Perez, AI (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, 9000 Rockville Pike,Bldg 10 Rm 6N115, Bethesda, MD 20892 USA. OI Trapani, Valentina/0000-0002-0259-6624 NR 28 TC 75 Z9 76 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2002 VL 61 IS 1 BP 13 EP 19 DI 10.1124/mol.61.1.13 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509FE UT WOS:000173135000003 PM 11752201 ER PT J AU Cooper, RA Ferdig, MT Su, XZ Ursos, LMB Mu, JB Nomura, T Fujioka, H Fidock, DA Roepe, PD Wellems, TE AF Cooper, RA Ferdig, MT Su, XZ Ursos, LMB Mu, JB Nomura, T Fujioka, H Fidock, DA Roepe, PD Wellems, TE TI Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum SO MOLECULAR PHARMACOLOGY LA English DT Article ID DRUG-RESISTANCE; HEMATIN POLYMERIZATION; ANTIMALARIAL ACTIVITY; HEME POLYMERIZATION; IN-VITRO; BINDING; EFFLUX; ACCUMULATION; INHIBITION; SELECTION AB Chloroquine resistance (CQR) in Plasmodium falciparum is associated with multiple mutations in the digestive vacuole membrane protein PfCRT. The chloroquine-sensitive (CQS) 106/1 line of P. falciparum has six of seven PfCRT mutations consistently found in CQR parasites from Asia and Africa, The missing mutation at position 76 (K76T in reported population surveys) may therefore be critical to CQR. To test this hypothesis, we exposed 106/1 populations (10(9)-10(10) parasites) to a chloroquine (CQ) concentration lethal to CQS parasites. In multiple independent experiments, surviving CQR parasites were detected in the cultures after 28 to 42 days. These parasites showed novel K76N or K761 PfCRT mutations and corresponding CQ IC50 values that were similar to8- and 12-fold higher than that of the original 106/1 IC50. A distinctive feature of the K761 line relative to 106/1 parasites was their greatly increased sensitivity to quinine (QN) but reduced sensitivity to its enantiomer quinidine (QD), indicative of a unique stereospecific response not observed in other CQR lines. Furthermore, verapamil had the remarkable effect of antagonizing the QN response while potentiating the QD response of K761 parasites. In our single-step drug selection protocol, the probability of the simultaneous selection of two specific mutations required for CQR is extremely small. We conclude that the K76N or K761 change added to the other pre-existing mutations in the 106/1 PfCRT protein was responsible for CQR. The various mutations that have now been documented at PfCRT position 76 (K76T, K76N, K761) suggest that the loss of lysine is central to the CQR mechanism. C1 NIAID, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Dept Chem, Washington, DC USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Program Tumor Biol, Washington, DC USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY USA. RP Wellems, TE (reprint author), NIAID, NIH, 4 Ctr Dr,Room 4-126,MSC 0425, Bethesda, MD 20892 USA. RI Ferdig, Michael/C-6627-2016; OI Fidock, David/0000-0001-6753-8938; Su, Xinzhuan/0000-0003-3246-3248 FU NIAID NIH HHS [R01-AI45957, R01 AI050234] NR 45 TC 171 Z9 176 U1 0 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2002 VL 61 IS 1 BP 35 EP 42 DI 10.1124/mol.61.1.35 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509FE UT WOS:000173135000006 PM 11752204 ER PT J AU Peoples, RW Ren, H AF Peoples, RW Ren, H TI Inhibition of N-methyl-D-aspartate receptors by straight-chain diols: Implications for the mechanism of the alcohol cutoff effect SO MOLECULAR PHARMACOLOGY LA English DT Article ID CEREBELLAR GRANULE CELLS; ETHANOL INHIBITION; HIPPOCAMPAL-NEURONS; GLYCINE; RELEASE; PROTEIN; SLICES; INTOXICATION; ANESTHETICS; CHANNELS AB n-Alkanol inhibition of N-methyl-D-aspartate (NMDA) receptors exhibits a "cutoff" effect: alcohols with up to eight to nine carbon atoms inhibit the receptor, whereas larger alcohols do not. This phenomenon was originally proposed to result from size exclusion; i.e., alcohols above the cutoff are too large to bind to an amphiphilic site on the receptor. In the present study, 1,Ohm-diols with 3 to 14 carbon atoms inhibited NMDA-activated current in Chinese hamster ovary and human embryonic kidney 293 cells transiently expressing NR1 and NR2B NMDA receptor subunits. Results of fluctuation analysis experiments were consistent with a similar mechanism of inhibition of NMDA-activated current by alcohols and diols. The average change in apparent energy of binding of the diols caused by addition of a methylene group was 2.1 kJ/mol, which is consistent with an important role of hydrophobic interactions. Because 1,Ohm-diols with 9 to 14 carbons inhibited NMDA-activated current, despite having molecular volumes exceeding that at the cutoff point for 1-alkanols, a size exclusion mechanism seems inadequate to explain the cutoff effect. A disparity in hydrophobicity values at the cutoff for alcohols and diols, however, revealed that hydrophobicity could also not entirely explain the cutoff phenomenon. From these results, it seems that the cutoff effect on NMDA receptors results primarily from the inability of long-chain alcohols to achieve adequate concentrations at their site of action due to low aqueous solubility, although other factors may also contribute to the effect. C1 NIAAA, Unit Cellular Neuropharmacol, LMCN, NIH, Bethesda, MD 20892 USA. RP Peoples, RW (reprint author), NIAAA, Unit Cellular Neuropharmacol, LMCN, NIH, Pk 5 Bldg,Rm 150,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. NR 37 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2002 VL 61 IS 1 BP 169 EP 176 DI 10.1124/mol.61.1.169 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509FE UT WOS:000173135000020 PM 11752218 ER PT J AU Uhl, GR Hall, FS Sora, I AF Uhl, GR Hall, FS Sora, I TI Cocaine, reward, movement and monoamine transporters SO MOLECULAR PSYCHIATRY LA English DT Review DE reward; cocaine; aversion; knockout mouse; reinforcement; polygenic ID HUMAN DOPAMINE TRANSPORTER; DEFICIT HYPERACTIVITY DISORDER; CORTICOTROPIN-RELEASING FACTOR; VENTRAL TEGMENTAL AREA; MICE LACKING; GENE POLYMORPHISMS; NUCLEUS-ACCUMBENS; IN-VIVO; PARKINSONS-DISEASE; 6-HYDROXYDOPAMINE LESIONS AB Recent evidence enriches our understanding of the,molecular sites of action of cocaine reward and locomotor stimulation. Dopamine transporter blockade by cocaine appears a sufficient explanation for cocaine-induced locomotion. Variation in DAT appears to cause differences in locomotion without drug stimulation. However, previously-held views that DAT blockade was the sole site for cocaine reward have been replaced by a richer picture of multitransporter involvement with the rewarding and aversive, actions of, cocaine. These new insights, derived from studies of knockout mice with simultaneous deletions and/or blockade of multiple transporters, provide a novel model for the rewarding action of this heavily-abused substance and implicate multiple monoamine systems in cocaine's hedonic activities. C1 NIDA, IRP, Mol Neurobiol Branch, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), Box 5180, Baltimore, MD 21224 USA. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 103 TC 151 Z9 154 U1 4 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 1 BP 21 EP 26 DI 10.1038/sj/mp/4000964 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 509BB UT WOS:000173123500007 PM 11803442 ER PT J AU Bennett, AJ Lesch, KP Heils, A Long, JC Lorenz, JG Shoaf, SE Champoux, M Suomi, SJ Linnoila, MV Higley, JD AF Bennett, AJ Lesch, KP Heils, A Long, JC Lorenz, JG Shoaf, SE Champoux, M Suomi, SJ Linnoila, MV Higley, JD TI Early experience and serotonin transporter gene variation interact to influence primate CNS function SO MOLECULAR PSYCHIATRY LA English DT Article DE early experience; 5-HTTLPR; rhesus monkey; rearing; CSF5-HIAA; maternal separation; social deprivation; stress; development ID ANXIETY-RELATED TRAITS; MONOAMINE METABOLITE CONCENTRATIONS; REGULATORY REGION POLYMORPHISM; RHESUS-MONKEYS; CEREBROSPINAL-FLUID; PROMOTER POLYMORPHISM; PERSONALITY-TRAITS; NO ASSOCIATION; 5-HYDROXYINDOLEACETIC ACID; SEASONAL-VARIATION AB Nonhuman primates offer unique opportunities to study the effects of genes, environments, and their interaction, on physiology and complex behavior. We examined genotype and early environment contributions to CNS function in a large sample of rhesus monkeys. In humans, length variation of the serotonin (5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) that results in allelic variation in 5-HTT expression is associated with decreased serotonergic function and 5-HT-mediated psychopathology. We report that an analogous variation of the gene's regulatory region in monkeys interacts with early experience to affect central 5-HT functioning. Monkeys with deleterious early rearing experiences were differentiated by genotype in cerebrospinal fluid concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, while monkeys reared normally were not. These findings demonstrate an environment-dependent effect of the rh5-HTTLPR genotype on CNS 5-HT function and suggest nonhuman primates may provide an important avenue for investigating gene/environment interactions using candidate genes for physiological and behavioral traits. C1 NIAAA, Clin Studies Lab, Primate Unit, Poolesville, MD 20837 USA. Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. NIAAA, Neurogenet Lab, Poolesville, MD 20837 USA. NICHHD, Lab Comparat Ethol, Poolesville, MD USA. RP Bennett, AJ (reprint author), NIAAA, Clin Studies Lab, Primate Unit, POB 529,Fisher Ave, Poolesville, MD 20837 USA. EM allysonb@niaaa.nih.gov RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 39 TC 402 Z9 407 U1 7 U2 44 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 1 BP 118 EP 122 DI 10.1038/sj/mp/4000949 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 509BB UT WOS:000173123500023 PM 11803458 ER PT J AU Crook, JM Akil, M Law, BCW Hyde, TM Kleinman, JE AF Crook, JM Akil, M Law, BCW Hyde, TM Kleinman, JE TI Comparative analysis of group II metabotropic glutamate receptor immunoreactivity in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects SO MOLECULAR PSYCHIATRY LA English DT Article DE mGluR2/3; Western immunoblotting; immunocytochemistry; glutamate neurotransmission; Brodmann's area 46 ID EXTRACELLULAR LEVELS; G-PROTEIN; KETAMINE; NMDA; AGONIST; MODEL; ACID; LOCALIZATION; ANTAGONISTS; DOPAMINE AB Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, and a key neurotransmitter in prefrontal cortical function. Converging lines of evidence implicate prefrontal cortical dysfunction in the neurobiology of schizophrenia. Thus, aberrant glutamate neurotransmission may underlie schizophrenia and other complex disorders of behavior. Group II metabotropic receptors (mGluRs) are important modulators of glutamatergic and non-glutamatergic neurotransmission. Moreover, in an animal model, an agonist for group II mGluRs has been shown to reverse the behavioral, locomotor, and cognitive effects of the psychotomimetic drug phencyclidine. Accordingly, group II mGluRs constitute attractive targets for the pharmacotherapeutics and study of schizophrenia. Using immunocytochemistry and Western immunoblotting, we compared the localization and levels of group II mGluRs in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects. Consistent with previous reports, we found that immunolabeling of group II mGluRs is prominent in Brodmann's area 46. The majority of labeling was present on axon terminals distributed in a lamina-specific fashion. No apparent difference in the cellular localization or laminar distribution of immunoreactive, group II mGluRs was noted between the two diagnostic groups. Similarly, the levels of receptor immunoreactivity determined by quantitative Western immunoblotting were comparable between schizophrenic patients and normal subjects. We conclude that while the function of group II mGluRs in Brodmann's area 46 of dorsolateral prefrontal cortex may be: altered in patients with schizophrenia, this is not evident at the level of protein expression using an antibody against mGluR2 and mGluR3. C1 NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Hyde, TM (reprint author), NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Bldg 10,Room 4N,306 MSC 1385, Bethesda, MD 20892 USA. NR 51 TC 44 Z9 44 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 2 BP 157 EP 164 DI 10.1038/sj.mp.4000966 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 520UJ UT WOS:000173799500007 PM 11840308 ER PT J AU Gold, PW Chrousos, GP AF Gold, PW Chrousos, GP TI Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states SO MOLECULAR PSYCHIATRY LA English DT Review DE atypical depression; corticotropin releasing hormone (CRH); melancholic depression; norepinephrine (NE); stress ID CORTICOTROPIN-RELEASING HORMONE; MEDIAL PREFRONTAL CORTEX; PITUITARY-ADRENAL AXIS; CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; PLASMA NOREPINEPHRINE LEVELS; SEASONAL AFFECTIVE-DISORDER; SYMPATHETIC NERVOUS-SYSTEM; CHRONIC FATIGUE SYNDROME; BONE-MINERAL DENSITY AB Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-ad renal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to Impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic sub-types, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency In atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately. In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction. C1 NIMH, Clin Neuroendocrinol Branch, Intramural Res Program, Clin Ctr,NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Intramural Res Program, NIH, Bethesda, MD USA. RP Gold, PW (reprint author), NIMH, Clin Neuroendocrinol Branch, Intramural Res Program, Clin Ctr,NIH, Room 2D-46-1284, Bethesda, MD 20892 USA. EM philgold@codon.nih.gov NR 160 TC 706 Z9 730 U1 11 U2 77 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 3 BP 254 EP 275 DI 10.1038/sj/mp/4001032 PG 22 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 538MY UT WOS:000174820800006 PM 11920153 ER PT J AU Reyes, GD Esterling, LE Corona, W Ferraren, D Rollins, DY Padigaru, M Yoshikawa, T Monje, VD Detera-Wadleigh, S AF Reyes, GD Esterling, LE Corona, W Ferraren, D Rollins, DY Padigaru, M Yoshikawa, T Monje, VD Detera-Wadleigh, S TI Map of candidate genes and STSs on 18p11.2, a bipolar disorder and schizophrenia susceptibility region SO MOLECULAR PSYCHIATRY LA English DT Letter ID GENOME C1 NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Univ Philippines, Los Banos Coll, Natl Inst Mol Biol & Biotechnol, Laguna, Philippines. Univ Philippines, Coll Sci, Natl Inst Mol Biol & Biotechnol, Quezon City 1101, Philippines. RP Detera-Wadleigh, S (reprint author), NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM sevilla@helix.nih.gov NR 8 TC 12 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 4 BP 337 EP 339 DI 10.1038/sj/mp/4001000 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 544VQ UT WOS:000175182700003 PM 11986976 ER PT J AU Toyota, T Yamada, K Saito, K Detera-Wadleigh, SD Yoshikawa, T AF Toyota, T Yamada, K Saito, K Detera-Wadleigh, SD Yoshikawa, T TI Association analysis of adenylate cyclase type 9 gene using pedigree disequilibrium test in bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID ILLNESS; LOCUS; SCAN C1 RIKEN, Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama 3510198, Japan. Tokyo Med & Dent Univ, Dept Neuropsychiat, Tokyo, Japan. Natl Inst Mental Hlth, Intramural Res Program, Bethesda, MD 20892 USA. RP Yoshikawa, T (reprint author), RIKEN, Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama 3510198, Japan. NR 10 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 5 BP 450 EP 452 DI 10.1038/sj.mp.4000992 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 568HB UT WOS:000176535400007 PM 12082561 ER PT J AU Zubenko, GS Hughes, HB Stiffler, JS Zubenko, WN Kaplan, BB AF Zubenko, GS Hughes, HB Stiffler, JS Zubenko, WN Kaplan, BB TI D2S2944 identifies a likely susceptibility locus for recurrent, early-onset, major depression in women SO MOLECULAR PSYCHIATRY LA English DT Article DE recurrent; early-onset; major depressive disorder; mood disorders; alcohol and substance use disorders; genetics; susceptibility genes in women; sex-specificity; D2S2944 ID ALZHEIMERS-DISEASE; AFFECTIVE-DISORDERS; PSYCHIATRIC-DISORDERS; UNIPOLAR DEPRESSION; FAMILY HISTORY; PANIC DISORDER; RISK; TWIN; ILLNESS; TRANSMISSION AB Recurrent, early-onset, major depressive disorder (RE-MDD) is a strongly familial condition whose malignant effects have a significant negative impact on the health and longevity of patients and their family members. Sixteen of the 19 candidate susceptibility loci identified by a recent genome survey revealed allelic associations with RE-MDD in men or women, but not in both sexes. The association of D2S2944 alleles and genotypes with RE-MDD and related disorders was evaluated using a case-control study design employing 100 adults with RE-MDD and 100 adult controls who had no personal or family history of mental disorders. The results of the case-control study were subsequently evaluated in a sample of 81 families ascertained through probands with RE-MDD using the transmission/disequilibrium test. The frequency of the D2S2944 124-bp allele among women with RE-MDD was approximately three times that for female controls (P = 0.0003). Women who carried the D2S2944 124-by allele revealed a significantly elevated risk of developing RE-MDD, as indicated by an odds ratio of 4.5 compared to female controls (P < 0.001). In contrast, men with RE-MDD did not have an increased frequency of this allele compared to male controls, and men who were carriers did not exhibit an increased risk of developing RE-MDD or related disorders. Our findings also suggest that the D2S2944 124-by allele increases the risk of alcohol and other substance use disorders among women with RE-MDD. The transmission/disequilibrium test provided confirmatory evidence of these sex-specific findings within families. The results of this study confirm the existence of sex-specific susceptibility loci for RE-MDD, and suggest that there may be important differences in the molecular pathophysiology of RE-MDD in men and women. Alternatively, our findings may reflect the existence of sex-specific differences in the molecular mechanisms that determine resilience to endogenous or environmental depressogenic stimuli. The identification and characterization of the D2S2944 susceptibility locus for RE-MDD and related substance use disorders is likely to provide important new insights into the clinical biology, treatment, and prevention of these disorders. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Carnegie Mellon Univ, Mellon Coll Sci, Dept Biol Sci, Pittsburgh, PA USA. NIMH, Lab Mol Biol, Bethesda, MD USA. RP Zubenko, GS (reprint author), WPIC, Rm E1230 3811 O Hara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH43261, MH60866, MH48969, MH00540, MH30915] NR 56 TC 31 Z9 34 U1 3 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 5 BP 460 EP 467 DI 10.1038/sj.mp.4001121 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 568HB UT WOS:000176535400009 PM 12082563 ER PT J AU Gabry, KE Chrousos, GP Rice, KC Mostafa, RM Sternberg, E Negrao, AB Webster, EL McCann, SM Gold, PW AF Gabry, KE Chrousos, GP Rice, KC Mostafa, RM Sternberg, E Negrao, AB Webster, EL McCann, SM Gold, PW TI Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs SO MOLECULAR PSYCHIATRY LA English DT Article DE functional gastrointestinal disorders; corticotropin-releasing; type 1 receptor; peptic ulcer; irritable bowel; nonpeptide; antagonist ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; PEPTIC-ULCER DISEASE; PITUITARY-ADRENAL AXIS; COLONIC MOTOR FUNCTION; RECEPTOR ANTAGONIST; FACTOR CRF; GASTROINTESTINAL MOTILITY; ACID SECRETION; DUODENAL-ULCER AB When exposed to prolonged stress, rats develop gastric ulceration, enhanced colon motility with depletion of its mucin content and signs of physiological and behavioral arousal. In this model, we tested whether antidepressants (fluoxetine and bupropion), anxiolytics (diazepam and buspirone) or the novel nonpeptide corticotropin-releasing hormone (CRH) type-1 receptor (CRH-R1) antagonist, antalarmin, modify these responses. Fluoxetine, bupropion, diazepam and antalarmin all suppressed stress-induced gastric ulceration in male Sprague-Dawley rats exposed to four hours of plain immobilization. Antalarmin produced the most pronounced anti-ulcer effect and additionally suppressed the stress-induced colonic hypermotility, mucin depletion, autonomic hyperarousal and struggling behavior. Intraperitoneal CRH administration reproduced the intestinal but not the gastric responses to stress while vagotomy antagonized the stress-induced gastric ulceration but not the intestinal responses. We conclude that brain CRH-R1 and vagal pathways are essential for gastric ulceration to occur in response to stress and that peripheral CRH-R1 mediates colonic hypermotility and mucin depletion in this model. Nonpeptide CRH-R1 antagonists may therefore be prophylactic against stress ulcer in the critically ill and therapeutic for other pathogenetically related gastrointestinal disorders such as peptic ulcer disease and irritable bowel syndrome. C1 NIMH, IRP, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Intramural Res Program, NIH, Bethesda, MD USA. NIDDKD, Lab Med Chem, Intramural Res Program, Bethesda, MD USA. Univ Pittsburgh, Ctr Med, Dept Surg, Pittsburgh, PA USA. Louisiana State Univ, Pennington Biomed Res Labs, Baton Rouge, LA USA. RP Gabry, KE (reprint author), NIMH, IRP, Clin Neuroendocrinol Branch, NIH, Bldg 10,Rm 2D-46, Bethesda, MD 20892 USA. RI Negrao, Andre Brooking/C-9526-2014 OI Negrao, Andre Brooking/0000-0002-8133-6723 NR 85 TC 45 Z9 49 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 5 BP 474 EP 483 DI 10.1038/sj.mp.4001031 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 568HB UT WOS:000176535400011 PM 12082565 ER PT J AU Straub, RE MacLean, CJ Ma, Y Webb, BT Myakishev, MV Harris-Kerr, C Wormley, B Sadek, H Kadambi, B O'Neill, FA Walsh, D Kendler, KS AF Straub, RE MacLean, CJ Ma, Y Webb, BT Myakishev, MV Harris-Kerr, C Wormley, B Sadek, H Kadambi, B O'Neill, FA Walsh, D Kendler, KS TI Genome-wide scans of three independent sets of 90 Irish multiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes SO MOLECULAR PSYCHIATRY LA English DT Review DE schizophrenia; linkage; genome scan; Irish ID NONPARAMETRIC LINKAGE ANALYSIS; D22S278 MARKER ALLELES; ROSCOMMON FAMILY; DETECT LINKAGE; VULNERABILITY LOCUS; SUGGESTIVE EVIDENCE; TRANSMISSION DISEQUILIBRIUM; CHROMOSOME-15 LOCUS; FINNISH POPULATION; CANDIDATE REGIONS AB From our linkage study of Irish families with a high density of schizophrenia, we have previously reported evidence for susceptibility genes in regions 5q21-31, 6p24-21, 8p22-21, and 10p15-p11. In this report, we describe the cumulative results from independent genome scans of three a priori random subsets of 90 families each, and from multipoint analysis of all 270 families in ten regions. Of these ten regions, three (13q32, 18p11-q11, and 18q22-23) did not generate scores above the empirical baseline pal scan results, and one (6q13-26) generated a weak signal. Six other regions produced more positive pairwise and multipoint results. They showed the following maximum multipoint H-LOD (heterogeneity LOD) and NPL scores: 2p14-13: 0.89 (P = 0.06) and 2.08 (P = 0.02), 4q24-32: 1.84 (P = 0.007) and 1.67 (P = 0.03), 5q21-31: 2.88 (P = 0.0007), and 2.65 (P = 0.002), 6p25-24: 2.13 (P = 0.005) and 3.59 (P = 0.0005), 6p23: 2.42 (P = 0.001) and 3.07 (P = 0.001), 8p22-21: 1.57 (P = 0.01) and 2.56 (P = 0.005), 10p15-11: 2.04 (P = 0.005) and 1.78 (P = 0.03). The degree of 'internal replication' across subsets differed, with 5q, 6p, and 8p being most consistent and 2p and 10p being least consistent. On 6p, the data suggested the presence of two susceptibility genes, in 6p25-24 and 6p23-22. Very few families were positive on more than one region, and little correlation between regions was evident, suggesting substantial locus heterogeneity. The levels of statistical significance were modest, as expected from loci contributing to complex traits. However, our internal replications, when considered along with the positive results obtained in multiple other samples, suggests that most of these six regions are likely to contain genes that influence liability to schizophrenia. C1 Commonwealth Biotechnol Inc, Richmond, VA USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Genaissance Pharmaceut Inc, New Haven, CT USA. Hlth Res Board, Dublin, Ireland. Queens Univ Belfast, Dept Psychiat, Belfast, Antrim, North Ireland. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. RP Straub, RE (reprint author), NIMH, Clin Brain Disorders Branch, IRP, NIH, Bldg 10,Room 4N-311,MSC 1385, Bethesda, MD 20892 USA. EM straubr@intra.nimh.nih.gov RI O'Neill, Francis/C-5582-2008; Webb, Bradley/B-1459-2009; OI Webb, Bradley/0000-0002-0576-5366; O'Neill, Francis Anthony/0000-0002-7531-7657 FU NIMH NIH HHS [MH41953, MH45390, MH52537] NR 115 TC 114 Z9 119 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 6 BP 542 EP 559 DI 10.1038/sj.mp.4001051 PG 18 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 577TT UT WOS:000177078500007 PM 12140777 ER PT J AU Vawter, MP Thatcher, L Usen, N Hyde, TM Kleinman, JE Freed, WJ AF Vawter, MP Thatcher, L Usen, N Hyde, TM Kleinman, JE Freed, WJ TI Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE synaptophysin; synapsin; schizophrenia; bipolar disorder; mood disorder; hippocampus ID MEDIAL TEMPORAL-LOBE; NEUROTRANSMITTER RELEASE; SYNAPTIC PATHOLOGY; PREFRONTAL CORTEX; POSTMORTEM BRAIN; GENE-EXPRESSION; SYNAPTOPHYSIN; NEUROPATHOLOGY; TISSUE; PHOSPHOPROTEINS AB Several studies suggest that decreased expression of presynaptic proteins may be characteristic of schizophrenia. We examined one such protein, synapsin, in schizophrenia and bipolar disorder. Samples of hippocampal tissue from controls (n = 13), patients with schizophrenia to = 16), or bipolar disorder (n = 6), and suicide victims (n = 7) were used. The membrane and cytosolic fractions were analyzed by Western immunoblotting for synapsin using an antibody that detects synapsin la, IIa, and IIIa proteins. Synaptophysin was also measured for comparison. Total synapsin was decreased significantly in patients with schizophrenia (P = 0.034) and in bipolar disorder (P = 0.00008) as compared to controls. The synapsin/synaptophysin ratios were decreased in schizophrenia and bipolar disorder, and additionally in suicide victims (P = 0.014). Age, postmortem interval, percentage of protein extracted, and pH of brain were not different between groups. No changes in total synapsin or synaptophysin in the hippocampus were produced by injecting rats with either lithium or haloperidol for 30 days. Reductions in synapsin in both patients with schizophrenia (synapsin IIa and IIIa) and bipolar disorder (synapsin Ia, IIa and IIIa) imply that altered or reduced synaptic function in the hippocampus may be involved in these disorders. C1 NIDA, Cellular Neurobiol Branch, IRP, Baltimore, MD 21224 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Irvine, CA USA. RP Freed, WJ (reprint author), NIDA, Cellular Neurobiol Branch, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 44 TC 131 Z9 140 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 6 BP 571 EP 578 DI 10.1038/sj.mp.4001158 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 577TT UT WOS:000177078500010 PM 12140780 ER PT J AU Bosetti, F Rintala, J Seemann, R Rosenberger, TA Contreras, MA Rapoport, SI Chang, MC AF Bosetti, F Rintala, J Seemann, R Rosenberger, TA Contreras, MA Rapoport, SI Chang, MC TI Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E-2 concentration in rat brain SO MOLECULAR PSYCHIATRY LA English DT Article DE lithium; arachidonic acid; cyclooxygenase; phospholipase A(2); prostaglandin; brain; rat; chronic; bipolar disorder ID SLEEP-WAKE REGULATION; ARACHIDONIC-ACID; DOCOSAHEXAENOIC ACID; SIGNAL-TRANSDUCTION; TREATMENT DECREASES; MOLECULAR TARGETS; BIPOLAR DISORDER; MESSENGER-RNA; FATTY-ACIDS; GENE AB Rats treated with lithium chloride for 6 weeks have been reported to demonstrate reduced turnover of arachidonic acid (AA) in brain phospholipids, and decreases in mRNA and protein levels, and enzyme activity, of AA-selective cytosolic phospholipase A(2) (cPLA(2)). We now report that chronic lithium administration to rats significantly reduced the brain protein level and enzyme activity of cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also reduced the brain concentration of prostaglandin E-2 (PGE(2)), a bioactive product of AA formed via the COX reaction. COX-1 and the Ca2+ independent iPLA(2) (type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA(2) and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bosetti, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 10,Rm 6N202, Bethesda, MD 20892 USA. NR 52 TC 92 Z9 93 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 8 BP 845 EP 850 DI 10.1038/sj.mp.4001111 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 593WT UT WOS:000178018000008 PM 12232777 ER PT J AU Ohtsuki, T Ishiguro, H Detera-Wadleigh, SD Toyota, T Shimizu, H Yamada, K Yoshitsugu, K Hattori, E Yoshikawa, T Arinami, T AF Ohtsuki, T Ishiguro, H Detera-Wadleigh, SD Toyota, T Shimizu, H Yamada, K Yoshitsugu, K Hattori, E Yoshikawa, T Arinami, T TI Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees SO MOLECULAR PSYCHIATRY LA English DT Article DE HTR4; schizophrenia; affective disorder; polymorphism; haplotype; transmission disequilibrium test; association ID CENTRAL-NERVOUS-SYSTEM; 5-HT4 RECEPTORS; SPLICE VARIANTS; CLONING; MEMORY; RAT AB Possible irregularities in serotonergic neurotransmission have been suggested as causes of a variety of neuropsychiatric diseases. We performed mutation and association analyses of the HTR4 gene, on 5q32, encoding the serotonin 4 receptor in mood disorders and schizophrenia. Mutation analysis was performed on the HTR4 exons and exon/intron boundaries in 48 Japanese patients with mood disorders and 48 patients with schizophrenia. Eight polymorphisms and four rare variants were identified. Of these, four polymorphisms at or in close proximity to exon d, g.83097C/T (HTR4-SVR (splice variant region) SNP1), g.83159G/A (HTR4-SVRSNP2), g.83164 (T)9-10 (HTR4-SVRSNP3), and g.83198A/G (HTR4-SVRSNP4), showed significant association with bipolar disorder with odds ratios of 1.5 to 2. These polymorphisms were in linkage disequilibrium, and only three common haplotypes were observed. One of the haplotypes showed significant association with bipolar disorder (P=0.002). The genotypic and haplotypic associations with bipolar disorder were confirmed by transmission disequilibrium test in the NIMH Genetics Initiative Bipolar Pedigrees with ratios of transmitted to not transmitted alleles of 1.5 to 2.0 (P=0.01). The same haplotype that showed association with bipolar disorder was suggested to be associated with schizophrenia in the case-control analysis (P=0.003) but was not confirmed when Japanese schizophrenia families were tested. The polymorphisms associated with mood disorder were located within the region that encodes the divergent C-terminal tails of the 5-HT4 receptor. These findings suggest that genomic variations in the HTR4 gene may confer susceptibility to mood disorder. C1 Univ Tsukuba, Inst Basic Med Sci, Dept Med Genet, Tsukuba, Ibaraki 3058575, Japan. Natl Inst Mental Hlth Intramural Res Program, Bethesda, MD USA. RIKEN Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama, Japan. Hokushin Gen Hosp, Dept Neuropsychiat, Nagano, Japan. RP Arinami, T (reprint author), Univ Tsukuba, Inst Basic Med Sci, Dept Med Genet, Tsukuba, Ibaraki 3058575, Japan. FU NIMH NIH HHS [U01 MH46282, U01 MH46274, U01 MH46280] NR 16 TC 45 Z9 47 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 9 BP 954 EP 961 DI 10.1038/sj.mp.4001133 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 610GQ UT WOS:000178952700009 PM 12399948 ER PT J AU Yoshida-Hiroi, M Bradbury, MJ Eisenhofer, G Hiroi, N Vale, WW Novotny, GE Hartwig, HG Scherbaum, WA Bornstein, SR AF Yoshida-Hiroi, M Bradbury, MJ Eisenhofer, G Hiroi, N Vale, WW Novotny, GE Hartwig, HG Scherbaum, WA Bornstein, SR TI Chromaffin cell function and structure is impaired in corticotropin-releasing hormone receptor type 1-null mice SO MOLECULAR PSYCHIATRY LA English DT Article DE CRH receptor type 1; chromaffin cell; catecholamine; ACTH; adrenal; mouse ID PHENYLETHANOLAMINE-N-METHYLTRANSFERASE; TRANSGENIC MICE; ADRENAL-MEDULLA; STRESS-RESPONSE; NEUROPEPTIDE-Y; MESSENGER-RNA; GLUCOCORTICOID RECEPTOR; DIFFERENTIAL REGULATION; TYROSINE-HYDROXYLASE; GENE-EXPRESSION AB Corticotropin-releasing hormone (CRH) is both a main regulator of the hypothalamic-pituitary-adrenocortical axis and the autonomic nervous system. CRH receptor type 1 (CRHR1)-deficient mice demonstrate alterations in behavior, impaired stress responses with adrenocortical insufficiency and aberrant neuroendocrine development, but the adrenal medulla has not been analyzed in these animals. Therefore we studied the production of adrenal cat-echolamines, expression of the enzyme responsible for catecholamine biosynthesis neuropeptides and the ultrastructure of chromaffin cells in CRHR1 null mice. In addition we examined whether treatment of CRHR1 null mice with adrenocorticotropic hormone (ACTH) could restore function of the adrenal medulla. CRHR1 null mice received saline or ACTH, and wildtype or heterozygous mice injected with saline served as controls. Adrenal epinephrine levels in saline-treated CRHR1 null mice were 44% those of controls (P <0.001), and the phenylethanolamine N-methyltransferase (PNMT) mRNA levels in CRHR1 null mice were only 25% of controls (P <0.001). ACTH treatment increased epinephrine and PNMT mRNA level in CRHR1 null mice but failed to restore them to normal levels. Proenkephalin mRNA in both saline- and ACTH-treated CRHR1 null mice were higher than in control animals (215.8% P <0.05, 268.9% P <0.01) whereas expression of neuropeptide Y and chromogranin B did not differ. On the ultrastructural level, chromaffin cells in saline-treated CRHR1 null mice exhibited a marked depletion in epinephrine-storing secretory granules that was not completely normalized by ACTH-treatment. In conclusion, CRHR1 is required for a normal chromaffin cell structure and function and deletion of this gene is associated with a significant impairment of epinephrine biosynthesis. C1 NINDS, Clin Neurocardiol Sect & Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA USA. Univ Dusseldorf, Inst Neuroanat, Dusseldorf, Germany. Univ Dusseldorf, Dept Endocrinol, Dusseldorf, Germany. Univ Dusseldorf, Dept Anat, Dusseldorf, Germany. RP Yoshida-Hiroi, M (reprint author), NINDS, Clin Neurocardiol Sect & Surg Neurol Branch, NIH, Bldg 10,10 Ctr Dr,Rm 6N252, Bethesda, MD 20892 USA. NR 52 TC 18 Z9 19 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 9 BP 967 EP 974 DI 10.1038/sj.mp.4001143 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 610GQ UT WOS:000178952700011 PM 12399950 ER PT J AU Wersinger, SR Ginns, EI O'Carrol, AM Lolait, SJ Young, WS AF Wersinger, SR Ginns, EI O'Carrol, AM Lolait, SJ Young, WS TI Vasopressin V1b receptor knockout reduces aggressive behavior in male mice SO MOLECULAR PSYCHIATRY LA English DT Article DE homologous recombination; aggression; memory; vasopressin 1b receptor; knockout ID MESSENGER-RIBONUCLEIC-ACID; ANTERIOR HYPOTHALAMUS; SOCIAL RECOGNITION; RAT-BRAIN; ARGININE-VASOPRESSIN; GOLDEN-HAMSTERS; LATERAL SEPTUM; OXYTOCIN; STRESS; GENE AB Increased aggression is commonly associated with many neurological and psychiatric disorders. Current treatments are largely empirical and are often accompanied by severe side effects, underscoring the need for a better understanding of the neural bases of aggression. Vasopressin, acting through its la receptor subtype, is known to affect aggressive behaviors. The vasopressin 1b receptor (V1bR) is also expressed in the brain, but has received much less attention due to a lack of specific drugs. Here we report that mice without the V1bR exhibit markedly reduced aggression and modestly impaired social recognition. By contrast, they perform normally in all the other behaviors that we have examined, such as sexual behavior, suggesting that reduced aggression and social memory are not simply the result of a global deficit in sensorimotor function or motivation. Fos-mapping within chemosensory responsive regions suggests that the behavioral deficits in V1bR knockout mice are not due to defects in detection and transmission of chemosensory signals to the brain. We suggest that V1bR antagonists could prove useful for treating aggressive behavior seen, for example, in dementias and traumatic brain injuries. C1 NIMH, Sect Neural Gene Express, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Worcester, MA USA. Univ Bristol, Univ Res Ctr Neuroendocrinol, Bristol BS8 1TH, Avon, England. RP Young, WS (reprint author), NIMH, Sect Neural Gene Express, Bldg 36,Rm 2A11,MSC 4068, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 53 TC 197 Z9 202 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 9 BP 975 EP 984 DI 10.1038/sj.mp.4001195 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 610GQ UT WOS:000178952700012 PM 12399951 ER PT J AU Webster, MJ Knable, MB O'Grady, J Orthmann, J Weickert, CS AF Webster, MJ Knable, MB O'Grady, J Orthmann, J Weickert, CS TI Regional specificity of brain gluclocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders SO MOLECULAR PSYCHIATRY LA English DT Article DE bipolar disorder; depression; schizophrenia; glucocorticoid receptors; frontal cortex; temporal cortex; hippocampus ID MAJOR DEPRESSIVE DISORDER; DEXAMETHASONE-SUPPRESSION TEST; GLIAL-CELL DENSITY; GLUCOCORTICOID-RECEPTOR; GENE-EXPRESSION; RAT-BRAIN; PREFRONTAL CORTEX; MINERALOCORTICOID RECEPTOR; HIPPOCAMPAL VOLUME; RIBONUCLEIC-ACID AB Glucocorticoid receptors (GR) mediate the direct effects of glucocorticoids released in response to stress and the regulation of the hypothalamic-pituitary-adrenocortical (HPA) system through a negative feedback mechanism. Individuals with major mental illness, who often exhibit hypercortisolemia, may have down-regulated levels of GR mRNA. In situ hybridization for GR mRNA was performed on post-mortem specimens from patients suffering from depression, bipolar disorder, schizophrenia and from normal controls (n = 15 per group). In frontal cortex, GR mRNA levels were decreased in layers III-VI in the subjects with depression and schizophrenia. In inferior temporal cortex, GR mRNA levels were decreased in layer IV in all three diagnostic groups. In the entorhinal cortex, GR mRNA levels were decreased in layers III and VI in the bipolar group. In hippocampus, GR mRNA levels were reduced in the dentate gyrus, CA(4), CA(3) and CA(1) in the schizophrenia group. In the subiculum, GR mRNA levels were reduced in the bipolar group. These results suggest that GR dysregulation occurs in all three major psychiatric illnesses with variability according to anatomical site. The severity and heterogeneity of this reduction may underlie some of the clinical heterogeneity seen in these disorders. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn Lab Brain Res, Bethesda, MD 20814 USA. NIMH, Intramural Res Program, Clin Brain Disorders Branch, Bethesda, MD USA. RP Webster, MJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn Lab Brain Res, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM websterm@stanleyresearch.org RI Shannon Weickert, Cynthia/G-3171-2011 NR 94 TC 228 Z9 230 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 9 BP 985 EP 994 DI 10.1038/sj.mp.4001139 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 610GQ UT WOS:000178952700013 PM 12399952 ER PT J AU Champoux, M Bennett, A Shannon, C Higley, JD Lesch, KP Suomi, SJ AF Champoux, M Bennett, A Shannon, C Higley, JD Lesch, KP Suomi, SJ TI Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates SO MOLECULAR PSYCHIATRY LA English DT Article DE behavioral genetics; attention; infant; temperament; Macaca mulatta ID DOPAMINE-D4 RECEPTOR; MACACA-MULATTA; TEMPERAMENT; INFANTS; NEUROGENESIS; PROMOTER; 5-HTTLPR; MACAQUES; NEURONS; CORTEX AB A polymorphism in the serotonin (5-HT) transporter gene regulatory region (5-HTTLPR) is associated with measures of 5-HT transporter (5-HTT) expression and 5-HT-mediated behaviors in humans. An analogous length variation of the 5-HTTLPR has been reported in rhesus monkeys (rh5-HTTLPR). A retrospective association study was conducted on 115 rhesus macaque infants either homozygous for the long 5HTTLPR variant (I/I) or heterozygous for the short and long form (I/s). To assess contributions of genotype and early rearing environment, 36 mother-reared monkeys (I/I = 26, I/s = 10) and 79 nursery-reared monkeys (I/I = 54, I/s = 25) were assessed on days 7, 14, 21, and 30 of life on a standardized primate neurobehavioral test designed to measure orienting, motor maturity, reflex functioning, and temperament. Both mother-reared and nursery-reared heterozygote animals demonstrated increased affective responding relative to I/I homozygotes. Nursery-reared, but not mother-reared, IN infants exhibited lower orientation scores than their I/I counterparts. These results demonstrate the contributions of rearing environment and genetic background, and their interaction, in a nonhuman primate model of behavioral development. C1 NICHHD, Lab Comparat Ethl, Anim Ctr, NIH, Poolesville, MD 20837 USA. NIAAA, Clin Studies Lab, Primate Unit, Anim Ctr,NIH, Poolesville, MD USA. Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. RP Champoux, M (reprint author), NICHHD, Lab Comparat Ethl, Anim Ctr, NIH, POB 529, Poolesville, MD 20837 USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 27 TC 246 Z9 247 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 10 BP 1058 EP 1063 DI 10.1038/sj.mp.4001157 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 623EC UT WOS:000179689500006 PM 12476320 ER PT J AU Fogdell-Hahn, A Soldan, SS Jacobson, S AF Fogdell-Hahn, A Soldan, SS Jacobson, S TI Association of chronic progressive neurological disease and ubiquitous viral agents: lessons from human herpesvirus 6 and multiple sclerosis SO MOLECULAR PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Microbiology Immunology and Toxicology of Autism and Other Neurodevelopmental Disorders CY FEB 11-14, 2001 CL COLD SPRING HARBOR, NEW YORK ID POLYMERASE CHAIN-REACTION; HHV-6; COMPLEMENT; ANTIBODIES; INFECTION; RESPONSES; VARIANT; MS C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. NR 30 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 SU 2 BP S29 EP S31 DI 10.1038/sj.mp.4001172 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 579AZ UT WOS:000177154400013 PM 12142941 ER PT J AU Manji, HK Zarate, CA AF Manji, HK Zarate, CA TI Molecular and cellular mechanisms underlying mood stabilization in bipolar disorder: implications for the development of improved therapeutics SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID MANIC-DEPRESSIVE ILLNESS; LITHIUM TREATMENT; MORTALITY; PATHOPHYSIOLOGY; LAMOTRIGINE; MAINTENANCE; IMPAIRMENT; SYMPTOMS; DISEASE C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Bldg 49,Room B1EE16,49 Convent Dr,MSC 4405, Bethesda, MD 20892 USA. NR 47 TC 21 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 SU 1 BP S1 EP S7 DI 10.1038/sj.mp.4001068 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 539XT UT WOS:000174898700001 PM 11986989 ER PT J AU Manji, HK Chen, G AF Manji, HK Chen, G TI PKC, MAP kinases and the bcl-2 family of proteins as long-term targets for mood stabilizers SO MOLECULAR PSYCHIATRY LA English DT Article DE neuroplasticity; cell survival; bipolar; manic; lithium; antidepressant; MAP kinase ID MANIC-DEPRESSIVE ILLNESS; TRANSCRIPTION FACTOR; SIGNALING PATHWAYS; CHRONIC LITHIUM; HUMAN BRAIN; CELL-DEATH; IN-VITRO; DISORDERS; SURVIVAL; ABNORMALITIES AB The complexity of the unique biology of bipolar disorder-which includes the predisposition to episodic, and often progressive, mood disturbance-and the dynamic nature of compensatory processes in the brain, coupled with limitations in experimental design, have hindered our ability to identify the underlying pathophysiology of this fascinating neuropsychiatric disorder. Although we have yet to identify the specific abnormal genes in mood disorders, recent studies have implicated critical signal transduction pathways as being integral to the pathophysiology and treatment of bipolar disorder. In particular, a converging body of preclinical data has shown that chronic lithium and valproate, at therapeutically relevant concentrations, regulate the protein kinase C signaling cascade. This has led to the investigation of the antimanic efficacy of tamoxifen (at doses sufficient to inhibit protein kinase C), with very encouraging preliminary results. A growing body of data also suggests that impairments of neuroplasticity and cellular resilience may also underlie the pathophysiology of bipolar disorder. It is thus noteworthy that mood stabilizers, such as lithium and valproate, indirectly regulate a number of factors involved in cell survival pathways-including cAMP response element binding protein, brain derived neurotrophic factor, bcl-2 and mitogen-activated protein kinases-and may thus bring about some of their delayed long-term beneficial effects via under-appreciated neurotrophic effects. The development of novel treatments, which more directly target molecules involved in critical central nervous system cell survival and cell death pathways, has the potential to enhance neuroplasticity and cellular resilience, thereby modulating the long-term course and trajectory of these devastating illnesses. C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Bldg 49,Room B1EE16,49 Convent Dr,MSC 4405, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 64 TC 97 Z9 100 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 SU 1 BP S46 EP S56 DI 10.1038/sj.mp.4001018 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 539XT UT WOS:000174898700007 PM 11986995 ER PT J AU Swedo, SE AF Swedo, SE TI Pediatric autoirnmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) SO MOLECULAR PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Microbiology Immunology and Toxicology of Autism and Other Neurodevelopmental Disorders CY FEB 11-14, 2001 CL COLD SPRING HARBOR, NEW YORK ID RHEUMATIC-FEVER; SYDENHAM CHOREA C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Swedo, SE (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NR 12 TC 38 Z9 39 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 SU 2 BP S24 EP S25 DI 10.1038/sj.mp.4001170 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 579AZ UT WOS:000177154400011 PM 12142939 ER PT J AU Hummer, G AF Hummer, G TI Fast-growth thermodynamic integration: Results for sodium ion hydration SO MOLECULAR SIMULATION LA English DT Article DE nonequilibrium molecular dynamics; ion solvation; free energy perturbation theory; Monte Carlo simulation ID FREE-ENERGY DIFFERENCES; MOLECULAR-DYNAMICS SIMULATIONS; SOLVATION FREE-ENERGIES; FINITE-SIZE CORRECTIONS; COMPUTER-SIMULATIONS; ELECTRON-TRANSFER; MEAN-FORCE; NONEQUILIBRIUM MEASUREMENTS; PERTURBATION CALCULATIONS; WATER AB Slow-growth thermodynamic integration (TI) is a simple method to calculate free energy differences in fluid and macromolecular systems. A recently derived identity (Jarzynski, C. Phys. Rev. Lett. 78, 2690, 1997) permits the calculation of free energy differences from repeated TIs at arbitrary growth rates. Here, I investigate the quantitative accuracy of the resulting 'fast-growth' TI for the charging of a sodium ion in water. To estimate the corresponding free energy of hydration, I use simple expressions involving the means and variances of the non-equilibrium work. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Building 5, Bethesda, MD 20892 USA. EM hummer@helix.nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 50 TC 18 Z9 18 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0892-7022 J9 MOL SIMULAT JI Mol. Simul. PD JAN-FEB PY 2002 VL 28 IS 1-2 BP 81 EP 90 DI 10.1080/08927020290004395 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 561DH UT WOS:000176122400007 ER PT J AU Ling, ZD Gayle, DA Ma, SY Lipton, JW Tong, CW Hong, JS Carvey, PM AF Ling, ZD Gayle, DA Ma, SY Lipton, JW Tong, CW Hong, JS Carvey, PM TI In utero bacterial endotoxin exposure causes loss of tyrosine hydroxylase neurons in the postnatal rat midbrain SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; TNF-alpha; IL-1 beta; dopamine; prenatal infection; risk factors for Parkinson's disease; cytokines ID TUMOR-NECROSIS-FACTOR; HUMAN FETAL MEMBRANES; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; DOPAMINERGIC-NEURONS; AMNIOTIC-FLUID; FACTOR-ALPHA; HISTOLOGIC CHORIOAMNIONITIS; MESENCEPHALIC CULTURES; SIGNAL-TRANSDUCTION AB We investigated whether in utero exposure to the Gram(-) bacteriotoxin lipopolysaccharide (LPS) induces dopamine (DA) neuron loss in rats. The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) kills DA neurons and is elevated in the brains of patient,, with Parkinson's disease (PD). LPS is a potent inducer of TNF-alpha, and both are increased in the chorioamniotic environment of women who have bacterial vaginosis (BV) during pregnancy, suggesting that BV might interfere with the normal development of fetal DA neurons. Gravid female rats were injected intraperitoneally with either LPS or normal saline at embryonic day 10.5 and their pups were killed at postnatal day 21. The brains of the pups were assessed for DA and TNF-alpha levels and DA cell counts in the mesencephalon using tyrosine hydroxylase immunoreactive (THir) cells as a DA neuron marker. Prenatal LPS exposure significantly reduced striatal DA (29%) and increased DA activity (72%) as well as TNF-alpha (101%). Stereological cell counts in the mesencephalon were also significantly reduced (27%) by prenatal LPS exposure. Prenatal exposure to LPS, as might occur in humans with BV, produces a significant loss of THir cells in rats that is still present 33 days following a single injection of LPS. Since this cell loss is well past the normal phase of DA neuron apoptosis that occurs in early postnatal life, rats so exposed may have a permanent loss of DA neurons, suggesting that prenatal infections may represent risk factors for PD. (C) 2001 Movement Disorder Society. C1 Rush Presbyterian St Lukes Med Ctr, Dept Pharmacol, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Dept Pediat, Chicago, IL 60612 USA. NIEHS, Neuropharmacol Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Ling, ZD (reprint author), Tech 2000,Suite 260,2242 W Harrison St, Chicago, IL 60612 USA. FU NIEHS NIH HHS [ES10776] NR 68 TC 158 Z9 168 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 2002 VL 17 IS 1 BP 116 EP 124 DI 10.1002/mds.10078 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 517JC UT WOS:000173606500019 PM 11835448 ER PT J AU Hallett, M AF Hallett, M TI Cortical control of brainstem motor systems SO MOVEMENT DISORDERS LA English DT Article; Proceedings Paper CT 2nd European Meeting on Brain Stem Reflexes, Functions, and Related Movement Disorders CY APR, 2001 CL AMSTERDAM, NETHERLANDS SP Movement Disorder Soc, SmithKline Beecham, Eli Lilly Nederland, Medtronics, Ispen, 4th May Fdn, RA Laan Fdn DE cortical motor control; cranial nerves; bulbospinal control; brainstem ID PRIMATE SUPERIOR COLLICULUS; UNDERLYING RETICULAR-FORMATION; MOVEMENT-RELATED NEURONS; LIMB MUSCLE-ACTIVITY; RED NUCLEUS; PEDUNCULOPONTINE NUCLEUS; MACAQUE MONKEY; CORTEX; STIMULATION; PROJECTIONS C1 NINCDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINCDS, Human Motor Control Sect, NIH, Bldg 10 Rm 5N226 10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. NR 36 TC 3 Z9 3 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PY 2002 VL 17 SU 2 BP S23 EP S26 DI 10.1002/mds.10053 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 519BG UT WOS:000173703200008 PM 11836748 ER PT J AU Resnick, HE Stansberry, KB Harris, TB Tirivedi, M Smith, K Morgan, P Vinik, AI AF Resnick, HE Stansberry, KB Harris, TB Tirivedi, M Smith, K Morgan, P Vinik, AI TI Diabetes, peripheral, neuropathy, and old age disability SO MUSCLE & NERVE LA English DT Article DE aged; diabetes; disability; electrophysiology; neuropathy ID RISK-FACTORS; POSTURAL INSTABILITY; SENSORY NEUROPATHY; GRIP STRENGTH; FALLS; HEALTH; AMERICANS; ABNORMALITIES; PREVALENCE; PREDICTOR AB The purpose of this study was to determine whether peripheral neuropathy explains the apparent association between diabetes and disability in old age, and to evaluate the utility of lower extremity function tests in older diabetic adults With and without neuropathy. We evaluated 39 adults, aged 70-79 years, for pressure sensation (log(10)g), vibration perception threshold (VPT; microns), and electrophysiologic function of the peroneal nerve. The subjects included patients with established diabetic neuropathy (DN; n = 14), diabetic controls without neuropathy (DC; n = 13), and nondiabetic controls (NDC; n = 12). Nonparametric statistical methods were used to relate neuropathy measures to performance in tests of walking speed, static and dynamic balance, coordination, and ankle strength (kilograms). Significant age-adjusted correlations were observed between measures of sensory neuropathy and a variety of performance measures, and electrophysiologic measures were related to static balance. DN subjects had significantly higher pressure sensation than NDC (5.17 vs 3.38g, P < 0.05), higher VPT (62.5 vs 21.7 m, P < 0.05), and lower peroneal motor response amplitudes at multiple sites. Pressure sensation and nerve conduction measures did not differ between DC and NDC. Compared with NDC, DN subjects performed significantly worse on tests of walking speed (0.99 vs 1.34 m/s; P < 0.05), static balance (4.9 vs 20.4 s; P < 0.05), dynamic balance (9.23 vs 25.52 s; P < 0.05), and coordination (6.73 vs 4.76 s; P < 0.05). No differences were observed in these measures between DC and NDC. Observed differences in physical abilities between older diabetic and nondiabetic adults may have been due to the subset of diabetic individuals with peripheral neuropathy. Quantitative measures of sensory and motor nerve function have distinct effects on physical performance. Interventions aimed at reducing the impact of diabetes-associated disability in old age may have the greatest impact among people with peripheral neuropathy. (C) 2002 John Wiley & Sons, Inc. C1 Medstar Res Ltd, Washington, DC 20010 USA. Eastern Virginia Med Sch, Strelitz Diabet Inst, Norfolk, VA 23501 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Resnick, HE (reprint author), Medstar Res Ltd, 108 Irving St NW,Annex 5, Washington, DC 20010 USA. NR 44 TC 67 Z9 70 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JAN PY 2002 VL 25 IS 1 BP 43 EP 50 DI 10.1002/mus.1217 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 505RC UT WOS:000172928500008 PM 11754184 ER PT J AU Pettit, RK Hamel, E Verdier-Pinard, P Roberson, RW Hazen, KC Pettit, GR Crews, LC AF Pettit, RK Hamel, E Verdier-Pinard, P Roberson, RW Hazen, KC Pettit, GR Crews, LC TI Antifungal and cancer cell growth inhibitory activities of 1-(3 ',4 ',5 '-trimethoxyphenyl)-2-vitro-ethylene SO MYCOSES LA English DT Article DE 1-(3 ',4 ',5 '-trimethoxyphenyl)-2-vitro-ethylene; anti-cancer; antifungal; tubulin ID CANDIDA-ALBICANS; IN-VITRO; TUBULIN; AGENTS; COLCHICINE; ANALOGS; TRENDS AB The antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'-trimethoxyphenyl)-2-vitro-ethylene (TMPN) were examined. TMPN was fungicidal for the majority of 132 reference strains and clinical isolates tested, including those resistant to fluconazole, ketoconazole, amphotericin B or flucytosine. Minimum fungicidal concentration/minimum inhibitory concentration (MFC/MIC) ratios were less than or equal to 2 for 96% of Cryptococcus neoformans clinical isolates and 71% of Candida albicans clinical isolates. TMPN was fungicidal for a variety of other basidiomycetes, endomycetes and hyphomycetes, and its activity was unaffected by alterations in media pH. The frequency of occurrence of fungal spontaneous mutations to resistance was < 10(-6). Kill-curve analyses confirmed the fungicidal action of TMPN, and demonstrated that killing was concentration- and tithe-dependent. At sub-MIC exposure to TMPN, C. albicans did not exhibit yeast/hyphae switching. TMPN was slightly cytotoxic for murine and human cancer cell lines (GI(50) = 1-4 mug ml(-1)), and weakly inhibited mammalian tubulin polymerization (IC50 = 0.60 mug ml(-1)). C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA. Arizona State Univ, Dept Mol & Cellular Biol, Tempe, AZ 85287 USA. Arizona State Univ, Dept Plant Biol & Chem, Tempe, AZ 85287 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diagnosis, Screening Technol Branch,Dev Therapeut Program, Frederick, MD USA. Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA. RP Pettit, RK (reprint author), Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. NR 24 TC 4 Z9 4 U1 0 U2 2 PU BLACKWELL VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0933-7407 J9 MYCOSES JI Mycoses PY 2002 VL 45 IS 3-4 BP 65 EP 74 DI 10.1046/j.1439-0507.2002.00722.x PG 10 WC Dermatology; Mycology SC Dermatology; Mycology GA 548RY UT WOS:000175404500001 PM 12000503 ER PT J AU Frei, KP Schiffmann, R AF Frei, KP Schiffmann, R TI Myoclonus in Gaucher disease SO MYOCLONUS AND PAROXYSMAL DYSKINESIAS SE ADVANCES IN NEUROLOGY LA English DT Article ID BRAIN-STEM RESPONSE; NEGATIVE MYOCLONUS; GAZE PALSY; INFANTILE; TYPE-3; PATHOPHYSIOLOGY; NEUROPATHOLOGY; PSYCHOSINE; EPILEPSY; ABR C1 Parkinsons & Movement Disorders Inst, Fountain Valley, CA USA. NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. RP Frei, KP (reprint author), Parkinsons & Movement Disorders Inst, Fountain Valley, CA USA. NR 37 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 J9 ADV NEUROL JI Adv.Neurol. PY 2002 VL 89 BP 41 EP 48 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BV80M UT WOS:000180075900007 PM 11968465 ER PT J AU Hallett, M AF Hallett, M TI Neurophysiology of brainstem myoclonus SO MYOCLONUS AND PAROXYSMAL DYSKINESIAS SE ADVANCES IN NEUROLOGY LA English DT Article ID RETICULAR REFLEX MYOCLONUS; UREA-INDUCED MYOCLONUS; POSTHYPOXIC MYOCLONUS; POSTANOXIC COMA; PIRACETAM; FEATURES C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 27 TC 7 Z9 8 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 J9 ADV NEUROL JI Adv.Neurol. PY 2002 VL 89 BP 99 EP 102 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BV80M UT WOS:000180075900012 PM 11968477 ER PT J AU Frucht, SJ Leurgans, SE Hallett, T Fahn, S AF Frucht, SJ Leurgans, SE Hallett, T Fahn, S TI The unified myoclonus rating scale SO MYOCLONUS AND PAROXYSMAL DYSKINESIAS SE ADVANCES IN NEUROLOGY LA English DT Article ID RELIABILITY; PIRACETAM; VALIDITY; EPILEPSY C1 Columbia Univ, Columbia Presbyterian Med Ctr, Neurol Inst, Dept Neurol, New York, NY 10032 USA. Rush Univ, Rush Med Coll, Dept Neurol Sci, Chicago, IL 60612 USA. Rush Univ, Rush Med Coll, Dept Prevent Med, Chicago, IL 60612 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Frucht, SJ (reprint author), Columbia Univ, Columbia Presbyterian Med Ctr, Neurol Inst, Dept Neurol, New York, NY 10032 USA. NR 10 TC 68 Z9 71 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 J9 ADV NEUROL JI Adv.Neurol. PY 2002 VL 89 BP 361 EP 376 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BV80M UT WOS:000180075900034 PM 11968461 ER PT B AU Cragg, GM Newman, DJ AF Cragg, GM Newman, DJ BE Rauter, AP Palma, FB Justino, J Araujo, ME PinaDosSantos, S TI Industrial applications. Natural products for medicinal purposes. Drugs from nature: Present developments and future prospects SO NATURAL PRODUCTS IN THE NEW MILLENNIUM: PROSPECTS AND INDUSTRIAL APPLICATION SE PROCEEDINGS OF THE PHYTOCHEMICAL SOCIETY OF EUROPE LA English DT Proceedings Paper CT Meeting of the Phytochemical-Society-of-Europe CY APR 02-05, 2000 CL FUND CALOUSTE GULBENKIAN, LISBON, PORTUGAL SP ATRAL-CIPAN, Caixa Gerak Depositios, Camara Municipal Lisboa, Univ Lisboa, Ctr Informat Fac Ciencias, Compal, Dias Sousa S A, ELNOR, Embaixada Espanha, Embaixada Franca, Fund Calouste Gulbenkian, Fund Fac Ciencias, Fund Luso-Amer Desenvolvimento, Fund Apioi Comunidade Cienf, Fund Ciencia Tecnol, Georg Thieme Verlag, Inst Italiano Cultura Portugal, Inst Politecn Santarem, Lab Estudos Farmaceut, Lusodiete, Papelaria A Desportiva, PE BIOSYST, POSTUGAK TELECON, PRISFAR, Produtos Farmacut S A, Reagentes 5, Univ Lisboa, Reitoria, Secretaria Estado Mercados Agricolas Qualidade Alimentar, SOQUIMICA, SPRINGER VERLAG GmbH & Co KG, TAP AIR PORTUGAL, British Council, Turismo Lisboa, Visitors & Convent Bureau, UNICAM, UNICER, WATERS, XEROX HO FUND CALOUSTE GULBENKIAN ID POLYKETIDE SYNTHASES; MICROBIAL DIVERSITY; DISCOVERY; BRYOSTATIN-1; COMMUNITIES; CHEMISTRY; AGENTS AB Nature has been a source of medicinal treatments for thousands of years. While plants were the major source of medicines for millennia, the discovery of the penicillins in the 1930s ushered in the golden age of antibiotics and a revolution in chemotherapy. More recently, marine organisms have provided a host of novel bioactive chemotypes. Advances in the description of the human genome, as well as the genomes of pathogenic microbes and parasites, are resulting in the determination of the structures of many of the proteins associated with disease processes. Novel molecular targets based on these proteins are being developed as high throughput assays, which require expanded and novel chemical diversity for screening. Much of the world's biological diversity remains unexplored as a source of novel drug leads, and the search for new bioactive agents from natural sources, including extreme environmental niches, is expanding. The potential for drug discovery is being further enhanced, with advances in procedures for microbial cultivation and the extraction of nucleic acids from environmental samples providing access to the vast untapped reservoir of microbial genetic and metabolic diversity. Genetic manipulation of microbial biosynthetic pathways is further expanding this potential to include the biosynthesis of bioactive products not generated naturally. The unique molecules generated by nature provide scaffolds for elaboration by combinatorial chemical techniques, as well as challenges to organic chemists, not only in their total synthesis, but also in the identification of simpler pharmacophores, which may prove to be equal or more effective chemotherapeutic agents. Nature thus provides access to unique molecular diversity, but the investigation of these resources requires multi-disciplinary, international collaboration in the discovery and development process. C1 NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 44 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-1047-8 J9 PR PHYT SOC PY 2002 VL 47 BP 285 EP 297 PG 13 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA BV96V UT WOS:000180547900030 ER PT J AU D'Orazi, G Cecchinelli, B Bruno, T Manni, I Higashimoto, Y Saito, S Gostissa, M Coen, S Marchetti, A Del Sal, G Piaggio, G Fanciulli, M Appella, E Soddu, S AF D'Orazi, G Cecchinelli, B Bruno, T Manni, I Higashimoto, Y Saito, S Gostissa, M Coen, S Marchetti, A Del Sal, G Piaggio, G Fanciulli, M Appella, E Soddu, S TI Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis SO NATURE CELL BIOLOGY LA English DT Article ID P53-DEPENDENT APOPTOSIS; NUCLEAR-BODIES; IN-VITRO; PML; MDM2; INHIBITION; EXPRESSION; SUMO-1 AB Phosphorylation of p53 at Ser 46 was shown to regulate p53 apoptotic activity. Here we demonstrate that homeodomain-interacting protein kinase-2 (HIPK2), a member of a novel family of nuclear serine/threonine kinases, binds to and activates p53 by directly phosphorylating it at Ser 46. HIPK2 localizes with p53 and PML-3 into the nuclear bodies and is activated after irradiation with ultraviolet. Antisense inhibition of HIPK2 expression reduces the ultraviolet-induced apoptosis. Furthermore, HIPK2 and p53 cooperate in the activation of p53-dependent transcription and apoptotic pathways. These data define a new functional interaction between p53 and HIPK2 that results in the targeted subcellular localization of p53 and initiation of apoptosis. C1 Regina Elena Inst Canc Res, Mol Oncogenesis Lab, I-00158 Rome, Italy. Regina Elena Inst Canc Res, Cell Metab & Pharmacokinet Lab, I-00158 Rome, Italy. Univ G DAnnunzio, Dept Oncol & Neurosci, I-66013 Chieti, Italy. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Interuniv Consortium Biotechnol, Natl Lab, I-34012 Trieste, Italy. Dept Biochem Biophys & Chem Macromol, I-34100 Trieste, Italy. RP D'Orazi, G (reprint author), Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Via Messi Oro 156, I-00158 Rome, Italy. OI DEL SAL, GIANNINO/0000-0003-2185-6003; MARCHETTI, ALESSANDRA/0000-0001-9706-848X; piaggio, giulia/0000-0003-2114-1892 NR 35 TC 435 Z9 443 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2002 VL 4 IS 1 BP 11 EP 19 DI 10.1038/ncb714 PG 9 WC Cell Biology SC Cell Biology GA 513MC UT WOS:000173381500010 PM 11780126 ER PT J AU Veigel, C Wang, F Bartoo, ML Sellers, JR Molloy, JE AF Veigel, C Wang, F Bartoo, ML Sellers, JR Molloy, JE TI The gated gait of the processive molecular motor, myosin V SO NATURE CELL BIOLOGY LA English DT Article ID ACTIN; MOVEMENT; KINETICS; BINDING AB Class V myosins are actin-based molecular motors involved in vesicular and organellar transport. Single myosin V molecules move processively along F-actin, taking several 36-nm steps for each diffusional encounter. Here we have measured the mechanical interactions between mouse brain myosin V and rabbit skeletal F-actin. The working stroke produced by a myosin V head is similar to25 nm, consisting of two separate mechanical phases (20 + 5 nm). We show that there are preferred myosin binding positions (target zones) every 36 nm along the actin filament, and propose that the 36-nm steps of the double-headed motor are a combination of the working stroke (25 nm) of the bound head and a biased, thermally driven diffusive movement (11 nm) of the free head onto the next target zone. The second phase of the working stroke (5 nm) acts as a gate - like an escapement in a clock, coordinating the ATPase cycles of the two myosin V heads. This mechanism increases processivity and enables a single myosin V molecule to travel distances of several hundred nanometres along the actin filament. C1 Univ York, Dept Biol, York YO10 5YW, N Yorkshire, England. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Veigel, C (reprint author), Univ York, Dept Biol, POB 373, York YO10 5YW, N Yorkshire, England. NR 22 TC 266 Z9 269 U1 4 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2002 VL 4 IS 1 BP 59 EP 65 DI 10.1038/ncb732 PG 7 WC Cell Biology SC Cell Biology GA 513MC UT WOS:000173381500017 PM 11740494 ER PT J AU Liu, PT Jenkins, NA Copeland, NG AF Liu, PT Jenkins, NA Copeland, NG TI Efficient Cre-IoxP-induced mitotic recombination in mouse embryonic stem cells SO NATURE GENETICS LA English DT Article ID GENETIC MOSAICS; PRADER-WILLI; DROSOPHILA; MICE; SEGREGATION; CHROMOSOMES; REGION; MODEL AB FLP/FRT-induced mitotic recombination provides a powerful method for creating genetic mosaics in Drosophila and for discerning the function of recessive genes in a heterozygous individual. Here we show that mitotic recombination can be reproducibly induced in mouse embryonic stem (ES) cells, by Cre/loxP technology, at frequencies ranging from 4.2 x 10(-5) (Snrpn) to 7.0 x 10(-3) (D7Mit178) for single allelic loxP sites, and to 5.0 x 10(-2) (D7Mit178) for multiple allelic lox sites, after transient Cre expression. Notably, much of the recombination occurs in G2 and is followed by X segregation, where the recombinant chromatids segregate away from each other during mitosis. It is X segregation that is useful for genetic mosaic analysis because it produces clones of homozygous mutant daughter cells from heterozygous mothers. Our studies confirm the predictions made from studies in Drosophila(1) that suggest that X segregation will not be limited to organisms with strong mitotic pairing, because the forces (sister-chromatid cohesion) responsible for X segregation are an elemental feature of mitosis in all eukaryotes. Our studies also show that genetic mosaic analysis in mice is feasible, at least for certain chromosomal regions. C1 NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Copeland, NG (reprint author), NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. NR 31 TC 67 Z9 69 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2002 VL 30 IS 1 BP 66 EP 72 DI 10.1038/ng788 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 508TL UT WOS:000173105600015 PM 11740496 ER PT J AU Muegge, K AF Muegge, K TI Preparing the target for the bullet SO NATURE IMMUNOLOGY LA English DT Editorial Material ID CELL-DIFFERENTIATION; TRANSCRIPTION; CHROMATIN; INDUCTION C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, SAIC, Frederick, MD 21702 USA. RP Muegge, K (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, SAIC, Frederick, MD 21702 USA. NR 12 TC 19 Z9 19 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2002 VL 3 IS 1 BP 16 EP 17 DI 10.1038/ni0102-16 PG 2 WC Immunology SC Immunology GA 509LF UT WOS:000173148700009 PM 11753404 ER PT J AU Aliberti, J Hieny, S Sousa, CRE Serhan, CN Sher, A AF Aliberti, J Hieny, S Sousa, CRE Serhan, CN Sher, A TI Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity SO NATURE IMMUNOLOGY LA English DT Article ID DENDRITIC CELLS; TOXOPLASMA-GONDII; IFN-GAMMA; T-CELLS; INFLAMMATION; RESPONSES; INTERLEUKIN-12; MOBILIZATION; NEUTROPHILS; ACTIVATION AB Lipoxins are eicosanoid mediators that show potent inhibitory effects on the acute inflammatory process. We show here that the induction of lipoxin A(4) (LXA(4)) accompanied the In vivo suppression of interleukin 12 (IL-12) responsiveness of murine splenic dendritic cells (DCs) after microbial stimulation with an extract of Toxoplasma gondii. This paralysis of DC function could not be triggered in mice that were deficient in a key lipoxygenase involved in LXA4 biosynthesis. In addition, DCs pre-treated with LXA4 became refractory to microbial stimulation for IL-12 production In vitro and mice injected with a stable LXA(4) analog showed reduced splenic DC mobilization and IL-12 responses in vivo. Together, these findings indicate that the induction of lipoxins in response to microbial stimulation can provide a potent mechanism for regulating DC function during the innate response to pathogens. C1 Natl Inst Allergy & Infect Dis, Lab Parasit Dis, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. Imperial Canc Res Fund, Immunobiol Lab, London, England. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med,Ctr Expt T, Boston, MA USA. Imperial Canc Res Fund, Immunobiol Lab, London, England. Natl Allergy & Infect Dis, Lab Parasit Dis, Immunobiol Sect, NIH, Bethesda, MD USA. RP Aliberti, J (reprint author), Natl Inst Allergy & Infect Dis, Lab Parasit Dis, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 FU NIDCR NIH HHS [P01-DE13499]; NIGMS NIH HHS [GM-38765] NR 32 TC 179 Z9 190 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2002 VL 3 IS 1 BP 76 EP 82 DI 10.1038/ni745 PG 7 WC Immunology SC Immunology GA 509LF UT WOS:000173148700018 PM 11743584 ER PT J AU Schatzkin, A Gail, M AF Schatzkin, A Gail, M TI The promise and peril of surrogate end points in cancer research SO NATURE REVIEWS CANCER LA English DT Review ID HUMAN PAPILLOMAVIRUS INFECTION; CERVICAL INTRAEPITHELIAL NEOPLASIA; RECTAL MUCOSAL PROLIFERATION; RANDOMIZED CONTROLLED TRIAL; COLONIC EPITHELIAL-CELLS; POSTMENOPAUSAL WOMEN; BREAST-CANCER; COLORECTAL TUMORIGENESIS; HORMONE LEVELS; LOW-FAT AB Both experimental and observational studies of cancer need to have an end point. Traditionally, in aetiological and prevention studies, that end point has been the incidence of cancer itself, whereas in therapeutic trials, the end point is usually time to cancer recurrence or death. But cancer takes a long time to develop in an individual and is rare in the population. Therefore, aetiological studies and prevention trials must be large and lengthy to be meaningful. Similarly, many therapeutic trials require a long follow-up of large numbers of patients. Surrogate end points - markers of preclinical cancer or of imminent recurrence - are therefore an attractive alternative. But how can we be sure that a study with a surrogate outcome gives us the right answer about the true end point? C1 NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. RP Schatzkin, A (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. NR 54 TC 74 Z9 76 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2002 VL 2 IS 1 BP 19 EP 27 DI 10.1038/nrc702 PG 9 WC Oncology SC Oncology GA 635KH UT WOS:000180397700011 PM 11902582 ER PT J AU Gottesman, MM Fojo, T Bates, SE AF Gottesman, MM Fojo, T Bates, SE TI Multidrug resistance in cancer: Role of ATP-dependent transporters SO NATURE REVIEWS CANCER LA English DT Review ID ACUTE MYELOID-LEUKEMIA; P-GLYCOPROTEIN EXPRESSION; MDR1 GENE-EXPRESSION; CAUSE PSEUDOXANTHOMA ELASTICUM; BLOOD-BRAIN-BARRIER; HUMAN LUNG-CANCER; PHASE-I TRIAL; POTENT CYCLOPROPYLDIBENZOSUBERANE MODULATOR; FAMILIAL INTRAHEPATIC CHOLESTASIS; CASSETTE ABC TRANSPORTER AB Chemotherapeutics are the most effective treatment for metastatic tumours. However, the ability of cancer cells to become simultaneously resistant to different drugs - a trait known as multidrug resistance - remains a significant impediment to successful chemotherapy. Three decades of multidrug-resistance research have identified a myriad of ways in which cancer cells can elude chemotherapy, and it has become apparent that resistance exists against every effective drug, even our newest agents. Therefore, the ability to predict and circumvent drug resistance is likely to improve chemotherapy. C1 Ctr Canc Res, Lab Cell Biol & Canc Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), Ctr Canc Res, Lab Cell Biol & Canc Therapeut Branch, NIH, Bldg 37,Rm 1A09, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 165 TC 2759 Z9 2898 U1 76 U2 490 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2002 VL 2 IS 1 BP 48 EP 58 DI 10.1038/nrc706 PG 11 WC Oncology SC Oncology GA 635KH UT WOS:000180397700014 PM 11902585 ER PT J AU O'Shea, JJ Ma, A Lipsky, P AF O'Shea, JJ Ma, A Lipsky, P TI Cytokines and autoimmunity SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID T-CELLS; INTERFERON-BETA; SYSTEMIC LUPUS; SELF-TOLERANCE; CROHNS-DISEASE; GENETIC MODELS; TNF-ALPHA; INTERLEUKIN-2; SUSCEPTIBILITY; EXPRESSION AB Cytokines have crucial functions in the development, differentiation and regulation of immune cells. As a result, dysregulation of cytokine production or action is thought to have a central role in the development of autoimmunity and autoimmune disease. Some cytokines, such as interleukin-2, tumour-necrosis factor and interferons - ostensibly, the 'bad guys' in terms of disease pathogenesis - are well known for the promotion of immune and inflammatory responses. However, these cytokines also have crucial immunosuppressive functions and so, paradoxically, can also be 'good guys'. The balance between the pro-inflammatory and immunosuppressive functions of these well-known cytokines and the implications for the pathogenesis of autoimmune disease is the focus of this review. C1 NIAMSD, Lymphocyte Cell Biol Sect, Arthritis & Rheumat Branch, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. RP O'Shea, JJ (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Arthritis & Rheumat Branch, NIH, Bldg 10 Room 9N252,10 Ctr Dr,MSC-1820, Bethesda, MD 20892 USA. NR 47 TC 356 Z9 368 U1 4 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2002 VL 2 IS 1 BP 37 EP 45 DI 10.1038/nri702 PG 9 WC Immunology SC Immunology GA 635KP UT WOS:000180398300022 PM 11905836 ER PT J AU Goldstein, DS Katzper, M Linares, O Kopin, IJ AF Goldstein, DS Katzper, M Linares, O Kopin, IJ TI Kinetic model for the fate of 6-[F-18]fluorodopamine in the human heart: a novel means to examine cardiac sympathetic neuronal function SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE positron; fluorodopamine; sympathetic; norepinephrine; modeling ID INNERVATION; 6-FLUORODOPAMINE; NEUROTRANSMITTERS; METABOLISM; FAILURE AB After injection of 6-[F-18]fluorodopamine, thoracic positron emission tomographic scanning visualizes the sympathetic innervation of the heart. This report introduces a kinetic model that relates 6-[F-18]fluorodopamine positron emission tomographic scanning results to specific aspects of cardiac sympathoneural function. Inputs were the 6-[F-18]fluorodopamine concentration in arterial blood and the estimated contribution of circulating metabolites of 6-[F-18]fluorodopamine. All of the three compartments in the model were intraneuronal. Two compartments corresponded to vesicles in sympathetic nerves, consistent with the "multiple vesicular pool" hypothesis from preclinical studies. The model successfully fit the empirical time-activity curve for myocardial 6-[F-18]fluorodopamine-derived radioactivity and predicted correctly the effects of several neuropharmacological and physiological manipulations on the time-activity curve. Myocardial cell uptake of metabolites of 6-[F-18]fluorodopamine from the circulation could explain an immediate peak of 6-[F-18]fluorodopamine-derived radioactivity. The model seems useful in predicting effects of altered cardiac sympathetic function on time-activity curves for myocardial 6-[F-18]fluorodopamine-derived radioactivity in humans. C1 NINCDS, NIH, Bethesda, MD 20892 USA. NINCDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Goldstein, DS (reprint author), NINCDS, NIH, Bldg 10,Room 6N252,10 Ctr Dr MSC-1620, Bethesda, MD 20892 USA. NR 24 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD JAN PY 2002 VL 365 IS 1 BP 38 EP 49 DI 10.1007/s002100100426 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 510HP UT WOS:000173202900006 PM 11862332 ER PT J AU Roschke, AV Stover, K Tonon, G Schaffer, AA Kirsch, IR AF Roschke, AV Stover, K Tonon, G Schaffer, AA Kirsch, IR TI Stable karyotypes in epithelial cancer cell lines despite high rates of ongoing structural and numerical chromosomal instability SO NEOPLASIA LA English DT Article DE structural chromosomal instability; numerical chromosomal instability; karyotypic progression; spectral karyotyping (SKY); comparative genomic hybridization (CGH) ID CYTOGENETIC CHARACTERIZATION; COLORECTAL ADENOCARCINOMAS; INSITU HYBRIDIZATION; MISMATCH REPAIR; EVOLUTION; CARCINOGENESIS; ABNORMALITIES; AMPLIFICATION; ABERRATIONS; NEOPLASIA AB Most human tumors and tumor cell lines exhibit numerical and structural chromosomal abnormalities. The goal of this study was to determine the ongoing rates of structural and numerical instability in selected cancer cell lines and to investigate the consequences of these rates to karyotypic progression. We studied two colorectal (HCT-116 and HT-29) and two ovarian (SKOV-3 and OVCAR-8) cancer cell lines and their single cell subclones. We found that the signature karyotypes of all four cell lines were distinct and each aberrant. Whereas high rates of ongoing structural and/or numerical chromosomal instability could be demonstrated in all cell lines, there was a relative stability of the consensus karyotype over many generations. No new clonal structural chromosomal reconfigurations emerged and the few numerical changes of karyotypes were restricted to abnormal chromosomes. This implies a kind of genomic optimization under the conditions of cell culture and suggests a link between genomic stabilization and cell propagation. We have been able to support this possibility by computer modeling. We did not observe a profound difference in the rates of numerical or structural instability in the cell lines with a replication error phenotype (RER+) versus the other cell lines. C1 NCI, Genet Branch, Ctr Canc Res, NNMC, Bethesda, MD 20889 USA. NIH, Computat Biol Branch, Natl Biotechnol Ctr, Bethesda, MD 20892 USA. RP Kirsch, IR (reprint author), NCI, Genet Branch, Ctr Canc Res, NNMC, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. RI Schaffer, Alejandro/F-2902-2012 NR 34 TC 72 Z9 72 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JAN-FEB PY 2002 VL 4 IS 1 BP 19 EP 31 DI 10.1038/sj.neo.7900197 PG 13 WC Oncology SC Oncology GA 513ZU UT WOS:000173412000004 PM 11922387 ER PT J AU Jakubikova, J Duraj, J Hunakova, L Chorvath, B Sedlak, J AF Jakubikova, J Duraj, J Hunakova, L Chorvath, B Sedlak, J TI PK11195, an isoquinoline carboxamide ligand of the mitochondrial benzodiazepine receptor, increased drug uptake and facilitated drug-induced apoptosis in human multidrug-resistant leukemia cells in vitro SO NEOPLASMA LA English DT Article DE Benzodiazepine receptor ligand; PK11195; apoptosis; drug uptake; flow cytometry; DNA electrophoresis; MDR-1 multidrug resistance; human myeloid leukemia cells; human ovarian carcinoma cells ID HUMAN BREAST-CANCER; PERMEABILITY TRANSITION PORE; P-GLYCOPROTEIN; GLIOMA-CELLS; PROLIFERATION; EXPRESSION; INHIBITION; COMPLEXES; KINASE; LINES AB The isoquinoline peripheral benzodiazepine receptor ligand PK11195 increased drug (daunomycin)- and fluorochrome (calcein-AM) uptake and induced apoptosis detected by flow cytometry (FCM) technique, DNA electrophoretic analysis and poly(ADP-ribose) polymerase (PARP) cleavage in human multidrug-resistant myeloid leukemia (HL-60/VCR) and ovarian carcinoma (A2780/ADR) cells in vitro. The position of PK11195 with respect to drug-resistance modulator (DRM) efficiency, compared to the reference DRMs with the aid of FCM technique, was as follows: PSC833 > verapamil > PK11195 > vincristine. Our data show up to now not indicated observation that PK11195 possesses multidrug resistance modulating activity. C1 Slovak Acad Sci, Canc Res Inst, Bratislava 83391, Slovakia. NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Jakubikova, J (reprint author), Slovak Acad Sci, Canc Res Inst, Bratislava 83391, Slovakia. NR 30 TC 14 Z9 15 U1 0 U2 0 PU VEDA, SLOVAK ACADEMY SCIENCES PI BRASTISLAVA PA DUBRAVSKA CESTA 9, 842 34 BRASTISLAVA, SLOVAKIA SN 0028-2685 J9 NEOPLASMA JI Neoplasma PY 2002 VL 49 IS 4 BP 231 EP 236 PG 6 WC Oncology SC Oncology GA 596XK UT WOS:000178191600004 PM 12382020 ER PT J AU Meyer-Lindenberg, A AF Meyer-Lindenberg, A TI Neuroimaging of working memory in schizophrenia: new approaches SO NERVENHEILKUNDE LA German DT Article DE working memory; schizophrenia; functional connectivity; dopamine; prefrontal cortex ID DORSOLATERAL PREFRONTAL CORTEX; BRAIN; DYSFUNCTION; DOPAMINE; TRANSIENTS; HYPOTHESIS; DISORDER; RAT; PET AB New methodological approaches for analysing working memory in schizophrenia are reviewed. Working memory, clearly based in neurobiology and closely linked with the psychopathology and symptomatology of the disorder, is an especially attractive area of inquiry in biological psychiatry. After a brief summary of previous results, we discuss two recent results of our group demonstrating alterations in functionally linked networks during working memory in schizophrenia and the connection between frontal lobae activation and dopaminergic disinhibition. C1 NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Meyer-Lindenberg, A (reprint author), NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bldg 10,Room 4C 101,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 31 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0722-1541 J9 NERVENHEILKUNDE JI Nervenheilkunde PY 2002 VL 21 IS 7 BP 356 EP 362 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 596LE UT WOS:000178165700007 ER PT S AU Optican, LM Quaia, C AF Optican, LM Quaia, C BE Kaminski, HJ Leigh, RJ TI Distributed model of collicular and cerebellar function during saccades SO NEUROBIOLOGY OF EYE MOVEMENTS: FROM MOLECULES TO BEHAVIOR SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiology of Eye Movement - From Molecules to Behavior CY OCT 04-06, 2001 CL CASE WESTERN RESERVE UNIV, CLEVELAND, OHIO SP NY Acad Sci, Univ Hosp Cleveland, Evenor Armington Fund HO CASE WESTERN RESERVE UNIV DE saccades; control system; modeling; movement; brain; superior colliculus; cerebellum; vermis; fastigial nucleus ID MONKEY SUPERIOR COLLICULUS; NEURAL-NETWORK MODEL; EYE-MOVEMENTS; ALERT MONKEY; FASTIGIAL NUCLEUS; MOTOR CONTROL; GENERATION; NEURONS; MICROSTIMULATION; INACTIVATION AB How does the brain tell the eye where to go? Classical models of rapid eye movements are lumped control systems that compute analogs of physical signals such as desired eye displacement, instantaneous error, and motor drive. Components of these lumped models do not correspond well with anatomical and physiological data. We have developed a more brain-like, distributed model (called a neuromimetic model), in which the superior colliculus (SC) and cerebellum (CB) play novel roles, using information about the desired target and the movement context to generate saccades. It suggests that the SC Is neither sensory nor motor; rather it encodes the desired sensory consequence of the saccade in retinotopic coordinates. It also suggests a non-computational scheme for motor control by the cerebellum, based on context learning and a novel spatial mechanism, the pilot map. The CB learns to use contextual information to initialize the pilot signal that will guide the saccade to its goal. The CB monitors feedback information to steer and stop the saccade, and thus replaces the classical notion of a displacement integrator. One consequence of this model is that no desired eye movement signal is encoded explicitly in the brain; rather it is distributed across activity in both the SC and CB. Another Is that the transformation from spatially coded sensory information to temporally coded motor information is Implicit in the velocity feedback loop around the CB. No explicit spatial-to-temporal transformation with a normalization step is needed. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Univ Trieste, DEEI, I-34127 Trieste, Italy. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. NR 48 TC 41 Z9 42 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-394-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 956 BP 164 EP 177 PG 14 WC Multidisciplinary Sciences; Ophthalmology SC Science & Technology - Other Topics; Ophthalmology GA BU36T UT WOS:000175781500015 PM 11960802 ER PT S AU Goldberg, ME Bisley, J Powell, KD Gottlieb, J Kusunoki, M AF Goldberg, ME Bisley, J Powell, KD Gottlieb, J Kusunoki, M BE Kaminski, HJ Leigh, RJ TI The role of the lateral intraparietal area of the monkey in the generation of saccades and visuospatial attention SO NEUROBIOLOGY OF EYE MOVEMENTS: FROM MOLECULES TO BEHAVIOR SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Neurobiology of Eye Movement - From Molecules to Behavior CY OCT 04-06, 2001 CL CASE WESTERN RESERVE UNIV, CLEVELAND, OH SP NY Acad Sci, Univ Hosp Cleveland, Evenor Armington Fund HO CASE WESTERN RESERVE UNIV DE parietal; saccade; monkey; attention; salience ID POSTERIOR PARIETAL CORTEX; REPRESENTATION; NEURONS; MOVEMENTS; RESPONSES; SALIENCE; FIELDS; SPACE AB The brain cannot monitor or react towards the entire world at a given time. Instead, using the process of attention, it selects objects in the world for further analysis. Neuronal activity In the monkey intraparietal area has the properties appropriate for a neuronal substrate of attention: instead of all objects being represented in the parietal cortex, only salient objects are. Such objects can be salient because of their physical properties (recently flashed objects or moving objects) or because they can be made important to the animal by virtue of a task. Although lateral intraparietal area (LIP) neurons respond through the delay period of a memory-guided saccade, they also respond in an enhanced manner to distractors flashed during the delay period of a memory-guided saccade being generated to a position outside the receptive field. This activity parallels the monkey's psychophysical attentional process: attention is ordinarily pinned at the goal of a memory-guided saccade, but it shifts briefly to the locus of a task-irrelevant distractor flashed briefly during the delay period and then returns to the goal. Although neurons in LIP have been implicated as being directly involved in the generation of saccadic eye movements, their activity does not predict where, when, or if a saccade will occur. The ensemble of activity in LIP, however, does accurately describe the locus of attention. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. UCL, London WC1E 6BT, England. Columbia Univ, Ctr Neurobiol & Behav, Dept Neurol, David Mahoney Ctr Mind & Brain, New York, NY 10032 USA. Columbia Univ, Ctr Neurobiol & Behav, Dept Psychiat, David Mahoney Ctr Mind & Brain, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Goldberg, ME (reprint author), NEI, Sensorimotor Res Lab, 49 Convent Dr,Room 2A-50, Bethesda, MD 20892 USA. EM meg@lsr.nei.nih.gov OI Bisley, James/0000-0002-2841-0306 NR 20 TC 106 Z9 107 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-394-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 956 BP 205 EP 215 PG 11 WC Multidisciplinary Sciences; Ophthalmology SC Science & Technology - Other Topics; Ophthalmology GA BU36T UT WOS:000175781500018 PM 11960805 ER PT S AU Takemura, A Kawano, K Quaia, C Miles, FA AF Takemura, A Kawano, K Quaia, C Miles, FA BE Kaminski, HJ Leigh, RJ TI Population coding in cortical area MST SO NEUROBIOLOGY OF EYE MOVEMENTS: FROM MOLECULES TO BEHAVIOR SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiology of Eye Movement - From Molecules to Behavior CY OCT 04-06, 2001 CL CASE WESTERN RESERVE UNIV, CLEVELAND, OHIO SP NY Acad Sci, Univ Hosp Cleveland, Evenor Armington Fund HO CASE WESTERN RESERVE UNIV DE vergence eye movements; disparity-selective neurons; population coding ID VERGENCE EYE-MOVEMENTS; LATENCY DISPARITY VERGENCE; DIMENSIONAL ARM MOVEMENTS; PRIMATE MOTOR CORTEX; SUPERIOR COLLICULUS; FUNCTIONAL-PROPERTIES; DRAWING MOVEMENTS; VESTIBULOOCULAR REFLEX; BINOCULAR DISPARITY; RETICULAR-FORMATION AB Disparity steps applied to large patterns elicit vergence eye movements at ultrashort latencies. Disparity tuning curves, describing the dependence of the amplitude of the initial vergence responses on the amplitude of the disparity steps, resemble the derivative of a gaussian and indicate that appropriate servo-like behavior occurs only with small disparity steps (<1 degree). Lesion data from monkeys suggest that these vergence responses are mediated, at least in part, by neurons in the medial superior temporal area of the cerebral cortex, and we here review a recent study of the associated single unit activity in that area. Few medial superior temporal neurons have disparity tuning curves whose shapes resemble the tuning curve for vergence. Yet, when the disparity tuning curves for all of the disparity-sensitive cells recorded from a given monkey are summed together, they match the tuning curves for the vergence responses of that monkey very closely, even reproducing that animal's idiosyncracies. When all of the spike trains elicited by a given disparity step are summed together to give an average discharge profile for the whole population of recorded cells, many are noisy, but others that are less so match the temporal profile of the motor response, vergence velocity, quite well. We conclude that the discharges of the disparity-sensitive cells in the medial superior temporal area each represent only a very limited aspect of the sensory stimulus (and/or associated motor response?), but when pooled together, they provide a complete description of the vergence velocity motor response: population coding. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Adv Ind Sci & Technol, AIST, Neurosci Res Inst, Tsukuba, Ibaraki 3058568, Japan. Univ Trieste, Dipartimento Elettron Elettrotecn & Informat, I-34100 Trieste, Italy. RP Miles, FA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 51 TC 9 Z9 9 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-394-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 956 BP 284 EP 296 PG 13 WC Multidisciplinary Sciences; Ophthalmology SC Science & Technology - Other Topics; Ophthalmology GA BU36T UT WOS:000175781500025 PM 11960812 ER PT S AU Hertle, RW Maybodi, M Reed, GF Guerami, AH Yang, DS Fitzgibbona, EJ AF Hertle, RW Maybodi, M Reed, GF Guerami, AH Yang, DS Fitzgibbona, EJ BE Kaminski, HJ Leigh, RJ TI Latency of dynamic and gaze-dependent optotype recognition in patients with infantile nystagmus syndrome versus control subjects SO NEUROBIOLOGY OF EYE MOVEMENTS: FROM MOLECULES TO BEHAVIOR SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiology of Eye Movement - From Molecules to Behavior CY OCT 04-06, 2001 CL CASE WESTERN RESERVE UNIV, CLEVELAND, OHIO SP NY Acad Sci, Univ Hosp Cleveland, Evenor Armington Fund HO CASE WESTERN RESERVE UNIV DE dynamic optotype recognition; gaze-dependent optotype recognition; infantile nystagmus syndrome; visual acuity ID VISUAL-ACUITY; DEFICIENT C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NEI, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA. RP Hertle, RW (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. NR 4 TC 7 Z9 7 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-394-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 956 BP 601 EP 603 PG 3 WC Multidisciplinary Sciences; Ophthalmology SC Science & Technology - Other Topics; Ophthalmology GA BU36T UT WOS:000175781500092 PM 11960879 ER PT J AU Romero, SG Manly, CF Grafman, J AF Romero, SG Manly, CF Grafman, J TI Investigating cognitive neuroplasticity in single cases: Lessons learned from applying functional neuroimaging techniques to the traditional neuropsychological case study framework SO NEUROCASE LA English DT Article DE neuroplasticity; skill learning; functional magnetic resonance imaging; neuroimaging ID RIGHT-HEMISPHERE; METABOLIC ABNORMALITIES; CORTICAL PLASTICITY; ISCHEMIC STROKE; BRAIN; CORTEX; RECOVERY; REORGANIZATION; ACTIVATION; REHABILITATION AB We summarize two case studies as a context for discussing the use of neuroimaging as a convergent methodology in the study of neuroplasticity in single subjects. Throughout this paper we argue for a different approach for including neuroimaging in these types of study. Previous case studies of neuroplasticity in patients (ours as well as others reported elsewhere) have added neuroimaging to the traditional neuropsychological framework of comparing patient results with matched control groups, and synthesized results through descriptions of anatomical and behavioral dissociations. This type of approach is referred to as the comparison approach. We advocate a different approach that builds on findings from previous behavioral skill learning research. Specifically, we propose adding neuroimaging throughout learning or recovery of the ability of interest and making inferences from systematic changes in activation topography and intensity that occur within the context of predicted behavioral changes. We dub this approach the online approach. This approach should allow future investigators to circumvent many of the interpretation pitfalls that are common in comparison studies. 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. OI Grafman, Jordan H./0000-0001-8645-4457 NR 66 TC 3 Z9 3 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PY 2002 VL 8 IS 5 BP 355 EP 368 DI 10.1093/neucas/8.5.355 PG 14 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 636PX UT WOS:000180466100003 PM 12499410 ER PT J AU Kim, SY Jeitner, TM Steinert, PM AF Kim, SY Jeitner, TM Steinert, PM TI Transglutaminase in disease SO NEUROCHEMISTRY INTERNATIONAL LA English DT Review DE Transglutaminases; disease; Alzheimer's disease ID CATALYZED CROSS-LINKING; PAIRED HELICAL FILAMENTS; INCLUSION-BODY MYOSITIS; PROGRESSIVE SUPRANUCLEAR PALSY; AMINO-ACID SEQUENCE; KETOGLUTARATE DEHYDROGENASE COMPLEX; CONGENITAL RECESSIVE ICHTHYOSIS; AMYOTROPHIC-LATERAL-SCLEROSIS; DEPENDENT DIABETES-MELLITUS; ALPHA-SYNUCLEIN FRAGMENT AB Transglutaminases (TGases) are enzymes that are widely used in many biological systems for generic tissue stabilization purposes. Mutations resulting in lost activity underlie several serious disorders. In addition, new evidence documents that they may also be aberrantly activated in tissues and cells and contribute to a variety of diseases, including neuro degenerative diseases such as Alzheimer's and Huntington's diseases. In these cases, the TGases appear to be a factor in the formation of inappropriate proteinaceous aggregates that may be cytotoxic. In other cases such as celiac disease, however, TGases are involved in the generation of autoantibodies. Further, in diseases such as progressive supranuclear palsy, Huntington's, Alzheimer's and Parkinson's diseases, the aberrant activation of TGases may be caused by oxidative stress and inflammation. This review will examine the role and activation of TGases in a variety of diseases. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NIH, NIAMS, Skin Biol Lab, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Burke Med Res Inst, White Plains, NY 10605 USA. RP Kim, SY (reprint author), NIH, NIAMS, Skin Biol Lab, Bethesda, MD 20892 USA. FU NIA NIH HHS [P01 AG1930] NR 218 TC 114 Z9 119 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD JAN PY 2002 VL 40 IS 1 BP 85 EP 103 DI 10.1016/S0197-0186(01)00064-X PG 19 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 510UA UT WOS:000173224600010 PM 11738475 ER PT S AU Eskandari, F Sternberg, EM AF Eskandari, F Sternberg, EM BE Cutolo, M Bijlsma, JWJ Lahita, RG Masi, AT Straub, RH Bradlow, HL TI Neural-immune interactions in health and disease SO NEUROENDOCRINE IMMUNE BASIS OF THE RHEUMATIC DISEASES II, PROCEEDINGS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Conference on Neuroendocrine Immune Basis of the Rheumatic Diseases CY SEP 21-23, 2001 CL GENOA, ITALY SP Int Soc Neuroimmunomodulat, NY Acad Sci, German Soc Rheumatol, German Soc Clin Immunol, British Soc Rheumatol, Spanish Soc Rheumatol, Italian Soc Rheumatol, MURST, Univ Genova, Dept Internal Med, Sch Med, Abiogen Pharma SpA, Eli Lilly Italiana SpA, Fidia SpA, Wyeth Lederle, Ist Gentili, Sigma Tau SpA, Schering Plough SpA, Rudolf Schoen Fdn, Ravizza Farmaceut SpA, Procter & Gamble SRL, Merck Sharp & Dohme Italia DE neuroimmune; neuroendocrine; immune; hypothalamic-pituitary-adrenal axis ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; NORADRENERGIC SYMPATHETIC INNERVATION; VASOACTIVE-INTESTINAL-PEPTIDE; TO-BRAIN COMMUNICATION; CENTRAL-NERVOUS-SYSTEM; LEWIS RATS; SECRETION INVITRO; HETEROLOGOUS DESENSITIZATION; RHEUMATOID-ARTHRITIS AB Many lines of research have established the numerous routes by which the immune and central nervous systems (CNS) communicate. The CNS signals the immune system via hormonal and neuronal pathways and the immune system signals the CNS through similar routes via immune mediators and cytokines. The primary hormonal pathway by which the CNS regulates the immune system is the hypothalamic-pituitary-adrenal (HPA) axis, through the hormones of the neuroendocrine stress response. The sympathetic nervous system regulates immune system function primarily via adrenergic neurotransmitters released through neuronal routes. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. Glucocorticoids are the main effector endpoint of the neuroendocrine response system. C1 NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Integrat Neural Immune Program, NIH, Bldg 10,Rm 2D46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 73 TC 130 Z9 137 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-392-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 966 BP 20 EP 27 PG 8 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Rheumatology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Rheumatology GA BU83N UT WOS:000177157700004 PM 12114255 ER PT S AU Cid, MC Schnaper, HW Kleinman, HK AF Cid, MC Schnaper, HW Kleinman, HK BE Cutolo, M Bijlsma, JWJ Lahita, RG Masi, AT Straub, RH Bradlow, HL TI Estrogens and the vascular endothelium SO NEUROENDOCRINE IMMUNE BASIS OF THE RHEUMATIC DISEASES II, PROCEEDINGS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Conference on Neuroendocrine Immune Basis of the Rheumatic Diseases CY SEP 21-23, 2001 CL GENOA, ITALY SP Int Soc Neuroimmunomodulat, NY Acad Sci, German Soc Rheumatol, German Soc Clin Immunol, British Soc Rheumatol, Spanish Soc Rheumatol, Italian Soc Rheumatol, MURST, Univ Genova, Dept Internal Med, Sch Med, Abiogen Pharma SpA, Eli Lilly Italiana SpA, Fidia SpA, Wyeth Lederle, Ist Gentili, Sigma Tau SpA, Schering Plough SpA, Rudolf Schoen Fdn, Ravizza Farmaceut SpA, Procter & Gamble SRL, Merck Sharp & Dohme Italia DE estrogens; vascular endothelium; angiogenesis ID FIBROBLAST-GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ATHEROSCLEROTIC CORONARY-ARTERIES; SYSTEMIC LUPUS-ERYTHEMATOSUS; HORMONE-REPLACEMENT THERAPY; ACTIVATED PROTEIN-KINASE; SMOOTH-MUSCLE CELLS; POSTMENOPAUSAL WOMEN; RHEUMATOID-ARTHRITIS AB Estrogens exert important regulatory functions on vessel wall components, which may contribute to the increased prevalence and severity of certain chronic inflammatory and autoimmune diseases in females and the lower cardiovascular risk observed in premenopausal women. Endothelial cells have been recently identified as targets for estrogens, and estrogen receptors have been demonstrated in endothelial cells from various vascular beds. This review focuses on the regulatory function of estrogens in endothelial cell responses relevant to vessel inflammation, injury, and repair; estrogen effects on nitric oxide production and release; estrogen modulation of endothelial cell adhesion molecule expression; and estrogen regulation of angiogenesis. The mechanisms through which estrogen regulates endothelial cell functions are complex and involve both genomic and nongenomic mechanisms. C1 Univ Barcelona, Dept Internal Med, Hosp Clin, Inst Invest Biomed August Pi & Sunyer,IDIBAPS, E-08036 Barcelona, Spain. Northwestern Univ, Dept Pediat Nephrol, Chicago, IL 60611 USA. NIDR, Craniofacial Dev & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Cid, MC (reprint author), Univ Barcelona, Dept Internal Med, Hosp Clin, Inst Invest Biomed August Pi & Sunyer,IDIBAPS, Villarroel,170, E-08036 Barcelona, Spain. OI Cid Xutgla, Maria Cinta/0000-0002-4730-0938 FU NHLBI NIH HHS [R01 HL053918] NR 75 TC 80 Z9 84 U1 1 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-392-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 966 BP 143 EP 157 PG 15 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Rheumatology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Rheumatology GA BU83N UT WOS:000177157700017 PM 12114268 ER PT S AU Elenkov, IJ Chrousos, GP AF Elenkov, IJ Chrousos, GP BE Cutolo, M Bijlsma, JWJ Lahita, RG Masi, AT Straub, RH Bradlow, HL TI Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity SO NEUROENDOCRINE IMMUNE BASIS OF THE RHEUMATIC DISEASES II, PROCEEDINGS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Conference on Neuroendocrine Immune Basis of the Rheumatic Diseases CY SEP 21-23, 2001 CL GENOA, ITALY SP Int Soc Neuroimmunomodulat, NY Acad Sci, German Soc Rheumatol, German Soc Clin Immunol, British Soc Rheumatol, Spanish Soc Rheumatol, Italian Soc Rheumatol, MURST, Univ Genova, Dept Internal Med, Sch Med, Abiogen Pharma SpA, Eli Lilly Italiana SpA, Fidia SpA, Wyeth Lederle, Ist Gentili, Sigma Tau SpA, Schering Plough SpA, Rudolf Schoen Fdn, Ravizza Farmaceut SpA, Procter & Gamble SRL, Merck Sharp & Dohme Italia DE glucocorticoids; catecholamines; autoimmunity; inflammation; interleukin-12; interleukin-10, Th1cells, Th2 cells, rheumatoid arthritis; multiple sclerosis ID TUMOR-NECROSIS-FACTOR; CORTICOTROPIN-RELEASING HORMONE; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLLAGEN-INDUCED ARTHRITIS; INDUCED IL-12 PRODUCTION; MAST-CELL DEGRANULATION; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; HUMAN-MONOCYTES AB Recent evidence indicates that glucocorticolds and catecholamines, the major stress hormones, inhibit the production of proinflammatory cytokines, such as interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma, whereas they stimulate the production of antiinflammatory cytokines, such as IL-10, IL-4, and transforming growth factor (TGF)-beta. Thus, systemically, an excessive immune response, through activation of the stress system, stimulates an important negative feedback mechanism, which protects the organism from an "overshoot" of proinflammatory cytokines and other products of activated macrophages with tissue-damaging potential. Conversely, in certain local responses and under certain conditions, stress hormones actually may boost regional immune responses, through induction of TNF-alpha, IL-1, and IL-8, and by inhibiting TGF-beta production. Therefore, conditions that are associated with significant changes in stress system activity, such as acute or chronic stress, cessation of chronic stress, severe exercise, and pregnancy and the postpartum period, through modulation of the systemic or local pro/antiinflammatory cytokine balance, may suppress or potentiate autoimmune diseases activity and/or progression. C1 Georgetown Univ, Med Ctr, Div Rheumatol Allergy & Immunol, Washington, DC 20007 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Elenkov, IJ (reprint author), Georgetown Univ, Med Ctr, Div Rheumatol Allergy & Immunol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 74 TC 506 Z9 531 U1 5 U2 45 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-392-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 966 BP 290 EP 303 PG 14 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Rheumatology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Rheumatology GA BU83N UT WOS:000177157700035 PM 12114286 ER PT J AU Jafarian-Tehrani, M Sternberg, EM AF Jafarian-Tehrani, M Sternberg, EM TI Neuroendocrine-immune modulation of autoimmune/inflammatory diseases SO NEUROENDOCRINE-IMMUNE INTERACTIONS SE FRONTIERS OF HORMONE RESEARCH LA English DT Review ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING-FACTOR; SYMPATHETIC NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; STRESS DIFFERENTIALLY AFFECTS; NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; MESSENGER-RNA; LEWIS RATS C1 NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, Clin Neuroendocrinol Branch, NIH, Bldg 10,Rm 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 88 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 J9 FRONT HORM RES JI Front.Horm.Res. PY 2002 VL 29 BP 69 EP 82 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BU23U UT WOS:000175454300004 PM 11789349 ER PT J AU Husain, FT Nandipati, G Braun, AR Cohen, LG Tagamets, MA Horwitz, B AF Husain, FT Nandipati, G Braun, AR Cohen, LG Tagamets, MA Horwitz, B TI Simulating Transcranial magnetic stimulation during PET with a large-scale neural network model of the prefrontal cortex and the visual system SO NEUROIMAGE LA English DT Article ID HUMAN MOTOR CORTEX; CEREBRAL BLOOD-FLOW; WORKING-MEMORY; BRAIN-STIMULATION; HUMAN HAND; INHIBITION; NEURONS; CONNECTIVITY; RELEVANCE; RESPONSES AB Transcranial magnetic stimulation (TMS) exerts both excitatory and inhibitory effects on the stimulated neural tissue, although little is known about the neurobiological mechanisms by which it influences neuronal function. TMS has been used in conjunction with PET to examine interregional connectivity of human cerebral cortex. To help understand how TMS affects neuronal function, and how these effects are manifested during functional brain imaging, we simulated the effects of TMS on a large-scale neurobiologically realistic computational model consisting of multiple, interconnected regions that performs a visual delayed-match-to-sample task. The simulated electrical activities in each region of the model are similar to those found in single-cell monkey data, and the simulated integrated summed synaptic activities match regional cerebral blood flow (rCBF) data obtained in human PET studies. In the present simulations, the excitatory and inhibitory effects of TMS on both locally stimulated and distal sites were studied using simulated behavioral measures and simulated PET rCBF results. The application of TMS to either excitatory or inhibitory units of the model, or both, resulted in an increased number of errors in the task performed by the model. In experimental studies, both increases and decreases in rCBF following TMS have been observed. In the model, increasing TMS intensity caused an increase in rCBF when TMS exerted a predominantly excitatory effect, whereas decreased rCBF following TMS occurred if TMS exerted a predominantly inhibitory effect. We also found that regions both directly and indirectly connected to the stimulating site were affected by TMS. (C) 2002 Elsevier Science. C1 NIDCD, Language Sect, NIH, Bethesda, MD 20892 USA. NINCDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Funct Neuroimaging Lab, Baltimore, MD 21228 USA. RP Husain, FT (reprint author), NIDCD, Language Sect, NIH, Bldg 10,Room 6C420,MSC 1591,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 64 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN PY 2002 VL 15 IS 1 BP 58 EP 73 DI 10.1006/nimg.2001.0966 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 509XJ UT WOS:000173174900006 PM 11771974 ER PT J AU Birn, RM Cox, RW Bandettini, PA AF Birn, RM Cox, RW Bandettini, PA TI Detection versus estimation in event-related fMRI: Choosing the optimal stimulus timing SO NEUROIMAGE LA English DT Article DE event-related fMRI; detection; estimation; optimization ID FUNCTIONAL MRI; BRAIN ACTIVITY; MEMORIES; DESIGNS AB With the advent of event-related paradigms in functional MRI, there has been interest in finding the optimal stimulus timing, especially when the interstimulus interval is varied during the imaging run. Previous works have proposed stimulus timings to optimize either the estimation of the impulse response function (IRF) or the detection of signal changes. The purpose of this paper is to clarify that estimation and detection are fundamentally different goals and to determine the optimal stimulus timing and distribution with respect to both the accuracy of estimating the IRF and the power of detection assuming a particular hemodynamic model. Simulated stimulus distributions are varied systematically, from traditional blocked designs to rapidly varying event related designs. These simulations indicate that estimation of the hemodynamic impulse response function is optimized when stimuli are frequently alternated between task and control states, with shorter interstimulus intervals and stimulus durations, whereas the detection of activated areas is optimized by blocked designs. The stimulus timing for a given experiment should therefore be generated with the required detectability and estimation accuracy. (C) 2002 Elsevier Science. C1 NIMH, 3T Funct Neuroimaging Core, Bethesda, MD 20892 USA. NIMH, Sci & Stat Comp Core, Bethesda, MD 20892 USA. RP Birn, RM (reprint author), NIMH, 3T Funct Neuroimaging Core, Bethesda, MD 20892 USA. NR 23 TC 119 Z9 121 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN PY 2002 VL 15 IS 1 BP 252 EP 264 DI 10.1006/nimg.2001.0964 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 509XJ UT WOS:000173174900025 PM 11771993 ER PT J AU Gerrity, TR Bates, J Bell, DS Chrousos, G Furst, G Hedrick, T Hurwitz, B Kula, RW Levine, SM Moore, RC Schondorf, R AF Gerrity, TR Bates, J Bell, DS Chrousos, G Furst, G Hedrick, T Hurwitz, B Kula, RW Levine, SM Moore, RC Schondorf, R TI Chronic fatigue syndrome: What role does the autonomic nervous system play in the pathophysiology of this complex illness? SO NEUROIMMUNOMODULATION LA English DT Review DE chronic fatigue syndrome; autonomic nervous system; orthostatic hypotension; neuroendocrine system; immune system AB Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races and socioeconomic groups and both genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the autonomic nervous system (ANS). A symposium was organized in December 2000 to explore the possibility of an association between ANS dysfunction and CFS, with special emphasis on the interactions between ANS dysfunction and other abnormalities noted in the immune and endocrine systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting. Copyright (C) 2002 S. Karger AG, Basel. C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NIH, Bethesda, MD 20892 USA. Univ Miami, Miami, FL 33152 USA. Long Isl Coll Hosp, New York, NY USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. RP Gerrity, TR (reprint author), Care Of Walker Vicki, CFIDS Assoc Amer Inc, POB 220398, Charlotte, NC 28222 USA. NR 3 TC 20 Z9 20 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2002 VL 10 IS 3 BP 134 EP 141 DI 10.1159/000067176 PG 8 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 632UK UT WOS:000180241400003 PM 12481153 ER PT J AU Franchimont, D Kino, T Galon, J Meduri, GU Chrousos, G AF Franchimont, D Kino, T Galon, J Meduri, GU Chrousos, G TI Glucocorticoids and inflammation revisited: The state of the art SO NEUROIMMUNOMODULATION LA English DT Article DE glucocorticoids; cortisol; inflammation; HPA axis; DNA microarray; glucocorticoid resistance ID PITUITARY-ADRENAL AXIS; RESPIRATORY-DISTRESS SYNDROME; INHALED CORTICOSTEROID-THERAPY; NECROSIS-FACTOR-ALPHA; T-CELL DEVELOPMENT; KAPPA-B ACTIVITY; HUMAN MONOCYTES; SEPTIC SHOCK; RECEPTOR-BETA; IN-VITRO AB Glucocorticoids have been used in the treatment of inflammatory and autoimmune diseases and to prevent graft rejection for over 50 years. These hormones exert their effects through cytoplasmic, heat shock protein-bound glucocorticoid receptors that translocate into the nucleus, where they regulate the transcriptional activity of responsive genes by binding to specific promoter DNA sequences (transactivation) or by interacting with transcription factors (transrepression). By interacting with different signaling pathways, newly characterized nuclear receptor coregulators enhance or diminish the actions of glucocorticoids, thus explaining the gene-, cell-, tissue- and context-dependent actions of glucocorticoids. Glucocorticoids modulate genes involved in the priming of the innate immune response, while their actions on the adaptive immune response are to suppress cellular [T helper (Th)1-directed] immunity and promote humoral (Th2-directed) immunity and tolerance. The past decade has produced new insights into the mechanisms of glucocorticoid sensitivity and resistance of inflammatory, autoimmune and allergic diseases. Both the quality and severity of the inflammatory stimulus, as well as the genetics and constitution of the patient, play key roles in the glucocorticoid sensitivity, dependency and resistance of these diseases. Although glucocorticoids increase susceptibility to opportunistic infections, they are also highly beneficial in the presence of serious systemic inflammation, such as that observed in septic shock and acute respiratory distress syndrome, when administered in a sustained fashion throughout the course of the disease. Glucocorticoids produce their cardiovascular, metabolic and antigrowth side effects through molecular mechanisms distinct from those involved in immunomodulation. Fortunately, the first generation of tissue- and immune- versus cardiovascular/ metabolic effect-selective glucocorticoids is available for study and further improvement. 'Designer' glucocorticoids promise to be a great new advance in the therapy of inflammatory diseases. Copyright (C) 2003 S. Karger AG, Basel. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Erasme Univ Hosp, Gastroenterol Internal Med Dept, B-1070 Brussels, Belgium. Inst Curie, INSERM 255, Paris, France. Univ Tennessee, Ctr Hlth Sci, Div Pulm Med, Dept Med,Memphis Lung Res Progam, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Div Crit Care Med, Dept Med,Memphis Lung Res Progam, Memphis, TN 38163 USA. RP Franchimont, D (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 74 TC 32 Z9 35 U1 2 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2002 VL 10 IS 5 BP 247 EP 260 DI 10.1159/000069969 PG 14 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 681RR UT WOS:000183049600001 PM 12759562 ER PT B AU Hallett, M AF Hallett, M BE Battistin, L Dam, M Tonin, P TI Advances in stroke rehabilitation SO NEUROLOGICAL REHABILITATION, PROCEEDINGS LA English DT Proceedings Paper CT 3rd World Congress in Neurological Rehabilitation CY APR 02-06, 2002 CL VENICE, ITALY ID PERIPHERAL-NERVE STIMULATION; MOTOR RECOVERY; DOUBLE-BLIND; HAND; MOVEMENT; THERAPY; CORTEX; HUMANS; CELLS; GRASP AB Following hemiparetic stroke, recovery of motor function is often not adequate. There are now multiple approaches that seem promising for promoting recovery of the weakened limb, and they are often guided by new understandings of brain plasticity. Use of a body part enhances its function, as has been demonstrated, for example, by constraint-induced movement therapy. The ipsilateral hemisphere can contribute to motor control as demonstrated with bilateral, symmetical ann movement training. Sensory stimulation and reduction of inhibition enhances plasticity, and preliminary, evidence suggests that these can be efficacious. Pharmacological agents, such as amphetamine, may be useful. TMS has theoretical value. Spasticity can be reduced. Cortical activity can drive a prosthesis. Lost tissue might be replaced so the brain might be rewired. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-2402-4 PY 2002 BP 201 EP 206 AR UNSP C402R9036 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BU78A UT WOS:000176996900035 ER PT J AU Lee, J Chan, SL Mattson, MP AF Lee, J Chan, SL Mattson, MP TI Adverse effect of a presenilin-1 mutation in microglia results in enhanced nitric oxide and inflammatory cytokine responses to immune challenge in the brain SO NEUROMOLECULAR MEDICINE LA English DT Article DE Alzheimer's disease; amyloid; astrocytes; calcium; hippocampus; inflammation; interleukin-1; tumor necrosis factor; vaccine ID AMYLOID BETA-PEPTIDE; PROTECTS HIPPOCAMPAL-NEURONS; APP23 TRANSGENIC MICE; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; ALZHEIMERS-DISEASE; DIETARY RESTRICTION; MESSENGER-RNA; CORTICAL-NEURONS; SENILE PLAQUES AB Inflammatory processes involving glial cell activation are associated with amyloid plaques and neurofibrillary tangles, the cardinal neuropathological lesions in the brains of Alzheimer's disease (AD) patients, However, it is unclear whether these inflammatory processes occur as a response to neuronal degeneration or might represent more seminal events in the disease process. Some cases of AD are caused by mutations in presenilin-1 (PSI), and it has been shown that PSI mutations perturb neuronal calcium homeostasis, promote increased production of amyloid beta-peptide (Abeta), and render neurons vulnerable to synaptic dysfunction, excitotoxicity, and apoptosis. Although glial cells express PSI, it is not known if PSI mutations alter glial cell functions. We now report on studies of glial cells in PSI mutant knockin mice that demonstrate an adverse effect PSI mutations in microglial cells. Specifically, PSI mutant mice exhibit an enhanced inflammatory cytokine response to immune challenge with bacterial lipopolysaccharide (LPS). LPS-induced levels of mRNAs encoding tumor necrosis fctor-alpha (TNFalpha), interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist, and IL-6 are significantly greater in the hippocampus and cerebral cortex of PSI mutant mice as compared to wild-type mice. In contrast, the cytokine responses to LPS in the spleen is unaffected by the PSI mutation. Studies of cultured microglia from PSI mutant and wild-type mice reveal that PSI is expressed in microglia and that the PSI mutation confers a heightened sensitivity to LPS, as indicated by superinduction of inducible nitric oxide synthase (NOS) and activation of mitogen-activated protein kinase (MAPK). These findings demonstrate an adverse effect of PSI mutations on microglial cells that results in their hyper-activation under pro-inflammatory conditions, which may, together with direct effects of mutant PSI in neurons, contribute to the neurodegenerative process in AD. These findings also have important implications for development of a "vaccine" for the prevention or treatment of AD. C1 Natl Inst Aging Gerontol Res Ctr, Lab Neurosci, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), Natl Inst Aging Gerontol Res Ctr, Lab Neurosci, 5600 Nathan Shock Dr-4F 02, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013 NR 57 TC 68 Z9 69 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 2 IS 1 BP 29 EP 45 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 608VJ UT WOS:000178867600003 PM 12230303 ER PT J AU Chan, SL Furukawa, K Mattson, MP AF Chan, SL Furukawa, K Mattson, MP TI Presenilins and APP in neuritic and synaptic plasticity - Implications for the pathogenesis of Alzheimer's disease SO NEUROMOLECULAR MEDICINE LA English DT Review DE Alzheimer's disease; calcium; glutamate receptors; hippocampus; learning and memory; LTP; LTD ID AMYLOID-PRECURSOR PROTEIN; LONG-TERM POTENTIATION; GLYCOGEN-SYNTHASE KINASE-3-BETA; CAPACITATIVE CALCIUM-ENTRY; TRANSCRIPTION FACTOR LEF-1; NEURONAL CA2+ HOMEOSTASIS; CELL-ADHESION MOLECULES; HEPARIN-BINDING DOMAIN; HUMAN CORTICAL-NEURONS; HIPPOCAMPUS IN-VIVO AB A key neuropathological hallmark of Alzheimer's disease (AD) is the loss of neocortical and hippocampal synapses, which is closely correlated with the degree of memory impairment. Mutations in the genes encoding the amyloid precursor protein (APP) and presenilins are responsible from some cases of early-onset autosomal-dominant AD. This article reviews the current understanding of how alterations in the cellular functions of APP and presenilins may result in the dysfunction and degeneration of synapses in AD. APP mutations result in increased production/ aggregation of amyloid beta-peptide (Abeta), which induces oxidative stress, resulting in the impairment of synaptic membrane ion, glutamate, and glucose transporters. APP mutations may also compromise the production and/or function of secreted forms of APP that are believed to play important roles in learning and memory processes. Presenilin (PS1) mutations result in a major defect in endoplasmic reticulum (ER) calcium regulation, which may perturb synaptic function in ways that lead to impaired synaptic plasticity and neuronal degeneration. Studies in transgenic mice that express APP and PS1 mutations have provided evidence that the mutations result in altered cellular calcium homeostasis and synaptic plasticity, and impaired learning and memory. This article provides a brief review of the pathophysiological interactions of APP and presenilins with synaptic proteins, and discusses how AD-linked mutations in APP and PS1 may disrupt synaptic processes that contribute to memory formation. C1 NIA, Gerontol Res Ctr, Lab Neurosci, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Chan, SL (reprint author), NIA, Gerontol Res Ctr, Lab Neurosci, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 241 TC 45 Z9 50 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 2 IS 2 BP 167 EP 196 DI 10.1385/NMM:2:2:167 PG 30 WC Neurosciences SC Neurosciences & Neurology GA 610VL UT WOS:000178982100006 PM 12428810 ER PT J AU Gilman, CP Mattson, MP AF Gilman, CP Mattson, MP TI Do apoptotic mechanisms regulate synaptic plasticity and growth-cone motility? SO NEUROMOLECULAR MEDICINE LA English DT Review DE actin microfilaments; bax; calcium; caspase; growth cone; mitochondria; p53 tumor suppressor; Par-4 ID AMYLOID-PRECURSOR PROTEIN; P75 NEUROTROPHIN RECEPTOR; NF-KAPPA-B; CELL-ADHESION MOLECULES; LONG-TERM POTENTIATION; FACTOR AP-1 ACTIVATION; HIPPOCAMPAL-NEURONS; CALCIUM HOMEOSTASIS; NEURODEGENERATIVE DISORDERS; BETA-PEPTIDE AB Signals between neurons are transduced primarily by receptors, and second messenger and kinase cascades, located in pre- and postsynaptic terminals. Such synaptic signaling pathways include those activated by neurotransmitters, cytokines, neurotrophic factors, and cell-adhesion molecules. Many of these signaling systems are also localized in the growth cones of axons and dendrites, where they control pathfinding and synaptogenesis during development. Although it has been known for decades that such signaling pathways can affect the survival of neurons, by promoting or preventing a form of programmed cell death known as apoptosis, we have discovered that apoptotic biochemical cascades can exert local actions on the functions and structural dynamics of growth cones and synapses. In this article, we provide a brief background on apoptotic biochemical cascades, and present examples of studies in this laboratory that have identified novel apoptotic and anti-apoptotic signaling mechanisms that are activated and act locally in synapses, growth cones, and dendrites to modify their structure and function. Apoptotic synaptic cascades that may play roles in neuronal plasticity include activation of caspases that can cleave certain types of ionotropic glutamate-receptor subunits and thereby modify synaptic plasticity. Caspases may also cleave cytoskeletal protein substrates in growth cones of developing neurons and may thereby regulate neurite outgrowth. Par-4 and the tumor-suppressor protein p53 are pro-apoptotic proteins that may also function in synaptic and developmental plasticity. Examples of anti-apoptotic signals that regulate the plasticity of growth cones and synapses include neurotrophic factor-activated kinase cascades, calcium-mediated actin depolymerization, and activation of the transcription factor NF-kappaB. The emerging data strongly suggest that many of the signaling mechanisms that control apoptosis are also involved in regulating the structural and functional plasticity of neuronal circuits under physiological conditions. C1 NIA, Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 123 TC 83 Z9 88 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 2 IS 2 BP 197 EP 214 DI 10.1385/NMM:2:2:197 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 610VL UT WOS:000178982100007 PM 12428811 ER PT J AU Mattson, MP Liu, D AF Mattson, MP Liu, D TI Energetics and oxidative stress in synaptic plasticity and neurodegenerative disorders SO NEUROMOLECULAR MEDICINE LA English DT Review DE Alzheimer's; ATP; calcium; hippocampus; mitochondria; neurotrophic; Parkinson; superoxide ID LONG-TERM POTENTIATION; AMYLOID BETA-PEPTIDE; AMYOTROPHIC-LATERAL-SCLEROSIS; MEMBRANE LIPID-PEROXIDATION; MITOCHONDRIAL-FUNCTION; NITRIC-OXIDE; DIETARY RESTRICTION; GLUTAMATE TRANSPORT; PRECURSOR PROTEIN; HIPPOCAMPAL-NEURONS AB As in other cells, neurons use adenosine triphosphate (ATP) as an energy source to drive biochemical processes involved in various cell functions, and produce reactive oxygen species (ROS) as "by products" of oxidative phosphorylation. However, the electrical excitability and structural and synaptic complexity of neurons present unusual demands upon cellular systems that produce or respond to ATP and ROS. Mitochondria in axons and presynaptic terminals provide sources of ATP to drive the ion pumps that are concentrated in these structures to rapidly restore ion gradients following depolarization and neurotransmitter release. Mitochondria may also play important roles in the regulation of synaptic function because of their ability to regulate calcium levels and ROS production. ROS generated in response to synaptic activity are now known to contribute to the regulation of long-term structural and functional changes in neurons, and the best-known example is the nitric oxide radical. The high-energy demands of synapses, together with their high levels of ROS production, place them at risk during conditions of increased stress, which occur in aging, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, and after acute traumatic and ischemic insults. Energy depletion and/or increased oxidative damage to various synaptic proteins can result in a local dysregulation of calcium homeostasis and synaptic degeneration. Accordingly, recent studies have shown that dietary and pharmacological manipulations that improve energy efficiency and reduce oxyradical production can prevent synaptic degeneration and neuronal death in experimental models of neurodegenerative disorders. A better understanding of the molecular control of subcellular energy production and utilization, and of the functional relationships between energy metabolism, ion homeostasis, and cytoskeletal and vesicular dynamics, will provide novel insight into mechanisms of neuronal plasticity and disease. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 108 TC 134 Z9 137 U1 2 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 2 IS 2 BP 215 EP 231 DI 10.1385/NMM:2:2:215 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 610VL UT WOS:000178982100008 PM 12428812 ER PT J AU Cai, JL Rao, MS AF Cai, JL Rao, MS TI Stem cell and precursor cell therapy SO NEUROMOLECULAR MEDICINE LA English DT Review DE stem cells; progenitor cells; hematopoietic cells; neural stem cells; islet cells; replacement; repair; transplantation ID RAT SPINAL-CORD; CENTRAL-NERVOUS-SYSTEM; PROGENITOR CELLS; BONE-MARROW; NEURONAL DIFFERENTIATION; PARKINSONS-DISEASE; NEURAL PROGENITOR; DIABETES-MELLITUS; EMBRYONIC BRAIN; SCHWANN-CELLS AB Strategies for cell replacement therapy have been guided by the success in the hematopoietic stem cell field. In this review, we discuss the basis of this success and examine whether this stem cell transplant model can be replicated in other systems where stem cell therapy is being evaluated. We conclude that identifying the most primitive stem cell and using it for transplant therapy may not be appropriate in all systems. We suggest alternative strategies such as progenitor cell replacement, inductive factors, bioengineering organs, in utero transplants, or any approach that takes advantage of the unique properties of the tissue and the stem cell type which, are more likely to provide effective functional replacement. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Rao, MS (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 120 TC 12 Z9 14 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 2 IS 3 BP 233 EP 249 DI 10.1385/NMM:2:3:233 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 646AW UT WOS:000181013500001 PM 12622402 ER PT J AU Gary, DS Mattson, MP AF Gary, DS Mattson, MP TI PTEN regulates Akt kinase activity in hippocampal neurons and increases their sensitivity to glutamate and apoptosis SO NEUROMOLECULAR MEDICINE LA English DT Article DE Alzheimer's disease; epilepsy; kainic acid; seizures ID TUMOR-SUPPRESSOR PTEN; LHERMITTE-DUCLOS-DISEASE; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; NEGATIVE REGULATION; GERMLINE MUTATIONS; SOMA SIZE; SURVIVAL; EXPRESSION; GROWTH AB The tumor suppressor phosphatase PTEN can promote apoptosis of mitotic cells by inhibiting activation of the cell survival kinase Akt. PTEN is essential for normal embryonic development, PTEN expression is associated with neuronal differentiation, and deletion of PTEN in the mouse brain results in seizures, ataxia, and other abnormalities. However, the possible roles of PTEN in regulating neuronal survival are not known. We provide evidence that PTEN sensitizes hippocampal neurons to excitotoxic death in culture and in vivo. Overexpression of wildtype PTEN decreased, while a dominant-negative PTEN increased, levels of activated Akt in cultured hippocampal neurons. Wild-type PTEN promoted, while dominant-negative PTEN prevented, apoptotic death of neurons exposed to the excitatory amino acid neurotransmitter glutamate. Hippocampal neurons of mice with reduced PTEN levels were more resistant to seizure-induced death compared to wild-type littermates. These findings demonstrate a cell death function of PTEN in hippocampal neurons and identify PTEN as a potential therapeutic target for neurodegenerative disorders that involve excitotoxicity and apoptosis. The ability of PTEN to modify neuronal sensitivity to glutamate also suggests possible roles for PTEN in regulating developmental and synaptic plasticity. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 39 TC 51 Z9 57 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 2 IS 3 BP 261 EP 269 DI 10.1385/NMM:2:3:261 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 646AW UT WOS:000181013500003 PM 12622404 ER PT J AU Sambamurti, K Greig, NH Lahiri, DK AF Sambamurti, K Greig, NH Lahiri, DK TI Advances in the cellular and molecular biology of the beta-amyloid protein in Alzheimer's disease SO NEUROMOLECULAR MEDICINE LA English DT Review DE amyloid precursor protein; presenilin; BACE; Secretase; Abeta ID GAMMA-SECRETASE ACTIVITY; NECROSIS-FACTOR-ALPHA; MICROTUBULE-ASSOCIATED PROTEIN; DENSITY-LIPOPROTEIN RECEPTOR; PAIRED HELICAL FILAMENTS; PHOSPHOTYROSINE-BINDING DOMAIN; INSOLUBLE MEMBRANE COMPARTMENT; SHARE ANTIGENIC DETERMINANTS; FAMILIAL BRITISH DEMENTIA; MULTIPLE SYSTEM TAUOPATHY AB Alzheimer's disease (AD) is a progressive senile dementia characterized by deposition of a 4 kDa peptide of 39-42 residues known as amyloid beta-peptide (Abeta) in the form of senile plaques and the microtubule associated protein tau as paired helical filaments. Genetic studies have identified mutations in the Abeta precursor protein (APP) as the key triggers for the pathogenesis of AD. Other genes such as presenilins 1 and 2 (PS1/2) and apolipoprotein E (APOE) also play a critical role in increased Abeta deposition. Several biochemical and molecular studies using transfected cells and transgenic animals point to mechanisms by which Abeta is generated and aggregated to trigger the neurodegeneration that may cause AD. Three important enzymes collectively known as "secretases" participate in APP processing. An enzymatic activity, beta-secretase, cleaves APP on the amino side of Abeta producing a large secreted derivative, sAPPbeta, and an Abeta-bearing membrane-associated C-terminal derivative, CTFbeta, which is subsequently cleaved by the second activity, gamma-secretase, to release Abeta. Alternatively, a third activity, alpha-secretase, cleaves APP within Abeta to the secreted derivative sAPP(x and membrane-associated CTFalpha. The predominant secreted APP derivative is sAPPalpha. in most cell-types. Most of the secreted A is 40 residues long (Abeta40) although a small percentage is 42 residues in length (Abeta42). However, the longer Abeta42 aggregates more readily and was therefore considered to be the pathologically important form. Advances in our understanding of APP processing, trafficking, and turnover will pave the way for better drug discovery for the eventual treatment of AD. In addition, APP gene regulation and its interaction with other proteins may provide useful drug targets for AD. The emerging knowledge related to the normal function of APP will help in determining whether or not the AD associated changes in APP metabolism affect its function. The present review summarizes our current understanding of APP metabolism and function and their relationship to other proteins involved in AD. C1 Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. NIA, Drug Design & Dev Sect, Neurosci Lab, Baltimore, MD 21224 USA. Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. RP Sambamurti, K (reprint author), Mayo Clin, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. NR 318 TC 158 Z9 166 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 1 IS 1 BP 1 EP 31 DI 10.1385/NMM:1:1:1 PG 31 WC Neurosciences SC Neurosciences & Neurology GA 608UZ UT WOS:000178866400002 PM 12025813 ER PT J AU Chan, SL Pedersen, WA Zhu, HY Mattson, MP AF Chan, SL Pedersen, WA Zhu, HY Mattson, MP TI Numb modifies neuronal vulnerability to amyloid beta-peptide in an isoform-specific manner by a mechanism involving altered calcium homeostasis - Implications for neuronal death in Alzheimer's disease SO NEUROMOLECULAR MEDICINE LA English DT Article DE apoptosis; calcium; learning and memory; neurotrophic factor; NMDA; patch clamp; staurosporine ID PHOSPHOTYROSINE-BINDING DOMAIN; MEMBRANE LIPID-PEROXIDATION; MOUSE CORTICAL NEUROGENESIS; TROPHIC FACTOR WITHDRAWAL; HIPPOCAMPAL-NEURONS; MAMMALIAN NUMB; INDUCED APOPTOSIS; OXIDATIVE STRESS; NEURODEGENERATIVE DISORDERS; MITOCHONDRIAL DYSFUNCTION AB Increased production of neurotoxic forms of amyloid beta-peptide (Abeta) and abnormalities in neuronal calcium horneostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch, a membrane receptor that controls cell-fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase enzyme activity that involves the presenilin-1 (PS1) protein in which mutations cause early-onset inherited AD. The actions of Notch can be antagonized by Numb, an evolutionarily conserved protein that exists in four isoforms that differ in two functional domains: a phosphotyrosine-binding (PTB) domain and a proline-rich region (PRR). We now report that Numb isoforms containing a short PTB domain increase the vulnerability of PC12 cells to death induced by Abeta1-42 and by 4-hydroxynonenal, a lipid peroxidation product previously shown to mediate neurotoxic effects of Abeta. Dysregulation of cellular calcium homeostasis occurs in cells expressing Numb isoforms with a short PTB domain, and the death-promoting effect of Numb is abolished by pharmacological inhibition of calcium release. The levels of Numb are increased in cultured primary hippocampal neurons exposed to Abeta, suggesting a role for endogenous Numb in the neuronal death process. Furthermore, higher levels of Numb were detected in the cortex of mice expressing mutant amyloid precursor protein (APP) relative to age-matched wild-type mice. Our data identify a novel isoform-specific effect of Numb on neuronal life and death cell fate decisions potentially relevant to the pathogenesis of AD. Our findings also suggest that the effects of Numb on cell fate decisions, both during development of the nervous system and in neurode-genertive disorders, are mediated by changes in cellular calcium homeostasis. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 55 TC 23 Z9 25 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 1 IS 1 BP 55 EP 67 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 608UZ UT WOS:000178866400005 PM 12025816 ER PT J AU Lu, CB Fu, WM Salvesen, GS Mattson, MP AF Lu, CB Fu, WM Salvesen, GS Mattson, MP TI Direct cleavage of AMPA receptor subunit GluR1 and suppression of AMPA currents by caspase-3 - Implications for synaptic plasticity and excitotoxic neuronal death SO NEUROMOLECULAR MEDICINE LA English DT Article DE apoptosis; calcium; learning and memory; neurotrophic factor; NMDA; patch clamp; staurosporine ID HIPPOCAMPAL-NEURONS; CELL-DEATH; OXIDATIVE STRESS; NEURODEGENERATIVE DISORDERS; MEDIATED DEGRADATION; SIGNALING PATHWAYS; CEREBRAL-ISCHEMIA; ENERGY-METABOLISM; NERVOUS-SYSTEM; MESSENGER-RNA AB Cysteine proteases of the caspase family play central roles in excecuting the cell death process in neurons during development of the nervous system and in neurodegenerative disorders. Recent findings suggest that caspases may also play roles in modulating neuronal plasticity in the absence of cell death. We previously reported that caspases can be activated in dendrites and synapses in response to activation of glutamate receptors. In the present study we demonstrate that the GluR1 subunit of the AMPA subtype of glutamate receptor is directly cleaved by caspase-3, and provide evidence that the cleavage of this subunit modulates neuronal excitability in ways that suggest important roles for caspases in regulating synaptic plasticity and cell survival. Whole-cell patch-clamp recordings in cultured rat hippocampal neurons showed that caspase activation in response to apoptotic stimuli selectively decreases AMPA channel activity without decreasing NMDA channel activity. Perfusion of neurons with recombinant caspase-3 resulted in a decreased AMPA current, demonstrating that caspase-3 activity is sufficient to suppress neuronal responses to glutamate. Exposure of radiolabeled GluR1 to recombinant caspase-3 resulted in cleavage of GluR1, demonstrating that this glutamate receptor protein is a direct substrate of this caspase. Our findings suggest roles for caspases in the modulation of neuronal excitability in physiological settings, and also identify a mechanism whereby caspases ensure that neurons die by apoptosis rather than excitotoxic necrosis in developmental and pathological settings. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Burnham Inst, La Jolla, CA 92037 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 49 TC 47 Z9 49 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 1 IS 1 BP 69 EP 79 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 608UZ UT WOS:000178866400006 PM 12025817 ER PT J AU Cole, NB Murphy, DD AF Cole, NB Murphy, DD TI The cell biology of alpha-synuclein - A sticky problem? SO NEUROMOLECULAR MEDICINE LA English DT Review DE Parkinson's disease; synuclein; synapse; lipids; oligomerization; degradation ID A-BETA COMPONENT; RECESSIVE JUVENILE PARKINSONISM; UBIQUITIN-PROTEIN LIGASE; CHAPERONE-LIKE ACTIVITY; CENTRAL-NERVOUS-SYSTEM; ACID-BINDING PROTEINS; LEWY BODY DISEASE; ALZHEIMERS-DISEASE; SELF-OLIGOMERIZATION; PRECURSOR PROTEIN AB Parkinson's disease (PD) is the most common neurodegenerative motor disorder, marked by chronic progressive loss of neurons in the substantia nigra, thereby damaging purposeful control of movement. For decades, it was believed that PD was caused solely by environmental causes. However, the discovery of genetic factors involved in PD has revolutionized our attempts to understand the disease's pathology. PD now appears to be more polygenetic than previously thought and is most likely caused by a complex interaction of genetic risks and environmental exposures. The first gene found to be mutated in PD encodes for the presynaptic protein alpha-synuclein, which is also a major component of Lewy bodies and Lewy neurites, the neuropathological hallmarks of the disease. While these findings provide a classic example of how rare genetic mutations in disease can point to important pathways in idiopathic disease pathologies, much of the study of alpha-synuclein has focused on understanding how this protein undergoes the transition from an unfolded monomer to amorphous aggregates or Lewy body-like filaments rather than addressing what its fundamental function might be. Since alterations in synuclein function may predispose to the disease pathology of PD, regardless of the presence of genetic mutations, a more thorough understanding of the cellular regulation and function of alpha-synuclein may be of crucial importance to our understanding of this degenerating disorder. C1 NHGRI, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. RP Cole, NB (reprint author), NHGRI, Bethesda, MD 20892 USA. NR 128 TC 21 Z9 23 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 1 IS 2 BP 95 EP 109 DI 10.1385/NMM:1:2:95 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 608VG UT WOS:000178867400001 PM 12025860 ER PT J AU Haughey, NJ Liu, D Nath, A Borchard, AC Mattson, MP AF Haughey, NJ Liu, D Nath, A Borchard, AC Mattson, MP TI Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide - Implications for the pathogenesis of Alzheimer's disease SO NEUROMOLECULAR MEDICINE LA English DT Article DE apoptosis; bromodeoxyuridine; calcium; learning and memory; olfactory; stem cells; subventricular zone ID DENTATE GYRUS; HIPPOCAMPAL-NEURONS; OXIDATIVE STRESS; TRANSGENIC MICE; NEURODEGENERATIVE DISORDERS; ENRICHED ENVIRONMENT; PERFORANT PATH; OLFACTORY-BULB; STEM-CELLS; PROLIFERATION AB The adult mammalian brain contains populations of stem cells that can proliferate and then differentiate into neurons or glia. The highest concentration of such neural progenitor cells (NPC) is located in the subventricular zone (SVZ) and these cells can produce new olfactory bulb and cerebral cortical neurons. NPC may provide a cellular reservoir for replacement of cells lost during normal cell turnover and after brain injury. However, neurogenesis does not compensate for neuronal loss in age-related neurodegenerative disorders such as Alzheimer's disease (AD), suggesting the possibility that impaired neurogenesis contributes to the pathogenesis of such disorders. We now report that amyloid beta-peptide (Abeta), a self-aggregating neurotoxic protein thought to cause AD, can impair neurogenesis in the SVZ/cerebral cortex of adult mice and in human cortical NPC in culture. The proliferation and migration of NPC in the SVZ of amyloid precursor protein (APP) mutant mice, and in mice receiving an intraventricular infusion of Abeta, were greatly decreased compared to control mice. Studies of NPC neurosphere cultures derived from human embryonic cerebral cortex showed that Abeta can suppress NPC proliferation and differentiation, and can induce apoptosis. The adverse effects of Abeta on neurogenesis were associated with a disruption of calcium regulation in the NPC. Our data show that Abeta can impair cortical neurogenesis, and suggest that this adverse effect of Abeta contributes to the depletion of neurons and the resulting olfactory and cognitive deficits in AD. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 54 TC 142 Z9 163 U1 3 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 1 IS 2 BP 125 EP 135 DI 10.1385/NMM:1:2:125 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 608VG UT WOS:000178867400003 PM 12025858 ER PT B AU Wray, S AF Wray, S BE Handa, RJ Hayashi, S Terasawa, E Kawata, M TI Migration of luteinizing hormone-releasing hormone (LHRH) neurons: The road to reproductive function SO NEUROPLASTICITY, DEVELOPMENT, AND STEROID HORMONE ACTION LA English DT Proceedings Paper CT US/Japan Bilateral Symposium on Neuroplasticity, Development, and Steroid Hormone Action CY SEP, 2000 CL HONOLULU, HI SP Natl Sci Fdn, Japan Soc Promot Sci, NIH, Zenyaku Kogyo Co Ltd, Chugai Pharmaceut Co Ltd, Taisho Pharmaceut Co Ltd ID CELL-ADHESION MOLECULE; EMBRYONIC OLFACTORY PLACODE; MEDIAL BASAL HYPOTHALAMUS; CHICK-EMBRYO; RHESUS-MONKEY; EXPLANT CULTURES; DEVELOPING MOUSE; POLYSIALIC ACID; GNRH NEURONS; NASAL REGION C1 NINCDS, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINCDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 54 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 0-8493-0962-X PY 2002 BP 9 EP 19 PG 11 WC Biology; Endocrinology & Metabolism; Neurosciences SC Life Sciences & Biomedicine - Other Topics; Endocrinology & Metabolism; Neurosciences & Neurology GA BS93P UT WOS:000171437900002 ER PT J AU Lamar, M Price, CC Davis, KL Kaplan, E Libon, DJ AF Lamar, M Price, CC Davis, KL Kaplan, E Libon, DJ TI Capacity to maintain mental set in dementia SO NEUROPSYCHOLOGIA LA English DT Article DE Alzheimer's disease; vascular dementia; executive functions; frontal lobe functioning ID ISCHEMIC VASCULAR DEMENTIA; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; WORKING-MEMORY; IMPAIRMENT; DIAGNOSIS; FLUENCY AB Two experiments investigating the capacity to sustain mental set in dementia were conducted. Experiment 1 analyzed performance of a non-demented control group (NC), participants with Alzheimer's disease (AD) and participants with ischemic vascular dementia (IVD) on the Boston Revision of the Wechsler Memory Scale Mental Control subtest (MC). On simple tasks there were no between-group differences after controlling for time to completion. On complex tasks, NC participants outperformed both dementia groups and AD participants obtained higher accuracy indices than IVD participants. The IVD group produced a disproportionate number of commission errors regardless of task complexity. The AD group tended to produce more omission errors on more difficult measures of mental set. Individual task performance was divided into three sections-first, middle, and last. IVD participants made fewer and fewer correct responses over all three sections, whereas performance of AD participants leveled off by the middle section with no further decline. Experiment 2 compared letter fluency performance among NC, AD and IVD groups, and participants with dementia secondary to idiopathic Parkinson's disease (PD). For all letter cues, IVD and PD participants generated fewer responses than NC and AD participants. However, IVD and PD participants generated a larger proportion of words than AD and NC participants within the first 15 s. As the task progressed, the output of IVD and PD participants dropped precipitously. These findings indicate that failure to maintain mental set is not a diffuse or general cognitive disability. Rather, failure to maintain mental set in dementia may be best understood within the context of predictable and specific within-task time epochs. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Drexel Univ, Neuropsychol Program, Philadelphia, PA 19103 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Crozer Chester Med Ctr, Neuropsychol Serv, Upland, PA 19013 USA. Boston Univ, Med Ctr, Dept Neurol, Boston, MA USA. Boston Univ, Med Ctr, Dept Psychiat, Boston, MA USA. Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. Med Coll Penn & Hahnemann Univ, Dept Psychiat, Philadelphia, PA 19103 USA. RP Libon, DJ (reprint author), Drexel Univ, Neuropsychol Program, Philadelphia, PA 19103 USA. NR 29 TC 54 Z9 56 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2002 VL 40 IS 4 BP 435 EP 445 DI 10.1016/S0028-3932(01)00125-7 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 507XH UT WOS:000173056200007 PM 11684176 ER PT J AU Maki, PM Rich, JB Rosenbaum, RS AF Maki, PM Rich, JB Rosenbaum, RS TI Implicit memory varies across the menstrual cycle: estrogen effects in young women SO NEUROPSYCHOLOGIA LA English DT Article DE estrogen; menstrual cycle; cognition; memory; mood ID CEREBRAL BLOOD-FLOW; REPLACEMENT THERAPY; COGNITIVE FUNCTION; WORKING-MEMORY; POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE; STEROID-HORMONES; MENOPAUSAL WOMEN; EXPLICIT MEMORY; SEX-DIFFERENCES AB Evidence that ovarian steroid hormones such as estrogen and progesterone affect cognition comes front studies of memory in older women receiving estrogen replacement therapy and studies of sexually dimorphic skills in young women across the menstrual cycle. Sixteen women (ages 18-28) completed tests of memory (implicit category exemplar generation, category-cued recall, implicit fragmented object identification) and sexually dimorphic skills (fine motor coordination, verbal fluency, mental rotations) at the early follicular (low estrogen and progesterone) and midluteal (high estrogen and progesterone) phases of the menstrual cycle. Performance on category exemplar generation, a test of conceptual implicit memory, was better at the midluteal than the follicular phase. In contrast, performance on a test of explicit memory, category-cited recall, did not vary across the menstrual cycle. At Session 1, women in the follicular phase performed better on the fragmented object identification task than did those in the midluteal phase. This unexpected finding suggests that high levels of ovarian hormones might inhibit perceptual object priming. Results confirmed previous reports of decreased mental rotations and improved motor skills and fluency in the midluteal phase. Estradiol levels correlated positively with verbal fluency and negatively with mental rotations and perceptual priming, which suggest that estrogen. and not progesterone. was responsible for the observed changes in cognition. Mood did not vary across the cycle phases. Overall, the findings suggest that estrogen may facilitate the automatic activation of verbal representations in memory. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, Baltimore, MD 21224 USA. York Univ, Dept Psychol, Toronto, ON M3J 2R7, Canada. RP Maki, PM (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 54 TC 159 Z9 163 U1 3 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2002 VL 40 IS 5 BP 518 EP 529 DI 10.1016/S0028-3932(01)00126-9 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 517ZZ UT WOS:000173642400006 PM 11749982 ER PT J AU Mitchell, DGV Colledge, E Leonard, A Blair, RJR AF Mitchell, DGV Colledge, E Leonard, A Blair, RJR TI Risky decisions and response reversal: is there evidence of orbitofrontal cortex dysfunction in psychopathic individuals? SO NEUROPSYCHOLOGIA LA English DT Article DE decision-making; gambling task; risk; response inhibition; intradimensional/extradimensional shifts; response modulation ID VENTROMEDIAL PREFRONTAL CORTEX; FACIAL EXPRESSIONS; CRIMINAL PSYCHOPATHS; BASOLATERAL AMYGDALA; NEURAL RESPONSES; STARTLE REFLEX; DISTRESS CUES; EMOTION; DAMAGE; TENDENCIES AB This study investigates the performance of psychopathic individuals on tasks believed to be sensitive to dorsolateral prefrontal and orbitofrontal cortex (OFC) functioning. Psychopathic and non-psychopathic individuals, as defined by the Hare psychopathy checklist revised (PCL-R) [Hare, The Hare psychopathy checklist revised, Toronto, Ontario: Multi-Health Systems, 1991] completed a gambling task [Cognition 50 (1994) 7] and the intradimensional/extradimensional (ID/ED) shift task [Nature 380 (1996) 69]. On the gambling task, psychopathic participants showed a global tendency to choose disadvantageously. Specifically, they showed an impaired ability to show learning over the course of the task. On the ID/ED task, the performance of psychopathic individuals was not significantly different from incarcerated controls on attentional set-shifting, but significant impairments were found on response reversal. These results are interpreted with reference to an OFC and amygdala dysfunction explanation of psychopathy. Crown Copyright (C) 2002 Published by Elsevier Science Ltd. All rights reserved. C1 HMP Wormwood Scrubs, Dept Psychol, London, England. UCL, Dept Psychol, London, England. UCL, Inst Cognit Neurosci, London, England. RP Blair, RJR (reprint author), NIMH, 15 K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 71 TC 197 Z9 200 U1 9 U2 50 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2002 VL 40 IS 12 BP 2013 EP 2022 AR PII S0028-3932(02)00056-8 DI 10.1016/S0028-3932(02)00056-8 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 601AJ UT WOS:000178423700016 PM 12207998 ER PT J AU Rosen, VM Bergeson, JL Putnam, K Harwell, A Sunderland, T AF Rosen, VM Bergeson, JL Putnam, K Harwell, A Sunderland, T TI Working memory and apolipoprotein E: What's the connection? SO NEUROPSYCHOLOGIA LA English DT Article DE Alzheimer; APOE; working memory; central executive; divided attention; primacy ID SHORT-TERM-MEMORY; ALZHEIMERS-DISEASE; DIVIDED ATTENTION; EPSILON-4 ALLELE; E POLYMORPHISM; OLDER ADULTS; E GENOTYPE; DEMENTIA; RETRIEVAL; DECLINE AB Two robust findings in the Alzheimer's literature are that patients with Alzheimer's disease (AD) show executive function and primacy deficits. The present study examined whether we would find similar deficits when comparing two groups of middle-aged individuals who differed with respect to genetic risk for AD, based on their apolipoprotein E (APOE) genotype. All individuals were screened as normal on a battery of standardized cognitive measures. They were tested on the "Operation span task", which engages the central executive component of working memory [J. Exp. Psychol.: Gen. 128 (1999) 309, J. Exp. Psychol.: Gen. 126 (1997) 211, J. Mem. Language 39 (1998) 418] by dividing attention between processing math operations and remembering words. Individuals were grouped according to APOE genotype (64 carrier versus epsilon4 non-carrier), matched on age and education, and their Total span and Primacy scores were compared. Despite having no overt symptoms of dementia or deficits on a series of standardized psychometric tests, the epsilon4 carriers showed divided-attention and primacy deficits on the Operation span task, when compared to the epsilon4 non-carriers. As a point of comparison, Primacy scores were extracted from the first trial of the "Buschke selective reminding task" [J. Verbal Learn. Verbal Behav. 12 (1973) 543] for these same individuals, and no group differences were found. The Buschke task is a list-learning task that does not require divided attention. These findings suggested that the epsilon4 carriers were less able to divide their attention, when compared to the epsilon4 non-carriers. The findings provide the first direct evidence for a relationship between APOE genotype and cognitive performance on measures of divided attention and primacy with non-demented individuals who showed no cognitive impairments on standardized measures. Published by Elsevier Science Ltd. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Rosen, VM (reprint author), NIMH, Geriatr Psychiat Branch, 10 Ctr Dr,Bldg 10,Room 3N228, Bethesda, MD 20892 USA. NR 61 TC 73 Z9 77 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2002 VL 40 IS 13 BP 2226 EP 2233 AR PII S0028-3932(02)00132-X DI 10.1016/S0028-3932(02)00132-X PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 623RH UT WOS:000179716300003 PM 12417453 ER PT J AU Breier, JI Gray, LC Klaas, P Fletcher, JM Foorman, B AF Breier, JI Gray, LC Klaas, P Fletcher, JM Foorman, B TI Dissociation of sensitivity and response bias in children with attention deficit/hyperactivity disorder during central auditory masking SO NEUROPSYCHOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; SPEECH-PERCEPTION; DYSLEXIC ADULTS; SUSTAINED ATTENTION; PROCESSING DISORDER; DISCRIMINATION; ADHD; DISABILITIES; MEMORY; ADD AB Forty-three children (ages 7.0-14.5 years old) with and without attention deficit/hyperactivity disorder (ADHD), combined type had thresholds for detection of a 500-Hz pure tune estimated with and without a noise masker in the contralateral ear. The ear receiving the signal in the masked condition was varied randomly. A single-interval maximum-likelihood method estimated thresholds and false-alarm rate. Whereas the increase in threshold in children with ADHD in the presence of contralateral masking was comparable with controls, the increase in false-alarm rate was significantly greater. This dissociation between changes in sensitivity and response bias. in the presence of masking noise supports suggestions that children with ADHD have difficulty inhibiting maladaptive responses and indicates that this deficit is quantifiable using psychoacoustic methods. C1 Univ Texas, Sch Med, Dept Neurosurg, Hlth Sci Ctr, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Dept Otolaryngol, Houston, TX USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Med Illness Counseling Ctr, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, Houston, TX 77225 USA. RP Breier, JI (reprint author), Univ Texas, Sch Med, Dept Neurosurg, Hlth Sci Ctr, 6431 Fannin,Suite 7-148, Houston, TX 77030 USA. FU NICHD NIH HHS [1 R01 HD35938] NR 59 TC 11 Z9 11 U1 9 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2002 VL 16 IS 1 BP 28 EP 34 DI 10.1037//0894-4105.16.1.28 PG 7 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 520RK UT WOS:000173794700004 PM 11853354 ER PT J AU Tedeschi, G Bonavita, S McFarland, HF Richert, N Duyn, JH Frank, JA AF Tedeschi, G Bonavita, S McFarland, HF Richert, N Duyn, JH Frank, JA TI Proton MR spectroscopic imaging in multiple sclerosis SO NEURORADIOLOGY LA English DT Article DE proton magnetic resonance spectroscopy; multiple sclerosis ID MAGNETIC-RESONANCE SPECTROSCOPY; APPEARING WHITE-MATTER; IN-VIVO; N-ACETYLASPARTATE; AXONAL DAMAGE; METABOLIC ALTERATIONS; RAT-BRAIN; LESIONS; PATHOLOGY; DISABILITY AB We studied 24 patients with multiple sclerosis (MS) by proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess the neurochemical pathology of the white-matter lesions (WML) and normal-appearing white matter (NAWM). Our 1H-MRSI technique allowed simultaneous measurement of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr) signal intensities from four 15-mm slices divided into 0.84 ml single-volume elements. In WML we found significantly lower NAA/Cr and NAA/Cho ratios and a significantly higher Cho/Cr ratio than in NAWM or control white matter. In NAWM, NAA/Cr and Cho/Cr were significantly lower than in control white matter. 1H-MRSI was compatible with damage to myelin in WML, and with axonal damage and/or dysfunction in WML and NAWM. These findings extend data on involvement of NAWM in MS beyond the abnormalities visible on MRI. C1 Seconda Univ Napoli, Ist Sci Neurol, I-80138 Naples, Italy. NINCDS, Dept Neuroimaging, NIH, Bethesda, MD 20892 USA. NINCDS, Dept Neuroimmunol, NIH, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Tedeschi, G (reprint author), Seconda Univ Napoli, Ist Sci Neurol, Piazza Miraglia 2, I-80138 Naples, Italy. RI Duyn, Jozef/F-2483-2010 NR 40 TC 20 Z9 20 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD JAN PY 2002 VL 44 IS 1 BP 37 EP 42 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 518AL UT WOS:000173643700007 PM 11942498 ER PT J AU De Leonibus, E Mele, A Oliverio, A Pert, A AF De Leonibus, E Mele, A Oliverio, A Pert, A TI Distinct pattern of c-fos mRNA expression after systemic and intra-accumbens amphetamine and MK-801 SO NEUROSCIENCE LA English DT Article DE dopamine; glutamate; thalamus; locomotor activity; nucleus accumbens ID METHYL-D-ASPARTATE; RAT NUCLEUS-ACCUMBENS; METABOTROPIC GLUTAMATE RECEPTORS; LOCOMOTOR-ACTIVITY; HIPPOCAMPAL-FORMATION; PREFRONTAL CORTEX; DOPAMINE RELEASE; VENTRAL STRIATUM; NMDA; BEHAVIOR AB Pharmacological manipulation of both dopamine and glutamate systems affects motor responses in laboratory animals. The two systems, however, seem to act in opposite ways, since direct or indirect activation of dopamine receptors induces similar stimulatory effects to those seen following blockade of N-methyl-D-aspartate receptors. In the present study we compared the pattern of c-fos activation induced by systemic and intra-accumbens administration of the non-competitive N-methyl-D-aspartate antagonist MK-801 and the indirect dopamine agonist amphetamine. Systemic MK-801 induced c-fos mRNA expression in the motor cortex and preferentially in the motor thalamus, i.e. ventrolateral nucleus. Systemic amphetamine, on the other hand, enhanced c-fos mRNA expression in the shell of the accumbens and in limbic thalamic nuclei such as the anteroventral and anterodorsal nuclei. The main effect observed after intra-accumbens administrations of either drug was enhanced c-fos expression in the thalamus, somewhat similar to what seen following systemic administration. In fact also in this case there was a preferential activation of the limbic thalamus by amphetamine and the motor thalamus by MK-801. The present results confirm that different neural substrates underlie behavioral effects induced by systemic administrations of N-methyl-D-aspartate receptor antagonists and dopamine agonists. Further they suggest that intra-accumbens manipulation of the two neural systems could affect different efferent pathways from this structure activating different thalamic targets. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Roma La Sapienza, Dipartimento Genet & Biol Mol, I-00185 Rome, Italy. NIMH, BPB, NIH, Bethesda, MD 20892 USA. RP Mele, A (reprint author), Univ Roma La Sapienza, Dipartimento Genet & Biol Mol, P Aldo Moro 5, I-00185 Rome, Italy. RI Mele, Andrea/E-7741-2015 NR 55 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 115 IS 1 BP 67 EP 78 AR PII S0306-4522(02)00415-3 DI 10.1016/S0306-4522(02)00415-3 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 615DX UT WOS:000179231500007 PM 12401322 ER PT J AU Hall, FS Li, XF Sora, I Xu, F Caron, M Lesch, KP Murphy, DL Uhl, GR AF Hall, FS Li, XF Sora, I Xu, F Caron, M Lesch, KP Murphy, DL Uhl, GR TI Cocaine mechanisms: Enhanced cocaine, fluoxetine and nisoxetine place preferences following monoamine transporter deletions SO NEUROSCIENCE LA English DT Article DE cocaine; dopamine transporter; serotonin transporter; norepinephrine transporter; knockout mice; reward ID STRIATAL DOPAMINE RELEASE; RECEPTOR KNOCKOUT MICE; NUCLEUS-ACCUMBENS; IN-VIVO; CONDITIONED REWARD; SELF-STIMULATION; MEDIAN RAPHE; DRUG REWARD; OUT MICE; RATS AB Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine, serotonin and norepinephrine, producing subjective effects in humans that are both euphoric/rewarding and also fearful, jittery and aversive. Mice with gene knockouts of each of these transporters display cocaine reward, manifest by cocaine place preferences that are at least as great as wildtype values. Norepinephrine and serotonin receptor knockouts even display enhanced cocaine reward. One explanation for these observations could be that cocaine produces aversive or anhedonic effects by serotonin or norepinephrine receptor blockade in wildtype mice that are removed in serotonin or norepinephrine receptor knockouts, increasing net cocaine reward. Adaptations to removing one transporter could also change the rewarding valence of blocking the remaining transporters. To test these ideas, drugs that block serotonin transporter (fluoxetine), norepinephrine transporter (nisoxetine) or all three transporters (cocaine) were examined in single- or multiple-transporter knockout mice. Fluoxetine and nisoxetine acquire rewarding properties in several knockouts that are not observed in wildtype mice. Adding serotonin transporter knockout to norepinephrine transporter knockouts dramatically potentiates cocaine reward. These and previous data provide evidence that serotonin and norepinephrine transporter blockade can contribute to the net rewarding valence of cocaine. They identify neuroadaptations that may help to explain the retention of cocaine reward by dopamine and serotonin transporter knockout mice. They are consistent with emerging hypotheses that actions at the three primary brain molecular targets for cocaine each provide distinct contributions to cocaine reward and cocaine aversion in wildtype mice, and that this balance changes in mice that develop without dopamine, norepinephrine or serotonin transporters. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIDA, IRP, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. Duke Univ, Dept Cell Biol, Durham, NC 27710 USA. Duke Univ, Dept Med, Durham, NC 27710 USA. Duke Univ, HHMI, Durham, NC 27710 USA. Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany. NIMH, Clin Sci Lab, IRP, NIH, Bethesda, MD 20892 USA. RP Uhl, GR (reprint author), NIDA, IRP, Mol Neurobiol Branch, NIH, Box 5180, Baltimore, MD 21224 USA. RI Lesch, Klaus-Peter/J-4906-2013; Hall, Frank/C-3036-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X; Hall, Frank/0000-0002-0822-4063 NR 74 TC 79 Z9 80 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 115 IS 1 BP 153 EP 161 AR PII S0306-4522(02)00379-2 DI 10.1016/S0306-4522(02)00379-2 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 615DX UT WOS:000179231500015 PM 12401330 ER PT J AU Tao-Cheng, JH Vinade, L Pozzo-Miller, LD Reese, TS Dosemeci, A AF Tao-Cheng, JH Vinade, L Pozzo-Miller, LD Reese, TS Dosemeci, A TI Calcium/calmodulin-dependent protein kinase II clusters in adult rat hippocampal slices SO NEUROSCIENCE LA English DT Article DE CaMKII clusters; hippocampal cultures; ischemia; excitotoxicity; postsynaptic density ID PREPARATIVE METHODS; SELF-ASSOCIATION; BRAIN-SLICES; NEURONS; FORM AB We hake previously reported the formation of calcium/calmodulin-dependent protein kinase 11 (CaMKII) clusters similar to 110 nm in diameter in hippocampal neurons in culture and in the intact adult brain, under conditions that simulate ischemic stress and increase [Ca2+](i) [Dosemeci et al. (2000) J. Neurosci. 20, 3076-3084: Tao-Cheng et al. (200 1) Neuroscience 106. 69-78]. These observations suggest that ischemia-like conditions that prevail during the dissection of brain tissue for the preparation of hippocampal slices could lead to the formation of CaMKII clusters. We now show by pre-embedding immuno-electron microscopy that. indeed, CaMKH clusters are present in the CA1 pyramidal neurons in hippocampal slices from adult rats fixed immediately after dissection, and that the number of CaMKII clusters increases with the delay time between decapitation and fixation. Moreover, CaMKH clusters are typically localized near the endoplasmic reticulum. When acute slices are allowed to recover in oxygenated medium for 2 It. CaMKII clusters mostly disappear, indicating that clustering is reversible. Also, the postsynaptic density, another site for CaMKII accumulation under excitatory conditions. becomes thinner upon recovery. Treatment of recovered slices with high potassium for 90 s causes the re-appearance of CaMKH clusters in nearly all CA1 pyramidal cells examined. On the other hand, when dissociated hippocampal neurons in primary culture are exposed to the same depolarizing conditions, only similar to25%, of neurons exhibit CaMKII clusters. indicating a difference in the susceptibility of the neurons in culture and in acute slices to excitatory stimuli, Altogether these observations indicate that the effect of CaMKH clustering should be considered,when interpreting experimental results obtained with hippocampal slices, Published by Elsevier Science Ltd on behalf of IBRO. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. RP NINDS, Neurobiol Lab, NIH, Bldg 36,Room 2A21, Bethesda, MD 20892 USA. EM chengs@ninds.nih.gov NR 13 TC 22 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 115 IS 2 BP 435 EP 440 AR PII S0306-4522(02)00451-7 DI 10.1016/S0306-4522(02)00451-7 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 617PT UT WOS:000179370600011 PM 12421609 ER PT J AU Mizoguchi, H Wu, HE Narita, M Hall, FS Sora, I Uhl, GR Nagase, H Tseng, LF AF Mizoguchi, H Wu, HE Narita, M Hall, FS Sora, I Uhl, GR Nagase, H Tseng, LF TI Antagonistic property of buprenorphine for putative epsilon-opioid receptor-mediated G-protein activation by beta-endorphin in pons/medulla of the mu-opioid receptor knockout mouse SO NEUROSCIENCE LA English DT Article DE guanosine-5 '-O-(3-[S-35]thio)triphosphate binding; antagonist ID OPIATE RECEPTOR; GUANOSINE-5'-O-(3-THIO)TRIPHOSPHATE BINDING; RAT-BRAIN; MICE; AGONIST; POTENT; ENDOMORPHIN-1; STIMULATION; MODULATION; ANALGESIA AB beta-Endorphin is a non-selective opioid peptide which binds mu-, delta- and putative epsilon (beta-endorphin-sensitive non-mu-, non-delta- and non-kappa(1)-)-opioid receptors. We have previously reported that P-endorphin-produced G-protein activation is mediated by the stimulation of both mu- and putative E-opioid receptors. The present study was designed to further characterize this putative mu-opioid receptor-mediated G-protein activation in the pons/medulla membrane obtained from mice lacking mu-opioid receptor, using a guanosine-5'-O-(3-[S-35]thio)triphosphate ([S-35]GTPgammaS)-binding assay. beta-Endorphin and the mu-opioid receptor agonist [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO) increased the [S-35]GTPgammaS binding in a concentration-dependent manner (0.001-10 muM), and at 10 muM beta-endorphin and DAMGO produced approximately 250 and 120% increases of [S-35]GTPgammaS binding in the pons/medulla membrane obtained from wild-type mice, respectively. In the pons/medulla membrane obtained from p-opioid receptor knockout mice, beta-endorphin-stimulated [S-35]GTPgammaS binding was only partially attenuated and a more than 100% increase by 10 muM beta-endorphin still remained, while DAMGO failed to produce any increase in [S-35]GTPgammaS binding. The residual increase in [S-35]GTPgammas binding by 10 muM beta-endorphin in mu-opioid receptor knockout mice was partially but significantly attenuated by the putative c-opioid receptor partial agonist beta-endorphin (1-27), but not by the delta-opioid receptor antagonist naltrindole or the kappa(1)-receptor antagonist norbinaltorphimine. Furthermore, buprenorphine significantly attenuated the residual increase in [S-35]GTPgammaS binding by 10 muM beta-endorphin in mu-opioid receptor knockout mice. The present results indicate that beta-endorphin activates G-protein by stimulation of putative F-opioid receptors in the condition lacking the mu-opioid receptor, and buprenorphine acts as an antagonist for putative F-opioid receptors in this condition. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. Toray Industries Ltd, Pharmaceut Res Labs, Kamakura, Kanagawa 2488555, Japan. Tohoku Univ, Grad Sch Med, Dept Neurosci, Sendai, Miyagi 9808574, Japan. NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Hoshi Univ, Sch Pharm, Dept Toxicol, Tokyo 1428501, Japan. RP Tseng, LF (reprint author), Med Coll Wisconsin, Dept Anesthesiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU NIDA NIH HHS [DA03811] NR 27 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 115 IS 3 BP 715 EP 721 AR PII S0306-4522(02)00486-4 DI 10.1016/S0306-4522(02)00486-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 620FV UT WOS:000179524100007 PM 12435410 ER PT J AU Culmsee, C Gerling, N Lehmann, M Nikolova-Karakashian, M Prehn, JHM Mattson, MP Krieglstein, J AF Culmsee, C Gerling, N Lehmann, M Nikolova-Karakashian, M Prehn, JHM Mattson, MP Krieglstein, J TI Nerve growth factor survival signaling in cultured hippocampal neurons is mediated through TRKA and requires the common neurotrophin receptor p75 SO NEUROSCIENCE LA English DT Review DE NF-kappa B; PI3-kinase; Akt; bcl-2; shingosine kinase; glutamate ID NF-KAPPA-B; AFFINITY NGF RECEPTOR; NEUTRAL SPHINGOMYELINASE INHIBITOR; FOREBRAIN CHOLINERGIC NEURONS; FOCAL CEREBRAL-ISCHEMIA; BETA-PEPTIDE TOXICITY; RAT BASAL FOREBRAIN; AKT PROTEIN-KINASE; PC12 CELLS; INDUCED APOPTOSIS AB The role of the common neurotrophin receptor p75 (p75NTR) in neuronal survival and cell death remains controversial. On the one hand, p75NTR provides a positive modulatory influence on nerve growth factor (NGF) signaling through the high affinity neurotrophin receptor TrkA, and hence increases NGF survival signaling. However, p75NTR may also signal independently of TrkA, causing cell death or cell survival, depending on the cell type and stage of development. Here we demonstrate that TrkA is expressed in primary cultures of hippocampal neurons and is activated by NGF within 10 min of exposure. In primary hippocampal cultures neuroprotection by NGF against glutamate toxicity was mediated by NF-kappaB and accompanied by an increased expression of neuroprotective NF-kappaB target genes Bcl-2 and Bcl-xl. In mouse hippocampal cells lacking p75NTR (p75NTR-/-) activation of TrkA by NGF was not detectable. Moreover, neuroprotection by NGF against glutamate toxicity was abolished in p75NTR-/- neurons, and the expression of bcl-2 and bcl-xl was markedly reduced as compared to wildlype cells. NGF increased TrkA phosphorylation in hippocampal neurons and provided protection that required phosphoinositol-3-phosphate (PI3)-kinase activity and Akt phosphorylation, whereas the mitogen-activated protein kinases (MAPK), extracellular-regulated kinases (Erk) 1/2, were not involved. P75NTR signaling independent of TrkA, such as increased neutral sphingomyelinase (NSMase) activity causing enhanced levels of ceramide, were not detected after exposure of hippocampal neurons to NGF. Interestingly, inhibition of sphingosine-kinase blocked the neuroprotective effect of NGF, suggesting that sphingosine-1-phosphate was also involved in NGF-mediated survival in our cultured hippocampal neurons. Overall, our results indicate an essential role for p75NTR in supporting NGF-triggered TrkA signaling pathways mediating neuronal survival in hippocampal neurons. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Marburg, Inst Pharmakol & Toxikol, D-35032 Marburg, Germany. NIA, Neurosci Lab, Baltimore, MD USA. Univ Kentucky, Sch Med, Dept Physiol, Lexington, KY USA. Univ Munster, Univ Klinikum Munster, Interdisziplinares Zentrum Klin Forsch, Munster, Germany. RP Culmsee, C (reprint author), Univ Marburg, Inst Pharmakol & Toxikol, Ketzerbach 63, D-35032 Marburg, Germany. RI Mattson, Mark/F-6038-2012; Prehn, Jochen/A-3928-2010 OI Prehn, Jochen/0000-0003-3479-7794 NR 116 TC 109 Z9 118 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 115 IS 4 BP 1089 EP 1108 AR PII S0306-4522(02)00539-0 DI 10.1016/S0306-4522(02)00539-0 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 622VT UT WOS:000179668400010 PM 12453482 ER PT J AU Jeohn, GH Cooper, CL Jang, KJ Liu, B Lee, DS Kim, HC Hong, JS AF Jeohn, GH Cooper, CL Jang, KJ Liu, B Lee, DS Kim, HC Hong, JS TI Go6976 inhibits LPS-induced microglial TNF alpha release by suppressing p38 map kinase activation SO NEUROSCIENCE LA English DT Article DE brain inflammation; cytokine; endotoxin; microglia; mitogen-activated protein kinase; mouse ID NITRIC-OXIDE SYNTHASE; LIPOPOLYSACCHARIDE-INDUCED EXPRESSION; PROTEIN-TYROSINE KINASE; TOLL-LIKE RECEPTOR-4; GLIAL-CELLS; DOPAMINERGIC-NEURONS; SIGNAL-TRANSDUCTION; CYTOKINE PRODUCTION; HUMAN MONOCYTES; C-MU AB Microglial responses to endotoxin, including the synthesis of inflammatory factors, contribute to gliosis and neuron degeneration in cultured brain tissue. We have previously shown that Go6976, a protein kinase C (PKC) inhibitor, suppressed the lipopolysaccharide (LPS)-induced production of inflammatory factors in microglia and afforded marked protection of neurons from glia-mediated cytotoxicity. The purpose of this study was to identify the signal transduction pathway underlying the neuroprotective effect of Go6976. Go6976 suppressed the LPS-induced release of tumor necrosis factor alpha (TNFalpha) in the microglial cell line, BV2. We show in this study the inhibitory effect of Go6976 oil TNFalpha release occurring through suppression of p38 mitogen-activated protein kinase (MAPK) phosphorylation and not through a PKC mechanism. While Go6976 did not inhibit the activity of p38 MAPK directly, it did suppress its activation by phosphorylation, indicating the target of action of Go6976 is a signaling event upstream of p38 MAPK. Although Go6976 is considered a selective inhibitor of certain PKC isozymes, suppression of TNFalpha production was not mediated through inhibition of PKC activity. Go6976 appears to play a novel role in neuroprotection by suppressing the release of pro-inflammatory factors by inhibiting the activation of p38 MAPK in microglia, rather than a PKC isoform. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI liu, Bin/A-7695-2009 NR 39 TC 34 Z9 34 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 114 IS 3 BP 689 EP 697 AR PII S0306-4522(02)00356-1 DI 10.1016/S0306-4522(02)00356-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 601GZ UT WOS:000178439300016 PM 12220570 ER PT J AU Wen, H Jurkovicova, D Pickel, VM Gioio, AE Kaplan, BB AF Wen, H Jurkovicova, D Pickel, VM Gioio, AE Kaplan, BB TI Identification of a novel membrane-associated protein expressed in neurons of the squid and rodent nervous systems SO NEUROSCIENCE LA English DT Article DE novel mRNA; axon; synaptosome; mitochondrial-associated protein; squid; mouse brain ID MESSENGER-RNA; GIANT-AXON; SYNAPTOSOMAL FRACTION; LYMNAEA-STAGNALIS; LOCALIZATION; BRAIN; HYBRIDIZATION; MITOCHONDRIA; TRANSPORT; AXOPLASM AB In a previous communication, we reported the isolation of a novel cDNA clone (pA6) from a library constructed from squid axonal mRNAs. The partial cDNA clone contained a unique open reading frame that encoded 84 amino acids and was complementary to a moderately abundant mRNA approximately 550-600 nucleotides in length [Chun et al., J. Neurosci. Res. 49 (1997) 144-153]. In this report, we identify the pA6 gene product, and characterize its expression in the squid and rodent brain. Results of immunoblot analyses conducted in squid, using a polyclonal antibody raised against a synthetic peptide corresponding to the C-terminus of the putative protein, established the presence of two pA6 immunoreactive proteins of approximately 14 kDa and 26 kDa in size. In contrast, mouse brain contained only a single 26-kDa immunoreactive species. In both the squid and mouse brain, the expression of pA6 appears highly selective, being detected in certain neurons but not in non-neuronal cells, as judged by both in situ hybridization and immunocytochemistry. Findings derived from light microscopic, double-label immunohistofluorescence studies indicate that pA6 protein co-localizes with prohibitin, a mitochondrial marker protein. Consistent with these results, electron microscopy localized pA6 immunoreactivity to several membrane compartments to include the outer membrane of mitochondria, as well as to the smooth endoplasmic reticulum and tubulovesicles in dendrites, axons, and axon terminals of neurons in the rat brain. Taken together, these findings indicate that pA6 is a novel, membrane-associated protein, which is expressed in the distal structural/functional domains of neurons in both the invertebrate and vertebrate nervous systems. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Neurobiol & Neurosci, Div Neurobiol, New York, NY 10021 USA. RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, NIH, 9000 Rockville Pike,Bldg 10,Rm 4N222, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU NHLBI NIH HHS [HL 18974] NR 26 TC 4 Z9 4 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 114 IS 4 BP 995 EP 1004 AR PII S0306-4522(02)00362-7 DI 10.1016/S0306-4522(02)00362-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 613LZ UT WOS:000179134900017 PM 12379254 ER PT J AU Mansikka, H Zhou, L Donovan, DM Pertovaara, A Raja, SN AF Mansikka, H Zhou, L Donovan, DM Pertovaara, A Raja, SN TI The role of mu-opioid receptors in inflammatory hyperalgesia and alpha 2-adrenoceptor-mediated antihyperalgesia SO NEUROSCIENCE LA English DT Article DE pain; allodynia; carrageenan; morphine; dexmedetomidine ID DORSAL HORN NEURONS; RAT SPINAL-CORD; NOCICEPTIVE RESPONSES; CUTANEOUS HYPERALGESIA; INDUCED INHIBITION; INFLAMED TISSUE; MORPHINE; PAIN; DELTA; INVOLVEMENT AB The purpose of the present study was to investigate the role of mu-opioid receptor in inflammatory hyperalgesia in intact and in spinalized animals and the interaction between mu-opioid and alpha2-adrenergic receptor in acute pain and inflammatory hyperalgesia. Behavioral responses to mechanical and heat stimuli were studied in mu-opioid receptor knockout mice and wildtype control mice. Thermal nociception was evaluated by measuring paw withdrawal latencies to radiant heat applied to the hindpaws. Mechanical nociception was measured by von Frey monofilament applications to the hindpaws. Intraplantar carrageenan-induced (1 mg/40 mul) mechanical and heat hyperalgesia were compared in mu-opioid knockout and wildtype mice. The effect of systemically administered alpha2-adrenergic receptor agonist dexmedetomidine (1-10 mug/kg) was evaluated on mechanical and thermal withdrawal responses under normal and inflammatory state in knockout and wildtype mice. The role of mu-opioid receptor in descending modulation of nociception was studied by assessing mechanical and heat withdrawal responses before and after mid-thoracic spinalization. Withdrawal responses to radiant heat and von Frey monofilaments were similar in mu-opioid knockout and wildtype mice before and after the carrageenan induced hindpaw inflammation. Also, antinociceptive effects of dexmedetomidine in thermal and mechanical nociceptive tests were similar before carrageenan induced hindpaw inflammation. However, the potency of dexmedetomidine was significantly reduced in carrageenan-induced mechanical hyperalgesia in mu-opioid knockout mice compared to the wildtype control mice. Thermal and mechanical withdrawal responses were similar between mu-opioid knockout and wildtype mice before and after mid-thoracic spinalization. Our observations indicate that the mu-opioid receptors do not play an important role in alpha(2)-adrenergic receptor agonist-mediated acute antinociception. In addition, mu-opioid receptors are not tonically involved in the modulation of inflammation-induced mechanical and thermal hyperalgesia, and the supraspinal control of spinal reflexes. However, in the presence of inflammation, mu-opioid receptors play an important role in the antihyperalgesic actions of an alpha2-adrenergic receptor agonist. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD USA. NIA, Transgen Facil, IRP, NIH, Baltimore, MD 21224 USA. Turku Univ, Dept Physiol, Inst Biomed, Turku, Finland. Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. RP Mansikka, H (reprint author), Turku Univ Hosp, Dept Anesthesiol, POB 52, FIN-20521 Turku, Finland. OI Yang, Shuman/0000-0002-9638-0890; Pertovaara, Antti/0000-0002-8590-7220 FU NINDS NIH HHS [NS26363] NR 40 TC 22 Z9 22 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 113 IS 2 BP 339 EP 349 AR PII S0306-4522(02)00189-6 DI 10.1016/S0306-4522(02)00189-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 581XB UT WOS:000177318800009 PM 12127091 ER PT J AU Ichikawa, H Yamaai, T Jacobowitz, DM Mo, Z Xiang, M Sugimoto, T AF Ichikawa, H Yamaai, T Jacobowitz, DM Mo, Z Xiang, M Sugimoto, T TI Effect of Brn-3a deficiency on parvalbumin-, calbindin D-28k-, calretinin- and calcitonin gene-related peptide-immunoreactive primary sensory neurons in the trigeminal ganglion SO NEUROSCIENCE LA English DT Article DE transcription factor; knockout mouse; neurochemical substances; primary sensory neurons; immunohistochemistry ID TRANSCRIPTION FACTOR; DEVELOPMENTAL DEPENDENCY; RAT; INNERVATION; EXPRESSION; ENDINGS; DIFFERENTIATION; NEUROTROPHINS; SURVIVAL; PROTEIN AB Immunohistochemistry for parvalbumin, calbindin D-28k, calretinin and calcitonin gene-related peptide (CGRP) was performed on the trigeminal ganglion and oro-facial tissues in Brn-3a wildtype and knockout mice at embryonic day 18.5 and postnatal day 0. In wildtype mice, the trigeminal ganglion contained abundant parvalbumin-. calbindin D-28k- and CGRP-immunoreactive neurons while the ganglion was almost devoid of calretinin-immunoreactive neurons. In Brn-3a knockout mice, a 63% decrease of parvalbumin-immunoreactive neurons was detected. In contrast, the absence of Brn-3a dramatically increased the number of calbindin D-28k-immunoreactive (3.5-fold increase) and calretinin-immunoreactive neurons (91-fold increase). The number of CGRP-immunoreactive neurons, however, was not altered by the Brn-3a deficiency. Cell size analysis indicated that loss of Brn-3a increased the proportions of small ( < 100 μm(2)) parvalbumin-, calbindin D-28k- and CGRP-immunoreactive neurons while it decreased those of large (> 200 mum(2)) immunoreactive cells. Calretinin-immunoreactive neurons were either small or medium (100-200 mum(2)) in mutant mice. The oro-facial tissues contained parvalbumin, calbindin D-28k- and CGRP-immunoreactive fibers, but not calretinin-immunoreactive ones in wildtype mice. In Brn-3a knockout mice, the number of parvalbumin-immunoreactive fibers markedly decreased in the infraorbital nerve and parvalbumin-immunoreactive endings disappeared in the vibrissa. In contrast, the number of calbindin D-28k-immunoreactive fibers increased significantly in the infraorbital and mental nerves. In addition, calbindin D-28k-immunoreactive endings appeared in the vibrissa. As well, some fibers showed calretinin-immunoreactivity in the infraorbital nerve of the mutant. However, no obvious change of CGRP-immunoreactive fibers was observed in the oro-facial region of knockout mice. Taken together, our data suggest that Brn-3a deficiency has effects on the expression of neurochemical substances in the trigeminal ganglion. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Okayama Univ, Grad Sch Med & Dent, Dept Oral Funct & Anat, Okayama 7008525, Japan. Okayama Univ, Grad Sch Med & Dent, Biodent Res Ctr, Okayama 7008525, Japan. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat, Piscataway, NJ 08854 USA. RP Ichikawa, H (reprint author), Okayama Univ, Grad Sch Med & Dent, Dept Oral Funct & Anat, 2-5-1 Shikata Cho, Okayama 7008525, Japan. NR 30 TC 18 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 113 IS 3 BP 537 EP 546 AR PII S0306-4522(02)00182-3 DI 10.1016/S0306-4522(02)00182-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 590VH UT WOS:000177844300007 PM 12150774 ER PT J AU Torvinen, M Gines, S Hillion, J Latini, S Canals, M Ciruela, F Bordoni, F Staines, W Pedata, F Agnati, LF Lluis, C Franco, R Ferre, S Fuxe, K AF Torvinen, M Gines, S Hillion, J Latini, S Canals, M Ciruela, F Bordoni, F Staines, W Pedata, F Agnati, LF Lluis, C Franco, R Ferre, S Fuxe, K TI Interactions among adenosine deaminase, adenosine A(1) receptors and dopamine D-1 receptors in stably cotransfected fibroblast cells and neurons SO NEUROSCIENCE LA English DT Article DE adenosine deaminase; adenosine A(1)receptor; dopamine D-1 receptor; fibroblast cell line; neuronal primary cultures; heteromers ID OUTFLOW AB The role of adenosine deaminase in the interactions between adenosine A(1) and dopamine D-1 receptors was studied in a mouse fibroblast cell line stably cotransfected with human D-1 receptor and A(1) receptor cDNAs (A(1)D(1) cells). Confocal laser microscopy analysis showed a high degree of adenosine deaminase immunoreactivity on the membrane of the A(1)D(1) cells but not of the D-1 cells (only cotransfected with human D-1 receptor cDNAs). In double immunolabelling experiments in A(1)D(1) cells and cortical neurons a marked overlap in the distribution of the A(1) receptor and adenosine deaminase immunoreactivities and of the D-1 receptor and adenosine deaminase immunoreactivities was found. Quantitative analysis of A(1)D(1) cells showed that adenosine deaminase immunoreactivity to a large extent colocalizes with A(1) and D-1 receptor immunoreactivity, respectively. The A(1) receptor agonist caused in A(1)D(1) cells and in cortical neurons coaggregation of A(1) receptors and adenosine deaminase, and of D-1 receptors and adenosine deaminase. The A(1) receptor agonist-induced aggregation was blocked by R-deoxycoformycin, an irreversible adenosine deaminase inhibitor. The competitive binding experiments with the D-1 receptor antagonist [H-3]SCH-23390 showed that the D-1 receptors had a better fit for two binding sites for dopamine, and treatment with the A(1) receptor agonist produced a disappearance of the high-affinity site for dopamine at the D-1 receptor. R-Deoxycoformycin treatment, which has previously been shown to block the interaction between adenosine deaminase and A(1) receptors, and which is crucial for the high-affinity state of the A(1) receptor, also blocked the A, receptor agonist-induced loss of high-affinity D-1 receptor binding. The conclusion of the present studies is that the high-affinity state of the A(1) receptor is essential for the A(1) receptor-mediated antagonistic modulation of D-1 receptors and for the A(1) receptor-induced coaggregates of A(1) and adenosine deaminase, and of D-1 and adenosine deaminase. Thus, the confocal experiments indicate that both A(1) and D-1 receptors form agonist-regulated clusters with adenosine deaminase, where the presence of a structurally intact adenosine deaminase bound to A(1) receptors is important for the A(1)-D-1 receptor-receptor interaction at the level of the D-1 receptor recognition. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. Univ Florence, Dept Preclin & Clin Pharmacol, I-50134 Florence, Italy. Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy. NIDA, NIH, Baltimore, MD 21224 USA. RP Torvinen, M (reprint author), Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. RI Canals, Meritxell/A-6422-2013; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; OI Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Gines Padros, Silvia/0000-0002-9479-8185; Staines, Willim/0000-0002-7288-5026; Canals, Meritxell/0000-0002-7942-5006 NR 16 TC 37 Z9 37 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 113 IS 3 BP 709 EP 719 AR PII S0306-4522(02)00058-1 DI 10.1016/S0306-4522(02)00058-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 590VH UT WOS:000177844300024 PM 12150791 ER PT J AU Ikemoto, S AF Ikemoto, S TI Ventral striatal anatomy of locomotor activity induced by cocaine, D-amphetamine, dopamine and D-1/D-2 agonists SO NEUROSCIENCE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-for-Neuroscience CY OCT 23-28, 1999 CL MIAMI BEACH, FLORIDA SP Soc Neurosci DE nucleus accumbens core; shell; olfactory tubercle; ventral pallidum; SKF 38393; quinpirole ID NUCLEUS-ACCUMBENS CORE; MEDIAL PREFRONTAL CORTEX; FREELY MOVING RATS; EFFERENT PROJECTIONS; OLFACTORY TUBERCLE; EXTRACELLULAR DOPAMINE; MESOLIMBIC DOPAMINE; MOTOR COMPARTMENTS; DORSAL STRIATUM; SHELL AB The ventral striatum appears to play a critical role in mediating motoric effects (i.e. ambulatory activity and rearing) of psychostimulants such as cocaine. We evaluated whether sub-regions of the ventral striatum play differential roles in locomotion and rearing induced by various dopaminergic drugs. Injections Of D-amphetamine and dopamine stimulated locomotion and rearing with a similar potency at each of the sub-regions: the core, medial shell or medial tubercle. However, injections of mixtures of the D-1- and D-2-type agonists SKF 38393 and quinpirole or cocaine into the medial olfactory tubercle or the medial shell of the nucleus accumbens induced marked locomotion and rearing, while these injections into the core induced little or no locomotion or rearing. Furthermore, cocaine injections into the lateral or posterior tubercle produced marginal locomotion and rearing, while cocaine injections into regions just dorsal to these tubercle sites, the lateral portion of the shell or the ventral pallidum, did not produce any stimulating effect. We conclude that dopaminergic compounds induce vigorous locomotion and rearing in both core and shell; the relative roles of the core and shell differ depending on chemical compounds. Similar to the nucleus accumbens, the olfactory tubercle, particularly the medial portion, also mediates these behaviors induced by dopaminergic compounds. The medial ventral striatum (i.e. the medial tubercle and medial shell) plays a more important role in cocaine-induced locomotion and rearing than the lateral ventral striatum (i.e. the core, lateral shell and lateral tubercle). Moreover, the differential effects of cocaine between the medial and lateral portions of the shell on locomotion and rearing suggest more than two functional units (the core vs. the shell) within the accumbens. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Ikemoto, Satoshi/0000-0002-0732-7386 NR 51 TC 88 Z9 88 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 113 IS 4 BP 939 EP 955 AR PII S0306-4522(02)00247-6 DI 10.1016/S0306-4522(02)00247-6 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 592ZL UT WOS:000177966700019 PM 12182899 ER PT J AU Proescholdt, MG Chakravarty, S Foster, JA Foti, SB Briley, EM Herkenham, M AF Proescholdt, MG Chakravarty, S Foster, JA Foti, SB Briley, EM Herkenham, M TI Intracerebroventricular but not intravenous interleukin-1 beta induces widespread vascular-mediated leukocyte infiltration and immune signal mRNA expression followed by brain-wide glial activation SO NEUROSCIENCE LA English DT Article DE nuclear factor kappa B; meningitis; astrocytosis; cyclooxygenase-2; intercellular adhesion molecule-1; monocyte chemoattractant protein-1; cerebrospinal fluid ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; IN-SITU HYBRIDIZATION; NITRIC-OXIDE SYNTHASE; KAPPA-B ACTIVITY; RAT-BRAIN; MESSENGER-RNA; CEREBROSPINAL-FLUID; BACTERIAL-MENINGITIS AB Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that appears in brain and cerebrospinal fluid following peripheral immune challenges and central infections or injury. We examined the consequences of i.c.v. infusion of IL-1beta on mRNA expression of several immune markers and on recruitment of peripheral leukocytes. Awake rats were infused with IL-1beta (100 ng/rat) into the lateral ventricle, and 0.5, 2, 4, 8, 12, or 24 h later, animals were killed and their fresh-frozen brains processed for in situ hybridization and immunohistochemistry. Widespread vascular expression of inhibitory factor kappaBalpha (IkappaBalpha, marker of nuclear factor kappaBalpha transcriptional activity) and inducible cyclooxygenase (COX-2) mRNAs at 0.5-2 h was credited to movement of IL-1beta along ventricular, subarachnoid. and perivascular pathways to target endothelia that express type I IL-1beta receptor mRNA. Induction of monocyte chemoattractant protein-1 mRNA and intercellular adhesion molecule-1 (ICAM-1) immunostaining on endothelia began at 0.5-2 h. Leukocytes (neutrophils and monocytes, recognized by morphology and CD45 and ED1 immunostaining) appeared in meninges and blood vessels at 2-4 h and diffusely penetrated the parenchyma at 8-24 h. The leukocytes strongly expressed IL-1beta and inducible nitric oxide synthase mRNAs. Beginning at 4-12 h, astrocytes (glial acidic fibrillary protein mRNA. and protein and c-fos mRNA) and microglia (ionized calcium-binding adaptor molecule I mRNA and protein) showed widespread activation. Other rats received i.v. IL-1beta (6 mug/kg). Their brains showed induction of IkappaBalpha and COX-2 mR NAs in the vasculature at 2 It but none of the other sequelae. In summary, our data indicate that IL-1beta in the cerebrospinal fluid reaches its target receptors on the endothelia via perivascular volume transmission, up-regulates ICAM-1, and triggers a targeted leukocyte emigration and widespread glial activation stimulated perhaps by pro-inflammatory molecules expressed by leukocytes. The dramatic difference between i.c.v. and i.v. routes of administration underscores the potency of IL-1beta within the brain to dynamically affect the cellular trafficking component of 'immune privilege'. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, Bldg 36,Room 2D15, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 67 TC 63 Z9 65 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 112 IS 3 BP 731 EP 749 AR PII S0306-4522(02)00048-9 DI 10.1016/S0306-4522(02)00048-9 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 572JF UT WOS:000176770200023 PM 12074914 ER PT J AU Chefer, VI Shippenberg, TS AF Chefer, VI Shippenberg, TS TI Changes in basal and cocaine-evoked extracellular dopamine uptake and release in the rat nucleus accumbens during early abstinence from cocaine: Quantitative determination under transient conditions SO NEUROSCIENCE LA English DT Article DE cocaine; behavioral sensitization; no net flux microdialysis; dopamine release; dopamine uptake ID MICRODIALYSIS EXTRACTION FRACTION; BEHAVIORAL SENSITIZATION; PHARMACOLOGICAL CHARACTERIZATION; TRANSPORTER ACTIVITY; VENTRAL STRIATUM; IN-VITRO; SHELL; AMPHETAMINE; CORE; INVIVO AB Despite an abundance of studies on mechanisms of behavioral sensitization, considerable uncertainty exists as to whether alterations in dopamine neurotransmission underlie the exacerbated behavioral effects of cocaine observed during the early stages of abstinence. One of the factors contributing to the uncertainty and controversy may be the limitations in utilized measurement techniques (mostly conventional microdialysis). The techniques of quantitative microdialysis under transient conditions and rotating disk electrode voltammetry were used to characterize basal dopamine dynamics as well its time-related changes in extracellular dopamine concentrations and dopamine uptake that occur in response to an acute drug challenge in control animals and animals with previous history of cocaine. Basal extracellular dopamine concentrations were unaltered on abstinence day 3 From repeated cocaine administration (5 days, 20 mg/kg, i.p.). The extraction fraction of dopamine, an indirect measure of dopamine uptake, was significantly lower in cocaine-sensitized animals relative to controls. These two facts, taken together, suggest that basal dopamine release is depressed in cocaine-sensitized animals on abstinence day 3. At the same time, a cocaine challenge decreased the extraction fraction and increased the extracellular dopamine concentration in both experimental groups. The magnitude of the increase in extracellular dopamine concentration was greater in cocaine-sensitized animals, while the ability of cocaine to decrease the extraction fraction was unaltered, suggesting that the increase in extracellular dopamine concentration reflects an increase in drug-evoked dopamine release. Moreover, cocaine-pretreated rats demonstrated greater depolarization-induced dopamine release and the ability of dopamine D, receptor agonist, quinpirole. to inhibit release was decreased in these animals. These data demonstrate that a cocaine treatment regimen resulting in behavioral sensitization is associated with a reduction in basal dopamine release, an enhancement in both cocaine and K+-evoked dopamine release, and a subsensitivity of dopamine D-2 autoreceptors that regulate dopamine release in the nucleus accumbens. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIDA, Integrat Neurosci Unit, Behav Neurosci Lab, NIH,Intramural Res Program, Baltimore, MD 21224 USA. RP Chefer, VI (reprint author), NIDA, Integrat Neurosci Unit, Behav Neurosci Lab, NIH,Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 64 TC 43 Z9 43 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 112 IS 4 BP 907 EP 919 AR PII S0306-4522(02)00099-4 DI 10.1016/S0306-4522(02)00099-4 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 574TK UT WOS:000176905500016 PM 12088750 ER PT J AU Chen, R Cohen, LG Hallett, M AF Chen, R Cohen, LG Hallett, M TI Nervous system reorganization following injury SO NEUROSCIENCE LA English DT Review DE plasticity; reorganization; cortex; amputation; nerve injury ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; MASSIVE CORTICAL REORGANIZATION; UPPER-LIMB AMPUTATION; CEREBRAL-CORTEX; FUNCTIONAL REORGANIZATION; SOMATOSENSORY CORTEX; ADULT-RATS; CORTICOSPINAL PROJECTIONS; MOVEMENT REPRESENTATIONS AB Contrary to the classical view of a pre-determined wiring pattern, there is considerable evidence that cortical representation of body parts is continuously modulated in response to activity, behavior and skill acquisition. Both animal and human studies showed that following injury of the peripheral nervous system such as nerve injury or amputation, the somatosensory cortex that responded to the deafferented body parts become responsive to neighboring body parts. Similarly, there is expansion of the motor representation of the stump area following amputation. Reorganization of the sensory and motor systems following peripheral injury occurs in multiple levels including the spinal cord, brainstem, thalamus and cortex. In early-blind subjects, the occipital cortex plays an important role in Braille reading, suggesting that there is cross-modal plasticity. Functional recovery frequently occurs following a CNS injury such as stroke. Motor recovery from stroke may be associated with the adjacent cortical areas taking over the function of the damaged areas or utilization of alternative motor pathways. The ipsilateral motor pathway may mediate motor recovery in patients who undergo hemispherectomy early in life and in children with hemiplegic cerebral palsy, but it remains to be determined if it plays a significant role in the recovery of adult stroke. One of the challenges in stroke recovery is to identify which of the many neuroimaging and neurophysiological changes demonstrated are important in mediating recovery. The mechanism of plasticity probably differs depending on the time frame. Rapid changes in motor representations within minutes are likely due to unmasking of latent synapses involving modulation of GABAergic inhibition. Changes over a longer time likely involve other additional mechanisms such as long-term potentiation, axonal regeneration and sprouting. While cross-modal plasticity appears to be useful in enhancing the perceptions of compensatory sensory modalities, the functional significance of motor reorganization following peripheral injury remains unclear and some forms of sensory reorganization may even be associated with deleterious consequences like phantom pain. An understanding of the mechanism of plasticity will help to develop treatment programs to improve functional outcome. (C) 2002 Published by Elsevier Science Ltd on behalf of IBRO. C1 NINCDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NINCDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINCDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 108 TC 373 Z9 390 U1 7 U2 79 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 111 IS 4 BP 761 EP 773 AR PII S0306-4522(02)00025-8 DI 10.1016/S0306-4522(02)00025-8 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 563QJ UT WOS:000176266800004 PM 12031403 ER PT J AU Paletzki, RF AF Paletzki, RF TI Cloning and characterization of guanine deaminase from mouse and rat brain SO NEUROSCIENCE LA English DT Article DE striatum; guanase; dopamine; basal ganglia ID DOPAMINE RECEPTOR GENE; C-FOS; MATRIX COMPARTMENTS; EXPRESSION; COCAINE; STRIATUM; D1; NEURONS; AMPHETAMINE; ACTIVATION AB A search for genes differentially expressed in the rat striatum revealed a gene fragment with a ventral to dorsal striatal expression pattern. The sequence of the fragment was used to isolate mouse and rat clones that upon sequencing were identified as homologous to human guanine deaminase. Here we report the distribution of guanine deaminase in the rodent brain. In situ hybridization localization of the encoding mRNA showed a distribution primarily in forebrain areas including cortical pyramidal neurons. ventral striatal medium spiny ne irons, hippocampal pyramidal neurons in CA3-CA1 and granule cells in the dentate gyrus. and neurons of the amygdala. Immunohistochemistry using antibodies raised against peptide fragments derived from the guanine deaminase protein sequence showed localization of guanine deaminase in areas predicted by the mRNA distribution. In addition to immunolabeling of neurons in the cerebral cortex, hippocampus, striatum and amygdala there was also labeling in the terminal fields of these neurons including the thalamus. globus pailidum and substantia nigra. A functional histochemical assay that demonstrates the site of guanine deamination shows guanine deaminase activity in a pattern that matched the immunohistochemical localization. The cellular distribution of guanine deaminase to distal areas of the cell including terminals and dendrites was additionally demonstrated by the expression of recombinant guanine deaminase in transformed cortical neurons in culture. In summary we have described the isolation and characterization of mouse and rat guanine deaminase. The expression of guanine deaminase is primarily restricted to forebrain neurons. A histochemical assay was used to localize guanine deaminase activity to the dendrites and axons of neurons expressing guanine deaminase. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Paletzki, RF (reprint author), NINCDS, Mol Plast Sect, 36 Convent Dr,MSC 4135,Bldg 36,Room 4C-23, Bethesda, MD 20892 USA. NR 32 TC 23 Z9 23 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 109 IS 1 BP 15 EP 26 AR PII S0306-4522(01)00352-9 DI 10.1016/S0306-4522(01)00352-9 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 521VE UT WOS:000173861400003 PM 11784697 ER PT J AU Peng, Y Xu, RH Mei, JM Li, XP Yan, D Kung, HF Phang, JM AF Peng, Y Xu, RH Mei, JM Li, XP Yan, D Kung, HF Phang, JM TI Neural inhibition by c-jun as a synergizing factor in bone morphogenetic protein 4 signaling SO NEUROSCIENCE LA English DT Article DE Xenopus; embryo; development; neuralization; neural induction ID GROWTH-FACTOR-BETA; XENOPUS EMBRYOS; EPIDERMAL INDUCTION; MESODERM INDUCTION; EXPRESSION; ECTODERM; ACTIVIN; NEURALIZATION; TRANSCRIPTION; INITIATION AB The transcription factor, activator protein I (AP-1) complexes (c-Jun and c-Fos heterodimers) has been shown to interact with transforming growth factor beta signaling in mammalian cells and Drosophila embryo. Here we show that c-Jun alone is involved in the anti-neuralizing activity of bone morphogenetic protein 4, a transforming growth factor beta superfamily member, in Xenopus neurogenesis. Co-injection of mRNAs encoding c-jun and a dominant negative bone morphogenetic protein receptor completely inhibits dominant negative bone morphogenetic protein receptor-induced neuralization and reverses the epidermal fate in the animal cap. Surprisingly, a dominant negative c-Jun does not induce neural tissue in the animal cap, but it synergizes with dominant negative bone morphogenetic protein receptor for neural induction. Temporal analysis using a dexamethasone-inducible c-Jun shows that exogenous c-Jun activity must be turned on before or at stage I I to fulfill the anti-neuralizing effect. Neural inhibition by c-Jun does not occur until stage 13 suggesting that c-Jun probably acts by suppressing neural maintenance rather than neural initiation, This is also supported by the fact that c-Jun does not inhibit expression of the neural-initializing gene Zic-r1 but the neural cofactor Sox2, and that ectopic expression of Sox2 attenuates the anti-neuralizing effect of c-Jun. Finally, we display that the c-Jun effect is enhanced by an auto-regulatory loop between c-Jun and bone morphogenetic protein. These studies suggest that c-Jun/AP-1 is a converging point in both the fibroblast growth factor and transforming growth factor beta signaling pathways. Based on our findings, we propose that c-Jun synergizes with bone morphogenetic protein 4 signaling to inhibit neural development in Xenopus ectoderm. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab,Metab & Canc Susceptibil Sect, NIH, Frederick, MD 21702 USA. WiCell Res Inst, Madison, WI 53705 USA. First Mil Med Univ, Dept Otolaryngol, Guangzhou 510515, Peoples R China. Bar Ilan Univ, Canc Aids & Immunol Res Inst, IL-52900 Ramat Gan, Israel. Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China. RP Phang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab,Metab & Canc Susceptibil Sect, NIH, Bldg 560,Room 12-48, Frederick, MD 21702 USA. RI Xu, Ren-He/M-3125-2016 NR 32 TC 12 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 109 IS 4 BP 657 EP 664 AR PII S0306-4522(01)00526-7 DI 10.1016/S0306-4522(01)00526-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 526GB UT WOS:000174120800002 PM 11927148 ER PT J AU Serrano, J Alonso, D Encinas, JM Lopez, JC Fernandez, AP Castro-Blanco, S Fernandez-Vizarra, P Richart, A Bentura, ML Santacana, M Uttenthal, LO Cuttitta, F Rodrigo, J Martinez, A AF Serrano, J Alonso, D Encinas, JM Lopez, JC Fernandez, AP Castro-Blanco, S Fernandez-Vizarra, P Richart, A Bentura, ML Santacana, M Uttenthal, LO Cuttitta, F Rodrigo, J Martinez, A TI Adrenomedullin expression is up-regulated by ischemia-reperfusion in the cerebral cortex of the adult rat SO NEUROSCIENCE LA English DT Article DE immunohistochemistry; electron microscopy; pyramidal neuron; neuroprotection ID GUINEA-PIG BRAIN; NITRIC-OXIDE SYNTHASE; GENE-RELATED PEPTIDE; TUMOR-CELL LINES; HYPOTENSIVE PEPTIDE; CALCITONIN-GENE; FOREBRAIN SLICES; IMMUNOREACTIVITY; LOCALIZATION; SECRETION AB Changes in the pattern of adrenomedullin expression in the rat cerebral cortex after ischemia-reperfusion were studied by light and electron microscopic immunohistochemistry using a specific antibody against human adrenomedullin (22-52). Animals were subjected to 30 min of oxygen and glucose deprivation in a perfusion model simulating global cerebral ischemia, and the cerebral cortex was studied after 0, 2, 4, 6, 8, 10 or 12 It of reperfusion. Adrenomedullin immune reactivity was elevated in certain neuronal structures after 6-12 h of reperfusion as compared with controls, Under these conditions, numerous large pyramidal neurons and some small neurons were intensely stained in all cortical layers. The number of immunoreactive pre- and post-synaptic structures increased with the reperfusion time. Neurons immunoreactive for adrenomedullin presented a normal morphology whereas non-immunoreactive neurons were clearly damaged, suggesting a potential cell-specific protective role for adrenomedullin. The number and intensity of immunoreactive endothelial cells were also progressively elevated as the reperfusion time increased. In addition, the perivascular processes of glial cells and/or pericytes followed a similar pattern, suggesting that adrenomedullin may act as a vasodilator in the cerebrocortical circulation. In summary, adrenomedullin expression is elevated after the ischemic insult and seems to be part of CNS response mechanism to hypoxic injury. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 CSIC, Inst Cajal, Dept Neuroanat & Cell Biol, E-28002 Madrid, Spain. NCI, Dept Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. RP Rodrigo, J (reprint author), CSIC, Inst Cajal, Dept Neuroanat & Cell Biol, Avenida Doctor Acre 37, E-28002 Madrid, Spain. RI Encinas, Juan/E-3625-2010; Fernandez-Vizarra, Paula/H-5588-2012; Martinez, Alfredo/A-3077-2013; Lopez Ramos, Juan Carlos/K-9336-2014; OI Fernandez-Vizarra, Paula/0000-0002-0322-6844; Martinez, Alfredo/0000-0003-4882-4044; Encinas, Juan Manuel/0000-0002-0402-972X NR 60 TC 49 Z9 56 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 109 IS 4 BP 717 EP 731 AR PII S0306-4522(01)00532-2 DI 10.1016/S0306-4522(01)00532-2 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 526GB UT WOS:000174120800008 PM 11927154 ER PT J AU Toczek, MT Theodore, WH AF Toczek, MT Theodore, WH TI Cortical dysplasia and epilepsy - Functional imaging using single photon emission computed tomography and positron emission tomography SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Review ID NEURONAL MIGRATION DISORDERS; TEMPORAL-LOBE EPILEPSY; BENZODIAZEPINE-RECEPTOR-BINDING; INTRACTABLE PARTIAL EPILEPSY; TUBEROUS SCLEROSIS COMPLEX; C-11 FLUMAZENIL PET; PERI-ICTAL SPECT; SURGICAL-TREATMENT; INFANTILE SPASMS; BLOOD-FLOW AB Functional imaging using single photon emission CT and positron emission tomography have made important contributions to the evaluation of patients with medically intractable epilepsy and cortical dysplasia by identifying patients who previously were not considered surgical candidates. This article reviews the role of functional imaging in the presurgical evaluation of this patient population. C1 NINCDS, Epilepsy Res Branch, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Toczek, MT (reprint author), NINCDS, Epilepsy Res Branch, Clin Epilepsy Sect, NIH, 10 Ctr Dr,Bldg 10,Room 5N250,MSC 1408, Bethesda, MD 20892 USA. NR 121 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JAN PY 2002 VL 13 IS 1 BP 71 EP + DI 10.1016/S1042-3680(02)80008-0 PG 17 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 519TP UT WOS:000173741800008 PM 11754318 ER PT J AU Ferguson, SA Flynn, KM Delclos, KB Newbold, RR Gough, BJ AF Ferguson, SA Flynn, KM Delclos, KB Newbold, RR Gough, BJ TI Effects of lifelong dietary exposure to genistein or nonylphenol on amphetamine-stimulated striatal dopamine release in male and female rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE estrogen; striatum; dopamine; microdialysis; genistein; nonylphenol; endocrine disrupter ID TYROSINE KINASE INHIBITOR; ESTROGEN-RECEPTOR-BETA; SPRAGUE-DAWLEY RATS; SMOOTH-MUSCLE CELLS; SEX-DIFFERENCES; TISSUE DISTRIBUTION; CALCIUM CURRENTS; IN-VITRO; MICRODIALYSIS; CYCLE AB Estrogen modulates baseline and amphetamine-stimulated dopamine (DA) release in the adult female rat striatum. The isoflavone found in soybeans, genistein, is a phytoestrogen and may have comparable effects on striatal DA levels. Similarly, the industrial intermediate and potential endocrine disrupter, para-nonylphenol, has estrogen-like effects. Here. Sprague-Dawley rats were continuously exposed to phytoestrogen-free diets containing 0, 100, or 500 ppm genistein (Experiment 1) or 0 or 200, or 750 ppm nonylphenol (Experiment 2) beginning at conception and continuing throughout. To eliminate estrous cycle influences on DA levels, females were ovariectomized at adulthood. As adults. striatal levels of DA and its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) were measured in unanesthetized male and female rats via cerebral microdialysis before and for 200 min after an intraperitoneal injection of 2 mg/kg D-amphetamine. Although baseline 5-hydroxyindoleacetic acid (5-HIAA) levels indicated an isolated effect in genistein-treated females, there were no meaningful differences among treatment groups in baseline levels of DA. DOPAC, or HVA. However, dietary exposure to 500 ppm genistein significantly potentiated amphetamine-stimulated DA release in males and a similar trend was apparent, but not statistically significant, in females. Dietary exposure to 200 or 750 ppm nonylphenol had no significant effects in males or females. These results suggest that dietary genistein exposure may act similarly to estradiol in augmenting amphetamine-stimulated DA release. (C) 2002 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 53 TC 17 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2002 VL 24 IS 1 BP 37 EP 45 AR PII S0892-0362(01)00193-3 DI 10.1016/S0892-0362(01)00193-3 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 527UG UT WOS:000174205800005 PM 11836070 ER PT S AU Andoh, T Chock, PB Chiueh, CC AF Andoh, T Chock, PB Chiueh, CC BE Chiueh, CC Hong, JS Leong, SK TI Preconditioning-mediated neuroprotection - Role of nitric oxide, cGMP, and new protein expression SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci, Taiwanese Biosci Amer DE NOS1/nNOS; GSNO; cGMP; Bcl-2; Trx; MnSOD; preconditioning mechanism; neuroprotection ID OXIDATIVE STRESS; S-NITROSOGLUTATHIONE; RAT MODEL; ISCHEMIA; SYNTHASE; TOLERANCE; BRAIN; MYOCARDIUM; APOPTOSIS; INDUCTION AB Preconditioning adaptation induced by transient ischemia can increase brain tolerance to oxidative stress, but the underlying neuroprotective mechanisms are not fully understood. Recently, we developed a human brain-derived cell model to investigate preconditioning mechanism in SH-SY5Y neuroblastoma cells.(1) Our results demonstrate that a non-lethal serum deprivation-stress for 2 h (preconditioning stress) enhanced the tolerance to a subsequent lethal oxidative stress (24 h serum deprivation) and also to 1-methyl-4-phenyl-pyridinium (MPP+).(2) Two-hour non-lethal preconditioning stress increased the expression of neuronal nitric oxide (NOS1/nNOS) mRNA, Fos, Ref-1, NOS protein, and then nitric oxide ((NO)-N-.) production. As well as MnSOD expression, the (NO)-N-.-cGMP-PKG pathway mediated the preconditioning-induced upregulation of antiapoptotic protein Bcl-2 and the downregulation of adaptor protein p66(shc). We also propose that cGMP-mediated preconditioning-induced adaptation against oxidative stress may be due to the synthesis of a new protein, such as thioredoxin (Trx) since the protective effect can be blocked by Trx reductase inhibitors.(3) The antioxidative potency of Trx was approximately 100 and 1,000 times greater than GSNO and GSH, respectively. These results suggest that (NO)-N-.-cGMP-PKG signaling pathway plays an important role in the preconditioning-induced neuroprotection, and perhaps cardioprotection, against oxidative stress. C1 Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Dept Appl Pharmacol, Toyama 9300194, Japan. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. NIMH, Unit Neurogenerat & Neuroprotect, Clin Sci Lab, NIH,Clin Ctr, Bethesda, MD 20892 USA. RP Andoh, T (reprint author), Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Dept Appl Pharmacol, 2630 Sugitani, Toyama 9300194, Japan. NR 26 TC 52 Z9 57 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 1 EP 7 PG 7 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400001 PM 12076958 ER PT S AU Khaldi, A Chiueh, CC Bullock, MR Woodward, JJ AF Khaldi, A Chiueh, CC Bullock, MR Woodward, JJ BE Chiueh, CC Hong, JS Leong, SK TI The significance of nitric oxide production in the brain after injury SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci, Taiwanese Biosci Amer DE nitric oxide production; brain injury; NMDA receptor ID NMDA-RECEPTOR; CELL-DEATH; NEURONS; NEUROTOXICITY; ACTIVATION; NO; NITROSYLATION; MECHANISMS; CULTURES; DISEASE AB Glutamate toxicity has been implicated in many aspects of brain injury including traumatic, ischemic, and hemorrhagic damage. We have used in vitro as well as in vivo methods to measure NO production and to examine the role of NO in glutamate toxicity. In building our recombinant system, we used human kidney embryonic cells, HEK 293, as host for transfection of nNOS and NMDA receptor proteins. Cells cotransfected with NMDA and nNOS were more resistant to glutamate toxicity. This resistance correlated with NO production as measured by citrulline assay. Meanwhile, the production of NO did not significantly change the response of the NMDA receptor as seen by calcium studies. Moreover, in vivo, NO production was directly correlated with brain tissue oxygen tension in subarachnoid hemorrhage patients. These data and others point toward the importance of NO production in the response of brain to injury. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Neurosurg, Richmond, VA 23298 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. RP Khaldi, A (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Neurosurg, POB 980631, Richmond, VA 23298 USA. FU NIAAA NIH HHS [R01 AA009986] NR 26 TC 25 Z9 25 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 53 EP 59 PG 7 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400005 PM 12076962 ER PT S AU Rauhala, P Andoh, T Yeh, K Chiueh, CC AF Rauhala, P Andoh, T Yeh, K Chiueh, CC BE Chiueh, CC Hong, JS Leong, SK TI Contradictory effects of sodium nitroprusside and S-nitroso-N-acetylpenicillamine on oxidative stress in brain dopamine neurons in vivo SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci, Taiwanese Biosci Amer DE sodium nitroprusside; S-nitroso-N-acetylpenicillamine; oxidative stress; substantia nigra; lipid peroxidation; hydroxyl radical; caudate nucleus; iron ID NITRIC-OXIDE; PARKINSONIAN BRAIN; LIPID-PEROXIDATION; IRON CONTENT; NITROSOGLUTATHIONE; DISRUPTION; TOLERANCE; MANGANESE; GENE AB To investigate whether nitric oxide ((NO)-N-.) is neurotoxic or neuroprotective in the brain, we compared the in vivo role of S-nitroso-N-acetyl-penicillamine (SNAP) with that of sodium nitroprusside (SNP) on ferrous citrate-induced oxidative stress and neuronal loss in the rat nigrostriatal dopaminergic system. It is known that light irradiation releases (NO)-N-. from its donor compounds; these irradiated (NO)-N-. donors were used as sham controls in this study. Intranigral infusion of ferrous citrate (4.2 nmol) into the rat midbrain substantia nigra compacta area caused acute lipid peroxidation in the substantia nigra and chronic dopamine depletion in the caudate nucleus. Coinfusion of freshly prepared SNAP (0-8.4 nmol) or (NO)-N-. (about 2 nmol), but not SNP, rescued iron-induced dopamine depletion in the rat brain in vivo. In fact, SNP produced prooxidative effects similar to ferrous citrate both in vivo and in vitro, since SNP is a redox iron complex. Consistently, (NO)-N-. and SNAP inhibited, whereas SNP potentiated, (OH)-O-. generation and lipid peroxidation evoked by ferrous citrate in vitro. We previously reported that freshly prepared, but not irradiated, S-nitroso-L-glutathione (GSNO) protected brain dopamine neurons against oxidative stress in vivo. As well as these antioxidative properties, our recent reports (see Ref. 1) indicate that (NO)-N-./GSNO activated guanylyl cyclase, increased cGMP and that could lead to PKG-mediated expression of MnSOD, Bcl-2, and thioredoxin for preconditioning neuroprotection against 1-methyl-4-phenylpyridinium (MPP+).(1) In conclusion, (NO)-N-. and S-nitrosothiols (e.g., GSNO and SNAP) can scavenge reactive oxygen species and activate the heme moiety of guanylyl cyclase, resulting in protection of brain dopamine neurons through both antioxidative and antiapoptotic mechanisms. C1 Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland. Toyama Med & Pharmaceut Univ, Dept Appl Pharmacol, Toyama, Japan. NIMH, Clin Sci Lab, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Rauhala, P (reprint author), Univ Helsinki, Inst Biomed, POB 63, FIN-00014 Helsinki, Finland. OI Rauhala, Pekka/0000-0003-2036-3522 NR 34 TC 17 Z9 17 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 60 EP 72 PG 13 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400006 PM 12076963 ER PT S AU Espey, MG Miranda, KM Thomas, DD Xavier, S Citrin, D Vitek, MP Wink, DA AF Espey, MG Miranda, KM Thomas, DD Xavier, S Citrin, D Vitek, MP Wink, DA BE Chiueh, CC Hong, JS Leong, SK TI A chemical perspective on the interplay between NO, reactive oxygen species, and reactive nitrogen oxide species SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci, Taiwanese Biosci Amer DE oxidative stress; nitrosative stress; nitration; nitrite; peroxidase ID PROTEIN-TYROSINE NITRATION; ZINC SUPEROXIDE-DISMUTASE; NITRIC-OXIDE; NITROXYL ANION; IN-VIVO; BIOLOGICAL-SYSTEMS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; PHYSIOLOGICAL PH; AQUEOUS-SOLUTION AB Nitric oxide (nitrogen monoxide, NO) plays a veritable cornucopia of regulatory roles in normal physiology. In contrast, NO has also been implicated in the etiology and sequela of numerous neurodegenerative diseases that involve reactive oxygen species (ROS) and nitrogen oxide species (RNOS). In this setting, NO is often viewed solely as pathogenic; however, the chemistry of NO can also be a significant factor in lessening injury mediated by both ROS and RNOS. The relationship between NO and oxidation, nitrosation, and nitration reactions is summarized. The salient factors that determine whether NO promotes, abates, or interconnects these chemistries are emphasized. From this perspective of NO chemistry, the type, magnitude, location, and duration of either ROS or RNOS reactions may be predicted. C1 Natl Canc Inst, Radiat Biol Branch, Bethesda, MD 20892 USA. Duke Univ, Ctr Med, Dept Neurol, Durham, NC USA. RP Espey, MG (reprint author), Natl Canc Inst, Radiat Biol Branch, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 59 TC 82 Z9 82 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 195 EP 206 PG 12 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400018 PM 12076975 ER PT S AU Cooper, CL Jeohn, GH Tobias, P Hong, JS AF Cooper, CL Jeohn, GH Tobias, P Hong, JS BE Chiueh, CC Hong, JS Leong, SK TI Serum-dependence of LPS-induced neurotoxicity in rat cortical neurons SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci, Taiwanese Biosci Amer DE serum dependence; LPS-induced neurotoxicity; rat cortical neurons ID LIPOPOLYSACCHARIDE (LPS)-BINDING PROTEIN; NITRIC-OXIDE SYNTHASE; TOLL-LIKE RECEPTOR-4; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; LIPID-A BINDING; BACTERIAL-ENDOTOXIN; MICROGLIAL CELLS; GENE-EXPRESSION; EX-VIVO AB Previous studies have shown that the bacterial endotoxin, lipopolysaccharide (LPS), is neurotoxic both in vitro and in vivo. The rate of binding of LIPS to a target cell is greatly enhanced by serum in general and by LIPS binding protein (LBP) in particular. The purpose of the study described in this paper was to determine if microglia activation and LPS-induced neurotoxicity is serum or LBP dependent. A murine microglial cell line, BV2, was used to assess the serum dependence of nitric oxide production and tumor necrosis factor a release in microglia. Embryonic rat cortical neuron/glia mixed cultures were used to determine the serum dependence of LPS-induced neurotoxicity. Our results from both cell culture systems show that LPS-induced inflammatory responses are serum dependent at lower doses of LIPS and progressively become serum independent above 10 ng/ml. Purified human recombinant LBP reconstitutes the lost LPS-induced inflammatory responses in primary and immortalized cell cultures treated with heat-denatured serum and appears to account for the serum dependence. These data suggest that the cell surface signaling receptor for LPS at the low and high concentrations are likely to differ, consistent with the existence of a variety of LIPS receptors. C1 Truman State Univ, Div Sci, Kirksville, MO 63501 USA. NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. RP Cooper, CL (reprint author), Truman State Univ, Div Sci, Kirksville, MO 63501 USA. NR 50 TC 7 Z9 7 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 306 EP 317 PG 12 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400026 PM 12076983 ER PT S AU Liu, B Gao, HM Wang, JY Jeohn, GH Cooper, CL Hong, JS AF Liu, B Gao, HM Wang, JY Jeohn, GH Cooper, CL Hong, JS BE Chiueh, CC Hong, JS Leong, SK TI Role of nitric oxide in inflammation-mediated neurodegeneration SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LA SP Soc Neurosci, Taiwanese Bioscientists Amer DE inflammation; lipopolysaccharide; naloxone; neurodegeneration; neuroprotection; nitric oxide; opioids; superoxide ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; NECROSIS-FACTOR-ALPHA; NEURONAL CELL-DEATH; CORTICAL NEURON/GLIA CULTURES; ACTIVATED PROTEIN-KINASES; RETINAL GANGLION-CELLS; D-ASPARTATE RECEPTORS; HIGH-DOSE NALOXONE; ALZHEIMERS-DISEASE; INTERFERON-GAMMA AB Increasing evidence has suggested that inflammation in the brain is closely associated with the pathogenesis of several degenerative neurologic disorders, including Parkinson's disease, Alzheimer's diseases, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. The hallmark of brain inflammation is the activation of glial cells, especially that of microglia that produce a variety of proinflammatory and neurotoxic factors, including cytokines, fatty acid metabolites, free radicals-such as nitric oxide (NO) and superoxide. Excessive production of NO, as a consequence of nitric oxide synthase induction in activated glia, has been attributed to participate in neurodegeneration. Using primary mixed neuron-glia cultures and glia-enriched cultures prepared from embryonic rodent brain tissues, we have systemically studied the relationship between the production of NO and neurodegeneration in response to stimulation by the inflammagen lipopolysaccharide. This review summarizes our recent findings on the kinetics of NO generation, the relative contribution of microglia and astrocytes to NO accumulation, the relationship between NO, production and neurodegeneration, and points of intervention along the pathways associated with NO generation to achieve neuroprotection. We also describe our results relating to the effect of several opioid-related agents on microglial activation and neuroprotection. Among these agents, the opioid receptor antagonist naloxone, especially its non-opioid enantiomer (+)-naloxone, promises to be of potential therapeutic value for the treatment of inflammation-related diseases. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Durham, NC 27710 USA. RP Liu, B (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, F1-01,POB 12233, Durham, NC 27710 USA. EM liu3@niehs.nih.gov RI gao, huiming/C-8454-2012; liu, Bin/A-7695-2009 NR 99 TC 256 Z9 271 U1 3 U2 13 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 318 EP 331 PG 14 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400027 PM 12076984 ER PT S AU Jeohn, GH Cooper, CL Wilson, B Chang, RCC Jang, KJ Kim, HC Liu, B Hong, JS AF Jeohn, GH Cooper, CL Wilson, B Chang, RCC Jang, KJ Kim, HC Liu, B Hong, JS BE Chiueh, CC Hong, JS Leong, SK TI p38 MAP kinase is involved in lipopolysaccharide-induced dopaminergic neuronal cell death in rat mesencephalic neuron-glia cultures SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci, Taiwanese Biosci Amer DE neurotoxicity; glia; lipopolysaccharide; endotoxin; nitric oxide; p38 MAP kinase; SB202190; GW274150; iNOS ID NITRIC-OXIDE SYNTHASE; ACTIVATED PROTEIN-KINASES; CENTRAL-NERVOUS-SYSTEM; BETA-AMYLOID PROTEIN; TOLL-LIKE RECEPTOR-4; TYROSINE KINASE; ALZHEIMERS-DISEASE; MICROGLIAL CELLS; INDUCED EXPRESSION; BACTERIAL LIPOPOLYSACCHARIDE AB Immune stimulants, such as the bacterial endotoxin, lipopolysaccharide (LPS), the human immunodeficiency virus-1 coat protein gp120, or beta-amyloid peptides, lead to glial activation and production of various immune mediators, such as nitric oxide (NO) and proinflammatory cytokines in the brain. These mediators appear to contribute to neuronal cell death in neurodegenerative diseases. However, the signaling pathways, which mediate the neurotoxic effect by the endotoxin, are not understood. The purpose of this study was to determine the role of mitogen-activated protein kinase (MAPK) in LPS-induced neurodegeneration using mesencephalic dopaminergic neuron/glia cultures. We have found that the p38 MAPK is important in LPS-induced death of mesencephalic neurons in rat neuron-glia mixed cultures. Upon treatment with 10 ng/ml LPS, the number of dopaminergic neurons decreased by 80% within 48 h, preceded by a significant production of NO by glia. Neuroprotection by selective inhibition of p38 MAPK activity paralleled a decrease in LPS-induced inducible nitric oxide synthase (iNOS) expression. These events were significantly reduced by the selective p38 MAPK inhibitor, SB202190, but not by the inactive analogue SB202474. Inhibition of iNOS activity and NO production by treatment with GW274150 was also neuroprotective. Although the p38 MAPK inhibitor afforded significant neuroprotection from LPS toxicity in the neuron-glia mixed culture, it failed to protect dopaminergic neurons from 6-hydroxy-dopamine-induced toxicity, which acts directly on dopaminergic neurons by inducing hydroxyl radical formation from the mitochondria. The results suggest that p38 MAPK in glia plays a significant role in the LPS-induced death of mesencephalic neurons through induction of nitric oxide synthase and resulting NO production. C1 NIEHS, Neuropharmacol Sect, LPC, NIH, Res Triangle Pk, NC 27709 USA. Truman State Univ, Div Sci, Kirksville, MO USA. Kangwon Natl Univ, Dept Pharm, Chunchon 200701, South Korea. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, LPC, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Chang, Raymond Chuen-Chung/C-1107-2009; liu, Bin/A-7695-2009 OI Chang, Raymond Chuen-Chung/0000-0001-8538-7993; NR 58 TC 41 Z9 50 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 332 EP 346 PG 15 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400028 PM 12076985 ER PT S AU Jeohn, GH Cooper, CL Jang, KJ Kim, HC Hong, JS AF Jeohn, GH Cooper, CL Jang, KJ Kim, HC Hong, JS BE Chiueh, CC Hong, JS Leong, SK TI Go6976 protects mesencephalic neurons from lipopolysaccharide-elicited death by inhibiting p38 MAP kinase phosphorylation SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci, Taiwanese Biosci Amer DE BV2; microglia; tumor necrosis factor alpha; endotoxin; nitric oxide; inflammation; neurodegeneration ID NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; BETA-AMYLOID PROTEIN; CELL-WALL COMPONENTS; TOLL-LIKE RECEPTOR-4; TYROSINE KINASE; ALZHEIMERS-DISEASE; MICROGLIAL CELLS; GLIAL-CELLS; INDUCED EXPRESSION AB Glial activation is associated with inflammation-related neuron degeneration in the brain. A variety of protein kinases are assumed to contribute to the expression of inflammation-related products, such as nitric oxide (NO) and proinflammatory cytokines, however, the mechanisms of glial activation and glia-mediated neurotoxicity remain unclear. We found that the indolocarbazole, Go6976, originally known as a selective protein kinase C (PKC) inhibitor, protects neurons from glia-mediated damage and suppresses lipopolysaccharide (LPS)-induced microglial production of inflammatory factors. The purpose of the study we report here was to determine the mechanism underlying the neuroprotective effect of Go6976 in mesencephalic neuron/glia cultures. Go6976 suppressed LPS-induced neurotoxicity in mesencephalic neuron/glia cultures and the protective effect of Go6976 paralleled the suppression of p38 mitogen activated protein kinase (MAPK) activation and inhibition of NO production. Go6976 did not directly inhibit the activity of p38 MAPK; rather, the inhibitor suppressed the phosphorylation of p38 MAPK, suggesting that the target of Go6976 is a signaling event upstream of p38 MAPK. Although Go6976 was originally known to be a selective PKC inhibitor, the neuroprotection was not mediated through its reputed effects on PKC activity. This paper demonstrates that the neuroprotective effect of Go6976 against LPS-induced damage is mediated through the inhibition of proinflammatory factors, such as NO from microglia, by inhibiting the phosphorylation of p38 MAPK. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Truman State Univ, Div Sci, Kirksville, MO USA. Kangwon Natl Univ, Dept Pharm, Chunchon 200701, South Korea. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 52 TC 10 Z9 10 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 347 EP 359 PG 13 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400029 PM 12076986 ER PT S AU Mohanakumar, KP Thomas, B Sharma, SM Muralikrishnan, D Chowdhury, R Chiueh, CC AF Mohanakumar, KP Thomas, B Sharma, SM Muralikrishnan, D Chowdhury, R Chiueh, CC BE Chiueh, CC Hong, JS Leong, SK TI Nitric oxide - An antioxidant and neuroprotector SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LA SP Soc Neurosci, Taiwanese Bioscientists Amer DE free radical scavenger; inducible nitric oxide synthase mRNA; nitroglycerine; MPTP; hydroxyl radicals; nitric oxide donors; ferrous citrate ID PARKINSONS-DISEASE; IN-VIVO; DOPAMINERGIC NEUROTOXICITY; SODIUM-NITROPRUSSIDE; MPTP NEUROTOXICITY; HYDROXYL RADICALS; OXIDATIVE STRESS; SYNTHASE; MICE; INHIBITION AB Indirect evidence, including neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-neurotoxicity by nitric oxide synthase (NOS) inhibitors and resistance of transgenic animals deficient in NOS, is controversial. We have reviewed evidence in favor of oxidative stress during the development of MPTP-neurotoxicity and the influence of antioxidants, including nitric oxide (NO) and NO donors, on MPTP-induced dopaminergic neurotoxicity. Systemic administration of MPTP causes dose-dependent generation of hydroxyl radicals (OH) in vivo in the striatum in mice; OH scavengers protect dopaminergic neurons from this insult. On the other hand the role of NO in MPTP-neurotoxicity is controversial. Hitherto, no direct evidence for the involvement of NO in MPTP neurotoxicity has been available. MPTP does not affect inducible-NOS mRNA level or its expression in SN or the striatum. Nitroglycerine, a NO donor, can attenuate MPTP-induced dopamine depletion in the striatum by virtue of its OH scavenging action. Several other NO donors have also been shown to scavenge the OH generated, following Fenton chemistry in vitro, and to protect against in vivo dopaminergic neurotoxicity by small mass iron complex formation. This evidence suggests that NO renders protection against MPTP-induced OH-mediated nigrostriatal lesions, acting as an antioxidant. C1 Indian Inst Chem Biol, Lab Expt & Clin Neurosci, Kolkata 700032, W Bengal, India. Indian Inst Chem Biol, Div Biophys, Kolkata 700032, W Bengal, India. NIMH, Unit Neurotox & Neuroprotect, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Mohanakumar, KP (reprint author), Indian Inst Chem Biol, Lab Expt & Clin Neurosci, 4 Raja SC Mullick Rd, Kolkata 700032, W Bengal, India. EM mohankumar@iicb.res.in NR 39 TC 73 Z9 75 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 389 EP 401 PG 13 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400033 PM 12076990 ER PT S AU Wang, Y Chang, CF Morales, M Chiang, YH Hoffer, J AF Wang, Y Chang, CF Morales, M Chiang, YH Hoffer, J BE Chiueh, CC Hong, JS Leong, SK TI Protective effects of glial cell line-derived neurotrophic factor in ischemic brain injury SO NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Neuroscience CY NOV 04-09, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci, Taiwanese Biosci Amer DE cerebral ischemia; MCA ligation; GDNF ID CEREBRAL-ARTERY OCCLUSION; MIDBRAIN DOPAMINERGIC-NEURONS; KAINATE-INDUCED EXCITATION; FACTOR MESSENGER-RNA; NITRIC-OXIDE; RAT-BRAIN; 1,25-DIHYDROXYVITAMIN D-3; IN-VITRO; NEUROBLASTOMA-CELLS; TOPICAL APPLICATION AB Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta (TGF-beta) superfamily, has been shown to have trophic activity on dopaminergic neurons. Recent studies indicate that GDNF can protect the cerebral hemispheres from damage induced by middle cerebral arterial ligation. We found that such neuroprotective effects are mediated through specific GDNF receptor alpha-1 (GFRalpha1). Animals with a deficiency in GFRalpha-1 have less GDNF-induced neuroprotection. Ischemia also enhances nitric oxide synthase (NOS) activity, which can be attenuated by GDNF. These.data suggest that GDNF can protect against ischemic injury through a GFRalpha-1/NOS mechanism. We also found that the receptor for GDNF, GFRalpha1, and its signaling moiety c-Ret were upregulated, starting immediately after ischemia. This upregulation suggests that activation of an endogenous neuroprotective mechanism occurs so that responsiveness of GDNF can be enhanced at very early stages during ischemia. C1 NIDA, IRP, NIH, Baltimore, MD 21224 USA. Natl Def Med Ctr, Triserv Gen Hosp, Taipei, Taiwan. RP Wang, Y (reprint author), NIDA, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 64 TC 69 Z9 76 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-366-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 962 BP 423 EP 437 PG 15 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BU76R UT WOS:000176952400036 PM 12076993 ER PT J AU Thomas, DD Miranda, KM Espey, MG Citrin, D Jourd'Heuil, D Paolocci, N Hewett, SJ Colton, CA Grisham, MB Feelisch, M Wink, DA AF Thomas, DD Miranda, KM Espey, MG Citrin, D Jourd'Heuil, D Paolocci, N Hewett, SJ Colton, CA Grisham, MB Feelisch, M Wink, DA TI Guide for the use of nitric oxide (NO) donors as probes of the chemistry of NO and related redox species in biological systems SO NITRIC OXIDE, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID S-NITROSOTHIOLS; HYDROGEN-PEROXIDE; NITROSATIVE STRESS; ENDOTHELIAL-CELLS; GUANYLATE-CYCLASE; PHYSIOLOGICAL PH; AQUEOUS-SOLUTION; SMOOTH-MUSCLE; CYCLIC-GMP; IN-VIVO C1 NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Albany Med Coll, Ctr Cardiovasc Sci, Albany, NY 12208 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Med, Dept Biomed Engn, Baltimore, MD 21287 USA. Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA. Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, Shreveport, LA 71130 USA. RP Thomas, DD (reprint author), NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009; Feelisch, Martin/C-3042-2008; OI Feelisch, Martin/0000-0003-2320-1158; Hewett, Sandra/0000-0002-2987-3791 NR 83 TC 51 Z9 52 U1 0 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 359 BP 84 EP 105 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BV73H UT WOS:000179915100008 PM 12481562 ER PT J AU Kiesewetter, DO Jagoda, EM Starrett, JE Gribkoff, VK Hewawasam, P Srinivas, N Salazar, D Eckelman, WC AF Kiesewetter, DO Jagoda, EM Starrett, JE Gribkoff, VK Hewawasam, P Srinivas, N Salazar, D Eckelman, WC TI Radiochemical synthesis and biodistribution of a novel maxi-K potassium channel opener SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE PET; biodistribution; brain; maxi-K; MaxiPost; BMS-204352 ID LARGE-CONDUCTANCE; STROKE AB The racemate 1, ((+/-)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)- 2H-indol-21-one), is a potent, specific and novel opener of cloned large-conductance, calcium-activated (maxi-K) potassium channels. One of its enantiomers, BMS-204352 (Maxi-Post(TM)), is undergoing clinical evaluation for efficacy in patients with suspected acute stroke. In the current study, we have prepared [F-18]-labeled 1 using a silver assisted nucleophilic substitution to examine its distribution and disposition in the rat, with particular emphasis on the brain. Biodistribution Studies in rats confirm that brain uptake is rapid and occurs at high levels, and indicate that a major fraction of the compound in the brain does not accumulate by a specific, saturable mechanism. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIH, Ctr Clin, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Wallingford, CT 06492 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Lawrenceville, NJ USA. RP Kiesewetter, DO (reprint author), NIH, Ctr Clin, Positron Emiss Tomog Dept, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 9 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2002 VL 29 IS 1 BP 55 EP 59 DI 10.1016/S0969-8051(01)00281-5 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 513DT UT WOS:000173363200007 PM 11786276 ER PT J AU Ma, DS Lu, F Overstreet, T Milenic, DE Brechbiel, MW AF Ma, DS Lu, F Overstreet, T Milenic, DE Brechbiel, MW TI Novel chelating agents for potential clinical applications of copper SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Cu-67; Cu-64; copper; chelating agents; serum stability; radiopharmaceuticals ID NON-HODGKINS-LYMPHOMA; SUPEROXIDE-DISMUTASE; IRON COMPLEXES; IN-VITRO; RADIOPHARMACEUTICALS; RADIOIMMUNOTHERAPY; CIS,CIS-1,3,5-TRIAMINOCYCLOHEXANE; LIGAND; CU-67; PET AB Copper offers a unique selection of radioisotopes. (Cu-60, Cu-61, Cu-62, Cu-64, and Cu-67) with half-lives ranging from 9.8 min to 61.9 h suitable for imaging and/or radiotherapy. In peptide/antibody targeted radiotherapy one of the most studied chelating agents for copper, 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA), has been employed in clinical trials, but transchelation to ceruloplasmin and/or superoxide dismutase in vivo has been noted. In this study, a series of novel hexadentate chelating agents based on N,N',N"-tris(2-pyridylmethyl)-1,3,5-cis,cis,-triaminocyclohexane (tachpyr) have been synthesized and the serum stability of their copper complexes was evaluated as compared to TETA. Copper complexes of tachpyr modified at the 3, 4, or 5 position or with replacement of pyridine by imidazole have serum stability comparable to Cu[TETA]. When the complexes were cross-challenged, Cu[TETA] versus tachpyr or 1,3,5-cis,cis-triaminocyclohexane-N,N',N"-tris-(2-methyl-(N-methylimidazole)) (IM), tachpyr and IM appear to have superior copper chelation ability to TETA. When challenged by a large excess of non-radioactive copper, copper exchange with the tachpyr radio-copper complex was observed. However, tachpyr clearly exhibited a significant preference for Cu(II) over Zn(II) or Fe(III), Therefore, tachpyr, 1,3,5-cis,cis,-triaminocyclohexane-N,N',N"-tri-(3-methyl-2-methylpyridineimine) (tachpyr(3-Me)), 1,3,5-cis,cis,-triaminocyclohexane-N,N',N"-tri-(4-methyl-2-methylpyridineimine) (tachpyr(4-Me)), 1,3,5-cis,cis,-triaminocyclohexane-N,N',N"-tri-(5-methyl-2-methylpyridineimine) (tachpyr(5-Me)) and IM easily form copper complexes with high stability. These novel chelating agents provide an attractive lead for creation of new copper radiopharmaceuticals for diagnosis and therapy applications. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bldg 10,Room B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 45 Z9 45 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2002 VL 29 IS 1 BP 91 EP 105 DI 10.1016/S0969-8051(01)00287-6 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 513DT UT WOS:000173363200011 PM 11786280 ER PT J AU Ma, Y Huang, BX Channing, MA Eckelman, WC AF Ma, Y Huang, BX Channing, MA Eckelman, WC TI Quantification of Kryptofix 2.2.2 in 2-[F-18]FDG and other radiopharmaceuticals by LC/MS/MS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Kryptofix 2.2.2; 2-[F-18]FDG; LC/MS/MS ID CHROMATOGRAPHY AB A high-performance liquid chromatography-tandem mass spectrometric method (LC/MS/MS) was developed and validated for the quantitative analysis of Kryptofix (K-222) in the radiopharmaceuticals of 2-deoxy-2-[F-18] fluoro-D-glucose (2-[F-18]FDG) and 3-(3-((3-fluoropropyl)(thio)-1,2,5-thiadiazol-4-yl)-1,2,5,-tetrahydro-1-methylpyridine (FPTZTP). With an internal standard, the limit of quantitation for K-222 was 1.0 mg/ml. This is so far the most sensitive method for the quantification of K-222. Excellent linearity RSQ = 0.9997) was obtained over the range of 1.0-100 ng/ml. Good precision and accuracy were also observed. The method is amenable to the validation of radiosynthetic methods. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIH, Warren G Magnuson Clin Ctr, PET Dept, Bethesda, MD 20892 USA. RP Huang, BX (reprint author), NIH, Warren G Magnuson Clin Ctr, PET Dept, Bldg 10,Room 1C 401, Bethesda, MD 20892 USA. NR 7 TC 14 Z9 19 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2002 VL 29 IS 1 BP 125 EP 129 DI 10.1016/S0969-8051(01)00269-4 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 513DT UT WOS:000173363200014 PM 11786283 ER PT J AU Baxevanis, AD AF Baxevanis, AD TI The Molecular Biology Database Collection: 2002 update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-GENOME AB The Molecular Biology Database Collection is an online resource listing key databases of value to the biological community. This Collection is intended to bring fellow scientists' attention to high-quality databases that are available throughout the world, rather than just be a lengthy listing of all available databases. As such, this up-to-date listing is intended to serve as the initial point from which to find specialized databases that may be of use in biological research. The databases included in this Collection provide new value to the underlying data by virtue of curation, new data connections or other innovative approaches. Short, searchable summaries and updates for each of the databases included in the Collection are available through the Nucleic Acids Research Web site at http://nar.oupjournals.org. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), NHGRI, Genome Technol Branch, NIH, Bldg 50,Room 5222, Bethesda, MD 20892 USA. NR 4 TC 31 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2002 VL 30 IS 1 BP 1 EP 12 DI 10.1093/nar/30.1.1 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FB UT WOS:000173077100001 PM 11752241 ER PT J AU Wheeler, DL Church, DM Lash, AE Leipe, DD Madden, TL Pontius, JU Schuler, GD Schriml, LM Tatusova, TA Wagner, L Rapp, BA AF Wheeler, DL Church, DM Lash, AE Leipe, DD Madden, TL Pontius, JU Schuler, GD Schriml, LM Tatusova, TA Wagner, L Rapp, BA TI Database resources of the National Center for Biotechnology Information: 2002 update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN; TOOL; ENTREZ; SEQUENCES AB In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources that operate on the data in GenBank and a variety of other biological data made available through NCBI's web site. NCBI data retrieval resources include Entrez, PubMed, LocusLink and the Taxonomy Browser. Data analysis resources include BLAST, Electronic PCR, OrfFinder, RefSeq, UniGene, HomoloGene, Database of Single Nucleotide Polymorphisms (dbSNP), Human Genome Sequencing, Human MapViewer, Human!VMouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB) and the Conserved Domain Database (CDD). Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at http://www.ncbi.nlm.nih.gov. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Wheeler, DL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20892 USA. OI Lash, Alex/0000-0003-3787-1590; Schriml, Lynn/0000-0001-8910-9851 NR 27 TC 152 Z9 159 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2002 VL 30 IS 1 BP 13 EP 16 DI 10.1093/nar/30.1.13 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FB UT WOS:000173077100002 PM 11752242 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Rapp, BA Wheeler, DL AF Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Rapp, BA Wheeler, DL TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSED SEQUENCE TAGS; DATABASE AB The GenBank sequence database incorporates publicly available DNA sequences of more than 105 000 different organisms, primarily through direct submission of sequence data from individual laboratories and large-scale sequencing projects. Most submissions are made using the BankIt (web) or Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical literature via PubMed. Sequence similarity searching is provided by the BLAST family of programs. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. NCBI also offers a wide range of World Wide Web retrieval and analysis services based on GenBank data. The GenBank database and related resources are freely accessible via the NCBI home page at http://www.ncbi.nlm.nih.gov. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Benson, DA (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 385 Z9 397 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2002 VL 30 IS 1 BP 17 EP 20 DI 10.1093/nar/30.1.17 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FB UT WOS:000173077100003 PM 11752243 ER PT J AU Kreppel, L Kimmel, AR AF Kreppel, L Kimmel, AR TI Genomic database resources for Dictyostelium discoideum SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ORGANIZATION; SEQUENCE AB Dictyostelium is an attractive model system for the study of mechanisms basic to cellular function or complex multicellular developmental processes. Recent advances in Dictyosteliumgenomics have generated a wide spectrum of resources. However, much of the current genomic sequence information is still not currently available through GenBank or related databases. Thus, many investigators are unaware that extensive sequence data from Dictyostelium has been compiled, or of its availability and access. Here, we discuss progress in Dictyostelium genomics and gene annotation, and highlight the primary portals for sequence access, manipulation and analysis (http://genome.imb-jena.de/dictyostelium/; http://dictygenome.bcm.tmc.edu/; http://www.sanger. ac.uk/Projects/D_discoideum/; http://www.csm.biol. tsukuba.ac.jp/cDNAproject.html). C1 NIDDKD, Lab Cellular & Dev Biol 50 3351, NIH, Bethesda, MD 20892 USA. RP Kimmel, AR (reprint author), NIDDKD, Lab Cellular & Dev Biol 50 3351, NIH, Bethesda, MD 20892 USA. NR 16 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2002 VL 30 IS 1 BP 84 EP 86 DI 10.1093/nar/30.1.84 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FB UT WOS:000173077100021 PM 11752261 ER PT J AU Twigger, S Lu, J Shimoyama, M Chen, D Pasko, D Long, H Ginster, J Chen, CF Nigam, R Kwitek, A Eppig, J Maltais, L Maglott, D Schuler, G Jacob, H Tonellato, PJ AF Twigger, S Lu, J Shimoyama, M Chen, D Pasko, D Long, H Ginster, J Chen, CF Nigam, R Kwitek, A Eppig, J Maltais, L Maglott, D Schuler, G Jacob, H Tonellato, PJ TI Rat Genome Database (RGD): mapping disease onto the genome SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HYPERTENSION; LOCI AB The Rat Genome Database (RGD, http://rgd.mcw.edu) is an NIH-funded project whose stated mission is 'to collect, consolidate and integrate data generated from ongoing rat genetic and genomic research efforts and make these data widely available to the scientific community'. In a collaboration between the Bioinformatics Research Center at the Medical College of Wisconsin, the Jackson Laboratory and the National Center for Biotechnology Information, RGD has been created to meet these stated aims. The rat is uniquely suited to its role as a model of human disease and the primary focus of RGD is to aid researchers in their study of the rat and in applying their results to studies in a wider context. In support of this we have integrated a large amount of rat genetic and genomic resources in RGD and these are constantly being expanded through ongoing literature and bulk dataset curation. RGD version 2.0, released in June 2001, includes curated data on rat genes, quantitative trait loci (QTL), microsatellite markers and rat strains used in genetic and genomic research. VCMap, a dynamic sequence-based homology tool was introduced, and allows researchers of rat, mouse and human to view mapped genes and sequences and their locations in the other two organisms, an essential tool for comparative genomics. In addition, RGD provides tools for gene prediction, radiation hybrid mapping, polymorphic marker selection and more. Future developments will include the introduction of disease-based curation expanding the curated information to cover popular disease systems studied in the rat. This will be integrated with the emerging rat genomic sequence and annotation pipelines to provide a high-quality disease-centric resource, applicable to human and mouse via comparative tools such as VCMap. RGD has a defined community outreach focus with a Visiting Scientist program and the Rat Community Forum, a web-based forum for rat researchers and others interested in using the rat as an experimental model. Thus, RGD is not only a valuable resource for those working with the rat but also for researchers in other model organisms wishing to harness the existing genetic and physiological data available in the rat to complement their own work. C1 Med Coll Wisconsin, Bioinformat Res Ctr, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Tonellato, PJ (reprint author), Med Coll Wisconsin, Bioinformat Res Ctr, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. FU NHLBI NIH HHS [HL64541, R01 HL064541] NR 17 TC 63 Z9 64 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2002 VL 30 IS 1 BP 125 EP 128 DI 10.1093/nar/30.1.125 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FB UT WOS:000173077100033 PM 11752273 ER PT J AU Edgar, R Domrachev, M Lash, AE AF Edgar, R Domrachev, M Lash, AE TI Gene Expression Omnibus: NCBI gene expression and hybridization array data repository SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-MICROARRAY AB The Gene Expression Omnibus (GEO) project was initiated in response to the growing demand for a public repository for high-throughput gene expression data. GEO provides a flexible and open design that facilitates submission, storage and retrieval of heterogeneous data sets from high-throughput gene expression and genomic hybridization experiments. GEO is not intended to replace in house gene expression databases that benefit from coherent data sets, and which are constructed to facilitate a particular analytic method, but rather complement these by acting as a tertiary, central data distribution hub. The three central data entities of GEO are platforms, samples and series, and were designed with gene expression and genomic hybridization experiments in mind. A platform is, essentially, a list of probes that define what set of molecules may be detected. A sample describes the set of molecules that are being probed and references a single platform used to generate its molecular abundance data. A series organizes samples into the meaningful data sets which make up an experiment. The GEO repository is publicly accessible through the World Wide Web at http://www.ncbi.nlm.nih.gov/geo. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Lister Hill Ctr, Bethesda, MD 20894 USA. RP Lash, AE (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Lister Hill Ctr, 8600 Rockville Pike, Bethesda, MD 20894 USA. OI Lash, Alex/0000-0003-3787-1590 NR 7 TC 3965 Z9 4023 U1 15 U2 109 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2002 VL 30 IS 1 BP 207 EP 210 DI 10.1093/nar/30.1.207 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FB UT WOS:000173077100055 PM 11752295 ER PT J AU Wang, YL Anderson, JB Chen, J Geer, LY He, SQ Hurwitz, DI Liebert, CA Madej, T Marchler, GH Marchler-Bauer, A Panchenko, AR Shoemaker, BA Song, JS Thiessen, PA Yamashita, RA Bryant, SH AF Wang, YL Anderson, JB Chen, J Geer, LY He, SQ Hurwitz, DI Liebert, CA Madej, T Marchler, GH Marchler-Bauer, A Panchenko, AR Shoemaker, BA Song, JS Thiessen, PA Yamashita, RA Bryant, SH TI MMDB: Entrez's 3D-structure database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN AB Three-dimensional structures are now known within many protein families and it is quite likely, in searching a sequence database, that one will encounter a homolog with known structure. The goal of Entrez's 3D-structure database is to make this information, and the functional annotation it can provide, easily accessible to molecular biologists. To this end Entrez's search engine provides three powerful features. (i) Sequence and structure neighbors; one may select all sequences similar to one of interest, for example, and link to any known 3D structures. (ii) Links between databases; one may search by term matching in MEDLINE, for example, and link to 3D structures reported in these articles. (iii) Sequence and structure visualization; identifying a homolog with known structure, one may view molecular-graphic and alignment displays, to infer approximate 3D structure. In this article we focus on two features of Entrez's Molecular Modeling Database (MMDB) not described previously: links from individual biopolymer chains within 3D structures to a systematic taxonomy of organisms represented in molecular databases, and links from individual chains (and compact 3D domains within them) to structure neighbors, other chains (and 3D domains) with similar 3D structure. MMDB may be accessed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014 NR 14 TC 25 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2002 VL 30 IS 1 BP 249 EP 252 DI 10.1093/nar/30.1.249 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FB UT WOS:000173077100067 PM 11752307 ER PT J AU Marchler-Bauer, A Panchenko, AR Shoemaker, BA Thiessen, PA Geer, LY Bryant, SH AF Marchler-Bauer, A Panchenko, AR Shoemaker, BA Thiessen, PA Geer, LY Bryant, SH TI CDD: a database of conserved domain alignments with links to domain three-dimensional structure SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HIDDEN MARKOV-MODELS; SEQUENCE AB The Conserved Domain Database (CDD) is a compilation of multiple sequence alignments representing protein domains conserved in molecular evolution. It has been populated with alignment data from the public collections Pfam and SMART, as well as with contributions from colleagues at NCBI. The current version of CDD (v.1.54) contains 3693 such models. CDD alignments are linked to protein sequence and structure data in Entrez. The molecular structure viewer Cn3D serves as a tool to interactively visualize alignments and three-dimensional structure, and to link three-dimensional residue coordinates to descriptions of evolutionary conservation. CDD can be accessed on the World Wide Web at http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. Protein query sequences may be compared against databases of position-specific score matrices derived from alignments in CDD, using a service named CD-Search, which can be found at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi. CD-Search runs reverse-position-specific BLAST (RPS-BLAST), a variant of the widely used PSI-BLAST algorithm. CD-Search is run by default for protein-protein queries submitted to NCBI's BLAST service at http://www.ncbi.nlm.nih.gov/BLAST. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Marchler-Bauer, A (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 NR 13 TC 419 Z9 430 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2002 VL 30 IS 1 BP 281 EP 283 DI 10.1093/nar/30.1.281 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FB UT WOS:000173077100075 PM 11752315 ER PT J AU Sullivan, S Sink, DW Trout, KL Makalowska, I Taylor, PM Baxevanis, AD Landsman, D AF Sullivan, S Sink, DW Trout, KL Makalowska, I Taylor, PM Baxevanis, AD Landsman, D TI The Histone Database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESOLUTION; FOLD; H2A; H4 AB Histone proteins are often noted for their high degree of sequence conservation. It is less often recognized that the histones are a heterogeneous protein family. Furthermore, several classes of non-histone proteins containing the histone fold motif exist. Novel histone and histone fold protein sequences continue to be added to public databases every year. The Histone Database (http://genome.nhgri.nih.gov/histones/) is a searchable, periodically updated collection of histone fold-containing sequences derived from sequence-similarity searches of public databases. Sequence sets are presented in redundant and non-redundant FASTA form, hotlinked to GenBank sequence files. Partial sequences are also now included in the database, which has considerably augmented its taxonomic coverage. Annotated alignments of full-length non-redundant sets of sequences are now available in both web-viewable (HTML) and downloadable (PDF) formats. The database also provides summaries of current information on solved histone fold structures, post-translational modifications of histones, and the human histone gene complement. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Landsman, D (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 45,Room 6AN12J,43 Ctr Dr,MSC 6510, Bethesda, MD 20892 USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 18 TC 46 Z9 47 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2002 VL 30 IS 1 BP 341 EP 342 DI 10.1093/nar/30.1.341 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FB UT WOS:000173077100091 PM 11752331 ER PT J AU Terry, P Rohan, TE Wolk, A Maehle-Schmidt, M Magnusson, U AF Terry, P Rohan, TE Wolk, A Maehle-Schmidt, M Magnusson, U TI Fish consumption and breast cancer risk SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID FATTY-ACIDS; ADIPOSE-TISSUE; DIETARY FACTORS; MEAT INTAKE; ASSOCIATION; DISEASE; PROTEIN; HAWAII; FRANCE; WOMEN AB The omega-3 fatty acids, especially long-chain eicosapentaenoic acid (20:5n-3) and docosahexaenoic (22:6n-3) contained in "fatty" fish, have consistently been shown to retard the growth of breast cancer in vitro and in animal experiments. In contrast, studies of the association between fish consumption and breast cancer risk in human populations have not consistently shown inverse associations. However, previous studies have not considered the specific types of fish consumed. Using data from a large, nationwide case-control study conducted in Sweden, we examined the association between consumption of fatty and lean fish and breast cancer risk. Odds ratios (OR) and 95% confidence intervals were computed from unconditional logistic regression models. High consumption of fish was weakly associated with reduced breast cancer risk, and the association was, not statistically significant. With multivariate adjustment, the OR for women with the highest consumption (greater than or equal to3.5 servings/wk) compared with women with the lowest (virtually none) was 0.88 (95% confidence interval = 0.60-1.29, P for trend = 0.15); When type of fish was examined separately, the association was similar for fatty and lean fish. C1 Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. RP Terry, P (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM Terry2@niehs.nih.gov NR 41 TC 20 Z9 20 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2002 VL 44 IS 1 BP 1 EP 6 DI 10.1207/S15327914NC441_1 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 659NV UT WOS:000181784200001 PM 12672635 ER PT J AU Walcott, FL Hauptmann, M Duphorne, CM Pillow, PC Strom, SS Sigurdson, AJ AF Walcott, FL Hauptmann, M Duphorne, CM Pillow, PC Strom, SS Sigurdson, AJ TI A case-control study of dietary phytoestrogens and testicular cancer risk SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID GERM-CELL CANCER; HISTORY QUESTIONNAIRE; PHYSICAL-ACTIVITY; EPIDEMIOLOGY; HORMONES; DATABASE; LIGNANS; TESTIS; BREAST; CANADA AB A few dietary studies have found elevated testicular cancer risks for higher red meat, fat, and milk intakes and lower intakes of fruits, vegetables, and fiber. Because hormonal modulation by dietary intake of plant estrogens could affect risk of testicular cancer, we chose to explore the possible relationship between dietary phytoestrogens and testicular cancer. We conducted a hospital-based case-control study of 159 testicular cancer cases diagnosed between 1996 and 1996 and 136 adult friend-matched controls at the University of Texas M D. Anderson Cancer Center. Amounts of phytoestrogenic compounds in foods were added to the National Cancer Institute's DietSys program and then grouped into prelignans, lignans, flavonoids, isoflavonoids, phytosterols, and coumestrol for statistical analysis, expressed per 1,000 kcal. The results of multivariate logistic regression analysis showed, after ad. justment for age, education, income, ethnicity, cryptorchidism, body mass index, baldness unrelated to therapy, severe acne in adolescence, early puberty, daily fiber and fat intake, and total daily calories, no discernable monotonic increased or decreased risk estimates across quartiles of phytoestrogen intake. A U-shaped pattern was observed for lignans and coumestrol. Further evaluation of this pattern by cubic spline parameterization did fit the data, but the data were also consistent with no effect. This hypothesis-generating study does not support the premise that dietary phytoestrogens increase or decrease testicular cancer risk in young men. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7092,MSC 7238, Bethesda, MD 20892 USA. EM sigurdsa@mail.nih.gov FU NCI NIH HHS [R25-CA-57730] NR 44 TC 30 Z9 30 U1 0 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2002 VL 44 IS 1 BP 44 EP 51 DI 10.1207/S15327914NC441_6 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 659NV UT WOS:000181784200006 PM 12672640 ER PT J AU Martin, KR Saulnier, MJ Kari, FW Barrett, JC French, JE AF Martin, KR Saulnier, MJ Kari, FW Barrett, JC French, JE TI Timing of supplementation with the antioxidant N-acetyl-L-cysteine reduces tumor multiplicity in novel, cancer-prone p53 haploinsufficient Tg.AC (v-Ha-ras) transgenic mice but has no impact on malignant progression SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID MOUSE SKIN; OXIDATIVE STRESS; REDOX REGULATION; BETA-CAROTENE; ACETYLCYSTEINE; CARCINOGENESIS; PREVENTION; PROMOTION; INITIATION; RESPONSES AB Epidemiological studies support the protective role of dietary antioxidants in preventing cancer. However, emerging evidence suggests that antioxidant supplements may actually exacerbate carcinogenesis. We explored this paradox in a model containing two common genotypic characteristics of human cancers. We selected p53 haploinsufficient Tg.AC (nu-Ha-ras) mice as a model, because it contains an activated, carcinogen-inducible ras oncogene and an inactivated p53 tumor suppressor gene. These mice develop chemically induced benign and malignant skin tumors rapidly. Mice were fed basal diet with or without 3% N-acetyl-L-cysteine (NAC) before and after topical application of the carcinogen benzo[a]pyrene (64 mug twice per week for 7 wk) until 50% of mice within a group displayed at least one lesion. Half each of mice fed the basal and the NAC-supplemented diet were then switched to the alternate diet. Mice fed the NAC-supplemented diet or switched from the NAC-supplemented to the basal diet displayed 38% and 26% reductions, respectively, in tumor multiplicity and a 15% reduction if switched from the basal to the NAC-supplemented diet. Although latency was unaffected, NAC induced a lag in tumor incidence, which exceeded 90% at 10 wk for all groups. The timing of NAC supplementation did not affect malignant progression. Thus dietary NAC was chemoprotective by slowing tumorigenesis but did not affect malignant conversion. C1 Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. NIEHS, Transgen Carcinogenesis Unit, Lab Environm Carcinogenesis & Mutagenesis, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Martin, KR (reprint author), Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. NR 41 TC 8 Z9 8 U1 2 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2002 VL 43 IS 1 BP 59 EP 66 DI 10.1207/S15327914NC431_7 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 616QF UT WOS:000179313900007 PM 12467136 ER PT J AU Rodriguez-Burford, C Steele, VE Anderson, AS Stockard, CR Weiss, HL Eto, I Johanning, GL Grizzle, WE Grubbs, CJ AF Rodriguez-Burford, C Steele, VE Anderson, AS Stockard, CR Weiss, HL Eto, I Johanning, GL Grizzle, WE Grubbs, CJ TI Effects of body weight gain reduction resulting from chemopreventive agent treatment on mammary gland morphology SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID GROWTH-FACTOR-I; DIETARY RESTRICTION; CALORIC RESTRICTION; TUMOR PROMOTION; CELL-PROLIFERATION; ENERGY RESTRICTION; INDUCED INHIBITION; FOOD RESTRICTION; RATS; CARCINOGENESIS AB Moderate reductions (less than or equal to15%) in body weight gain, similar to those observed after administration of some chemopreventive agents in chemically induced mammary cancer models, will result in decreased mammary cancers (up to 55%). The objective of this study was to determine whether changes in mammary gland differentiation, proliferation, apoptosis, and estradiol and progesterone levels are affected by moderate reductions in body weight induced after chemopreventive agent treatment and dietary restriction. The body weights of female Sprague-Dawley rats were reduced by dietary restrictions to match those of rats receiving 4-hydroxyphenylretinamide (4-HPR) at a dose known to inhibit methylnitrosourea (MNU)-induced mammary cancers. 4-HPR supplementation or dietary restrictions began 1 wk before MNU administration at 50 days of age. Mammary gland differentiation, proliferation, apoptosis, and serum levels of estradiol and progesterone were measured at 50, 57, and 71 days of age. Casein expression, proliferating cellular nuclear antigen expression, and apoptosis were not significantly different from controls in the dietary-restricted group. Proliferating cellular nuclear antigen expression was significantly lower in 4-HPR-treated animals than in controls at 57 days of age. ne diameter of the mammary gland ducts was smaller at 71 days of age in the treatment groups. A decrease in estradiol levels for each group was observed at 50 days of age, but not at later time points. Progesterone levels were reduced in the 4-HPR group, but not in the dietary-restricted group, during each time period. It would appear that the observed decrease in mammary cancers observed with moderate reductions in body weight gain might be due to multiple related factors different from those related to 4-HPR treatment. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Chemoprevent Ctr, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Biostat Unit, Birmingham, AL 35294 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Rodriguez-Burford, C (reprint author), BDB 11,1530 3rd Ave S, Birmingham, AL 35294 USA. FU NCI NIH HHS [N01-CN-65025-MAO, N01-CN-75101-MAO] NR 40 TC 2 Z9 2 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2002 VL 43 IS 1 BP 67 EP 75 DI 10.1207/S15327914NC431_8 PG 9 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 616QF UT WOS:000179313900008 PM 12467137 ER PT J AU Wan, XS Serota, DG Ware, JH Crowell, JA Kennedy, AR AF Wan, XS Serota, DG Ware, JH Crowell, JA Kennedy, AR TI Detection of Bowman-Birk inhibitor and anti-Bowman-Birk inhibitor antibodies in sera of humans and animals treated with Bowman-Birk inhibitor concentrate SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID PROTEASE INHIBITOR; ORAL LEUKOPLAKIA; MICE; DIMETHYLHYDRAZINE; CARCINOGENESIS; SUPPRESSION; MODULATION AB The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor with anticarcinogenic activities. BBI, in the form of BBI concentrate (BBIC), is currently being evaluated in clinical trials as a human cancer-preventive agent. In the present study, an enzyme-linked immunosorbent assay was used to measure BBI concentrations in serum samples collected from human subjects and animals treated with BBIC. The results demonstrate that the serum BBI concentration was higher than the baseline level for the patients after treatment with BBIC at 100-800 chymotrypsin-inhibitor units/day for 0.5, 1, 2, 4, and 6 mo. The increase in serum BBI concentration was also observed in dogs treated with BBIC at 100-1,000 mg/kg/day for 52 wk, and the increase was dose dependent. The results also indicate that anti-BBI antibodies were present in animals and the serum levels of anti-BBI antibodies increased significantly in mice treated with BBIC at 100-1,000 mg/kg/day for 15 and 26 wk. The increase in the serum level of anti-BBI antibodies in dogs treated with BBIC was not statistically significant, and no increase in the serum level of anti-BBI antibodies was observed in human subjects after BBIC treatment. These results suggest that orally ingested BBI is absorbed by human subjects and animals and that some animals develop antibodies to BBI in response to treatment with BBIC. C1 Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. MPI Res, Mattawan, MI 49071 USA. NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Rockville, MD 20852 USA. RP Wan, XS (reprint author), Univ Penn, Dept Radiat Oncol, 195 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. NR 23 TC 10 Z9 10 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2002 VL 43 IS 2 BP 167 EP 173 DI 10.1207/S15327914NC432_7 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 636AN UT WOS:000180432500007 PM 12588697 ER PT J AU Chen, HL Tucker, KL Graubard, BI Heineman, EF Markin, RS Potischman, NA Russell, RM Weisenburger, DD Ward, MH AF Chen, HL Tucker, KL Graubard, BI Heineman, EF Markin, RS Potischman, NA Russell, RM Weisenburger, DD Ward, MH TI Nutrient intakes and adenocarcinoma of the esophagus and distal stomach SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID GASTRIC-CANCER RISK; UNITED-STATES; VITAMIN-E; GASTROESOPHAGEAL REFLUX; COLORECTAL ADENOMAS; BODY-MASS; CARDIA; DIET; CAROTENOIDS; ALCOHOL AB We studied the relationship between nutrient intakes and adenocarcinoma of the esophagus and distal stomach among 124 esophageal adenocarcinoma cases, 124 distal stomach cancer cases, and 449 controls in a population-based case-control study in eastern Nebraska. The residual method was used to adjust nutrient intake quartiles or tertiles for energy intake. We observed significant inverse associations with risk of esophageal adenocarcinoma for dietary intakes of total vitamin A [highest vs. lowest quartile, multi-variate odds ratio (OR) = 0.5, P for trend = 0.05], beta-cryptoxanthin (OR = 0.5, P = 0.05), riboflavin (OR = 0.5, P = 0.01), folate (OR = 0.5, P = 0.03), zinc (OR = 0.5, P = 0.05), dietary fiber (OR = 0.5, P = 0.05), protein (OR = 0.5, P = 0.02), and carbohydrate (OR = 0.4, P = 0.02). For distal stomach cancer, only vitamin C (OR = 0.6, P = 0.04), dietary fiber (OR = 0.4, P = 0.007), and carbohydrate (OR = 0.4, P = 0.004) were inversely associated with risk. Our analyses shoved significant interaction between dietary fat intake, but not intakes of other nutrients, and respondent type for both cancer sites. Subgroup analyses among self-respondents revealed positive associations between saturated fat intake and risk of esophageal adenocarcinoma (OR = 1.0, 4.1, and 4.6 for intake tertiles, P for trend = 0.02) and risk of distal stomach cancer (OR = 1.0, 1.2, and 3.6, P = 0.03). However, no such associations were found among proxy respondents. Our data suggest that greater intake of dietary fiber, certain carotenoids, and vitamins may decrease the risk of esophageal adenocarcinoma, whereas greater intake of saturated fat may increase the risk of esophageal adenocarcinoma and distal stomach cancer. C1 Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. RP Chen, HL (reprint author), Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X; Chen, Honglei/0000-0003-3446-7779 NR 59 TC 98 Z9 104 U1 0 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2002 VL 42 IS 1 BP 33 EP 40 DI 10.1207/S15327914NC421_5 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 590CG UT WOS:000177799500005 PM 12235648 ER PT J AU Martin, LJ Mahaney, MC Almasy, L MacCluer, JW Blangero, J Jaquish, CE Comuzzie, AG AF Martin, LJ Mahaney, MC Almasy, L MacCluer, JW Blangero, J Jaquish, CE Comuzzie, AG TI Leptin's sexual dimorphism results from genotype by sex interactions mediated by testosterone. SO OBESITY RESEARCH LA English DT Article DE Mexican Americans; variance decomposition; body fat; sex hormones ID PROOPIOMELANOCORTIN GENE-EXPRESSION; BODY-FAT DISTRIBUTION; SERUM LEPTIN; MEXICAN-AMERICANS; PLASMA LEPTIN; OBESE GENE; REPRODUCTIVE FUNCTION; PEDIGREE ANALYSIS; ADIPOSE-TISSUE; FEMALE MICE AB Objective: Recent studies have reported the existence of marked sexual dimorphism in serum leptin levels in humans, with women having approximately three times the levels of men. As we have shown for other measures of adiposity, such sexual dimorphism can arise from a special case of genotype by environment interaction, that of genotype by sex interaction. Research Methods and Procedures: Using maximum likelihood-based variance decomposition techniques, we examined the genetic and environmental architecture of sexual dimorphism in serum leptin levels in 1147 Mexican Americans from the San Antonio Family Heart Study. Results: Both the genetic and environmental variances for this trait differed significantly between the sexes (p < 0.001 and p < 0.01, respectively), with women displaying larger values for both components. We found significant evidence that different genes influence variation in serum leptin levels between the two sexes (p = 0.05). Furthermore, this pattern of sexual dimorphism in serum leptin levels persisted even after accounting for the effects of either the percentage of body fat or total body fat. However, this pattern of sexual dimorphism was eliminated after accounting for the effects of testosterone. Discussion: These findings suggest that the sexual dimorphism seen in leptin levels is not simply explained as differences in total adiposity between the sexes. We conclude that the genes, which influence variation in serum leptin levels, are differentially expressed depending on sex, and that the sexes also show differences in response of the expression of this obesity-related trait to unmeasured residual effects. C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. Natl Heart Lung & Blood Inst, Bethesda, MD USA. RP Martin, LJ (reprint author), SW Fdn Biomed Res, Dept Genet, Box 760549, San Antonio, TX 78245 USA. RI Martin, Lisa/E-2425-2016 OI Martin, Lisa/0000-0001-8702-9946 FU NHLBI NIH HHS [HL45522]; NIDDK NIH HHS [DK44297]; NIGMS NIH HHS [GM15803]; NIMH NIH HHS [MH59890] NR 54 TC 40 Z9 43 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD JAN PY 2002 VL 10 IS 1 BP 14 EP 21 DI 10.1038/oby.2002.3 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 510ZH UT WOS:000173237100003 PM 11786597 ER PT J AU Frijhoff, AFW Conti, CJ Senderowicz, AM AF Frijhoff, AFW Conti, CJ Senderowicz, AM TI Second symposium of novel molecular targets for cancer therapy SO ONCOLOGIST LA English DT Editorial Material DE antineoplastic agents; therapy-related cancer; clinical trials; cell cycle; angiogenesis; molecular targets ID TUMOR ANGIOGENESIS; KINASE; GROWTH; EXPRESSION; INHIBITION; MODULATORS; PROTEIN; UCN-01 C1 NIDCR, NIH, Oral & Pharyngeal Canc Branch, Mol Therapeut Unit, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Res, Smithville, TX USA. RP Senderowicz, AM (reprint author), NIDCR, NIH, Oral & Pharyngeal Canc Branch, Mol Therapeut Unit, Bldg 30,Room 211,30 Convent Dr, Bethesda, MD 20892 USA. NR 27 TC 2 Z9 2 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 SU 3 BP 1 EP 3 DI 10.1634/theoncologist.7-suppl_3-1 PG 3 WC Oncology SC Oncology GA 586MJ UT WOS:000177587500001 PM 12165649 ER PT J AU Senderowicz, AM AF Senderowicz, AM TI The cell cycle as a target for cancer therapy: Basic and clinical findings with the small molecule inhibitors flavopiridol and UCN-01 SO ONCOLOGIST LA English DT Article; Proceedings Paper CT 2nd Symposium of Novel Molecular Targets for Cancer Therapy CY OCT 04-05, 2001 CL BUENOS AIRES, ARGENTINA SP Natl Inst Hlth, Natl Inst Dent & Craniofacial Res, Natl Inst Hlth, Natl Canc Inst, Int Soc Translat Res DE cell cycle; cyclin-dependent kinases; flavopiridol; UCN-01; phase I trials; clinical trials ID DEPENDENT KINASE INHIBITOR; BREAST-CARCINOMA CELLS; S-PHASE CHECKPOINT; RNA-POLYMERASE-II; PROTEIN-KINASE; LUNG-CANCER; P-TEFB; RADIOSENSITIZING AGENT; REFRACTORY NEOPLASMS; IN-VIVO AB Many tumor types are associated with genetic changes in the retinoblastoma pathway, leading to hyperactivation of cyclin-dependent kinases and incorrect progression through the cell cycle. Small-molecule cyclin-dependent kinase inhibitors are being developed as therapeutic agents. Of these, flavopiridol and UCN-01 are being explored in cancer patients in phase I and phase 11 clinical trials, both as single agents and in combination with conventional chemotherapeutic agents. The present article discusses the mechanisms of action of flavopiridol and UCN-01 as well as the outcome of clinical trials with these novel agents. C1 NIDCR, NIH, Oral & Pharyngeal Canc Branch, Mol Therapeut Unit, Bethesda, MD 20892 USA. RP Senderowicz, AM (reprint author), NIDCR, NIH, Oral & Pharyngeal Canc Branch, Mol Therapeut Unit, Bldg 30,Room 211,30 Convent Dr, Bethesda, MD 20892 USA. NR 72 TC 87 Z9 94 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 SU 3 BP 12 EP 19 PG 8 WC Oncology SC Oncology GA 586MJ UT WOS:000177587500003 PM 12165651 ER PT J AU Espinoza-Delgado, I AF Espinoza-Delgado, I TI Cancer vaccines SO ONCOLOGIST LA English DT Article; Proceedings Paper CT 2nd Symposium of Novel Molecular Targets for Cancer Therapy CY OCT 04-05, 2001 CL BUENOS AIRES, ARGENTINA SP Natl Inst Hlth, Natl Inst Dent & Craniofacial Res, Natl Inst Hlth, Natl Canc Inst, Int Soc Translat Res DE cancer; vaccines; immunotherapy; dendritic cells ID COLONY-STIMULATING FACTOR; CYTOTOXIC T-LYMPHOCYTES; PULSED DENDRITIC CELLS; ANTI-CD20 MONOCLONAL-ANTIBODY; RECOMBINANT INTERLEUKIN-2 THERAPY; TUMOR-INFILTRATING LYMPHOCYTES; ACTIVE SPECIFIC IMMUNOTHERAPY; HIGH-DOSE INTERFERON-ALPHA-2B; METASTATIC MELANOMA PATIENTS; COOPERATIVE-ONCOLOGY-GROUP AB Although cancer immunotherapy was initiated by William Coley more than a century ago, the field of cancer vaccines is in an early stage of development. Only recently, major advances in cellular and molecular immunology have allowed a comprehensive understanding of the complex and high rate of interactions between the immune system and tumor cells. We have learned that these tumor-immune system interactions may result either in strong immune antitumor response or tolerance to tumor-associated antigens. This article will discuss the profound interest in cancer vaccines derived from their potential to induce antitumor responses in vivo. Substantial data from several preclinical models and early human clinical trials have confirmed the ability of cancer vaccines to induce immune responses that are tumor-specific and, in some cases, associated with clinical responses. One future challenge will be to determine how to appropriately stimulate the pathways leading to effective interaction among antigen-presenting cells, T lymphocytes, and tumor cells. It also is critical to develop monitoring strategies that may allow the identification of patients who may benefit from cancer vaccines. C1 Natl Inst Aging, Hematol Oncol Sect, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Espinoza-Delgado, I (reprint author), Natl Inst Aging, Hematol Oncol Sect, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr,Room 4C10, Baltimore, MD 21224 USA. NR 131 TC 19 Z9 22 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 SU 3 BP 20 EP 33 DI 10.1634/theoncologist.7-suppl_3-20 PG 14 WC Oncology SC Oncology GA 586MJ UT WOS:000177587500004 PM 12165652 ER PT J AU von Eschenbach, AC AF von Eschenbach, AC TI NCI remains committed to current mammography guidelines SO ONCOLOGIST LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP von Eschenbach, AC (reprint author), NCI, Bethesda, MD 20892 USA. NR 3 TC 13 Z9 13 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 3 BP 170 EP 171 DI 10.1634/theoncologist.7-3-170 PG 2 WC Oncology SC Oncology GA 563BR UT WOS:000176234200001 PM 12065784 ER PT J AU Fox, E Curt, GA Balis, FM AF Fox, E Curt, GA Balis, FM TI Clinical trial design for target-based therapy SO ONCOLOGIST LA English DT Article DE clinical trials; drug development; pharmacokinetics; pharmacodynamics; molecular targets ID ACUTE PROMYELOCYTIC LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; TRANS-RETINOIC ACID; ANTICANCER AGENTS; PHASE-I; INHIBITOR; EFFICACY; FARNESYL; GROWTH AB Anticancer drug discovery has shifted from an empiric random screening directed approach to a more rational and mechanistic, target-based approach, which reflects our rapidly expanding knowledge of the pathogenesis of a variety of forms of cancer at the molecular level, providing new targets for drug discovery and development. The clinical development of target-based anticancer drugs will require fundamental changes to the traditional clinical trial design and end points that have been used for conventional cytotoxic drugs. In the phase I and H settings, traditional end points (toxicity and response) may not be suitable for more selective, cytostatic target-based agents, and these end points may be replaced by biological or pharmacokinetic end points to define the optimal doses and the therapeutic effects of these drugs on their targets. For phase III trials, measurable clinical benefit will continue to be the primary end point. As our understanding of the complex pathways and networks controlling cell signaling, proliferation, and cell death expands, we must learn how and when to use agents to target specific steps in malignant transformation and proliferation, and we must adapt clinical trial design to test the clinical utility of this promising new class of anticancer drugs. C1 NCI, Pediat Oncol Branch, CCR, Bethesda, MD 20892 USA. RP Fox, E (reprint author), NCI, Pediat Oncol Branch, CCR, Bldg 10-Room 13C103,10 Ctr Dr,MSC 1920, Bethesda, MD 20892 USA. NR 38 TC 84 Z9 86 U1 0 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 5 BP 401 EP 409 DI 10.1634/theoncologist.7-5-401 PG 9 WC Oncology SC Oncology GA 611XM UT WOS:000179043200003 PM 12401902 ER PT J AU Low, J Swain, SM AF Low, J Swain, SM TI Current management of menopausal symptoms in cancer patients - The Barton/Loprinzi/Gostout article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID POSTMENOPAUSAL WOMEN; BREAST-CANCER; ESTROGEN; TRIAL C1 NCI, Med Branch, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2002 VL 16 IS 1 BP 76 EP + PG 3 WC Oncology SC Oncology GA 513HQ UT WOS:000173372800013 ER PT S AU Hattery, D Gerdelman, K Hekmat, F Chernomordik, V Paul, S Eidsath, A Pursley, R Atkinson, J Mulshine, J Gandjbakhche, A AF Hattery, D Gerdelman, K Hekmat, F Chernomordik, V Paul, S Eidsath, A Pursley, R Atkinson, J Mulshine, J Gandjbakhche, A BE Alfano, RR TI Diffuse reflectance Spectroscopy to quantify inflammation of the oral epithelium in vivo SO OPTICAL BIOPSY IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Biopsy IV CY JAN 21-23, 2002 CL SAN JOSE, CA SP SPIE ID PHOTON MIGRATION; IN-VIVO; TISSUE AB Recent studies suggest that inflammatory cell products may contribute to the evolution of particular cancers leading to new chemoprevention trials exploring the benefit of anti-inflammatory drugs such as aspirin and related products. As part of a prospective trial evaluating this anti-inflammatory strategy for oral cancer, we evaluated a non-invasive optical system to determine if we could use an indirect measure of oral inflammation, mucosal thickness, as a monitoring parameter to evaluate the effectiveness of anti-inflammatory drug therapy. Diffuse reflectance spectroscopy has the potential for probing near-surface structures, however, traditional methods for accounting for scattering of photons are generally invalid for typical epithelial thicknesses. Monte Carlo simulations have shown that, with proper scaling, a simple photon model may be used to predict photon behavior under these conditions. A differential measure, which is very sensitive to small changes, has been shown to have the potential to quantify epithelial thickness. A simple prototype device has been brought from desk, to bench and bedside in a rapid manner to fill a need for a non-invasive measure of oral inflammation. From the theory, a simple feature has been identified that corresponds to patient oral inflammation. Preliminary results from this work are presented and indicate that further development of the approach to enable quantification of epithelial thickness in vivo is warranted. Keywords: oral, spectroscopy, inflammation, diffuse-reflectance, leukoplakia, chemoprevention. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Hattery, D (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bldg 12a,Room 2041, Bethesda, MD 20892 USA. NR 19 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 0-8194-4352-2 J9 P SOC PHOTO-OPT INS PY 2002 VL 4613 BP 59 EP 70 DI 10.1117/12.465230 PG 12 WC Engineering, Biomedical; Optics; Physics, Applied; Spectroscopy SC Engineering; Optics; Physics; Spectroscopy GA BU69V UT WOS:000176733000011 ER PT S AU Costes, S Slobodskaya, O Cho, E Tsopanomichalou, M Pavlakis, GN Lockett, S AF Costes, S Slobodskaya, O Cho, E Tsopanomichalou, M Pavlakis, GN Lockett, S BE Farkas, DL Leif, RC TI FRAP model to determine the bi-directional transport rate of GFP across the nuclear membrane and the mobile fraction in the cytoplasm and nucleus SO OPTICAL DIAGNOSTICS OF LIVING CELLS V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Diagnostics of Living Cells V CY JAN 23-25, 2002 CL SAN JOSE, CA SP SPIE AB A mathematical model was developed to predict the bi-directional transport rate of fluorescent proteins across the nuclear membrane during a fluorescence recovery after photobleaching (FRAP) experiment. The model assumes that the total amount of fluorescent protein remains the same in the cell (i.e. no production, loss or exchange with the outside of the cell) and that the cell is in a state of equilibrium; i.e. proteins are leaving and entering the nucleus at an equal rate. The latter assumption has the advantage of not needing to take into account the method of protein transport (e.g. active or passive). The model includes correction for the photobleaching that happens during image acquisition following the deliberate photobleach. In this study, the green fluorescent protein (GFP) was transfected into cells in order to study its free behavior. In the FRAP experiments, either the entire nucleus and part of the cytoplasm or only part of the cytoplasm was photobleached followed by time-series imaging of the fluorescence redistribution. The model was fitted to the curves of intensity loss or recovery after photobleaching using numerical, nonlinear methods. In addition, the mobile fractions of free GFP in the cytoplasm and the nucleus could be determined. C1 NCI, SAIC Frederick, Image Anal Lab, Ft Detrick, MD 21702 USA. RP Costes, S (reprint author), NCI, SAIC Frederick, Image Anal Lab, POB B, Ft Detrick, MD 21702 USA. RI Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 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 0-8194-4361-1 J9 P SOC PHOTO-OPT INS PY 2002 VL 4622 BP 32 EP 39 DI 10.1117/12.468359 PG 8 WC Cell Biology; Engineering, Biomedical; Instruments & Instrumentation; Optics SC Cell Biology; Engineering; Instruments & Instrumentation; Optics GA BU73F UT WOS:000176855500004 ER PT J AU Turner, RJ Sugiya, H AF Turner, RJ Sugiya, H TI Understanding salivary fluid and protein secretion SO ORAL DISEASES LA English DT Article ID PAROTID ACINAR-CELLS; VESICLE-ASSOCIATED MEMBRANE-PROTEIN-2; GTP-BINDING PROTEIN; NA+-K+-2CL(-) COTRANSPORTER; REGULATED EXOCYTOSIS; CYCLIC-AMP; AMYLASE SECRETION; UP-REGULATION; GRANULE MEMBRANES; PHOSPHOLIPASE-D C1 NIDCR, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Nihon Univ, Sch Dent, Dept Physiol, Matsudo, Chiba 271, Japan. RP Turner, RJ (reprint author), NIDCR, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Rm 1A01,10 Ctr Dr MSC 1190, Bethesda, MD 20892 USA. NR 62 TC 123 Z9 128 U1 0 U2 13 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JAN PY 2002 VL 8 IS 1 BP 3 EP 11 DI 10.1034/j.1601-0825.2002.10815.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 533XT UT WOS:000174556100002 PM 11936453 ER PT J AU Kleinman, DV AF Kleinman, DV TI Comments upon the opening of the fourth international workshop on the oral manifestations of HIV infection, Skukuza, South Africa SO ORAL DISEASES LA English DT Editorial Material DE oral manifestations; HIV infection; AIDS ID HIV/AIDS C1 NIDR, Bethesda, MD 20892 USA. RP Kleinman, DV (reprint author), NIDR, Bldg 31,Room 2C39,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 12 TC 8 Z9 9 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1354-523X J9 ORAL DIS JI Oral Dis. PY 2002 VL 8 SU 2 BP 6 EP 8 DI 10.1034/j.1601-0825.2002.00002.x PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 570MT UT WOS:000176662600002 PM 12164662 ER PT J AU Williams, DM Leigh, J Ramirez-Amador, V Kaonga, K Russo, D Schiodt, M AF Williams, DM Leigh, J Ramirez-Amador, V Kaonga, K Russo, D Schiodt, M TI Host pathogen interaction and the development of oral lesions SO ORAL DISEASES LA English DT Article; Proceedings Paper CT 4th International Workshop on the Oral Manifestations of HIV Infection CY JUL, 2000 CL SKUKUZA, SOUTH AFRICA DE recurrent aphthous stomatitis; disseminated interstitial lymphocytosis syndrome; lymphoma ID TUMOR-NECROSIS-FACTOR; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RECURRENT APHTHOUS STOMATITIS; INFILTRATIVE LYMPHOCYTOSIS SYNDROME; PAROTID-GLAND ENLARGEMENT; EFFUSION LYMPHOMA-CELLS; FACTOR-ALPHA PRODUCTION; 65-KDA STRESS PROTEIN; HIV-INFECTED PATIENTS; NON-HODGKINS-LYMPHOMA AB The aetiologies of oral ulceration, disseminated interstitial lymphocytosis syndrome and oral lymphomas have been reviewed, with emphasis on the role of HIV infection in the primary causation or modification of the presentation of these entities. There is a paucity of evidence to explain why oral ulceration is so severe in HIV infection, and why major ulceration affects the oropharynx. A number of mechanisms have been proposed to account for the development of lymphomas in patients with HIV infection, including a genetic predisposition, decreased immunosurveillance due to HIV infection, alteration of endothelial cell function and dysregulation of cytokine networks. From this review, it was concluded that there is a need for a prospective multicentre study, to elucidate the aetiological mechanisms involved in lymphomas of the oral regions in this patient group. It was concluded that, although there is anecdotal evidence implicating tobacco use in the aetiology of the lesions reviewed, this is insufficient to allow definitive statements to be made and further systematic evaluation is indicated. C1 Barts & London Queen Marys Sch Med & Dent, London E1 2AD, England. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Univ Autonoma Metropolitana Xochimilco, Mexico City, DF, Mexico. Univ Teaching Hosp, Lusaka, Zambia. NIH, Bethesda, MD 20892 USA. Copenhagen Cty Univ Hosp, Glostrup, Denmark. RP Williams, DM (reprint author), Barts & London Queen Marys Sch Med & Dent, Turner St, London E1 2AD, England. NR 77 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1354-523X J9 ORAL DIS JI Oral Dis. PY 2002 VL 8 SU 2 BP 120 EP 125 AR UNSP ODIC23 DI 10.1034/j.1601-0825.8.s2.2.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 570MT UT WOS:000176662600023 PM 12164645 ER PT B AU Cohen, LK AF Cohen, LK BE Inglehart, MR Bagramian, RA TI Oral health-related quality of life SO ORAL HEALTH-RELATED QUALITY OF LIFE LA English DT Proceedings Paper CT Workshop on Oral Health-Related Quality of Life CY MAY, 2000 CL UNIV MICHIGAN, SCH DENT, ANN ARBOR, MI SP NIDCR HO UNIV MICHIGAN, SCH DENT C1 NIDCR, Off Int Hlth, NIH, Bethesda, MD USA. RP Cohen, LK (reprint author), NIDCR, Off Int Hlth, NIH, Bethesda, MD USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 0-86715-421-7 PY 2002 BP VII EP VIII PG 2 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA BV92K UT WOS:000180400900001 ER PT B AU Bryant, PS Kleinman, DV AF Bryant, PS Kleinman, DV BE Inglehart, MR Bagramian, RA TI Research on oral health-related quality of life: Current status and future directions SO ORAL HEALTH-RELATED QUALITY OF LIFE LA English DT Proceedings Paper CT Workshop on Oral Health-Related Quality of Life CY MAY, 2000 CL UNIV MICHIGAN, SCH DENT, ANN ARBOR, MI SP NIDCR HO UNIV MICHIGAN, SCH DENT ID OF-LIFE; SOCIAL IMPACT; ADULTS; OUTCOMES C1 NIDCR, Behav & Social Sci Res Program, Div Populat & Hlth Promot, Bethesda, MD USA. RP Bryant, PS (reprint author), NIDCR, Behav & Social Sci Res Program, Div Populat & Hlth Promot, Bethesda, MD USA. NR 34 TC 0 Z9 0 U1 1 U2 1 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 0-86715-421-7 PY 2002 BP 193 EP 204 PG 12 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA BV92K UT WOS:000180400900018 ER PT J AU MacPhail, LA Komaroff, E Alves, MEAF Navazesh, M Phelan, JA Redford, M AF MacPhail, LA Komaroff, E Alves, MEAF Navazesh, M Phelan, JA Redford, M TI Differences in risk factors among clinical types of oral candidiasis in the Women's Interagency HIV Study SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID OROPHARYNGEAL CANDIDIASIS; ERYTHEMATOUS CANDIDIASIS; DENTURE STOMATITIS; INFECTED PATIENTS; ALBICANS; LESIONS; RATES; ASSOCIATION; FREQUENCY; THERAPY AB Objectives. The purpose of this study was to determine the prevalence and concurrence/associations of oral candidiasis types and multiple risk factors in women. Study design. A cross-sectional analysis of baseline data for 577 human immunodeficiency virus (HIV)-seropositive and 152 HIV-seronegative women from the Women's Interagency HIV Study was conducted. Pseudomembranous candidiasis (PC) and erythematous (EC) candidiasis, angular cheilitis (AC), and denture stomatitis (DS) were studied, and bivariate and multivariate regression analyses were performed. Results. Prevalences were 8% for PC, 7% for EC, 18% for DS, and 3% for AC; all except AC usually occurred alone. HIV seropositivity was associated with PC, EC, and DS, but not AC. Among HIV-seropositive women, low CD4 cell counts were associated with PC, but not with EC or DS. Heroin/methadone use was associated with PC and EC; salivary hypofunction was associated with PC; high viral load was associated with EC, and poor oral hygiene, with EC and DS. Conclusions. Risk factors varied among candidiasis types, suggesting differences in pathogenic mechanisms and usefulness as markers of HIV infection/progression. C1 Temple Univ, Sch Dent, Dept Oral & Maxillofacial Pathol Med & Surg, Philadelphia, PA 19140 USA. NIDCR, Clin Trials & Epidemiol Studies Program, NIH, Bethesda, MD USA. NYU, Coll Dent, Div Biol Sci Med & Surg, Dept Oral Pathol, New York, NY USA. Univ So Calif, Dept Dent Med & Publ Hlth, Los Angeles, CA USA. Univ Illinois, Chicago, IL USA. SUNY Stony Brook, Sch Med, Dept Prevent Med, Stony Brook, NY 11794 USA. New England Res Inst, Watertown, MA 02172 USA. RP MacPhail, LA (reprint author), Temple Univ, Sch Dent, Dept Oral & Maxillofacial Pathol Med & Surg, 3223 N Broad St, Philadelphia, PA 19140 USA. FU PHS HHS [U01 A134989] NR 37 TC 13 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 2002 VL 93 IS 1 BP 45 EP 55 DI 10.1067/moe.2002.120050 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 516LE UT WOS:000173554100011 PM 11805777 ER PT J AU Snow, JB AF Snow, JB TI Progress in the prevention of otitis media through immunization SO OTOLOGY & NEUROTOLOGY LA English DT Article DE conjugated vaccine; detoxified lipooligosaccharide; Moraxella catarrhalis; nontypeable Haemophilus influenzae; otitis media; respiratory syncytial virus; Streptococcus pneumoniae ID DETOXIFIED LIPOOLIGOSACCHARIDE; CHILDREN; PROTEINS; VACCINE AB Objective: To review the progress that has been made in developing effective vaccines against the major bacterial pathogens responsible for acute otitis media. Data Source: Review of the literature with the aid of the MEDLINE database using the search terms otitis media and otitis media and vaccine. Data Extraction: Data were collected from clinical trials and laboratory studies. Findings: The heptavalent pneumococcal conjugated vaccine, Prevnar, reduced the incidence of acute otitis media from all causes by 7% in one study and by 6% in another study. For culture-positive pneumococcal otitis media, the point estimate of efficacy was 66.7% in one study, and the reduction in incidence was 34% in another study. A Phase I clinical trial has been completed successfully for a conjugated vaccine against nontypeable Haemophilus influenzae (NTHi), which has high immunogenicity for mice and rabbits, induces complement- mediated bactericidal activity against NTHi in rabbits, and is protective against NTHi otitis media in chinchillas. A conjugated vaccine against Moraxella catarrhalis elicits strong immune responses in mice and rabbits and induces complement-mediated bactericidal activity in rabbits. Conclusion: The prevention of otitis media is likely to require multivalent pneumococcal, NTHi, and M. catarrhalis vaccines, and these vaccines likely can be developed within a decade. C1 NIH, Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RP Snow, JB (reprint author), 33506 Tuckahoe River Rd, Easton, MD 21601 USA. NR 12 TC 1 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2002 VL 23 IS 1 BP 1 EP 2 DI 10.1097/00129492-200201000-00001 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 513CM UT WOS:000173360400001 PM 11773835 ER PT J AU Hediger, ML Overpeck, MD Ruan, WJ Troendle, JF AF Hediger, ML Overpeck, MD Ruan, WJ Troendle, JF TI Birthweight and gestational age effects on motor and social development SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID LOW-BIRTH-WEIGHT; PRETERM BIRTH; BODY-COMPOSITION; SCREENING-TEST; CHILDREN BORN; UNITED-STATES; INFANTS BORN; GROWTH; TERM; COHORT AB The number of children at risk for delays in motor and social development (MSD) associated with preterm delivery and low birthweight is increasing, but such children are generally not seen as being in need of evaluation. The objective of these analyses was to determine whether there are independent effects of birthweight and gestational age on MSD and the magnitude of effects. Subjects were a representative sample of 4621 US-born singleton children, aged 2-47 months, examined in the third National Health and Nutrition Examination Survey (1988-94). MSD was assessed using an age-appropriate scale. Birthweight and gestational age were taken from birth certificates. Mexican-American and 'other' race/ethnicity (other than non-Hispanic-white, non-Hispanic black or Mexican-American), low parental education level, older maternal age, higher birth order, low birthweight (LBW, <2500 g) and preterm delivery (<37 weeks) were all found to be associated with significant (P < 0.01) delays in MSD. Three per cent of the infants and children were preterm LBW and 2.2% term LBW (<2500 g, 37-44 weeks). Adjusting for socio-demographic factors, preterm LBW children had lower MSD scores (-1.5+/-0.3 points, P < 0.0001) through early childhood, as did term LBW children (-0.8+/-0.4 points, P < 0.03). For females, LBW was the most important perinatal predictor of a lowered score (-0.9+/-0.3 points compared with normal birthweight, P < 0.04). For males, scores were additionally decreased by -0.1+/-0.03 points/week (P = 0.001) of early delivery LBW children had less muscle mass, but adjusting for muscularity did not diminish the effects of birth size on MSD. LBW status and preterm delivery are associated independently with small, but measurable, delays in MSD through early childhood and should be considered along with other known risk factors for development delays in determining the need for developmental evaluation. C1 NICHHD, DESPR, NIH, Bethesda, MD 20892 USA. US Hlth Resources & Serv Adm, Maternal & Child Hlth Bur, Rockville, MD 20857 USA. RP Hediger, ML (reprint author), NICHHD, DESPR, NIH, Bldg 6100,Room 7B03,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 72 Z9 73 U1 1 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2002 VL 16 IS 1 BP 33 EP 46 DI 10.1046/j.1365-3016.2002.00393.x PG 14 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 519ZH UT WOS:000173755000007 PM 11856453 ER PT J AU Miller, AM Harwood, RL AF Miller, Amy M. Harwood, Robin L. TI The Cultural Organization of Parenting: Change and Stability of Behavior Patterns During Feeding and Social Play Across the First Year of Life SO PARENTING-SCIENCE AND PRACTICE LA English DT Article AB Objective. This study explores the cultural patterning of maternal beliefs and practices across the first year of life among middle-class Anglo and Puerto Rican mother-infant dyads in two daily situations, feeding and social play. Design. Sixty middle-class mothers (32 Anglo from northeastern Connecticut, and 28 Puerto Rican from San Juan, Puerto Rico) were interviewed regarding their long-term socialization goals and videotaped in their homes during feeding and social play when their infants were 4-, 8-, and 12-months of age. Results. Group comparisons revealed that across time and contexts the Anglo mothers were more likely to show patterns of beliefs and behaviors that emphasized the infant's personal choice and mastery of the situation, whereas the Puerto Rican mothers were more likely to show patterns of beliefs and behaviors that emphasized the infant's interdependence on the mother. The groups did not differ in nurturant behaviors toward their infants. Conclusions. The organization of feeding and social play differs by culture. Within this larger cultural frame, mother-infant interactions differ by context and adjust to universal aspects of infant development. C1 [Miller, Amy M.] NICHD, Bethesda, MD 20892 USA. [Harwood, Robin L.] Univ Connecticut, Storrs, CT 06269 USA. RP Miller, AM (reprint author), NICHD, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. EM am371e@nih.gov NR 33 TC 21 Z9 23 U1 0 U2 5 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2002 VL 2 IS 3 BP 241 EP 272 AR PII 785828747 DI 10.1207/S15327922PAR0203_03 PG 32 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA V12OE UT WOS:000207607700003 ER PT J AU Bornstein, MH Venuti, P Hahn, CS AF Bornstein, Marc H. Venuti, Paola Hahn, Chun-Shin TI Mother-Child Play in Italy: Regional Variation, Individual Stability, and Mutual Dyadic Influence SO PARENTING-SCIENCE AND PRACTICE LA English DT Article AB Objective. This longitudinal study assessed similarities and differences in exploratory, symbolic, and social play in mother-child dyads in the south and north of Italy. Design. Altogether, 89 mothers and their children were observed and recorded at home when children were 13 and 20 months of age. From videotapes, exploratory, symbolic, and social play were coded and analyzed. Results. Children did not differ in their play with mothers across region and play type, but they played less in exploratory and more in symbolic modes as they grew. At 13 months, mothers in the south did not differ from mothers in the north in engaging in exploratory or symbolic play with their children; at 20 months, mothers in the south engaged in more demonstrations of exploratory and mothers in the north more demonstrations of symbolic play. Mothers in the south and north engaged in equivalent social play at the two ages, but northern mothers verbally praised their children more at the two ages. Child play was not stable, and mothers' play only irregularly stable. In both regions at both ages, individual variation in children's exploratory and symbolic play was specifically associated with individual variation in mothers' exploratory and symbolic play, respectively, but mothers' play did not predict children's play, nor did children's play predict mothers' play. Mothers' social play was not predictive of child play, although verbal praise was associated with child play. Conclusions. These data highlight the universality of general developmental processes in play as well as specific intra-cultural variation in parenting and child development. C1 [Bornstein, Marc H.; Hahn, Chun-Shin] NICHHD, Bethesda, MD 20892 USA. [Venuti, Paola] Univ Trent, SSIS Polo Rovereto, Fac Sociol, I-38100 Trento, Italy. RP Bornstein, MH (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 87 TC 13 Z9 14 U1 2 U2 2 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2002 VL 2 IS 3 BP 273 EP 301 AR PII 785828748 DI 10.1207/S15327922PAR0203_04 PG 29 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA V12OE UT WOS:000207607700004 ER PT J AU Early, DM Rimm-Kaufman, SE Cox, MJ Saluja, G Pianta, RC Bradley, RH Payne, CC AF Early, Diane M. Rimm-Kaufman, Sara E. Cox, Martha J. Saluja, Gitanjali Pianta, Robert C. Bradley, Robert H. Payne, C. Chris TI Maternal Sensitivity and Child Wariness in the Transition to Kindergarten SO PARENTING-SCIENCE AND PRACTICE LA English DT Article AB Objective. This study tested maternal sensitivity as a moderator of the stability of wary behavior between 15 months and the transition to school. Design. Observational data from 15-month-old children and their mothers, kindergarten teacher reports, and maternal reports during the transition to kindergarten from 215 children from 3 sites (North Carolina, Virginia, and Arkansas) of the National Institute of Child Health and Human Development (NICHD; 1994), Study of Early Child Care are used. Results. Findings indicate significant stability of inhibition from 15 months to the transition to kindergarten and a significant interaction between maternal sensitivity and 15-month wariness in predicting inhibition in the transition to kindergarten. Among children who displayed wariness at 15 months, greater maternal sensitivity was associated with less inhibition during the transition to kindergarten. For children who did not display wariness at 15 months, there was no relation between maternal sensitivity and inhibition in the transition to kindergarten. Conclusions. These findings suggest moderate stability of this early temperamental characteristic and point to the importance of responsive parenting in its modification. C1 [Early, Diane M.] Univ N Carolina, Frank Porter Graham Child Dev Inst, Chapel Hill, NC 27599 USA. [Rimm-Kaufman, Sara E.; Pianta, Robert C.] Univ Virginia, Charlottesville, VA 22903 USA. [Cox, Martha J.] Univ N Carolina, Chapel Hill, NC USA. [Saluja, Gitanjali] NIH, Bethesda, MD USA. [Bradley, Robert H.] Univ Arkansas, Little Rock, AR 72204 USA. [Payne, C. Chris] Univ N Carolina, Greensboro, NC 27412 USA. RP Early, DM (reprint author), Univ N Carolina, Frank Porter Graham Child Dev Inst, CB 8040, Chapel Hill, NC 27599 USA. EM diane_early@unc.edu NR 56 TC 23 Z9 23 U1 1 U2 10 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2002 VL 2 IS 4 BP 355 EP 377 AR PII 785828681 DI 10.1207/S15327922PAR0204_02 PG 23 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA V12OF UT WOS:000207607800002 ER PT J AU Magalhaes, R Gehrke, T Souto-Carneiro, MM Kriegsmann, J Krenn, V AF Magalhaes, R Gehrke, T Souto-Carneiro, MM Kriegsmann, J Krenn, V TI Extensive plasma cell infiltration with crystal IgG inclusions and mutated IgV(H) gene in an osteoarthritis patient with lymphoplasmacellular synovitis. A case report SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE plasma cells; osteoarthritis; crystal inclusions; IgV(H) genes ID STORING HISTIOCYTOSIS; B-CELLS; GERMINAL-CENTERS; LIGHT-CHAIN; TISSUE; ARTHRITIS; CRYOIMMUNOGLOBULINS; DIFFERENTIATION; SPECIFICITY; DEPOSITS AB The presence of immunoglobulin crystal inclusions in plasma cells from plasmacytomas and B-NHLs (linked to overstimulation and overproduction) has been frequently reported. Our case describes a lymphoplasma-cellular synovitis in a patient with osteoarthritis (OA) showing an unusually high plasma cell infiltration and for the first time crystals in plasma cells. Using immunohistochemistry, these crystals were identified as being IgG with a balanced lambdalkappa ratio. IgV(H) gene analysis (n = 5 clones) showed that they were somatically mutated (R/S of CDR > 3); in one case, an insertion of 9 nucleotides on the CDR2 region was observed. High R/S values in the CDR indicated antigen selectivity and affinity (4/5). Since no germinal centers could be detected and the analyzed B cells showed antigen selectivity, it may be concluded that already antigenically activated B cells migrated into the synovium and locally differentiated into plasma cells, leading to the extensive infiltration observed. Rheumatoid fibroblasts were shown to support terminal B cell differentiation. Our data suggests that the ability of fibroblasts to activate B cells is not only restricted to RA, but also occurs in OA. The intense plasma cell infiltration contributed to further cartilage damage by altering the microenvironment of the nourishing synovial tissue or by the local production of pathogenic autoantibodies. C1 Humboldt Univ, Charite, Inst Pathol, D-10115 Berlin, Germany. ENDO Klin, Hamburg, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. Gemeinschaftspraxis Pathol, Trier, Germany. RP Krenn, V (reprint author), Humboldt Univ, Charite, Inst Pathol, Schumannstr 20-21, D-10115 Berlin, Germany. RI Souto-Carneiro, Margarida/C-4386-2016 OI Souto-Carneiro, Margarida/0000-0001-6923-0590 NR 28 TC 7 Z9 7 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2002 VL 198 IS 1 BP 45 EP 50 DI 10.1078/0344-0338-00183 PG 6 WC Pathology SC Pathology GA 524QQ UT WOS:000174024700008 PM 11866210 ER PT J AU Matsui, K Takano, Y Yu, ZX Hi, JES Stetler-Stevenson, WG Travis, WD Ferrans, VJ AF Matsui, K Takano, Y Yu, ZX Hi, JES Stetler-Stevenson, WG Travis, WD Ferrans, VJ TI Immunohistochemical study of endothelin-1 and matrix metalloproteinases in plexogenic pulmonary arteriopathy SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE pulmonary hypertension; plexogenic pulmonary arteriopathy; matrix metalloproteinases; membrane-type matrix metalloproteinases endothelin-1; immunohistochemistry; confocal microscopy ID VASCULAR SMOOTH-MUSCLE; TISSUE INHIBITORS; IV COLLAGENASE; GROWTH-FACTOR; CELLS; EXPRESSION; HYPERTENSION; ATHEROSCLEROSIS; ANGIOGENESIS; ACTIVATION AB The matrix metalloproteinases (MMPs) and endothelin-1, a potent vasoconstrictor and mitogen for smooth muscle cells, have been shown to be involved in the pathogenesis of various vascular disorders. However, the expression of endothelin-1 and the activation of MMPs have not been fully evaluated in plexogenic pulmonary arteriopathy (PPA). Immunohistochemical and confocal microscopic studies were conducted to evaluate the reactivity of lung tissue from six patients with pulmonary hypertension for alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, factor VIII, endothelin-1, various types of MMPs (MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9), membrane type-MMPs (MT-MMPs), tissue inhibitors of MMPs (TIMPs), and type IV collagen. Four major arterial morphological abnormalities were recognized in PPA: muscularization of pulmonary arterioles, onion-skin lesions, cellular and mature plexiform lesions, and atheromas in elastic pulmonary arteries. Reactivity for MMP-2 and MT-1-MMP was found in endothelial cells and, to a lesser extent, in myofibroblasts proliferating in various lesions of PPA. Increased expression of endothelin-1 was observed in the latter cells and in endothelial cells. Some myofibroblasts were positive for MMP-3 and MMP-7 in the vascular lesions except for mature plexiform lesions. MMP-1, MMP-9 and TIMP-2 tended to be positive only in the atheromatous lesions. Staining for type IV collagen showed focal thinning and discontinuities of the endothelial basement membrane in plexiform lesions. This study demonstrates colocalization of MMP-2 with MT-1-MMP and increased expression of endothelin-1 in various arterial lesions of PPA. These changes may play important roles in the remodeling of arterial structures, particularly of basement membranes, in this disorder. C1 Toyama Med & Pharmaceut Univ, Fac Med, Dept Pathol, Toyama 9300194, Japan. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. RP Matsui, K (reprint author), Toyama Med & Pharmaceut Univ, Fac Med, Dept Pathol, 2630 Sugitani, Toyama 9300194, Japan. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 24 TC 14 Z9 15 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2002 VL 198 IS 6 BP 403 EP 412 DI 10.1078/0344-0338-00273 PG 10 WC Pathology SC Pathology GA 578RB UT WOS:000177131800004 PM 12166897 ER PT J AU Newman, TS Tang, N Dong, C Choyke, P AF Newman, TS Tang, N Dong, C Choyke, P TI Slice-adaptive histogram for improvement of anatomical structure extraction in volume data SO PATTERN RECOGNITION LETTERS LA English DT Article DE segmentation; anatomical feature extraction; histogramming; volume data ID IMAGE SEGMENTATION; MR AB The slice-adaptive histogramming method for improving coarse segmentation of structures from volume data (especially extraction of anatomical structures in the lower,torso from computerized tomography data) is introduced. The method uses a series of local histograms to enable a final segmentation that can adapt to slice-to-slice intensity variations. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Alabama, Dept Comp Sci, Huntsville, AL 35899 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Newman, TS (reprint author), Univ Alabama, Dept Comp Sci, N300 Techonol Hall, Huntsville, AL 35899 USA. NR 28 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8655 J9 PATTERN RECOGN LETT JI Pattern Recognit. Lett. PD JAN PY 2002 VL 23 IS 1-3 BP 25 EP 38 DI 10.1016/S0167-8655(01)00087-3 PG 14 WC Computer Science, Artificial Intelligence SC Computer Science GA 496LZ UT WOS:000172398200003 ER PT J AU Offit, PA Quarles, J Gerber, MA Hackett, CJ Marcuse, EK Kollman, TR Gellin, BG Landry, S AF Offit, PA Quarles, J Gerber, MA Hackett, CJ Marcuse, EK Kollman, TR Gellin, BG Landry, S TI Addressing parents' concerns: Do multiple vaccines overwhelm or weaken the infant's immune system? SO PEDIATRICS LA English DT Article DE multiple vaccines; immunity; parental concerns ID MUMPS-RUBELLA VACCINE; SEVERE COMBINED IMMUNODEFICIENCY; DIPHTHERIA-TETANUS-PERTUSSIS; RESPIRATORY-TRACT INFECTION; HEPATITIS-B VACCINE; ANTIBODY-RESPONSE; POLIOVIRUS VACCINES; MATERNAL ANTIBODIES; VARICELLA VACCINE; HEALTHY-CHILDREN AB Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines. Implicit in this concern is that the infant's immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system. In this review, we will examine the following: 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines; 2) the theoretic capacity of an infant's immune system; 3) data that demonstrate that mild or moderate illness does not interfere with an infant's ability to generate protective immune responses to vaccines; 4) how infants respond to vaccines given in combination compared with the same vaccines given separately; 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children; and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Infect Dis Sect, Philadelphia, PA 19104 USA. Wistar Inst Anat & Biol, Philadelphia, PA USA. NIAID, Div Infect Dis, NIH, Bethesda, MD 20892 USA. NIAID, Div Allergy Immunol & Tranplantat, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Childrens Hosp & Reg Med Ctr, Infect Dis Sect, Seattle, WA USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA USA. Vanderbilt Med Coll, Dept Prevent Med, Nashville, TN USA. RP Offit, PA (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Infect Dis Sect, Abramson Res Bldg,Room 1202C,3516 Civ Ctr Blvd, Philadelphia, PA 19104 USA. OI Hackett, Charles/0000-0003-4586-9669 NR 63 TC 114 Z9 120 U1 0 U2 28 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2002 VL 109 IS 1 BP 124 EP 129 DI 10.1542/peds.109.1.124 PG 6 WC Pediatrics SC Pediatrics GA 507BJ UT WOS:000173006600036 PM 11773551 ER PT J AU Gawrisch, K Koenig, BW AF Gawrisch, K Koenig, BW TI Lipid-peptide interaction investigated by NMR SO PEPTIDE-LIPID INTERACTIONS SE CURRENT TOPICS IN MEMBRANES LA English DT Review ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; MEMBRANE-BOUND CONFORMATION; PROTEIN SECONDARY STRUCTURE; N-15 CHEMICAL-SHIFT; NOESY CROSS-RELAXATION; ECHO DOUBLE-RESONANCE; FD COAT PROTEIN; PHOSPHOLIPID-BILAYERS; MODEL MEMBRANES C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Res Ctr Julich, Inst Biol Struct, IBI 2, D-52425 Julich, Germany. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RI Koenig, Bernd/B-4315-2008 OI Koenig, Bernd/0000-0002-5300-6276 NR 121 TC 2 Z9 2 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 J9 CURR TOP MEMBR PY 2002 VL 52 BP 163 EP 190 PG 28 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BU06A UT WOS:000174887600006 ER PT J AU Watanabe, K AF Watanabe, K TI Perceptual grouping by motion precedes relative localisation of visual stimuli SO PERCEPTION LA English DT Meeting Abstract C1 NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2002 VL 31 SU S BP 109 EP 109 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 594MZ UT WOS:000178055500336 ER PT J AU Kingman, A Albandar, JM AF Kingman, A Albandar, JM TI Methodological aspects of epidemiological studies of periodontal diseases SO PERIODONTOLOGY 2000 LA English DT Article ID ATTACHMENT LEVEL MEASUREMENTS; ADULTS 30 YEARS; UNITED-STATES; SEVERITY; PREVALENCE; HEALTH; EXTENT; RELIABILITY; ERRORS; INDEX C1 NIDCR, Div Populat & Hlth Promot Sci, NIH, Bethesda, MD USA. RP Kingman, A (reprint author), NIDCR, Div Populat & Hlth Promot Sci, NIH, Bethesda, MD USA. OI Albandar, Jasim M./0000-0001-7801-3811 NR 35 TC 127 Z9 135 U1 0 U2 6 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6713 J9 PERIODONTOL 2000 JI Periodontol. 2000 PY 2002 VL 29 BP 11 EP 30 DI 10.1034/j.1600-0757.2002.290102.x PG 20 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 568MP UT WOS:000176546200002 PM 12102701 ER PT J AU Ziegler, RG Vogt, TM AF Ziegler, RG Vogt, TM TI Tomatoes, lycopene, and risk of prostate cancer SO PHARMACEUTICAL BIOLOGY LA English DT Article DE carotenoids; chemoprevention; epidemiology; lycopene; prostate cancer; tomatoes ID PLASMA LYCOPENE; BETA-CAROTENE; CARDIOVASCULAR-DISEASE; FRUIT CONSUMPTION; DIETARY-INTAKE; SERUM; VEGETABLES; NUTRITION; RETINOL; COHORT AB Like other carotenoids, lycopene can protect plants from photo-oxidation damage, but its role in humans is unclear. In the United States, tomatoes provide 85-90% of dietary lycopene, with two-thirds contributed by tomato products. Tomatoes are also rich in vitamins C and A, folate, potassium, and several non-nutrient phytochemicals. Increased lycopene and tomato intake has been hypothesized to decrease the risk of prostate cancer, the most commonly diagnosed cancer among U. S. men. Of the 15 epidemiologic studies - 3 prospective and 12 retrospective - to evaluate this relationship, approximately half reported reductions in risk with increased intake (relative risks similar to0.6-0.8 between extremes of intake). Protective effects were most consistently seen with cooked tomato products, possibly because of enhanced lycopene bioavailability, and in U. S. white men. The three prospective studies of prediagnostic blood lycopene levels, a biomarker which integrates intake, absorption, and metabolism, and prostate cancer have also not concurred. However, they do suggest that risk may be reduced (relative risks similar to0.5-0.8) in U. S. white men, possibly because of relatively high circulating lycopene or linked dietary patterns and lifestyles. Thus, at present, epidemiologic research does not persuasively support or refute the protective promise of lycopene and tomatoes. Future research should focus on dietary and lifestyle determinants of blood lycopene levels, improved assessment of tomato product intake and incorporation of updated lycopene databases, direct measurement of lycopene in prostate tissue, and development of reliable intermediate markers of prostate carcinogenesis. C1 NCI, Off Director, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Ziegler, RG (reprint author), NCI, Off Director, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Execut Plaza S,Room 8098, Bethesda, MD 20892 USA. NR 47 TC 2 Z9 2 U1 0 U2 6 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2002 VL 40 SU S BP 59 EP 69 DI 10.1076/phbi.40.7.59.9177 PG 11 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 549LX UT WOS:000175446400008 ER PT J AU Hawthorne, M Steele, V Mehta, RG AF Hawthorne, M Steele, V Mehta, RG TI Evaluation of selected chemopreventive agents present in common foods in mouse mammary gland organ culture SO PHARMACEUTICAL BIOLOGY LA English DT Article DE mammary glands; organ culture; chemoprevention; natural products; preneoplastic lesions ID CANCER; PREVENTION; INDUCTION AB Prevention of cancer by natural and synthetic non-toxic chemopreventive agents has become a major research area in the past 15 years. The naturally occurring chemopreventive agents from the herbal medicine and edible plants can be evaluated in a variety of bioassays and identified for their activity as cancer preventive agents. We have adapted a mouse mammary gland organ culture assay (MMOC) for evaluating chemically pure chemopreventive agents for their activity to inhibit 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary alveolar lesions (MAL). Here, we report a list of 32 agents that are found in the herbs or edible foods and showing inhibition of more than 55% in MMOC. From the studies reported in the literature it appears that there is a good correlation between the effects in MMOC and effects observed with in vivo carcinogenesis models. Recently, we have modified the MMOC assay to evaluate efficacy of chemopreventive agents specifically the ones that may have anti-estrogenic activity. Thus, MMOC provides a valuable tool for preliminary evaluation of chemopreventive agents prior to conducting a long-term animal carcinogenesis studies. C1 Univ Illinois, Coll Med, Dept Surg Oncol, Chicago, IL 60612 USA. NCI, Chemoprevent Agent Dev Grp, Bethesda, MD 20892 USA. RP Mehta, RG (reprint author), Univ Illinois, Coll Med, Dept Surg Oncol, 840 S Wood St,M-C820, Chicago, IL 60612 USA. NR 24 TC 4 Z9 4 U1 1 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2002 VL 40 SU S BP 70 EP 74 DI 10.1076/phbi.40.7.70.9175 PG 5 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 549LX UT WOS:000175446400009 ER PT J AU Moaddel, R Cloix, JF Ertem, G Wainer, IW AF Moaddel, R Cloix, JF Ertem, G Wainer, IW TI Multiple receptor liquid chromatographic stationary phases: The co-immobilization of nicotinic receptors, gamma-amino-butyric acid receptors, and N-methyl D-Aspartate receptors SO PHARMACEUTICAL RESEARCH LA English DT Article DE multiple-receptor; immobilized receptor; frontal affinity chromatography; nicotinic receptor; GABA(A) receptor; NMDA receptor ID GLUTAMATE RECEPTORS; LIGAND C1 Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA. Univ Orleans, UPRES EA 2633, Orleans 2, France. Georgetown Univ, Lombardi Canc Ctr, Dept Oncol, Washington, DC 20007 USA. NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA. FU NIGMS NIH HHS [1R41GM61408-01] NR 10 TC 30 Z9 32 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JAN PY 2002 VL 19 IS 1 BP 104 EP 107 DI 10.1023/A:1013619802766 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 516YL UT WOS:000173584300016 PM 11837693 ER PT J AU Pickworth, WB Moolchan, ET Berlin, I Murty, R AF Pickworth, WB Moolchan, ET Berlin, I Murty, R TI Sensory and physiologic effects of menthol and nonmenthol cigarettes with differing nicotine delivery SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE placebo cigarettes; menthol; denicotinized; smoking; African Americans ID SMOKING-BEHAVIOR; WITHDRAWAL; BINDING; SMOKERS AB Many smokers choose menthol-flavored cigarettes, however, the influence of menthol on the effects of smoke-delivered nicotine is unknown. Research and commercial cigarettes, menthol and nonmenthol, that delivered a wide range of nicotine were evaluated. Menthol (n = 18) and nonmenthol (n = 18) cigarette smokers participated in a single session during which three cigarettes were smoked 45 min apart, in random order. Federal Trade Commission (FTC) nicotine yields of the three cigarettes were: research, low yield, 0.2 mg, commercial cigarettes (average), 1.2 mg; research, high yield, 2.5 mg. Commercial and high-yield cigarettes increased heart rate (HR) and blood pressure more than low-yield cigarettes; although, no differences in exhaled carbon monoxide (CO) occurred. Participants smoked commercial cigarettes faster and with fewer puffs than either of the research cigarette indicating production differences can affect topography. There was a significant group by cigarette interaction on satisfaction, and relief from cigarette craving. High-yield nonmenthol cigarettes reduced craving and were rated as more satisfying than high-yield menthol cigarettes. No differences between menthol and nonmenthol cigarettes on other subjective measures (strength, psychological reward negative effects) were observed. Our findings indicate that nicotine delivery, but not mentholation, influences cardiovascular and most subjective measures. These results illustrate the importance of threshold levels of nicotine on subjective responses to cigarette smoking. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIDA, Addict Res Ctr, Clin Pharmacol Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Pickworth, WB (reprint author), NIDA, Addict Res Ctr, Clin Pharmacol Branch, Intramural Res Program, POB 5180, Baltimore, MD 21224 USA. NR 30 TC 26 Z9 27 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN-FEB PY 2002 VL 71 IS 1-2 BP 55 EP 61 DI 10.1016/S0091-3057(01)00623-2 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 518UY UT WOS:000173687300006 PM 11812507 ER PT J AU Stevenson, GW Canadas, F Gomez-Serrano, M Ullrich, T Zhang, XY Rice, KC Riley, AL AF Stevenson, GW Canadas, F Gomez-Serrano, M Ullrich, T Zhang, XY Rice, KC Riley, AL TI Delta opioid discrimination learning in the rat - Assessment with the selective delta agonist SNC80 SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE delta opioid; SNC80; naltrindole; drug discrimination teaming; conditioned taste aversion; rat ID DRUG DISCRIMINATION; STIMULUS PROPERTIES; KAPPA-RECEPTOR; RHESUS-MONKEYS; MU-RECEPTOR; NARCOTIC DISCRIMINATION; MORPHINE; BW373U86; PIGEONS; SUBSTITUTION AB The majority of reports assessing opioid drug discrimination learning (DDL) have concentrated on characterizing the stimulus properties of compounds selective for mu and kappa opioid receptors. Assessments of delta opioid DDL have been limited and, to date, these assessments have been restricted to the monkey and pigeon. No assessment of delta stimulus control has been examined in rodents. To that end, the present experiment examined discriminative control by the selective delta agonist SNC80 in rats and its generalization to and antagonism by compounds relatively selective to the delta and mu receptor subtypes using the conditioned taste aversion baseline of DDL. Animals injected with 5.6 mg/kg of SNC80 prior to a saccharin-LiCl pairing and with the SNC80 vehicle prior to saccharin alone acquired the discrimination within seven conditioning cycles. The discriminative effects of SNC80 were maximal at 20 min, partial at 120 min, and lost at 240 min. The discrimination was dose dependent in that as the dose of SNC80 increased, the amount of saccharin consumed decreased. In subsequent generalization tests, the delta agonist SNC162 produced SNC80-appropriate responding at a dose of 18 mg/kg. Conversely, the mu agonist morphine produced vehicle-appropriate responding at all doses tested. These selective generalization patterns with SNC162 and morphine suggest that the discriminative effects of SNC80 are mediated at the. delta, but not the mu, receptor, a conclusion supported by the fact that SNC80's discriminative control was completely blocked by the delta-selective antagonist NTI, but not by the mu-selective antagonist naltrexone. The present findings indicate that not only do rats readily discriminate both mu- and kappa-selective agonists from their respective vehicles, but they also discriminate compounds that are selective for the delta receptor subtype, thus extending the class of compounds that can serve such discriminative functions for the rat. (C) 2002 Elsevier Science Inc. All rights reserved. C1 American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Stevenson, GW (reprint author), American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA. NR 56 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN-FEB PY 2002 VL 71 IS 1-2 BP 283 EP 292 DI 10.1016/S0091-3057(01)00658-X PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 518UY UT WOS:000173687300033 PM 11812534 ER PT J AU Fricker, G Miller, DS AF Fricker, G Miller, DS TI Relevance of multidrug resistance proteins for intestinal drug absorption in vitro and in vivo SO PHARMACOLOGY & TOXICOLOGY LA English DT Review ID CACO-2 CELL MONOLAYERS; ORGANIC ANION TRANSPORTER; MDR1A P-GLYCOPROTEIN; HIV PROTEASE INHIBITORS; ISOLATED BRUSH-BORDER; RAT SMALL-INTESTINE; IN-VIVO; GRAPEFRUIT JUICE; CYCLOSPORINE-A; APICAL MEMBRANE AB Multidrug resistance proteins (p-glycoprotein and mrps) are becoming increasingly important to explain the pharmacokinetics and action of drugs. Located in epithelial and endothelial cells of the gastrointestinal tract, liver, kidney, blood brain barrier, choroid plexus and other organs, they are critical determinants for the movement of a large number of commonly prescribed drugs across cellular barriers. Here we provide a brief overview of the role of multidrug resistance proteins in drug absorption from the gastrointestinal tract. We address the different types of multidrug resistance proteins involved, describe experimental models to study the influence of these proteins on transcellular transport and discuss the impact of multidrug resistance proteins on overall drug bioavailability in vivo. C1 Univ Heidelberg, Inst Pharmaceut & Biopharm, D-69120 Heidelberg, Germany. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Fricker, G (reprint author), Univ Heidelberg, Inst Pharmaceut Technol & Biopharm, Neuenheimer Feld 366, D-69120 Heidelberg, Germany. NR 114 TC 48 Z9 52 U1 1 U2 4 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PD JAN PY 2002 VL 90 IS 1 BP 5 EP 13 DI 10.1034/j.1600-0773.2002.900103.x PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 523VH UT WOS:000173977600004 PM 12005113 ER PT J AU Berezhkovskii, AM Weiss, GH AF Berezhkovskii, AM Weiss, GH TI Detailed description non-Markov of a two-state system SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE dwell time; renewal theory AB A two-state system in which transitions between the states are made randomly, is often used as a model of different phenomena in several fields. Both the probability density for the cumulative dwell-time in one of the states during a fixed observation time T, and the distribution of the number of transitions made during that time are known. We calculate the joint distribution of these two correlated random variables, showing that at long times it approaches a two-dimensional Gaussian form. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIH, Lab Math & Stat Computat, Ctr Informat Technol, Bethesda, MD 20892 USA. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Weiss, GH (reprint author), NIH, Lab Math & Stat Computat, Ctr Informat Technol, Bldg 12 A,Room 2007, Bethesda, MD 20892 USA. NR 7 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD JAN 1 PY 2002 VL 303 IS 1-2 BP 1 EP 12 DI 10.1016/S0378-4371(01)00431-9 PG 12 WC Physics, Multidisciplinary SC Physics GA 509LZ UT WOS:000173150400001 ER EF