FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kakizaki, S Yamamoto, Y Ueda, A Moore, R Sueyoshi, T Negishi, M AF Kakizaki, S Yamamoto, Y Ueda, A Moore, R Sueyoshi, T Negishi, M TI Phenobarbital induction of drug/steroid-metabolizing enzymes and nuclear receptor CAR SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article; Proceedings Paper CT 12th International Symposium on Cellular Biology of Cytochrome P450 Regulation CY SEP, 2001 CL LA GRANDE MOTTE, FRANCE DE metabolizing enzyme; nuclear receptor; phenobarbital ID MOUSE CYP2B10 GENE; CYTOCHROME-P450 GENES; ENHANCER MODULE; ACTIVATION; PXR AB Phenobarbital (PB) increases hepatic drug/steroid-metabolic capability by coordinately activating transcription of the genes encoding various metabolizing enzymes. The nuclear receptor CAR was first implicated as a transcription factor that activates the cytochrome P450 Cyp2b10 gene. In response to PB, CAR forms a heterodimer with the retinoid X receptor (RXR), binds to a PB response element (typified by DR-4 motif), and activates transcription of the gene. In the CAR-null mouse, PB does not only induce the Cyp2b10 gene, but also induces genes encoding various metabolizing enzymes. Thus, CAR is a general nuclear receptor that is essential for PB induction of drug/steroid metabolizing enzymes. PB also induces amino levulinate synthase 1 (ALAS-1), the rate-limiting enzyme in heme biosynthesis, to increase heme supply. However, PB induction of the synthase occurs in CAR-null mice, suggesting that CAR does not coordinate the heme synthesis for the induction of drug/steroid metabolism. (C) 2002 Published by Elsevier Science B.V. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 23 TC 44 Z9 47 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD FEB 17 PY 2003 VL 1619 IS 3 BP 239 EP 242 AR PII S0304-4165(02)00482-8 DI 10.1016/S0304-4165(02)00482-8 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 648FW UT WOS:000181140200004 PM 12573483 ER PT J AU Fons, RD Bogert, BA Hegde, RS AF Fons, RD Bogert, BA Hegde, RS TI Substrate-specific function of the translocon-associated protein complex during translocation across the ER membrane SO JOURNAL OF CELL BIOLOGY LA English DT Article DE protein translocation; endoplasmic reticulum; secretion; translocon; signal sequence ID ENDOPLASMIC-RETICULUM MEMBRANE; SIGNAL-SEQUENCE RECEPTOR; PRION PROTEIN; POLYPEPTIDE TRANSLOCATION; TRANSMEMBRANE DOMAIN; SECRETORY PROTEINS; SEC PROTEINS; RECOGNITION; COMPONENTS; RIBOSOME AB Although the transport of model proteins across the mammalian ER can be reconstituted with purified Sec61p complex, TRAM, and signal recognition particle receptor, some substrates, such as the prion protein (PrP), are inefficiently or improperly translocated using only these components. Here, we purify a factor needed for proper translocation of PrP and identify it as the translocon-associated protein (TRAP) complex. Surprisingly, TRAP also stimulates vectorial transport of many, but not all, other substrates in a manner influenced by their signal sequences. Comparative analyses of several natural signal sequences suggest that a dependence on TRAP for translocation is not due to any single physical parameter, such as hydrophobicity of the signal sequence. instead, a functional property of the signal, efficiency of its post-targeting role in initiating substrate translocation, correlates inversely with TRAP dependence. Thus, maximal translocation independent of TRAP can only be achieved with a signal sequence, such as the one from prolactin, whose strong interaction with the translocon mediates translocon gating shortly after targeting. These results identify the TRAP complex as a functional component of the translocon and demonstrate that it acts in a substrate-specific manner to facilitate the initiation of protein translocation. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, 18 Lib Dr,Bldg 18,Room 101, Bethesda, MD 20892 USA. OI Hegde, Ramanujan/0000-0001-8338-852X NR 42 TC 127 Z9 133 U1 4 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB 17 PY 2003 VL 160 IS 4 BP 529 EP 539 DI 10.1083/jcb.200210095 PG 11 WC Cell Biology SC Cell Biology GA 647JT UT WOS:000181090200007 PM 12578908 ER PT J AU Yu, Q Erman, B Bhandoola, A Sharrow, SO Singer, A AF Yu, Q Erman, B Bhandoola, A Sharrow, SO Singer, A TI In vitro evidence that cytokine receptor signals are required for differentiation of double positive thymocytes into functionally mature CD8(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE coreceptor reversal; kinetic signaling; positive selection; IL-7 ID INTERLEUKIN-7 RECEPTOR; GAMMA CHAIN; LINEAGE COMMITMENT; GENE-EXPRESSION; DEFICIENT MICE; CD4 GENE; SELECTION; THYMUS; BCL-2; LYMPHOCYTES AB CD4(+)8(+) double positive (DP) thymocytes differentiate into CD4(+) and CD8(+) mature T cells in response to TCR signals. However, TCR signals that are initiated in DP thymocytes are unlikely to persist throughout all subsequent differentiation steps, suggesting that other signals must sustain thymocyte differentiation after TCR signaling has ceased. Using an in vitro experimental system, we now demonstrate that cytokine receptor signals, such as those transduced by IL-7 receptors, are required for differentiation of signaled DP thymocytes into functionally mature CD8(+) T cells as they: (a) up-regulate Bcl-2 expression to maintain thymocyte viability; (b) enhance CD4 gene silencing; (c) promote functional maturation;and (d) up-regulate surface expression of glucose transporter molecules, which improve nutrient uptake and increase metabolic activity. IL-7Rs appear to be unique among cytokine receptors in maintaining the viability of newly generated CD4(-)8(+) thymocytes, whereas several different cytokine receptors can provide the trophic/differentiative signals for subsequent CD8(+) thymocyte differentiation and maturation. Thus, cytokine receptors provide both survival and trophic/differentiative signals with varying degrees of redundancy that are required for differentiation of signaled DP thymocytes into functionally mature CD8(+) T cells. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 38 TC 85 Z9 87 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 17 PY 2003 VL 197 IS 4 BP 475 EP 487 DI 10.1084/jem.20021765 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 648YM UT WOS:000181179400008 PM 12591905 ER PT J AU Djousse, L Rothman, KJ Cupples, LA Levy, D Ellison, RC AF Djousse, L Rothman, KJ Cupples, LA Levy, D Ellison, RC TI Effect of serum albumin and bilirubin on the risk of myocardial infarction (the Framingham Offspring Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; C-REACTIVE PROTEIN; ARTERY DISEASE; ASSOCIATION AB We used data collected on participants in the Framingham Offspring Study to test the hypothesis that low levels of serum albumin and low levels of serum bilirubin have synergistic effects on the risk of myocardial infarction. After adjustment for traditional risk factors, our findings suggest that low albumin and low bilirubin levels are associated with a greater than expected risk of myocardial infarction in men and women. C1 Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Djousse, L (reprint author), Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Dept Med, Room B-612,715 Albany St, Boston, MA 02118 USA. RI Djousse, Luc/F-5033-2017; OI Djousse, Luc/0000-0002-9902-3047; Ellison, Robert Curtis/0000-0002-0582-7467; Cupples, L. Adrienne/0000-0003-0273-7965; Rothman, Kenneth/0000-0003-2398-1705 FU NHLBI NIH HHS [N01-HC-38038] NR 13 TC 44 Z9 46 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 15 PY 2003 VL 91 IS 4 BP 485 EP + DI 10.1016/S0002-9149(02)03256-3 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 648LK UT WOS:000181152700027 PM 12586275 ER PT J AU North, KE Howard, BV Welty, TK Best, LG Lee, ET Yeh, JL Fabsitz, RR Roman, MJ MacCluer, JW AF North, KE Howard, BV Welty, TK Best, LG Lee, ET Yeh, JL Fabsitz, RR Roman, MJ MacCluer, JW TI Genetic and environmental contributions to cardiovascular disease risk in American indians - The Strong Heart Family Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cardiovascular diseases; environment; genetic predisposition to disease; Indians; North American; risk factors ID TRAIT LINKAGE ANALYSIS; AGED 45-74 YEARS; PIMA-INDIANS; DIABETES-MELLITUS; COMPONENTS; PEDIGREES; HYPERTENSION; POPULATIONS; PREVALENCE AB The aims of the Strong Heart Family Study are to clarify the genetic determinants of cardiovascular disease (CVD) risk in American Indians and to map and identify genes for CVD susceptibility. The authors describe the design of the Strong Heart Family Study, (conducted between 1998 and 1999) and evaluate the heritabilities. of CVD risk factors in American Indians from this study. In the first phase of the study, approximately 950 individuals, aged 18 years or more, in 32 extended families, were examined. The examination consisted of a personal interview, physical examination, laboratory tests, and an ultrasound examination of the carotid arteries. The phenotypes measured during the physical examination included anthropometry, lipoproteins, blood pressure, glycemic status, and clotting factors. Heritabilities for CVD risk factor phenotypes were estimated using a variance component approach and the program SOLAR. After accounting for the effects of covariates, the authors detected significant heritabilities for many CVD risk factor phenotypes (e.g., high density lipoprotein cholesterol (heritability = 0.50) and diastolic blood pressure (heritability = 0.34)). These results suggest that heredity explains a substantial proportion of the variability of CVD risk factors and that these heritabilities are large enough to warrant a search for major risk factor genes. C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78284 USA. Medstar Res Inst, Washington, DC USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. Univ Oklahoma, Hlth Sci Ctr, Sch Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, New York, NY USA. RP North, KE (reprint author), Bank Amer Ctr, Dept Epidemiol, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA. EM kari_north@unc.edu FU NHLBI NIH HHS [U01 HL41642, U01 HL41652, U01 HL65520, U01HL41654, U01HL65521] NR 32 TC 103 Z9 105 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 15 PY 2003 VL 157 IS 4 BP 303 EP 314 DI 10.1093/aje/kwf208 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 646WB UT WOS:000181057800006 PM 12578801 ER PT J AU Winterer, G Smolka, M Samochowiec, J Ziller, M Mahlberg, R Gallinat, J Rommelspacher, HP Herrmann, WM Sander, T AF Winterer, G Smolka, M Samochowiec, J Ziller, M Mahlberg, R Gallinat, J Rommelspacher, HP Herrmann, WM Sander, T TI Association of EEG coherence and an exonic GABA(B)R1 gene polymorphism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE EEG coherence; GABA(B) receptor gene polymorphism; chromosome 6p21.3; intermediate phenotype ID IDIOPATHIC GENERALIZED EPILEPSY; TO-NOISE RATIO; RECEPTOR ANTAGONISTS; SUSCEPTIBILITY LOCUS; GENOMIC STRUCTURE; ABSENCE SEIZURES; SCHIZOPHRENIA; CHROMOSOME-6; ACTIVATION; VARIANTS AB The GABA(B) receptor 1 gene is mapped to chromosome 6p21.3 within the HLA class I region close to the HLA-F gene. Susceptibility loci for epilepsy and schizophrenia have been mapped in this region. Based on pharmacological evidence, it has been suggested that GABA(B) receptors may play a crucial role in the synchronization of EEG oscillations, which in turn can be abnormal in neuropsychiatric disorders. In the present study, the hypothesis was tested, whether three exonic variants of the gene encoding the human GABA(B) receptor (GABA(B)R1) modify cortical synchronization measured as scalp-recorded EEG-coherence. Two principal components of EEG coherence (frontal coherence, parietotemporal coherence) were investigated in 104 healthy subjects during three conditions: resting EEG, activated EEG, and event-related EEG. No significant associations were found between the frontal coherence component and any polymorphism or between the parietotemporal coherence component and the exon 1a1 polymorphism. However, parietotemporal coherence showed statistically highly significant associations across all three experimental conditions with exon 7 and trend associations with exon 11. The results provide evidence that the translated polymorphism of exon 7 maybe functionally meaningful and impact cortical EEG oscillations. Since variations of EEG coherence have been described for several neuropsychiatric disorders, the present association should be tested in clinical samples using EEG coherence as an intermediate phenotype. (C) 2003 Wiley-Liss, Inc. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Univ Hosp benjamin Franklin, Dept Psychiat, D-1000 Berlin, Germany. Humboldt Univ, Univ Hosp Charite, Dept Neurol, Berlin, Germany. Pomerenian Acad Med, Dept Psychiat, Szczecin, Poland. RP Winterer, G (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Room 4S235 MSC 1379,10 Ctr Dr, Bethesda, MD 20892 USA. RI Smolka, Michael/B-4865-2011; Samochowiec, Jerzy/G-8175-2014 OI Smolka, Michael/0000-0001-5398-5569; Samochowiec, Jerzy/0000-0003-1438-583X NR 51 TC 23 Z9 26 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD FEB 15 PY 2003 VL 117B IS 1 BP 51 EP 56 DI 10.1002/ajmg.b.10031 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 670HN UT WOS:000182401600009 PM 12555235 ER PT J AU Cohen, HJ Harris, T Pieper, CF AF Cohen, HJ Harris, T Pieper, CF TI Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; DEGRADATION PRODUCT-D; D-DIMER; CARDIOVASCULAR-DISEASE; OLDER PERSONS; PLASMINOGEN-ACTIVATOR; MYOCARDIAL-INFARCTION; INFECTIOUS-DISEASES; GENE-EXPRESSION AB PURPOSE: This study was performed to determine the effects of markers of inflammation (interleukin 6) and coagulation (D-dimer) on mortality and functional status in older persons. METHODS: Subjects were selected for the Duke Established Populations for Epidemiologic Studies of the Elderly. In 1992, 2569 subjects, (age > 71 years) were interviewed, of whom 1723 had interleukin-6 and D-dimer measurements. Values of interleukin 6 and D-dimer were categorized into quartiles. Outcomes were mortality (through 5 years) and functional status (through 4 years). Relative risks were estimated with proportional hazards models that adjusted for potential confounders. RESULTS: The relative risk of mortality was 1.28 (95% confidence interval [Cl]: 0.98 to 1.69; P = 0.06) for those with only interleukin-6 levels in the highest quartile, 1.53 (95%CI: 1.18 to 1.97; P = 0.001) for subjects with only D-dimer levels in the highest quartile, and 2.00 (95% CI: 1.53 to 2.62;P = 0.0001) for those with levels of both in the highest quartile, as compared with those who were not in either of the highest quartiles. Those with high interleukin-6 and high D-dimer levels had the greatest declines in all measures of function. CONCLUSION: Activation of the coagulation and inflammatory pathways is associated with mortality and decline in function, and may be part of the explanation for the development of a frailty phenotype in the elderly. (C) 2003 by Excerpta Medica Inc. C1 Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. Duke Univ, Med Ctr, Claude D Pepper Older Amer Independence Ctr, Durham, NC 27710 USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. Vet Adm Med Ctr, Durham, NC 27705 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Cohen, HJ (reprint author), Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Box 3003, Durham, NC 27710 USA. EM cohen015@mc.duke.edu FU NIA NIH HHS [N01 AG-12102, 5 P60 AG-11268, R01 AG-12765] NR 50 TC 181 Z9 185 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB 15 PY 2003 VL 114 IS 3 BP 180 EP 187 DI 10.1016/S0002-9343(02)01484-5 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 653YZ UT WOS:000181465800002 PM 12637131 ER PT J AU Dams, R Murphy, CM Choo, RE Lambert, WE De Leenheer, AP Huestis, MA AF Dams, R Murphy, CM Choo, RE Lambert, WE De Leenheer, AP Huestis, MA TI LC-atmospheric pressure chemical ionization-MS/MS analysis of multiple illicit drugs, methadone, and their metabolites in oral fluid following protein precipitation SO ANALYTICAL CHEMISTRY LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; ABUSE-TREATMENT PATIENTS; LIQUID-CHROMATOGRAPHY; SALIVA; SWEAT; TOXICOLOGY; MATRICES AB A quantitative LC-APCI-MS/MS method for simultaneous determination of multiple illicit drugs, methadone, and their metabolites in oral fluid was developed and validated. Sample pretreatment was limited to acetonitrile protein precipitation. LC separation was performed in 25.5 min, with a total analysis time of 35 min. Identification and quantitation were based on selected reaction monitoring. Calibration by linear regression analysis utilized deuterated internal standards and a weighing factor 1/x. limits of detection and lower limits of quantitation (LOQ) were established between 0.25 and 5 ng/ mL and 0.5-10 ng/mL, respectively. linearity was obtained with an average correlation coefficient (R-2) of > 0.99, over a dynamic range from the LOQ up to maximum 500 ng/mL. The method demonstrated good accuracy, intra- and interbatch precision, recovery, and stability for all compounds. No oral fluid matrix effect was observed throughout the chromatographic run. Protein precipitation provided a fast and simple sample pretreatment, while LC-APCI-MS/MS proved to be a sensitive and rugged quantitative method for multiple illicit and legal drugs in oral fluid. The method proved to be suitable for the evaluation of oral fluid as an alternative matrix to urine for monitoring illicit drug use and for determining oral fluid methadone concentrations in pregnant opiate and/or cocaine addicts. C1 NIDA, Baltimore, MD 21224 USA. State Univ Ghent, Toxicol Lab, B-9000 Ghent, Belgium. RP Murphy, CM (reprint author), NIDA, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 16 TC 54 Z9 55 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD FEB 15 PY 2003 VL 75 IS 4 BP 798 EP 804 DI 10.1021/ac026111t PG 7 WC Chemistry, Analytical SC Chemistry GA 647CF UT WOS:000181073800014 PM 12622369 ER PT J AU King, MT AF King, MT TI Thermodynamics of the reduction of NADP with 2-propanol catalyzed by an NADP-dependent alcohol dehydrogenase SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE acetone; alcohol dehydrogenase; enthalpy; entropy; equilibrium constant; Gibbs free energy; isopropyl alcohol; NADP; NADPH; 2-propanol; thermodynamics ID SACCHAROMYCES-CEREVISIAE; PURIFICATION; BACTERIA AB The apparent equilibrium constant of the biochemical reaction, 2-propanol + NADP(ox) = acetone + NADP(red), was determined at I = 0.25 M over a wide range of pH (5.63 to 8.02) and temperature (5 to 40degreesC). The reaction was catalyzed by an NADP-dependent alcohol dehydrogenase. The results were used to calculate thermodynamic quantities for the chemical (ionic) reference reaction: 2-propanol + NADP(ox)(3-) = acetone + NADP(red)(4-) + H+. The thermodynamic quantities for this reference reaction are as follows: equilibrium constant K = (5.98 +/- 0.46) x 10(-10); standard molar Gibbs energy change Delta(r)G(0) = (52.65 +/- 0.19) kJ mol(-1); standard molar enthalpy change Delta(r)H(0) = (38.9 +/- 0.6) kJ mol(-1); and standard molar entropy change Delta(r)S(0) = - (46.1 +/- 2.2)JK(-1) mol(-1). All of these results pertain to 25 degreesC (298.15 K) and I = 0. The results also lead, in conjunction with tabulated thermodynamic quantities, to the standard electromotive force E-0 = -0.140 V for the reduction of NADP(ox)(3-) to NADP(red)(4-). ox red, Published by Elsevier Science (USA). C1 NIAAA, Lab Metab & Mol Biol, Unit Metab Control, Rockville, MD 20852 USA. RP King, MT (reprint author), NIAAA, Lab Metab & Mol Biol, Unit Metab Control, 12501 Washington Ave, Rockville, MD 20852 USA. NR 18 TC 7 Z9 7 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 15 PY 2003 VL 410 IS 2 BP 280 EP 286 DI 10.1016/S0003-9861(02)00692-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 646FJ UT WOS:000181024100011 PM 12573288 ER PT J AU Sitkovsky, MV AF Sitkovsky, MV TI Use of the A(2A) adenosine receptor as a physiological immunosuppressor and to engineer inflammation in vivo SO BIOCHEMICAL PHARMACOLOGY LA English DT Editorial Material DE inflammation; adenosine; engineering; cytokines; tissue damage; cancer immunotherapy ID TOXIC LYMPHOCYTES-T; MESSENGER-RNA EXPRESSION; NECROSIS-FACTOR-ALPHA; EXTRACELLULAR ATP; MAST-CELLS; REPERFUSION INJURY; DEAMINASE DEFICIENCY; A(3) RECEPTORS; MEDIATED CYTOTOXICITY; PURINERGIC RECEPTOR AB Inflammation must be inhibited in order to treat, e.g., sepsis or autoimmune diseases or must be selectively enhanced to improve. for example, immunotherapies of tumors or the development of vaccines. Predictable enhancement of inflammation depends upon the knowledge of the "natural" pathways by which it is down-regulated in vivo. Extracellular adenosine and A(2A) adenosine (purinergic) receptors were identified recently as anti-inflammatory signals and as sensors of excessive inflammatory tissue damage, respectively (Ohta A and Sitkovsky M, Nature 2001;414:916-20). These molecules may function as an important part of a physiological "metabolic switch" mechanism, whereby the inflammatory stimuli-produced local tissue damage and hypoxia cause adenosine accumulation and signaling through cyclic AMP-elevating A(2A) adenosine receptors in a delayed negative feedback manner. Patterns of A(2A) receptor expression are activation- and differentiation-dependent, thereby allowing for the "acquisition" of an immunosuppressive "OFF button" and creation of a time-window for immunomodulation. Identification of A(2A) adenosine receptors as "natural" brakes of inflammation provided a useful framework for understanding how tissues regulate inflammation and how to enhance or decrease (engineer) inflammation by targeting this endogenous anti-inflammatory pathway, These findings point to the need of more detailed testing of anti-inflammatory agonists of A(2A) receptors and create a previously unrecognized strategy to enhance inflammation and targeted tissue damage by using antagonists of A(2A) receptors. It is important to further identify the contributions of different types of immune cells at different stages of the inflammatory processes in different tissues to enable the "tailored" treatments with drugs that modulate the signaling through A(2A) purinergic receptors. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 113 TC 110 Z9 113 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD FEB 15 PY 2003 VL 65 IS 4 BP 493 EP 501 AR PII S0006-2952(02)01548-4 DI 10.1016/S0006-2952(02)01548-4 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 645VA UT WOS:000180999200001 PM 12566076 ER PT J AU Gao, ZG Melman, N Erdmann, A Kim, SG Muller, CE Ijzerman, AP Jacobson, KA AF Gao, ZG Melman, N Erdmann, A Kim, SG Muller, CE Ijzerman, AP Jacobson, KA TI Differential allosteric modulation by amiloride analogues of agonist and antagonist binding at A(1) and A(3) adenosine receptors SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE adenosine receptors; allosteric modulation; amiloride; sodium ions; cyclic AMP; receptor binding ID DOPAMINE-RECEPTORS; ACID(B) RECEPTORS; SODIUM; ADENOSINE-A1-RECEPTOR; ACTIVATION; SERIES AB The diuretic drug amiloride and its analogues were found previously to be allosteric modulators of antagonist binding to A(2A) adenosine receptors. In this study, the possibility of the allosteric modulation by amiloride analogues of antagonist binding at A(1) and A(3) receptors, as well as agonist binding at A(1). A(2A), and A(3) receptors, was explored. Amiloride analogues increased the dissociation rates of two antagonist radioligands, [H-3]8-cyclopentyl-1,3-diproplxanthine ([H-3]DPCPX) and [H-3]8-ethyl-4-methyl-2-phenyl-(8R)-4,5,7,8-tetrahydro-1H-imidazo[2, 1-i]purin-5-one ([H-3]PSB-11), from A(1) and A(3) receptors, respectively. Amiloride and 5-(N,N-dimethyl)amiloride (DMA) were more potent at A(1) receptors than at A(3) receptors, while 5-(N.N-hexamethylene)amiloride (HMA) was more potent at A(3) receptors. Thus, amiloride analogues are allosteric inhibitors of antagonist binding at A(1), A(2A), and A(3) adenosine receptor subtypes. In contrast to their effects on antagonist-occupied receptors, amiloride analogues did not affect the dissociation rates of the A(1) agonist [H-3]N-6-[(R)-phenyhsopropyl]adenosine ([H-3]R-PIA) from A(1) receptors or the A(2A) agonist [H-3]2-[p-(2-carboxvethyl)phenyl-ethylamino]-5'-N-ethylearboxamidoadenosine ([H-3]CGS21680) from A(2A) receptors. The dissociation rate of the A(3) agonist radioligand [I-125]N-6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide ([I-125]-AB-MECA) from A(3) receptors was decreased significantly by amiloride analogues. The binding modes of amiloride analogues at agonist-occupied and antagonist-occupied receptors differed markedly, which was demonstrated in all three subtypes of adenosine receptors tested in this study. The effects of the amiloride analogues on the action of the A(3) receptor agonist were explored further using a cyclic AMP functional assay in intact CHO cells expressing the human A(3) receptor. Both binding and functional assays support the allosteric interactions of amiloride analogues with A(3) receptors, (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Bonn, Inst Pharmaceut, D-53115 Bonn, Germany. Leiden Univ, Div Med Chem, Leiden Amsterdam Ctr Drug Res, NL-2300 RA Leiden, Netherlands. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009; Muller, Christa/C-7748-2014 OI Jacobson, Kenneth/0000-0001-8104-1493; Muller, Christa/0000-0002-0013-6624 NR 32 TC 26 Z9 26 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD FEB 15 PY 2003 VL 65 IS 4 BP 525 EP 534 AR PII S0006-2952(02)01556-3 DI 10.1016/S0006-2952(02)01556-3 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 645VA UT WOS:000180999200004 PM 12566079 ER PT J AU Stastny, J Konstantinidis, A Schwarz, MJ Rosenthal, NE Vitouch, O Kasper, S Neumeister, A AF Stastny, J Konstantinidis, A Schwarz, MJ Rosenthal, NE Vitouch, O Kasper, S Neumeister, A TI Effects of tryptophan depletion and catecholamine depletion on immune parameters in patients with seasonal affective disorder in remission with light therapy SO BIOLOGICAL PSYCHIATRY LA English DT Article DE seasonal affective disorder; pathophysiology; tryptophan depletion; catecholamine depletion; immunological parameters ID MAJOR DEPRESSION; CYTOKINES; INTERLEUKIN-6; PSYCHIATRY; NEOPTERIN; MARKERS; SYSTEM; STRESS; HUMANS; BRAIN AB Background: Altered immunologic parameters are found in symptomatic depressed patients relative to remitted depressed patients and healthy controls. We investigated whether tryptophan depletion and catecholamine depletion induce alterations in immunologic parameters in patients with seasonal affective disorder remitted on light therapy, and whether these changes are associated with changes in mood. Methods: Remitted patients with seasonal effective disorder underwent tryptophan depletion, catecholamine depletion, and sham depletion in a prospective randomized, double-blind crossover design. Measures of depression, plasma levels of tryptophan and catecholamine metabolites, and plasma levels of cytokines (sIL-4, IL-6, neopterin, sTNF-R1 and sTNF-R2) were obtained at baseline, and 7, 24, and 30 hours after monoamine depletion. Results: Tryptophan depletion decreased plasma total and free tryptophan levels; catecholamine depletion decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Tryptophan depletion and catecholamine depletion, but not sham depletion, induced a transient exacerbation of depressive symptoms (p < .001); plasma neopterin levels increased during tryptophan depletion and catecholamine depletion (p < .05). Tryptophan depletion and catecholamine depletion induced a transient reduction of plasma sIL-4 levels (p < .05). A significant correlation was found between sIL-4R levels and depression ratings after tryptophan depletion (r = -.61, p < .05). Conclusions: The monoamine depletion-induced alterations of Immoral and cellular immunity suggest a potential role of immunologic parameters in the pathophysiology of seasonal affective disorder; however, the results must be considered preliminary and require further study. (C) 2003 Society, of Biological Psychiatry. C1 NIMH, Mood Anxiety Disorders Program, Bethesda, MD 20892 USA. Max Planck Inst Human Dev, Berlin, Germany. Univ Vienna, Dept Gen Psychiat, Vienna, Austria. Univ Munich, Psychiat Hosp, Dept Neurochem, Munich, Germany. RP Neumeister, A (reprint author), NIMH, Mood Anxiety Disorders Program, North Dr,Bldg 15K,Rm 200, Bethesda, MD 20892 USA. NR 31 TC 11 Z9 12 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 2003 VL 53 IS 4 BP 332 EP 337 AR PII S0006-3223(03)01453-1 DI 10.1016/S0006-3223(02)01453-1 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 643QH UT WOS:000180871600007 PM 12586452 ER PT J AU Abe, K Yarovinsky, FO Murakami, T Shakhov, AN Tumanov, AV Ito, D Drutskaya, LN Pfeffer, K Kuprash, DV Komschlies, KL Nedospasov, SA AF Abe, K Yarovinsky, FO Murakami, T Shakhov, AN Tumanov, AV Ito, D Drutskaya, LN Pfeffer, K Kuprash, DV Komschlies, KL Nedospasov, SA TI Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; PERIPHERAL LYMPHOID ORGANS; ALPHA-DEFICIENT MICE; TISSUE CHEMOKINE SLC; LYMPHOTOXIN-ALPHA; GM-CSF; ABNORMAL-DEVELOPMENT; LANGERHANS CELLS AB TNF/LTalpha/LTbeta (tumor necrosis factor/lymphotoxin-alpha/lymphotoxin-beta) triple knockout (KO) mice show a significant reduction of dendritic cell (DC) number in the spleen, presumably due to defective recruitment and/or production. To distinguish between these possibilities, DCs were generated from bone marrow (BM) cultures prepared from wild-type (wt) and mutant mice in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield of CD11c(+) major histocompatibility complex (MHC) class II+ DCs generated from TNF/LTalpha/LTP-/- BM culture was significantly reduced compared with wt BM culture. In order to further dissect the individual pathways responsible for defective DC properties observed in TNF/LTalpha/LTP-/- mice, the panel of TNF/LT ligand and receptor single KO mice were used. the production of DCs from BM culture was significantly reduced in TNF-/- and TNF receptor (TNFR) p55(-/-) mice, but normal in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice. Recombinant TNF (rTNF) exogenously added to TNF/LTalpha/LTbeta(-/-) BM cultures could reverse this defect, and blocking antibodies showed partial effect on BFA cultures of wt mice. Conversely, numbers of mature DCs in spleen were significantly decreased in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice, but not in TNF-/- and TNFRp55(-/-) mice. These results reveal 2 distinct contributions of fkF/LT cytokines. First, TNF acting through TNF receptor is involved in the development/ maturation of DCs in BM progenitor cultures, but this function appears to be redundant in vivo. Second, the microenvironment in peripheral lymphoid organs associated with LTalpha/LTbeta-LTbetaR Signaling and chemokine production is critical for recruitment efficiency of DCs, and this pathway is indispensable. (C) 2003 by The American Society of Hematology. C1 NCI, SAIC Frederick, Basic Res Program, Ctr Canc Res,Lab Mol Immunoregulat, Ft Detrick, MD 21702 USA. NCI, SAIC Frederick, Ctr Canc Res, Expt Immunol Lab, Ft Detrick, MD 21702 USA. NCI, SAIC Frederick, Baic Res Program, Ft Detrick, MD 21702 USA. Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia. Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia. Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-8000 Munich, Germany. RP Nedospasov, SA (reprint author), NCI, SAIC Frederick, Basic Res Program, Ctr Canc Res,Lab Mol Immunoregulat, Bldg 560,Room 31-70, Ft Detrick, MD 21702 USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; FU NCI NIH HHS [N01-CO-12400] NR 42 TC 59 Z9 63 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2003 VL 101 IS 4 BP 1477 EP 1483 DI 10.1182/blood.V101.4.1477 PG 7 WC Hematology SC Hematology GA 643DM UT WOS:000180846700041 PM 12560241 ER PT J AU Aoki, Y Feldman, GM Tosato, G AF Aoki, Y Feldman, GM Tosato, G TI Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma SO BLOOD LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKINS-LYMPHOMA; ENDOTHELIAL GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; LEUKEMIA-CELLS; VIRAL IL-6; ACTIVATION; TRANSDUCER; TRANSCRIPTION-3 AB Despite some exciting new leads in molecular pathogenesis, AIDS-defining primary effusion lymphoma (PEL) remains a fatal malignancy. The lack of substantial progress in the management of PEL demands innovative treatment approaches. Targeting intracellular molecules critical to cell survival is one unexplored strategy for treating PEL. Here we show that inhibition of signal transducer and activator of transcription-3 (STAT3) leads to apoptosis in PEL cells. STAT3 is constitutively phosphorylated in PEL cell lines BC-1, BCBL-1, and VG-1. Transduction of dominant-negative STAT3 and pharmacological STAT3 inhibition caused caspase-dependent cell death. Although STAT3 activation is known to induce expression of Bcl-2 family proteins, PEL cell apoptosis was independent of Bcl-2, BCI-X-L, or Mcl-1 protein expression. Instead, STAT3 inhibition induced transcriptional repression of survivin, a recently identified inhibitor of apoptosis. Forced overexpression of survivin rescued VG-1 cells from apoptosis induced by STAT3 inhibition. Our findings suggest that activated STAT3 signaling directly contributes to malignant progression of PEL by preventing apoptosis, acting through the prosurvival protein survivin. Since constitutive STAT3 activation and survivin expression have been widely documented in different types of cancers, their linkage may extend to many malignancies and be critical to their pathogenesis. (C) 2003 by The American Society of Hematology. C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20014 USA. RP Aoki, Y (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,12N226, Bethesda, MD 20892 USA. NR 52 TC 291 Z9 304 U1 0 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2003 VL 101 IS 4 BP 1535 EP 1542 DI 10.1182/blood-2002-07-2130 PG 8 WC Hematology SC Hematology GA 643DM UT WOS:000180846700049 PM 12393476 ER PT J AU Bharadwaj, RR Trainor, CD Pasceri, P Ellis, J AF Bharadwaj, RR Trainor, CD Pasceri, P Ellis, J TI LCR-regulated transgene expression levels depend on the Oct-1 site in the AT-rich region of beta-globin intron-2 SO BLOOD LA English DT Article ID LOCUS-CONTROL REGION; NUCLEOSOME-POSITIONING SEQUENCES; PROPER DEVELOPMENTAL CONTROL; YEAST ARTIFICIAL CHROMOSOME; MATRIX ATTACHMENT REGIONS; GENE-EXPRESSION; GAMMA-GLOBIN; BINDING-SITES; DNA-BINDING; MICE AB Human beta-globin transgenes regulated by the locus control region (LCR) express at all integration sites in transgenic mice. For such LCR activity at ectopic sites, the 5'HS3 element requires the presence of the AT-rich region (ATR) in beta-globin intron-2. Here, we examine the dependence of 5'HS3 LCR activity on transcription factor binding sites in the ATR. In vitro DNasel footprint analysis and electrophoretic mobility shift assays of the ATR identified an inverted double Gata-1 site composed of 2 noncanonical sequences (GATT and GATG) and an Oct-1 consensus site. Mutant Oct-1, Gata-1, or double mutant sites were created in the ATR of the BGT50 construct composed of a 5'HS3 beta/gamma-globin hybrid transgene. Transgenes with double mutant sites expressed at all sites of integration, but mean expression levels in transgenic mice were reduced from 64% per copy (BGT50) to 37% (P < .05). Mutation of the inverted double Gata-1 site had no effect at 64% per copy expression levels. In contrast, mutation of the Oct-1 site alone reduced per-copy expression levels to 31 % (P < .05). We conclude that the ability of 5'HS3 to activate expression from all transgene integration sites is dependent on sequences in the ATR that are not bound at high affinity by transcription factors. In addition, the Oct-1 site in the ATR is required for high-level 5'HS3 beta/gamma-globin transgene expression and should be retained in LCRbeta-globin expression cassettes designed for gene therapy. (C) 2003 by The American Society of Hematology. C1 Hosp Sick Children, Dev Biol Program, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ellis, J (reprint author), Hosp Sick Children, Dev Biol Program, Elm Bldg,Room 8154,555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Ellis, James/F-4789-2011 NR 52 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2003 VL 101 IS 4 BP 1603 EP 1610 DI 10.1182/blood-2002-07-2086 PG 8 WC Hematology SC Hematology GA 643DM UT WOS:000180846700059 PM 12393478 ER PT J AU Clark, AS West, KA Blumberg, PM Dennis, PA AF Clark, AS West, KA Blumberg, PM Dennis, PA TI Altered protein kinase C (PKC) isoforms in non-small cell lung cancer cells: PKC delta promotes cellular survival and chemotherapeutic resistance SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; ACTIVATION; APOPTOSIS; TRANSFORMATION; ISOZYMES; MECHANISM; 3-KINASE; PATHWAY; PDK-1 AB Drugs that target protein kinase C (PKC) are now being evaluated in patients with non-small cell lung cancer (NSCLC), but the role of PKC in NSCLC cells remains unclear. We report here that NSCLC cell lines show enhanced phosphorylation and altered expression of specific PKC isoforms compared with normal lung epithelial cells. PKC inhibition variably increased apoptosis, with rottlerin, a PKCdelta inhibitor, being most effective and potentiating chemotherapy-induced apoptosis, especially with trastuzumab. Consistent with PKCdelta being anti-apoptotic in NSCLC cells, transient transfection of a kinase-dead mutant of PKCdelta increased apoptosis and potentiated chemotherapy-induced apoptosis. Our studies provide a rationale for targeting PKC isoforms in NSCLC cells, especially PKCdelta. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20889 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 36 TC 125 Z9 129 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2003 VL 63 IS 4 BP 780 EP 786 PG 7 WC Oncology SC Oncology GA 645XV UT WOS:000181006500010 PM 12591726 ER PT J AU De Flora, S Balansky, RM D'Agostini, F Izzotti, A Camoirano, A Bennicelli, C Zhang, ZQ Wang, Y Lubet, RA You, M AF De Flora, S Balansky, RM D'Agostini, F Izzotti, A Camoirano, A Bennicelli, C Zhang, ZQ Wang, Y Lubet, RA You, M TI Molecular alterations and lung tumors in p53 mutant mice exposed to cigarette smoke SO CANCER RESEARCH LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; CHEMOPREVENTIVE AGENTS; DNA-ADDUCTS; CHRONIC INHALATION; CANCER; MODULATION; RATS; MOUSE; PCNA; CARCINOGENICITY AB Mutations and deletions in p53 are the most common genetic lesions in human cancer, and an extraordinarily high incidence of lung cancer occurs in smokers suffering from Li-Fraumeni syndrome, which is characterized by germ-line inactivation of one p53 allele. In contrast, p53 mutations are infrequent in lung tumors formed in A/J mice. Moreover, despite the dominant role of cigarette smoke in the epidemiology of human lung cancer, it is very difficult to reproduce the lung tumorigenicity of this complex mixture in animal models. We used a transgenic mouse with a dominant-negative p53 mutation to examine the effects of a mutant p53 on smoke-induced lung carcinogenesis in mice. p53 mutant (UL53-3. X A/J)F-1 mice of both genders and their wild-type (wt) littermate controls were exposed whole-body to environmental cigarette smoke (ECS) for up to 9.5 months. Untreated mutant mice of both genders underwent an early stimulus of bronchial cell proliferation, and an age-related formation of DNA adducts in lung and heart. In males, there was an age-related increase of micronucleated normochromatic erythrocytes in peripheral blood and an impairment of body weight gain. These findings underscore a physiological protective role of p53 in wt A/J mice. The response of wt and mutant mice to ECS was similar in terms of oxidative DNA damage in lung and heart, proliferation of the bronchial epithelium, and levels of p53 oncoprotein, as assessed after exposure for 28 days. In contrast, ECS-exposed mutant mice underwent a lower induction of apoptosis in bronchial epithelium, a greater formation of DNA adducts in lung and heart, and a more intense cytogenetic damage, shown by a higher frequency of micronuclei in pulmonary alveolar macrophages and in peripheral blood normochromatic erythrocytes. Interestingly, at the end of the experiment, DNA adducts were not repaired in either wt or mutant mice after discontinuing exposure to ECS for I week. A weak but significant increase of lung tumor incidence and multiplicity was induced in p53 mutant (UL53-3 X A/J)F1 mice after exposure to ECS for either 5 months, followed by recovery in air for 4.5 months, or 9.5 continuative months. Conversely, no tumorigenic effect was observed in their wt littermate controls, carrying a 99.9% A/J background and 5% FVB genome. This contrasts with the weakly positive results obtained in previous studies using wt A/J mice. Thus, in agreement with the results of previous lung tumorigenicity studies performed with the smoke carcinogens benzo(a)pyrene and 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone, (UL53-3 X A/J)F1 mice carrying a mutant p53 transgene appear to be more sensitive to ECS than the corresponding wt littermate controls. These findings provide evidence that p53 mutations play a role in smoke-related carcinogenesis not only in humans but also in A/J mice. C1 Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. Ohio State Univ, Div Human Canc Genet, Columbus, OH 43210 USA. NCI, Rockville, MD 20892 USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. OI izzotti, alberto/0000-0002-8588-0347 FU NCI NIH HHS [N01-CN-05122, N01-CN-75008] NR 50 TC 52 Z9 53 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2003 VL 63 IS 4 BP 793 EP 800 PG 8 WC Oncology SC Oncology GA 645XV UT WOS:000181006500012 PM 12591728 ER PT J AU Chen, YJ Vortmeyer, A Zhuang, ZP Huang, S Jensen, RT AF Chen, YJ Vortmeyer, A Zhuang, ZP Huang, S Jensen, RT TI Loss of heterozygosity of chromosome 1q in gastrinomas: Occurrence and prognostic significance SO CANCER RESEARCH LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; PANCREATIC ENDOCRINE TUMORS; COMPARATIVE GENOMIC HYBRIDIZATION; PREDICTS POOR-PROGNOSIS; SUPPRESSOR GENE KISS1; ALLELIC LOSS; HEPATOCELLULAR-CARCINOMA; METASTATIC GASTRINOMAS; NEUROENDOCRINE TUMORS; THYROID-CARCINOMA AB A proportion of gastrinomas demonstrates aggressive growth, and most deaths occur in this group. Little is known about the molecular pathogenesis of growth of this tumor, and there are no predictive factors that are useful in an individual patient. Chromosome 1 (Chr 1) loss of heterozygosity (LOH) is frequent in a number of nonendocrine tumors and in a few endocrine tumors, and its presence can correlate with tumor aggressiveness and survival. In gastrointestinal endocrine tumors including gastrinomas, little data are available on Chr 1 LOH, and the limited results are contradictory. In the present study we determine whether Chr 1 LOH occurs in gastrinomas and is associated with aggressive growth by performing Chr 1 allelotyping with microsatellite markers in microdissected tumor tissue from 27 human gastrinomas and the leukocyte DNA of the patients. Detailed clinical pathological correlations were possible, because tumor growth in all of the patients was prospectively assessed with yearly imaging studies. Twelve gastrinomas (44%) had Chr 1 LOH, and in all of the cases 1q LOH occurred. 1q LOH was associated with aggressive growth (P = 0.0004), presence of liver metastases (P = 0.019), and postoperative development of hepatic metastases (P = 0.017). Eight (75%) of the 12 tumors with 1q LOH had 1q31-32 LOH over a 17.3 cM region, whereas LOH in 6 tumors (50%) occurred at 1q21-23 over a 12.3 cM area. The presence of 1q31-32 LOH and 1q21-23 LOH correlated with aggressive tumor growth (P = 0.0056 and P = 0.0031, respectively), and with postoperative development of liver metastases (P = 0.0114 and P = 0.011, respectively). These data suggest that 1q LOH is not infrequent in gastrinomas and could be a molecular/genetic prognostic factor for aggressive growth that could be useful clinically. The high frequent allelic loss at 1q31-32 as well as 1q21-23, which was associated with tumor aggressive growth, suggests these two regions harbor putative tumor suppressor gene(s) that are important for aggressive growth of this tumor. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 55 TC 31 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2003 VL 63 IS 4 BP 817 EP 823 PG 7 WC Oncology SC Oncology GA 645XV UT WOS:000181006500016 PM 12591732 ER PT J AU Poguet, AL Legrand, C Feng, X Yen, PM Meltzer, P Samarut, J Flamant, F AF Poguet, AL Legrand, C Feng, X Yen, PM Meltzer, P Samarut, J Flamant, F TI Microarray analysis of knockout mice identifies cyclin D2 as a possible mediator for the action of thyroid hormone during the postnatal development of the cerebellum SO DEVELOPMENTAL BIOLOGY LA English DT Article ID DEVELOPING RAT CEREBELLUM; BRAIN-DEVELOPMENT; GRANULE NEURONS; GENE-EXPRESSION; SONIC HEDGEHOG; MUTANT MICE; TR-ALPHA; HYPOTHYROIDISM; DIFFERENTIATION; BETA AB Thyroid hormone is a major regulator of postnatal brain development, but the precise molecular mechanisms underlying its action in this organ remain poorly understood. We used microarray analysis to identify new target genes in brain. Thyroid hormone treatment of hypothyroid Pax8(-/-) knockout mice, which lack thyroid follicular cells, had a very limited global effect on brain transcripts. This analysis mainly identified cyclin D2 as a new thyroid hormone target gene in the cerebellum of hypothyroid mice. Thyroid hormone receptor (TRalpha and/or TRbeta) knockout mice studies provided further genetic evidence that cyclin D2 is likely to mediate the antiapoptotic effect exerted by thyroid hormone on the cerebellum external granular layer neuroblasts but that this transcriptional activation is not directly exerted by the thyroid hormone receptors. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Ecole Normale Super Lyon, CNRS, UMR 5665, Biol Cellulaire & Mol Lab, F-69364 Lyon 07, France. NIDDK, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Samarut, J (reprint author), Ecole Normale Super Lyon, CNRS, UMR 5665, Biol Cellulaire & Mol Lab, LA INRA913,46 Allee Italie, F-69364 Lyon 07, France. NR 47 TC 44 Z9 46 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD FEB 15 PY 2003 VL 254 IS 2 BP 188 EP 199 DI 10.1016/S0012-1606(02)00039-8 PG 12 WC Developmental Biology SC Developmental Biology GA 649TB UT WOS:000181223100003 PM 12591240 ER PT J AU Bilski, P Hideg, K Kalai, T Bilska, MA Chignell, CF AF Bilski, P Hideg, K Kalai, T Bilska, MA Chignell, CF TI Interaction of singlet molecular oxygen with double fluorescent and spin sensors SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE free radicals; singlet oxygen; quenching; double fluorescent; spin sensors ID ROSE-BENGAL; AQUEOUS-SOLUTION; CATIONIC SURFACTANT; PHOTOOXIDATION; PHOTOSENSITIZATION; PHOTOINHIBITION; PHOTOPROCESSES; OXIDATION; LEAVES; EOSIN AB Double fluorescent and spin sensors were recently used to detect transient oxidants via simultaneous fluorescence change and production of the nitroxide radical detected by electron paramagnetic resonance. One such oxidant, singlet molecular oxygen (O-1(2)), was detected in thylakoid membrane using these probes. In the present study, we investigated the total (physical and chemical) quenching of O-1(2), phosphorescence by sensors composed of the 2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrole moiety attached to xanthene or dansyl fluorophores. We found that the quenching rate constants were in the range (2-7) x 10(7) M-1 s(-1) in acetonitrile and D2O. Quenching of O-1(2) is usually an additive process in which different functional groups may contribute. We estimated that the O-1(2) quenching by the amine fragments was ca. one to two orders of magnitude lower than that for the complete molecules. Our data suggest that the incorporation of a fluorescent chromophore results in additional strong quenching of O-1(2), which may in turn decrease the nitroxide yield via the O-1(2) chemical path, possibly having an effect on quantitative interpretations. We have also found that probes with the dansyl fluorophore photosensitized O-1(2) upon UV excitation with the quantum yield of 0.087 in acetonitrile at 366 nm. This result shows that care must be taken when the dansyl-based sensors are used in experiments requiring UV irradiation. We hope that our results will contribute to a better characterization and wider use of these novel double sensors. Published by Elsevier Science Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Pecs, Inst Organ & Med Chem, Pecs, Hungary. RP Bilski, P (reprint author), POB 12233, Res Triangle Pk, NC 27709 USA. NR 23 TC 17 Z9 17 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB 15 PY 2003 VL 34 IS 4 BP 489 EP 495 DI 10.1016/S0891-5849(02)01330-8 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 641FF UT WOS:000180733700010 PM 12566074 ER PT J AU Love, DC Kochran, J Cathey, RL Shin, SH Hanover, JA AF Love, DC Kochran, J Cathey, RL Shin, SH Hanover, JA TI Mitochondrial and nucleocytoplasmic targeting of O-linked GlcNAc transferase SO JOURNAL OF CELL SCIENCE LA English DT Article DE OGT; O-GlcNAc; glycan-dependent signaling; mitochondria ID PANCREATIC BETA-CELLS; N-ACETYLGLUCOSAMINE; INSULIN-RESISTANCE; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; HEXOSAMINE BIOSYNTHESIS; TRANSGENIC MICE; NUCLEAR-PORE; TETRATRICOPEPTIDE REPEATS; SUBCELLULAR-DISTRIBUTION; GLYCOSYLATION AB O-linked GlcNAc transferase (OGT) mediates a novel glycan-dependent signaling pathway, but the intracellular targeting of OGT is poorly understood. We examined the localization of OGT by immunofluorescence microscopy, subcellular fractionation and immunoblotting using highly specific affinity-purified antisera. In addition to the expected nuclear localization, we found that OGT was highly concentrated in mitochondria. Since the mitochondrial OGT (103 kDa) was smaller than OGT found in other compartments (116 kDa) we reasoned that it was one of two predicted splice variants of OGT. The N-termini of these isoforms are unique; the shorter form contains a potential mitochondrial targeting sequence. We found that when epitope-tagged, the shorter form (mOGT; 103 kDa) concentrated in HeLa cell mitochondria, whereas the longer form (ncOGT, 116 kDa) localized to the nucleus and cytoplasm. The N-terminus of mOGT was essential for proper targeting. Although mOGT appears to be an active transferase, O-linked GlcNAc-modified substrates do not accumulate in mitochondria. Using immunoelectron microscopy and mitochondrial fractionation, we found that mOGT was tightly associated with the mitochondrial inner membrane. The differential localization of mitochondrial and nucleocytoplasmic isoforms of OGT suggests that they perform unique intracellular functions. C1 Hoffmann La Roche Inc, Dept Metab Dis, Nutley, NJ 07110 USA. NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 42 TC 94 Z9 94 U1 1 U2 12 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 FEB 15 PY 2003 VL 116 IS 4 BP 647 EP 654 DI 10.1242/jcs.00246 PG 8 WC Cell Biology SC Cell Biology GA 649VD UT WOS:000181227900008 PM 12538765 ER PT J AU Strachan, GD Jordan-Sciutto, KL Rallapalli, R Tuan, RS Hall, DJ AF Strachan, GD Jordan-Sciutto, KL Rallapalli, R Tuan, RS Hall, DJ TI The E2F-1 transcription factor is negatively regulated by its interaction with the MDMX protein SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE E2F-1; MDMX; interaction; two-hybrid screen ID S-PHASE CHECKPOINT; RETINOBLASTOMA PROTEIN; ONCOPROTEIN MDM2; IN-VIVO; P53; BINDING; APOPTOSIS; FAMILY; GENE; TRANSACTIVATION AB Several proteins with important roles in oncogenesis have been shown to regulate the function of the E2F-1 transcription factor, which is known to activate the expression of genes required for proliferation and apoptosis. Here we identify the MDMX oncoprotein as an E2F-1-binding factor, from a yeast-two hybrid screen using a portion of the E2F-1 protein as "bait." We demonstrate that the region within MDMX needed for the E2F-1:MDMX interaction is located in the central part of the protein, C-terminal of the p53-binding domain. The region within E2F-1 needed for this association is adjacent to the DNA binding domain. Further, when expressed in vivo or in vitro the MDMX protein migrates as two isoforms on SDS-PAGE, the faster migrating isoform having the stronger affinity for the E2F-1 proteins. It appears that this interaction reduces the ability of E2F-1 to bind DNA. Expression of MDMX along with E2F-1 and Dp-1 in Saos2 cells reduces the ability of E2F-1 to bind to its consensus DNA sequence, without altering E2F-1 protein levels. These data indicate that the MDMX protein is capable of associating with E2F-1 and negatively regulating its DNA binding ability. Published 2003 Wiley-Liss, lnc. C1 NIAMS, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD USA. Univ Penn, Sch Dent Med, Dept Pathol, Philadelphia, PA 19104 USA. RP Hall, DJ (reprint author), NIAMS, Cartilage Biol & Orthopaed Branch, NIH, 9000 Rockville Pike,Bldg 13,3W17,MSC 5755, Bethesda, MD USA. RI Jordan-Sciutto, Kelly/A-1046-2007 FU NINDS NIH HHS [NS41202] NR 38 TC 15 Z9 15 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. PD FEB 15 PY 2003 VL 88 IS 3 BP 557 EP 568 DI 10.1002/jcb.10318 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 640LJ UT WOS:000180690100013 PM 12532331 ER PT J AU Ortaldo, JR Young, HA AF Ortaldo, JR Young, HA TI Expression of IFN-gamma upon triggering of activating Ly49D NK receptors in vitro and in vivo: Costimulation with IL-12 or IL-18 overrides inhibitory receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; TYROSINE PHOSPHATASE; SIGNAL-TRANSDUCTION; VIRUS-INFECTION; LY-49D; CYTOTOXICITY; RECOGNITION; CYTOKINE; PHOSPHORYLATION; RECRUITMENT AB NK cells can express both activating and inhibitory Ly49 receptors on their cell surface. When cells expressing both receptors are presented with a ligand, inhibition dominates the functional outcome. In this report we demonstrate that costimulation of the activating Ly49D murine NK cell receptor with IL-12 or IL-18 is capable of over-riding the inhibitory Ly49G2 receptor blockade for cytokine production both in vitro and in vivo. This synergy is mediated by and dependent upon Ly49D-expressing NK cells and results in significant systemic expression of IFN-gamma. This would place NK cells and their activating Ly-49 receptors as important initiators of microbial, antiviral, and antitumor immunity and provide a mechanism for the release of activating Ly49 receptors from inhibitory receptor blockade. The Journal of Immunology, 2003. C1 Natl Canc Inst, Ctr Canc Res, Expt Immunol Lab, Ft Detrick, MD 21702 USA. RP Ortaldo, JR (reprint author), Natl Canc Inst, Ctr Canc Res, Expt Immunol Lab, B-560,Rm 31-93, Ft Detrick, MD 21702 USA. NR 32 TC 49 Z9 50 U1 1 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 FEB 15 PY 2003 VL 170 IS 4 BP 1763 EP 1769 PG 7 WC Immunology SC Immunology GA 642ZC UT WOS:000180836400021 PM 12574340 ER PT J AU Johnson, DR AF Johnson, DR TI Locus-specific constitutive and cytokine-induced HLA class I gene expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-I; NF-KAPPA-B; CELL-ADHESION MOLECULE-1; HUMAN ENDOTHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; STIMULATED RESPONSE ELEMENT; IFN-GAMMA; LEUKOCYTE ANTIGEN; HEAVY-CHAIN; TRANSCRIPTIONAL REGULATION AB Cytokine induction of the MHC class I genes increases the nascent molecules available for binding potentially antigenic peptides. The human H chain loci, HLA-A, -B, and -C, encode highly homologous and polymorphic mRNAs. Here, these transcripts were resolved and measured by competitive PCR of cDNA using locus-specific primers. Endothelial cells expressed many HLA-A and -B, but fewer HLA-C, transcripts. In contrast, HeLa cells expressed many HLA-A and -C, but fewer HLA-B, transcripts. The inflammatory cytokines TNF-alpha, IFN-beta, and IFN-gamma induced HLA-B strongly, but HLA-A and -C weakly in both cell types. Combined treatment with IFNs and TNF further increased HLA-A and -B, but not HLA-C transcripts. The constitutive and inducible activities of transfected promoters correlated well with mRNA levels. The weak IFN response of the HLA-A2 promoter was not due to variations in the IFN consensus sequence, the site alpha, or a 3-bp insertion between them. The HLA-Cw6 promoter was less TNF responsive due to a variant kappaB enhancer, which also reduced the IFN responses. The NF-kappaB subunit RelA strongly activated the HLA-A2 and -B7 promoters but only weakly activated the HLA-Cw6 promoter due to the variant kappaB. Cotransfecting NF-kappaB1 with RelA further increased activity of the HLA-A2 and -B7, but not HLA-Cw6, promoters. All three promoters were activated by MHC class II trans-activator, but not CREB-binding protein, whereas IFN regulatory factor-1 and -2 weakly activated the HLA-B7 and -Cw6, but not HLA-A2, promoters. These studies illustrate common and locus-specific mechanisms that may be targeted to modulate immune reactions. C1 Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Johnson, DR (reprint author), NIAID, Div Allergy Immunol & Transplantat, 6700-B Rockledge Dr, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R29 AI 35099] NR 55 TC 35 Z9 37 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 FEB 15 PY 2003 VL 170 IS 4 BP 1894 EP 1902 PG 9 WC Immunology SC Immunology GA 642ZC UT WOS:000180836400037 PM 12574356 ER PT J AU Steel, C Nutman, TB AF Steel, C Nutman, TB TI CTLA-4 in filarial infections: Implications for a role in diminished T cell reactivity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN LYMPHATIC FILARIASIS; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; ONCHOCERCA-VOLVULUS; IMMUNE-RESPONSE; BRUGIA-PAHANGI; PROTECTIVE IMMUNITY; BANCROFTIAN FILARIASIS; HELMINTH INFECTIONS; REGULATORY CELLS; KNOCKOUT MICE AB To determine the role that CTLA-4 might play in mediating the diminished parasite Ag-specific T cell responsiveness that is characteristically seen in filaria-infected patients, several study populations and methods were used. First, quantitative assessment of mRNA expression determined that PBMC from uninfected adolescents exposed in utero to microfilarial (Mf) Ag demonstrated a strong up-regulation of CTLA-4 to the Mf stage of the parasite in contrast to that observed in cells from children born of uninfected mothers (p = 0.005). Next, the frequency of CTLA-4 expression was examined using flow cytometry in cells from filaria-infected and -uninfected individuals ex vivo. Individuals born in filarial endemic regions of the world (with long-standing infections) had greater percentages of CD4(+)CTLA-4(+) cells than did expatriate infected or uninfected individuals (P = 0.005 and 0.05, respectively); in addition, Mf(+) patients demonstrated higher frequencies of CD4(+)CTLA-4(+) and CD8(+)CTLA-4(+) cells (P = 0.027 and 0.037, respectively) than did Mf(-) infected individuals. Of interest, the greatest intensity of CTLA-4 expression occurred in CD4(+)CD25(+) cells, a population purported to include suppressor cells. Finally, in vitro blocking of CTLA-4 expression in PBMC from filaria-infected individuals induced a mean increase of 44% in IL-5 production to Mf Ag, whereas there was a concurrent mean decrease of 42% in IFN-gamma production, suggesting that CTLA-4 also acts to alter the Th1/Th2 balance in filaria-infected individuals. Together, these data indicate a significant role for CTLA-4 in regulating the host response to filarial infections and that factors such as length of exposure and patency are important codeterminants. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Steel, C (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. NR 61 TC 66 Z9 71 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 FEB 15 PY 2003 VL 170 IS 4 BP 1930 EP 1938 PG 9 WC Immunology SC Immunology GA 642ZC UT WOS:000180836400042 PM 12574361 ER PT J AU Poehlein, CH Hu, HM Yamada, J Assmann, K Alvord, WG Urba, WJ Fox, BA AF Poehlein, CH Hu, HM Yamada, J Assmann, K Alvord, WG Urba, WJ Fox, BA TI TNF plays an essential role in tumor regression after adoptive transfer of perforin/IFN-gamma double knockout effector T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPH-NODE CELLS; ANTITUMOR IMMUNE-RESPONSE; COLONY-STIMULATING FACTOR; ACTIVATED KILLER-CELLS; INFILTRATING LYMPHOCYTES; IFN-GAMMA; INTERFERON-GAMMA; NECROSIS-FACTOR; MURINE TUMOR; IN-VIVO AB We have recently shown that effector T cells (T-E) lacking either perforin or IFN-gamma are highly effective mediators of tumor regression. To rule out compensation by either mechanism, TE deficient in both perforin and IFN-gamma (perforin knockout (PKO)/IFN-gamma knockout (GKO)) were generated. The adoptive transfer of PKO/GKO T, mediated complete tumor regression and cured wild-type animals with established pulmonary metastases of the B16BL6-D5 (D5) melanoma cell line. PKO/GKO T-E also mediated tumor regression in D5 tumor-bearing PKO, GKO, or PKO/GKO recipients, although in PKO/GKO recipients efficacy was reduced. PKO/GKO T-E exhibited tumor-specific TNF-alpha production and cytotoxicity in a 24-h assay, which was blocked by the soluble TNFRII-human IgG fusion protein (TNFRII:Fc). Blocking TNF in vivo by administering soluble TNFR 11 fusion protein (TNFRII:Fc) significantly reduced the therapeutic efficacy of PKO/GKO, but not wild-type T-E. This study identifies perforin, IFN-gamma and TNF as a critical triad of effector molecules that characterize therapeutic antitumor T cells. These insights could be used to monitor and potentially tune the immune response to cancer vaccines. C1 Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Lab Mol & Tumor Immunol, Portland, OR 97213 USA. Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Lab Clin Res, Portland, OR 97213 USA. Oregon Hlth & Sci Univ, Oregon Grad Inst, Dept Biochem & Mol Biol, Portland, OR 97202 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97202 USA. Oregon Hlth & Sci Univ, Oregon Canc Ctr, Portland, OR 97202 USA. NCI, Frederick Canc Res & Dev Ctr, Data Management Serv, Frederick, MD 21702 USA. RP Fox, BA (reprint author), Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Lab Mol & Tumor Immunol, 4805 NE Gilsan St, Portland, OR 97213 USA. FU NCI NIH HHS [1R01 CA 92254-01, 1R01 CA 80964-03] NR 54 TC 49 Z9 51 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 FEB 15 PY 2003 VL 170 IS 4 BP 2004 EP 2013 PG 10 WC Immunology SC Immunology GA 642ZC UT WOS:000180836400051 PM 12574370 ER PT J AU Johnson, TR Parker, RA Johnson, JE Graham, BS AF Johnson, TR Parker, RA Johnson, JE Graham, BS TI IL-13 is sufficient for respiratory syncytial virus G glycoprotein-induced eosinophilia after respiratory syncytial virus challenge SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-HELPER CELL; CONTROL PULMONARY INFLAMMATION; RECOMBINANT VACCINIA VIRUSES; ATTACHMENT G-PROTEIN; BALB/C MICE; HOST-DEFENSE; IN-VIVO; CYTOKINE EXPRESSION; LYMPHOCYTE ACTIVITY; EPITHELIAL-CELLS AB Although well studied in settings of helminth infection and allergen sensitization, the combined contributions of IL-4 and IL-13 and their signaling pathways in models of viral pathogenesis have not been reported. Using a murine model of respiratory syncytial virus (RSV) infection, we evaluated the contribution of IL-13, alone and in conjunction with IL-4, during immunization with recombinant vaccinia virus expressing RSV G glycoprotein (vvGs) or with formalin-inactivated RSV (FI-RSV). We showed that both IL-4 and IL-13 activity must be inhibited to modulate G-specific responses resulting in severe RSV-induced disease. Inhibition of IL-4 or IL-13 activity alone had minimal impact on disease in vvGs-immunized mice. However, treatment of IL-4-deficient mice with IL-13Ra during vvGs immunization reduced IL-5, IL-13, and eotaxin production and pulmonary eosinophilia after RSV challenge. In contrast, FI-RSV-induced immune responses were diminished when either IL-4 or IL-13 activity was blocked. After RSV challenge, these type 2 T cell responses were also diminished in vvGs-primed IL-4Ralpha-deficient mice. Our data suggest that secreted vvGs uses mechanisms requiring signaling through the IL-4Ralpha-chain by either IL-4 or IL-13 for induction of eosinophilia and is the first description of the relative contributions of IL-4, IL-13, and their receptors in viral pathogenesis. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Med & Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. Harvard Univ, Sch Med, Dept Med Biostat, Boston, MA 02115 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr MSC 3017,Bldg 40,Room 2504, Bethesda, MD 20892 USA. FU PHS HHS [R01 33933] NR 75 TC 60 Z9 60 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 FEB 15 PY 2003 VL 170 IS 4 BP 2037 EP 2045 PG 9 WC Immunology SC Immunology GA 642ZC UT WOS:000180836400055 PM 12574374 ER PT J AU Kossmann, T Morganti-Kossmann, MC Orenstein, JM Britt, WJ Wahl, SM Smith, PD AF Kossmann, T Morganti-Kossmann, MC Orenstein, JM Britt, WJ Wahl, SM Smith, PD TI Cytomegalovirus production by infected astrocytes correlates with transforming growth factor-beta release SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR; IMMUNE-DEFICIENCY-SYNDROME; NERVOUS-SYSTEM; FACTOR-ALPHA; VIRUS; GROWTH-FACTOR-BETA-1; FACTOR-BETA-1; LOCALIZATION; EXPRESSION; INDUCTION AB Cytomegalovirus (CMV) encephalitis is well documented in immunosuppressed persons, but its pathogenesis has received little investigative attention. The examination of brain tissue from 2 patients with acquired immunodeficiency syndrome who had CMV encephalitis showed colocalization of CMV inclusions and transforming growth factor (TGF)-beta in cells that contained astrocyte-specific glial filaments. To investigate the relationship between CMV and TGF-beta in the brain, an ex vivo murine model of CMV-infected astrocytes was established. Cultures of primary murine (strain FVB/N) astrocytes inoculated with murine (Smith strain) CMV expressed, over time, increasing amounts of infectious CMV in parallel with increasing levels of TGF-beta mRNA and peptide. Astrocyte release of CMV declined in the presence of antibody to TGF-beta and increased substantially after the addition of exogenous TGF-beta. These findings suggest that CMV infection of astrocytes induces the production of TGF-beta, which in turn enhances productive CMV expression. C1 Univ Alabama, Dept Med Gastroenterol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. VA Med Ctr, Birmingham, AL USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. Natl Inst Dent & Crainofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Smith, PD (reprint author), Univ Alabama, Dept Med Gastroenterol, 633 Zeigler Res Bldg,703 S 19th St, Birmingham, AL 35294 USA. FU NIAID NIH HHS [AI35602]; NICHD NIH HHS [HD41361]; NIDDK NIH HHS [DK47322] NR 43 TC 20 Z9 22 U1 0 U2 1 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 FEB 15 PY 2003 VL 187 IS 4 BP 534 EP 541 DI 10.1086/373995 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 643WJ UT WOS:000180884500002 PM 12599069 ER PT J AU Philpott, S Weiser, B Tarwater, P Vermund, SH Kleeberger, CA Gange, SJ Anastos, K Cohen, M Greenblatt, RM Kovacs, A Minkoff, H Young, MA Miotti, P Dupuis, M Chen, CH Burger, H AF Philpott, S Weiser, B Tarwater, P Vermund, SH Kleeberger, CA Gange, SJ Anastos, K Cohen, M Greenblatt, RM Kovacs, A Minkoff, H Young, MA Miotti, P Dupuis, M Chen, CH Burger, H TI CC chemokine receptor 5 genotype and susceptibility to transmission of human immunodeficiency virus type 1 in women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INJECTION-DRUG USERS; HIV-1 INFECTION; SEX-DIFFERENCES; RNA LEVELS; HETEROSEXUAL TRANSMISSION; DISEASE PROGRESSION; VIRAL LOAD; RESISTANCE; GENE; INDIVIDUALS AB The human gene for CC chemokine receptor 5, a coreceptor for human immunodeficiency virus type 1 (HIV-1), affects susceptibility to infection. Most studies of predominantly male cohorts found that individuals carrying a homozygous deleted form of the gene, Delta32, were protected against transmission, but protection did not extend to Delta32 heterozygotes. The role played by this mutation in HIV-1 transmission to women was studied in 2605 participants in the Women's Interagency HIV Study. The Delta32 gene frequency was 0.026 for HIV-1-seropositive women and 0.040 for HIV-1-seronegative women, and statistical analyses showed that Delta32 heterozygotes were significantly less likely to be infected (odds ratio, 0.63 [95% confidence interval, 0.44-0.90]). The CCR5 Delta32 heterozygous genotype may confer partial protection against HIV-1 infection in women. Because Delta32 is rare in Africans and Asians, it seems plausible that differential genetic susceptibility, in addition to social and behavioral factors, may contribute to the rapid heterosexual spread of HIV-1 in Africa and Asia. C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA. Albany Med Coll, Dept Med, Albany, NY USA. SUNY Hlth Sci Ctr, Dept Obstet Gynecol, Brooklyn, NY USA. Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Univ Alabama, Dept Epidemiol & Int Hlth, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Cook Cty Hosp, Dept Med, Chicago, IL 60612 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA. Los Angeles Cty, Dept Pediat, Los Angeles, CA USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. RP Burger, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, 120 New Scotland Ave, Albany, NY 12208 USA. OI Gange, Stephen/0000-0001-7842-512X; Vermund, Sten/0000-0001-7289-8698 FU NIAID NIH HHS [R01 AI052065-01, R01 AI052065, R01-AI-42555, U01 AI031834, U01 AI034989, U01 AI034993, U01 AI034994, U01 AI035004, U01 AI042590, U01-AI-31834, U01-AI-34989, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-42590]; NICHD NIH HHS [1F32-HD08478-01, F32 HD008478, U01 HD032632, U01-HD-32632] NR 38 TC 22 Z9 22 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 15 PY 2003 VL 187 IS 4 BP 569 EP 575 DI 10.1086/367995 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 643WJ UT WOS:000180884500006 PM 12599073 ER PT J AU Matsumoto, M Hoe, NP Liu, MY Beres, SB Sylva, GL Brandt, CM Haase, G Musser, JM AF Matsumoto, M Hoe, NP Liu, MY Beres, SB Sylva, GL Brandt, CM Haase, G Musser, JM TI Intrahost sequence variation in the streptococcal inhibitor of complement gene in patients with human pharyngitis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT American-Society-for-Microbiology Conference on Streptococcal Genetics CY APR 14-17, 2002 CL ASHEVILLE, NORTH CAROLINA SP Amer Soc Microbiol ID GROUP-A STREPTOCOCCUS; EXTRACELLULAR PROTEIN; PYOGENES; STRAINS; IDENTIFICATION; VARIANTS; EPIDEMIC; DISEASE AB Selection of new variants of the streptococcal inhibitor of complement protein has been implicated in the perpetuation of epidemics caused by serotype M1 strains of group A Streptococcus (GAS). The frequency at which new streptococcal inhibitor of complement (Sic) variants arise in an infected individual is not known. To study this issue, the sic gene was sequenced in 100 isolates cultured from throat swabs of each of 20 patients with acute pharyngitis caused by serotype M1 GAS. Five patients were infected with GAS populations expressing 2 Sic variants characterized by deletion of a region of the protein. In contrast, no intrahost variation was detected in the number of a pentanucleotide repeat (CAAAA) that controls production of a bacterial cell-surface collagen-like protein by slipped-strand mispairing. Sic variation occurs at a sufficient frequency in vivo to result in mixed infections on the mucosal surface of human hosts, potentially contributing to pathogen survival. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Rhein Westfal TH Aachen, Univ Hosp, Natl Reference Ctr Streptococci, Aachen, Germany. Rhein Westfal TH Aachen, Inst Med Microbiol, Aachen, Germany. RP Musser, JM (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. RI Haase, Gerhard/C-6492-2009 OI Haase, Gerhard/0000-0001-7771-3189 NR 22 TC 19 Z9 20 U1 0 U2 5 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 FEB 15 PY 2003 VL 187 IS 4 BP 604 EP 612 DI 10.1086/367993 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 643WJ UT WOS:000180884500010 PM 12599077 ER PT J AU Ballou, WR Reed, JL Noble, W Young, NS Koenig, S AF Ballou, WR Reed, JL Noble, W Young, NS Koenig, S TI Safety and immunogenicity of a recombinant parvovirus B19 vaccine formulated with MF59C.1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 01, 2001 CL BALTIMORE, MARYLAND SP Pediat Acad Soc ID CELL-LINE; INFECTION; PREGNANCY; TRIAL AB A recombinant human parvovirus B19 vaccine (MEDI-491; MedImmune) composed of the VP1 and VP2 capsid proteins and formulated with MF59C.1 adjuvant was evaluated in a randomized, double-blind, phase 1 trial. Parvovirus B19-seronegative adults (n = 24) received either 2.5 or 25 mug MEDI-491 at 0, 1, and 6 months. MEDI-491 was safe and immunogenic. All volunteers developed neutralizing antibody titers that peaked after the third immunization and were sustained through study day 364. C1 Medimmune Inc, Gaithersburg, MD 20878 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Ballou, WR (reprint author), Medimmune Inc, 35 W Watkins Mill Rd, Gaithersburg, MD 20878 USA. NR 15 TC 55 Z9 65 U1 0 U2 1 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 FEB 15 PY 2003 VL 187 IS 4 BP 675 EP 678 DI 10.1086/368382 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 643WJ UT WOS:000180884500018 PM 12599085 ER PT J AU Gao, HM Hong, JS Zhang, WQ Liu, B AF Gao, HM Hong, JS Zhang, WQ Liu, B TI Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: Relevance to the etiology of Parkinson's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE pesticide; inflammation; microglia; NADPH oxidase; Parkinson's disease; synergistic neurotoxicity ID ALZHEIMERS-DISEASE; MICROGLIA; BRAIN; EXPOSURE; RISK; CULTURES; INJURY AB Parkinson's disease (PD) is characterized by a progressive degeneration of the nigrostriatal dopaminergic pathway resulting in movement disorders. Although its etiology remains unknown, PD may be the final outcome of interactions among multiple factors, including exposure to environmental toxins and the occurrence of inflammation in the brain. In this study, using primary mesencephalic cultures, we observed that nontoxic or minimally toxic concentrations of the pesticide rotenone (0.5 nM) and the inflammogen lipopolysaccharide (LPS) (0.5 ng/ml) synergistically induced dopaminergic neurodegeneration. The synergistic neurotoxicity of rotenone and LPS was observed when the two agents were applied either simultaneously or in tandem. Mechanistically, microglial NADPH oxidase-mediated generation of reactive oxygen species appeared to be a key contributor to the synergistic dopaminergic neurotoxicity. This conclusion was based on the following observations. First, inhibition of NADPH oxidase or scavenging of free radicals afforded significant neuroprotection. Second, rotenone and LPS synergistically stimulated the NADPH oxidase-mediated release of the superoxide free radical. Third and most importantly, rotenone and LPS failed to induce the synergistic neurotoxicity as well as the production of superoxide in cultures from NADPH oxidase-deficient animals. This is the first demonstration that low concentrations of a pesticide and an inflammogen work in synergy to induce a selective degeneration of dopaminergic neurons. Findings from this study may be highly relevant to the elucidation of the multifactorial etiology of PD and the discovery of effective therapeutic agents for the treatment of the disease. C1 NIEHS, Nueropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Dalian Med Univ, Dept Physiol, Dalian 116027, Peoples R China. RP Liu, B (reprint author), NIEHS, Nueropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI gao, huiming/C-8454-2012; liu, Bin/A-7695-2009 NR 41 TC 158 Z9 170 U1 2 U2 24 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 FEB 15 PY 2003 VL 23 IS 4 BP 1228 EP 1236 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 647LM UT WOS:000181094300017 PM 12598611 ER PT J AU Walter, L Franklin, A Witting, A Wade, C Xie, YH Kunos, G Mackie, K Stella, N AF Walter, L Franklin, A Witting, A Wade, C Xie, YH Kunos, G Mackie, K Stella, N TI Nonpsychotropic cannabinoid receptors regulate microglial cell migration SO JOURNAL OF NEUROSCIENCE LA English DT Article DE microglia; migration; cannabinoids; glutamate; purinergic; kinase ID ACTIVATED PROTEIN-KINASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS MODEL; FATTY-ACID ETHANOLAMIDES; CB2 RECEPTOR; ENDOGENOUS CANNABINOIDS; SELECTIVE ANTAGONIST; SIGNAL-TRANSDUCTION; CONTROL SPASTICITY; BRAIN AB During neuroinflammation, activated microglial cells migrate toward dying neurons, where they exacerbate local cell damage. The signaling molecules that trigger microglial cell migration are poorly understood. In this paper, we show that pathological overstimulation of neurons by glutamate plus carbachol dramatically increases the production of the endocannabinoid 2-arachidonylglycerol (2-AG) but only slightly increases the production of anandamide and does not affect the production of two putative endocannabinoids, homo-gamma-linolenylethanolamide and docosatetraenylethanolamide. We further show that pathological stimulation of microglial cells with ATP also increases the production of 2-AG without affecting the amount of other endocannabinoids. Using a Boyden chamber assay, we provide evidence that 2-AG triggers microglial cell migration. This effect of 2-AG occurs through CB2 and abnormal-cannabidiol-sensitive receptors, with subsequent activation of the extracellular signal-regulated kinase 1/2 signal transduction pathway. It is important to note that cannabinol and cannabidiol, two nonpsychotropic ingredients present in the marijuana plant, prevent the 2-AG-induced cell migration by antagonizing the CB2 and abnormal-cannabidiol-sensitive receptors, respectively. Finally, we show that microglial cells express CB2 receptors at the leading edge of lamellipodia,which is consistent with the involvement of microglial cells in cell migration. Our study identifies a cannabinoid signaling system regulating microglial cell migration. Because this signaling system is likely to be involved in recruiting microglial cells toward dying neurons, we propose that cannabinol and cannabidiol are promising nonpsychotropic therapeutics to prevent the recruitment of these cells at neuroinflammatory lesion sites. C1 Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Nat Inst Drug Abuse & Alcoholism, NIH, Bethesda, MD 20892 USA. RP Stella, N (reprint author), Univ Washington, Dept Pharmacol, 1959 NE Pacific St, Seattle, WA 98195 USA. RI Mackie, Kenneth/B-7358-2011; Mackie, Ken/E-3715-2013 OI Mackie, Ken/0000-0001-8501-6199 FU NIDA NIH HHS [DA11322, DA00286, DA14486] NR 74 TC 361 Z9 374 U1 4 U2 24 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 FEB 15 PY 2003 VL 23 IS 4 BP 1398 EP 1405 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 647LM UT WOS:000181094300034 PM 12598628 ER PT J AU Jackson, DA McDowell, JC Dean, A AF Jackson, DA McDowell, JC Dean, A TI beta-Globin locus control region HS2 and HS3 interact structurally and functionally SO NUCLEIC ACIDS RESEARCH LA English DT Article ID KRUPPEL-LIKE FACTOR; DNASEI HYPERSENSITIVE SITES; FACTOR EKLF; TRANSCRIPTION FACTOR; GENE-EXPRESSION; ERYTHROID-CELLS; CHROMATIN STRUCTURE; TARGETED DELETION; TRANSGENIC MICE; GAMMA-GLOBIN AB The overall structure of the DNase I hypersensitive sites (HSs) that comprise the beta-globin locus control region (LCR) is highly conserved among mammals, implying that the HSs have conserved functions. However, it is not well understood how the LCR HSs, either individually or collectively, activate transcription. We analyzed the interactions of HS2, HS3 and HS4 with the human epsilon- and beta-globin genes in chromatinized episomes in fetal/embryonic K562 cells. Only HS2 activates transcription of the epsilon-globin gene, while all three HSs activate the beta-globin gene. HS3 stimulates the beta-globin gene constitutively, but HS2 and HS4 transactivation requires expression of the transcription factor EKLF, which is not present in K562 cells but is required for beta-globin expression in vivo. To begin addressing how the individual HSs may interact with one another in a complex, we linked the beta-globin gene to both the HS2 and HS3. HS2 and HS3 together resulted in synergistic stimulation of beta-globin transcription. Unexpectedly, mutated, inactive forms of HS2 impeded the activation of the beta-globin gene by HS3. Thus, there appear to be distinct interactions among the HSs and between the HSs and the globin genes. These preferential, non-exclusive interactions may underlie an important structural and functional cooperativity among the regulatory sequences of the beta-globin locus in vivo. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, A (reprint author), Bldg 50,Room 3154,50 South Dr,MSC 8028, Bethesda, MD 20892 USA. RI Jackson, David/E-9984-2014 NR 54 TC 15 Z9 15 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 FEB 15 PY 2003 VL 31 IS 4 BP 1180 EP 1190 DI 10.1093/nar/gkg217 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647VQ UT WOS:000181115100015 PM 12582237 ER PT J AU Schaal, TD Mallet, WG McMinn, DL Nguyen, NV Sopko, MM John, S Parekh, BS AF Schaal, TD Mallet, WG McMinn, DL Nguyen, NV Sopko, MM John, S Parekh, BS TI Inhibition of human papilloma virus E2 DNA binding protein by covalently linked polyamides SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PYRROLE-IMIDAZOLE POLYAMIDES; IRREGULAR NUCLEIC-ACIDS; TUMOR-SUPPRESSOR GENES; MINOR-GROOVE BINDERS; NUCLEOSOME CORE DNA; STRUCTURAL BASIS; TRANSCRIPTION FACTORS; CRYSTAL-STRUCTURE; SMALL MOLECULES; RECOGNITION AB Polyamides are a class of heterocyclic small molecules with the potential of controlling gene expression by binding to the minor groove of DNA in a sequence-specific manner. To evaluate the feasibility of this class of compounds as antiviral therapeutics, molecules were designed to essential sequence elements occurring numerous times in the HPV genome. This sequence element is bound by a virus-encoded transcription and replication factor E2, which binds to a 12 bp recognition site as a homodimeric protein. Here, we take advantage of polyamide:DNA and E2:DNA co-crystal structural information and advances in polyamide synthetic chemistry to design tandem hairpin polyamides that are capable of displacing the major groove-binding E2 homodimer from its DNA binding site. The binding of tandem hairpin polyamides and the E2 DNA binding protein to the DNA site is mutually exclusive even though the two ligands occupy opposite faces of the DNA double helix. We show with circular permutation studies that the tandem hairpin polyamide prevents the intrinsic bending of the E2 DNA site important for binding of the protein. Taken together, these results illustrate the feasibility of inhibiting the binding of homodimeric, major groove-binding transcription factors by altering the local DNA geometry using minor groove-binding tandem hairpin polyamides. C1 NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Parekh, BS (reprint author), NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bldg 41,Room B307, Bethesda, MD 20892 USA. NR 70 TC 28 Z9 28 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 FEB 15 PY 2003 VL 31 IS 4 BP 1282 EP 1291 DI 10.1093/nar/gkg206 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647VQ UT WOS:000181115100026 PM 12582248 ER PT J AU Dagdug, L Berezhkovskii, AM Weiss, GH AF Dagdug, L Berezhkovskii, AM Weiss, GH TI Smoluchowski-like theory for trapping kinetics in a slab SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE constrained Brownian motion; Wiener sausage volume; path integral ID WIENER SAUSAGE; STATIC TRAPS; DIFFUSION AB The theory of diffusion-limited reactions is traditionally developed in terms of unconstrained diffusion in an unbounded volume. The Smoluchowski mean-field theory predicts an exponential decay of the survival probability for particles that diffuse among randomly placed static traps. This means that the ensemble of traps may be considered as a uniform absorbing continuum. It is shown that this picture is also correct in the case of constrained diffusion, more specifically for diffusion in a slab constrained by two parallel absorbing planes. (C) 2002 Published by Elsevier Science B.V. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Dagdug, L (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD FEB 15 PY 2003 VL 318 IS 3-4 BP 341 EP 346 AR PII S0378-4371(02)01380-8 DI 10.1016/S0378-4371(02)01380-8 PG 6 WC Physics, Multidisciplinary SC Physics GA 642YP UT WOS:000180835200004 ER PT J AU Wu, A Yamada, K Neville, DM Awwad, M Wain, JC Shimizu, A Gojo, S Kitamura, H Colvin, RB Cooper, DKC Sykes, M Sachs, DH AF Wu, A Yamada, K Neville, DM Awwad, M Wain, JC Shimizu, A Gojo, S Kitamura, H Colvin, RB Cooper, DKC Sykes, M Sachs, DH TI Xenogeneic thymus transplantation in a pig-to-baboon model SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; SKIN-GRAFT TOLERANCE; THYMECTOMIZED MICE; INDUCTION; CELLS; BARRIER; MHC; ALLOGRAFTS; CHILDREN; SWINE AB Background We have tested whether fetal porcine thymic tissue transplantation can lead to tolerance across a discordant (pig-to-baboon) xenogeneic barrier. Methods. Six baboons underwent a conditioning regimen with thymectomy, splenectomy, and anti-monkey CD3 antibody conjugated to a diphtheria toxin binding site mutant (FN18-CRM9). Porcine fetal or neonatal thymic tissue was transplanted into three baboons. Three control baboons received either no transplanted pig tissue (n=1) or adult pig lymph node (n=2). Cellular responses and skin xenografts were used to test for tolerance. Results. Experimental baboons: After T-cell depletion and thymic transplantation, recovery of thymus-dependent naive-type CD4 cells (CD4/CD45RA(high)) and in vitro xenogeneic hyporesponsiveness were observed. No sensitization of alpha-galactosyl antibody responses was observed. The thymic grafts survived up to 48 days. Porcine skin xenografts were performed in two of these animals with survival of 22 and 24 days. Control baboons: Only two of these animals were completely T-cell depleted, and both failed to recover thymus-dependent T cells (CD4/CD45RA(high)). In one animal, general in vitro hyporesponsiveness was observed, with subsequent death from infection. The second animal demonstrated delayed recovery of T cells and prolonged general hyporesponsiveness in vitro. Neither animal demonstrated prolongation of porcine skin grafts compared with allografts (both rejected by day 13). Conclusions. Porcine thymic tissue is able to induce xenogeneic hyporesponsiveness. More efficient thymic engraftment may allow this approach to induce xenograft tolerance. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. Immerge Bio Therapeut, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sachs, DH (reprint author), Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 21 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 2003 VL 75 IS 3 BP 282 EP 291 DI 10.1097/01.TP.0000044137.97841.99 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 646UH UT WOS:000181053100008 PM 12589146 ER PT J AU Mulherin, SA O'Brien, TR Ioannidis, JPA Goedert, JJ Buchbinder, SP Coutinho, RA Jamieson, BD Meyer, L Michael, NL Pantaleo, G Rizzardi, GP Schuitemaker, H Sheppard, HW Theodorou, ID Vlahov, D Rosenberg, PS AF Mulherin, SA O'Brien, TR Ioannidis, JPA Goedert, JJ Buchbinder, SP Coutinho, RA Jamieson, BD Meyer, L Michael, NL Pantaleo, G Rizzardi, GP Schuitemaker, H Sheppard, HW Theodorou, ID Vlahov, D Rosenberg, PS CA Int Meta-Analysis HIV Host Genetic TI Effects of CCR5-Delta 32 and CCR2-64I alleles on HIV-1 disease progression: the protection varies with duration of infection SO AIDS LA English DT Article DE AIDS; alleles; CCR5; CCR2; chemokine receptors; HIV-1 ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; CHEMOKINE RECEPTOR; AIDS PROGRESSION; HIV-1-INFECTED PATIENTS; TYPE-1 INFECTION; CLINICAL COURSE; GENE DELETION; CELL COUNTS; CCR5 LOCUS AB Objective: To examine temporal variation in the effects of CCR5-Delta32 and CCR2-641 chemokine receptor gene polymorphisms on HIV-1 disease progression. Design: Pooled analysis of individual patient data from 10 cohorts of HIV-1 seroconverters from the United States, Europe, and Australia. Methods: We studied HIV-1 seroconverters of European (n = 1635) or African (n = 215) ancestry who had been genotyped for CCR5-A32 and CCR2-641. We used Cox proportional hazards models with time-varying coefficients to determine whether the genetic protection against AIDS (1987 case definition) and death varied with time since seroconversion. Results: Protection against AIDS conferred by CCR5-A32 held constant at a 31% (RH 0.69, 95% Cl 0.54, 0.88) reduction in risk over the course of HIV-1 infection, whereas protection against death held constant at a 39% reduction in risk (RH 0.61, 95% Cl 0.45, 0.88). When the period from AIDS to death was isolated, the survival benefit of CCR5-A32 diminished 2 years after AIDS. Protection against AIDS conferred by CCR2-641 was greatest early in the disease course. Compared with individuals without CCR5-Delta32 or CCR2-641, individuals with one or two copies of CCR2-641 had a 58% lower risk of AIDS during the first 4 years after seroconversion (RH 0.42, 95% CI 0.23,0.76), a 19% lower risk during the subsequent 4 years (RH 0.81, 95% Cl 0.59, 1.12), and no significant protection thereafter. Conclusion: The protection against AIDS provided by CCR5-Delta32 is continuous during the course of infection. In contrast, the protection provided by CCR2-641 is greatest early in the course of infection. (C) 2003 Lippincott Williams Wilkins. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Rockville, MD 20852 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. Ioannina Biomed Res Inst, GR-45110 Ioannina, Greece. San Francisco Dept Publ Hlth, HIV Res Stn, San Francisco, CA 94102 USA. Municipal Hlth Serv Amsterdam, Dept Publ Hlth & Environm, Amsterdam, Netherlands. Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Dept Med, Los Angeles, CA 90095 USA. Hop Bicetre, INSERM, U292, Serv Epidemiol, F-94276 Le Kremlin Bicetre, France. Walter Reed Army Med Ctr, Div Retrovirol, Rockville, MD 20850 USA. CHU Vaudois, Lab AIDS Immunopathogenesis, CH-1011 Lausanne, Switzerland. Univ Amsterdam, Acad Med Ctr, Sanquin Res CLB & Lanssteiner Lab, Dept Clin Viroimmunol, NL-1105 AZ Amsterdam, Netherlands. Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Berkeley, CA 94704 USA. Hop La Pitie Salpetriere, Lab Cent Immunol Cellulaire & Tissulaire, F-75013 Paris, France. CNRS, UMR 7627, F-75013 Paris, France. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY 10029 USA. RP Rosenberg, PS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, DHHS,NIH, 6120 Execut Blvd,Room 7006, Rockville, MD 20852 USA. RI Ioannidis, John/G-9836-2011; Pantaleo, Giuseppe/K-6163-2016 FU NIAID NIH HHS [5T32 AI 07001] NR 38 TC 78 Z9 86 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD FEB 14 PY 2003 VL 17 IS 3 BP 377 EP 387 DI 10.1097/01.aids.0000050783.28043.3e PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 653KR UT WOS:000181434800012 PM 12556692 ER PT J AU Goedert, JJ Charurat, M Blattner, WA Hershow, RC Pitt, J Diaz, C Mofenson, LM Green, K Minkoff, H Paul, ME Thomas, DL Whitby, D AF Goedert, JJ Charurat, M Blattner, WA Hershow, RC Pitt, J Diaz, C Mofenson, LM Green, K Minkoff, H Paul, ME Thomas, DL Whitby, D CA Women Infants Transmission Study TI Risk factors for Kaposi's sarcoma-associated herpesvirus infection among HIV-1-infected pregnant women in the USA SO AIDS LA English DT Article DE herpesvirus; Kaposi's sarcoma; hepatitis; drug users; seroprevalence; heterosexual transmission; risk factors ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN-HERPESVIRUS-8 INFECTION; SEXUAL TRANSMISSION; HOMOSEXUAL MEN; PERINATAL TRANSMISSION; DNA-SEQUENCES; ANTIBODIES; AIDS; PERFORMANCE; TRANSFUSION AB Objectives: We sought to identify risk factors for infection with the Kaposi's Sarcoma-associated herpesvirus (KSHV) among pregnant women and to examine a reported association of KSHV with injecting drug use (IDU) and hepatitis C virus (HCV) infection. Design: Cross-sectional evaluation of questionnaire data and KSHV and HCV seroprevalence in the Women and Infants Transmission Study. Methods: In sera collected from HIV-1-infected pregnant women (n = 887) and, at age 12 months, their offspring (n = 900) at six sites in the USA and Puerto Rico, KSHV and HCV antibodies were detected with sensitive and specific enzyme immunoassays. Risk of KSHV was estimated by the unadjusted and adjusted odds ratio (ORadj) and 95% confidence interval (CI). The geographic referent sites were Chicago and Boston. Results: Forty-seven (5.3%) of the women and three (0.3%) of the infants were KSHV seropositive. In univariate and multivariate analyses, KSHV in the women was associated with enrollment in Puerto Rico, Houston or Brooklyn (ORadj, 4.3; 95% Cl, 1.8-10.4) or Manhattan (ORadj, 9.8; 95% Cl, 3.7-25.6); non-completion of high school (ORadj, 1.8; 95% Cl, 0.9-3.4); the number of sexually transmitted diseases (ORadj, 1.4; 95% Cl, 1.0-1.9 per disease); and especially with IDU and HCV infection (ORadj, 3.5; 95% Cl, 1.5-7.9). Conclusions: Transmission of KSHV by blood inoculation may be highly inefficient, but our data support the hypothesis that it does occur. Large formal studies to evaluate whether KSHV transmission occurs via transfusion are needed to inform decisions regarding screening volunteer blood donors to protect the blood supply. (C) 2003 Lippincott Williams Wilkins. C1 NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Univ Illinois, Coll Med, Chicago, IL USA. Sch Publ Hlth, Chicago, IL USA. Columbia Univ Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA. Univ Puerto Rico, San Juan, PR 00936 USA. NICHHD, Pediat Adolescent & Mat AIDS Branch, NIH, Rockville, MD USA. Univ Massachusetts, Sch Med, Worcester, MA USA. SUNY Brooklyn, Dept Obstet & Gynecol, Brooklyn, NY USA. Baylor Coll Med, Houston, TX 77030 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. NCI, AIDS Vaccine Program, Viral Epidemiol Sect, Frederick, MD 21701 USA. NCI, Frederick, MD USA. RP Goedert, JJ (reprint author), 6120 Execut Blvd,Suite 8012, Rockville, MD 20892 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 37 TC 29 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD FEB 14 PY 2003 VL 17 IS 3 BP 425 EP 433 DI 10.1097/01.aids.0000042958.95433.88 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 653KR UT WOS:000181434800017 PM 12556697 ER PT J AU Freitas, F Keim, CN Kachar, B Farina, M Lins, U AF Freitas, F Keim, CN Kachar, B Farina, M Lins, U TI Envelope ultrastructure of uncultured naturally occurring magnetotactic cocci SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE cell surface ultrastructure; freeze-etching; magnetotactic bacterium; S-layer; capsule ID S-LAYER; MINERAL PRECIPITATION; MICROBIAL BIOFILMS; BACTERIA; MAGNETOSOMES; SPIRILLUM; CANADA; RIVER AB Magnetotactic bacteria are microorganisms that respond to magnetic fields. We studied the surface ultrastructure of uncultured magnetotactic cocci collected from a marine environment by transmission electron microscopy using freeze-fracture and freeze-etching. All bacteria revealed a Gram-negative cell wall. Many bacteria possessed extensive capsular material and a S-layer formed by particles arranged with hexagonal symmetry. No indication of a metal precipitation on the surface of these microorganisms was observed. Numerous membrane vesicles were observed on the surface of the bacteria. Flagella were organized in bundles originated in a depression on the surface of the cells. Occasionally, a close association of the flagella with the magnetosomes that remained attached to the replica was observed. Capsules and S-layers are common structures in magnetotactic cocci from natural sediments and may be involved in inhibition of metal precipitation on the cell surface or indirectly influence magnetotaxis. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 Univ Fed Rio de Janeiro, Inst Microbiol Prof Paulo Goes, Dept Microbiol, CCS, BR-21941590 Rio De Janeiro, RJ, Brazil. Univ Fed Rio de Janeiro, CCS, Inst Ciencias Biomed, BR-21941590 Rio De Janeiro, RJ, Brazil. Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RP Lins, U (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol Prof Paulo Goes, Dept Microbiol, CCS, Bloco 1, BR-21941590 Rio De Janeiro, RJ, Brazil. RI Keim, Carolina/E-3658-2013; Farina, Marcos/I-3744-2014; Lins, Ulysses/N-7282-2015 OI Keim, Carolina/0000-0002-3208-4128; Lins, Ulysses/0000-0002-1786-1144 NR 31 TC 11 Z9 14 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD FEB 14 PY 2003 VL 219 IS 1 BP 33 EP 38 DI 10.1016/S0378-1097(02)01187-4 PG 6 WC Microbiology SC Microbiology GA 651EE UT WOS:000181306900006 PM 12594020 ER PT J AU Luo, J Sun, YB Lin, H Qian, Y Li, Z Leonard, SS Huang, CS Shi, XL AF Luo, J Sun, YB Lin, H Qian, Y Li, Z Leonard, SS Huang, CS Shi, XL TI Activation of JNK by vanadate induces a Fas-associated death domain (FADD)-dependent death of cerebellar granule progenitors in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; PROGRAMMED CELL-DEATH; PHOSPHOTYROSINE PHOSPHATASE INHIBITORS; TERMINAL KINASE PATHWAY; NERVE GROWTH-FACTOR; JURKAT T-CELLS; INDUCED APOPTOSIS; PROTEIN-KINASE; TRANSCRIPTION FACTOR; CD95 FAS/APO-1 AB Apoptosis is a highly regulated process that plays a critical role in neuronal development as well as the homeostasis of the adult nervous system. Vanadate, an environmental toxicant, causes developmental defects in the central nervous system. Here, we demonstrated that vanadate induced apoptosis in cultured cerebellar granule progenitors (CGPs). Treatment of cultured CGPs with vanadate activated ERKs and JNKs but not p38 MAPK and also induced c-Jun phosphorylation. In addition, vanadate induced FasL production, Fas (CD95) aggregation, and its association with the Fas-associated death domain (FADD), as well as the activation of caspase-8. Furthermore, vanadate generated reactive oxygen species (ROS) in CGPs; however, ROS was not involved in vanadate-mediated MAPK activation. Vanadate-induced FasL expression was ROS-dependent but JNK-independent. In contrast, vanadate-elicited Fas aggregation and Fas-FADD association, as well as caspase-8 activation, were dependent on JNK activation but were minimally regulated by ROS generation. The hydrogen peroxide scavenger, catalase, blocked vanadate-induced FasL expression and partially mitigated vanadate-induced cell death. On the other hand, dominant negative FADD and caspase-8 inhibitor completely eliminated vanadate-induced apoptosis. Thus, JNK signaling plays a major role in vanadate-mediated activation of the Fas-FADD-caspase-8 pathway that accounts for vanadate-induced apoptosis of CGPs. C1 W Virginia Univ, Sch Med, Robert C Byrd Hlth Sci Ctr, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. NIOSH, Pathol & Physiol Res Branch, NIH, Morgantown, WV 26506 USA. NYU, Med Ctr, Nelson Inst Environm Med, Tuxedo Pk, NY 10987 USA. RP Luo, J (reprint author), W Virginia Univ, Sch Med, Robert C Byrd Hlth Sci Ctr, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. RI Shi, Xianglin/B-8588-2012; OI Huang, Chuanshu/0000-0003-4133-5096 FU NCI NIH HHS [CA90385]; NIAAA NIH HHS [AA12968] NR 93 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 4542 EP 4551 DI 10.1074/jbc.M208295200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900026 PM 12454017 ER PT J AU Andersen, JF Francischetti, IMB Valenzuela, JG Schuck, P Ribeiro, JMC AF Andersen, JF Francischetti, IMB Valenzuela, JG Schuck, P Ribeiro, JMC TI Inhibition of hemostasis by a high affinity biogenic amine-binding protein from the saliva of a blood-feeding insect SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RHODNIUS-PROLIXUS; NITRIC-OXIDE; PLATELET-AGGREGATION; BLOODSUCKING INSECT; HISTAMINE-BINDING; HEME PROTEIN; PURIFICATION; CLONING; NITROPHORIN-2; KINETICS AB The saliva of the blood-feeding insect Rhodnius prolixus contains numerous pharmacologically active substances. Included among these are a number of lipocalin proteins that bind various ligands important in hemostasis and inflammation. One such protein is a biogenic amine-binding protein (ABP) that binds serotonin, epinephrine, and norepinephrine. Based on amino acid alignments, it is most similar to the nitrophorin group of lipocalins found in the same insect species. Physiologically, this protein appears to act as both a vasodilator and platelet aggregation inhibitor. This protein inhibits smooth muscle contraction of the rat uterus in response to serotonin and of the rabbit aorta in response to norepinephrine. Platelet aggregation induced by a combination of low concentrations of ADP and either serotonin or epinephrine is inhibited because of the binding of serotonin and epinephrine. Potentiation of aggregation induced by low concentrations of collagen along with serotonin or epinephrine is also inhibited. Dissociation constants for biogenic amines were measured using isothermal titration calorimetry and the Hummel-Dreyer method of equilibrium gel filtration. In this manner, K-d values of 102, 24, and 345 nM were found for serotonin, norepinephrine, and epinephrine, respectively. Molecular modeling of AEP suggests that ligand binding is mediated by interaction with the side chains of aromatic amino acids and charged residues that line the binding pocket. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Off Director, Bethesda, MD 20892 USA. RP Andersen, JF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rm 126,Bldg 4,4 Ctr Dr, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966; Ribeiro, Jose/0000-0002-9107-0818 NR 30 TC 54 Z9 55 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 4611 EP 4617 DI 10.1074/jbc.M211438200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900035 PM 12464610 ER PT J AU Sijbrandi, R Urbanus, ML ten Hagen-Jongman, CM Bernstein, HD Oudega, B Otto, BR Luirink, J AF Sijbrandi, R Urbanus, ML ten Hagen-Jongman, CM Bernstein, HD Oudega, B Otto, BR Luirink, J TI Signal recognition particle (SRP)-mediated targeting and sec-dependent translocation of an extracellular Escherichia coli protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AUTOTRANSPORTER PROTEINS; MEMBRANE-PROTEINS; INNER MEMBRANE; SECRETION; PATHWAY; EXPORT; YIDC AB Hemoglobin protease (Hbp) is a hemoglobin-degrading protein that is secreted by a human pathogenic Escherichia coli strain via the autotransporter mechanism. Little is known about the earliest steps in autotransporter secretion, i.e. the targeting to and translocation across the inner membrane. Here, we present evidence that Hbp interacts with the signal recognition particle (SRP) and the Sec-translocon early during biogenesis. Furthermore, Hbp requires a functional SRP targeting pathway and Sec-translocon for optimal translocation across the inner membrane. SecB is not required for targeting of Hbp but can compensate to some extent for the lack of SRP. Hbp is synthesized with an unusually long signal peptide that is remarkably conserved among a subset of autotransporters. We propose that these autotransporters preferentially use the co-translational SRP/Sec route to avoid adverse effects of the exposure of their mature domains in the cytoplasm. C1 Vrije Univ Amsterdam, Dept Mol Microbiol, NL-1081 HV Amsterdam, Netherlands. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Luirink, J (reprint author), Vrije Univ Amsterdam, Dept Mol Microbiol, Boelelaan 1087, NL-1081 HV Amsterdam, Netherlands. NR 31 TC 85 Z9 90 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 4654 EP 4659 DI 10.1074/jbc.M211630200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900040 PM 12466262 ER PT J AU Kobrinsky, E Schwartz, E Abernethy, DR Soldatov, NM AF Kobrinsky, E Schwartz, E Abernethy, DR Soldatov, NM TI Voltage-gated mobility of the Ca2+ channel cytoplasmic tails and its regulatory role SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; SHAKER POTASSIUM CHANNEL; CALCIUM-CHANNEL; ALPHA(1C) SUBUNIT; FUNCTIONAL EXPRESSION; CARBOXYL-TERMINUS; LIVING CELLS; BETA-SUBUNIT; INACTIVATION; CALMODULIN AB Transient increase in intracellular free Ca2+ concentration generated by the voltage-gated Ca(v)1.2 channels acts as an important intracellular signal. By using fluorescence resonance energy transfer combined with patch clamp in living cells, we present evidence for voltage-gated mobility of the cytoplasmic tails of the Ca(v)1.2 channel and for its regulatory role in intracellular signaling. Anchoring of the C-terminal tail to the plasma membrane caused an inhibition of its state-dependent mobility, channel inactivation, and CREB-dependent transcription. Release of the tail restored these functions suggesting a direct role for voltage-gated mobility of the C-terminal tail in Ca2+ signaling. C1 NIA, NIH, Baltimore, MD 21224 USA. RP Soldatov, NM (reprint author), NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 43 TC 40 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 5021 EP 5028 DI 10.1074/jbc.M211254200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900087 PM 12473653 ER PT J AU Kim, SJ Beard, WA Harvey, J Shock, DD Knutson, JR Wilson, SH AF Kim, SJ Beard, WA Harvey, J Shock, DD Knutson, JR Wilson, SH TI Rapid segmental and subdomain motions of DNA polymerase beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TIME-RESOLVED FLUORESCENCE; TRYPTOPHAN RESIDUES; STOCHASTIC SIMULATION; CATALYTIC MECHANISM; CRYSTAL-STRUCTURES; RNA-POLYMERASE; DOMAIN; SITE; COMPLEXES; DYNAMICS AB DNA polymerase (pol) beta is a two-domain DNA repair enzyme that undergoes structural transitions upon binding substrates. Crystallographic structures indicate that these transitions include movement of the amino-terminal 8-kDa lyase domain relative to the 31-kDa polymerase domain. Additionally, a polymerase subdomain moves toward the nucleotide-binding pocket after nucleotide binding, resulting in critical contacts between alpha-helix N and the nascent base pair. Kinetic and structural characterization of pol beta has suggested that these conformational changes participate in stabilizing the ternary enzyme-substrate complex facilitating chemistry. To probe the microenvironment and dynamics of both the lyase domain and alpha-helix N in the polymerase domain, the single native tryptophan (Trp-325) of wild-type enzyme was replaced with alanine, and tryptophan was strategically substituted for residues in the lyase domain (F25W/W325A) or near the end of alpha-helix N (L287W/W325A). Influences of substrate on the fluorescence anisotropy decay of these single tryptophan forms of pol beta were determined. The results revealed that the segmental motion of alpha-helix N was rapid (similar to1 ns) and far more rapid than the step that limits chemistry. Binding of Mg2+ and/or gapped DNA did not cause a noticeable change in the rotational correlation time or angular amplitude of tryptophan in alpha-helix N. More important, binding of a correct nucleotide significantly limited the angular range of the nanosecond motion within alpha-helix N. In contrast, the segmental motion of the 8-kDa domain was "frozen" upon DNA binding alone, and this restriction did not increase further upon nucleotide binding. The dynamics of alpha-helix N are discussed from the perspective of the "open" to "closed" conformational change of pol beta deduced from crystallography, and the results are more generally discussed in the context of reaction cycle-regulated flexibility for proteins acting as molecular motors. C1 NHLBI, NIH, Biophys Chem Lab, Bethesda, MD 20892 USA. NIEHS, Struct Biol Lab, NIEHS, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NHLBI, NIH, Biophys Chem Lab, Bethesda, MD 20892 USA. NR 48 TC 38 Z9 38 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 5072 EP 5081 DI 10.1074/jbc.M208472200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900093 PM 12458221 ER PT J AU Kovanen, PE Rosenwald, A Fu, J Hurt, EM Lam, LT Giltnane, JM Wright, G Staudt, LM Leonard, WJ AF Kovanen, PE Rosenwald, A Fu, J Hurt, EM Lam, LT Giltnane, JM Wright, G Staudt, LM Leonard, WJ TI Analysis of gamma(c)-family cytokine target genes - Identification of dual-specificity phosphatase 5 (DUSP5) as a regulator of mitogen-activated protein kinase activity in interleukin-2 signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL PROLIFERATION; RECEPTOR-ALPHA GENE; IL-2 RECEPTOR; ERYTHROPOIETIN RECEPTORS; GROWTH-FACTOR; IN-VIVO; CHAIN; EXPRESSION; TRANSDUCTION; LYMPHOCYTES AB Interleukin (IL)-2, IL-4, IL-7, IL-99 IL-15, and IL-21 form a family of cytokines based on their sharing the common cytokine receptor gamma chain, gamma(c), which is mutated in X-linked severe combined immunodeficiency (SCID). As a step toward further elucidating the mechanism of action of these cytokines in T-cell biology, we compared the gene expression profiles of IL-2, IL-4, IL-7, and IL-15 in T cells using cDNA microarrays. IL-2, IL-7, and IL-15 each induced a highly similar set of genes, whereas IL-4 induced distinct genes correlating with differential STAT protein activation by this cytokine. One gene induced by IL-2, IL-7, and IL-15 but not IL-4 was dual-specificity phosphatase 5 (DUSP5). In IL-2-dependent CTLL-2 cells, we show that IL-2-induced ERK-1/2 activity was inhibited by wild type DUSP5 but markedly increased by an inactive form of DUSP5, suggesting a negative feedback role for DUSP5 in IL-2 signaling. Our findings provide insights into the shared versus distinctive actions by different members of the yc family of cytokines. Moreover, we have identified a DUSP5-dependent negative regulatory pathway for MAPK activity in T cells. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RI Giltnane, Jennifer/D-2584-2013 NR 54 TC 72 Z9 74 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 5205 EP 5213 DI 10.1074/jbc.M209015200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900109 PM 12435740 ER PT J AU Liu, SH Leppla, SH AF Liu, SH Leppla, SH TI Cell surface tumor endothelium marker 8 cytoplasmic tail-independent anthrax toxin binding, proteolytic processing, oligomer formation, and internalization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UROKINASE PLASMINOGEN-ACTIVATOR; PROTECTIVE ANTIGEN; LETHAL FACTOR; DIPHTHERIA-TOXIN; MAMMALIAN-CELLS; GLYCOSYL-PHOSPHATIDYLINOSITOL; EUKARYOTIC CELLS; MACROPHAGES; RECEPTOR; FURIN AB The interaction of anthrax toxin protective antigen (PA) and target cells was assessed, and the importance of the cytosolic domain of tumor endothelium marker 8 (TEM8) in its function as a cellular receptor for PA was evaluated. PA binding and proteolytic processing on the Chinese hamster ovary cell surface occurred rapidly, with both processes nearly reaching steady state in 5 min. Remarkably, the resulting PA63 fragment was present on the cell surface only as an oligomer, and furthermore, the oligomer was the only PA species internalized, suggesting that oligomerization of PA63 triggers receptor-mediated endocytosis. Following internalization, the PA63 oligomer was rapidly and irreversibly transformed to an SDS/heat-resistant form, in a process requiring an acidic compartment. This conformational change was functionally correlated with membrane insertion, channel formation, and translocation of lethal factor into the cytosol. To explore the role of the TEMS cytosolic tail, a series of truncated TEM8 mutants was transfected into a PA receptor-deficient Chinese hamster ovary cell line. Interestingly, all of the cytosolic tail truncated TEMS mutants functioned as PA receptors, as determined by PA binding, processing, oligomer formation, and translocation of an lethal factor fusion toxin into the cytosol. Moreover, cells transfected with a TEM8 construct truncated before the predicted transmembrane domain failed to bind PA, demonstrating that residues 321-343 are needed for cell surface anchoring. Further evidence that the cytosolic domain plays no essential role in anthrax toxin action was obtained by showing that TEMS anchored by a glycosylphosphatidylinositol tail also functioned as a PA receptor. C1 NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Microbial Pathogenesis Sect, NIH, Bldg 30, Rm 303,MSC 4350, Bethesda, MD 20892 USA. NR 41 TC 104 Z9 109 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 5227 EP 5234 DI 10.1074/jbc.M210321200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900111 PM 12468536 ER PT J AU Bienstock, RJ Skorvaga, M Mandavilli, BS Van Houten, B AF Bienstock, RJ Skorvaga, M Mandavilli, BS Van Houten, B TI Structural and functional characterization of the human DNA repair helicase XPD by comparative molecular modeling and site-directed mutagenesis of the bacterial repair protein UvrB SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; SECONDARY STRUCTURE PREDICTION; AMINO-ACID-SEQUENCE; HEPATITIS-C VIRUS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; XERODERMA-PIGMENTOSUM; THERMUS-THERMOPHILUS; RNA HELICASE; ACTIVE-SITE AB A molecular model for the human nucleotide excision repair protein, XPD, was developed based on the structural and functional relationship of the protein with a bacterial nucleotide excision repair (NER) protein, UvrB. Whereas XPD does not share significant sequence identity with UvrB, the proteins share seven highly conserved helicase motifs that define a common protein structural template. They also have similar functional roles in their ATPase activity and the ability to unwind DNA and verify damaged strands in the process of NER. The validity of using the crystal structure of UvrB as a template for the development of an XPD model was tested by mimicking human disease-causing mutations (XPD: R112H, D234N, R601L) in UvrB (E110R, D338N, R506A) and by mutating two highly conserved residues (XPD, His-237 and Asp-609; UvrB, H341A and D510A). The XPD structural model can be employed in understanding the molecular mechanism of XPD human disease causing mutations. The value of this XPD model demonstrates the generalized approach for the prediction of the structure of a mammalian protein based on the crystal structure of a structurally and functionally related bacterial protein sharing extremely low sequence identity (<15%). C1 NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Comp Sci Lab, NIH, Res Triangle Pk, NC 27709 USA. Slovak Acad Sci, Canc Res Inst, Dept Mol Genet, Bratislava 83391, Slovakia. RP Van Houten, B (reprint author), NIEHS, Genet Mol Lab, NIH, POB 12233,Mail Drop D3-01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Bienstock, Rachelle/0000-0001-5228-3610 NR 62 TC 25 Z9 25 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 5309 EP 5316 DI 10.1074/jbc.M210159200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900122 PM 12458209 ER PT J AU Zhou, JZ Fariss, RN Zelenka, PS AF Zhou, JZ Fariss, RN Zelenka, PS TI Synergy of epidermal growth factor and 12(S)-hydroxyeicosatetraenoate on protein kinase C activation in lens epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; FACTOR RECEPTORS; RAT LENS; IN-VIVO; PHOSPHORYLATION; ACID; TRANSLOCATION; 12(S)-HETE; PDK-1; PKC AB 12(S)-Hydroxyeicosatetraenoic acid (12(S)HETE) is a bioactive metabolite of arachidonic acid synthesized by 12-lipoxygenase. The 12-lipoxygenase blocker, baicalein, prevents epidermal growth factor (EGF)-induced activation of protein kinase C (PKC) alpha and beta in lens epithelial cells, whereas supplementation with 12(S)HETE reverses this effect, suggesting that EGF and 12(S)HETE may work together to activate PKC. This study investigates the mechanism of PKCbeta activation by EGF and 12(S)HETE. 12(S)HETE alone directed translocation of PKCbeta through the C1 rather than the C2 domain, without activating phosphoinositide 3-kinase (PI3K) or MAPK signaling or increasing intracellular calcium concentration. In the presence of baicalein, EGF triggered an asymmetric phosphorylation of the EGF receptor initiating signaling through PI3K and MAPK, but not PLCgamma. Together, 12(S)HETE and EGF synergistically increased phosphorylation of PKCbeta in the activation loop and C terminus as well as PKCbeta-specific activity. PI3K inhibitors blocked phosphorylation, but MEK1 inhibitors did not. Microvesicles containing phosphatidylinositol 3,4,5-trisphosphate mimicked the action of EGF on PKCbeta activity in the presence of 12(S)HETE. Kinase-inactive PKCbeta mutations in either activation loop or C terminus were effectively translocated by 12(S)HETE, as was PKCbeta in the presence of chelerythrine or Go-6983. These findings indicate that unphosphorylated PKCbeta is translocated to the membrane by 12(S)HETE and phosphorylated by EGF-dependent PI3K signaling, to generate catalytically competent PKCbeta. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Zelenka, PS (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Rm 214,6 Ctr Dr,MSC 2730, Bethesda, MD 20892 USA. NR 44 TC 20 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 5388 EP 5398 DI 10.1074/jbc.M209695200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900131 PM 12464613 ER PT J AU Bartolini, M Andrisano, V Wainer, IW AF Bartolini, M Andrisano, V Wainer, IW TI Development and characterization of an immobilized enzyme reactor based on glyceraldehyde-3-phosphate dehydrogenase for on-line enzymatic studies SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 26th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2002) CY JUN 02-07, 2002 CL MONTREAL, CANADA DE immobilized enzymes; kinetic studies; enzymes; glyceraldehyde-3-phosphate dehydrogenase AB The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been extensively studied as a target for new drugs to be used in the treatment of various parasitic diseases. The standard approach to the determination of GAPDH activity utilizes solubilized free enzyme and is limited by the enzyme's low stability. In the current study the stability of GAPDH was significantly increased through the covalent immobilization of the enzyme on a wide-pore silica support containing glutaraldehyde (Glut-P). The optimal conditions for the immobilization were: 100 mg Glut-P stationary phase, similar to 150 mug of enzyme dissolved in pyrophosphate buffer (15 mM, pH 8.5). The mixture was gently agitated for 6 h at 4 degreesC. Under these conditions 91.3% of protein was immobilized on 100 mg of Glut-P support with retention of 2.97% of the initial enzymatic activity. The activity of the immobilized GAPDH was stable for over 30 days. The GAPDH-Glut-P stationary phase was packed into a glass column to produce a GAPDH immobilized enzyme reactor (GAPDH-IMER). The activity and kinetic parameters of the GAPDH-IMER were investigated and the results demonstrated that the enzyme retained its activity and sensitivity to the competitive inhibitor agaric acid. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Bologna, Dept Pharmaceut Sci, Bologna, Italy. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI ANDRISANO, VINCENZA/0000-0003-4396-1904; Bartolini, Manuela/0000-0002-2890-3856 NR 16 TC 32 Z9 33 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD FEB 14 PY 2003 VL 987 IS 1-2 BP 331 EP 340 AR PII S0021-9673(02)01809-5 DI 10.1016/S0021-9673(02)01809-5 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 643YE UT WOS:000180890500037 PM 12613827 ER PT J AU Kibardin, AV Mirkina, II Baranova, EV Zakeyeva, IR Georgiev, GP Kiselev, SL AF Kibardin, AV Mirkina, II Baranova, EV Zakeyeva, IR Georgiev, GP Kiselev, SL TI The differentially spliced mouse tagL gene, homolog of tag7/PGRP gene family in mammals and Drosophila, can recognize gram-positive and gram-negative bacterial cell wall independently of T phage lysozyme homology domain SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE TagL; PGRP; innate immunity; pattern recognition receptor ID TOLL-LIKE RECEPTOR-2; LIPOTEICHOIC ACID; INNATE IMMUNITY; PEPTIDOGLYCAN; PROTEIN; COMPONENTS; LIPOPOLYSACCHARIDE; SHOCK; CD14; DEGRADATION AB Tag7/PGRP, a recently characterized antimicrobial protein, is conserved from insects to mammals. Recently its involvement in Toll signalling in Drosophila was demonstrated. A number of genes representing a new family homologous to PGRP were identified in Drosophila and human. Here we describe a splicing pattern of the tagL gene, mouse member of tag7/PGRP family. Some of the identified splice variants lacked characteristics for the family T phage lysozyme homology domain (also known as PGRP domain). Accordingly to the predicted transmembrane domains, mouse TagL may be secreted as inducible proteins or retained on intracellular membranes. All detected splice variant isoforms of TagL bound Gram-positive, Gram-negative bacteria and peptidoglycan. This binding did not depend on the presence of T phage lysozyme homology domain but was associated with the C-terminal portion of the polypeptides. Thus, this variety of isoforms of a single gene may play a role in circulating bacteria recognition in mammals. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Russian Acad Sci, Inst Gene Biol, Moscow 119334, Russia. NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Kiselev, SL (reprint author), Russian Acad Sci, Inst Gene Biol, Moscow 119334, Russia. OI kiselev, sergey/0000-0001-7921-6987 NR 40 TC 18 Z9 22 U1 3 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD FEB 14 PY 2003 VL 326 IS 2 BP 467 EP 474 DI 10.1016/S0022-2836(02)01401-8 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647AK UT WOS:000181068900010 PM 12559914 ER PT J AU Lawrence, DC Stover, CC Noznitsky, J Wu, ZR Summers, MF AF Lawrence, DC Stover, CC Noznitsky, J Wu, ZR Summers, MF TI Structure of the intact stem and bulge of HIV-1 psi-RNA stem-loop SL1 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE huamn immunodeficiency virus type-1 (HIV-1); ribonucleic acid (RNA); NMR structure; dimer initiation site (DIS) ID HUMAN-IMMUNODEFICIENCY-VIRUS; DIPOLAR COUPLING INTERACTIONS; DIMERIZATION INITIATION SITE; TYPE-1 PACKAGING SIGNAL; IRREGULAR NUCLEIC-ACIDS; MAJOR SPLICE DONOR; NUCLEOCAPSID PROTEIN; CRYSTAL-STRUCTURE; NMR-SPECTROSCOPY; CIS-ELEMENTS AB The Psi-RNA packaging signal of the human immunodeficiency virus type-1 (HIV-1) genome contains a 35 nucleotide stem-loop, termed SL1, which is important for efficient genome packaging during virus assembly and for reverse transcription during infectivity. The predicted secondary structure of SL1 consists of an upper stem with a GC-rich loop that facilitates dimerization, a lower stem, and an intervening bulge (G5, A24-G25-G26) that is both strictly conserved and essential for efficient packaging of the viral genome. The structure of the upper stem in both the kissing and duplex dimer forms have been determined recently. Here, we report the structure of an engineered form of SL1 (SL1(m)) that contains a GAGA tetra-loop substituted for the GC-rich loop. This construct does not aggregate and remains monomeric at concentrations up to 1 mM, enabling structural studies of the intact stems and bulge. The structure was refined using H-1 -C-13 residual dipolar couplings. The upper stem (C6-G12, C17-G23) is in close agreement with X-ray structures of kissing and duplex dimer forms of related oligoribonucleotides, and nucleotides C1-G4 and C27-G30 form the expected A-helical lower stem. Residues G5 and A24 of the predicted bulge form a G-A mismatch that stacks with the upper stem, and residues G25 and G26 stack between the G-A mismatch and the lower stem in a manner that produces a hole in the center of the bulge and a 25(+/-4)degrees bend between the upper and lower stems. SL1(m) exhibits relatively poor affinity for the HIV-1 nucleocapsid protein, suggesting that the bulge plays other roles in genome packaging. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland Baltimore Cty, Howard Hughes Med Inst, Baltimore, MD 21250 USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Summers, MF (reprint author), Univ Maryland Baltimore Cty, Howard Hughes Med Inst, 1000 Hilltop Circle, Baltimore, MD 21250 USA. FU NIGMS NIH HHS [GM42561] NR 85 TC 53 Z9 53 U1 2 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD FEB 14 PY 2003 VL 326 IS 2 BP 529 EP 542 DI 10.1016/S0022-2836(02)01305-0 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647AK UT WOS:000181068900016 PM 12559920 ER PT J AU Jamieson, TA Brizel, DM Killian, JK Oka, Y Jang, HS Fu, XL Clough, RW Vollmer, RT Anscher, MS Jirtle, RL AF Jamieson, TA Brizel, DM Killian, JK Oka, Y Jang, HS Fu, XL Clough, RW Vollmer, RT Anscher, MS Jirtle, RL TI M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis SO BMC CANCER LA English DT Article ID FACTOR-II RECEPTOR; SQUAMOUS-CELL CARCINOMA; II/MANNOSE 6-PHOSPHATE RECEPTOR; TUMOR-SUPPRESSOR GENE; HEPATOCELLULAR CARCINOMAS; CHROMOSOMAL ALTERATIONS; FIELD CANCERIZATION; GROWTH; EXPRESSION; IGF2R AB Background: The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis. Methods: M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months. Results: M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity. Conclusions: This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy. C1 Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. SE Georgia Reg Med Ctr, Radiat Oncol Ctr, Brunswick, GA USA. NIH, Pathol Lab, Bethesda, MD 20892 USA. Fukuoka Univ, Chikushi Hosp, Dept Gastroenterol, Fukuoka 81401, Japan. Uijongbo St Marys Hosp, Dept Radiat Oncol, Uijongbo, South Korea. Fudan Univ, Canc Hosp, Dept Radiat Oncol, Shanghai 200433, Peoples R China. Vet Affairs Med Ctr, Dept Pathol, Durham, NC USA. RP Jirtle, RL (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. EM tjamieson@yahoo.com; brizel@radonc.duke.edu; kkillian@nih.gov; weareduke@yahoo.co.jp; hsjang11@cmc.cuk.ac.kr; fuxl-c@online.sh.cn; clough@radonc.duke.edu; voll002@duke.edu; anscher@radonc.duke.edu; jirtle@radonc.duke.edu FU NCI NIH HHS [R01 CA025951, CA25951]; NIEHS NIH HHS [R01 ES008823, ES08823] NR 51 TC 35 Z9 36 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD FEB 13 PY 2003 VL 3 AR 4 DI 10.1186/1471-2407-3-4 PG 9 WC Oncology SC Oncology GA 659EE UT WOS:000181763900001 PM 12589712 ER PT J AU Daly, JW AF Daly, JW TI Ernest Guenther award in chemistry of natural products. Amphibian skin: A remarkable source of biologically active arthropod alkaloids SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID POISON FROGS DENDROBATIDAE; TANDEM MASS-SPECTROMETRY; SODIUM-CHANNEL; ACETYLCHOLINE-RECEPTOR; PUMILIOTOXIN ALKALOIDS; DIETARY ALKALOIDS; RAY-ANALYSIS; DECAHYDROQUINOLINES; QUINOLIZIDINES; PYRROLIZIDINES C1 NIDDKD, Bioorgan Chem Lab, Sect Pharmacodynam, NIH, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, Sect Pharmacodynam, NIH, Bethesda, MD 20892 USA. EM jdaly@nih.gov NR 56 TC 95 Z9 97 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD FEB 13 PY 2003 VL 46 IS 4 BP 445 EP 452 DI 10.1021/jm0204845 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 642ZE UT WOS:000180836600001 PM 12570366 ER PT J AU Pettit, GR Anderson, CR Herald, DL Jung, MK Lee, DJ Hamel, E Pettit, RK AF Pettit, GR Anderson, CR Herald, DL Jung, MK Lee, DJ Hamel, E Pettit, RK TI Antineoplastic agents. 487. Synthesis and biological evaluation of the antineoplastic agent 3,4-methylenedioxy-5,4 '-dimethoxy-3 '-amino-Z-stilbene and derived amino acid amides SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID COMBRETASTATIN A-4 PRODRUG; ANTIMITOTIC AGENT; ANALOGS; TUBULIN; GROWTH; CANCER; COLCHICINE; DESIGN AB An efficient synthesis of 3,4-methylenedioxy-5,4'-dimethoxy-3'-amino-Z-stilbene (1c) and hydrochloride (1d) is reported. The nitrostilbene intermediate 6a was obtained via a Wittig reaction using phosphonium salt 4 and 3-nitro-4-methoxybenzaldehyde 5. A one-step reduction using zinc in acetic acid produced the synthetic objective amine 1c. The coupling of this amine with various Fmoc amino acids, followed by cleavage of the a-amine protecting group, resulted in a series of new cancer cell growth inhibitory amides. Amine 1c, hydrochloride 1d, glycine amide 3b, and tyrosine amide 3f had the highest level (GI(50) = 10(-2)-10(-3) mug/mL) of activity against a panel of six human and one animal (P388) cancer cell lines. Amine 1c and its hydrochloride 1d, potently inhibited tubulin polymerization by binding at the colchicine site, while the amides had little activity against purified tubulin. Nevertheless, most of the amides caused a marked increase in the mitotic index of treated cells, indicating that tubulin was their intracellular target. C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, NIH, Frederick, MD 21702 USA. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Screening Technol Branch,NIH, Frederick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, POB 872404, Tempe, AZ 85287 USA. EM bpettit@asu.edu FU NCI NIH HHS [N01-CO-1240, CA44344-05-12] NR 26 TC 39 Z9 39 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD FEB 13 PY 2003 VL 46 IS 4 BP 525 EP 531 DI 10.1021/jm020204l PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 642ZE UT WOS:000180836600009 PM 12570374 ER PT J AU Katoch-Rouse, R Pavlova, OA Caulder, T Hoffman, AF Mukhin, AG Horti, AG AF Katoch-Rouse, R Pavlova, OA Caulder, T Hoffman, AF Mukhin, AG Horti, AG TI Synthesis, structure-activity relationship, and evaluation of SR141716 analogues: Development of central cannabinoid receptor ligands with lower lipophilicity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID F-18 SR144385; CB1 RECEPTOR; RADIOLIGAND; ANTAGONISTS AB Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented. C1 NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Cellular Neurophysiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Horti, AG (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. EM ahorti@intra.nida.nih.gov RI Hoffman, Alexander/H-3035-2012 OI Hoffman, Alexander/0000-0002-2676-0628 NR 17 TC 89 Z9 89 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD FEB 13 PY 2003 VL 46 IS 4 BP 642 EP 645 DI 10.1021/jm020157x PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 642ZE UT WOS:000180836600021 PM 12570386 ER PT J AU Watford, WT O'Shea, JJ AF Watford, WT O'Shea, JJ TI Autoimmunity - A case of mistaken identity SO NATURE LA English DT Editorial Material C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Watford, WT (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr MSC-1820, Bethesda, MD 20892 USA. NR 10 TC 10 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 13 PY 2003 VL 421 IS 6924 BP 706 EP 708 DI 10.1038/421706a PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 644UP UT WOS:000180938000027 PM 12610607 ER PT J AU Hill, JM Zalos, G Halcox, JPJ Schenke, WH Waclawiw, MA Quyyumi, AA Finkel, T AF Hill, JM Zalos, G Halcox, JPJ Schenke, WH Waclawiw, MA Quyyumi, AA Finkel, T TI Circulating endothelial progenitor cells, vascular function, and cardiovascular risk SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY-ARTERY DISEASE; POSTNATAL NEOVASCULARIZATION; ATHEROSCLEROSIS; DYSFUNCTION; INCREASE; THERAPY; BLOOD; VIVO AB BACKGROUND: Cardiovascular risk factors contribute to atherogenesis by inducing endothelial-cell injury and dysfunction. We hypothesized that endothelial progenitor cells derived from bone marrow have a role in ongoing endothelial repair and that impaired mobilization or depletion of these cells contributes to endothelial dysfunction and cardiovascular disease progression. METHODS: We measured the number of colony-forming units of endothelial progenitor cells in peripheral-blood samples from 45 men (mean [+/-SE] age, 50+/-2 years). The subjects had various degrees of cardiovascular risk but no history of cardiovascular disease. Endothelium-dependent and endothelium-independent function was assessed by high-resolution ultrasonography of the brachial artery. RESULTS: We observed a strong correlation between the number of circulating endothelial progenitor cells and the subjects' combined Framingham risk factor score (r=-0.47, P=0.001). Measurement of flow-mediated brachial-artery reactivity also revealed a significant relation between endothelial function and the number of progenitor cells (r=0.59, P<0.001). Indeed, the levels of circulating endothelial progenitor cells were a better predictor of vascular reactivity than was the presence or absence of conventional risk factors. In addition, endothelial progenitor cells from subjects at high risk for cardiovascular events had higher rates of in vitro senescence than cells from subjects at low risk. CONCLUSIONS: In healthy men, levels of endothelial progenitor cells may be a surrogate biologic marker for vascular function and cumulative cardiovascular risk. These findings suggest that endothelial injury in the absence of sufficient circulating progenitor cells may affect the progression of cardiovascular disease. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. RP Finkel, T (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10-6N-240,10 Ctr Dr, Bethesda, MD 20892 USA. OI Halcox, Julian/0000-0001-6926-2947 NR 38 TC 2276 Z9 2547 U1 17 U2 92 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 13 PY 2003 VL 348 IS 7 BP 593 EP 600 DI 10.1056/NEJMoa022287 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 644HY UT WOS:000180912900004 PM 12584367 ER PT J AU Fisher, B Anderson, S Bryant, J AF Fisher, B Anderson, S Bryant, J TI Breast-conserving surgery for breast cancer - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID RANDOMIZED CLINICAL-TRIAL C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 13 PY 2003 VL 348 IS 7 BP 659 EP 660 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 644HY UT WOS:000180912900018 ER PT J AU Levy, D Kenchaiah, S Vasan, RS AF Levy, D Kenchaiah, S Vasan, RS TI Heart failure - Incidence and survival - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 13 PY 2003 VL 348 IS 7 BP 660 EP 660 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 644HY UT WOS:000180912900020 ER PT J AU Le, SY Chen, JH Konings, D Maizel, JV AF Le, SY Chen, JH Konings, D Maizel, JV TI Discovering well-ordered folding patterns in nucleotide sequences SO BIOINFORMATICS LA English DT Article ID RNA SECONDARY STRUCTURE; REV-RESPONSE ELEMENT; TARGET SEQUENCE; THERMODYNAMICS; CONSERVATION; INFORMATION; EXPRESSION; PREDICTION; REGIONS AB Motivation: Growing evidence demonstrates that local well-ordered structures are closely correlated with cis-acting elements in the post-transcriptional regulation of gene expression. The prediction of a well-ordered folding sequence (WFS) in genomic sequences is very helpful in the determination of local RNA elements with structure-dependent functions in mRNAs. Results: In this study, the quality of local WFS is assessed by the energy difference (E-diff) between the free energies of the global minimal structure folded in the segment and its corresponding optimal restrained structure (ORS). The ORS is an optimal structure under the condition in which none of the base-pairs in the global minimal structure is allowed to form. Those WFSs in HIV-1 mRNA, various ferritin mRNAs and genomic sequences containing let-7 RNA gene were searched by a novel method, ed_scan. Our results indicate that the detected WFSs are coincident with known Rev response element in HIV-1 mRNA, iron-responsive elements in ferritin mRNAs and small let-7 RNAS in Caenorhabditis elegans, Caenorhabditis briggsae and Drosophila melanogaster genomic sequences. Statistical significance of the WFS is addressed by a quantitative measure Zscr(e) that is a z-score of Ediff and extensive random simulations. We suggest that WFSs with high statistical significance have structural roles involving their sequence information. C1 NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NCI, Adv Biomed Comp Ctr, SAIC, FCRDC, Frederick, MD 21702 USA. RP Le, SY (reprint author), NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Bldg 469,Room 151, Frederick, MD 21702 USA. NR 26 TC 21 Z9 22 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD FEB 12 PY 2003 VL 19 IS 3 BP 354 EP 361 DI 10.1093/bioinformatics/btf826 PG 8 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 651CP UT WOS:000181303000005 PM 12584120 ER PT J AU Clore, GM Kuszewski, J AF Clore, GM Kuszewski, J TI Improving the accuracy of NMR structures of RNA by means of conformational database potentials of mean force as assessed by complete dipolar coupling cross-validation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MACROMOLECULAR STRUCTURE DETERMINATION; THEOPHYLLINE-BINDING RNA; NUCLEIC-ACID DATABASE; B-DNA DODECAMER; FREE R-VALUE; STRUCTURE REFINEMENT; MOLECULAR-DYNAMICS; RIBOSOMAL-SUBUNIT; RESOLUTION; MAGNITUDE AB The description of the nonbonded contact terms used in simulated annealing refinement can have a major impact on nucleic acid structures generated from NMR data. Using complete dipolar coupling cross-validation, we demonstrate that substantial improvements in coordinate accuracy of NMR structures of RNA can be obtained by making use of two conformational database potentials of mean force: a nucleic acid torsion angle database potential consisting of various multidimensional torsion angle correlations; and an RNA specific base-base positioning potential that provides a simple geometric, statistically based, description of sequential and nonsequential base-base interactions. The former is based on 416 nucleic acid crystal structures solved at a resolution of less than or equal to2 Angstrom and an R-factor less than or equal to25%; the latter is based on 131 RNA crystal structures solved at a resolution of less than or equal to3 Angstrom and an R-factor of less than or equal to25%, and includes both the large and small subunits of the ribosome. The application of these two database potentials is illustrated for the structure refinement of an RNA aptamer/theophylline complex for which extensive NOE and residual dipolar coupling data have been measured in solution. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Div Computat Biosci, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 35 TC 53 Z9 54 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD FEB 12 PY 2003 VL 125 IS 6 BP 1518 EP 1525 DI 10.1021/ja028383j PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 643BN UT WOS:000180842200031 PM 12568611 ER PT J AU Boukari, H Nossal, R Sackett, DL AF Boukari, H Nossal, R Sackett, DL TI Stability of drug-induced tubulin rings by fluorescence correlation spectroscopy SO BIOCHEMISTRY LA English DT Article ID HYDRODYNAMIC PROPERTIES; MICROTUBULE DYNAMICS; VINCA DOMAIN; DOLASTATIN-10; BINDING; CRYPTOPHYCIN-1; POLYMERIZATION; MACROMOLECULES; CYTOTOXICITY; AGGREGATION AB Fluorescence correlation spectroscopy (FCS) was applied to investigate the stability of tubulin rings that result from the interaction of alphabeta-tubulin dimers with three vinca domain-binding peptides-cryptophycin 1, hemiasterlin, and dolastatin 10. These peptides inhibit tubulin polymerization into microtubules and, instead, induce the formation of single-walled tubulin rings of 23.8 nm mean diameter for cryptophycin and 44.6 nm mean diameter for hemiasterlin and dolastatin, as revealed by electron microscopy on micromolar drug-tubulin samples. However, the hydrodynamic diameter and the apparent number of fluorescent particles, determined from analysis of FCS measurements obtained from nanomolar drug-tubulin samples, indicate variation in the stability of the rings depending on the drug and the tubulin concentration. Cryptophycin-tubulin rings appear to be the most stable even with tubulin concentration as low as 1 nM, whereas hemiasterlin-tubulin rings are the least, depolymerizing even at relatively high concentrations (100 nM). In contrast, the dolastatin-tubulin rings demonstrate an intermediate level of stability, depolymerizing significantly only at tubulin concentrations below 10 nM. We also compare the stability results with those of cytotoxicity measurements taken on several cell lines and note a rough correlation between the cytotoxicity of the drugs in cell cultures and the stability of the corresponding drug-induced rings. C1 NICHHD, LIMB, NIH, Bethesda, MD 20892 USA. RP Boukari, H (reprint author), NICHHD, LIMB, NIH, Bldg 9,Room 1E116,9 Mem Dr, Bethesda, MD 20892 USA. NR 37 TC 25 Z9 26 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 11 PY 2003 VL 42 IS 5 BP 1292 EP 1300 DI 10.1021/bi026751q PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 643DQ UT WOS:000180847000013 PM 12564932 ER PT J AU McDermott, MM Guralnik, JM Greenland, P Pearce, WH Criqui, MH Liu, K Taylor, L Chan, CL Sharma, L Schneider, JR Ridker, PM Green, D Quann, M AF McDermott, MM Guralnik, JM Greenland, P Pearce, WH Criqui, MH Liu, K Taylor, L Chan, CL Sharma, L Schneider, JR Ridker, PM Green, D Quann, M TI Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease SO CIRCULATION LA English DT Article DE statins; peripheral vascular disease; inflammation ID COA-REDUCTASE INHIBITOR; HYPERCHOLESTEROLEMIC PATIENTS; SUBSEQUENT DISABILITY; CHOLESTEROL; SIMVASTATIN; SERUM; CLASSIFICATION; INTERLEUKIN-6; ASSOCIATION; EXPRESSION AB Background-We determined whether statin use (versus nonuse) is associated with superior lower-extremity functioning independently of cholesterol levels and other confounders in patients with and without peripheral arterial disease. Methods and Results-Participants included 392 men and women with an ankle brachial index (ABI) <0.90 and 249 with ABI 0.90 to 1.50. Functional outcomes included 6-minute walk distance and 4-meter walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age, sex, ABI, comorbidities, education level, medical insurance status, cholesterol, and other confounders, participants taking statins had better 6-minute walk performance (1276 versus 1218 feet, P=0.045), faster walking velocity (0.93 versus 0.89 m/s, P=0.006), and a higher summary performance score (10.2 versus 9.4, P<0.001) than participants not taking statins. Positive associations were attenuated slightly after additional adjustment for C-reactive protein level but remained statistically significant for walking velocity and the summary performance score. We did not find significant associations between lower-extremity functioning and aspirin, ACE inhibitors, vasodilators, or beta-blockers. Conclusions-Statin use is associated with superior leg functioning compared with no statin use, independent of cholesterol levels and other potential confounders. These data suggest that non-cholesterol-lowering properties of statins may favorably influence functioning in persons with and without peripheral arterial disease. C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Oregon Hlth Sci Med Ctr, Portland, OR USA. Northwestern Univ, Evanston Hosp, Evanston, IL 60201 USA. Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. RP McDermott, MM (reprint author), 675 N St Clair,Suite 18-200, Chicago, IL 60611 USA. FU NCRR NIH HHS [RR-00048]; NHLBI NIH HHS [R01-HL58099, R01-HL64739] NR 27 TC 145 Z9 150 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 11 PY 2003 VL 107 IS 5 BP 757 EP 761 DI 10.1161/01.CIR.0000050380.64025.07 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 648LY UT WOS:000181153900022 PM 12578881 ER PT J AU Shevell, M Ashwal, S Donley, D Flint, J Gingold, M Hirtz, D Majnemer, A Noetzel, M Sheth, RD AF Shevell, M Ashwal, S Donley, D Flint, J Gingold, M Hirtz, D Majnemer, A Noetzel, M Sheth, RD TI Practice parameter: Evaluation of the child with global developmental delay - Report of the quality standards subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society SO NEUROLOGY LA English DT Review ID IDIOPATHIC MENTAL-RETARDATION; FRAGILE-X-SYNDROME; CRYPTIC TELOMERIC REARRANGEMENTS; LEVEL LEAD-EXPOSURE; CEREBRAL-PALSY; RETT-SYNDROME; CONGENITAL HYPOTHYROIDISM; SUBTELOMERIC REARRANGEMENTS; CHROMOSOMAL REARRANGEMENTS; COGNITIVE-DEVELOPMENT AB Objective: To make evidence-based recommendations concerning the evaluation of the child with a nonprogressive global developmental delay. Methods: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. Results: Global developmental delay is common and affects 1% to 3% of children. Given yields of about 1%, routine metabolic screening is not indicated in the initial evaluation of a child with global developmental delay. Because of the higher yield (3.5% to 10%), even in the absence of dysmorphic features or features suggestive of a specific syndrome, routine cytogenetic studies and molecular testing for the fragile X mutation are recommended. The diagnosis of Rett syndrome should be considered in girls with unexplained moderate to severe developmental delay. Additional genetic studies (e.g., subtelomeric chromosomal rearrangements) may also be considered in selected children. Evaluation of serum lead levels should be restricted to those children with identifiable risk factors for excessive lead exposure. Thyroid studies need not be undertaken (unless clinically indicated) if the child underwent newborn screening. An EEG is not recommended as part of the initial evaluation unless there are historical features suggestive of epilepsy or a specific epileptic syndrome. Routine neuroimaging, with MRI preferred to CT, is recommended particularly if abnormalities are found on physical examination. Because of the increased incidence of visual and auditory impairments, children with global developmental delay may undergo appropriate visual and audiometric assessment at the time of diagnosis. Conclusions: A specific etiology can be determined in the majority of children with global developmental delay. Certain routine screening tests are indicated and depending on history and examination findings, additional specific testing may be performed. C1 Loma Linda Univ, Sch Med, Dept Pediat, Loma Linda, CA 92350 USA. McGill Univ, Dept Neurol Neurosurg, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. McGill Univ, Sch Phys & Occupat Therapy, Montreal, PQ H3A 2T5, Canada. Montreal Childrens Hosp, Div Pediat Neurol, Montreal, PQ H3H 1P3, Canada. Univ Oxford, Div Psychiat, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. NINDS, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA. Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. RP Ashwal, S (reprint author), Loma Linda Univ, Sch Med, Dept Pediat, 11175 Coleman Pavil, Loma Linda, CA 92350 USA. NR 122 TC 303 Z9 328 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 11 PY 2003 VL 60 IS 3 BP 367 EP 380 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 646BG UT WOS:000181014500004 PM 12578916 ER PT J AU Lipton, RB Scher, AI Steiner, TJ Bigal, ME Kolodner, K Liberman, JN Stewart, WF AF Lipton, RB Scher, AI Steiner, TJ Bigal, ME Kolodner, K Liberman, JN Stewart, WF TI Patterns of health care utilization for migraine in England and in the United States SO NEUROLOGY LA English DT Article ID DISABILITY ASSESSMENT; AMERICAN MIGRAINE; HEADACHE SUFFERERS; MEDICATION USE; YOUNG-ADULTS; DIAGNOSIS; PREVALENCE; RELIABILITY; COMORBIDITY; WORKPLACE AB Objective: To assess patterns of medical consultation, diagnosis, and medication use in representative samples of adults with migraine in England and the United States. Methods: Validated computer-assisted telephone interviews were conducted in the United Kingdom (n = 4,007) and the United States (n = 4,376). Individuals who reported six or more headaches per year meeting the criteria for migraine were interviewed. Results: Patients with migraine in the United Kingdom were more likely to have consulted a doctor for headache at least once in their lifetime (86% vs 69%, p < 0.0001), but also were more likely to have lapsed from medical care (37% vs 21%, p < 0.001). In the United States, patients with migraine who had consulted made more office visits for headache and were more likely to see a specialist. In the United States, but not in the United Kingdom, women with migraine were more likely than men to consult doctors for headache. Patients with migraine in the United Kingdom were more likely to receive a medical diagnosis of migraine (UK 67%, US 56%; p < 0.05). Patterns of medication use were similar in both countries, with most people treating with over-the-counter (OTC) medications. Substantial disability occurred in a high proportion of those who never consulted (UK 60%, US 68%), never received a correct medical diagnosis (UK 64%, US 77%), and treated only with OTC medication (UK 72%, US 70%). Conclusion: Medically unrecognized migraine remains an important health problem both in the United States and the United Kingdom. Furthermore, there may be barriers to consultation for men in the United States that do not operate in the United Kingdom. C1 Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. New England Ctr Headache, Stamford, CT USA. NINDS, NIH, Neuroepidemiol Branch, Bethesda, MD USA. Univ London Imperial Coll Sci Technol & Med, Div Neurosci, London, England. Advance PCS, Hunt Valley, MD USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. RP Lipton, RB (reprint author), Albert Einstein Coll Med, Dept Neurol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. NR 36 TC 93 Z9 93 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 11 PY 2003 VL 60 IS 3 BP 441 EP 448 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 646BG UT WOS:000181014500015 PM 12578925 ER PT J AU Ananthan, S Kezar, HS Saini, SK Khare, NK Davis, P Dersch, CM Porreca, F Rothman, RB AF Ananthan, S Kezar, HS Saini, SK Khare, NK Davis, P Dersch, CM Porreca, F Rothman, RB TI Synthesis, opioid receptor binding, and functional activity of 5 '-substituted 17-cyclopropylmethylpyrido[2 ',3 ': 6,7]morphinans SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID MESSAGE ADDRESS CONCEPT; ANTAGONIST ACTIVITY; HIGHLY POTENT; NALTRINDOLE; DERIVATIVES; GUANIDINES; ANALOGS; DESIGN; MICE AB A series of naltrexone-derived pyridomorphinans possessing various substituents at the 5'-position on the pyridine ring were synthesized and evaluated for opioid receptor binding in rodent brain membranes and functional activity in smooth muscle preparations. While the introduction of aromatic I-pyrrolyl group (6h) improved the 8 affinity and 6 antagonist potency of the parent compound (3), the introduction of guanidine group (6i) transformed it to a K selective ligand in opioid receptor binding and [S-35]GTP-gamma-S functional assays. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. Univ Arizona, Hlth Sci Ctr, Dept Pharmacol, Tucson, AZ 85724 USA. NIDA, Clin Psychopharmacol Sect, IRP, Baltimore, MD 21224 USA. RP Ananthan, S (reprint author), So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. FU NIDA NIH HHS [DA08883] NR 25 TC 10 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD FEB 10 PY 2003 VL 13 IS 3 BP 529 EP 532 AR PII S0960-894X(02)00934-4 DI 10.1016/S0960-894X(02)00934-4 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 645BV UT WOS:000180957100046 PM 12565965 ER PT J AU Hsin, LW Prisinzano, T Wilkerson, CR Dersch, CM Horel, R Jacobson, AE Rothman, RB Rice, KC AF Hsin, LW Prisinzano, T Wilkerson, CR Dersch, CM Horel, R Jacobson, AE Rothman, RB Rice, KC TI Synthesis and dopamine transporter affinity of chiral 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(2-hydroxypropyl)piperazines as potential cocaine abuse therapeutic agents SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID 1-<2-ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES GBR-12935; RHESUS-MONKEYS; 1-<2-(DIPHENYLMETHOXY)ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES; INHIBITORS; ANALOGS AB A series of optically pure phenyl-and non-phenyl-substituted 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(2-hydroxypropyl)piperazines was synthesized and their binding affinity for dopamine transporter (DAT) was investigated. The analogues with a hydroxyl group in the S configuration were more selective for the DAT over the serotonin transporter (SERT) than the corresponding R enantiomers. Compound (+)-11 showed high affinity and selectivity for DAT over the SERT and, therefore, is a potential candidate for the development of a long-acting cocaine abuse therapeutic agent. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Clin Psychopharmacol Sect, Addict Res Ctr, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RI Prisinzano, Thomas/B-7877-2010; OI HSIN, LING-WEI/0000-0001-5018-4491 NR 16 TC 14 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD FEB 10 PY 2003 VL 13 IS 3 BP 553 EP 556 AR PII S0960-894X(02)00940-X DI 10.1016/S0960-894X(02)00940-X PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 645BV UT WOS:000180957100051 PM 12565970 ER PT J AU Steeg, PS Palmieri, D Ouatas, T Salerno, M AF Steeg, PS Palmieri, D Ouatas, T Salerno, M TI Histidine kinases and histidine phosphorylated proteins in mammalian cell biology, signal transduction and cancer SO CANCER LETTERS LA English DT Review DE Map kinase; RAS; histidine; cancer; signal transduction; Nm23; histone; G protein; phosphorylation ID NUCLEOSIDE DIPHOSPHATE KINASE; PHOSPHOLIPASE-D ACTIVITY; BREAST-CARCINOMA CELLS; GTP-BINDING PROTEINS; ENZYMATIC-ACTIVITY; BETA-SUBUNIT; HISTONE H4; ANNEXIN-I; PHOSPHOHISTIDINE INTERMEDIATE; ADENOCARCINOMA CELLS AB Intensive investigation of protein tyrosine, serine and threonine phosphorylation has lead to advances in signal transduction research and cancer treatment. This feature summarizes research on mammalian proteins exhibiting histidine phosphorylation. Histidine kinases are well known in prokaryotic and lower eukaryotic systems where they form the 'two-component' signal transduction system. The relative invisibility of histidine phosphorylation in mammalian cells may result from technical obstacles such as its acid lability, which precludes detection in electrophoretic systems, amino acid sequencing, etc. Emerging data have identified mammalian histidine kinases for the kinase suppressor of ras, a scaffold molecule for the Map kinase pathway, as well as histone H4, aldolase C and the beta-subunit of heterotrimeric G proteins. Additional mammalian proteins of interest to signal transduction and cancer research exhibit histidine phosphorylation, including P-selectin, annexin I and the 20S proteasome. Other candidate histidine phosphorylated proteins are identified. These data suggest the existence of another series of phosphorylation patterns in signal transduction. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Womens Canc Sect, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Pathol Lab, Canc Res Ctr, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. RI Palmieri, Diane/B-4258-2015 NR 99 TC 61 Z9 71 U1 5 U2 12 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 10 PY 2003 VL 190 IS 1 BP 1 EP 12 DI 10.1016/S0304-3835(02)00499-8 PG 12 WC Oncology SC Oncology GA 643TT UT WOS:000180877100001 PM 12536071 ER PT J AU Zhang, YJ Chen, Y Ahsan, H Lunn, RM Lee, PH Chen, CJ Santella, RM AF Zhang, YJ Chen, Y Ahsan, H Lunn, RM Lee, PH Chen, CJ Santella, RM TI Inactivation of the DNA repair gene O-6-methylguanine-DNA methyltransferase by promoter hypermethylation and its relationship to aflatoxin B-1-DNA adducts and p53 mutation in hepatocellular carcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE epigenetic changes; hypermethylation; hepatocellular carcinoma; CpG island; O-6-methylguanine-DNA methyltransferase ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY; SMOKING-RELATED INCREASE; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; COLORECTAL TUMORIGENESIS; MGMT EXPRESSION; HUMAN COLON; HOT-SPOTS; METHYLATION; CANCER; LUNG AB O-6-methylguanine-DNA methyltransferase (MGMT) is a repair protein that specifically removes promutagenic alkyl groups from the O-6 position of guanine in DNA. MGMT is transcriptionally silenced by promoter hypermethylation in several human cancers. Methylation-specific PCR (MSP) was used to analyze the MGMT promoter methylation status of 83 hepatocellular carcinomas (HCC) and 2 HCC cell lines (HepG2 and Hep3B). Hypermethylation was detected in 32 of 83 (39%) HCC tissues, but it was not found in either HCC cell line. We also analyzed MGMT expression by immunohistochemical analysis of HCC tissue samples. The presence of aberrant hypermethylation was associated with loss of MGMT protein. The relationship between methylation status and risk factors and tumor markers including environmental exposure to aflatoxin B-1 (AFB(1)), measured as DNA adducts, and status of tumor suppressor gene p53 was also investigated. A statistically significant association was found between MGMT promoter hypermethylation and high level of AFB(1)-DNA adducts in tumor tissues (OR = 5.05, 95% CI = 1.29-19.73). A significant association was also found between methylation and p53 mutation status (OR = 2.97, 95% CI = 1.09-8.11). These results suggest that epigenetic inactivation of MGMT plays an important role in the development of HCC and exposure to environmental carcinogens may be related to altered methylation of genes involved in cancer development. The role of chemical carcinogens in hypermethylation needs further investigation. (C) 2002 Wiley-Liss, Inc. C1 Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. NIEHS, Res Triangle Pk, NC 27709 USA. Natl Taiwan Univ, Coll Med, Dept Surg, Taipei, Taiwan. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. RP Santella, RM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, Rm 505,701 W 168th St, New York, NY 10032 USA. RI Chen, Chien-Jen/C-6976-2008; OI LEE, PO-HUANG/0000-0001-5831-035X FU NIEHS NIH HHS [ES 05116, P30 ES 09089] NR 35 TC 47 Z9 52 U1 1 U2 8 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 PD FEB 10 PY 2003 VL 103 IS 4 BP 440 EP 444 DI 10.1002/ijc.10852 PG 5 WC Oncology SC Oncology GA 630JZ UT WOS:000180104900002 PM 12478658 ER PT J AU Sharp, GB Mizuno, T Cologne, JB Fukuhara, T Fujiwara, S Tokuoka, S Mabuchi, K AF Sharp, GB Mizuno, T Cologne, JB Fukuhara, T Fujiwara, S Tokuoka, S Mabuchi, K TI Hepatocellular carcinoma among atomic bomb survivors: Significant interaction of radiation with hepatitis C virus infections SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE radiation; hepatitis B; hepatitis C; hepatocellular carcinoma ID PRIMARY LIVER-CANCER; TOBACCO SMOKING; ALCOHOL-CONSUMPTION; AFLATOXIN EXPOSURE; BREAST-CANCER; MORTALITY; RISK; THOROTRAST; JAPAN; EPIDEMIOLOGY AB We conducted a nested case-control study within the cohort of Japanese survivors of the 1945 atomic bombings to study the joint effects of HBV and HCV with radiation on the risk of HCC. Among subjects who received autopsies during 1954-1988, we analyzed archival tissue samples for 238 pathologically confirmed HCC cases and 894 controls who died from diseases other than liver cancer. Using logistic regression and adjusting for potential confounders and other factors, we found a statistically significant, supermultiplicative interaction between A bomb radiation and HCV in the etiology of HCC. Compared to subjects who were negative for HCV and radiation, ORs of HCC for HCV-positive subjects showed a statistically significant, greater than multiplicative increase for liver irradiation exposures in the second (>0.018-0.186 Sv, p = 0.04) and third (>0.186 Sv, p = 0.05) tertiles of non-zero radiation exposure but not for first tertile exposure (>0-0.018 Sv, p = 0.86). Limiting analysis to subjects without cirrhosis, HCV-infected subjects were at 58.0-fold (95% CI 1.99-infinity) increased risk of HCC per Sv of radiation exposure (p = 0.017), a supermultiplicative interaction between radiation and HCV that was not found among subjects with cirrhosis (p = 0.67). We found no evidence of interaction between HBV infection and radiation exposure in the etiology of HCC, regardless of cirrhosis status (P = 0.58). We conclude that among survivors of the nuclear bombings of Hiroshima and Nagasaki, subjects who were both HCV-positive and radiation-exposed were at a significantly, super-multiplicatively increased risk of HCC without concurrent cirrhosis. (C) 2002 Wilely-Liss, Inc. C1 Radiat Effects Res Fdn, Dept Epidemiol, Minami Ku, Hiroshima 7320815, Japan. Natl Acad Sci, Washington, DC 20418 USA. Radiat Effects Res Fdn, Dept Radiobiol & Mol Epidemiol, Hiroshima, Japan. Radiat Effects Res Fdn, Dept Stat, Hiroshima, Japan. Hiroshima Prefectural Hosp, Dept Pathol, Hiroshima, Japan. Radiat Effects Res Fdn, Dept Clin Studies, Hiroshima, Japan. NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Sharp, GB (reprint author), Radiat Effects Res Fdn, Dept Epidemiol, Minami Ku, 5-2 Hijiyama Pk, Hiroshima 7320815, Japan. OI Cologne, John/0000-0003-1540-6639 FU NCPDCID CDC HHS [NCI 48938-001] NR 46 TC 21 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 10 PY 2003 VL 103 IS 4 BP 531 EP 537 DI 10.1002/ijc.10862 PG 7 WC Oncology SC Oncology GA 630JZ UT WOS:000180104900015 PM 12478671 ER PT J AU Freedman, DM Sigurdson, A Rao, RS Hauptmann, M Alexander, B Mohan, A Doody, MM Linet, MS AF Freedman, DM Sigurdson, A Rao, RS Hauptmann, M Alexander, B Mohan, A Doody, MM Linet, MS TI Risk of melanoma among radiologic technologists in the United States SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE occupational radiation exposure; radiologic technologists; melanoma ID INDUCED SKIN-CANCER; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; SUN EXPOSURE; MORTALITY; RADIATION; EPIDEMIOLOGY; EMPLOYEES; REGISTRY; DEATH AB Our study examines the risk of melanoma among medical radiation workers in the U.S. Radiologic Technologists (USRT) study. We evaluated 68,588 white radiologic technologists (78.8% female), certified during 1926-1982, who responded to a baseline questionnaire (1983-1989) and were free of cancer other than nonmelanoma skin at that time. Participants were followed through completion of a second questionnaire (1994-1998). We identified 207 cases, 193 subjects who reported first primary melanoma and 14 decedents with melanoma listed as an underlying or contributory cause of death. We examined risks of occupational radiation exposures using work history information on practices, procedures, and protective measures reported on the baseline questionnaire. Based on Cox proportional hazards regression, melanoma was significantly associated with established risk factors, including constitutional characteristics (skin tone, eye and hair color), personal history of nonmelanoma skin cancer, family history of melanoma and indicators of residential sunlight exposure. Melanoma risk was increased among those who first worked before 1950 (RR = 1.8, 95% CI = 0.6-5.5), particularly among those who worked 5 or more years before 1950 (RR = 2.4; 0.7-8.7; p (trend) for years worked before 1950 = 0.03), when radiation exposures were likely highest. Risk was also modestly elevated among technologists who did not customarily use a lead apron or shield when they first began working (RR = 1.4; 0.8-2.5). Clarifying the possible role of exposure to chronic ionizing radiation in melanoma is likely to require nested case-control studies within occupational cohorts, such as this one, which will assess individual radiation doses, and detailed information about sun exposure, sunburn history and skin susceptibility characteristics. Published 2002 Wiley-Liss, Inc(dagger). C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. Univ Minnesota, Div Environm & Occupat Hlth, Minneapolis, MN USA. RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Execut Plaza S,Room 7087,6120 Execut Plaza Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01 CP 51016, N02 CP 81005, N02 CP 81121, N01 CP 15673] NR 41 TC 35 Z9 35 U1 3 U2 7 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 PD FEB 10 PY 2003 VL 103 IS 4 BP 556 EP 562 DI 10.1008/ijc.10854 PG 7 WC Oncology SC Oncology GA 630JZ UT WOS:000180104900019 PM 12478675 ER PT J AU Eng, SR Koziov, S Turner, EE AF Eng, SR Koziov, S Turner, EE TI Unaltered expression of Bcl-2 and TAG-1/axonin-1 precedes sensory apoptosis in Brn3a knockout mice SO NEUROREPORT LA English DT Article DE axonin-1; Bcl-2; Brn3a; dorsal root ganglion; POU-clomain; TAG-1; trigerminal ganglion ID FAMILY TRANSCRIPTION FACTOR; SECRETED PROTEIN AXONIN-1; CELL-DEATH; NEURITE FASCICULATION; AXONAL OUTGROWTH; NEURONAL DEATH; NERVOUS-SYSTEM; GROWTH; DIFFERENTIATION; ACTIVATION AB Mice lacking the POU-domain transcription factor Brn3a exhibit growth defects in trigeminal axons, undergo extensive sensory cell death in late gestation, and die at birth. Based on tissue culture studies, the mediator of apoptosis Bcl-2 has been suggested as a target of Brn3a regulation which could affect sensory viability in these mice. In addition, Bcl-2 and the neural cell adhesion moleculeTAG-1/axonin-1 have both been implicated in sensory axon guidance. In this study we examined wild-type and Brn3a knockout embryos for alterations in the expression of these genes. Trigeminal ganglia were harvested from embryonic day 13.5 mouse embryos, and Bcl-2 and TAG-1 expression were measured by RT-PCR.TAG-1 expression was also examined in the embryonic trigeminal and dorsal root ganglia by immunohistochemistry. The developing trigeminal ganglia of Brn3a knockout mice exhibit similar levels of Bcl-2 and TAG-1 mRNA expression. Immunohistochemical staining of TAG-1 also appeared to be quantitatively similar in the sensory axons of wild-type and knockout embryos. It is unlikely that Bcl-2 is a regulatory target of Brn3a, or that either of these factors mediates the defects in axon guidance and neuronal survival observed in the sensory ganglia of Brn3a knockout mice. C1 Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Turner, EE (reprint author), Univ Calif San Diego, Dept Psychiat, 0603,9500 Gilman Dr, La Jolla, CA 92093 USA. OI Turner, Eric/0000-0001-5499-6788 FU NICHD NIH HHS [HD33442]; NIMH NIH HHS [MH01581, MH58447] NR 31 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 10 PY 2003 VL 14 IS 2 BP 173 EP 176 DI 10.1097/01.wnr.0000053760.76853.08 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 653TE UT WOS:000181452500002 PM 12598723 ER PT J AU Wisor, JP Wurts, SW Hall, FS Lesch, KP Murphy, DL Uhl, GR Edgar, DM AF Wisor, JP Wurts, SW Hall, FS Lesch, KP Murphy, DL Uhl, GR Edgar, DM TI Altered rapid eye movement sleep timing in serotonin transporter knockout mice SO NEUROREPORT LA English DT Article DE depression; REM sleep; serotonin; serotonin uptake inhibitors ID REM-SLEEP; PARADOXICAL SLEEP; OUT MICE; POLYMORPHISM; DEPRIVATION; DEPRESSION; GENE; RECEPTORS; PROMOTER; NEURONS AB The monoamine neurotransmitter serotonin has long been implicated in development and maintenance of sleep patterns, yet the role of the serotonin transporter (SERT) in these processes has not been evaluated in detail. We report that genetically engineered SERT knockout mice exhibit more REM sleep (REMS) than wild type littermates (11 vs 7% of recording time under baseline conditions) and display more frequent REMS bouts that last longer. This phenotype resembles the previously reported long-term effect of repeated treatment with SERT inhibitor compounds rather than the acute REMS suppressing effect of treatment with such compounds, and is thus likely to reflect neuroadaptations to the absence of SERT, rather than an acute effect of its absence in the adult. While electroencephalographic (EEG) spectra did not differ between SERT knockout and wild type mice during non-REM sleep (NREMS) or REMS, the dynamics of the EEG during the transition from NREMS to REMS differed between the genotypes. The surge in EEG power in both the 6-9 Hz and 10-16 Hz ranges that occurs just prior to the onset of REMS (pre-REMS power surge) is of greater magnitude in SERT knockout mice than in wild type littermate controls. This observation contrasts with the reduced magnitude pre-REMS power surge observed in rats subjected to REMS deprivation relative to yoked controls. These results indicate that the pre-REMS power surge is influenced by REMS history and by monoaminergic transmission. Genetic differences in serotonin systems and developmental exposure to SERT blockers are likely to exert effects on REMS. C1 Stanford Univ, Sleep & Circadian Neurobiol Lab, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. NIDA, Mol Neurobiol Branch, NIH, DHH5, Lexington, KY USA. NIMH, Clin Sci Lab, Intramural Res Program, NIH,DHH5, Bethesda, MD USA. Univ Wurzburg, Dept Psychiat, D-97070 Wurzburg, Germany. RP Wisor, JP (reprint author), Stanford Univ, Sleep & Circadian Neurobiol Lab, Dept Psychiat & Behav Sci, 701 Welch Rd,Suite 2226, Palo Alto, CA 94304 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 FU NHLBI NIH HHS [HL61594, HL64243]; NIMH NIH HHS [MH11660] NR 25 TC 41 Z9 43 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 10 PY 2003 VL 14 IS 2 BP 233 EP 238 DI 10.1097/01.wnr.0000054963.21656.bf PG 6 WC Neurosciences SC Neurosciences & Neurology GA 653TE UT WOS:000181452500015 PM 12598736 ER PT J AU Kiyatkin, EA Brown, PL AF Kiyatkin, EA Brown, PL TI Naloxone depresses cocaine self-administration and delays its initiation on the following day SO NEUROREPORT LA English DT Article DE brain temperature; drug-taking behavior; motivational arousal; neural activation; rats; reinforcement; reward ID RATS; NALTREXONE; MEDIATION; ACQUISITION; ADDICTION; HEROIN AB While dopamine mechanisms play a crucial role in cocaine-taking behavior, the contribution of endogenous opioid systems is less clear. We assessed the effects of opioid receptor blockade by naloxone (1 mg/kg, s.c.) on the daily performance and subsequent initiation of cocaine self-administration in trained rats. Naloxone decreased self-administration rate by approximately half, with the effect varying from complete blockade to no change. On the day following naloxone treatment, the latencies from the drug availability cue to the first self-administration were consistently longer than before naloxone treatment. Measurement of brain temperature and behavioral observations suggested a lower than normal level of motivational arousal as a factor for slow initiation of cocaine-taking behavior. After the first drug infusion, however, performance was uniformly normal. These data suggest endogenous opioid systems play a role in cocaine-taking behavior and indicate a residual inhibitory consequence of naloxone treatment on the initiation of this behavior. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov NR 21 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 10 PY 2003 VL 14 IS 2 BP 251 EP 255 DI 10.1097/01.wnr.0000054964.21656.71 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 653TE UT WOS:000181452500019 PM 12598740 ER PT J AU Liu, DX Wang, X Zhang, ZP Teng, CT AF Liu, DX Wang, X Zhang, ZP Teng, CT TI An intronic alternative promoter of the human lactoferrin gene is activated by Ets SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE alternative promoter; lactoferrin gene; delta lactoferrin; Ets; GFP; transfection ID MYELOID TRANSCRIPTION FACTOR; C/EBP-EPSILON; BINDING-SITES; MESSENGER-RNA; PROTEIN; IDENTIFICATION; CELLS; MOUSE; DNA; DIFFERENTIATION AB Lactoferrin expresses in a variety of tissues and involves in various aspects of host defense mechanisms. The lactoferrin gene is differentially regulated through multiple signaling pathways. Recently, an alternative form of human lactoferrin mRNA (DeltaLF) was found in normal human tissues but absent from the tumor cells. In this study, we identified the transcription start sites of the DeltaLF in mammary gland and bone marrow and demonstrated that the DeltaLF is the product of an alternative (P2) promoter present in the first intron of the lactoferrin gene. The P2 promoter has high activity in Jurkat and U937 and low activity in RL95-2 and HEC-1B cell lines. Nonetheless, the promoter activity in HEG-1B cells was dramatically enhanced with overexpression of the Ets-1 transcription factor. The GFP-tagged lactoferrin is present in the cytoplasm whereas GFP-tagged DeltaLF is found in both nucleus and cytoplasm as examined by fluorescence and confocal microscopy. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233,MD E2-01, Res Triangle Pk, NC 27709 USA. NR 35 TC 22 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 7 PY 2003 VL 301 IS 2 BP 472 EP 479 DI 10.1016/S0006-291X(02)03077-2 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 647NG UT WOS:000181099100034 PM 12565886 ER PT J AU Zhang, YF Hoon, MA Chandrashekar, J Mueller, KL Cook, B Wu, DQ Zuker, CS Ryba, NJP AF Zhang, YF Hoon, MA Chandrashekar, J Mueller, KL Cook, B Wu, DQ Zuker, CS Ryba, NJP TI Coding of sweet, bitter, and umami tastes: Different receptor cells sharing similar signaling pathways SO CELL LA English DT Article ID PHOSPHOLIPASE-C; TRP CHANNEL; TRANSDUCTION; RESPONSES; FAMILY; MICE; MOUSE; RAT; IDENTIFICATION; DISCRIMINATION AB Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, abolish sweet, amino acid, and bitter taste reception, but do not impact sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction converge on common signaling molecules. Using PLCbeta2 taste-blind animals, we then examined a fundamental question in taste perception: how taste modalities are encoded at the cellular level. Mice engineered to rescue PLCbeta2 function exclusively in bitter-receptor expressing cells respond normally to bitter tastants but do not taste sweet or amino acid stimuli. Thus, bitter is encoded independently of sweet and amino acids, and taste receptor cells are not broadly tuned across these modalities. C1 Univ Calif San Diego, Howard Hughes Med Inst, Dept Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Howard Hughes Med Inst, Dept Neurosci, La Jolla, CA 92093 USA. Natl Inst Dent & Craniofacial Res, NIH, DHHS, Bethesda, MD 20892 USA. RP Zuker, CS (reprint author), Univ Calif San Diego, Howard Hughes Med Inst, Dept Biol, La Jolla, CA 92093 USA. NR 41 TC 676 Z9 746 U1 18 U2 106 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD FEB 7 PY 2003 VL 112 IS 3 BP 293 EP 301 DI 10.1016/S0092-8674(03)00071-0 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 650FK UT WOS:000181252200002 PM 12581520 ER PT J AU Park, G Przyborowska, AM Ye, N Tsoupas, NM Bauer, CB Broker, GA Rogers, RD Brechbiel, MW Planalp, RP AF Park, G Przyborowska, AM Ye, N Tsoupas, NM Bauer, CB Broker, GA Rogers, RD Brechbiel, MW Planalp, RP TI Steric effects caused by N-alkylation of the tripodal chelator N,N ',N ''-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (tachpyr): structural and electronic properties of the Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes SO DALTON TRANSACTIONS LA English DT Article ID JAHN-TELLER DISTORTIONS; METAL-COMPLEXES; CRYSTAL-STRUCTURES; CIS,CIS-1,3,5-TRIAMINOCYCLOHEXANE; AGENTS; RADIOPHARMACEUTICALS; COPPER(II); ZINC(II) AB The effects of steric hindrance on the complexation of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) by chelators based on cis, cis-1,3,5-triaminocyclohexane (tach) have been studied. The chelators studied are the 2-methylpyridyl pendant-arm derivatives of tach, 'tachpyr'(N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane),and the N-alkylated analogs '(N-Me),tachpyr' (N,N',N"-trimethyl-NN',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane) and '(N-Et)(3)tachpyr' (N,N',N"-triethyl-N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane). Hexacoordinate complexes, [(ML)-L-II]X-2 resulted from reaction of the appropriate metal ion salts with L in alcoholic medium (M = Mn, Co, Ni, Cu, Zn; L = tachpyr, (N-Me)(3)tachpyr, (N-Et)(3)tachpyr; X = ClO4-, NO3-, Cl-). The Mn(II) and Co(II) complexes have high-spin electron configurations, based on solution magnetic susceptibility, electronic spectral and/or X-ray crystallographic studies. However, solution visible-near IR electronic spectra and single-crystal X-ray crystallography demonstrate weakened bonding in the complexes of (N-R)(3)tachpyr relative to tachpyr, due to steric effects of methyl or ethyl groups on coordinated tach amines. Structures of [Zn(tachpyr)](2+) and [Ni(tachpyr)](2+) indicate a clear preference of tachpyr and derivatives for octahedral geometry, while [Cu((N-Me),tachpyr)](2+) exhibits a classic Jahn-Teller tetragonal distortion. The complex [Mn(tachpyr)](ClO4)(2) demonstrates a striking influence of the metal ion on the coordination geometry, with a trigonal-prismatic coordination of Mn(II) and considerable distortion of the tach-amino donor groups. The coordination geometry and distortions are attributed to the large size of high-spin d(5) Mn(II) and the absence of ligand-field stabilization energy, coupled with the observed preference of tachpyr derivatives for octahedral geometry. The [M-II(tachpyr)](2+) complexes (M = Co, Ni, Cu and Zn) are inert in aqueous pH 5.5 media. However, all metal complexes of N-alkylated tachpyr, as well as [Mn(tachpyr)](ClO4)(2), dissociate metal ion in aqueous pH 5.5 medium, consistent with their steric hindrance and distortions respectively. C1 Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. Bruker AXS Inc, Madison, WI 53711 USA. NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Planalp, RP (reprint author), Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 35 TC 8 Z9 8 U1 3 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-9226 J9 DALTON T JI Dalton Trans. PD FEB 7 PY 2003 IS 3 BP 318 EP 324 DI 10.1039/b209228j PG 7 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 651VB UT WOS:000181341800010 ER PT J AU Song, CC Wang, Q Li, CCH AF Song, CC Wang, Q Li, CCH TI ATPase activity of p97-valosin-containing protein (VCP) - D2 mediates the major enzyme activity, and D1 contributes to the heat-induced activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VALOSIN-CONTAINING PROTEIN; SENSITIVE FUSION PROTEIN; SACCHAROMYCES-CEREVISIAE; TYROSINE PHOSPHORYLATION; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTOR; MEMBRANE-FUSION; AAA ATPASE; PROTEASOME; BINDING AB The 97-kDa valosin-containing protein (p97-VCP) plays a role in a wide variety of cellular activities, many of which are regulated by the ubiquitin-proteasome (Ub-Pr)-mediated degradation pathway. We previously demonstrated that VCP binds to multi-ubiquitin chains and may act as a molecular chaperone that targets the ubiquitinated substrates to the proteasome for degradation. In this report, we show that although the ubiquitin chain-binding activity, carried out by the N-terminal 200 residues (N domain), is necessary for the degradation of proteasome substrates, it is not sufficient. Using in vitro degradation assays, we demonstrated that the entire VCP molecule, consisting of the N domain and two ATPase domains D1 and D2, is required for mediating the Ub-Pr degradation. The ATPase activity of VCP requires Mg2+, and is stimulated by high temperature. Under optimal conditions, VCP hydrolyzes ATP with a K-m of similar to0.33 mm and a V-max of similar to0.52 nmol P-i min(-1) mug(-1). At a physiological temperature, mutation in D2 significantly inhibits the ATPase activity, while that in D1 has little effect. Interestingly, mutations in D1, but not D2, abolish the heat-stimulated ATPase activity. Thus, we provide the first demonstration that the ATPase activity of VCP is required for mediating the Ub-Pr degradation, that D2 accounts for the major ATPase activity, and that D1 contributes to the heat-induced activity. C1 NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Basic Res Lab, Frederick, MD 21702 USA. RP Li, CCH (reprint author), NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 47 TC 120 Z9 121 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 7 PY 2003 VL 278 IS 6 BP 3648 EP 3655 DI 10.1074/jbc.M208422200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 643PM UT WOS:000180869700018 PM 12446676 ER PT J AU Colombo, C Haluzik, M Cutson, JJ Dietz, KR Marcus-Samuels, B Vinson, C Gavrilova, O Reitman, ML AF Colombo, C Haluzik, M Cutson, JJ Dietz, KR Marcus-Samuels, B Vinson, C Gavrilova, O Reitman, ML TI Opposite effects of background genotype on muscle and liver insulin sensitivity of lipoatrophic mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADIPOSE-TISSUE; DIABETES-MELLITUS; LIPOPROTEIN-LIPASE; SKELETAL-MUSCLE; GLUCOSE-UPTAKE; MOUSE; RESISTANCE; PROTEIN; EXPRESSION; LEPTIN AB The metabolic phenotype of the A-ZIP/F-1 (AZIP) lipoatrophic mouse is different depending on its genetic background. On both the FVB/N (FVB) and C57BL/6J (B6) backgrounds, AZIP mice have a similarly severe lack of white adipose tissue and comparably increased insulin levels and triglyceride secretion rates. However, on the B6 background, the AZIP mice have less hyperglycemia, lower circulating triglyceride and fatty acid levels, and lower mortality. AZIP characteristics that are more severe on the B6 background include increased liver size and liver triglyceride content. A unifying hypothesis is that the B6 strain has higher triglyceride clearance into the liver, with lower triglyceride levels elsewhere. This may account for the observation that the B6 AZIP mice have less insulin-resistant muscles and more insulin-resistant livers, than do the FVB AZIP mice. B6 wild type, as well as B6 AZIP, mice have increased triglyceride clearance relative to FVB, which may be explained in part by higher serum lipase levels and liver CD36/fatty acid translocase mRNA levels. Thus, it is likely that increased triglyceride clearance in B6, as compared with FVB, mice contributes to the strain differences in insulin resistance and lipid metabolism. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Reitman, ML (reprint author), Merck Res Labs, POB 2000,RY80M-213, Rahway, NJ 07065 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 54 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 7 PY 2003 VL 278 IS 6 BP 3992 EP 3999 DI 10.1074/jbc.M207665200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 643PM UT WOS:000180869700061 PM 12456680 ER PT J AU Zhao, WQ Chen, GH Chen, H Pascale, A Ravindranath, L Quon, MJ Alkon, DL AF Zhao, WQ Chen, GH Chen, H Pascale, A Ravindranath, L Quon, MJ Alkon, DL TI Secretion of annexin II via activation of insulin receptor and insulin-like growth factor receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; SIGNAL-TRANSDUCTION; PHOSPHORYLATION; TETRAMER; IDENTIFICATION; PARTICIPATION; ASSOCIATION; AGGREGATION; EXOCYTOSIS; SUBSTRATE AB Annexin II is secreted into the extracellular environment, where, via interactions with specific proteases and extracellular matrix proteins, it participates in plasminogen activation, cell adhesion, and tumor metastasis and invasion. However,; mechanisms regulating annexin II transport across the cellular membrane are unknown. In this study, we used coimmunoprecipitation to show that Annexin-II was bound to insulin and insulin-like growth factor-1 (IGF-1) receptors in PC12 cells and NIH-3T3 cells overexpressing insulin (NIH-3T3(IR)) or IGF-1 receptor (NIH-3T3(IGF-IR)). Stimulation of insulin and IGF-1 receptors, by insulin caused a temporary dissociation of annexin II from these receptors, which was accompanied by;an increased amount of extracellular annexin II detected in the media of PC12, NIH-3T3(IR), and NIH-3T3(IGF-IR) cells but not in that of untransfected NIH-3T3 cells. Activation of a different growth factor receptor, the platelet-derived growth factor receptor, did not produce such results. Tyrphostin AG1024, a tyrosine kinase inhibitor of insulin and IGF-1 receptor, was shown to inhibit annexin II secretion along with reduced receptor phosphorylation. Inhibitors of a few downstream signaling enzymes including phosphatidylinositol 3-kinase, pp60c-Src, and protein kinase C had no effect on insulin-induced annexin II secretion, suggesting a possible direct link between receptor activation and annex in II secretion. Immunocytochemistry revealed that insulin also induced transport of the membrane-bound form of annexin II to the outside layer of the cell membrane and appeared to promote cell aggregation. These results suggest that the insulin receptor and its signaling pathways may participate in molecular mechanisms mediating annexin II secretion. C1 Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. NCCAM, LCI, Diabet Unit, NIH, Bethesda, MD 20892 USA. Univ Pavia, Dept Expt & Appl Pharmacol, I-27100 Pavia, Italy. RP Zhao, WQ (reprint author), Blanchette Rockefeller Neurosci Inst, 9601 Med Ctr Dr,Acad & Res Bldg,3rd Fl, Rockville, MD 20850 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 37 TC 33 Z9 36 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 7 PY 2003 VL 278 IS 6 BP 4205 EP 4215 DI 10.1074/jbc.M210545200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 643PM UT WOS:000180869700088 PM 12431980 ER PT J AU Ozola, V Thorand, M Diekmann, M Qurishi, R Schumacher, B Jacobson, KA Muller, CE AF Ozola, V Thorand, M Diekmann, M Qurishi, R Schumacher, B Jacobson, KA Muller, CE TI 2-phenylimidazo[2,1-i]purin-5-ones: Structure-activity relationships and characterization of potent and selective inverse agonists at human A(3) adenosine receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID ANTAGONIST RADIOLIGAND; DERIVATIVES; BINDING; ISOQUINOLINE; MEMBRANES; SUBTYPES; LIGANDS; CELLS; A(1) AB Structure-activity relationships of 2-phenyl-imidazo[2,1-i]purin-5-ones as ligands for human A(3) adenosine receptors (ARs) were investigated. An ethyl group in the 8-position of the imidazoline ring of 4-methyl-2-phenyl-imidazopurinone leading to chiral compounds was found to increase affinity for human A3 ARs by several thousand-fold. Propyl substitution instead of methyl at N4 decreased A(3) affinity but increased A(1) affinity leading to potent A(1)-selective AR antagonists. The most potent A(1) antagonist of the present series was (S)-S-ethyl-2-phenyl-4-propyl-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one (S-3) exhibiting a K-i value of 7.4 nM at rat A(1) ARs and greater than 100-fold selectivity versus rat A(2A) and human A(3) ARs. At human A(1) ARs 2-phenylimidazo[2,1-i]purin-5-ones were generally less potent and therefore less A(1)-selective (S-3: K-i=98 nM). 2-, 3-, or 4-Mono-chlorination of the 2-phenyl ring reduced A(3) affinity but led to an increase in affinity for A(1) ARs, whereas di- (3,4-dichloro) or polychlorination (2,3,5-trichloro) increased A(3) affinity. The most potent and selective A(3) antagonist of the present series was the trichlorophenyl derivative (R)-8-ethyl-4-methyl-2-(2,3,5-trichlorophenyl)-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one (R-8) exhibiting a subnanomolar K-i value at human A(3) ARs and greater than 800-fold selectivity versus the other AR subtypes. Methylation of 4-alkyl-2-phenyl-substituted imidazo[2,1-i]purin-5-ones led exclusively to the N9-methyl derivatives, which exhibited largely reduced AR affinities as compared to the unmethylated compounds. [S-35]GTPgammaS binding studies of the most potent 2-phenyl-imidazo[2,1-i] purin-5-ones at membranes of Chinese hamster ovary cells expressing the human A(3) AR revealed that the compounds were inverse agonists at A(3) receptors under standard test conditions. Due to their high A(3) affinity, selectivity, and relatively high water-solubility, 2-phenyl-imidazo[2,1-i]purin-5-ones may become useful research tools. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Bonn, Pharmaceut Inst Poppelsdorf, D-53115 Bonn, Germany. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Muller, CE (reprint author), Univ Bonn, Pharmaceut Inst Poppelsdorf, Kreuzbergweg 26, D-53115 Bonn, Germany. RI Jacobson, Kenneth/A-1530-2009; Muller, Christa/C-7748-2014 OI Jacobson, Kenneth/0000-0001-8104-1493; Muller, Christa/0000-0002-0013-6624 NR 29 TC 35 Z9 35 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD FEB 6 PY 2003 VL 11 IS 3 BP 347 EP 356 AR PII S0968-0896(02)00456-X DI 10.1016/S0968-0896(02)00456-X PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 639CE UT WOS:000180609400005 PM 12517430 ER PT J AU Miyashiro, KY Beckel-Mitchener, A Purk, TP Becker, KG Barret, T Liu, L Carbonetto, S Weiler, IJ Greenough, WT Eberwine, J AF Miyashiro, KY Beckel-Mitchener, A Purk, TP Becker, KG Barret, T Liu, L Carbonetto, S Weiler, IJ Greenough, WT Eberwine, J TI RNA cargoes associating with in cellular functioning in Fmrl Fmr1 reveal deficits null mice SO NEURON LA English DT Article ID X MENTAL-RETARDATION; FRAGILE-X; MESSENGER-RNA; PROTEIN FMRP; KNOCKOUT MICE; BINDING; IDENTIFICATION; LOCALIZATION; TRANSLATION; EXPRESSION AB The Fragile X mental retardation-1 (Fmr1) gene encodes a multifunctional protein, FMRP, with intrinsic RNA binding activity. We have developed an approach, antibody-positioned RNA amplification (APRA), to identify the RNA cargoes associated with the in vivo configured FMRP messenger ribonucleoprotein (mRNP) complex. Using APRA as a primary screen, putative FMRP RNA cargoes were assayed for their ability to bind directly to FMRP using traditional methods of assessing RNA-protein interactions, including UV-crosslinking and filter binding assays. Approximately 60% of the APRA-defined mRNAs directly associate with FMRP. By examining a subset of these mRNAs and their encoded proteins in brain tissue from Fmr1 knockout mice, we have observed that some of these cargoes as well as the proteins they encode show discrete changes in abundance and/or differential subcellular distribution. These data are consistent with spatially selective regulation of multiple biological pathways by FMRP. C1 Univ Penn, Sch Med, Dept Pharmacol, Dept Psychiat, Philadelphia, PA 19104 USA. McGill Univ, Dept Neurol & Neurosurg, Neurosci Res Ctr, Montreal, PQ H3A 2B4, Canada. Univ Illinois, WM Keck Ctr Comparat & Funct Genomics, Urbana, IL 61801 USA. NIA, DNA Array Unit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Illinois, Beckman Inst, Dept Psychol, Dept Psychiat,Neurosci Program, Urbana, IL 61801 USA. RP Eberwine, J (reprint author), Univ Penn, Sch Med, Dept Pharmacol, Dept Psychiat, Philadelphia, PA 19104 USA. RI Eberwine, James/B-2247-2010 FU NIA NIH HHS [AG9900]; NICHD NIH HHS [HD37175]; NIMH NIH HHS [MH58561, MH64272] NR 56 TC 327 Z9 334 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB 6 PY 2003 VL 37 IS 3 BP 417 EP 431 DI 10.1016/S0896-6273(03)00034-5 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 647FF UT WOS:000181081600008 PM 12575950 ER PT J AU Zhang, L Li, PP Feng, X Barker, JL Smith, SV Rubinow, DR AF Zhang, L Li, PP Feng, X Barker, JL Smith, SV Rubinow, DR TI Sex-related differences in neuronal cell survival and signaling in rats SO NEUROSCIENCE LETTERS LA English DT Article DE dimorphism; ERK1; ERK2; Akt; neuron; apoptosis ID SYSTEM AB While substantial and compelling evidence exists for sex-related differences in gross and microscopic brain structure, our understanding of the cellular mechanisms that give rise to these sexual dimorphisms is in its infancy. To investigate possible underlying mechanisms for sex-related differences in neuronal development, we examined neuronal survival and transductional signaling in male and female rat primary cortical neuronal cultures. We found that following 14 days in culture, the total number of surviving neurons was significantly higher in female cultures derived from either cortical plate (cp) or ventricular zone (vz), the regions where differentiating (cp) and proliferating (vz) cells are located. In addition, sex-related differences in the levels of phospho-ERK1 and Akt were also observed. Female cortical cultures had significantly higher levels of ERK1 in both cp and vz and higher levels of Akt in cp. No sex-related differences in Bcl-2 were observed. These data suggest that dimorphisms in cell survival may underlie enhanced neuronal survival (or decreased apoptosis) in female brain. Further, the appearance of sex-related differences at cellular and signaling levels in cortical neuronal cultures demonstrates that the effects of gender are not limited to parts of the brain mediating reproduction. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Lab Mol Pathol, NIH, Bethesda, MD 20892 USA. NIMH, Neurophysiol Lab, NINDS, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Zhang, L (reprint author), NIMH, Behav Endocrinol Branch, NIH, Bldg 10,Room 3N238,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. NR 12 TC 39 Z9 39 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 6 PY 2003 VL 337 IS 2 BP 65 EP 68 DI 10.1016/S0304-3940(02)01179-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 641QF UT WOS:000180756100001 PM 12527389 ER PT J AU Wright, TC Schiffman, M AF Wright, TC Schiffman, M TI Adding a test for human papillomavirus DNA to cervical cancer screening. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wright, TC (reprint author), Columbia Univ Coll Phys & Surg, Dept Pathol, 630 W 168th St, New York, NY 10032 USA. NR 3 TC 144 Z9 151 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 6 PY 2003 VL 348 IS 6 BP 489 EP 490 DI 10.1056/NEJMp020178 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 642JY UT WOS:000180801400002 PM 12571255 ER PT J AU Crowder, C Kopantzev, E Williams, K Lengel, C Miki, T Rudikoff, S AF Crowder, C Kopantzev, E Williams, K Lengel, C Miki, T Rudikoff, S TI An unusual H-Ras mutant isolated from a human multiple myeloma line leads to transformation and factor-independent cell growth SO ONCOGENE LA English DT Article DE Ras; mutation; transformation; growth factor independence ID GUANINE-NUCLEOTIDE-BINDING; N-RAS; K-RAS; ACTIVATING MUTATIONS; STRUCTURAL DIFFERENCES; TRANSDUCTION PATHWAY; SIGNAL-TRANSDUCTION; FACTOR RECEPTOR-3; LIVER-TUMORS; PRODUCT P21 AB Multiple myeloma (MM) is an incurable plasma cell malignancy. To investigate biochemical lesions associated,with MM, we constructed an expression cDNA library from the OPM-2 human myeloma line. A highly transforming H-Ras mutant was identified by transfection analysis using NIH 3T3 cells. DNA sequencing demonstrated a single-point mutation at position 117 located in the guanine nucleotide-binding site resulting in a lysine-to-glutamic acid substitution. This mutant, H-Ras (K117E), was found to be constitutively activated in terms of GTP binding. We compared the biological effects of H-Ras (K117E) and H-Ras (G12V) in 32D murine hematopoietic progenitor cells. Whereas both Ras proteins are constitutively activated, 32D cells expressing H-Ras (G12V) are still dependent on IL-3 for survival and proliferation while cells carrying H-Ras (K117E) become IL-3 independent. Similar experiments conducted with the B9 line, an IL-6-dependent hybridoma, also demonstrated that B9/H-Ras (KI17E) became IL-6-independent. Expression of H-Ras (K117E) in the human IL-6-dependent ANBL-6 myeloma line resulted in enhanced proliferation at suboptimal concentrations of IL-6. These observations suggest that H-Ras mutations at the binding site for the GTP nucleotide ring structure may also represent activating lesions and have additional biological effects when compared to previously described Ras mutants. C1 NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. NCI, Mol Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. RP Rudikoff, S (reprint author), NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. NR 56 TC 12 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 6 PY 2003 VL 22 IS 5 BP 649 EP 659 DI 10.1038/sj.onc.1206180 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 639RB UT WOS:000180642100002 PM 12569357 ER PT J AU Liu, PC Koeller, DM Kaler, SG AF Liu, PC Koeller, DM Kaler, SG TI Genomic organization of ATOX1, a human copper chaperone SO BMC GENETICS LA English DT Article ID OCCIPITAL HORN-SYNDROME; ATX1 GENE; HOMEOSTASIS; HAH1 AB Background: Copper is an essential trace element that plays a critical role in the survival of all living organisms. Menkes disease and occipital horn syndrome ( OHS) are allelic disorders of copper transport caused by defects in a X-linked gene (ATP7A) that encodes a P-type ATPase that transports copper across cellular membranes, including the trans-Golgi network. Genetic studies in yeast recently revealed a new family of cytoplasmic proteins called copper chaperones which bind copper ions and deliver them to specific cellular pathways. Biochemical studies of the human homolog of one copper chaperone, ATOX1, indicate direct interaction with the Menkes/OHS protein. Although no disease-associated mutations have been reported in ATOX1, mice with disruption of the ATOX1 locus demonstrate perinatal mortality similar to that observed in the brindled mice ( Mo-br), a mouse model of Menkes disease. The cDNA sequence for ATOX1 is known, and the genomic organization has not been reported. Results: We determined the genomic structure of ATOX1. The gene contains 4 exons spanning a genomic distance of approximately 16 kb. The translation start codon is located in the 3' end of exon 1 and the termination codon in exon 3. We developed a PCR-based assay to amplify the coding regions and splice junctions from genomic DNA. We screened for ATOX1 mutations in two patients with classical Menkes disease phenotypes and one individual with occipital horn syndrome who had no alterations detected in ATP7A, as well as an adult female with chronic anemia, low serum copper and evidence of mild dopamine-beta-hydroxylase deficiency and no alterations in the ATOX1 coding or splice junction sequences were found. Conclusions: In this study, we characterized the genomic structure of the human copper chaperone ATOX1 to facilitate screening of this gene from genomic DNA in patients whose clinical or biochemical phenotypes suggest impaired copper transport. C1 NICHHD, Unit Pediat Genet, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. RP Kaler, SG (reprint author), NICHHD, Unit Pediat Genet, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. NR 13 TC 37 Z9 39 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD FEB 5 PY 2003 VL 4 AR 4 DI 10.1186/1471-2156-4-4 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 647CX UT WOS:000181075800001 PM 12594858 ER PT J AU Kozikowski, AP Sun, HY Brognard, J Dennis, PA AF Kozikowski, AP Sun, HY Brognard, J Dennis, PA TI Novel PI analogues selectively block activation of the pro-survival serine/threonine kinase Akt SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID INHIBITION; PATHWAY; RAF C1 Georgetown Univ, Drug Discovery Program, Dept Neurol, Washington, DC 20007 USA. Natl Canc Inst, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20889 USA. RP Kozikowski, AP (reprint author), Georgetown Univ, Drug Discovery Program, Dept Neurol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. EM kozikowa@georgetown.edu FU NCI NIH HHS [CA61015-07] NR 12 TC 182 Z9 188 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD FEB 5 PY 2003 VL 125 IS 5 BP 1144 EP 1145 DI 10.1021/ja0285159 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 640XB UT WOS:000180713000018 PM 12553797 ER PT J AU Merz, CNB Johnson, BD Sharaf, BL Bittner, V Berga, SL Braunstein, GD Hodgson, TK Matthews, KA Pepine, CJ Reis, SE Reichek, N Rogers, WJ Pohost, GM Kelsey, SF Sopko, G AF Merz, CNB Johnson, BD Sharaf, BL Bittner, V Berga, SL Braunstein, GD Hodgson, TK Matthews, KA Pepine, CJ Reis, SE Reichek, N Rogers, WJ Pohost, GM Kelsey, SF Sopko, G CA WISE Study Grp TI Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: A report from the NHLBI-sponsored WISE study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-DISEASE; MYOCARDIAL-INFARCTION; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; DIABETIC WOMEN; SOCIAL-STATUS; ESTROGEN; RISK; AMENORRHEA; MORTALITY AB OBJECTIVES We sought to evaluate hypoestrogenemia of hypothalamic origin and its association with angiographic coronary artery disease (CAD) in premenopausal women. BACKGROUND Coronary artery disease in premenopausal women appears to have a particularly poor prognosis. Primate animal data suggest that premenopausal CAD is strongly determined by psychosocial stress-induced central disruption of ovulatory cycling and resulting hypoestrogenemia. METHODS We assessed reproductive hormone blood levels and angiographic CAD using core laboratories in 95 premenopausal women with coronary risk factors who were enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation and were undergoing coronary angiography for evaluation for suspected ischemia. RESULTS Premenopausal women with angiographic CAD (n = 13) had significantly lower estradiol, bioavailable estradiol, and follicle-stimulating hormone (FSH) (all p < 0.05) than women without angiographic CAD (n = 82), even after controlling for age. Hypoestrogenemia of hypothalamic origin, defined as estradiol <184 pmol/l (50 pg/ml), FSH <10 IU/l, and luteinizing hormone <10 IU/l, was significantly more prevalent among the women with CAD than those without CAD (9/13 [69%] vs. 24/82 [29%], respectively, p = 0.01). Hypoestrogenemia of hypothalamic origin was the most powerful predictor of angiographic CAD in a multivariate model (odds ratio [OR] 7.4 [confidence interval (CI) 1.7 to 33.3], p = 0.008). Anxiolytic/sedative/hypnotic and antidepressant medication use were independent predictors of hypoestrogenemia of hypothalamic origin in a multivariate model (OR 4.6 [Cl 1.3 to 15.7], p = 0.02, OR 0.10 [CI 0.01 to 0.92], p = 0.04, respectively). CONCLUSIONS Among premenopausal women undergoing coronary angiography for suspected myocardial ischemia, disruption of ovulatory cycling characterized by hypoestrogenemia of hypothalamic origin appears to be associated with angiographic CAD. C1 Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Rhode Isl Hosp, Div Cardiol, Providence, RI USA. Univ Alabama Birmingham, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. Univ Pittsburgh, Div Reprod Endocrinol, Pittsburgh, PA USA. Univ Florida, Dept Med, Div Cardiol, Gainesville, FL USA. Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. Allegheny Univ Hlth Sci, Dept Med, Div Cardiol, Pittsburgh, PA USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Merz, CNB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, WISE Coordinating Ctr, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM merz@cshs.org RI Reis, Steven/J-3957-2014; OI Bittner, Vera/0000-0001-9456-850X NR 45 TC 79 Z9 81 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 5 PY 2003 VL 41 IS 3 BP 413 EP 419 DI 10.1016/S0735-1097(02)02763-8 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 641RN UT WOS:000180759800009 ER PT J AU Vourlekis, JS Szabo, E AF Vourlekis, JS Szabo, E TI Predicting success in cancer prevention trials SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RETINOIC ACID RECEPTOR; CELL LUNG-CANCER; 2ND PRIMARY TUMORS; 13-CIS-RETINOIC ACID; GROWTH-INHIBITION; BETA EXPRESSION; CYCLIN D1; CHEMOPREVENTION; ISOTRETINOIN; SUPPRESSION C1 NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, Dept Hlth & Human Serv,NIH, 6130 Execut Blvd,Rm 2132, Bethesda, MD 20892 USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 5 PY 2003 VL 95 IS 3 BP 178 EP 179 PG 2 WC Oncology SC Oncology GA 642DF UT WOS:000180788400001 PM 12569132 ER PT J AU Carney, PA Miglioretti, DL Yankaskas, BC Kerlikowske, K Rosenberg, R Rutter, CM Geller, BM Abraham, LA Taplin, SH Dignan, M Cutter, G Ballard-Barbash, R AF Carney, PA Miglioretti, DL Yankaskas, BC Kerlikowske, K Rosenberg, R Rutter, CM Geller, BM Abraham, LA Taplin, SH Dignan, M Cutter, G Ballard-Barbash, R TI Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CANCER RISK; SENSITIVITY; ESTROGEN; WOMEN; ASSOCIATION; SPECIFICITY; PROGESTIN; HISTORY; TRIAL AB Background: The relationships among breast density, age, and use of hormone replacement therapy (HRT) in breast cancer detection have not been fully evaluated. Objective: To determine how breast density, age, and use of HRT individually and in combination affect the accuracy of screening mammography. Design: Prospective cohort study. Setting: 7 population-based mammography registries in North Carolina; New Mexico; New Hampshire; Vermont; Colorado; Seattle, Washington; and San Francisco, California. Participants: 329 495 women 40 to 89 years of age who had 463 372 screening mammograms from 1996 to 1998; 2223 women received a diagnosis of breast cancer. Measurements: Breast density, age, HRT use, rate of breast cancer occurrence, and sensitivity and specificity of screening mammography. Results: Adjusted sensitivity ranged from 62.9% in women with extremely dense breasts to 87.0% in women with almost entirely fatty breasts; adjusted sensitivity increased with age from 68.6% in women 40 to 44 years of age to 83.3% in women 80 to 89 years of age. Adjusted specificity increased from 89.1% in women with extremely dense breasts to 96.9% in women with almost entirely fatty breasts. In women who did not use HRT, adjusted specificity increased from 91.4% in women 40 to 44 years of age to 94.4% in women 80 to 89 years of age. In women who used HRT, adjusted specificity was about 91.7% for all ages. Conclusions: Mammographic breast density and age are important predictors of the accuracy of screening mammography. Although HRT use is not an independent predictor of accuracy, it probably affects accuracy by increasing breast density. C1 Dartmouth Coll, Sch Med, Dept Community & Family Med, Lebanon, NH 03756 USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Vermont, Burlington, VT 05405 USA. AMC Canc Res Ctr, Denver, CO USA. NCI, Bethesda, MD 20892 USA. RP Carney, PA (reprint author), Dartmouth Coll, Sch Med, Dept Community & Family Med, 1 Med Ctr Dr,HB 7925, Lebanon, NH 03756 USA. FU NCI NIH HHS [UO1CA70013, R01 CA80888, UO1CA63731, UO1CA63736, UO1CA63740, UO1CA69976, UO1CA70040, UO1CA86076, UO1CA86082] NR 33 TC 490 Z9 503 U1 1 U2 16 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 4 PY 2003 VL 138 IS 3 BP 168 EP 175 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 646DB UT WOS:000181018600002 PM 12558355 ER PT J AU Gu, YJ Xiao, B Wargo, HL Bucher, MH Singh, SV Ji, XH AF Gu, YJ Xiao, B Wargo, HL Bucher, MH Singh, SV Ji, XH TI Residues 207, 216, and 221 and the catalytic activity of mGSTA1-1 and mGSTA2-2 toward benzo[a]pyrene-(7R,8S)-diol-(9S,10R)-epoxide SO BIOCHEMISTRY LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; POLYCYCLIC AROMATIC-HYDROCARBONS; SUBSTRATE-BINDING SITE; AMINO-ACID SUBSTITUTIONS; REGION DIOL EPOXIDES; EXCEPTIONAL ACTIVITY; OPTICAL ENANTIOMERS; CONJUGATION; P1-1; 7-BETA,8-ALPHA-DIHYDROXY-9-ALPHA,10-ALPHA-OXY-7,8,9,10-TETRAHYDROBENZO(A )PYRENE AB Murine class alpha glutathione S-transferase subunit types A2 (mGSTA2-2) and A1 (mGSTA1-1) have high catalytic efficiency for glutathione (GSH) conjugation of the ultimate carcinogenic metabolite of benzo[a]pyrene, (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene, [(+)-anti-BPDE]. Only 10 residues differ between the sequences of mGSTA1-1 and 2-2. However, the catalytic efficiency of mGSTA1-1 for GSH conjugation of (+)-anti-BPDE is >3-fold higher as compared with mGSTA2-2. The crystal structure of mGSTA1-1 in complex with the GSH conjugate of (+)-anti-7,8-dihydroxy9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (GSBpd) reveals that R216 and 1221 in the last helix play important roles in catalysis [Gu, Y., Singh, S. V., and Ji, X. (2000) Biochemistry 39, 12552-12557]. The crystal structure of mGSTA2-2 in complex with GSBpd has been determined, which reveals a different binding mode of GSBpd. Comparison of the two structures suggests that residues 207 and 221 are responsible for the different binding mode of GSBpd and therefore contribute to the distinct catalytic efficiency of the two isozymes. C1 NCI, Ctr Macromol Crystallog, Frederick, MD 21702 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15261 USA. RP Ji, XH (reprint author), NCI, Ctr Macromol Crystallog, Frederick, MD 21702 USA. RI Gu, Yijun/B-6017-2012; Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [CA55589, R01 CA76348] NR 34 TC 4 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 4 PY 2003 VL 42 IS 4 BP 917 EP 921 DI 10.1021/bi026778+ PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 640NQ UT WOS:000180695200010 PM 12549910 ER PT J AU Kwong, RY Schussheim, AE Rekhraj, S Aletras, AH Geller, N Davis, J Christian, TF Balaban, RS Arai, AE AF Kwong, RY Schussheim, AE Rekhraj, S Aletras, AH Geller, N Davis, J Christian, TF Balaban, RS Arai, AE TI Detecting acute coronary syndrome in the emergency department with cardiac magnetic resonance imaging SO CIRCULATION LA English DT Article DE emergency department; magnetic resonance imaging; myocardial infarction; ischemia; troponin ID ACUTE MYOCARDIAL-INFARCTION; BEAM COMPUTED-TOMOGRAPHY; ACUTE CHEST PAIN; NONDIAGNOSTIC ELECTROCARDIOGRAMS; STRESS ECHOCARDIOGRAPHY; CONTRAST ENHANCEMENT; MISSED DIAGNOSES; ARTERY DISEASE; TROPONIN-I; PERFUSION AB Background-Managing chest pain in the emergency department remains a challenge with current diagnostic strategies. We hypothesized that cardiac MRI could accurately identify patients with possible or probable acute coronary syndrome. Methods and Results-The diagnostic performance of MRI was evaluated in a prospective study of 161 consecutive patients. Enrollment required 30 minutes of chest pain compatible with myocardial ischemia but an ECG not diagnostic of acute myocardial infarction. MRI was performed at rest within 12 hours of presentation and included perfusion, left ventricular function, and gadolinium-enhanced myocardial infarction detection. MRI was interpreted qualitatively but also analyzed quantitatively. The sensitivity and specificity, respectively, for detecting acute coronary syndrome were 84% and 85% by MRI, 80% and 61% by an abnormal ECG, 16% and 95% for strict ECG criteria for ischemia (ST depression or T-wave inversion), 40% and 97% for peak troponin-I, and 48% and 85% for a TIMI risk score greater than or equal to3. The MRI was more sensitive than strict ECG criteria for ischemia (P < 0.001), peak troponin-I (P < 0.001), and the TIMI risk score (P=0.004), and MRI was more specific than an abnormal ECG (P < 0.001). Multivariate logistic regression analysis showed MRI was the strongest predictor of acute coronary syndrome and added diagnostic value over clinical parameters (P < 0.001). Conclusions-Resting cardiac MRI exhibited diagnostic operating characteristics suitable for triage of patients with chest pain in the emergency department. Performed urgently to evaluate chest pain, MRI accurately detected a high fraction of patients with acute coronary syndrome, including patients with enzyme-negative unstable angina. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Suburban Hosp, Bethesda, MD USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room BID416,MSC 106110 Ctr Dr, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Aletras, Anthony/0000-0002-3786-3817 NR 39 TC 203 Z9 214 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 4 PY 2003 VL 107 IS 4 BP 531 EP 537 DI 10.1161/01.CIR.0000047527.11221.29 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 644GA UT WOS:000180908500007 PM 12566362 ER PT J AU Springer, MS Murphy, WJ Eizirik, E O'Brien, SJ AF Springer, MS Murphy, WJ Eizirik, E O'Brien, SJ TI Placental mammal diversification and the Cretaceous-Tertiary boundary SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mammalia; molecular clock; placentalia; phylogeny ID MOLECULAR EVIDENCE; EUTHERIAN MAMMALS; FOSSIL RECORD; EVOLUTION; ORIGINS; RADIATION; TIME; PHYLOGENETICS; ECHOLOCATION; TIMESCALE AB Competing hypotheses for the timing of the placental mammal radiation focus on whether extant placental orders originated and diversified before or after the Cretaceous-Tertiary (K/T) boundary. Molecular studies that have addressed this issue suffer from single calibration points, unwarranted assumptions about the molecular clock, and/or taxon sampling that lacks representatives of all placental tal orders. We investigated this problem using the largest available molecular data set for placental mammals, which includes segments of 19 nuclear and three mitochondrial genes for representatives of all extant placental orders. We used the Thorne/Kishino method, which permits simultaneous constraints from the fossil record and allows rates of molecular evolution to vary on different branches of a phylogenetic tree. Analyses that used different sets of fossil constraints , different priors for the base of Placentalia, and different data partitions all support interordinal divergences in the Cretaceous followed by intraordinal diversification mostly after the K/T boundary. Four placental orders show intraordinal diversification that pre-dates the K/T boundary, but only by an average of 10 million years. In contrast to some molecular studies that date the rat-mouse split as old as 46 million years, our results show improved agreement with the fossil record and place this split at 16-23 million years. To test the hypothesis that molecular estimates of Cretaceous divergence times are an artifact of increased body size subsequent to the K/T boundary, we also performed analyses with a "K/T body size" taxon set. In these analyses, interordinal splits remained in the Cretaceous. C1 Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Springer, MS (reprint author), Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. EM mark.springer@ucr.edu RI Eizirik, Eduardo/K-8034-2012 OI Eizirik, Eduardo/0000-0002-9658-0999 NR 47 TC 539 Z9 564 U1 15 U2 94 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1056 EP 1061 DI 10.1073/pnas.0334222100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100053 PM 12552136 ER PT J AU Egland, KA Vincent, JJ Strausberg, R Lee, B Pastan, I AF Egland, KA Vincent, JJ Strausberg, R Lee, B Pastan, I TI Discovery of the breast cancer gene BASE using a molecular approach to enrich for genes encoding membrane and secreted proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EPITHELIAL-CELLS; EXPRESSION; ONCOGENE; PROGRAM AB To identify unknown membrane proteins that could be used as targets for breast and prostate cancer immunotherapies and secreted proteins to be used as diagnostic markers, a cDNA library was generated from membrane-associated polyribosomal RNA derived from four breast cancer cell lines, one normal breast cell line, and a prostate cancer cell line. The membrane-associated polyribosomal cDNA library was subtracted with RNA from normal brain, liver, lung, kidney, and muscle. Of the 15,581 clones sequenced from the subtracted cDNA library, sequences from 10,506 clones map to known genes, but 5,075 sequences, representing 3,181 unique transcripts, are not associated with known genes. As one example, we experimentally investigated expression of a previously uncharacterized breast cancer gene that encodes a secreted protein designated BASE (breast cancer and salivary gland expression). BASE is expressed in many breast cancers but not in essential normal tissues including the five organs used for subtraction. Further analysis of this library should yield additional gene products of use in the diagnosis or treatment of breast or prostate cancer. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Canc Genom Off, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. NR 23 TC 37 Z9 40 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1099 EP 1104 DI 10.1073/pnas.0337425100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100061 PM 12538848 ER PT J AU Michalek, J Collins, RH Durrani, HP Vaclavkova, P Ruff, LE Douek, DC Vitetta, ES AF Michalek, J Collins, RH Durrani, HP Vaclavkova, P Ruff, LE Douek, DC Vitetta, ES TI Definitive separation of graft-versus-leukemia- and graft-versus-host-specific CD4(+) T cells by virtue of their receptor beta loci sequences SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BONE-MARROW TRANSPLANTATION; MYELOID-LEUKEMIA; V-BETA; DISEASE; REPERTOIRE; LYMPHOCYTES; INFUSIONS; RESPONSES; PATIENT; CLONES AB Although graft-versus-host (GVH) disease (GVHD) is usually associated with graft versus leukemia (GVL), GVIL can occur in the absence of clinical GVHD. There is evidence to suggest that GVL and GVH are mediated by different clones of T cells. The objective of this study was to identify the two types of T cells based on their receptor sequences. To this end we used irradiated nonleukemic cells from recipients as stimulator cells in a primary mixed leukocyte reaction (MLR). The activated CD4(+) donor T cells that expressed CD25 were purified by cell sorting. To prepare GVL-specific T cells, alloreactive T cells in the primary MLR were first depleted with an anti-CD25 immunotoxin. The remaining T cells had negligible alloreactivity in a secondary MLR. The allodepleted cells were then stimulated by using purified leukemia cells from the same individual as stimulator cells, and the CD25(+)-activated cells were purified by cell sorting. The GVL- and GVH-specific T cells were analyzed for their T cell receptor (TCR) clonality by using anchored RT-PCR of all the TCRbeta locus complementarity-determining region 3 (CDR3) sequences. By comparing TCRbeta CDR3 sequences from transformed bacterial colonies, we were able to demonstrate that T cells mediating GVH were different from those mediating GVIL in each of the eight HLA-mismatched and one HLA-matched donor/recipient pairs. By using the appropriate TCRbeta CDR3-specific primers and probes, the GVH- and GVL-specific clones were monitored in a recipient undergoing an allogeneic stem cell transplant from her HLA-matched related donor. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Ctr Canc Immunobiol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Bone Marrow Transplant Program, Dallas, TX 75390 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Vitetta, ES (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Ctr Canc Immunobiol, 6000 Harry Hines Blvd, Dallas, TX 75390 USA. NR 33 TC 80 Z9 81 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1180 EP 1184 DI 10.1073/pnas.0337543100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100075 PM 12531922 ER PT J AU Mezey, E Key, S Vogelsang, G Szalayova, I Lange, GD Crain, B AF Mezey, E Key, S Vogelsang, G Szalayova, I Lange, GD Crain, B TI Transplanted bone marrow generates new neurons in human brains SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; STROMAL CELLS DIFFERENTIATE; STEM-CELLS; IN-VIVO; PROGENITOR CELLS; VISUAL-CORTEX; K+ CHANNEL; ADULT MICE; HEPATOCYTES; EXPRESSION AB Adult bone marrow stem cells seem to differentiate into muscle, skin, liver, lung, and neuronal cells in rodents and have been shown to regenerate myocardium, hepatocytes, and skin and gastrointestinal epithelium in humans. Because we have demonstrated previously that transplanted bone marrow cells can enter the brain of mice and differentiate into neurons there, we decided to examine postmortem brain samples from females who had received bone marrow transplants from male donors. The underlying diseases of the patients were lymphocytic leukemia and genetic deficiency of the immune system, and they survived between 1 and 9 months after transplant. We used a combination of immunocytochemistry (utilizing neuron-specific antibodies) and fluorescent in situ hybridization histochemistry to search for Y chromosome-positive cells. In all four patients studied we found cells containing Y chromosomes in several brain regions. Most of them were nonneuronal (endothelial cells and cells in the white matter), but neurons were certainly labeled, especially in the hippocampus and cerebral cortex. The youngest patient (2 years old), who also lived the longest time after transplantation, had the greatest number of donor-derived neurons (7 in 10,000). The distribution of the labeled cells was not homogeneous. There were clusters of Y-positive cells, suggesting that single progenitor cells underwent clonal expansion and differentiation. We conclude that adult human bone marrow cells can enter the brain and generate neurons just as rodent cells do. Perhaps this phenomenon could be exploited to prevent the development or progression of neurodegenerative diseases or to repair tissue damaged by infarction or trauma. C1 NINDS, ISHF, NIH, Bethesda, MD 20892 USA. NIMH, Genet Lab, LOG, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. NINDS, Instrument & Comp Sect, NIH, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NINDS, ISHF, NIH, Bldg 36,3D06, Bethesda, MD 20892 USA. NR 41 TC 398 Z9 442 U1 4 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1364 EP 1369 DI 10.1073/pnas.0336479100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100106 PM 12538864 ER PT J AU Wang, L Liu, H Harvey-White, J Zimmer, A Kunos, G AF Wang, L Liu, H Harvey-White, J Zimmer, A Kunos, G TI Endocannabinoid signaling via cannabinoid receptor 1 is involved in ethanol preference and its age-dependent decline in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GAMMA-S BINDING; NUCLEUS-ACCUMBENS; CB1 RECEPTORS; SYNAPTIC TRANSMISSION; FEEDING-BEHAVIOR; KNOCKOUT MICE; FOOD-INTAKE; RAT-BRAIN; G-PROTEIN; DOPAMINE AB Cannabinoids and ethanol can activate the same reward pathways, which could suggest endocannabinoid involvement in the rewarding effects of ethanol. The high ethanol preference of young (6-10 weeks) C57BL/6J mice is reduced by the cannabinoid receptor 1 (CB1) antagonist SR141716A to levels observed in their CB1 knockout littermates or in old (26-48 weeks) wild-type mice, in both of which ethanol preference is unaffected by SR141716A. Similarly, SR141716A inhibits food intake in food-restricted young, but not old, wild-type mice. There are no age-dependent differences in the tissue levels of the endocannabinoids anandamide and 2-arachidonoylglycerol or the density of CB1 in the hypothalamus, limbic forebrain, amygdala, and cerebellum. CB1-stimulated guanosine 5'-[gamma-thio]triphosphate (GTP[gammaS]) binding is selectively reduced in the limbic forebrain of old compared with young wild-type mice. There is no age-dependent difference in G(i) or G(o) subunit protein expression in the limbic forebrain, and the selective reduction in GTP[gammaS] labeling in tissue from old mice is maintained in a receptor/G protein reconstitution assay by using functional bovine brain G protein. These findings suggest that endocannabinoids acting at CB1 contribute to ethanol preference, and decreased coupling of CB1 to G proteins in the limbic forebrain by mechanisms other than altered receptor or G protein levels may be involved in the age-dependent decline in the appetite for both ethanol and food. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany. RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RI Zimmer, Andreas/B-8357-2009 NR 47 TC 200 Z9 206 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1393 EP 1398 DI 10.1073/pnas.0336351100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100111 PM 12538878 ER PT J AU Bellgowan, PSF Saad, ZS Bandettini, PA AF Bellgowan, PSF Saad, ZS Bandettini, PA TI Understanding neural system dynamics through task modulation and measurement of functional MRI amplitude, latency, and width SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EVENT-RELATED FMRI; TIME-RESOLVED FMRI; INFERIOR PREFRONTAL CORTEX; WORD-LIKE STIMULI; HEMODYNAMIC-RESPONSE; BRAIN ACTIVITY; LEXICAL-DECISION; MENTAL ROTATION; FRONTAL-CORTEX; ACTIVATION AB Estimates of hemodynamic amplitude, delay, and width were combined to investigate system dynamics involved in lexical decision making. Subjects performed a lexical decision task using word and nonword stimuli rotated 0degrees, 60degrees, or 120degrees. Averaged hemodynamic responses to repeated stimulation were fit to a Gamma-variate function convolved with a heavyside function of varying onset and duration to estimate each voxel's activation delay and width. Consistent with prolonged reaction times for the rotated stimuli and nonwords, the motor cortex showed delayed hemodynamic onset for both conditions. Language areas such as the lingual gyrus, middle temporal gyrus, fusiform gyrus, and precuneus all showed delayed hemodynamic onsets to rotated stimuli but not to nonword stimuli. The inferior frontal gyrus showed both increased onset latency for rotated stimuli and a wider hemodynamic response to nonwords, consistent with prolonged processing in this area during the lexical decision task. Phonological processing areas such as superior temporal and angular gyrus showed no delay or width difference for rotated stimuli. These results suggest that phonological routes but not semantic routes to the lexicon can proceed regardless of stimulus orientation. This study demonstrates the utility of estimating hemodynamic delay and width in addition to amplitude allowing for more quantitative measures of brain function such as mental chronometry. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NIMH, Sci & Stat Comp Core, Bethesda, MD 20892 USA. RP Bellgowan, PSF (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI Bandettini, Peter/F-5871-2012 NR 52 TC 71 Z9 72 U1 3 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1415 EP 1419 DI 10.1073/pnas.0337747100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100115 PM 12552093 ER PT J AU Iyer, LM Anantharaman, V Aravind, L AF Iyer, LM Anantharaman, V Aravind, L TI Ancient conserved domains shared by animal soluble guanylyl cyclases and bacterial signaling proteins SO BMC GENOMICS LA English DT Article ID NITRIC-OXIDE SYNTHASE; DEINOCOCCUS-RADIODURANS; SECONDARY STRUCTURE; OXYGEN SENSOR; GGDEF DOMAIN; BOVINE LUNG; GAF DOMAIN; PSI-BLAST; BINDING; PREDICTION AB Background: Soluble guanylyl cyclases (SGCs) are dimeric enzymes that transduce signals downstream of nitric oxide (NO) in animals. They sense NO by means of a heme moiety that is bound to their N-terminal extensions. Results: Using sequence profile searches we show that the N-terminal extensions of the SGCs contain two globular domains. The first of these, the HNOB (Heme NO Binding) domain, is a predominantly alpha-helical domain and binds heme via a covalent linkage to histidine. Versions lacking this conserved histidine and are likely to interact with heme non-covalently. We detected HNOB domains in several bacterial lineages, where they occur fused to methyl accepting domains of chemotaxis receptors or as standalone proteins. The standalone forms are encoded by predicted operons that also contain genes for two component signaling systems and GGDEF-type nucleotide cyclases. The second domain, the HNOB associated (HNOBA) domain occurs between the HNOB and the cyclase domains in the animal SGCs. The HNOBA domain is also detected in bacteria and is always encoded by a gene, which occurs in the neighborhood of a gene for a HNOB domain. Conclusion: The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals. The HNOBA domain functionally interacts with the HNOB domain, and possibly binds a ligand, either in cooperation, or independently of the latter domain. Phyletic profiles and phylogenetic analysis suggest that the HNOB and HNOBA domains were acquired by the animal lineage via lateral transfer from a bacterial source. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Iyer, LM (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 47 TC 100 Z9 103 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD FEB 3 PY 2003 VL 4 AR 5 DI 10.1186/1471-2164-4-5 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 654RK UT WOS:000181509700001 PM 12590654 ER PT J AU Kunkel, TA Pavlov, YI Bebenek, K AF Kunkel, TA Pavlov, YI Bebenek, K TI Functions of human DNA polymerases eta, kappa and iota suggested by their properties, including fidelity with undamaged DNA templates SO DNA REPAIR LA English DT Article; Proceedings Paper CT Workshop on DNA Repair CY OCT 04-07, 2001 CL FALLEN LEAF LAKE, CALIFORNIA DE Y-family DNA polymerases; DNA replication fidelity; somatic hypermutation ID BASE EXCISION-REPAIR; PHOSPHATE LYASE ACTIVITY; CYTIDINE DEAMINASE AID; SOMATIC HYPERMUTATION; XERODERMA-PIGMENTOSUM; ERROR-PRONE; LESION-BYPASS; IN-VITRO; DEPENDENT REPLICATION; THYMINE DIMER AB Human DNA polymerases eta, kappa and iota are template-dependent, Y-family DNA polymerases that have been implicated in translesion DNA synthesis (TLS) in human cells. Here, we briefly review evidence that these exonuclease-deficient polymerases copy undamaged DNA with very low fidelity and unusual error specificity. Based on the base substitution specificity and other biochemical properties of DNA polymerases eta and iota, we consider the possibility that they participate in specialized DNA transactions that repair damaged DNA and/or generate mutations in the variable regions of immunoglobulin genes. Published by Elsevier Science B.V. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 102 TC 98 Z9 103 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD FEB 3 PY 2003 VL 2 IS 2 BP 135 EP 149 AR PII S1568-7864(02)00224-0 DI 10.1016/S1568-7864(02)00224-0 PG 15 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 641WQ UT WOS:000180770400002 PM 12531385 ER PT J AU Fowler, RG White, SJ Koyama, C Moore, SC Dunn, RL Schaaper, RM AF Fowler, RG White, SJ Koyama, C Moore, SC Dunn, RL Schaaper, RM TI Interactions among the Escherichia coli mutT, mutM, and mutY damage prevention pathways SO DNA REPAIR LA English DT Article; Proceedings Paper CT Workshop on DNA Repair CY OCT 04-07, 2001 CL FALLEN LEAF LAKE, CALIFORNIA DE oxidation damage; 8-oxodGTP; 8-oxoguanine; mutators; spontaneous mutations ID FORMAMIDOPYRIMIDINE-DNA GLYCOSYLASE; STATE KINETIC-ANALYSIS; GENERATES G.C->T.A TRANSVERSIONS; STEADY-STATE; REVERSE-TRANSCRIPTASE; NUCLEOTIDE INSERTION; REPLICATION FIDELITY; IONIZING-RADIATION; ENDONUCLEASE-VIII; POLYMERASE-BETA AB We have investigated in detail the interactions between the Escherichia coli mutT, mutM, and mutY error-prevention systems. Jointly, these systems protect the cell against the effects of the oxidative stress product, 8-oxoguanine (8-oxoG), a base analog with ambiguous base-pairing properties, pairing with either A or C during DNA synthesis. mutT mutator strains display a specific increase in A.T --> C.G transversions, while mutM and mutY mutator strains show specific G.C --> T.A increases. To study in more detail the in vivo processing of the various mutational intermediates leading to A.T --> C.G and G.C --> T.A transversions, we analyzed defined A.T --> C.G and G.C --> T.A events in strains containing all possible combinations of these mutator alleles. We report three major findings. First, we do not find evidence that the mutT allele significantly increases G.C --> T.A transversions in either mut(+), mutM, mutY or mutMmutY backgrounds. We interpret this result to indicate that incorporation of 8-oxodGTP opposite template C may not be frequent relative to incorporation opposite template A. Second, we show that mutT-induced A.T --> C.G transversions are significantly reduced in strains carrying mutY and mutMmutY deficiencies suggesting that 8-oxoG, when present in DNA, preferentially mispairs with dATP. Third, the mutY and mutMmutY deficiencies also decrease A.T --> C.G transversions in the muT(+) background, suggesting that, even in the presence of functional MutT protein, A.T --> C.G transversions may still result from 8-oxodGTP misincorporation. (C) 2002 Elsevier Science B.V. All rights reserved. C1 San Jose State Univ, Dept Biol Sci, San Jose, CA 95192 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Fowler, RG (reprint author), San Jose State Univ, Dept Biol Sci, San Jose, CA 95192 USA. NR 61 TC 75 Z9 80 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD FEB 3 PY 2003 VL 2 IS 2 BP 159 EP 173 AR PII S1568-7864(02)00193-3 DI 10.1016/S1568-7864(02)00193-3 PG 15 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 641WQ UT WOS:000180770400004 PM 12531387 ER PT J AU Ladd, PD Wilson, DM Kelley, MR Skalnik, DG AF Ladd, PD Wilson, DM Kelley, MR Skalnik, DG TI Identification of the human HEX1/hExo1 gene promoter and characterization of elements responsible for promoter activity SO DNA REPAIR LA English DT Article; Proceedings Paper CT Workshop on DNA Repair CY OCT 04-07, 2001 CL FALLEN LEAF LAKE, CALIFORNIA DE HEX1/hExo1; electrophoretic mobility shift assay; transient transfection; hematopoiesis; DNA recombination and repair; RAD2 nucleases ID SACCHAROMYCES-CEREVISIAE; MISMATCH REPAIR; DNA-REPLICATION; IN-VIVO; TRANSCRIPTION FACTOR; EXONUCLEASE-I; CROSSING-OVER; RECOMBINATION; EXO1; EXPRESSION AB HEX1/hExo1 is a Class III nuclease of the RAD2 family with 5' to 3' exonuclease and flap structure-specific endonuclease activities. HEX1/hExo1 is expressed at low levels in a wide variety of tissues, but at higher levels in fetal liver and adult bone marrow, suggesting HEX1/hExo1 is important for hematopoietic stem cell development. A putative HEX1/hExo1 promoter fragment extending from -6240 to +1600bp exhibits cell-type specific activity in transient transfection assays. This fragment directs high luciferase reporter gene expression in the hematopoietic cell line K562, chronic myelogenous leukemia cells, but low luciferase expression in the non-hematopoiefic cell line HeLa, human cervical carcinoma cells. Deletion studies identified a fragment spanning -688 to + 1600 bp that exhibits full transcriptional activity while a slightly shorter fragment from -658 to + 1600 bp exhibits significantly decreased promoter activity. In vitro binding assays revealed DNA-binding activities that interact with -687 to -681 bp and -665 to -658 bp elements. Oligonucleotide competition and antibody disruption studies determined that the transcription factor CREB-1 recognizes the -687 to -681 bp element, while transcription factors Sp1 and Sp3 recognize the -665 to -658 bp element. Mutation of either the CREB-1 or Sp1/Sp3 binding sites dramatically reduces HEX1/hExo1 promoter activity and elimination of both elements abolishes promoter activity. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat,Sect Pediat Hematol Oncol, Indianapolis, IN 46202 USA. NIA, Gerontol Res Ctr, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Skalnik, DG (reprint author), Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. FU NCI NIH HHS [CA 76643]; NIEHS NIH HHS [ES 05865, ES 03456]; NINDS NIH HHS [NS 38506] NR 45 TC 3 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD FEB 3 PY 2003 VL 2 IS 2 BP 187 EP 198 AR PII S1568-7864(02)00195-7 DI 10.1016/S1568-7864(02)00195-7 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 641WQ UT WOS:000180770400006 PM 12531389 ER PT J AU Abrami, L Liu, SH Cosson, P Leppla, SH van der Goot, FG AF Abrami, L Liu, SH Cosson, P Leppla, SH van der Goot, FG TI Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process SO JOURNAL OF CELL BIOLOGY LA English DT Article DE anthrax toxin; rafts; microdomains; clustering; protective antigen ID PROTECTIVE ANTIGEN; LETHAL FACTOR; CELL-SURFACE; SERINE PALMITOYLTRANSFERASE; PROTEOLYTIC ACTIVATION; MEMBRANE MICRODOMAINS; ANCHORED PROTEINS; EPITHELIAL-CELLS; EUKARYOTIC CELLS; KINASE-KINASE AB The protective antigen (PA) of the anthrax toxin binds to a cell surface receptor and thereby allows lethal factor (LF) to be taken up and exert its toxic effect in the cytoplasm. Here, we report that clustering of the anthrax toxin receptor (ATR) with heptameric PA or with an antibody sandwich causes its association to specialized cholesterol and glycosphingolipid-rich microdomains of the plasma membrane (lipid rafts). We find that although endocytosis of ATR is slow, clustering it into rafts either via PA heptamerization or using an antibody sandwich is necessary and sufficient to trigger efficient internalization and allow delivery of LF to the cytoplasm. Importantly, altering raft integrity using drugs prevented LF delivery and cleavage of cytosolic MAPK kinases, suggesting that lipid rafts could be therapeutic targets for drugs against anthrax. Moreover, we show that internalization of PA is dynamin and Eps15 dependent, indicating that the clathrin-dependent pathway is the major route of anthrax toxin entry into the cell. The present work illustrates that although the physiological role of the ATR is unknown, its trafficking properties, i.e., slow endocytosis as a monomer and rapid clathrin-mediated uptake on clustering, make it an ideal anthrax toxin receptor. C1 Univ Geneva, Dept Genet & Microbiol, CH-1211 Geneva 4, Switzerland. Univ Geneva, Dept Morphol, CH-1211 Geneva, Switzerland. NIAID, Microbial Pathogenesis Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP van der Goot, FG (reprint author), Univ Geneva, Dept Genet & Microbiol, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. RI van der Goot, Francoise/B-2279-2012; OI van der Goot, Gisou/0000-0002-8522-274X NR 45 TC 322 Z9 334 U1 2 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB 3 PY 2003 VL 160 IS 3 BP 321 EP 328 DI 10.1083/jcb.200211018 PG 8 WC Cell Biology SC Cell Biology GA 643AY UT WOS:000180840800007 PM 12551953 ER PT J AU Liu, XL Adams, A Wildt, KF Aronow, B Feigenbaum, L Bosselut, R AF Liu, XL Adams, A Wildt, KF Aronow, B Feigenbaum, L Bosselut, R TI Restricting Zap70 expression to CD4(+)CD8(+) thymocytes reveals a T cell receptor-dependent proofreading mechanism controlling the completion of positive selection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T cell development; thymus; antigen receptor rearrangement; transgenic trace; adenosine deaminase ID NEGATIVE SELECTION; ANTIGEN RECEPTOR; LINEAGE COMMITMENT; TRANSGENIC MICE; MAP KINASE; INTERLEUKIN-7 RECEPTOR; IN-VIVO; THYMUS; DIFFERENTIATION; REQUIREMENT AB Although T cell receptor (TCR) signals are essential for intrathymic T cell-positive selection, it remains controversial whether they only serve to initiate this process, or whether they are required throughout to promote thymocyte differentiation and survival. To address this issue, we have devised a novel approach to interfere with thymocyte TCR signaling in a developmental stage-specific manner in vivo. We have reconstituted mice deficient for Zap70, a tyrosine kinase required for TCR signaling and normally expressed throughout T cell development, with a Zap70 transgene driven by the adenosine deaminase (ADA) gene enhancer, which is active in CD4(+)CD8(+) thymocytes but inactive in CD4(+) or CD8(+) single-positive (SP) thymocytes. In such mice, termination of Zap70 expression impaired TCR signal transduction and arrested thymocyte development after the initiation, but before the completion, of positive selection. Arrested thymocytes had terminated Rag gene expression and up-regulated TCR and Bcl-2 expression, but failed to differentiate into mature CD4(+) or CD8(+) SP thymocytes, to be rescued from death by neglect or to sustain interleukin 7Ralpha expression. These observations identify a TCR-dependent proofreading mechanism that verifies thymocyte TCR specificity and differentiation choices before the completion of positive selection. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Cincinnnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, NIH, Bldg 10,Room 1B43, Bethesda, MD 20892 USA. RI Aronow, Bruce/F-8438-2012 NR 66 TC 34 Z9 35 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 3 PY 2003 VL 197 IS 3 BP 363 EP 373 DI 10.1084/jem.20021698 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 644XE UT WOS:000180945200010 PM 12566420 ER PT J AU Jerebko, AK Malley, JD Franaszek, M Summers, RM AF Jerebko, AK Malley, JD Franaszek, M Summers, RM TI Multiple neural network classification scheme for detection of colonic polyps in CT colonography data sets SO ACADEMIC RADIOLOGY LA English DT Article DE colon neoplasms, CT; colon neoplasms, diagnosis; computers, diagnostic aid; computers, neural network AB Rationale and Objectives. A new classification system for colonic polyp detection, designed to increase sensitivity and reduce the number of false-positive findings with computed tomographic colonography, was developed and tested in this study. Materials and Methods. The system involves classification by a committee of neural networks (NNs), each using largely distinct subsets of features selected from a general set. Back-propagation NNs trained with the Levenberg-Marquardt algorithm were used as primary classifiers (committee members). The set of features included region density, Gaussian and mean curvature and sphericity, lesion size, colon wall thickness, and the means and standard deviations of all of these values. Subsets of variables were initially selected because of their effectiveness according to training and test sample misclassification rates. The final decision for each case is based on the majority vote across the networks and reflects the weighted votes of all networks. The authors also introduce a smoothed cross-validation method designed to improve estimation of the true misclassification rates by reducing bias and variance. Results. This committee method reduced the false-positive rate by 36%, a clinically meaningful reduction, and improved sensitivity by an average of 6.9% compared with decisions made by any single NN. The overall sensitivity and specificity were 82.9% and 95.3%, respectively, when sensitivity was estimated by means of smoothed cross-validation. Conclusion. The proposed method of using multiple classifiers and majority voting is recommended for classification tasks with large sets of input features, particularly when selected feature subsets may not be equally effective and do not provide satisfactory true- and false-positive rates. This approach reduces variance in estimates of misclassification rates. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 12 TC 58 Z9 60 U1 0 U2 2 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2003 VL 10 IS 2 BP 154 EP 160 DI 10.1016/S1076-6332(03)80039-9 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 640QB UT WOS:000180698500005 PM 12583566 ER PT J AU Boudreau, DM Leveille, SG Gray, SL Black, DJ Guralnik, JM Ferrucci, L LaCroix, AZ AF Boudreau, DM Leveille, SG Gray, SL Black, DJ Guralnik, JM Ferrucci, L LaCroix, AZ TI Risks for frequent antimicrobial-treated infections in postmenopausal women SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE antimicrobial treatment; chronic disease; infections; older women; pharmacy record method; risk factors for infection ID PNEUMONIA; HEALTH; DEPRESSION; SMOKING; DISEASE AB Background and aims: Infections are a major cause of morbidity and mortality in older adults. Little is known about factors that alter the susceptibility to infection in the older population. This study in postmenopausal women examines health-related conditions and behavioral factors that may increase the risk of frequent infections, defined as having, on average, one or more infections per year. Methods: A prospective cohort study with 5 years of follow-up was conducted in 1320 women aged 55 to 80 years. The subjects were Group Health Cooperative of Puget Sound (GHC) enrollees screened for a large fracture prevention trial who also participated in a survey of dietary and supplemental vitamin use. The main outcome, total number of infection events per subject, was derived from a new method of identifying outpatient infections based on the antimicrobial prescription fills recorded in GHC automated pharmacy records. Results: Prevalent lung disease (OR=6.1, 95% CI 2.8-13.4), receiving a prescription for vitamin C (OR=2.1, 95% CI 1.4-3.4), and the second and third tertiles of the Chronic Disease Score (OR=1.7, 95% CI 1.1-2.7 and OR=2.4, 95% CI 1.5-3.9, respectively) were associated with 5 or more antimicrobial-treated infections during follow-up. A body mass index (BMI) of less than 22 kg/m(2) (OR=0.6, 95% CI 0.3-1.0) was suggestive of an association, Conclusions: The study provides new information on risk factors for outpatient infections and raises new questions regarding the susceptibility to frequent infections in older women. In addition, the automated pharmacy record method used in this study offers a low-cost alternative for use in future epidemiologic research. C1 Univ Washington, Sch Pharm, Seattle, WA 98195 USA. HRCA Res & Training Inst, Boston, MA USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. RP Boudreau, DM (reprint author), Grp Hlth Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. FU NIA NIH HHS [K08AG00808-01] NR 23 TC 1 Z9 1 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD FEB PY 2003 VL 15 IS 1 BP 12 EP 18 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 683WD UT WOS:000183173300003 PM 12841413 ER PT J AU Melzer, D Guralnik, JM Brock, D AF Melzer, D Guralnik, JM Brock, D TI Prevalence and distribution of hip and knee joint replacements and hip implants in older Americans by the end of life SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE disability; elderly; hip; hip implants; joint replacement; knee; mobility ID RACIAL-DIFFERENCES; UNITED-STATES; ARTHROPLASTY; DISABILITY; TRENDS; FRACTURES; OUTCOMES; AGE AB Background and aims: Hip and knee replacements have become increasingly common in the older population but the prevalence of these procedures and the potential impact on functioning towards the end of life have not been previously described. The aim of this study was to estimate the rates and distribution of hip and knee joint replacements and hip implants (surgical pins, screws, rods, plates, etc.) in people aged 65 and over who died in the US in 1993, and to measure mobility outcomes during their last year of life. Methods: Data were drawn from the 1993 National Mortality Followback Survey; 7684 deaths in people aged 65 years or over were included. From these data full informant interviews were available for 6586 (86%). Three hundred and forty-four decedents had hip joint replacements, 357 had hip implants, and 102 had knee joint replacements. Replicate methods were used to obtain weighted estimates for all decedents in the 1993 US base population. Results: Of female and male decedents, 15.5% (95% CI: 14.3-16.7) and 6.1% (95% CI: 3.9-8.2), respectively, had received the studied devices. About 80% of these had been implanted more than a year before death. There were large differences in the risks of receiving a hip joint replacement or a hip implant depending on gender, education and race. About 60% of recipients either had no difficulty in getting around their own homes during the lost year of life or had difficulty lasting less than 6 months. Conclusions: Implanted hip and knee devices were common in older people who died in the US in 1993. Large sociodemographic differences in those who received vs those who did not were present at the end of life. While difficulty in walking is the main indication for joint replacements, a majority of those receiving replacements experienced less than 6 months of mobility difficulties in their own homes during the lost year of their lives. C1 Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 2SR, England. NIA, Epidemiol Demog & Biometry Lab, Bethesda, MD 20892 USA. RP Melzer, D (reprint author), Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Forvie Site,Robinson Way, Cambridge CB2 2SR, England. OI Melzer, David/0000-0002-0170-3838 NR 25 TC 25 Z9 25 U1 0 U2 2 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD FEB PY 2003 VL 15 IS 1 BP 60 EP 66 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 683WD UT WOS:000183173300010 PM 12841420 ER PT J AU Schito, ML Goel, A Song, Y Inman, JK Fattah, RJ Rice, WG Turpin, JA Sher, A Appella, E AF Schito, ML Goel, A Song, Y Inman, JK Fattah, RJ Rice, WG Turpin, JA Sher, A Appella, E TI In vivo antiviral activity of novel human immunodeficiency virus type 1 nucleocapsid p7 zinc finger inhibitors in a transgenic murine model SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID PROTEASE INHIBITORS; IN-VITRO; ANTIRETROVIRAL THERAPY; REVERSE TRANSCRIPTION; GENE-EXPRESSION; HIV-1 INFECTION; DNA-SYNTHESIS; MOUSE MODEL; MICE; AZODICARBONAMIDE AB Control of human immunodeficiency virus through the use of inexpensive chemotherapeutics, with minimal side effects and decreased potential for engendering resistant virus, is a long-term therapeutic goal. In principle, this goal can be accomplished if viral replication in reservoirs of chronically and latently infected cells is addressed. As a first step, we have developed novel antiviral compounds based on a 2-mercaptobenzamide thioester chemotype, including the pyridinioalkanoyl thioesters, which specifically target the zinc fingers of the human immunodeficiency virus nucleocapsid protein (NCp7). Using these compounds in a murine transgenic model, in which infectious human immunodeficiency virus is induced from an integrated provirus, we show inhibition of transgenic spleen cell p24 expression with potencies comparable to acute infection assays using human peripheral blood lymphocytes. More importantly, transgenic mice treated in vivo with two 2-mercaptobenzamide thioesters expressed significantly lower plasma p24, and splenocytes from these animals produced fewer infectious virions. Thus, these thioesters may provide an effective means for inhibiting the expression of human immunodeficiency virus from integrated viral reservoirs. C1 NCI, Chem Immunol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Achillon Pharmaceut, New Haven, CT 06510 USA. NIAID, Bioorgan Chem Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. So Res Inst, Infect Dis Res Dept, Frederick, MD 21701 USA. RP Schito, ML (reprint author), NCI, Chem Immunol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 39 TC 26 Z9 28 U1 0 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD FEB PY 2003 VL 19 IS 2 BP 91 EP 101 DI 10.1089/088922203762688595 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 646RL UT WOS:000181048000002 PM 12639244 ER PT J AU Enoch, MA Schuckit, MA Johnson, BA Goldman, D AF Enoch, MA Schuckit, MA Johnson, BA Goldman, D TI Genetics of alcoholism using intermediate phenotypes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholism; anxiety; genes; serotonin transporter; catechol-O-methyltransferase ID EVENT-RELATED POTENTIALS; ANXIETY-RELATED TRAITS; VOLTAGE-ALPHA EEG; SEROTONIN TRANSPORTER; USE DISORDERS; 5-HT3 RECEPTORS; LOW-LEVEL; POLYMORPHISM; DEPENDENCE; GENOTYPE AB This article represents the proceedings of a symposium at the 2002 meeting of the Research Society on Alcoholism in San Francisco, CA. It was organized by Mary-Anne Enoch and David Goldman and chaired by David Goldman. The presentations were (1) Two functional polymorphisms and their intermediate phenotypes in complex behaviors: COMT/executive cognition and anxiety and HTT/anxiety, by David Goldman; (2) Role of the EEG in determining genetic risk for alcoholism and anxiety disorders, by Mary-Anne Enoch; (3) The response to alcohol as an intermediate phenotype for alcoholism, by Marc A. Schuckit; and (4) Pharmacogenomic approaches to alcoholism treatment: toward a hypothesis, by Bankole A. Johnson. C1 NIAAA, DICBR, LNG, Lab Neurogenet,NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Psychiat, Sch Med, San Diego Vet Affairs Med Ctr, San Diego, CA 92103 USA. Univ Texas, Dept Psychiat & Pharmacol, San Antonio, TX 78285 USA. RP Enoch, MA (reprint author), NIAAA, DICBR, LNG, Lab Neurogenet,NIH, 12420 Parklawn Dr,Pk 5 Bldg,Room 451,MSC 8110, Bethesda, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIAAA NIH HHS [AA05526, AA10522-05, AA10522-0551] NR 57 TC 46 Z9 47 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2003 VL 27 IS 2 BP 169 EP 176 DI 10.1097/01.ALC.0000052702.77807.8C PG 8 WC Substance Abuse SC Substance Abuse GA 648VW UT WOS:000181172400003 PM 12605066 ER PT J AU Hasin, DS Schuckit, MA Martin, CS Grant, BF Bucholz, KK Helzer, JE AF Hasin, DS Schuckit, MA Martin, CS Grant, BF Bucholz, KK Helzer, JE TI The validity of DSM-IV alcohol dependence: What do we know and what do we need to know? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dependence; alcohol abuse; validity; reliability; DSM-IV; diagnosis ID SUBSTANCE USE DISORDERS; INTERVIEW SCHEDULE AUDADIS; 5-YEAR CLINICAL COURSE; SAMPLE HEAVY DRINKERS; III-R; ICD-10 ALCOHOL; DRUG MODULES; PSYCHIATRIC-DIAGNOSIS; ADOLESCENT DRINKERS; ABUSE DIAGNOSES AB This article presents the proceedings of a symposium at the 2002 RSA Meeting in San Francisco, California. Deborah S. Hasin organized the symposium and co-chaired it with Marc Schuckit. The purpose of the symposium was to provide an overview of what is known about the validity of DSM-IV and ICD-10 alcohol dependence and abuse, with a focus on work done since 1994. Presentations included: (1) Validity of DSM-III-R alcohol dependence in adolescents, by Christopher S. Martin; (2) Reliability and validity of DSM and ICD formulations of alcohol use disorders: findings from epidemiology, by Bridget F. Grant; (3) Validity and reliability of the alcohol-dependence phenotype in the context of genetic studies, by Kathleen K. Bucholz; and (4) DSM-IV and beyond: uniting the clinical utility of categories with the precision of dimensions, by John E. Helzer. The findings supported the validity of DSM-IV alcohol dependence across numerous study designs and samples, suggested some value in a dimensional dependence measure, and raised questions about the validity of the diagnosis of alcohol abuse as currently defined. Marc Schuckit, as discussant for the symposium, placed the issues in perspective for the upcoming DSM-V. C1 Columbia Univ, New York State Psychiat Inst, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Columbia Univ, Mailman Sch Publ Hlth, Div Epidemiol, New York, NY USA. San Diego VA Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. NIAAA, Div Biometry & Epidemiol, Bethesda, MD USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Vermont, Hlth Behav Res Ctr, Burlington, VT USA. RP Hasin, DS (reprint author), Columbia Univ, New York State Psychiat Inst, 1051 Riverside Dr,Box 123, New York, NY 10032 USA. FU NIAAA NIH HHS [K02 AA00151] NR 59 TC 127 Z9 128 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2003 VL 27 IS 2 BP 244 EP 252 DI 10.1097/01.ALC.0000060878.61384.ED PG 9 WC Substance Abuse SC Substance Abuse GA 648VW UT WOS:000181172400010 PM 12605073 ER PT J AU Hilton, ME Fleming, M Glick, H Gutman, MA Lu, Y McKay, J McLellan, AT Manning, W Meadows, J Mertens, JR Moore, C Mullahy, J Mundt, M Parthasarathy, S Polsky, D Ray, GT Sterling, S Weisner, C AF Hilton, ME Fleming, M Glick, H Gutman, MA Lu, Y McKay, J McLellan, AT Manning, W Meadows, J Mertens, JR Moore, C Mullahy, J Mundt, M Parthasarathy, S Polsky, D Ray, GT Sterling, S Weisner, C TI Services integration and cost-effectiveness SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 25th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 28-JUL 03, 2002 CL SAN FRANCISCO, CALIFORNIA SP Res Soc Alcoholism DE alcohol treatment; services integration; cost effectiveness; health services research; economic methods ID SUBSTANCE-ABUSE TREATMENT; BRIEF PHYSICIAN ADVICE; PROBLEM DRINKERS; DRUG-TREATMENT; MENTAL-HEALTH; ALCOHOL; CARE; INTERVENTIONS; CLIENTS; WOMEN AB Alcohol treatment services are increasingly combined with other health and social services to address the needs of multiple-problem clients. Hence, it has been of growing policy interest to find the most effective and the most cost-effective ways of linking these services. This symposium presents some recent studies in this area. The small but growing body of studies in this area, has great potential to inform public policy debates. C1 NIAAA, Div Clin & Prevent Res, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Family Med, Madison, WI USA. Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Chicago, Dept Hlth Studies, Chicago, IL USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA USA. RP Hilton, ME (reprint author), NIAAA, Div Clin & Prevent Res, 6000 Execut Blvd,Ste 505, Bethesda, MD 20892 USA. FU NIAAA NIH HHS [R01-AA12664, R37-AA10359]; NIDA NIH HHS [R01-DA10572] NR 24 TC 5 Z9 5 U1 5 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2003 VL 27 IS 2 BP 271 EP 280 DI 10.1097/01.ALC.0000052707.99429.8C PG 10 WC Substance Abuse SC Substance Abuse GA 648VW UT WOS:000181172400013 PM 12605076 ER PT J AU Crews, FT Miller, MW Ma, W Nixon, K Zawada, WM Zakhari, S AF Crews, FT Miller, MW Ma, W Nixon, K Zawada, WM Zakhari, S TI Neural stem cells and alcohol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE stem cell proliferation; neural stem cells; alcohol use; transplantation ID RAT CEREBRAL-CORTEX; CENTRAL-NERVOUS-SYSTEM; DENTATE GYRUS; ADULT-RAT; PRENATAL EXPOSURE; PROGENITOR CELLS; DOPAMINERGIC-NEURONS; SUBVENTRICULAR ZONE; RECEPTOR ACTIVATION; ETHANOL EXPOSURE AB This article summarizes the proceedings of a symposium held at the 2002 Research Society on Alcoholism Meeting in San Francisco, California. The aim of this symposium was to review research on the effects of ethanol on neural stems cells and neurogenesis. Ethanol is known to alter neurogenesis during development; however, recent studies indicate that the brain forms new neurons from stem cells throughout life. Furthermore, stem cells can be transplanted into the brain, creating exciting new possibilities to study brain function. The symposium covered these research areas. Dr. Michael W. Miller reviewed knowledge on the effects of ethanol on stem cell proliferation and differentiation during development. Dr. Wu Ma described studies in culture indicating that (1) neural stem cells express functional muscarinic acetylcholine receptors (mAchR), (2) mAchR-mediated proliferation involves Ca2+ signaling and mitogen-activated protein kinase phosphorylation, and (3) phosphoinositol-3 kinase is a downstream effector for mAchR-mediated cell proliferation via activation of Akt. Drs. Kim Nixon and Fulton T. Crews followed with in vivo studies on ethanol's effects on adult neural stem cell proliferation and differentiation. Dr. W. Michael Zawada described studies directed at dopamine neuron cell transplants into mammalian central nervous system. These studies clearly establish that ethanol has significant effects on stem cells. C1 Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. SUNY Upstate Med Univ, Syracuse, NY 13210 USA. USN, Res Lab, Washington, DC 20375 USA. NIAAA, Rockville, MD 20852 USA. NIH, Bethesda, MD 20892 USA. RP Crews, FT (reprint author), Univ N Carolina, Bowles Ctr Alcohol Studies, Thurston Bowles Bldg,B7178, Chapel Hill, NC 27599 USA. NR 128 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2003 VL 27 IS 2 BP 324 EP 335 DI 10.1097/01.ALC.0000042581.46630.C5 PG 12 WC Substance Abuse SC Substance Abuse GA 648VW UT WOS:000181172400019 PM 12605082 ER PT J AU Knatterud, GL White, C Geller, NL Campeau, L Forman, SA Domanski, M Forrester, JS Gobel, FL Herd, JA Hickey, A Hoogwerf, BJ Hunninghake, DB Terrin, ML Rosenberg, Y AF Knatterud, GL White, C Geller, NL Campeau, L Forman, SA Domanski, M Forrester, JS Gobel, FL Herd, JA Hickey, A Hoogwerf, BJ Hunninghake, DB Terrin, ML Rosenberg, Y CA Post CABG Investigators TI Angiographic changes in saphenous vein grafts are predictors of clinical outcomes SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY DISEASE; PROGNOSTIC-SIGNIFICANCE; BYPASS GRAFT; PROGRESSION; EVENTS; ATHEROSCLEROSIS AB Background Previous studies have suggested that angiographic evidence of disease progression in coronary arteries increases the risk of subsequent coronary clinical events. This study ascertained whether patients enrolled in-the Post Coronary Artery Bypass Graft Clinical Trial (POST CABG) who had substantial progression of atherosclerosis in greater than or equal to1 saphenous vein grafts (on the basis of assessment of baseline and follow-up angiograms obtained 4-5 years after study entry), but who had not reported clinical symptoms before follow-up angiography, were at a higher risk of subsequent events than patients who did not have substantial progression of atherosclerosis (decrease greater than or equal to0.6 mm in lumen diameter at site of greatest change from baseline). Methods All 1351 patients enrolled in the trial underwent baseline angiography; only the 961 patients who had follow-up angiography and no coronary events before the follow-up study were included in this analysis. The clinical center staff contacted patients to ascertain the events that had occurred after follow-up angiography (approximately 3.4 years later). Results Sixty-nine patients had died; 870 patients or relatives were interviewed, and 22 patients could not be contacted. Univariable estimates of relative risk associated with substantial progression ranged from 2.2 (P < .001) for cardiovascular death or nonfatal myocardial infarction to 3.3 (P < .001) for revascularization. Multivariable and univariable estimates of risk were similar. Conclusions The findings provide evidence that patients who had substantial progression of atherosclerosis in vein grafts are at an increased risk for subsequent coronary events and suggest that angiographic changes in vein grafts are appropriate surrogate measures for clinical outcomes. C1 Univ Minnesota, Heart Dis Prevent Clin, Minneapolis, MN USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Baylor Coll Med, Houston, TX 77030 USA. Minneapolis Heart Inst Fdn, Minneapolis, MN USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Univ Minnesota, Angiogram Reading Ctr, Minneapolis, MN USA. Maryland Med Res Inst, POST CABG Coordinating Ctr, Baltimore, MD 21210 USA. RP Knatterud, GL (reprint author), Maryland Med Res Inst, POST CABG Coordinating Ctr, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. FU NHLBI NIH HHS [N01-HC-75076] NR 12 TC 13 Z9 13 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD FEB PY 2003 VL 145 IS 2 BP 262 EP 269 DI 10.1067/mhj.2003.113 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647MU UT WOS:000181097500017 PM 12595843 ER PT J AU Parikh, SJ Yanovski, JA AF Parikh, SJ Yanovski, JA TI Calcium intake and adiposity SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review DE calcium; dairy products; body weight; fatty acid synthase; fat absorption ID DIETARY-FAT ABSORPTION; INSULIN-RESISTANCE; BODY-WEIGHT; INTRACELLULAR CALCIUM; PHYSICAL-ACTIVITY; AGOUTI GENE; WOMEN; OBESITY; HYPERTENSION; METABOLISM AB Limited epidemiologic and experimental data support the possibility that dietary calcium intake plays a role in human body weight regulation. The aim of this review was to present the data from human studies that link calcium and dairy intake to body weight, describe the existing evidence for an effect of calcium intake on body weight from animal models of obesity, present evidence of a role for intracellular calcium in the regulation of lipogenesis and lipolysis, elucidate the potential suggested relation between dietary calcium intake and intracellular calcium concentrations, and outline the effects of calcium supplementation on dietary fat absorption. We suggest that these data support the need for large, population-based clinical trials to assess the effects of supplemental calcium and other components of dairy products on human body weight. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Parikh, SJ (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10N262,MSC 1862, Bethesda, MD 20892 USA. FU NICHD NIH HHS [Z01 HD-00641]; NIH HHS [Y2-OD-2067] NR 55 TC 118 Z9 124 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2003 VL 77 IS 2 BP 281 EP 287 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 637LG UT WOS:000180512200002 PM 12540383 ER PT J AU Sun, SS Chumlea, WC Heymsfield, SB Lukaski, HC Schoeller, D Friedl, K Kuczmarski, RJ Flegal, KM Johnson, CL Hubbard, VS AF Sun, SS Chumlea, WC Heymsfield, SB Lukaski, HC Schoeller, D Friedl, K Kuczmarski, RJ Flegal, KM Johnson, CL Hubbard, VS TI Development of bioelectrical impedance analysis prediction equations for body composition with the use of a multicomponent model for use in epidemiologic surveys SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE bioelectrical impedance analysis; prediction equations; total body water; fat-free mass; multicomponent model; epidemiologic surveys ID FAT-FREE MASS; CROSS-VALIDATION; WATER; AGE; CHILDREN; NUTRITION; HEALTH AB Background: Previous studies to develop and validate bioelectrical impedance analysis (BIA) equations to predict body composition were limited by small sample sizes, sex specificity, and reliance on reference methods that use a 2-component model. Objective: This study was designed to develop sex-specific BIA equations to predict total body water (TBW) and fat-free mass (FFM) with the use of a multicomponent model for children and adults. Design: Data from 5 centers were pooled to create a sample of 1474 whites and 355 blacks aged 12-94 y. TBW was measured by dilution, and FFM was estimated with a multicomponent model based on densitometry, isotope dilution, and dual-energy X-ray absorptiometry. Results: The final race-combined TBW prediction equations included stature(2)/resistance and body weight (R-2 = 0.84 and 0.79 and root mean square errors of 3.8 and 2.6 L for males and females, respectively; CV: 8%) and tended to underpredict TBW in black males (2.0 L) and females (1.4 L) and to over-predict TBW in white males (0.5 L) and females (0.3 L). The race-combined FFM prediction equations contained the same independent variables (R-2 = 0.90 and 0.83 and root mean square errors of 3.9 and 2.9 kg for males and females, respectively; CV: approximate to6%) and tended to underpredict FFM in black males (2.1 kg) and females (1.6 kg) and to overpredict FFM in white males (0.4 kg) and females (0.3 kg). Conclusion: These equations have excellent precision and are recommended for use in epidemiologic studies to describe normal levels of body composition. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. NIDDKD, Div Nutr Res, Bethesda, MD 20892 USA. NIH, Div Digest Dis & Nutr, Frederick, MD USA. Mil Med Res & Mat Command, Mil Operat Med Program, Frederick, MD USA. Univ Wisconsin, Madison, WI USA. ARS, USDA, Grand Forks Human Nutr Res Ctr, Grand Forks, ND USA. Columbia Univ, St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY USA. Wright State Univ, Sch Med, Dept Community Hlth, Dayton, OH USA. RP Sun, SS (reprint author), Lifespan Hlth Res Ctr, Dept Community Hlth, 3171 Res Blvd, Kettering, OH 45420 USA. RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X; Friedl, Karl/0000-0002-3134-8427 FU NICHD NIH HHS [HD 12252, HD 13404, HD 27063] NR 36 TC 283 Z9 294 U1 3 U2 16 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2003 VL 77 IS 2 BP 331 EP 340 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 637LG UT WOS:000180512200010 PM 12540391 ER PT J AU Tylavsky, FA Lohman, TG Dockrell, M Lang, T Schoeller, DA Wan, JY F'uerst, T Cauley, TA Nevitt, M Harris, TB AF Tylavsky, FA Lohman, TG Dockrell, M Lang, T Schoeller, DA Wan, JY F'uerst, T Cauley, TA Nevitt, M Harris, TB TI Comparison of the effectiveness of 2 dual-energy X-ray absorptiometers with that of total body water and computed tomography in assessing changes in body composition during weight change SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE body composition; dual-energy X-ray absorptiometry; DXA; computed tomography; weight loss; lean body mass; fat mass; total body water ID FAT-FREE MASS; OBESE WOMEN; CROSS-CALIBRATION; LABELED WATER; PENCIL-BEAM; DEXA; ADULTS; VALIDATION; HYDRATION; VALIDITY AB Background: Little information is available on the assessment of changes in body composition as a function of weight change with the use of the fan beam of dual-energy X-ray absorptiometry (DXA). Objective: The objective was to determine the accuracy of the fan beam of the QDR 4500A densitometer and the pencil beam of the QDR 2000 densitometer in estimating changes in whole-body lean soft tissue mass (LSTMDXA) and fat mass (FM) with weight change. Design: Thirty-seven subjects who lost 5.7 +/- 4.5 kg were measured before and after weight change. Using total body water and computed tomography (CT) of the midthigh, we compared changes in FFMTBW and LSTMCT with changes in LSTMDXA. Results: Overall, compared with TBW, the fan beam gave a larger estimate of change ((x) over bar +/- SD) in LSTM (fan beam - TBW: -0.7 +/- 1.6 kg) than did the pencil beam (pencil beam - TBW: -0.1 +/- 1.6 kg)When the change in LSTM obtained with the fan beam and pencil beam was regressed against the change in FFMTBW, the slope of the line for the fan beam was 0.97 (r(2=) 0.61) and that for the pencil beam was 0.86 (r(2=) 0.61). Regression analysis showed that the results between the 2 units were not interchangeable. For the midthigh region, the change in LSTMCT. was moderately correlated with the change in LSTMDXA, with the fan beam arid pencil beam. Conclusions: The measurement of change in LSTM with the fan and pencil beams provides the same relation to changes in FFM assessed by TBW, but the 2 systems are not interchangeable. C1 NIA, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. SYNARC Inc, San Francisco, CA USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Arizona, Tucson, AZ USA. Univ Tennessee, Memphis, TN USA. RP Tylavsky, FA (reprint author), Dept Prevent Med, 66 N Pauline St,Suite 633, Memphis, TN 38105 USA. RI Lang, Thomas/B-2685-2012; Cauley, Jane/N-4836-2015 OI Lang, Thomas/0000-0002-3720-8038; Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2102, N01-AG-6-2106] NR 31 TC 43 Z9 43 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2003 VL 77 IS 2 BP 356 EP 363 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 637LG UT WOS:000180512200013 PM 12540394 ER PT J AU Booth, SL Broe, KE Gagnon, DR Tucker, KL Hannan, M McLean, RR Daawson-Hughes, B Wilson, PWF Cupples, L Kiel, DP AF Booth, SL Broe, KE Gagnon, DR Tucker, KL Hannan, M McLean, RR Daawson-Hughes, B Wilson, PWF Cupples, L Kiel, DP TI Vitamin K intake and bone mineral density in women and men SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin K intake; bone mineral density; hip; spine; Framingham Heart Study ID SERUM UNDERCARBOXYLATED OSTEOCALCIN; PHYSICAL-ACTIVITY SCALE; HIP FRACTURE; ELDERLY WOMEN; OSTEOPOROSIS; RISK; PASE; VALIDITY; ADULTS; HEALTH AB Background: Low dietary vitamin K intake has been associated with as increased risk of hip fracture in men and women. Few data exist on the association between dietary vitamin K intake and bone mineral density (BMD). Objective: We studied cross-sectional associations between self-reported dietary vitamin K intake and BMD of the hip and spine in men and women aged 29-86 y. Design: BMD was measured at the hip and spine in 1112 men and 1479 women ((x) over bar +/- SD age: 59 +/- 9 y) who participated in the Framingham Heart Study (1996-2000). Dietary and supplemental intakes of vitamin K were assessed with the use of a food-frequency questionnaire. Additional covariates included age, body mass index, smoking status, alcohol use, physical activity score, and menopause status and current estrogen use among the women. Results: Women in the lowest quartile of vitamin K intake ((x) over bar: 70.2 mug/d) had significantly (P less than or equal to 0.005) lower mean (+/-SEM) BMD at the femoral neck (0.854 +/- 0.006 g/cm(2)) and spine (1.140 +/- 0.010 g/cm(2)) than did those in the highest quartile of vitamin K intake ((x) over bar: 309 mug/d): 0.888 +/- 0.006 and 1.190 +/- 0.010 g/cm(2), respectively. These associations remained after potential confounders were controlled for and after stratification by age or supplement use. No significant association was found between dietary vitamin K intake and BMD in men. Conclusions: Low dietary vitamin K intake was associated with low BMD in women, consistent with previous reports that low dietary vitamin K intake: is associated with an increased risk of hip fracture. In contrast, there was no association between dietary vitamin K intake and BMD in men. C1 Tufts Univ, Jean Mayer USDA, HNRCA, Boston, MA 02111 USA. Harvard Univ, Sch Med, Hebrew Rehabil Ctr Aged Res, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Training Inst, Div Aging, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. NHLBI, Framingham, MA USA. RP Booth, SL (reprint author), Tufts Univ, Jean Mayer USDA, HNRCA, 711 Washington St, Boston, MA 02111 USA. RI Tucker, Katherine/A-4545-2010; OI Kiel, Douglas/0000-0001-8474-0310; Tucker, Katherine/0000-0001-7640-662X FU NHLBI NIH HHS [N01-HC-38038]; NIAMS NIH HHS [R01 AR/AG 41398] NR 25 TC 111 Z9 120 U1 1 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2003 VL 77 IS 2 BP 512 EP 516 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 637LG UT WOS:000180512200034 PM 12540415 ER PT J AU Attia, P Phan, GQ Duray, PH Rosenberg, SA AF Attia, P Phan, GQ Duray, PH Rosenberg, SA TI Parathyroid hormone-related protein and hypercalcemia in patients with metastatic melanoma - Case report and review SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE metastatic melanoma; hypercalcemia; parathyroid hormone-related protein; PTH-rP ID HUMORAL HYPERCALCEMIA; MALIGNANT-MELANOMA; CANCER; HYPERPARATHYROIDISM AB Hypercalcemia associated with malignancy has been attributed to osteolytic processes secondary to bony metastases and to humoral factors causing increased bone resorption and decreased renal excretion of calcium. Parathyroid hormone-related protein (PTH-rP) is a humoral factor that has been associated with hypercalcemia in renal cell carcinoma, squamous cell carcinoma, and bladder carcinoma. Hypercalcemia does occur in patients with melanoma; however, few studies have reported on hypercalcemia in these patients, and even fewer have described a direct connection to PTH-rP. We here report a patient with stage IV malignant melanoma presenting with severe hypercalcemia associated with elevated PTH-rP levels. Immunohistochemistry showed strong expression of PTH-rP in biopsy of the patient's subcutaneous masses. In addition, we found a 4.9% incidence of hypercalcemia in 1, 146 consecutive patients treated for metastatic melanoma at the Surgery Branch of the National Cancer Institute between January 1, 1988 and March 31, 2000. Thus, PTH-rP may play a significant role in severe hypercalcemia in patients with metastatic melanoma. The discovery of PTH-rP and relevant literature will also be reviewed. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42,9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 14 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 2003 VL 26 IS 1 BP 42 EP 45 DI 10.1097/00000421-200302000-00009 PG 4 WC Oncology SC Oncology GA 693GK UT WOS:000183708600009 PM 12576923 ER PT J AU Sausville, JE Salloum, RG Sorbara, L Kingma, DW Raffeld, M Kreitman, RJ Imus, PD Venzon, D Stetler-Stevenson, M AF Sausville, JE Salloum, RG Sorbara, L Kingma, DW Raffeld, M Kreitman, RJ Imus, PD Venzon, D Stetler-Stevenson, M TI Minimal residual disease detection in hairy cell leukemia - Comparison of flow cytometric immunophenotyping with clonal analysis using consensus primer polymerase chain reaction for the heavy chain gene SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE hairy cell leukemia; flow cytometry; polymerase chain reaction; PCR ID EXPRESSION; DISORDERS; LYMPHOMAS AB We studied 86 specimens from 24 patients with hairy cell leukemia (HCL) to determine the sensitivity of routine flow cytometry (FC) and consensus primer PCR (cpPCR) in this disease. FC was more sensitive, detecting HCL in 48 (56%) of 86 specimens, while clonal B-cell populations were detected by cpPCR in only 23 (27%) of 86 specimens. FC and cpPCR were both more sensitive than morphologic examination. A positive cpPCR result is associated with higher tumor cell numbers than a negative cpPCR result, as determined by FC (P =.0017). We determined cutoff values for number of tumor cells at which cpPCR is consistently positive. At 6 8 tumor cells per microliter, cpPCR would be expected to be positive in at least 90% of the samples. FC was adequate in 86 cases (100%), while cpPCR was adequate in 74 cases (86%). FC is superior to cpPCR for detecting minimal residual HCL. It is more sensitive and more specific and permits quantitation of tumor cell number. C1 NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Pathol Lab, Canc Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 14 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2003 VL 119 IS 2 BP 213 EP 217 DI 10.1309/G6299513NGLCUB1K PG 5 WC Pathology SC Pathology GA 645EU UT WOS:000180963900006 PM 12579991 ER PT J AU Basso, O Weinberg, CR Baird, DD Wilcox, AJ Olsen, J AF Basso, O Weinberg, CR Baird, DD Wilcox, AJ Olsen, J TI Subfecundity as a correlate of preeclampsia: A study within the Danish National Birth Cohort SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; infertility; longitudinal studies; pre-eclampsia; pregnancy complications ID PREGNANCY-INDUCED HYPERTENSION; NULLIPAROUS WOMEN; RISK; ASSOCIATION; OUTCOMES; TIME; COMPLICATIONS; INFERTILITY; HYPOTHESIS; DISORDERS AB A long interpregnancy interval is associated with preeclampsia. If some women experiencing a long interval between births had difficulty conceiving, subfecundity and preeclampsia may share a common etiology. Therefore, the authors examined the association between subfecundity and preeclampsia. By using interview data collected during the second trimester of pregnancy (1998-2001) from women participating in the Danish National Birth Cohort, they identified 20,034 and 24,698 singleton livebirths to primiparous and multiparous women, respectively, for whom preeclampsia information was available from hospital birth records. Among women with no known hypertension, the authors estimated a higher risk of preeclampsia in those with longer times to pregnancy (TTPs), after adjustment for maternal age, prepregnancy body mass index, and smoking. Compared with primiparas who became pregnant right away (referent category), the risk of preeclampsia increased with TTP and then stabilized for women taking 6 months or longer to conceive, whose risk of preeclampsia increased by 50%. Multiparas also had an increased risk, but only those reporting a TTP longer than 12 months (odds ratio = 2.47, 95% confidence interval: 1.30, 4.69). The authors found that a long TTP was associated with preeclampsia, supporting the hypothesis that some factors delaying clinically recognized conception may also be in a causal pathway for preeclampsia. C1 Aarhus Univ, Danish Epidemiol Sci Ctr, DK-8000 Aarhus C, Denmark. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Basso, O (reprint author), Aarhus Univ, Danish Epidemiol Sci Ctr, Bldg 260,Vennelyst Blvd 6, DK-8000 Aarhus C, Denmark. RI Basso, Olga/E-5384-2010; OI Basso, Olga/0000-0001-9298-4921; Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 35 TC 59 Z9 59 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2003 VL 157 IS 3 BP 195 EP 202 DI 10.1093/aje/kwf194 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 641JF UT WOS:000180741100003 PM 12543618 ER PT J AU Hauptmann, M Mohan, AK Doody, MM Linet, MS Mabuchi, K AF Hauptmann, M Mohan, AK Doody, MM Linet, MS Mabuchi, K TI Mortality from diseases of the circulatory system in radiologic technologists in the United States SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cerebrovascular disorders; cohort studies; medical staff; mortality; myocardial ischemia; radiation ID CORONARY HEART-DISEASE; CANCER; WOMEN; RADIOTHERAPY; RISK AB Although increased mortality from diseases of the circulatory system has been observed in patients treated with radiotherapy, the effects of chronic low-dose radiation exposure are not clear. Among 90,284 US radiologic technologists who responded to a mailed questionnaire during 1983-1989, the authors evaluated mortality from circulatory system diseases through 1997 in relation to job history and work procedures as surrogates for radiation exposure. They used Poisson regression models stratified for sex, race, age, and calendar year and adjusted for smoking, body mass index, alcohol intake, marital status, parity, menopausal status, and history of myocardial infarction. A total of 1,107,100 person-years accrued, and 1,070 subjects died from circulatory system diseases. Relative risks for first employment during 1950-1959, 1940-1949, or before 1940, compared with 1960 and later, were 1.01 (95% confidence interval (CI): 0.78, 1.30), 1.14 (95% CI: 0.86, 1.50), and 1.42 (95% CI: 1.04, 1.94), respectively (trend p < 0.001). For the subset of deaths from cerebrovascular disease (n = 174), the respective relative risks were 0.90 (95% CI: 0.45, 1.78), 1.54 (95% CI: 0.74, 3.23), and 2.40 (95% CI: 1.09, 5.31) (trend p = 0.004), and for deaths from ischemic heart disease (n = 633), the relative risks were 0.98 (95% CI: 0.71, 1.35), 1.00 (95% CI: 0.71, 1.42), and 1.22 (95% CI: 0.81, 1.82) (trend p = 0.026). The relative risks for mortality from circulatory system diseases and the subset of cerebrovascular disease increased significantly with the number of years worked before 1950 (trend p = 0.007 and < 0.001, respectively). The data suggest increased mortality from diseases of the circulatory system with occupational radiation exposure before 1950 when radiation doses were likely high. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hauptmann, M (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-15673, N01-CP-51016, N02-CP-81005, N02-CP-81121] NR 30 TC 54 Z9 63 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2003 VL 157 IS 3 BP 239 EP 248 DI 10.1093/aje/kwf189 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 641JF UT WOS:000180741100009 PM 12543624 ER PT J AU Peck, JD Hulka, BS Savitz, DA Baird, D Poole, C Richardson, BE AF Peck, JD Hulka, BS Savitz, DA Baird, D Poole, C Richardson, BE TI Accuracy of fetal growth indicators as surrogate measures of steroid hormone levels during pregnancy SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE biological markers; birth weight; growth; hormones; placenta; pregnancy ID BREAST-CANCER RISK; MULTIPLE BIRTHS; MATERNAL RISK; CIGARETTE-SMOKING; TESTICULAR CANCER; ESTRADIOL; PLASMA; SERUM; WOMEN; MOTHERS AB This study evaluates the use of fetal growth characteristics as surrogate measures for steroid hormone exposures during pregnancy. The validity of using birth weight, birth length, ponderal index, and placental weight as indicators of pregnancy hormone exposures was assessed using third-trimester serum samples from 568 pregnant women who participated in the Child Health and Development Studies, Berkeley, California (1959-1966). The magnitude of the associations between birth characteristics and hormone concentrations was assessed using geometric means, Pearson's correlations, and linear and logistic regression. Accuracy was evaluated using sensitivity, specificity, and receiver operating characteristic curve analyses. The strongest and most consistent association observed was between birth weight and estriol levels. Despite a positive correlation (r = 0.32) and strong associations with high estriol levels (odds ratio for highest compared with lowest birth weight quartile = 6.63, 95% confidence interval: 3.20, 12.5), the predictive performance of birth weight as a proxy for estriol levels was poor (area under the receiver operating characteristic curve = 0.66, 95% confidence interval: 0.61, 0.71). Likewise, all fetal growth measures revealed little discriminatory ability as indicators of estriol, estrone, estradiol, or progesterone levels. Thus, observed associations with these surrogate measures may not be a reflection of pregnancy hormone exposure and should be interpreted with caution. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Texas A&M Univ, Dept Vet Anat & Publ Hlth, Div Publ Hlth, College Stn, TX USA. RP Peck, JD (reprint author), Texas A&M Univ, Syst Hlth Sci Ctr, Dept Epidemiol & Biostat, Sch Rural Publ Hlth, 3000 Briarcrest Dr,Suite 310, College Stn, TX 77802 USA. OI Baird, Donna/0000-0002-5544-2653 FU NCI NIH HHS [R03 CA 75953]; NICHD NIH HHS [N01HD63258] NR 68 TC 35 Z9 35 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2003 VL 157 IS 3 BP 258 EP 266 DI 10.1093/aje/kwf183 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 641JF UT WOS:000180741100011 PM 12543626 ER PT J AU Groves, FD Boice, JD Gail, MH Beebe, GW AF Groves, FD Boice, JD Gail, MH Beebe, GW TI Re: "Cancer in Korean War Navy technicians: Mortality survey after 40 years" - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Int Epidemiol Inst, Rockville, MD 20850 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA. RP Groves, FD (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2003 VL 157 IS 3 BP 279 EP 279 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 641JF UT WOS:000180741100015 ER PT J AU Mykytyn, K Nishimura, DY Searby, CC Beck, G Bugge, K Haines, HL Cornier, AS Cox, GF Fulton, AB Carmi, R Iannaccone, A Jacobson, SG Weleber, RG Wright, AF Riise, R Hennekam, RCM Luleci, G Berker-Karauzum, S Biesecker, LG Stone, EM Sheffield, VC AF Mykytyn, K Nishimura, DY Searby, CC Beck, G Bugge, K Haines, HL Cornier, AS Cox, GF Fulton, AB Carmi, R Iannaccone, A Jacobson, SG Weleber, RG Wright, AF Riise, R Hennekam, RCM Luleci, G Berker-Karauzum, S Biesecker, LG Stone, EM Sheffield, VC TI Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CHROMOSOME 16Q; OBESITY; DNA; IDENTIFICATION; MUTATIONS; LINKAGE; GENE AB Bardet-Biedl syndrome (BBS) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. Patients with BBS are also at increased risk for diabetes mellitus, hypertension, and congenital heart disease. BBS is known to map to at least six loci: 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although these loci were all mapped on the basis of an autosomal recessive mode of inheritance, it has recently been suggested-on the basis of mutation analysis of the identified BBS2, BBS4, and BBS6 genes-that BBS displays a complex mode of inheritance in which, in some families, three mutations at two loci are necessary to manifest the disease phenotype. We recently identified BBS1, the gene most commonly involved in Bardet-Biedl syndrome. The identification of this gene allows for further evaluation of complex inheritance. In the present study we evaluate the involvement of the BBS1 gene in a cohort of 129 probands with BBS and report 10 novel BBS1 mutations. We demonstrate that a common BBS1 missense mutation accounts for 80% of all BBS1 mutations and is found on a similar genetic background across populations. We show that the BBS1 gene is highly conserved between mice and humans. Finally, we demonstrate that BBS1 is inherited in an autosomal recessive manner and is rarely, if ever, involved in complex inheritance. C1 Univ Iowa, Howard Hughes Med Inst, Dept Pediat, Div Med Genet, Iowa City, IA 52242 USA. Univ Iowa, Dept Ophthalmol, Iowa City, IA 52242 USA. Ponce Sch Med, Dept Biochem, Ponce, PR USA. Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Ben Gurion Univ Negev, Genet Inst, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Soroka Med Ctr, IL-84105 Beer Sheva, Israel. Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Memphis, TN 38163 USA. Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Cent Hosp Hedmark, Dept Ophthalmol, Hamar, Norway. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. Arkdeniz Univ, Dept Med Biol Genet, Antalya, Turkey. NHGRI, NIH, Bethesda, MD 20892 USA. RP Sheffield, VC (reprint author), Univ Iowa, Howard Hughes Med Inst, Dept Pediat, Div Med Genet, Iowa City, IA 52242 USA. RI Karauzum, Sibel/C-4848-2016; Mykytyn, Kirk/E-3723-2011; OI Mykytyn, Kirk/0000-0002-0158-4592; Searby, Charles/0000-0002-8108-8782 FU NCRR NIH HHS [2G12RR03050, G12 RR003050]; NEI NIH HHS [R01 EY011298, R01-EY-11298]; NHLBI NIH HHS [P50 HL055006] NR 20 TC 62 Z9 64 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD FEB PY 2003 VL 72 IS 2 BP 429 EP 437 DI 10.1086/346172 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 640GK UT WOS:000180680000022 PM 12524598 ER PT J AU Weinberg, CR AF Weinberg, CR TI Studying parents and grandparents to assess genetic contributions to early-onset disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; TRANSMISSION TEST; ASSOCIATION; TRIADS; DESIGN AB Suppose DNA is available from affected individuals, their parents, and their grandparents. Particularly for early-onset diseases, maternally mediated genetic effects can play a role, because the mother determines the prenatal environment. The proposed maximum-likelihood approach for the detection of apparent transmission distortion treats the triad consisting of the affected individual and his or her two parents as the outcome, conditioning on grandparental mating types. Under a null model in which the allele under study does not confer susceptibility, either through linkage or directly, and when there are no maternally mediated genetic effects, conditional probabilities for specific triads are easily derived. A log-linear model permits a likelihood-ratio test (LRT) and allows the estimation of relative penetrances. The proposed approach is robust against genetic population stratification. Missing-data methods permit the inclusion of incomplete families, even if the missing person is the affected grandchild, as is the case when an induced abortion has followed the detection of a malformation. When screening multiple markers, one can begin by genotyping only the grandparents and the affected grandchildren. LRTs based on conditioning on grandparental mating types (i.e., ignoring the parents) have asymptotic relative efficiencies that are typically >150% (per family), compared with tests based on parents. A test for asymmetry in the number of copies carried by maternal versus paternal grandparents yields an LRT specific to maternal effects. One can then genotype the parents for only the genes that passed the initial screen. Conditioning on both the grandparents' and the affected grandchild's genotypes, a third log-linear model captures the remaining information, in an independent LRT for maternal effects. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), NIEHS, POB 12233,MD A3-03, Res Triangle Pk, NC 27709 USA. NR 11 TC 19 Z9 19 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD FEB PY 2003 VL 72 IS 2 BP 438 EP 447 DI 10.1086/346171 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 640GK UT WOS:000180680000023 PM 12533786 ER PT J AU Rao, DC Province, MA Leppert, MF Oberman, A Heiss, G Ellison, RC Arnett, DK Eckfeldt, JH Schwander, K Mockrin, SC Hunt, SC AF Rao, DC Province, MA Leppert, MF Oberman, A Heiss, G Ellison, RC Arnett, DK Eckfeldt, JH Schwander, K Mockrin, SC Hunt, SC TI A genome-wide affected sibpair linkage analysis of hypertension: The HyperGEN network SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE linkage; hypertension; genetics ID BLOOD-PRESSURE; FAMILY AB Results are reported here from a genome-wide linkage analysis of hypertension in a large sample of hypertensive (affected) sibpairs (650 African American and 915 white sibpairs) recruited by the HyperGEN Network of the National Heart, Lung and Blood Institute (NHLBI) Family Blood Pressure Program (FBPP). Analysis using MAPMAKER/SIBS suggests one interesting region with a LOD score of 2.08 at 63 cM from the p telomere on chromosome 2 in the African American sibpairs, which may harbor hypertension susceptibility genes. (C) 2003 American Journal of Hypertension, Ltd. C1 Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Univ Utah, Salt Lake City, UT USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Boston Univ, Med Ctr, Prevent Med & Epidemiol Sect, Boston, MA 02215 USA. Univ Minnesota, Hosp & Clin, Div Epidemiol, Minneapolis, MN USA. NHLBI, Bethesda, MD 20892 USA. RP Rao, DC (reprint author), Washington Univ, Sch Med, Div Biostat, 660 S Euclid Ave, St Louis, MO 63110 USA. EM rao@wubios.wustl.edu FU NHLBI NIH HHS [HL54472, HL54515, HL54473, HL54496, HL54509, HL54471, HL54495, HL54497] NR 9 TC 53 Z9 54 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD FEB PY 2003 VL 16 IS 2 BP 148 EP 150 AR PII S0895-7061(02)03247-8 DI 10.1016/S0895-7061(02)03247-8 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 639NN UT WOS:000180636200009 PM 12559683 ER PT J AU Frankenfield, DL Brier, ME Bedinger, MR Milam, RA Eggers, PW Cain, JA Aronoff, GR Frederick, PR AF Frankenfield, DL Brier, ME Bedinger, MR Milam, RA Eggers, PW Cain, JA Aronoff, GR Frederick, PR TI Comparison of urea reduction ratio and hematocrit data reported in different data systems: Results from the Centers for Medicare & Medicaid Services and The Renal Network Inc. SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE urea reduction ratio (URR); hematocrit; Centers for Medicare & Medicaid Services (CMS); The Renal Network Data System (TRNDS); NephTrak; reliability; dialysis adequacy; anemia management AB Background: Urea reduction ratio (URR) and hematocrit values reported on the Centers for Medicare & Medicaid Services (CMS) claims were compared with data from two different databases. Methods: URRs and hematocrits from two different CMS databases (National Claims History and End-Stage Renal Disease Clinical Performance Measures [CPM] Project) and one Network database (The Renal Network Data System [TRNDS]) were compared for October through December 1998 and December 1998, respectively. A sample of records from the regional database was validated by independent chart review. Results: Nationally, the percentage of agreement for patients with URRs of 65% or greater and less than 65% was 94% (kappa, 0.81; 95% confidence interval [CI], 0.80 to 0.83); regionally, the percentage of agreement was 95% (kappa, 0.85; 95% CI, 0.84 to 0.86). Nationally, linear regression of hematocrit values from both data sources yielded r(2)= 0.61 each month and r(2)= 0.70 for average values during the 3-month study period. Nationally, the percentage of agreement for patients with hematocrits of 33% or greater and less than 33% was 84% (kappa similar to 0.66) each month. Regionally, linear regression of monthly hematocrit values from both data sources yielded r(2) = 0.66, and percentage of agreement for patients with hematocrits of 33% or greater and less than 33% was 87% (kappa, 0.71; 95% CI, 0.70 to 0.73). Validation of a sample of records in the TRNDS database resulted in 98% agreement for patients with URRs of 65% or greater and less than 65% and 96% agreement for patients with hematocrits of 33% or greater and less than 33%. Conclusion: Although there is general agreement between clinical variables submitted on the claims and in the CPM Project, some variation exists. Data from either source yield the same information when classifying patients as above or below threshold values. C1 Ctr Medicare & Medicaid Serv, Ctr Beneficiary Choices, Baltimore, MD 21244 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Louisville, Dept Med, Louisville, KY 40292 USA. Renal Network Inc, Indianapolis, IN USA. RP Frankenfield, DL (reprint author), Ctr Medicare & Medicaid Serv, Ctr Beneficiary Choices, Mailstop S3-02-01,7500 Secur Blvd, Baltimore, MD 21244 USA. RI Brier, Michael/B-9805-2013 OI Brier, Michael/0000-0002-5952-9561 NR 6 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2003 VL 41 IS 2 BP 433 EP 441 DI 10.1053/ajkd.2003.50053 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 642EE UT WOS:000180790600020 PM 12552507 ER PT J AU Varkonyi, J Rosenbaum, H Baumann, N MacKenzie, JJ Simon, Z Aharon-Peretz, J Walker, JM Tayebi, N Sidransky, E AF Varkonyi, J Rosenbaum, H Baumann, N MacKenzie, JJ Simon, Z Aharon-Peretz, J Walker, JM Tayebi, N Sidransky, E TI Gaucher disease associated with Parkinsonism: Four further case reports SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Parkinson disease; glucocerebrosidase; enzyme replacement therapy; genotype/phenotype correlation ID SPINAL-CORD COMPRESSION; MUTATIONS; TRAITS; TYPE-1 AB Type 1 Gaucher disease is considered the non-neuronopathic form of this autosomal recessively inherited lysosomal storage disease. We report the simultaneous occurrence of Gaucher disease with parkinsonism in four adult patients. The patients had a relatively early onset of parkinsonian manifestations, and their disease was rapidly progressive and refractory to therapy. Each had a different Gaucher genotype, although four alleles carried the common N370S mutation. No mutations were identified in the genes for parkin or alpha-synuclein. The concurrence of these two phenotypes, both in this series of patients and in others in the literature, suggests a shared pathway, modifier, or other genetic etiology. C1 NIMH, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Dept Internal Med 3, H-1085 Budapest, Hungary. Techn Israel Inst Technol, Rambam Med Ctr, Dept Hematol, Haifa, Israel. Techn Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel. Grp Hosp Pitie Salpetriere, Neurochem Lab, F-75634 Paris, France. Queens Univ, Div Med & Mol Genet, Kingston, ON, Canada. Natl Inst Neurol & Psychiat, Budapest, Hungary. Rambam Med Ctr, Dept Neurol, Haifa, Israel. RP Sidransky, E (reprint author), NIMH, Sect Mol Neurogenet, NIH, 49 Convent Dr,MSC 4405,49-B1EE16, Bethesda, MD 20892 USA. EM sidranse@irp.nimh.nih.gov NR 19 TC 40 Z9 43 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD FEB 1 PY 2003 VL 116A IS 4 BP 348 EP 351 DI 10.1002/ajmg.a.10028 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 670HE UT WOS:000182400800007 PM 12522789 ER PT J AU Levy, LM AF Levy, LM TI MR identification of Chiari pathophysiology by using spatial and temporal CSF flow indices and implications for syringomyelia SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material C1 George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Levy, LM (reprint author), George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. NR 4 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2003 VL 24 IS 2 BP 165 EP 166 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 738UT UT WOS:000186306800001 PM 12591627 ER PT J AU Beck, RW Moke, PS Turpin, AH Ferris, FL Sangiovanni, JP Johnson, CA Birch, EE Chandler, DL Cox, TA Blair, RC Kraker, RT AF Beck, RW Moke, PS Turpin, AH Ferris, FL Sangiovanni, JP Johnson, CA Birch, EE Chandler, DL Cox, TA Blair, RC Kraker, RT TI A computerized method of visual acuity testing: Adaptation of the early treatment of diabetic retinopathy study testing protocol SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID AMBLYOPIA TREATMENT; CHARTS AB PURPOSE: To develop a computerized method of visual acuity testing for clinical research as an alternative to the standard Early Treatment for Diabetic Retinopathy Study (ETDRS) testing protocol, and to evaluate its test-retest reliability and concordance with standard ETDRS testing. DESIGN: Test-retest reliability study. METHODS: Multicenter setting of a study population of 265 patients at three clinical sites. Visual acuity was measured with both the electronic visual acuity testing algorithm (E-ETDRS) and standard ETDRS protocol (S-ETDRS) twice on one eye of each patient. E-ETDRS testing was conducted using the electronic visual acuity tester (EVA), which utilizes a programmed Palm (Palm, Inc, Santa Clara, California, USA) hand-held device communicating with a personal computer and 17-inch monitor at a test distance of 3 meters. RESULTS: For the E-ETDRS protocol, test-retest reliability was high (r = 0.99; with 89% and 98% of retests within 0.1 logMAR and 0.2 logMAR of initial tests, respectively) and comparable with that of S,ETDRS testing (r = 0.99; with 87% and 98% of retests within 0.1 logMAR and 0.2 logMAR of initial test, respectively). The E-ETDRS and S-ETDRS scores were highly correlated (r = 0.96 for initial tests and r = 0.97 for repeat tests). Based on estimates of 95% confidence intervals, a change in visual acuity of 0.2 logMAR (10 letters) from a baseline level is unlikely to be related to measurement variability using either the E,ETDRS or the S-ETDRS visual acuity testing protocol. CONCLUSIONS: The E-ETDRS protocol has high test-retest reliability and good concordance with S-ETDRS testing. The computerized method has advantages over the S-ETDRS testing in electronically capturing the data for each tested letter, requiring only a single distance for testing from 20/12 to 20/800, potentially reducing testing time, and potentially decreasing technician-related bias. (C) 2003 by Elsevier Science Inc. All rights reserved. C1 Jaeb Ctr Hlth Res, Tampa, FL 33613 USA. Curtin Univ, Bentley, WA, Australia. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Devers Eye Inst, Discoveries Sight Res Labs, Portland, OR USA. Retina Fdn SW, Dallas, TX USA. RP Beck, RW (reprint author), Jaeb Ctr Hlth Res, 3010 E 138th Ave,Suite 9, Tampa, FL 33613 USA. RI SanGiovanni, John Paul/A-7605-2008 FU NEI NIH HHS [EY13095] NR 17 TC 225 Z9 228 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2003 VL 135 IS 2 BP 194 EP 205 AR PII S0002-9394(02)01825-1 DI 10.1016/S0002-9394(02)01825-1 PG 12 WC Ophthalmology SC Ophthalmology GA 640VV UT WOS:000180709400011 PM 12566024 ER PT J AU Balaban, RS Bose, S French, SA Territo, PR AF Balaban, RS Bose, S French, SA Territo, PR TI Role of calcium in metabolic signaling between cardiac sarcoplasmic reticulum and mitochondria in vitro SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE adenosine 5 '-triphosphate; energy metabolism; calcium-adenosinetriphosphatase; reduced nicotinamide adenine dinucleotide; porcine heart ID OXIDATIVE-PHOSPHORYLATION; RESPIRATORY CONTROL; CANINE MYOCARDIUM; ENERGY-TRANSFER; PROTEIN-KINASE; HEART-MUSCLE; RAT-HEART; PHOSPHATE; CA2+; WORK AB The role of Ca2+ as a cytosolic signaling molecule between porcine cardiac sarcoplasmic reticulum (SR) ATPase and mitochondrial ATP production was evaluated in vitro. The Ca2+ sensitivity of these processes was determined individually and in a reconstituted system with SR and mitochondria in a 0.5: 1 protein-to-cytochrome aa(3) ratio. The half-maximal concentration (K-1/2) of SR ATPase was 335 nM Ca2+. The ATP synthesis dependence was similar with a K-1/2 of 243 nM for dehydrogenases and 114 nM for overall ATP production. In the reconstituted system, Ca2+ increased thapsigargin-sensitive ATP production (maximum similar to5-fold) with minimal changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH). NADH concentration remained stable despite graded increases in NADH turnover induced over a wide range of Ca2+ concentrations (0 to similar to500 nM). These data are consistent with a balanced activation of SR ATPase and mitochondrial ATP synthesis by Ca2+ that contributes to a homeostasis of energy metabolism metabolites. It is suggested that this balanced activation by cytosolic Ca2+ is partially responsible for the minimal alteration in energy metabolism intermediates that occurs with changes in cardiac workload in vivo. C1 NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Lab Cardiac Energet, NIH, Bldg 10,Rm B1D-416, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 41 TC 40 Z9 41 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 2003 VL 284 IS 2 BP C285 EP C293 DI 10.1152/ajpcell.00129.2002 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 635LK UT WOS:000180400200005 PM 12529248 ER PT J AU Chen, Y McCarron, RM Golech, S Bembry, J Ford, B Lenz, FA Azzam, N Spatz, M AF Chen, Y McCarron, RM Golech, S Bembry, J Ford, B Lenz, FA Azzam, N Spatz, M TI ET-1- and NO-mediated signal transduction pathway in human brain capillary endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Review DE capillary endothelium; endothelin-1; nitric oxide; calcium mobilization; cytoskeleton ID DEPENDENT PROTEIN-KINASE; VASODILATOR-STIMULATED PHOSPHOPROTEIN; SMOOTH-MUSCLE CELLS; NITRIC-OXIDE; CA2+ MOBILIZATION; HUMAN NEUTROPHILS; ACTIN-FILAMENTS; PHOSPHORYLATION; PATHOPHYSIOLOGY; PERMEABILITY AB Previous studies have demonstrated that functional interaction between endothelin (ET)-1 and nitric oxide (NO) involves changes in Ca2+ mobilization and cytoskeleton in human brain microvascular endothelial cells. The focus of this investigation was to examine the possible existence of analogous interplay between these vasoactive substances and elucidate their signal transduction pathways in human brain capillary endothelial cells. The results indicate that ET-1-stimulated Ca2+ mobilization in these cells is dose-dependently inhibited by NOR-1 (an NO donor). This inhibition was prevented by ODQ (an inhibitor of guanylyl cyclase) or Rp-8-CPT-cGMPS (an inhibitor of protein kinase G). Treatment of endothelial cells with 8-bromo-cGMP reduced ET-1-induced Ca2+ mobilization in a manner similar to that observed with NOR-1 treatment. In addition, NOR-1 or cGMP reduced Ca2+ mobilization induced by mastoparan (an activator of G protein), inositol 1,4,5-trisphosphate, or thapsigargin (an inhibitor of Ca2+-ATPase). Interestingly, alterations in endothelial cytoskeleton (actin and vimentin) were associated with these effects. The data indicate for the first time that the cGMP-dependent protein kinase colocalizes with actin. These changes were accompanied by altered levels of phosphorylated vasodilator-stimulated phosphoprotein, which were elevated in endothelial cells incubated with NOR-1 and significantly reduced by ODQ or Rp-8-CPT-cGMPS. The findings indicate a potential mechanism by which the functional interrelationship between ET-1 and NO plays a role in regulating capillary tone, microcirculation, and blood-brain barrier function. C1 USN, Med Res Ctr, Resuscitat Med Dept, Silver Spring, MD 20910 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NIMH, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21287 USA. RP McCarron, RM (reprint author), USN, Med Res Ctr, Resuscitat Med Dept, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. NR 42 TC 30 Z9 35 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 2003 VL 284 IS 2 BP C243 EP C249 DI 10.1152/ajpcell.00305.2002 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 635LK UT WOS:000180400200001 PM 12529247 ER PT J AU Singh, P Lu, X Cobb, S Miller, BT Tarasova, N Varro, A Owlia, A AF Singh, P Lu, X Cobb, S Miller, BT Tarasova, N Varro, A Owlia, A TI Progastrin(1-80) stimulates growth of intestinal epithelial cells in vitro via high-affinity binding sites SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE progastrin-preferring receptors; confocal microscopy; in vitro growth effects; Gly-gastrin ID COLON-CANCER-CELLS; GASTRIN RECEPTORS; ORNITHINE DECARBOXYLASE; EXPRESSION VECTOR; PROTEIN; INVITRO; MICE; PENTAGASTRIN; ABSENCE; LINE AB Proliferation and carcinogenesis of the large intestinal epithelial cells (IEC) cells is significantly increased in transgenic mice that overexpress the precursor progastrin (PG) peptide. It is not known if the in vivo growth effects of PG on IEC cells are mediated directly or indirectly. Full-length recombinant human PG (rhPG(1-80)) was generated to examine possible direct effects of PG on IEC cells. Surprisingly, rhPG (0.1-1.0 nM) was more effective than the completely processed gastrin 17 (G17) peptide as a growth factor. Even though IEC cells did not express CCK1 and CCK2 receptors (-R), fluorescently labeled G17 and Gly-extended G17 (G-Gly) were specifically bound to the cells, suggesting the presence of binding proteins other than CCK1-R and CCK2-R on IEC cells. High-affinity (K-d = 0.5-1.0 nM) binding sites for I-125-rhPG were discovered on IEC cells that demonstrated relative binding affinity for gastrin-like peptides in the order PG greater than or equal to COOH-terminally extended G17 greater than or equal to G-Gly > G17 > *CCK-8 (*significant difference; P < 0.05). In conclusion, our studies demonstrate for the first time direct growth effects of the full-length precursor peptide on IEC cells in vitro that are apparently mediated by the high-affinity PG binding sites that were discovered on these cells. C1 Univ Texas, Dept Anat & Neurosci, Med Branch, Galveston, TX 77555 USA. Elim Pharmaceut, San Francisco, CA 94080 USA. Univ Liverpool, Dept Physiol, Liverpool L69 3BX, Merseyside, England. NCI, Fredericksburg, MD 21702 USA. RP Singh, P (reprint author), Univ Texas, Dept Anat & Neurosci, Med Branch, Galveston, TX 77555 USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 FU NCI NIH HHS [CA-72992, CA-60087] NR 48 TC 44 Z9 44 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD FEB PY 2003 VL 284 IS 2 BP G328 EP G339 DI 10.1152/ajpgi.00351.2002 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 635LM UT WOS:000180400400019 PM 12388191 ER PT J AU Cross, HR Kranias, EG Murphy, E Steenbergen, C AF Cross, HR Kranias, EG Murphy, E Steenbergen, C TI Ablation of PLB exacerbates ischemic injury to a lesser extent in female than male mice: protective role of NO SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE ischemia; energetics; sarcoplasmic reticulum ID NITRIC-OXIDE SYNTHASE; CARDIAC SARCOPLASMIC-RETICULUM; ESTROGEN REPLACEMENT THERAPY; MYOCARDIAL-CONTRACTILITY; GLOBAL-ISCHEMIA; TRANSGENIC MICE; RAT-HEART; PHOSPHOLAMBAN; PHOSPHORYLATION; CALCIUM AB Recent studies suggest a role for phospholamban phosphorylation during ischemia and reperfusion. The role of phospholamban in ischemia was studied by subjecting hearts from male and female wild-type (MWT/FWT) and phospholamban-knockout (MKO/FKO) mice to 20 min of ischemia-40 min of reperfusion while P-31 NMR spectra were acquired. ATP and pH values fell lower during ischemia, and postischemic contractility was less, in MKO and FKO versus WT hearts. After shorter ischemia (15 min), recoveries of contraction, ATP, and pH were greater in FKO than MKO hearts. To examine the role of nitric oxide (NO) synthases (NOS) in the protection in FKO versus MKO hearts, we utilized 1 muM L-NAME, a NOS inhibitor, or 100 muM S-nitroso-N-acetylpenicillamine (SNAP), an NO donor. Recoveries of function, ATP, and pH were less in L-NAME-treated FKO than untreated FKO hearts and greater in SNAP-treated MKO than untreated MKO hearts. In conclusion, phospholamban ablation increased ischemic injury in both males and females; however, female hearts were less susceptible than male hearts. Protection in females was decreased by a NOS inhibitor and mimicked in males by an NO donor, implying that protection was NOS mediated. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. RP Cross, HR (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3712, Durham, NC 27710 USA. FU NCRR NIH HHS [P40RR12358]; NHLBI NIH HHS [HL-26057, HL-37952, HL-52318, HL-64018, R01 HL039752] NR 32 TC 52 Z9 52 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 2003 VL 284 IS 2 BP H683 EP H690 DI 10.1152/ajpheart.00567.2002 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 635LQ UT WOS:000180400800031 PM 12388218 ER PT J AU Verlander, JW Miller, RT Frank, AE Royaux, IE Kim, YH Weiner, ID AF Verlander, JW Miller, RT Frank, AE Royaux, IE Kim, YH Weiner, ID TI Localization of the ammonium transporter proteins RhBG and RhCG in mouse kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE RhB-glycoprotein; RhC-glycoprotein; collecting duct; intercalated cell; principal cell; immunohistochemistry; connecting segment ID CORTICAL COLLECTING DUCT; SACCHAROMYCES-CEREVISIAE; INTERCALATED CELLS; BICARBONATE TRANSPORT; RAT-KIDNEY; PSEUDOHYPHAL DIFFERENTIATION; PLANTS; GENE; SUBPOPULATIONS; IDENTIFICATION AB Ammonia is both produced and transported by renal epithelial cells, and it regulates renal ion transport. Recent studies have identified a family of putative ammonium transporters; mRNA for two members of this family, Rh B-glycoprotein (RhBG) and Rh C-glycoprotein (RhCG), is expressed in the kidney. The purpose of this study was to determine the cellular location of RhBG and RhCG protein in the mouse kidney. We generated RhBG- and RhCG-specific anti-peptide antibodies. Immunoblot analysis confirmed that both proteins were expressed in the mouse kidney. RhBG localization with immunohistochemistry revealed discrete basolateral labeling in the connecting segment (CNT) and in the majority of initial collecting tubule (ICT) and cortical collecting duct (CCD) cells. In the outer medullary collecting duct (OMCD) and inner medullary collecting duct (IMCD) only a subpopulation of cells exhibited basolateral immunoreactivity. Colocalization of RhBG with carbonic anhydrase II, the thiazide-sensitive transporter, and the anion exchangers AE1 and pendrin demonstrated RhBG immunoreactivity in all CNT cells and all CCD and ICT principal cells. In the ICT and CCD, basolateral RhBG immunoreactivity is also present in A-type intercalated cells but not in pendrin-positive CCD intercalated cells. In the OMCD and IMCD, only intercalated cells exhibit RhBG immunoreactivity. Immunoreactivity for a second putative ammonium transporter, RhCG, was present in the apical region of cells with almost the same distribution as RhBG. However, RhCG immunoreactivity was present in all CCD cells, and it was present in outer stripe OMCD principal cells, in addition to OMCD and IMCD intercalated cells. Thus the majority of RhBG and RhCG protein expression is present in the same epithelial cell types in the CNT and collecting duct but with opposite polarity. These findings suggest that RhBG and RhCG may play important and cell-specific roles in ammonium transport and signaling in these regions of the kidney. C1 Univ Florida, Coll Med, Div Nephrol Hypertens & Transplantat, Gainesville, FL 32610 USA. N Florida S Georgia Vet Hlth Syst, Gainesville, FL 32610 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Vet Affairs Med Ctr, Cleveland, OH 44106 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Weiner, ID (reprint author), Univ Florida, Coll Med, Div Nephrol Hypertens & Transplantat, POB 100224, Gainesville, FL 32610 USA. EM WeineID@ufl.edu RI Verlander, Jill/I-5991-2015; Weiner, Irving/G-6333-2016 OI Weiner, Irving/0000-0002-0046-0600 FU NIDDK NIH HHS [R01 DK045788] NR 42 TC 120 Z9 124 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 2003 VL 284 IS 2 BP F323 EP F337 DI 10.1152/ajprenal.00050.2002 PG 15 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 635LL UT WOS:000180400300009 PM 12388412 ER PT J AU Buerger, K Zinkowski, R Teipel, SJ Arai, H DeBernardis, J Kerkman, D McCulloch, C Padberg, F Faltraco, F Goernitz, A Tapiola, T Rapoport, SI Pirttila, T Moller, HJ Hampel, H AF Buerger, K Zinkowski, R Teipel, SJ Arai, H DeBernardis, J Kerkman, D McCulloch, C Padberg, F Faltraco, F Goernitz, A Tapiola, T Rapoport, SI Pirttila, T Moller, HJ Hampel, H TI Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231 SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Differentiation of geriatric major depression from Alzheimer's disease is hampered by overlapping symptoms. Increased CSF concentrations of tau protein phosphorylated at threonine 231 (p-tau(231)) have been suggested as a biomarker for Alzheimer's disease. The authors asked whether p-tau231 levels improve the differential diagnosis between geriatric major depression and Alzheimer's disease. Method: Included were 34 depression subjects, 64 with probable Alzheimer's disease, 17 with possible Alzheimer's disease, and 21 healthy comparison subjects. P-tau(231) concentrations were measured with an enzyme-linked immunosorbent assay. Results: P-tau(231) levels were significantly higher in Alzheimer's disease than in geriatric major depression patients and healthy comparison subjects. For differentiation of probable Alzheimer's disease from major depression, p-tau(231) correctly allocated 87% of subjects. When possible mild Alzheimer's disease was compared to major depression, p-tau(231) correctly allocated 78% of subjects. Conclusions: CSF p-tau(231) should be evaluated as a potential biological marker for differentiation of geriatric depression from Alzheimer's disease. C1 Univ Munich, Dementia Res Sect, D-80336 Munich, Germany. Univ Munich, Memory Clin, Alzheimer Mem Ctr, D-80336 Munich, Germany. Univ Munich, Dept Psychiat, Geriatr Psychiat Branch, D-80336 Munich, Germany. Mol Geriatr Corp, Vernon Hills, IL USA. Tohoku Univ, Sch Med, Dept Geriatr Med, Sendai, Miyagi 980, Japan. Kuopio Univ Hosp, Dept Neurol & Neurosci, SF-70210 Kuopio, Finland. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Buerger, K (reprint author), Univ Munich, Dementia Res Sect, Nussbaumstr 7, D-80336 Munich, Germany. NR 11 TC 56 Z9 61 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2003 VL 160 IS 2 BP 376 EP 379 DI 10.1176/appi.ajp.160.2.376 PG 4 WC Psychiatry SC Psychiatry GA 642DE UT WOS:000180788300028 PM 12562590 ER PT J AU Cain, VS Kington, RS AF Cain, VS Kington, RS TI Investigating the role of racial/ethnic bias in health outcomes SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID SOCIAL-CLASS; DISCRIMINATION; RACISM C1 NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Cain, VS (reprint author), NIH, Off Behav & Social Sci Res, 1 Ctr Dr,Bldg 1,Room 256, Bethesda, MD 20892 USA. EM virginia_cain@nih.gov NR 10 TC 19 Z9 20 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2003 VL 93 IS 2 BP 191 EP 192 DI 10.2105/AJPH.93.2.191 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 641AG UT WOS:000180721000007 PM 12554567 ER PT J AU Fee, E Brown, TM Beatty, RL AF Fee, E Brown, TM Beatty, RL TI A well baby clinic in Indianapolis SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2003 VL 93 IS 2 BP 271 EP 271 DI 10.2105/AJPH.93.2.271 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 641AG UT WOS:000180721000022 PM 12554582 ER PT J AU Glanz, K Croyle, RT Chollette, VY Pinn, VW AF Glanz, K Croyle, RT Chollette, VY Pinn, VW TI Cancer-related health disparities in women SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SOCIOECONOMIC-STATUS; UNITED-STATES; LOS-ANGELES; BREAST; OUTCOMES; RACE/ETHNICITY; POPULATIONS; COLON; RACE AB Objectives. This article synthesizes information about cancer in 9 populations of minority women: Mexican American, Puerto Rican, Cuban American, African American, Asian American, Native Hawaiian, American Samoan, American Indian, and Alaska Native. Methods. Cancer registry data, social indicators, government sources, and published articles were searched for information on the background and cancer experience of these 9 racial/ethnic groups, Results. Approximately 35 million women in these racial/ethnic groups live in the United States, and their numbers are increasing rapidly. Since 1992, incidence rates for major cancer sites have slowed or decreased among these groups, but declines in mortality have not occurred or have been smaller than for Whites. Gaps in early detection have narrowed, but minority women still lag behind Whites. Smoking and obesity remain common in these populations. Conclusions. More culturally appropriate interventions and research are needed, and these efforts must involve the community and raise the quality of health services. C1 Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Glanz, K (reprint author), Univ Hawaii, Canc Res Ctr Hawaii, 1960 East West Rd,Biomed Sci Bldg C-105, Honolulu, HI 96822 USA. NR 28 TC 38 Z9 38 U1 2 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2003 VL 93 IS 2 BP 292 EP 298 DI 10.2105/AJPH.93.2.292 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 641AG UT WOS:000180721000028 PM 12554589 ER PT J AU McLaren, CE Barton, JC Adams, PC Harris, EL Acton, RT Press, N Reboussin, DM McLaren, GD Sholinsky, P Walker, AP Gordeuk, VR Leiendecker-Foster, C Dawkins, FW Eckfeldt, JH Mellen, BG Speechley, M Thomson, E AF McLaren, CE Barton, JC Adams, PC Harris, EL Acton, RT Press, N Reboussin, DM McLaren, GD Sholinsky, P Walker, AP Gordeuk, VR Leiendecker-Foster, C Dawkins, FW Eckfeldt, JH Mellen, BG Speechley, M Thomson, E CA Hemochromatosis Iron Overload Stud TI Hemochromatosis and iron overload screening (HEIRS) study design for an evaluation of 100,000 primary care-based adults SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE genetic screening; hemochromatosis; HFE; iron overload; primary health care ID LONG-TERM SURVIVAL; HEREDITARY HEMOCHROMATOSIS; AFRICAN-AMERICANS; CAUCASIAN POPULATIONS; C282Y MUTATION; HFE GENOTYPES; BLOOD-DONORS; GENE; PREVALENCE; HEALTH AB Background: The HEIRS Study will evaluate the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of hemochromatosis and iron overload in a multiethnic, primary care-based sample of 100,000 adults over a 5-year period. Participants are recruited from 5 Field Centers. Laboratory testing and data management and analysis are performed in a Central Laboratory and Coordinating Center, respectively. Methods: Participants undergo testing for serum iron measures and common mutations of the hemochromatosis gene (HFE) on chromosome 6p and answer questions on demographics, health, and genetic testing attitudes. Participants with elevated values of transferrin saturation and serum ferritin and/or C282Y homozygosity are invited to undergo a comprehensive clinical examination (CCE), as are frequency-matched control subjects. These examinations provide data on personal and family medical history, lifestyle characteristics, physical examination, genetic counseling, and assessment of ethical, legal, and social implications. Primary and secondary causes of iron overload will be distinguished by clinical criteria. Iron overload will be confirmed by quantification of iron stores. Recruiting family members of cases will permit DNA analysis for additional genetic factors that affect iron overload. Results: Of the first 50,520 screened, 51% are white, 24% are African American, 11% are Asian, 11% are Hispanic, and 3% are of other, mixed, or unidentified race; 63% are female and 37% are male. Conclusions: Information from the HEIRS Study will inform policy regarding the feasibility, optimal approach, and potential individual and public health benefits and risks of primary care-based screening for iron overload and hemochromatosis. C1 Univ Calif Irvine, Div Epidemiol, Coll Med, Irvine, CA 92697 USA. So Iron Disorders Ctr, Birmingham, AL USA. London Hlth Sci Ctr, Dept Med, London, ON, Canada. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. Oregon Hlth & Sci Univ, Dept Publ Hlth & Preventat Med, Portland, OR 97201 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Calif Irvine, Coll Med, Div Hematol Oncol, Irvine, CA 92717 USA. Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. Univ Calif Irvine, Coll Med, Dept Pediat, Irvine, CA 92717 USA. Howard Univ, Dept Med, Washington, DC 20059 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Western Ontario, Dept Biostat & Epidemiol, London, ON N6A 3K7, Canada. NHGRI, Bethesda, MD 20892 USA. RP McLaren, CE (reprint author), Univ Calif Irvine, Div Epidemiol, Coll Med, Irvine, CA 92697 USA. FU NCRR NIH HHS [M01-RR10284, M01-RR00827]; NHLBI NIH HHS [N01-HC05191, N01-HC05189, N01-HC05186, N01-HC05185, N01-HC05190, N01-HC05192, N01-HC05188] NR 40 TC 87 Z9 88 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD FEB PY 2003 VL 325 IS 2 BP 53 EP 62 DI 10.1097/00000441-200302000-00001 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 647CC UT WOS:000181073400001 PM 12589228 ER PT J AU Contreras, JL Jenkins, S Eckhoff, DE Hubbard, WJ Lobashevsky, A Bilbao, G Thomas, FT Neville, DM Thomas, JM AF Contreras, JL Jenkins, S Eckhoff, DE Hubbard, WJ Lobashevsky, A Bilbao, G Thomas, FT Neville, DM Thomas, JM TI Stable alpha- and beta-islet cell function after tolerance induction to pancreatic islet allografts in diabetic primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE islet mass; islet transplantation; primates; tolerance ID INSULIN SECRETORY RESERVE; LONG-TERM SURVIVAL; TRANSPLANT RECIPIENTS; GLUCOSE DISAPPEARANCE; RHESUS-MONKEYS; MELLITUS; KIDNEY; ANTI-CD3-IMMUNOTOXIN; PERITRANSPLANT; REVERSAL AB Pancreatic islet transplantation (PIT) is an attractive alternative for type 1 diabetic patients. PIT is not yet an effective clinical reality due in part to early loss of functional islet mass. In addition, current immunosuppressive drugs have toxic effects on islets and increase the risk of morbidity and mortality. Precise and durable alpha- and beta-cell function is essential for the success of PIT. Therefore, it is important to establish whether PIT can produce adequate long-term metabolic control, especially in the absence of chronic immunosuppressive therapy (CIT). In the present study, the stability of functional alpha- and beta-cell mass and metabolic function was assessed in streptozotocin (STZ)-induced diabetic primates following PIT in the absence of CIT. Diabetes was induced in rhesus macaques with STZ, 140mg/kg. Hyperglycemia was reversed rapidly by PIT coupled with a 14-day tolerance induction protocol based on F(Ab)(2)-IT and DSG (n = 7). Two diabetic animals received the tolerance induction protocol without PIT. Acute rejection was presented in three animals at 70, 353 and 353 days post transplant in the tolerance induction protocol, whereas the controls [F(Ab)(2)-IT or DSG alone] showed early 10-day function but all lost islet function by days 15-70. One recipient [F(Ab)(2)-IT or DSGI died euglycemic after a surgical procedure on day 187. At 2 years, three animals studied had a normal FIM evaluated by oral glucose tolerance test, mixed meal test, acute insulin response to glucose, glucose disposal rate, and hyperinsulinemic hypoglycemic clamp. PIT in STZ-induced diabetic primates resulted in restoration of normal alpha- and beta-cell function. Operational tolerance induction was achieved with only peritransplant administration of F(Ab)(2)-IT and DSG sparing the animals from chronic exposure of diabetogenic immunosuppressive drugs. These results offer an exciting new potential for treatment of type 1 diabetes mellitus. C1 Univ Alabama, Dept Surg, Transplant Ctr, Birmingham, AL 35294 USA. Univ Alabama, Gene Therapy Ctr, Birmingham, AL 35294 USA. NIMH, Mol Biol Lab, Bethesda, MD 20800 USA. RP Thomas, JM (reprint author), Univ Alabama, Dept Surg, Transplant Ctr, Birmingham, AL 35294 USA. FU NIDDK NIH HHS [U19-DK57958] NR 39 TC 26 Z9 32 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2003 VL 3 IS 2 BP 128 EP 138 DI 10.1034/j.1600-6143.2003.00031.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 653UD UT WOS:000181454700005 PM 12603208 ER PT J AU Webb, C AF Webb, C TI A complete classification of Darwinian extinction in ecological interactions SO AMERICAN NATURALIST LA English DT Article DE natural selection; evolution; interaction; extinction; bifurcation; adaptive dynamics ID POPULATION-DYNAMICS; CHARACTER DISPLACEMENT; PARASITE VIRULENCE; NATURAL-SELECTION; SELF-EXTINCTION; EVOLUTION; MODELS; COMPETITION; CONSEQUENCES; SPECIATION AB The evolution of a population by individual-level natural selection can result in the population's extinction. Selection causes the spread of phenotypes with higher relative fitness, but at the same time, selection can also indirectly produce changes in the physical, biotic, or genotypical environment through population interactions (e. g., environment modification, interspecific interactions, and genomic conflict). Because fitness is environment dependent, this can cause mean fitness to decrease, resulting in extinction. I call this process "Darwinian extinction." Examples of Darwinian extinction include a variety of dynamics and modes of extinction, but the variation is constrained. I determine the complete classification of possible dynamics and modes of Darwinian extinction due to ecological interactions, using bifurcation theory and models with ecological and evolutionary changes occurring on different timescales. This classification is also extended to extinctions due to interactions within the population. The mode of extinction may be either sudden or gradual (requiring additional stochastic processes), and each mode has specific types of dynamics associated with it. Darwinian extinction is a robust and normal phenomenon, and this reasonably complete classification can help us understand more thoroughly its role in nature. C1 Cornell Univ, Dept Ecol & Evolut, Ithaca, NY 14852 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. EM ctwebb@princeton.edu NR 62 TC 48 Z9 50 U1 0 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0003-0147 EI 1537-5323 J9 AM NAT JI Am. Nat. PD FEB PY 2003 VL 161 IS 2 BP 181 EP U1 DI 10.1086/345858 PG 26 WC Ecology; Evolutionary Biology SC Environmental Sciences & Ecology; Evolutionary Biology GA 648LF UT WOS:000181152300002 PM 12675367 ER PT J AU Gonzalez, JM Rivas, G Minton, AP AF Gonzalez, JM Rivas, G Minton, AP TI Effect of large refractive index gradients on the performance of absorption optics in the Beckman XL-A/I analytical ultracentrifuge: an experimental study SO ANALYTICAL BIOCHEMISTRY LA English DT Article AB An analytical centrifuge cell was modified to detect refraction of light transmitted through the cell caused by refractive index gradients formed by sedimenting solute during centrifugation. Sedimentation velocity and sedimentation equilibrium experiments were carried out in this cell on solutions containing high concentrations of protein and polysaccharide in a Beckman-Coulter XLA analytical ultracentrifuge. Analysis of the results indicates that in the absence of an optical artifact easily recognized as a "black band," the dependence of apparent absorbance upon radial position reported by the instrument may be considered a reliable measure of the solute concentration gradient. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. CSIC, Ctr Invest Biol, Madrid 28006, Spain. RP Minton, AP (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. OI Rivas, German/0000-0003-3450-7478 NR 5 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 1 PY 2003 VL 313 IS 1 BP 133 EP 136 AR PII S0003-2697(02)00434-7 DI 10.1016/S0003-2697(02)00434-7 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 647KZ UT WOS:000181093100018 PM 12576068 ER PT J AU Glanton, CW Hypolite, IO Hshieh, PB Agodoa, LY Yuan, CM Abbott, KC AF Glanton, CW Hypolite, IO Hshieh, PB Agodoa, LY Yuan, CM Abbott, KC TI Factors associated with improved short term survival in obese end stage renal disease patients SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE obesity; body mass index; African American; Caucasian; female; complications; dialysis; USRDS; age; albumin; hemoglobin; weight; cardiovascular disease; human immunodeficiency virus; smoking; cancer ID BODY-MASS INDEX; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; PERITONEAL-DIALYSIS; SERUM CREATININE; HEART-FAILURE; RISK FACTOR; MORTALITY; WOMEN; TRANSPLANTATION AB PURPOSE: In contrast to its role in the general population, obesity, defined as body mass index (BMI) greater than or equal to 30 kg/m(2), has been associated with improved survival in patients with end stage renal disease (ESRD). This apparent benefit has not been explained. METHODS: Using the United States Renal Data System (USRDS), we performed an historical cohort study on 151,027 patients initiated on ESRD therapy between January 1, 1995 and June 30, 1997, who never received renal transplants, and who had information sufficient to calculate BMI. We explored the association of various comorbidities present at the time of dialysis initiation (from HCFA Form 2728) with the presence of obesity by logistic regression, and the association of obesity with patient survival, including specific causes of death, by Cox regression adjusting for factors known to be associated with survival in this population. RESULTS: Obese patients had an unadjusted two-year survival of 68% compared with 58% for non obese patients. Obesity was independently associated with a reduced risk of mortality among chronic dialysis patients (adjusted hazard ratio (AHR) 0.75, 95% confidence interval, 0.72-0.78), after controlling for all comorbidities and risk factors. However, there were significantly adverse interactions among whites (AHR 1.22, 1.14-1.30, across all causes of death) and females (AHR 1.12, 1.04-1.20, entirely due to an increased risk of infectious death). CONCLUSIONS: Obesity in patients presenting with ESRD is associated independently with reduced all cause mortality; however, the relationship is complex and is stronger in African Americans. In addition, subgroup analysis suggests that obesity is associated with increased risk of infectious death in females. Published by Elsevier Science Inc. C1 NIDDK, Off Minor Hlth Res Coordinat, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. RP Abbott, KC (reprint author), 7 Rudis Way, Gaithersburg, MD 20878 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 43 TC 56 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 2003 VL 13 IS 2 BP 136 EP 143 AR PII S1047-2797(02)00251-X DI 10.1016/S1047-2797(02)00251-X PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 643CU UT WOS:000180845000008 PM 12559673 ER PT J AU Zhai, SP Sausville, EA Senderowicz, AM Ando, Y Headlee, D Messmann, RA Arbuck, S Murgo, AJ Melillo, G Fuse, E Figg, WD AF Zhai, SP Sausville, EA Senderowicz, AM Ando, Y Headlee, D Messmann, RA Arbuck, S Murgo, AJ Melillo, G Fuse, E Figg, WD TI Clinical pharmacology and pharmacogenetics of flavopiridol 1-h i.v. infusion in patients with refractory neoplasms SO ANTI-CANCER DRUGS LA English DT Article DE clinical trial; flavopiridol; pharmacogenetics; pharmacokinetics; polymorphism; UDP-glucuronosyltransferases; UGT1A1 ID DEPENDENT KINASE INHIBITOR; BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE; BREAST-CARCINOMA CELLS; ACTIVE METABOLITE; DRUG FLAVOPIRIDOL; GILBERTS-SYNDROME; UGT1A1 PROMOTER; GLUCURONIDATION; IRINOTECAN; POLYMORPHISMS AB A phase I trial of flavopiridol administered as a 1-h Lv. infusion schedule was explored. Fifty-five patients were treated with flavopiridol at doses ranging from 12 to 78 mg/ m(2) daily for 5, 3 and 1 day every 3 weeks. Pharmacokinetic and pharmacodynamic analysis was performed together with analysis of a promoter polymorphism of the UGT1A1 gene. Peak concentrations and areas under the time-concentration curve of flavopiridol were linear within the doses studied. Estimated clearance was 13.8 +/- 4.9 l/h/m(2) (mean +/- SD), volume of distribution at steady-state was 64.9 +/- 43.4 l/m(2) and elimination half-life was 5.2 +/- 4.9h. Forty-nine of the 55 patients were genotyped for the promoter polymorphism. We found five (10%) homozygous and 11 (22%) heterozygous patients for UGT1A1*28, which alters the reference sequence (TA)(6)TAA to the variant (TA)(7)TAA by an extra TA dinucleotide insertion within the TATA box. One patient was heterozygous for the sequence of five TA repeats, (TA)(5)TAA. The remaining 32 patients did not have the UGT1A1*28 allele (homozygous for the reference sequence). Associations of the UGT1A1 promoter genotype with either the pharmacokinetic parameters or diarrhea (occurrence and severity) were not observed in this study. The pharmacogenetic analyses did not support that the UGT1A1 promoter polymorphisim could affect flavopiridol pharmacokinetics; and alter the incidence and severity of diarrhea induced by the drug. Anti-Cancer Drugs 14:125-135 (C) 2003 Lippincott Williams Wilkins. C1 NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Bethesda, MD USA. NCI, Dev Therapeut Program, Clin Trials Unit, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Bldg 10,Rm 5A01,MSC 1910,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 32 TC 17 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD FEB PY 2003 VL 14 IS 2 BP 125 EP 135 DI 10.1097/01.cad.0000054974.31252f7 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 653LX UT WOS:000181438700006 PM 12569299 ER PT J AU Wei, CJ Lei, BF Musser, JM Tu, SC AF Wei, CJ Lei, BF Musser, JM Tu, SC TI Isoniazid activation defects in recombinant Mycobacterium tuberculosis catalase-peroxidase (KatG) mutants evident in InhA inhibitor production SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; DRUG-RESISTANCE; GENE; MUTATIONS; OXIDATION; CHEMOTHERAPY; PURIFICATION; ETHIONAMIDE; KATG(S315T); MECHANISM AB Mycobacterium tuberculosis KatG catalyzes the activation of the antitubercular agent isoniazid to yield an inhibitor targeting enoyl reductase (InhA). However, no firm biochemical link between many KatG variants and isoniazid resistance has been established. In the present study, six distinct KatG variants identified in clinical Mycobacterium tuberculosis isolates resistant to isoniazid were generated by site-directed mutagenesis, and the recombinant mutant proteins (KatG(A110V), KatG(A139P), KatG(S315N) KatG(L619P), KatG(L634F), and KatG(D735A)) were purified and characterized with respect to their catalase-peroxidase activities (in terms of k(cat)/K-m), rates of free-radical formation from isoniazid oxidation, and, moreover, abilities to activate isoniazid. The A110V amino acid replacement did not result in significant alteration of KatG activities except that the peroxidase activity was enhanced. The other mutations, however, resulted in modestly reduced catalase and peroxidase catalytic efficiencies and, for the four mutants tested, significantly lower activities to oxidize isoniazid. Compared to the wild-type enzyme, the ability of the KatG(L634F), KatG(A139P), and KatG(D735A) variants to activate isoniazid decreased by 36%, 76%, and 73%, respectively, whereas the KatG(S315N) and KatG(L619P) variants completely lost their abilities to convert isoniazid into the InhA inhibitor. In addition, the inclusion of exogenous Mn2+ to the isoniazid activation reaction mix significantly improved the ability of wild-type and KatG mutants to produce the InhA inhibitor. C1 Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Tu, SC (reprint author), Univ Houston, Dept Biol & Biochem, 369 Sci & Res 2, Houston, TX 77204 USA. NR 44 TC 50 Z9 53 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2003 VL 47 IS 2 BP 670 EP 675 DI 10.1128/AAC.47.2.670-675.2003 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 639UB UT WOS:000180646800034 PM 12543676 ER PT J AU Callahan, LN Cooney, LW Metzler, DF Rezvani, DF Zhang, J Laughon, B Tseng, C Nasr, M AF Callahan, LN Cooney, LW Metzler, DF Rezvani, DF Zhang, J Laughon, B Tseng, C Nasr, M TI A publicly available database for compounds tested against HIV and other viral pathogens SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 6th International Conference on Antiviral Reasearch CY APR 27-MAY 01, 2003 CL SAVANNAH, GEORGIA SP Int Soc Antiviral Res C1 Cygnus Corp Inc, Rockville, MD 20852 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD FEB PY 2003 VL 57 IS 3 SI SI MA 52 BP A54 EP A54 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 673LM UT WOS:000182582500052 ER PT J AU Gabrielsen, B AF Gabrielsen, B TI Collaboration with the National Cancer Institute (NCI) in the development of antiviral therapeutics. SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 6th International Conference on Antiviral Reasearch CY APR 27-MAY 01, 2003 CL SAVANNAH, GEORGIA SP Int Soc Antiviral Res C1 NCI, Technol Transfer Branch, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD FEB PY 2003 VL 57 IS 3 SI SI MA 166 BP A89 EP A89 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 673LM UT WOS:000182582500168 ER PT J AU Huleihel, M Zalah, L Talyshinsky, M Marquez, VE Agbaria, R AF Huleihel, M Zalah, L Talyshinsky, M Marquez, VE Agbaria, R TI Dynamics of N-methanocarbathymidine antiherpetic activity SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 6th International Conference on Antiviral Reasearch CY APR 27-MAY 01, 2003 CL SAVANNAH, GEORGIA SP Int Soc Antiviral Res C1 Ben Gurion Univ Negev, Inst Appl Biosci, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RI HULEIHEL, MAHMOUD/F-1837-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD FEB PY 2003 VL 57 IS 3 SI SI MA 73 BP A62 EP A62 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 673LM UT WOS:000182582500074 ER PT J AU Roy, CJ Baker, R Washburn, K Bray, M AF Roy, CJ Baker, R Washburn, K Bray, M TI Aerosolized cidofovir is retained in the lung and protects mice against lethal intranasal cowpox virus infection SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 6th International Conference on Antiviral Reasearch CY APR 27-MAY 01, 2003 CL SAVANNAH, GEORGIA SP Int Soc Antiviral Res C1 USA, Med Res Inst Infect Dis, Dept Aerobiol & Prod Evaluat, Ft Detrick, MD 21702 USA. USA, Med Res Inst Infect Dis, Dept Viral Therapeut, Ft Detrick, MD 21702 USA. Stillmeadow Corp, Sugar Land, TX USA. NIAID, OCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD FEB PY 2003 VL 57 IS 3 SI SI MA 128 BP A78 EP A78 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 673LM UT WOS:000182582500129 ER PT J AU Mohan, P Chandra, RS Kleiner, DE Luban, NLC AF Mohan, P Chandra, RS Kleiner, DE Luban, NLC TI An unusual presentation of perinatally transmitted hepatitis C SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article ID CHILDREN AB A unique presentation of perinatally acquired hepatitis C (HCV) with acute jaundice and chronic aggressive liver disease in a previously asymptomatic preadolescent is described. The difficulties in establishing the diagnosis and the importance of confirmatory testing for HCV in cryptogenic liver disease are discussed. C1 George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Pediat Gastroenterol, Washington, DC 20052 USA. George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Nutr, Washington, DC 20052 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Mohan, P (reprint author), Childrens Natl Med Ctr, Dept Gastroenterol & Nutr, 111 Michigan Ave, Washington, DC 20001 USA. OI Kleiner, David/0000-0003-3442-4453 NR 6 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD FEB PY 2003 VL 88 IS 2 BP 160 EP 161 DI 10.1136/adc.88.2.160 PG 2 WC Pediatrics SC Pediatrics GA 641LG UT WOS:000180745800030 PM 12538325 ER PT J AU Kessler, RC Barker, PR Colpe, LJ Epstein, JF Gfroerer, JC Hiripi, E Howes, MJ Normand, SLT Manderscheid, RW Walters, EE Zaslavsky, AM AF Kessler, RC Barker, PR Colpe, LJ Epstein, JF Gfroerer, JC Hiripi, E Howes, MJ Normand, SLT Manderscheid, RW Walters, EE Zaslavsky, AM TI Screening for serious mental illness in the general population SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; PREVALENCE; LIFETIME AB Background: Public Law 102-321 established a block grant for adults with "serious mental illness" (SMI) and required the Substance Abuse and Mental Health Services Administration (SAMHSA) to develop a method to estimate the prevalence of SMI. Methods: Three SMI screening scales were developed for possible use in the SAMHSA National Household Survey on Drug Abuse: the Composite International Diagnostic Interview Short-Form (CIDI-SF) scale, the K10/K6 nonspecific distress scales, and the World Health Organization Disability Assessment Schedule (WHO-DAS). An enriched convenience sample of 155 respondents was administered all screening scales followed by the 12-month Structured Clinical Interview for DSM-IV and the Global Assessment of Functioning (GAF). We defined SMI as any 12-month DSM-IV disorder, other than a substance use disorder, with a GAF score of less than 60. Results: All screening scales were significantly related to SMI. However, neither the CIDI-SF nor the WHO-DAS improved prediction significantly over the K10 or K6 scales. The area under the receiver operating characteristic curve of SMI was 0.854 for K10 and 0.865 for K6. The most efficient screening scale, K6, had a sensitivity (SE) of 0.36 (0.08) and a specificity of 0.96 (0.02) in predicting SMI. Conclusions: The brevity and accuracy of the K6 and K10 scales make them attractive screens for SMI. Routine inclusion of either scale in clinical studies would create an important, and heretofore missing, crosswalk between community and clinical epidemiology. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Substance Abuse & Mental Hlth Serv Adm, Off Appl Studies, Rockville, MD USA. Substance Abuse & Mental Hlth Serv Adm, Div State & Community Syst Dev, Rockville, MD USA. NIMH, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave,Suite 215, Boston, MA 02115 USA. FU NIMH NIH HHS [R01MH49098, KO5 MH00507, R01 MH46376, R01 MH52861] NR 22 TC 1201 Z9 1215 U1 10 U2 95 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 2003 VL 60 IS 2 BP 184 EP 189 DI 10.1001/archpsyc.60.2.184 PG 6 WC Psychiatry SC Psychiatry GA 643RA UT WOS:000180873200009 PM 12578436 ER PT J AU den Heijer, T Geerlings, MI Hofman, A de Jong, FH Launer, LJ Pols, HAP Breteler, MMB AF den Heijer, T Geerlings, MI Hofman, A de Jong, FH Launer, LJ Pols, HAP Breteler, MMB TI Higher estrogen levels are not associated with larger hippocampi and better memory performance SO ARCHIVES OF NEUROLOGY LA English DT Article ID ENDOGENOUS SEX-HORMONES; ALZHEIMERS-DISEASE; REPLACEMENT THERAPY; COGNITIVE FUNCTION; POSTMENOPAUSAL WOMEN; CONTROLLED TRIAL; ROTTERDAM SCAN; OLDER WOMEN; RISK; ESTRADIOL AB Background: Estrogens may prevent cognitive decline and Alzheimer disease. Animal study findings have shown beneficial effects of estrogen on the brain, particularly on the hippocampus, a structure related to memory performance and early Alzheimer disease. Objective: To investigate whether higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes on magnetic resonance imaging and better memory performance. Design and Setting: Cross-sectional analysis within the Rotterdam Scan Study, a population-based study in the Netherlands of elderly subjects who do not have dementia. Participants: Two hundred ten women and 202 men, aged 60 to 90 years, with plasma levels of total estradiol and, in part, 162 women and 149 men also with levels of bioavailable and free estradiol. Main Outcome Measure: Hippocampal volumes on magnetic resonance imaging and memory performance (delayed recall). Results: Women with higher total estradiol levels had smaller hippocampal volumes and poorer memory performance -0.29 mL (95% confidence interval, -0.57 to -0.00) and -0.4 (95% confidence interval, -1.3 to 0.5) fewer words in delayed recall testing for the highest tertile compared with the lowest tertile. Similar inverse associations were found among bioavailable and free estradiol levels, hippocampal volumes, and memory. In men, no association was observed between estradiol levels and hippocampal. volume, but a trend was found for higher levels of total estradiol to be associated with poorer memory performance. Conclusion: Our data do not support the hypothesis that higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes and better memory performance. C1 Erasmus MC, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Univ Utrecht, Ctr Med, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. Natl Inst Aging, NIH, Bethesda, MD USA. RP Breteler, MMB (reprint author), Erasmus MC, Dept Epidemiol & Biostat, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI de Jong, Frank/A-9876-2011; Breteler, Monique /J-5058-2014 OI de Jong, Frank/0000-0003-3578-1065; FU NIMHD NIH HHS [MD817876] NR 41 TC 40 Z9 40 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2003 VL 60 IS 2 BP 213 EP 220 DI 10.1001/archneur.60.2.213 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 644PT UT WOS:000180927900009 PM 12580706 ER PT J AU Chaves, CJ Staroselskaya, I Linfante, I Llinas, R Caplan, LR Warach, S AF Chaves, CJ Staroselskaya, I Linfante, I Llinas, R Caplan, LR Warach, S TI Patterns of perfusion-weighted imaging in patients with carotid artery occlusive disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID HEMODYNAMIC FACTORS; CEREBRAL-ISCHEMIA; DIFFUSION; STENOSIS; STROKE; EMBOLISM AB Background: The importance of hemodynamic factors in the pathophysiology of stroke and transient ischemic attacks in patients with internal carotid artery (ICA) stenosis or occlusion remains controversial. Objective: To investigate whether perfusion-weighted imaging (PWI) could identify pathophysiologically meaningful categories in patients with symptomatic and asymptomatic ICA occlusive disease. Methods: Thirty-eight consecutive patients with occlusion (22 patients) or severe stenosis (16 patients) of the ICA, determined by ultrasonography or magnetic resonance angiography, were identified from the Beth Israel Deaconess Medical Center Stroke Database, Boston, Mass. Thirty-five patients were symptomatic (29 who had strokes and 6 who had transient ischemic attacks) and 3 were asymptomatic. All symptomatic patients underwent PWI within the first 24 hours after symptom onset. The patterns of PWI were analyzed according to the degree of ICA stenosis and the clinical presentation. Results: Three patterns of perfusion abnormalities were identified: extensive hypoperfusion involving the middle cerebral arterial and/or anterior cerebral arterial territories (25 patients), localized perfusion deficits involving predominantly the ipsilateral border zone areas (8 patients), and normal perfusion (5 patients). All 3 patterns were found whether or not the ICA was occluded. Patients who had acute stroke most frequently had extensive perfusion deficits involving 1 or 2 territories while patients who had transient ischemic attacks often had hypoperfusion affecting the border zone regions. All asymptomatic patients had normal perfusion. Conclusions: In our sample the pattern of PWI related to the clinical presentation but not to the degree of ICA disease (occlusive vs severe stenosis). Our study findings add further support to the hypothesis that hypoperfusion is a major contributing factor in the pathophysiology of carotid artery occlusive disease. C1 Lahey Clin Fdn, Stroke Serv, Burlington, MA 01805 USA. Lahey Clin Fdn, Dept Neurol, Burlington, MA 01805 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA. NINDS, NIH, Bethesda, MD USA. RP Chaves, CJ (reprint author), Lahey Clin Fdn, Stroke Serv, Burlington, MA 01805 USA. NR 18 TC 17 Z9 30 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2003 VL 60 IS 2 BP 237 EP 242 DI 10.1001/archneur.60.2.237 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 644PT UT WOS:000180927900012 PM 12580709 ER PT J AU Theodore, WH DeCarli, C Gaillard, WD AF Theodore, WH DeCarli, C Gaillard, WD TI Total cerebral volume is reduced in patients with localization-related epilepsy and a history of complex febrile seizures SO ARCHIVES OF NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; LONG-TERM; HIPPOCAMPAL SCLEROSIS; BRAIN-DAMAGE; CHILDREN; ATROPHY; CONVULSIONS; DURATION; ONSET AB Context: Febrile seizures may lead to later epilepsy. They have been associated with hippocampal atrophy but their effect on total cerebral volume is unknown. Objective: To compare total cerebral volume in patients with mesial temporal lobe epilepsy with and without a history of complex febrile seizures (CFS). Design: Survey. Setting: Epilepsy monitoring center. Subjects: Forty patients with localization-related epilepsy and temporal lobe onset determined by video electroencephalogram and 20 controls. Intervention: Magnetic resonance imaging measurement of cerebral volume. Main Outcome Measure: Total cerebral volume. Results: Patients with a history of CFS had significantly reduced total cerebral volume compared with patients without CFS. In addition, male patients with CFS had significantly lower total cerebral volume than male normal controls. There was no significant difference between patients without CFS, or all patients, and controls. Conclusion: Complex febrile seizures may have a global effect on brain development. C1 Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), Clin Epilepsy Sect, NIH, Bldg 10,Rm 5N-25, Bethesda, MD 20892 USA. RI DeCarli, Charles/B-5541-2009 NR 21 TC 36 Z9 37 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2003 VL 60 IS 2 BP 250 EP 252 DI 10.1001/archneur.60.2.250 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 644PT UT WOS:000180927900014 PM 12580711 ER PT J AU Gottsch, JD Seitzman, GD Margulies, EH Bowers, AL Michels, AJ Saha, S Jun, AS Stark, WJ Liu, SH AF Gottsch, JD Seitzman, GD Margulies, EH Bowers, AL Michels, AJ Saha, S Jun, AS Stark, WJ Liu, SH TI Gene expression in donor corneal endothelium SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INTRACELLULAR PH REGULATION; SERIAL ANALYSIS; CARBONIC-ANHYDRASE; RABBIT; BICARBONATE; EXCHANGE; FRESH; SAGE AB Objective: To report gene expression profiles of normal human corneal endothelium with microarray analysis and serial analysis of gene expression (SAGE). Methods: Corneal endothelium was removed from normal human corneas obtained from eye banks. Total RNA was isolated and SAGE analysis was performed. The same RNA source was used to construct a complementary DNA library that was hybridized to microarrays containing 12558 transcripts. Results: A total of 9530 SAGE tags were sequenced, representing 4724 unique tags. Microarray analysis identified 542 distinct transcripts. A database of human corneal endothelial gene expression was compiled. Of the SAGE tags, 1720 matched known genes, 478 corresponded to expressed sequence tags, and 2526 had no known match to public databases. The 5 most abundantly expressed SAGE tags were cytochrome c oxidase subunit II, adenosine triphosphate synthase F-0 subunit 6, carbonic anhydrase XII, 12S ribosomal RNA, and ferritin, heavy polypeptide 1. Thirty-four percent of the transcripts (n = 1616) were specific to the corneal endothelium, when compared with other publicly available SAGE libraries. The 5 most abundant unique tags were keratin 12, angiopoietinlike factor, annexin A8, and 2 tags with no match to the database. Many endothelial pump function enzymes were confirmed, including several plasma membrane Na+/K+ adenosine triphosphatases and a recently reported bicarbonate transporter. Conclusions: Corneal endothelial gene expression profiles by the current analysis provide an understanding of endothelial metabolism, structure, and function; enable comparisons to diseased endothelium; and provide baseline data that may lead to the discovery of novel endothelial genes. C1 Wilmer Eye Inst, Ctr Corneal Genet, Cornea & External Dis Serv, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Genet Mol Lab, Baltimore, MD 21205 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Gottsch, JD (reprint author), Johns Hopkins Univ Hosp, Wilmer Eye Inst, 600 N Wolfe St, Baltimore, MD 21287 USA. NR 17 TC 31 Z9 31 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 2003 VL 121 IS 2 BP 252 EP 258 PG 7 WC Ophthalmology SC Ophthalmology GA 644AM UT WOS:000180895800013 PM 12583793 ER PT J AU Nagler, RM Baum, BJ AF Nagler, RM Baum, BJ TI Prophylactic treatment reduces the severity of xerostomia following radiation therapy for oral cavity cancer SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; SALIVARY-GLAND FUNCTION; RAT SUBMANDIBULAR-GLAND; NECK-CANCER; INDUCED DAMAGE; IRRADIATION; HEAD; RADIOSENSITIVITY; STIMULATION; PROTECTION C1 Rambam Med Ctr, Dept Oral & Maxillofacial Surg, IL-31096 Haifa, Israel. Rambam Med Ctr, Oral Biochem Lab, IL-31096 Haifa, Israel. Rambam Med Ctr, Salivary Clin, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Fac Med, Haifa, Israel. Gene Therapy & Therapeut Branch, Natl Inst Dent & Cranifacial Res, NIH, Bethesda, MD USA. RP Nagler, RM (reprint author), Rambam Med Ctr, Dept Oral & Maxillofacial Surg, POB 9602, IL-31096 Haifa, Israel. NR 20 TC 38 Z9 40 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 2003 VL 129 IS 2 BP 247 EP 250 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 643CV UT WOS:000180845100020 PM 12578459 ER PT J AU Cassarino, DS Milas, M Folpe, AL AF Cassarino, DS Milas, M Folpe, AL TI Bilateral intrathyroidal lymphoepithelial cysts SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material C1 Emory Univ Hosp, Dept Pathol, Atlanta, GA 30322 USA. Emory Univ Hosp, Dept Surg, Atlanta, GA 30322 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Folpe, AL (reprint author), Emory Univ Hosp, Dept Pathol, 1364 Clifton Rd NE,H-175, Atlanta, GA 30322 USA. NR 3 TC 5 Z9 6 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2003 VL 127 IS 2 BP 251 EP 252 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 646RQ UT WOS:000181048400025 PM 12562250 ER PT J AU Friedman, SL Belsky, J Booth, C Bradley, RE Brownell, CA Campbell, SB Clarke-Stewart, A Hirsh-Pasek, K Houts, RM Huston, A Knoke, B McCartney, K McKenzie, TL Morrison, F Nader, PR O'Brien, M Parke, RD Owen, MT Phillips, D Pianta, R Spieker, S Vandell, DL Robeson, WW Weinraub, M AF Friedman, SL Belsky, J Booth, C Bradley, RE Brownell, CA Campbell, SB Clarke-Stewart, A Hirsh-Pasek, K Houts, RM Huston, A Knoke, B McCartney, K McKenzie, TL Morrison, F Nader, PR O'Brien, M Parke, RD Owen, MT Phillips, D Pianta, R Spieker, S Vandell, DL Robeson, WW Weinraub, M CA NICHHD Study Early Child Care Yo TI Frequency and intensity of activity of third-grade children in physical education SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID HEALTHFUL DIET; SCHOOL; ADOLESCENTS; EXERCISE; STUDENTS; FITNESS; SPARK AB Background: Health recommendations are for pre-adolescent children to have daily school physical education (PE) classes that engage children in moderate to vigorous physical activity at least 50% of class time. Objective: To observe activity of children in PE classes in third grades across 10 different sites. Design: Observational study. Setting: Six hundred eighty-four elementary schools in 10 sites. Subjects: A total of 8.14 children (414 boys, 400 girls; mean age, 9.0 years) enrolled in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. Methods: Each child was observed during I scheduled PE class. Main Outcome Measure: The SOFIT (System for Observing Fitness Instruction Time) observation method, a validated, heart rate observation system, yields levels of activity the child is engaged in as well as the lesson context, type of teacher, and location of the PE class. Results: Children averaged 2.1 PE lessons per week, of 33 minutes each. Only 5.9% of children had daily PE. Children accrued 4.8 very active and 11.9 minutes of moderate to vigorous physical activity per PE lesson, 15.0% and 37.0% of lesson time, respectively. Lesson length and number of minutes per week were similar for boys and girls; however, boys spent proportionately more PE time in very active and moderate to vigorous activity. This resulted in boys having a higher energy expenditure rate than girls. Conclusion: Children observed in this study received 25 min/wk of moderate to vigorous activity in school PE, falling far short of national recommendations. C1 NICHD, Off Extramural Policy, Off Director, Rockville, MD 20852 USA. RP Friedman, SL (reprint author), NICHD, Off Extramural Policy, Off Director, 6100 Execut Blvd,Room 4A01, Rockville, MD 20852 USA. OI Belsky, Jay/0000-0003-2191-2503; Pianta, Robert/0000-0002-6280-8051 NR 26 TC 25 Z9 27 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD FEB PY 2003 VL 157 IS 2 BP 185 EP 190 PG 6 WC Pediatrics SC Pediatrics GA 643DB UT WOS:000180845700013 ER PT J AU Bradley, RH Belsky, J Booth, C Spieker, S Burchinal, M Cox, M Campbell, S Clarke-Stewart, A Friedman, SL Hirsh-Pasek, K Weintraub, M Huston, A Jaeger, E Knoke, B McLeod, L Marshall, N Robeson, W McCartney, K Nader, P O'Brien, M Owen, MT Pianta, R Phillips, D Vandell, DL AF Bradley, RH Belsky, J Booth, C Spieker, S Burchinal, M Cox, M Campbell, S Clarke-Stewart, A Friedman, SL Hirsh-Pasek, K Weintraub, M Huston, A Jaeger, E Knoke, B McLeod, L Marshall, N Robeson, W McCartney, K Nader, P O'Brien, M Owen, MT Pianta, R Phillips, D Vandell, DL CA NICCHD Early Child Care Res Netw TI Child care and common communicable illnesses in children aged 37 to 54 months SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID OTITIS-MEDIA; RISK-FACTORS; RESPIRATORY ILLNESS; YOUNG-CHILDREN; ATTENDANCE; INFECTIONS; CENTERS; HEALTH; ARRANGEMENTS; DISEASE AB Objective: To examine the relationship between experience in child care and communicable illnesses (gastrointestinal tract infection, upper respiratory tract infection, and otitis media) in children aged 37 months to 54 months with particular focus on the effect of entry into child care after age 3 years. Design: Health, child care, and family data were obtained from more than 1100 participants in the National Institute of Child Health and Human Development Study of Early Child Care, a 10-site prospective study that began at birth. Longitudinal logistic regression analyses were performed using each type of communicable illness as the outcome variable, with family, child, and child care variables as predictors in the model. Results: For children aged 37 to 54 months, rates of upper respiratory tract illness, gastrointestinal tract illness, and ear infections were higher in those enrolled in child care arrangements with more than 6 children. During this period, children with experience in large-group care prior to age 3 years were less likely to be ill than children who entered child care for the first time after age 3 years. Even so, their rates were still higher than for those in small-group care or who were cared for at home between the ages of 37 and 54 months. Reported rates of respiratory tract and gastrointestinal tract illnesses were higher for European American than African American children. Number of hours per week in child care was not a factor. Conclusion: Children in child care arrangements with more than 6 other children experience more bouts of upper respiratory tract illness between the ages of 37 and 54 months. C1 NICHD, Early Child Care Res Network, CRMC, Rockville, MD 20852 USA. RP Bradley, RH (reprint author), NICHD, Early Child Care Res Network, CRMC, 6100 Execut Blvd,4B05, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012; OI McLeod, Lori/0000-0002-7837-8033; Marshall, Nancy L/0000-0002-4799-2030; Belsky, Jay/0000-0003-2191-2503; Pianta, Robert/0000-0002-6280-8051 NR 28 TC 45 Z9 45 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD FEB PY 2003 VL 157 IS 2 BP 196 EP 200 PG 5 WC Pediatrics SC Pediatrics GA 643DB UT WOS:000180845700015 PM 12580692 ER PT J AU Barter, PJ Brewer, HB Chapman, MJ Hennekens, CH Rader, DJ Tall, AR AF Barter, PJ Brewer, HB Chapman, MJ Hennekens, CH Rader, DJ Tall, AR TI Cholesteryl ester transfer protein - A novel target for raising HDL and inhibiting atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE HDL; LDL; reverse cholesterol transport; genetic CETP deficiency ID HIGH-DENSITY-LIPOPROTEINS; CORONARY HEART-DISEASE; APOLIPOPROTEIN-A-I; TRANSGENIC MICE; TAQIB POLYMORPHISM; MYOCARDIAL-INFARCTION; STANISLAS-COHORT; CETP GENE; PLASMA; DEFICIENCY AB Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from antiatherogenic HDLs to proatherogenic apolipoprotein B (apoB)-containing lipoproteins, including VLDLs, VLDL remnants, IDLs, and LDLs. A deficiency of CETP is associated with increased HDL levels and decreased LDL levels, a profile that is typically antiatherogenic. Studies in rabbits, a species with naturally high levels of CETP, support the therapeutic potential of CETP inhibition as an approach to retarding atherogenesis. Studies in mice, a species that lacks CETP activity, have provided mixed results. Human subjects with heterozygous CETP deficiency and an HDL cholesterol level >60 mg/dL have a reduced risk of coronary heart disease. Evidence that atherosclerosis may be increased in CETP-deficient subjects whose HDL levels are not increased is difficult to interpret and may reflect confounding or bias. Small-molecule inhibitors of CETP have now been tested in human subjects and shown to increase the concentration of HDL cholesterol while decreasing that of LDL cholesterol and apoB. Thus, it seems important and timely to test the hypothesis in randomized trials of humans that pharmacological inhibition of CETP retards the development of atherosclerosis. C1 Royal Adelaide Hosp, Hanson Inst, Adelaide, SA 5000, Australia. Royal Adelaide Hosp, Dept Cardiol, Adelaide, SA 5000, Australia. NHLBI, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth & Med Res, Paris, France. Hop Pitie, F-75651 Paris, France. Univ Penn, Med Ctr, Prevent Cardiol & Lipid Clin, Philadelphia, PA 19104 USA. Univ Miami, Sch Med, Mt Sinai Med Ctr, Miami Heart Inst, Miami, FL USA. Univ Miami, Sch Med, Dept Med & Epidemiol, Miami, FL USA. Univ Miami, Sch Med, Dept Publ Hlth, Miami, FL USA. Columbia Univ, Dept Med, Div Mol Med, New York, NY USA. RP Barter, PJ (reprint author), Heart Res Inst, 145 Missenden Rd, Sydney, NSW 2050, Australia. NR 65 TC 441 Z9 461 U1 6 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2003 VL 23 IS 2 BP 160 EP 167 DI 10.1161/01.ATV.0000054658.91146.64 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 648TD UT WOS:000181165900005 PM 12588754 ER PT J AU Memarzadeh, F Manning, A AF Memarzadeh, F Manning, A TI Reducing risks of surgery SO ASHRAE JOURNAL LA English DT Article ID AIR-FLOW C1 NIH, Off Res Serv, Div Engn Serv, Bethesda, MD 20892 USA. Flomer Inc, Southborough, MA USA. RP Memarzadeh, F (reprint author), NIH, Off Res Serv, Div Engn Serv, Bldg 10, Bethesda, MD 20892 USA. NR 16 TC 17 Z9 17 U1 1 U2 1 PU AMER SOC HEATING REFRIGERATING AIR-CONDITIONING ENG, INC, PI ATLANTA PA 1791 TULLIE CIRCLE NE, ATLANTA, GA 30329 USA SN 0001-2491 J9 ASHRAE J JI ASHRAE J. PD FEB PY 2003 VL 45 IS 2 BP 28 EP 33 PG 6 WC Thermodynamics; Construction & Building Technology; Engineering, Mechanical SC Thermodynamics; Construction & Building Technology; Engineering GA 643HH UT WOS:000180855500010 ER PT J AU Rosen, VM Caplan, L Sheesley, L Rodriguez, R Grafman, J AF Rosen, VM Caplan, L Sheesley, L Rodriguez, R Grafman, J TI An examination of daily activities and their scripts across the adult lifespan SO BEHAVIOR RESEARCH METHODS INSTRUMENTS & COMPUTERS LA English DT Article ID OLDER ADULTS; MEMORY; REPRESENTATION; KNOWLEDGE; SEQUENCE; YOUNG AB In two normative studies, we examined daily scripted activities from the perspective that scripts are frequency-based knowledge structures. In Study 1, individuals recorded their daily activities for 7 consecutive days. Fifteen activities that were reported with low, moderate, and high frequency were selected for Study 2, in which individuals generated a script for each activity. The 18 most frequently generated events from each script are reported, along with their centrality and distinctiveness rankings and the number of individuals reporting each event. Overall, the mean number of events generated increased with increasing script frequency, suggesting that script representations are subject to frequency effects. Also, we found a high level of consistency across the three age groups in the events generated in each script and in their corresponding rankings of centrality and distinctiveness. Finally, we found no evidence of age or gender bias in the frequency or recency of engaging in each of the scripted activities. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Rosen, VM (reprint author), NIMH, Geriatr Psychiat Branch, 10 Ctr Dr,Bldg 10,Room 3N228, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 21 TC 26 Z9 26 U1 1 U2 3 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0743-3808 J9 BEHAV RES METH INS C JI Behav. Res. Methods Instr. Comput. PD FEB PY 2003 VL 35 IS 1 BP 32 EP 48 DI 10.3758/BF03195495 PG 17 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA 662WE UT WOS:000181971400004 PM 12723778 ER PT J AU Tagamets, MA Horwitz, B AF Tagamets, MA Horwitz, B TI Synchronous dynamics for cognitive coordination: But how? SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Although interesting, the hypotheses proposed by Phillips & Silverstein lack unifying structure both in specific mechanisms and in cited evidence. They provide little to support the notion that low-level sensory processing and high-level cognitive coordination share dynamic grouping by synchrony as a common processing mechanism, We suggest that more realistic large-scale modeling at multiple levels is needed to address these issues. C1 Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Funct Neuroimaging Lab, Baltimore, MD 21227 USA. NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. RP Tagamets, MA (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Funct Neuroimaging Lab, Baltimore, MD 21227 USA. EM mtagamet@mprc.umaryland.edu; horwitzb@nidcd.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD FEB PY 2003 VL 26 IS 1 BP 106 EP + PG 15 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 836QB UT WOS:000222569500059 ER PT J AU Wrenn, CC Harris, AP Saavedra, MC Crawley, JN AF Wrenn, CC Harris, AP Saavedra, MC Crawley, JN TI Social transmission of food preference in mice: Methodology and application to galanin-overexpressing transgenic mice SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID RAT VENTRAL HIPPOCAMPUS; NONMATCHING-TO-SAMPLE; SPONTANEOUS-ALTERNATION PERFORMANCE; FOREBRAIN CHOLINERGIC SYSTEM; BASAL FOREBRAIN; ACETYLCHOLINE-RELEASE; ALZHEIMERS-DISEASE; PHOSPHOINOSITIDE TURNOVER; NOREPINEPHRINE RELEASE; PASSIVE-AVOIDANCE AB Social transmission of food preference (STFP) is a test of olfactory memory that can be used in mice. Confounds in STFP that can lead to misinterpretation of an STFP deficit as a memory impairment include changes in social interaction and olfaction. The issue of changes in social interaction was addressed by evaluating,an observer-centric and a demonstrator-centric method for scoring the interaction phase of STFP in mice. The demonstrator-centric method was applied to a line of STFP-impaired, galanin-overexpressing transgenic (GAL-tg). GAL-tg mice were impaired in STFP without deficits in social interaction. In tests of olfactory ability, GAL-tg mice were unimpaired on buried-food and habituation dishabituation tasks. The current studies describe an expanded method for using STFP in mice and confirm a deficit in olfactory memory in GAL-tg mice. C1 NIMH, Sect Behav Genom, Bethesda, MD 20892 USA. RP Wrenn, CC (reprint author), NIMH, Sect Behav Genom, Bldg 10,Room 4D11, Bethesda, MD 20892 USA. NR 87 TC 71 Z9 73 U1 0 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD FEB PY 2003 VL 117 IS 1 BP 21 EP 31 DI 10.1037/0735-7044.117.1.21 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 643PV UT WOS:000180870400003 PM 12619904 ER PT J AU Zhang, CF Dhanvantari, S Lou, H Loh, YP AF Zhang, CF Dhanvantari, S Lou, H Loh, YP TI Sorting of carboxypeptidase E to the regulated secretory pathway requires interaction of its transmembrane domain with lipid rafts SO BIOCHEMICAL JOURNAL LA English DT Article DE carboxypeptidase E; intracellular protein sorting; lipid rafts; pro-opiomelanocortin; regulated secretory pathway; sorting receptor ID INFLUENZA-VIRUS HEMAGGLUTININ; GPI-ANCHORED PROTEINS; TRANS-GOLGI NETWORK; GRANULE BIOGENESIS; CELL-SURFACE; CYTOPLASMIC DOMAIN; MEMBRANE-PROTEIN; IDENTIFICATION; ASSOCIATION; AGGREGATION AB Carboxypeptidase E (CPE) functions as a regulated secretory pathway sorting receptor for several prohormones, including pro-opiomelanocortin (POMC), proenkephalin and proinsulin. The association of CPE with lipid rafts in the trans-Golgi network and secretory granule membranes is necessary for its sorting receptor function. We now provide evidence that a domain within the C-terminal 25 residues of CPE functions as a signal for both raft association and the sorting of CPE to the regulated secretory pathway. A fusion protein containing the extracellular domain of the human interieukin-2 receptor Tac (N-Tac) and the C-terminal 25 amino acids of CPE was transfected into Neuro2A cells. This fusion protein floated in sucrose density gradients, indicating raft association, and co-localized with chromogranin A (CGA), a secretory granule marker. To define further a minimum sequence required for raft association and sorting, deletion mutants of CPE that lacked the C-terminal four or 15 residues (CPE-Delta4 and CPE-Delta15 respectively) were transfected into a clone of CPE-deficient Neuro2A cells. In contrast with full-length CPE, neither CPE-Delta4 nor CPE-Delta15 floated in sucrose density gradients. The sorting of both CPE-Delta4 and CPE-Delta15 to the regulated secretory pathway was impaired, as indicated by significantly increased basal secretion and a lack of response to stimulation. Additionally, there was a significant decrease in the co-localization of mutant CPE immunofluorescence with CGA when compared with full-length CPE. Finally, the sorting of the prohormone POMC to the regulated pathway was impaired in cells transfected with either CPE-Delta4 or CPE-Delta15. We conclude that the sorting of CPE to the regulated secretory pathway in endocrine cells is mediated by lipid rafts, and that the C-terminal four residues of CPE, i.e. Thr(431)-Leu-Asn-Phe(434), are required for raft association and sorting. C1 NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), Bldg 49,Room 5A38,MSC 4480,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Dhanvantari, Savita/B-5362-2015 NR 34 TC 39 Z9 40 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD FEB 1 PY 2003 VL 369 BP 453 EP 460 DI 10.1042/BJ20020827 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645VU UT WOS:000181001300004 PM 12403651 ER PT J AU Harper, JL Camerini-Otero, CS Li, AH Kim, SA Jacobson, KA Daly, JW AF Harper, JL Camerini-Otero, CS Li, AH Kim, SA Jacobson, KA Daly, JW TI Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE calcium channels; dihydropyridines; capacitative calcium influx; inositol trisphosphate; store-operated calcium channels ID ADENOSINE RECEPTOR ANTAGONISTS; CHANNELS; DERIVATIVES; INFLUX AB A series of 1,4-dihydropyridines (DHPs) were investigated as inhibitors of capacitative calcium influx through store-operated calcium (SOC) channels. Such channels activate after ATP-elicited release of inositol trisphosphate (IP3)-sensitive calcium stores in leukemia HL-60 cells. The most potent DHPs were those containing a 4-phenyl group with an electron-withdrawing substituent, such as m- or p-nitro- or in-trifluoromethyl (IC50 values: 3-6 muM). Benzyl esters, corresponding to the usual ethyl/methyl esters of the DHPs developed as L-type calcium channel blockers, retained potency at SOC channels, as did N-substituted DHPs. N-Methylation reduced by orders of magnitude the potency at L-type channels resulting in DHPs nearly equipotent at SOC and L-type channels. DHPs with N-ethyl, N-allyl, and N-propargyl groups also had similar potencies at SOC and L-type channels. Replacement of the usual 6-methyl group of DHPs with larger groups, such as cyclobutyl or phenyl, eliminated activity at the SOC channels; such DHPs instead elicited formation of inositol phosphates and release of IP3-sensitive calcium stores. Other DHPs also caused a release of calcium stores, but usually at significantly higher concentrations than those required for the inhibition of capacitative calcium influx. Certain DHPs appeared to cause an incomplete blockade of SOC channel-dependent elevations of calcium, suggesting the presence of more than one class of such channels in HL-60 cells. N-Methylnitrendipine (IC50 2.6 muM, MRS 1844) and N-propargylnifrendipine (IC50 1.7 muM, MRS 1845) represent possible lead compounds for the development of selective SOC channel inhibitors. Published by Elsevier Science Inc. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bldg 8,Rm 1A17, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031127-01] NR 20 TC 89 Z9 89 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD FEB 1 PY 2003 VL 65 IS 3 BP 329 EP 338 AR PII S0006-2952(02)01488-0 DI 10.1016/S0006-2952(02)01488-0 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 640GB UT WOS:000180679100005 PM 12527326 ER PT J AU Schwan, TG AF Schwan, TG TI Temporal regulation of outer surface proteins of the Lyme-disease spirochaete Borrelia burgdorferi SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Independent Meeting on Signalling the Future CY SEP 04-06, 2002 CL UNIV LIVERPOOL, LIVERPOOL, ENGLAND HO UNIV LIVERPOOL DE Ixodes scapularis; phenotypic changes; temperature regulation; tick feeding ID NYMPHAL IXODES-DAMMINI; OSPC GENE; DIFFERENTIAL EXPRESSION; MOLECULAR ANALYSIS; MEMBRANE-PROTEINS; CIRCULAR PLASMID; RICINUS TICKS; TRANSMISSION; ANTIBODY; MICE AB In the 20 years since the first agent of Lyme disease was discovered, much interest has focused on the possible biological roles of a few outer surface proteins (Osps) in the alternating life cycle that includes ticks and vertebrate hosts. Two major proteins, OspA and OspC, are differentially regulated by the spirochaete Borrelia burgdorferi during the several days when ticks feed. The reciprocal decrease in OspA with the rapid up-regulation of OspC by the spirochaetes when ticks are feeding suggests that OspA aids in spirochaete attachment while OspC assists in the dissemination of spirochaetes from tick to vertebrate. Future experiments in ticks with mutant spirochaetes that lack these proteins should clarify the speculative functions currently given to these proteins. C1 NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Schwan, TG (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 50 TC 50 Z9 50 U1 0 U2 4 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD FEB PY 2003 VL 31 BP 108 EP 112 PN 1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648QA UT WOS:000181161000023 PM 12546665 ER PT J AU Schulze, TG Chen, YS Badner, JA McInnis, MG DePaulo, JR McMahon, FJ AF Schulze, TG Chen, YS Badner, JA McInnis, MG DePaulo, JR McMahon, FJ TI Additional, physically ordered markers increase linkage signal for bipolar disorder on chromsome 18q22 SO BIOLOGICAL PSYCHIATRY LA English DT Article DE manic-depressive illness; parent-of-origin effect; genome sequence; microsatellites; affected sib-pair analysis; nonparametric LOD score ID GAMETIC DISEQUILIBRIUM; SUSCEPTIBILITY LOCUS; CHROMOSOME 21Q22; II DISORDER; GENOME SCAN; PEDIGREES; TRAITS; GENES; 13Q32 AB Background: We recently reported evidence of linkage of bipolar disorder to chromosome 18q, with a paternal logarithm of odds (LOD) score of 4.67 (p = .004) in a clinically defined subset of families. Like other linkage studies, we had to rely on imprecise genetic maps to establish the marker order. Here, we test for linkage in the same sample with a denser set of markers, now physically ordered according to the draft sequence of the human genome. Methods: Families were ascertained through probands with bipolar I disorder and diagnosed with reliable methods. Genotypes were generated for 12 microsatellite markers within an 11-centimorgan (cM) region of chromosome 18q22. Multipoint affected sib-pair linkage analysis was performed in a set of 16 nuclear families. Results: The additional markers significantly increased the total genetic information extracted from our sample. We also observed an increase in the LOD score (to 5.42, p = .0066) and linkage resolution. The approximate 1-LOD support interval is now 9 male cM. Conclusions: The results strengthen our previous findings and further define a region suitable for genetic fine-mapping analysis on chromosome 18q. Our data suggest that a dense set of markers, when physically ordered, can increase the informational value of genetic linkage signals. (C) 2003 Society of Biological Psychiatry. C1 NIMH, Bethesda, MD 20814 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. RP Schulze, TG (reprint author), NIMH, 15K North Dr,Bldg 36,Room 4C12,MSC 4095, Bethesda, MD 20814 USA. RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012; Schulze, Thomas/H-2157-2013 OI McInnis, Melvin/0000-0002-0375-6247; NR 25 TC 25 Z9 27 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 2003 VL 53 IS 3 BP 239 EP 243 DI 10.1016/S0006-3223(02)01492-0 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 640MP UT WOS:000180692800007 PM 12559657 ER PT J AU Cheng, JG Stewart, CL AF Cheng, JG Stewart, CL TI Loss of cyclooxygenase-2 retards decidual growth but does not inhibit embryo implantation or development to term SO BIOLOGY OF REPRODUCTION LA English DT Article DE decidua; female reproductive tract; implantation ID MOUSE UTERUS; MICE; EXPRESSION; ANGIOGENESIS; INTERLEUKIN-1-BETA; ESTROGEN AB Previous reports have described that female mice deficient in cyclooxygenase-2 (COX2) are largely infertile because of failure to ovulate, poor fertilization, and defective implantation and decidualization. In the present study, we reinvestigated reproduction in these mice and found they do show a reduction in the numbers of ovulated and fertilized eggs. However, we did not observe any substantial effect on embryo implantation frequencies or an inability of COX2-deficient females to support embryo development to weaning. Pseudopregnant COX2-null recipients do not show any alteration in the timing of implantation following blastocyst transfer, but they do show a delay in the initial rate of decidual growth after implantation that lags by approximately 24 h compared to that in heterozygous or wild-type recipients. These results support previous findings that COX2 has a role in mediating the initial uterine decidual response but is not essential to sustaining decidual growth and embryo development throughout the remainder of pregnancy. C1 NCI, Frederick Canc Res & Dev Ctr, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), NCI, Frederick Canc Res & Dev Ctr, Canc & Dev Biol Lab, Frederick, MD 21702 USA. NR 19 TC 25 Z9 26 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD FEB PY 2003 VL 68 IS 2 BP 401 EP 404 DI 10.1095/biolreprod.102.009589 PG 4 WC Reproductive Biology SC Reproductive Biology GA 639RY UT WOS:000180644200008 PM 12533402 ER PT J AU Baird, DD Weinberg, CR McConnaughey, DR Wilcox, AJ AF Baird, DD Weinberg, CR McConnaughey, DR Wilcox, AJ TI Rescue of the corpus luteum in human pregnancy SO BIOLOGY OF REPRODUCTION LA English DT Article DE corpus luteum; corpus luteum function; human chorionic gonadotropin; pregnancy; progesterone ID HUMAN CHORIONIC-GONADOTROPIN; HUMAN CORPORA-LUTEA; LUTEINIZING-HORMONE; URINARY ESTROGEN; PROGESTERONE METABOLITES; DIRECT RADIOIMMUNOASSAY; MENSTRUAL-CYCLE; IMPLANTATION; OVULATION; WOMEN AB Rescue of the corpus luteum from its programmed senescence maintains progesterone production required for pregnancy. In primates, chorionic gonadotropin produced by the developing conceptus acts as the primary luteotrophic signal. The purpose of this research was to assess corpus luteum rescue by examining changes in daily urinary progesterone metabolite levels during the first week after implantation. We determined the variability in progesterone metabolite profiles and evaluated its relationship to early pregnancy loss in 120 naturally conceived human pregnancies, including 43 early pregnancy losses. In other primates, an abrupt increase in the progesterone metabolite occurs at the time of implantation. This pattern occurred in an estimated 45% of the pregnancies in the present study. In the remaining pregnancies, there was a delayed rise (18%), neither a rise or decline (22%), or a decline (15%) during the week after implantation. The estimated rate of early pregnancy loss increased across these categories (from 5% loss with an abrupt rise at implantation to 100% loss with progesterone metabolite decline). Low urinary hCG levels in early pregnancy were significant determinants of a decline in postimplantation progesterone metabolite. However, preimplantation steroid metabolite levels were not significant, suggesting no inherent problem with the corpus luteum. Examination of individual progesterone metabolite profiles in relation to hCG profiles also indicated that few losses were caused by corpus luteum failure. Delineating the functional importance of an abrupt progesterone rise at the time of implantation may provide new strategies for promoting successful implantation in assisted reproduction. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. WESTAT Corp, Res Triangle Pk, NC 27709 USA. RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, Mail Drop A3-05,111 TW Alexander Dr,Bldg 101,Rm 3, Res Triangle Pk, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 44 TC 32 Z9 34 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD FEB PY 2003 VL 68 IS 2 BP 448 EP 456 DI 10.1095/biolreprod.102.008425 PG 9 WC Reproductive Biology SC Reproductive Biology GA 639RY UT WOS:000180644200013 PM 12533407 ER PT J AU Schmitz, S Wang, F Sellers, JR Molloy, JE Veigel, C AF Schmitz, S Wang, F Sellers, JR Molloy, JE Veigel, C TI Single molecule mechanics of myosin V constructs SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Natl Inst Med Res, London NW7 1AA, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 4A EP 4A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800015 ER PT J AU Korolkova, Y Zhang, M Liu, J Jiang, M Grishin, E Arseniev, A Kellogg, G Guy, HR Tseng, GN AF Korolkova, Y Zhang, M Liu, J Jiang, M Grishin, E Arseniev, A Kellogg, G Guy, HR Tseng, GN TI Probing the unique structure of HERG's outer vestibule using mutant cycle analysis. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Russian Acad Sci, Moscow 117997, Russia. Virginia Commonwealth Univ, Richmond, VA 23298 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 8A EP 8A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800036 ER PT J AU Chernomordik, LV Leikina, E Markovic, I Mittal, A Zhukovsky, M Zimmerberg, J Ramos, C Kozlov, MM AF Chernomordik, LV Leikina, E Markovic, I Mittal, A Zhukovsky, M Zimmerberg, J Ramos, C Kozlov, MM TI Protein-lipid interplay in fusion mediated by influenza virus hemagglutinin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, Bethesda, MD 20892 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RI Mittal, Aditya/E-3087-2010 OI Mittal, Aditya/0000-0002-4030-0951 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 11A EP 11A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800049 ER PT J AU Gunasekaran, K Ma, BY Nussinov, R AF Gunasekaran, K Ma, BY Nussinov, R TI Loops that trigger and modulate functions: An evolving common mechanism in enzymes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, NIH, LECB, Frederick, MD 21702 USA. Tel Aviv Univ, DHGMM, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 12A EP 13A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800057 ER PT J AU Smirnov, AV Schotte, F Anfinrud, P AF Smirnov, AV Schotte, F Anfinrud, P TI Ultrafast spectroscopic studies of crystalline and solution forms of photoactive yellow protein (PYP) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 12A EP 12A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800054 ER PT J AU Lopes, CMB Rohacs, T Czirjak, G Balla, T Logothetis, DE Enyedi, P AF Lopes, CMB Rohacs, T Czirjak, G Balla, T Logothetis, DE Enyedi, P TI PIP2 activates and mediates agonist-induced inhibition of 2-P domain K+ channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TX SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Semmelweis Univ, H-1085 Budapest, Hungary. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 16A EP 16A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800074 ER PT J AU Xu, X Spencer, NY Cho, M King, SB Huang, Z Gladwin, MT Hogg, N Kim-Shapiro, DB AF Xu, X Spencer, NY Cho, M King, SB Huang, Z Gladwin, MT Hogg, N Kim-Shapiro, DB TI Measurements of NO on the heme iron and beta-93 cysteine in hemoglobin during cycles of oxygenation and deoxygenation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 34A EP 34A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800158 ER PT J AU Keskin, O Tsai, CJ Wolfson, H Nussinov, R AF Keskin, O Tsai, CJ Wolfson, H Nussinov, R TI A new dataset of non-redundant protein/protein interfaces SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Koc Univ, TR-80910 Istanbul, Turkey. NCI, SAIC, LECB, Frederick, MD 21702 USA. Tel Aviv Univ, CSD, IL-69978 Tel Aviv, Israel. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 42A EP 42A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800198 ER PT J AU Hussein, Y Godde, JS Hawkins, ME Davenport, L AF Hussein, Y Godde, JS Hawkins, ME Davenport, L TI Binding of anionic porphyrin molecules to G-quadruplexed DNA using fluorescently labeled guanine-telomeric sequences. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 CUNY, Grad Ctr, Brooklyn, NY 11210 USA. CUNY Brooklyn Coll, Brooklyn, NY 11210 USA. Monmouth Coll, Monmouth, IL 61462 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 44A EP 44A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800209 ER PT J AU Feller, SE Gawrisch, K MacKerell, AD AF Feller, SE Gawrisch, K MacKerell, AD TI Structural and dynamic properties of polyunsaturated fatty acids from simulation and experiment SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Wabash Coll, Crawfordsville, IN 47933 USA. NIAAA, NIH, Rockville, MD 20852 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 47A EP 47A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800224 ER PT J AU Eldho, NV Gawrisch, K AF Eldho, NV Gawrisch, K TI Location, conformation and dynamics of anandamide in biomembranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 49A EP 49A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800235 ER PT J AU Hayakawa, E Pacifico, A Mitchell, DC Litman, BJ AF Hayakawa, E Pacifico, A Mitchell, DC Litman, BJ TI Effect of membrane curvature stress on rhodopsin activation and acyl chain packing SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAAA, Rockville, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 56A EP 56A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800273 ER PT J AU Misra, S Prag, G Jones, E Hurley, JH AF Misra, S Prag, G Jones, E Hurley, JH TI Crystal structure of a new ubiquitin binding domain, the CUE domain of yeast Vps9p SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 62A EP 62A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800302 ER PT J AU Maltsev, VA Undrovinas, AI AF Maltsev, VA Undrovinas, AI TI Inactivation of sodium current in adult human heart SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Henry Ford Hlth Syst, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 67A EP 67A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800325 ER PT J AU Sukhareva, M Kitaguchi, T Swartz, K AF Sukhareva, M Kitaguchi, T Swartz, K TI A mutation within the activation gate of the Shaker K+ channel decreasing single channel conductance SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NINDS, NIH, Bethesda, MD 20892 USA. RI Kitaguchi, Tetsuya/F-5260-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 74A EP 74A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800357 ER PT J AU Shrivastava, IH Guy, HR AF Shrivastava, IH Guy, HR TI Refinement of inward rectifying potassium channels (Kir2.1) structural models by molecular dynamics simulations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 78A EP 78A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800377 ER PT J AU Alkhalil, A Wagner, MA Desai, SA AF Alkhalil, A Wagner, MA Desai, SA TI A single channel explains the increased Cl- and sorbitol permeability of P-falciparum infected human RBCs. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAID, NIH, Bethesda, MD 20892 USA. RI Desai, Sanjay/B-7110-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 87A EP 87A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800420 ER PT J AU Bailey, BW Menon, G Mitchell, DC AF Bailey, BW Menon, G Mitchell, DC TI Alteration of cholesterol in synaptosomes is commensurate with reductions in GABA(A) receptor benzodiazepine binding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAAA, Bethesda, MD 20892 USA. RI Bailey, Brian/B-1732-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 87A EP 87A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800421 ER PT J AU Boukari, H Sackett, D Nossal, R Krueger, S Chernomordik, V AF Boukari, H Sackett, D Nossal, R Krueger, S Chernomordik, V TI Probing the stability of drug-induced tubulin polymers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NIST, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 114A EP 114A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800554 ER PT J AU Oke, O Burgess, S Wang, F Sellers, JR Knight, PJ Trinick, J AF Oke, O Burgess, S Wang, F Sellers, JR Knight, PJ Trinick, J TI Structural studies of mutant myosin V molecules SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 116A EP 116A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800563 ER PT J AU Sakamoto, T Wang, F Sellers, JR AF Sakamoto, T Wang, F Sellers, JR TI The processivity of a differential neck length myosin V mutants. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 116A EP 116A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800560 ER PT J AU Thirumurugan, K Burgess, SA Trinick, J Wang, F Sellers, JR White, HD Knight, PJ AF Thirumurugan, K Burgess, SA Trinick, J Wang, F Sellers, JR White, HD Knight, PJ TI Temperature effects on myosin V head conformation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. NHLBI, LMC, NIH, Bethesda, MD 20892 USA. Eastern Virginia Med Sch, Norfolk, VA 23507 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 116A EP 116A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800562 ER PT J AU White, HD Cartwright, SL Wang, F Sellers, RJ AF White, HD Cartwright, SL Wang, F Sellers, RJ TI Kinetics of product dissociation from actomyosinV-HMM. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Eastern Virginia Med Sch, Norfolk, VA 23507 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 116A EP 116A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800561 ER PT J AU Grisshammer, R White, JF AF Grisshammer, R White, JF TI Expression and purification of G-protein-coupled receptors for structure determination SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIDDK, HHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 126A EP 126A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800614 ER PT J AU Anderson, PS Schuck, PS Sundberg, EJ Mariuzza, RA AF Anderson, PS Schuck, PS Sundberg, EJ Mariuzza, RA TI Quantifying the energetics of cooperativity in a ternary protein complex. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Symphogen AS, DK-2800 Lyngby, Denmark. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 128A EP 128A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800623 ER PT J AU Schuck, P AF Schuck, P TI Hydrodynamic size-and-shape distributions of protein complexes by global modeling of sedimentation and dynamic light scattering SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 128A EP 128A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800624 ER PT J AU Hoskins, J Sharma, S Wickner, S AF Hoskins, J Sharma, S Wickner, S TI Protein recognition and remodeling by Clp/Hsp100 chaperones of E-coli and the role of chaperones in proteolysis. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 130A EP 130A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800631 ER PT J AU Luca, S White, JF Sohal, AK Fillipov, D van Boom, JH Grisshammer, R Baldus, M AF Luca, S White, JF Sohal, AK Fillipov, D van Boom, JH Grisshammer, R Baldus, M TI Studying the conformation of neurotensin bound to its G-protein-coupled receptor NTS-1 by 2D solid-state NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Max Planck Inst Biophys Chem, Solid State NMR, D-37077 Gottingen, Germany. NIH, Bethesda, MD 20892 USA. Leiden Univ, Leiden Inst Chem, NL-2300 RA Leiden, Netherlands. RI Baldus, Marc/C-2737-2009 OI Baldus, Marc/0000-0001-7068-5613 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 137A EP 137A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800663 ER PT J AU Davis, JS Epstein, ND AF Davis, JS Epstein, ND TI Crossbridge cycle reversibility back from tension generation to phosphate release is marked in slow, detectable in medium, and absent in fast muscle fibers contracting isometrically. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 140A EP 140A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800676 ER PT J AU Forbes, JG Jin, AJ Ma, K Wang, K AF Forbes, JG Jin, AJ Ma, K Wang, K TI Elasticity of the PEVK segment of titin is dominated by sequence-specific charge pairing interactions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIH, ORS, OD, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 140A EP 140A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800678 ER PT J AU Leuba, SH Ramjit, R Tomschik, M Smith, P Zlatanova, J AF Leuba, SH Ramjit, R Tomschik, M Smith, P Zlatanova, J TI Following single chromatin fiber assembly and disassembly by magnetic tweezers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Pittsburgh, Sch Med Cell Biol & Physiol, Pittsburgh, PA 15213 USA. Polytech Univ, MetroTech Ctr, Brooklyn, NY 11201 USA. NIH, ORS, Bethesda, MD 20892 USA. RI Zlatanova, Jordanka/B-3273-2009 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 142A EP 142A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800686 ER PT J AU Armstrong, N Mayer, ML Gouaux, E AF Armstrong, N Mayer, ML Gouaux, E TI Tuning activation of the AMPA-sensitive GluR2 ion channel by genetic adjustment of agonist-induced conformational changes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Columbia Univ, New York, NY 10032 USA. NIH, Lab Cellular & Mol Neurophysiol, Bethesda, MD 20892 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. RI Mayer, Mark/H-5500-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 146A EP 146A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800706 ER PT J AU Hirschberg, K Phair, RD Polishchuk, R Gerlich, D Patterson, G Lippincott-Schwartz, J AF Hirschberg, K Phair, RD Polishchuk, R Gerlich, D Patterson, G Lippincott-Schwartz, J TI The Golgi apparatus: a two phase membrane system for protein retention and secretory transport SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 147A EP 147A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800714 ER PT J AU Chen, YD Yan, B AF Chen, YD Yan, B TI Modeling the motility of single kinesin motor SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 149A EP 149A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800721 ER PT J AU Zanuy, D Gazit, E Nussinov, R AF Zanuy, D Gazit, E Nussinov, R TI Structural and Conformational investigations of amyloidogenic sequences: MD studies of IAPP peptides SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, SAIC, Frederick, MD 21702 USA. Tel Aviv Univ, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. NCI, NIH, Frederick, MD 21702 USA. RI Gazit, Ehud/C-3715-2011; Zanuy, David/G-3930-2014 OI Gazit, Ehud/0000-0001-5764-1720; Zanuy, David/0000-0001-7704-2178 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 155A EP 155A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800751 ER PT J AU Gunasekaran, K Haspel, N Tsai, CJ Kumar, S Wolfson, H Nussinov, R AF Gunasekaran, K Haspel, N Tsai, CJ Kumar, S Wolfson, H Nussinov, R TI Extended disordered proteins: An elegant solution to having large intermolecular interfaces, yet keeping smaller genome and cell sizes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, NIH, LECB, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. RI Wolfson, Haim/A-1837-2011; Haspel, Nurit/D-1961-2017 NR 0 TC 3 Z9 3 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 163A EP 163A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800791 ER PT J AU Harries, D Parsegian, VA AF Harries, D Parsegian, VA TI Protein denaturation by co-solutes from a simple lattice model SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, NIH, LPSB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 163A EP 163A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800792 ER PT J AU Whittington, KC Jozwiak, K Moaddel, R Wainer, IW AF Whittington, KC Jozwiak, K Moaddel, R Wainer, IW TI The comparison of two subtypes of the neuronal nicotinic acetylcholine receptor (alpha 3 beta 2 and alpha 3 beta 4) using nonlinear affinity chromatography technique for the screening of non-competitive inhibitors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Ctr Gerontol Res, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 167A EP 168A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800816 ER PT J AU Howard, KJ Ignatov, ME LeGrice, S Barkley, MD AF Howard, KJ Ignatov, ME LeGrice, S Barkley, MD TI Effect of the NNRTI efavirenz on subunit assembly of HIV-1 reverse transcriptase SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NCI, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 171A EP 171A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800835 ER PT J AU Barzilai, A Kumar, S Wolfson, H Nussinov, R Nussinov, R AF Barzilai, A Kumar, S Wolfson, H Nussinov, R Nussinov, R TI Are protein folding and function coupled? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NCI Frederick, LECB, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 174A EP 174A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800849 ER PT J AU Jie, Y Parsegian, VA Rau, DC AF Jie, Y Parsegian, VA Rau, DC TI A second structural phase of Spermidine condensed DNA. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Vermont, Burlington, VT 05405 USA. NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 180A EP 180A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800881 ER PT J AU Polozov, IV Veatch, SL Gawrisch, K AF Polozov, IV Veatch, SL Gawrisch, K TI Application of MAS (HNMR)-H-1 to study lipid rafts in cell membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAAA, NIH, LMBB, Rockville, MD 20852 USA. Univ Washington, Dept Phys, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 185A EP 185A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800907 ER PT J AU Leikina, E Mittal, A Kozlov, MM Chernomordik, LV AF Leikina, E Mittal, A Kozlov, MM Chernomordik, LV TI Fusion proteins located outside of the contact zone are involved in membrane fusion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RI Mittal, Aditya/E-3087-2010 OI Mittal, Aditya/0000-0002-4030-0951 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 194A EP 195A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800952 ER PT J AU Mittal, A Leikina, E Chernomordik, LV Bentz, J AF Mittal, A Leikina, E Chernomordik, LV Bentz, J TI Kinetic differentiation of HA fusion and hemifusion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. Drexel Univ, Philadelphia, PA 19104 USA. RI Mittal, Aditya/E-3087-2010 OI Mittal, Aditya/0000-0002-4030-0951 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 195A EP 195A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800953 ER PT J AU Ramos, C Melikov, K Zaitseva, E Wilson, K Chernomordik, L AF Ramos, C Melikov, K Zaitseva, E Wilson, K Chernomordik, L TI Using protein-free vesicles and quantitative fluorimetric assays to study the nuclear envelope assembly SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, LCMB, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. RI Melikov, Kamran/A-6604-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 195A EP 196A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800957 ER PT J AU Chanturiya, A Sokolov, V Passechnik, I Schubert, U Henklein, P Yewdell, J Zimmerberg, J AF Chanturiya, A Sokolov, V Passechnik, I Schubert, U Henklein, P Yewdell, J Zimmerberg, J TI Influenza a mitochondrial peptide PB1-F2 porates planar lipid membranes without formation of distinctive ion channels. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, LCMB, NIH, Bethesda, MD 20892 USA. Inst Electrochem, Moscow 117071, Russia. NIAID, LVD, NIH, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 204A EP 204A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800998 ER PT J AU Nossal, R Muthukumar, M AF Nossal, R Muthukumar, M TI Micelle-like model for the polymerization of clathrin baskets. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Amherst, MA 01003 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 209A EP 209A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801023 ER PT J AU Richard, JP Melikov, K Vives, E Ramos, C Verbeure, B Gait, MJ Chernomordik, LV Lebleu, B AF Richard, JP Melikov, K Vives, E Ramos, C Verbeure, B Gait, MJ Chernomordik, LV Lebleu, B TI Cell-penetrating peptides: a re-evaluation of the mechanism of cellular uptake. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Montpellier 2, UMR 5124 CNRS, Montpellier, France. NICHD, Lab Cell & Mol Biophys, Bethesda, MD 20892 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RI Melikov, Kamran/A-6604-2009 NR 0 TC 0 Z9 1 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 212A EP 212A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801038 ER PT J AU Wang, JL Roh, SH Kim, SH Lee, CW Kim, JI Swartz, KJ AF Wang, JL Roh, SH Kim, SH Lee, CW Kim, JI Swartz, KJ TI Functional mapping of the molecular surface of a gating modifier toxin for voltage-gated K+ channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NINDS, NIH, Bethesda, MD 20892 USA. KJIST, Kwangju, South Korea. NR 0 TC 2 Z9 2 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 218A EP 218A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801064 ER PT J AU Kitaguchi, T Sukhareva, M Swartz, KJ AF Kitaguchi, T Sukhareva, M Swartz, KJ TI The non-conducting mechanism of the V478W mutation in Shaker Kv channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NINDS, NIH, Bethesda, MD 20892 USA. RI Kitaguchi, Tetsuya/F-5260-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 219A EP 219A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801072 ER PT J AU Lee, HC Swartz, KJ AF Lee, HC Swartz, KJ TI Opening the shaker voltage-gated K+ channel with hanatoxin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 219A EP 220A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801073 ER PT J AU Soler-Llavina, G Holmgren, M Swartz, KJ AF Soler-Llavina, G Holmgren, M Swartz, KJ TI The conductance of the closed state in the shaker voltage-gated K+ channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 220A EP 220A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801074 ER PT J AU Li-Smerin, YY Swartz, KJ AF Li-Smerin, YY Swartz, KJ TI Toxins interacting with hyperpolarization-activated cation channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 222A EP 222A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801086 ER PT J AU Martyn, DA Adhikari, BB Gu, J Xu, SG Regnier, M Yu, LPC AF Martyn, DA Adhikari, BB Gu, J Xu, SG Regnier, M Yu, LPC TI Myofilament lattice and length dependence of equatorial X-ray reflections and stiffness in relaxed, skinned cardiac muscle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Washington, Seattle, WA 98195 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 240A EP 241A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801174 ER PT J AU Carroll, S Herrera, AH Horowits, R AF Carroll, S Herrera, AH Horowits, R TI N-RAP super repeats organize actin filaments during myofibril assembly in cultured chick cardiomyocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 254A EP 255A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801242 ER PT J AU Yang, D Zhu, WZ Song, LS Chakir, K Wang, W Wu, C Wang, Y Xiao, RP Chen, SRW Cheng, H AF Yang, D Zhu, WZ Song, LS Chakir, K Wang, W Wu, C Wang, Y Xiao, RP Chen, SRW Cheng, H TI Calmodulin regulation of cardiac excitation-contraction coupling SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIA, NIH, Baltimore, MD 21224 USA. Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. Univ Maryland, Baltimore, MD 21201 USA. Univ Calgary, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 260A EP 260A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801268 ER PT J AU Froehlich, J Albers, W Humphrey, P Clarke, RJ AF Froehlich, J Albers, W Humphrey, P Clarke, RJ TI The voltage-sensitive dye RH421 inhibits Na,K-ATPase by preventing E2P hydrolysis. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIA, NIH, Baltimore, MD 21224 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Sydney, Sydney, NSW 2006, Australia. RI Clarke, Ronald/L-5259-2016 OI Clarke, Ronald/0000-0002-0950-8017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 267A EP 267A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801304 ER PT J AU Lefman, J Zhang, PJ Kessel, M Juliani, J Hirai, T Weis, RM Peters, P Subramaniam, S AF Lefman, J Zhang, PJ Kessel, M Juliani, J Hirai, T Weis, RM Peters, P Subramaniam, S TI 3D imaging of cells using electron tomography SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Amherst, MA 01003 USA. Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. RI Hirai, Teruhisa/G-2105-2015 OI Hirai, Teruhisa/0000-0002-2114-8149 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 279A EP 280A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801366 ER PT J AU Borgnia, MJ Peijun, Z Shi, D Subramaniam, S Milne, JLS AF Borgnia, MJ Peijun, Z Shi, D Subramaniam, S Milne, JLS TI Automated data acquisition and structure refinement in electron cryo-microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, CCR, NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 280A EP 280A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801367 ER PT J AU Ishikawa, T Maurizi, MR Steven, AC AF Ishikawa, T Maurizi, MR Steven, AC TI Three-dimensional reconstruction of the ClpAP protein degradation machine by cryo-electron microscopy: mechanisms of ATP-dependent proteolysis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 281A EP 281A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801372 ER PT J AU Xu, JH Knutson, JR AF Xu, JH Knutson, JR TI Femtosecond fluorescence of tryptophan dipeptides in water SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NHLBI, LBC, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 287A EP 287A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801401 ER PT J AU Schmukler, RE Eidsath, A Button, D Sugar, IP Lindesay, J Khizder, K Ahmed, A AF Schmukler, RE Eidsath, A Button, D Sugar, IP Lindesay, J Khizder, K Ahmed, A TI Mammalian gene transfer by low-voltage Electroporation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Pore Squared Bioengn Inc, Gaithersburg, MD 20879 USA. NIH, DBEPS, ORS, OD, Bethesda, MD 20892 USA. Roche Biosci, Palo Alto, CA 94304 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Howard Univ, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 297A EP 297A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801454 ER PT J AU Klosek, MM Durell, SR Guy, HR AF Klosek, MM Durell, SR Guy, HR TI A statistical approach for identifying of structural/functional segments in ionic channel sequences using a new type of global profiles. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 306A EP 306A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801498 ER PT J AU Shafrir, Y Guy, RH AF Shafrir, Y Guy, RH TI An enhanced method for multi-sequence alignment of trans-membrane proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 306A EP 306A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801497 ER PT J AU Hess, ST Webb, WW AF Hess, ST Webb, WW TI Focal volume optics and experimental artifacts in confocal fluorescence correlation spectroscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 313A EP 313A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801530 ER PT J AU Rakowski, RF Artigas, P Holmgren, M Gadsby, DC De Weer, P AF Rakowski, RF Artigas, P Holmgren, M Gadsby, DC De Weer, P TI Na ion occupancy of the channels opened by palytoxin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Ohio Univ, Athens, OH 45701 USA. Rockefeller Univ, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 320A EP 320A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801567 ER PT J AU Rostovtseva, T Suzuki, M Youle, R Antonsson, B Colombini, M Bezrukov, S AF Rostovtseva, T Suzuki, M Youle, R Antonsson, B Colombini, M Bezrukov, S TI Could the pro-apoptotic proteins regulate VDAC channels? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, LPSB, NIH, Bethesda, MD 20892 USA. NINDS, SNB, NIH, Bethesda, MD 20892 USA. Serono, Pharmaceut, CH-1228 Geneva, Switzerland. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. RI Colombini, Marco/A-1540-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 323A EP 323A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801578 ER PT J AU Suh, KS Yuspa, SH AF Suh, KS Yuspa, SH TI CLIC 4, a p53 regulated intracellular chloride ion channel, translocates to the SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 323A EP 323A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801580 ER PT J AU Yue, WWY Buchanan, SK AF Yue, WWY Buchanan, SK TI Crystallographic analyses of iron-free and iron-loaded citrate bound to E.coli FecA receptor. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 325A EP 325A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801588 ER PT J AU Baumgart, T Hess, ST Feigenson, GW Webb, WW AF Baumgart, T Hess, ST Feigenson, GW Webb, WW TI Domain formation, morphology, and out-of-plane curvature in giant unilamellar vesicles with microscopic liquid/liquid phase coexistence SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Cornell Univ, Ithaca, NY 14853 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 326A EP 326A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801595 ER PT J AU Petrache, HI Tristram-Nagle, S Liu, YF Gawrisch, K Nagle, JF AF Petrache, HI Tristram-Nagle, S Liu, YF Gawrisch, K Nagle, JF TI Structure and interactions of DOPS vs. DOPC using NMR, volumetric and x-ray measurements SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, LPSB, NIH, Bethesda, MD 20892 USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. NIAAA, LMBB, NIH, Rockville, MD 20852 USA. RI Nagle, John/B-1917-2015 OI Nagle, John/0000-0002-9844-5934 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 326A EP 327A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801597 ER PT J AU Malnasi-Csizmadia, A Kovacs, M Fajer, PG Conibear, PB Woolley, RJ Bagshaw, CR AF Malnasi-Csizmadia, A Kovacs, M Fajer, PG Conibear, PB Woolley, RJ Bagshaw, CR TI Probes of the myosin cleft that sense actin binding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TX SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Eotvos Lorand Univ, H-1117 Budapest, Hungary. NHLBI, Bethesda, MD 20892 USA. FSU, Tallahassee, FL 32310 USA. Univ Leicester, Leicester LE1 7RH, Leics, England. RI Kovacs, Mihaly/A-6841-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 327A EP 327A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801601 ER PT J AU Knight, PJ Burgess, S Walker, M Wang, F Sellers, JR White, HD Trinick, J AF Knight, PJ Burgess, S Walker, M Wang, F Sellers, JR White, HD Trinick, J TI Motor domain strain and the origin of force in myosin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 328A EP 328A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801603 ER PT J AU Davis, RL Rodriguez, RC Binz, AK Biddison, WE Baker, BM AF Davis, RL Rodriguez, RC Binz, AK Biddison, WE Baker, BM TI Comparative studies of different T cell receptors that bind the same ligand in a topologically, thermodynamically, and kinetically similar manner SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Notre Dame, Notre Dame, IN 46556 USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 332A EP 332A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801624 ER PT J AU Niu, SL Tokumasu, F Jin, A Dvorak, J Litman, BJ AF Niu, SL Tokumasu, F Jin, A Dvorak, J Litman, BJ TI Characterization of micro-domain structure in ROS disk model membranes using differential scanning calorimetry and atomic force microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 332A EP 332A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801621 ER PT J AU Simon, JD Perry, JL Il'ichev, YV Pritchard, JB Bow, D AF Simon, JD Perry, JL Il'ichev, YV Pritchard, JB Bow, D TI Binding of ochratoxin a to human plasma proteins: Implications in toxicity mechanisms SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Duke Univ, Durham, NC 27705 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 332A EP 332A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801622 ER PT J AU Dimitriadis, EK Pascual, JC Horkay, F AF Dimitriadis, EK Pascual, JC Horkay, F TI Direct observations of cation-induced conformational changes of DNA adsorbed on hydrophilic and hydrophobic surfaces SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 DBEPS, NIH, Bethesda, MD 20892 USA. NICHD, LIMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 347A EP 347A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801696 ER PT J AU Nanda, H Sachs, JN Petrache, HI Woolf, TB AF Nanda, H Sachs, JN Petrache, HI Woolf, TB TI Dynamics of the glycophorin A transmembrane domain in water SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 350A EP 350A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801713 ER PT J AU Guo, FS Esser, L Maurizi, MR Xia, D AF Guo, FS Esser, L Maurizi, MR Xia, D TI Crystal structures of E.coli ClpA and ClpA(N)S SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 355A EP 355A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801738 ER PT J AU Ramagopal, UA Dauter, M Dauter, Z AF Ramagopal, UA Dauter, M Dauter, Z TI Sulfur SAD: What is the limit? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. Brookhaven Natl Lab, SAIC, Upton, NY 11973 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 355A EP 356A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801740 ER PT J AU Sokhansanj, BA Wilson, DM AF Sokhansanj, BA Wilson, DM TI Mathematical modeling of human DNA base excision repair SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. NIA, IRP, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 360A EP 360A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801762 ER PT J AU Jayaram, H Taraporewala, Z del Carpio, RV Patton, JT Prasad, BVV AF Jayaram, H Taraporewala, Z del Carpio, RV Patton, JT Prasad, BVV TI Structure function studies on NSP2 a protein involved in rotavirus genome replication and packaging SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Baylor Coll Med, Houston, TX 77030 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 361A EP 361A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801766 ER PT J AU Sidorova, N Hsieh, P AF Sidorova, N Hsieh, P TI MutS-DNA specific binding and its sensitivity to solution conditions. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, LPSB, NIH, Bethesda, MD 20892 USA. NIDDK, GBB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 364A EP 364A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801780 ER PT J AU Urbaneja, MA Cruceanu, M Williams, MC Gorelick, RJ Casas-Finet, JR AF Urbaneja, MA Cruceanu, M Williams, MC Gorelick, RJ Casas-Finet, JR TI Nucleic acid binding properties of HIV-1 gag sequences containing the nucleocapsid domain SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Northeastern Univ, Dept Phys, Boston, MA 02115 USA. Medimmune Inc, Gaithersburg, MD 20878 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 367A EP 368A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801799 ER PT J AU Kuzmin, P Akimov, S Cohen, F Zimmerberg, J AF Kuzmin, P Akimov, S Cohen, F Zimmerberg, J TI Rafts repel each other through tilt of their lipids at their boundary edges. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 AN Frumkin Electrochem Inst, Moscow 117071, Russia. Rush Med Coll, Chicago, IL 60612 USA. NICHD, LCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 370A EP 370A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801812 ER PT J AU Niu, SL Litman, BJ AF Niu, SL Litman, BJ TI Thermodynamic contribution of membrane lipid composition to cholesterol distribution in cell membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 370A EP 370A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801810 ER PT J AU Veatch, SL Gawrisch, K Keller, SL AF Veatch, SL Gawrisch, K Keller, SL TI Observing immiscible liquid phases in lipid bilayers containing cholesterol by fluorescence microscopy and NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Washington, Seattle, WA 98195 USA. NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 371A EP 371A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801816 ER PT J AU Eldho, NV Feller, SE Tristram-Nagle, S Polozov, IV Gawrisch, K AF Eldho, NV Feller, SE Tristram-Nagle, S Polozov, IV Gawrisch, K TI Polyunsaturated docosahexaenoic vs. docosapentaenoic acid - Differences in lipid matrix properties from the loss of one double bond SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAAA, NIH, Rockville, MD 20852 USA. Wabash Coll, Crawfordsville, IN 47933 USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 375A EP 375A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801835 ER PT J AU Petrache, HI Thurmond, RL Brown, MF AF Petrache, HI Thurmond, RL Brown, MF TI Material properties of DOPE/DOPC mixtures measured by POPC-d31 probesin solid-state 2H NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, LPSB, NIH, Bethesda, MD 20892 USA. Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 375A EP 375A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801834 ER PT J AU Wang, SQ Stern, MD Rios, E Cheng, HP AF Wang, SQ Stern, MD Rios, E Cheng, HP TI The quantal nature of Ca2+ sparks reveals nanoscopic interaction between ryanodine receptors in vivo SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIA, NIH, Baltimore, MD 21224 USA. Rush Univ, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 385A EP 385A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801886 ER PT J AU Song, LS Lederer, WJ Shou, WN Cheng, HP AF Song, LS Lederer, WJ Shou, WN Cheng, HP TI Modulation of RyR2 gating by FKBP12 in mouse myocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Maryland, Baltimore, MD 21201 USA. Indiana Univ, Indianapolis, IN 46202 USA. NIA, Baltimore, MD 21224 USA. RI Lederer, William/B-1285-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 429A EP 429A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802098 ER PT J AU Joubert, F Combs, C Balaban, RS AF Joubert, F Combs, C Balaban, RS TI Characterization of dehydrogenase (DH) activity using NADH ED-FRAP SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 457A EP 458A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802237 ER PT J AU Rosales, TJ Wu, X Brooks, B Xu, JH Knutson, J AF Rosales, TJ Wu, X Brooks, B Xu, JH Knutson, J TI Molecular dynamics simulations of perylene libration and rotations in hexadecane: Comparison with femtosecond upconversion data. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NHLBI, Natl Inst Hlth, Bethesda, MD 20894 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 465A EP 465A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802275 ER PT J AU Toptygin, D Xu, JH Savtchenko, RS Meadow, ND Roseman, S Knutson, JR Brand, L AF Toptygin, D Xu, JH Savtchenko, RS Meadow, ND Roseman, S Knutson, JR Brand, L TI Femtosecond relaxation dynamics of a single Trp in the E21W mutant of IIA(Glc). SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 478A EP 478A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802346 ER PT J AU Bakajin, O Lipman, EA Schuler, B Eaton, WA AF Bakajin, O Lipman, EA Schuler, B Eaton, WA TI Observations of time-resolved single molecule protein folding in a microfabricated mixer SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 LLNL, Livermore, CA 94550 USA. NIH, Bethesda, MD 20892 USA. Univ Potsdam, D-14476 Golm, Germany. RI Schuler, Benjamin/E-7342-2011 OI Schuler, Benjamin/0000-0002-5970-4251 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 491A EP 491A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802412 ER PT J AU Esser, L Wen, XL Li, YF Gao, XG Yu, CA Xia, D AF Esser, L Wen, XL Li, YF Gao, XG Yu, CA Xia, D TI Comparison of native and inhibitor-bound mitochondrial bc1 complexes: Insight into capture-and-release mechanism of ISP SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, NIH, Bethesda, MD 20892 USA. Oklahoma State Univ, Noble Res Ctr 246, Stillwater, OK 74078 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 493A EP 493A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802420 ER PT J AU Gao, XG Wen, XL Yu, CA Esser, L Yu, L Xia, D AF Gao, XG Wen, XL Yu, CA Esser, L Yu, L Xia, D TI The crystal structure of mitochondrial cytochrome bc1 in complex with famoxadone: The role of aromatic-aromatic interaction in inhibition SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NCI, NIH, Bethesda, MD 20892 USA. Oklahoma State Univ, Noble Res Ctr 246, Stillwater, OK 74078 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 503A EP 503A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802473 ER PT J AU Reily, MM Harvey, JJ Knutson, JR Han, MK Lewis, MS AF Reily, MM Harvey, JJ Knutson, JR Han, MK Lewis, MS TI HIV-1 integrase: Thermodynamics of oligomerization and the effects of DNA binding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 505A EP 505A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802480 ER PT J AU Petrache, HI Rau, DC Podgornik, R Parsegian, VA AF Petrache, HI Rau, DC Podgornik, R Parsegian, VA TI Swelling of neutral lipids driven by monovalent salts SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NICHD, LPSB, NIH, Baltimore, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 510A EP 511A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802508 ER PT J AU Alcaraz, A Nestorovich, EM Aguilella, VM Bezrukov, SM AF Alcaraz, A Nestorovich, EM Aguilella, VM Bezrukov, SM TI Salting out large pore ion selectivity: studies with OmpF SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Jaume 1, E-12080 Castellon, Spain. NIH, Bethesda, MD 20892 USA. RI Aguilella, Vicente/B-7592-2008; Alcaraz, Antonio/F-8498-2016 OI Aguilella, Vicente/0000-0002-2420-2649; NR 0 TC 1 Z9 1 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 533A EP 533A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802621 ER PT J AU Danelon, C Nestorovich, EM Winterhalter, M Bezrukov, SM AF Danelon, C Nestorovich, EM Winterhalter, M Bezrukov, SM TI Interaction of antibiotics with the OmpF channel: effect on translocation. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 IPBS, F-31077 Toulouse, France. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 534A EP 534A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802623 ER PT J AU Brown, CU Berrien, LSJ Nahirney, PC Gutierrez, G Wang, K AF Brown, CU Berrien, LSJ Nahirney, PC Gutierrez, G Wang, K TI Viscoelastic properties of the sonic muscle in the Type I Midshipman fish SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 561A EP 561A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802757 ER PT J AU Forbes, JG Morris, HD Wang, K AF Forbes, JG Morris, HD Wang, K TI High-resolution MRI of muscle fiber orientation in the sonic organ of the midshipman fish SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAMS, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 561A EP 561A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802758 ER PT J AU Gu, J Xu, SG Wang, K Yu, LC AF Gu, J Xu, SG Wang, K Yu, LC TI X-ray diffraction and structural modeling of the broad Z-bands of type 1 sonic muscle of midshipman fish SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 561A EP 561A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802756 ER PT J AU Lewis, MK Gutierrez-Cruz, G Wang, K AF Lewis, MK Gutierrez-Cruz, G Wang, K TI Nebulin interaction investigated with single molecule fluorescence microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 562A EP 563A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802763 ER PT J AU Lewis, MK Nahirney, PC Wang, K AF Lewis, MK Nahirney, PC Wang, K TI Structural attributes of a high endurance sonic muscle of the Midshipman fish SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 562A EP 562A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802759 ER PT J AU Xu, SG Gu, J Yu, LC AF Xu, SG Gu, J Yu, LC TI Structure of the thick filament reacted with BTS (N-benzyl-p-toluene sulphonamide) in skinned rabbit psoas muscle fibers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 562A EP 562A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802760 ER PT J AU Adhikari, BB Wang, K AF Adhikari, BB Wang, K TI Interplay of troponin- and myosin-based pathways of calcium activation in skeletal and cardiac muscle: The use of W7 and BDM as specific inhibitors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 569A EP 569A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802794 ER PT J AU Giulian, GG Hwang, JS Goldie, SN Krogmeier, JR Bardo, AM Goldner, LS Merril, CR AF Giulian, GG Hwang, JS Goldie, SN Krogmeier, JR Bardo, AM Goldner, LS Merril, CR TI Examination of dodecyl sulfate properties in SDS-PAGE SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIH, Bethesda, MD 20892 USA. NIST, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 583A EP 583A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802865 ER PT J AU Kobrinsky, E Abernethy, DR Soldatov, NM AF Kobrinsky, E Abernethy, DR Soldatov, NM TI Ca2+ signaling and voltage-gated mobility of Ca(v)1.2 channel C-terminal tail. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 583A EP 583A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802866 ER PT J AU Arie, T Jin, AJ Dvorak, JA AF Arie, T Jin, AJ Dvorak, JA TI Analyses of changes in the erythrocyte flicker phenomenon resulting from infection with Plasmodium falciparum malaria SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 NIAID, Natl Inst Hlth, Lab Malaria Res & Vector Biol, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 586A EP 586A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802881 ER PT J AU Ospeck, M Dong, XX Iwasa, KH AF Ospeck, M Dong, XX Iwasa, KH TI Limiting frequency of the cochlear amplifier based on electromotility of outer hair cells SO BIOPHYSICAL JOURNAL LA English DT Article ID GUINEA-PIG COCHLEA; BASILAR-MEMBRANE; PIEZOELECTRIC MODEL; MAMMALIAN COCHLEA; FORCE GENERATION; MOUSE COCHLEA; RESPONSES; MOTILITY; CURRENTS; HEARING AB Outer hair cells are the critical element for the sensitivity and sharpness of frequency selectivity of the ear. It is believed that fast motility (electromotility) of these cells is essential for this function. Indeed, force produced by outer hair cells follows their membrane potential very closely at least up to 60 kHz. However, it has been pointed out that the cell's receptor potential is attenuated by a low-pass RC circuit inherent to these cells, with the RC roll-off frequencies significantly lower than their operating frequencies. This would render electromotility ineffective in producing force. To address this issue, we assume that multiple degrees of freedom and vibrational modes due to the complex structure of the organ of Corti provide optimal phases for outer hair cells' force to cancel viscous drag. Our derived frequency limit depends on the drag-capacitance product, not directly on the RC time constant. With a reasonable assumption for the viscous drag, the estimated limit is 10-13 kHz, exceeding the RC corner frequency. Our analysis shows that a fast-activating potassium current can substantially extend the frequency limit by counteracting the capacitive current. C1 Natl Inst Deafness & Other Commun Disorders, Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), Natl Inst Deafness & Other Commun Disorders, Biophys Sect, NIH, Bldg 50,Room 4152,50 South Dr,MSC-8027, Bethesda, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 62 TC 35 Z9 36 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 BP 739 EP 749 PN 1 PG 11 WC Biophysics SC Biophysics GA 682ZV UT WOS:000183123700002 PM 12547758 ER PT J AU Berezhkovskii, AM Gopich, IV AF Berezhkovskii, AM Gopich, IV TI Translocation of rodlike polymers through membrane channels SO BIOPHYSICAL JOURNAL LA English DT Article ID LAPLACE TRANSFORMS; PORE; TRANSPORT; MOLECULES; MODEL; HOLE; ADSORPTION; INVERSION; DYNAMICS; ENTRY AB A theory of channel-facilitated transport of long rodlike macromolecules through thin membranes under the influence of a driving force of arbitrary strength is developed. Analytic expressions are derived for the translocation probability and the Laplace transform of the probability density of time that a macromolecule spends in the channel. We also derive expressions for the (conditional) probability densities of time spent in the channel by translocating and nontranslocating (returning back) macromolecules. These results are used to study how the distribution of the macromolecule lifetime in the channel depends on a polymer chain length and the driving force. It is shown that depending on the values of the parameters, the lifetime probability density may have one or two peaks. Our theory is a generalization of the theory developed by Lubensky and Nelson, who were inspired by recent experiments on driven translocation of single-stranded RNA and DNA molecules through single channels in narrow membranes. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Gopich, IV (reprint author), NIDDK, Phys Chem Lab, NIH, Bldg 5-136, Bethesda, MD 20892 USA. EM irinag@speck.niddk.nih.gov NR 33 TC 34 Z9 35 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 BP 787 EP 793 PN 1 PG 7 WC Biophysics SC Biophysics GA 682ZV UT WOS:000183123700007 PM 12547763 ER PT J AU Ross, PD Howard, FB AF Ross, PD Howard, FB TI The thermodynamic contribution of the 5-methyl group of thymine in the two- and three-stranded complexes formed by poly(dU) and poly(dT) with poly(dA) SO BIOPOLYMERS LA English DT Article DE thymine methyl group contribution; nucleic acid stability; poly(dU); poly(dT); poly(dA); thermodynamics of nucleic acid duplexes; thermodynamics of nucleic acid triplexes; differential scanning calorimetry ID A.U BASE-PAIRS; CONFORMATIONAL TRANSITIONS; NUCLEIC-ACIDS; TRIPLE-HELIX; DNA; STABILITY; DUPLEXES; EQUILIBRIA; ENERGETICS; STACKING AB To assess the thermodynamic contribution of the 5-methyl group of thymine, we have studied the two-stranded helical complexes poly(dA) . poly(dU) and poly(dA) . poly(dT) and the three-stranded complexes-poly(dA) . 2poly(dU), poly(dA) . poly,(dT) . poly(dU) and poly(dA) . 2poly(dT)-by, differential scanning calorimetry, and uv optical melting experiments. The thermodynamic quantities associated with the 3 --> 2, 2 --> 1, and 3 --> 1 melting transitions are found to vary with salt concentration and temperature in a more complex manner than commonly believed. The transition temperatures, T-m are generally not linear in the logarithm of concentration or activity of NaCl. The change in enthalpy and in entropy, upon melting varies with salt concentration and temperature, and a change in heat capacity accompanies each transition. The poly(dA) . 2poly(dU) triple helix is markedly, different from poly(dA) . 2poly(dT) in both its CD spectrum and thermodynamic behavior, while the poly(dA) . poly(dT) . poly(dU) triple helix resembles poly(dA) 2poly(dT) in these properties. In comparing poly(dA) . 2poly(dT) with either the poly(dA) poly(dT) . poly(dU) or the poly(dA) . 2poly(dU) triplexes, the substitution of thymine for uracil in the third strand results in an enhancement of stability against the 3 --> 2 dissociation of DeltaDeltaGdegrees = -135 +/- 85 cal (mol A)(-1) at 37degreesC. This represents a doubling of the absolute stability toward dissociation compared to the triplexes with poly(dU) as the third strand. The poly (dA) . poly (dT) duplex is more stable than poly(dA) . poly(dU) by DeltaDeltaGdegrees = -350 +/- 60 cal (mol base pair)(-1) at 37degreesC. Poly(dA) . poly(dT) has 50% greater stability than poly(dA) . poly(dU) as a result of the dT for dU substitution in the duplex. (C) 2003 Wiley Periodicals, Inc. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ross, PD (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 37 TC 16 Z9 16 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD FEB PY 2003 VL 68 IS 2 BP 210 EP 222 DI 10.1002/bip.10306 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 642PD UT WOS:000180812000006 PM 12548624 ER PT J AU Xiang, CC Chen, M Kozhich, OA Phan, QN Inman, JM Chen, Y Brownstein, MJ AF Xiang, CC Chen, M Kozhich, OA Phan, QN Inman, JM Chen, Y Brownstein, MJ TI Probe generation directly from small numbers of cells for DNA microarray studies SO BIOTECHNIQUES LA English DT Article ID GENE-EXPRESSION; CDNA MICROARRAYS; RNA AMPLIFICATION AB Recently, we described a technique that allows us to prepare probes for expression profiling from 0.5-1 mug RNA without template or signal amplification. However we were unable to use this method to study cells harvested by needle biopsy, cell sorting, or laser capture microdissection. Here we give a new protocol for amplifying RNA with multiple reaction cycles and preparing fluorescent probes from approximately 10 cells. We use random 9-mers with a T3 RNA polymerase recognition sequence on the 5' end for every round of cDNA synthesis except the first. The latter is primed with oligo(dT) with a T7 RNA polymerase recognition sequence on the 5' end. Results were highly reproducible and reliable, and the products generated using our method seemed comparable to those produced using the RiboAmp RNA kit when both were used to do two cycles of amplification. To test our methods utility, we lysed cells directly into reverse transcription buffer containing RNase inhibitor and performed three rounds of RNA amplification. The expression profiles of mouse C2 and NIH 3T3 cells obtained with 11 232-element arrays using amplified RNAs were similar to those seen when probes were prepared from unamplified templates. C1 NIMH, NHGRI, Genet Lab, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Brownstein, MJ (reprint author), NIMH, NHGRI, Genet Lab, Bldg 36,Room 3D06, Bethesda, MD 20892 USA. RI Brownstein, Michael/B-8609-2009 FU NCI NIH HHS [N01-CO-12400.] NR 15 TC 20 Z9 20 U1 1 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD FEB PY 2003 VL 34 IS 2 BP 386 EP + PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 643ZB UT WOS:000180892500020 PM 12613261 ER PT J AU Lillard, JW Singh, UP Boyaka, PN Singh, S Taub, DD McGhee, JR AF Lillard, JW Singh, UP Boyaka, PN Singh, S Taub, DD McGhee, JR TI MIP-1 alpha and MIP-1 beta differentially mediate mucosal and systemic adaptive immunity SO BLOOD LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-BETA; T-CELL PROLIFERATION; C CHEMOKINE RECEPTOR; IN-VIVO; EPITHELIAL-CELLS; CHOLERA-TOXIN; B-CELLS; REGULATED EXPRESSION; HUMAN HERPESVIRUS-8; MOLECULAR-CLONING AB Macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta are distinct but highly homologous CC chemokines produced by a variety of host cells in response to various external stimuli and share affinity for CCR5. To better elucidate the role of these CC chemokines in adaptive immunity, we have characterized. the affects of MIP-1alpha and MIP-1beta on cellular and humoral immune responses. MIP-1beta Stimulated strong antigen (Ag)-specific serum immunoglobulin G (IgG) and IgM responses, while MIP-1beta promoted lower IgG and IgM but higher serum IgA and IgE antibody (Ab) responses. MO-1ot elevated Ag-specific IgG1 and IgG2b followed by IgG2a and IgG3 subclass responses, while MIP-1beta only stimulated IgG1 and IgG2b subclasses. Correspondingly, MIP-1beta produced higher, titers of Ag-specific mucosal secretory IgA Ab levels when compared with MIP-1alpha. Splenic T cells from MIP-1alpha- or MIP-1beta-treated mice displayed higher Ag-specific Th1 (interferon-gamma [IFN-gamma]) as well as selective Th2 (interleukin-5 [IL-5] and IL-6) cytokine responses than did T cells from control groups. Interestingly, mucosally derived T cells from MIP-10-treated mice displayed higher levels of IL-4 and IL-6 compared with MIP-1alpha-treated mice. However, MIP-1alpha effectively enhanced Ag-specific cell-mediated immune responses. In correlation with their selective effects on humoral and cellular immune responses, these chemokines also differentially attract CD4(+) versus CD8(+) T cells and modulate CD40, CD80, and CD86 expressed by B220(+) cells as well as CD28, 4-1BB, and gp39 expression by CD4(+) and CD8(+) T cells in a dose-dependent fashion. Taken together, these studies suggest that these CC chemokines differentially enhance mucosal and serum humoral as well as cellular immune responses. (C) 2003 by The American Society of Hematology. C1 NIA, Immunol Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Alabama, Immunobiol Vaccine Ctr, Birmingham, AL USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Morehouse Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30310 USA. RP McGhee, JR (reprint author), Univ Alabama, Dept Microbiol, 845 19th St S,BBRB 761, Birmingham, AL 35294 USA. FU NCRR NIH HHS [RR03034]; NIAID NIH HHS [AI18958, AI43197]; NIDCD NIH HHS [DC04976]; NIDDK NIH HHS [DK58967, P30 DK54781]; NIGMS NIH HHS [GM08248] NR 72 TC 57 Z9 61 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2003 VL 101 IS 3 BP 807 EP 814 DI 10.1182/blood-2002-07-2305 PG 8 WC Hematology SC Hematology GA 640GG UT WOS:000180679700003 PM 12393512 ER PT J AU Rosenberg, PS Greene, MH Alter, BP AF Rosenberg, PS Greene, MH Alter, BP TI Cancer incidence in persons with Fanconi anemia SO BLOOD LA English DT Article ID HUMAN-PAPILLOMAVIRUS; ASSOCIATION; REGISTRY AB Fanconi anemia (FA) is an autosomal recessive condition associated with congenital abnormalities, progressive pancytopenia, and a predisposition to leukemia and solid tumors. We studied a retrospective cohort of North American patients with FA. We calculated relative risks of cancer compared to the general population and cause-specific hazards of the first major adverse outcomes of FA: bone marrow transplantation (BMT) for marrow complications, acute myeloid leukemia (AML), solid tumors, or death from bone marrow failure. We also estimated the cumulative incidence of each adverse event in the presence of the competing risks. Among 145 patients with FA, 9 developed leukemia and 14 developed a total of 18 solid tumors. The ratio of observed to expected cancers (O/E ratio) was 50 for all cancers, 48 for all solid tumors, and 785 for leukemia; these increased risks were statistically significant. The highest solid tumor O/E ratios were 4317 for vulvar cancer, 2362 for esophageal cancer, and 706 for head and neck cancer. Cause-specific hazards of both death and AML peaked at 1%/y in teenage years; the hazard of BIMT peaked at 4%/y at age 7. In contrast, the hazard of a solid tumor approached 8%/y by age 40 years. The cumulative incidence to age 48 was 10% for leukemia, 11% for death from marrow failure, 29% for a solid tumor, and 43% for BMT. The risk of a solid tumor may become even higher as death from aplastic anemia is reduced and as patients survive longer after BMT. (C) 2003 by The American Society of Hematology. C1 NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD USA. NCI, Biostat Branch, Rockville, MD USA. RP Alter, BP (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, 6120 Execut Blvd,Execut Plaza S,Rm 7020, Rockville, MD USA. NR 27 TC 226 Z9 230 U1 1 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2003 VL 101 IS 3 BP 822 EP 826 DI 10.1182/blood-2002-05-1498 PG 5 WC Hematology SC Hematology GA 640GG UT WOS:000180679700005 PM 12393424 ER PT J AU Tsujimura, H Tamura, T Gongora, C Aliberti, J Sousa, CRE Sher, A Ozato, K AF Tsujimura, H Tamura, T Gongora, C Aliberti, J Sousa, CRE Sher, A Ozato, K TI ICSBP/IRF-8 retrovirus transduction rescues dendritic cell development in vitro SO BLOOD LA English DT Article ID SEQUENCE-BINDING-PROTEIN; TOLL-LIKE RECEPTOR-2; IN-VIVO; TRANSCRIPTION FACTOR; IFN-GAMMA; TRANSACTIVATOR CIITA; MYELOID PROGENITORS; MOUSE MACROPHAGES; INTERFERON-GAMMA; IMMUNE-RESPONSE AB Dendritic cells (DCs) develop from bone marrow (BM) progenitor cells and mature in response to external signals to elicit functions important for innate and adaptive immunity. Interferon consensus sequence binding protein (ICSBP; also called interferon regulatory factor 8 [IRF-8]) is a hematopoietic cell-specific transcription factor expressed in BM progenitor cells that contributes to myeloid cell development. In light of our earlier observation that ICSBP-/- mice lack CD8alpha(+) DCs, we investigated the role of ICSBP in DC development in vitro in the presence of FIt3 ligand. Immature ICSBP-/- DCs developed from BM progenitor cells showed assorted defects, did not mature in response to activation signals, and failed to express CD8alpha and interleukin 12 (IL-12) p40, a feature consistent with ICSBP-/- DCs in vivo. We show that retroviral introduction of ICSBP restores the development of immature DCs that can fully mature on activation signals. All the defects seen with ICSBP-/- DCs were corrected after ICSBP transduction, including the expression. of CD8a and IL-12 p40 as well as major histocompatability complex class II and other costimulatory molecules. ICSBP is known to regulate gene expression by interacting with partner proteins PU.1 and IRFs, thereby binding to target elements ISRE and EICE. Analysis of a series of ICSBP mutants showed that the intact DNA-binding activity as well as the ability to interact with partner proteins are required for the restoration of DC development/maturation, pointing to the transcriptional function of ICSBP as a basis of restoration. Taken together, this study identifies ICSBP as a factor critical for both early differentiation and final maturation of DCs. (C) 2003 by The American Society of Hematology. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Canc Res United Kingdon, London Res Inst, Immunobiol Lab, London, England. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Rm 2A01,6 Ctr Dr MSC 2753, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013; OI Aliberti, Julio/0000-0003-3420-8478; Reis e Sousa, Caetano/0000-0001-7392-2119 NR 48 TC 74 Z9 76 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2003 VL 101 IS 3 BP 961 EP 969 DI 10.1182/blood-2002-05-1327 PG 9 WC Hematology SC Hematology GA 640GG UT WOS:000180679700027 PM 12393459 ER PT J AU Shi, YF Devadas, S Greeneltch, KM Yin, DL Mufson, RA Zhou, JN AF Shi, YF Devadas, S Greeneltch, KM Yin, DL Mufson, RA Zhou, JN TI Stressed to death: Implication of lymphocyte apoptosis for psychoneuroimmunology SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article; Proceedings Paper CT Scientific Meeting on Biological Mechanisms of Psychosocial Effects on Diseases (BiMPED) CY FEB 28-MAR 01, 2002 CL BETHESDA, MARYLAND DE chronic stress; endogenous opioids; Fas (CD95); apoptosis; corticosteroid; immunosuppression; lymphocytes ID CELL-MEDIATED-IMMUNITY; CENTRAL-NERVOUS-SYSTEM; OPIOID RECEPTOR TYPES; FAS-LIGAND; T-CELLS; CIRCULATING LYMPHOCYTES; IMMATURE THYMOCYTES; NITRIC-OXIDE; BONE-MARROW; IN-VIVO AB Psychological and physical stressors best exemplify the intercommunication of the immune and the nervous systems. It has been shown that stress significantly impacts leukocyte cellularity and immune responses and alters susceptibility to various diseases. While acute stress has been shown to enhance immune responses, chronic stress often leads to immuno suppression. Among many criteria examined upon exposure to chronic stress, the reduction in lymphocyte mitogenic response and lymphocyte cellularity are commonly assessed. We have reported that chronic restraint stress could induce lymphocyte reduction, an effect dependent on endogenous opioids. Interestingly, the effect of endogenous opioids was found to be exerted through increasing the expression of a cell death receptor, Fas, and an increased sensitivity of lymphocytes to apoptosis. Stress-induced lymphocyte reduction was not affected by adrenalectomy. In this review, based on available literature and our recent data, we will discuss the role of the hypothalamic-pituitary-adrenal axis and endogenous opioids and examine the mechanisms by which chronic stress modulates lymphocyte apoptosis. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Microbiol Mol Genet & Immunol, Piscataway, NJ 08854 USA. Amer Red Cross, Jerome H Holland Lab, Dept Immunol, Rockville, MD 20855 USA. NCI, Canc Immunol & Hematol Branch, Bethesda, MD 20892 USA. RP Shi, YF (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Microbiol Mol Genet & Immunol, 661 Hoes Lane, Piscataway, NJ 08854 USA. EM shiyu@umdnj.edu FU NIAID NIH HHS [AI50222, AI43384] NR 100 TC 41 Z9 42 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD FEB PY 2003 VL 17 SU 1 BP S18 EP S26 AR PII S0889-1591(02)00062-4 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 660AQ UT WOS:000181812100005 PM 12615182 ER PT J AU Stefanek, M McDonald, PG AF Stefanek, M McDonald, PG TI Biological mechanisms of psychosocial effects on disease: Implications for cancer control SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Editorial Material C1 NCI, Basic Biobehav Res Branch, Behav Res Program,Div Canc Control & Populat Sci, US Dept HHS, Bethesda, MD 20852 USA. RP Stefanek, M (reprint author), NCI, Basic Biobehav Res Branch, Behav Res Program,Div Canc Control & Populat Sci, US Dept HHS, 6130 Execut Blvd, Bethesda, MD 20852 USA. EM stefanem@mail.nih.gov; mcdonalp@mail.nih.gov NR 14 TC 1 Z9 1 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 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD FEB PY 2003 VL 17 SU 1 BP S1 EP S4 AR PII S0889-1591(02)00058-2 PG 4 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 660AQ UT WOS:000181812100001 ER PT J AU Smaili, SS Hsu, YT Carvalho, ACP Rosenstock, TR Sharpe, JC Youle, RJ AF Smaili, SS Hsu, YT Carvalho, ACP Rosenstock, TR Sharpe, JC Youle, RJ TI Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Review DE Ca2+; mitochondrial Ca2+ uptake; mitochondrial Ca2+ efflux; permeability transition; Bcl-2 family; Bax and apoptosis ID CYTOCHROME-C RELEASE; PERMEABILITY TRANSITION PORE; BCL-X-L; OXIDATIVE STRESS; PROAPOPTOTIC BAX; CA2+ SIGNALS; DYSFUNCTION; ACTIVATION; TRANSLOCATION; MECHANISMS AB Cellular Ca2+ signals are crucial in the control of most physiological processes, cell injury and programmed cell death through the regulation of a number of Ca2+-dependent enzymes such as phospholipases, proteases, and nucleases. Mitochondria along with the endoplasmic reticulum play pivotal roles in regulating intracellular Ca2+ content. Mitochondria are endowed with multiple Ca2+ transport mechanisms by which they take up and release Ca2+ across their inner membrane. During cellular Ca2+ overload, mitochondria take up cytosolic Ca2+ which in turn induces opening of permeability transition pores and disrupts the mitochondrial membrane potential (Deltapsi(m)). The collapse of Deltapsi(m) along with the release of cytochrome c from mitochondria is followed by the activation of caspases, nuclear fragmentation and cell death. Members of the Bcl-2 family are a group of proteins that play important roles in apoptosis regulation. Members of this family appear to differentially regulate intracellular Ca2+ level. Translocation of Bax, an apoptotic signaling protein, from the cytosol to the mitochondrial membrane is another step in this apoptosis signaling pathway. C1 Univ Fed Sao Paulo, Escola Paulista Med, Inst Farmacol, Dept Farmacol, Sao Paulo, Brazil. Univ So Carolina, Dept Biochem, Charleston, SC USA. NINDS, Biochem Sect, NIH, Bethesda, MD 20892 USA. RP Smaili, SS (reprint author), Rua Tres de Maio 100, BR-04044020 Sao Paulo, Brazil. RI Rosenstock, Tatiana/N-1949-2013 OI Rosenstock, Tatiana/0000-0003-1153-7412 NR 60 TC 76 Z9 85 U1 0 U2 3 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD FEB PY 2003 VL 36 IS 2 BP 183 EP 190 PG 8 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 648DZ UT WOS:000181135700004 PM 12563519 ER PT J AU Christov, K Ikui, A Shilkaitis, A Green, A Yao, RS You, M Grubbs, C Steele, V Lubet, R Weinstein, IB AF Christov, K Ikui, A Shilkaitis, A Green, A Yao, RS You, M Grubbs, C Steele, V Lubet, R Weinstein, IB TI Cell proliferation, apoptosis, and expression of cyclin D1 and cyclin E as potential biomarkers in tamoxifen-treated mammary tumors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE apoptosis; cyclin D1; mammary tumors; proliferation; tamoxifen ID SURGICAL-ADJUVANT-BREAST; N-NITROSOMETHYLUREA; ESTROGEN-RECEPTOR; CANCER; CARCINOGENESIS; PREVENTION; GLAND; LESIONS; THERAPY; GROWTH AB Tamoxifen has been widely used for treatment, and more recently, for the prevention of breast cancer. Since breast carcinomas are composed of heterogeneous populations of estrogen receptor-positive (ER+) cells, we hypothesized that tamoxifen may suppress tumor growth by differentially affecting cell proliferation and apoptosis. ER+ mammary tumors were induced in Sprague-Dawley rats by N-methyl-N-nitrosourea (MNU) and when they became palpable, the animals were treated for 5, 10, or 20 days with tamoxifen, 1.0 mg/kg body weight. Tamoxifen induced a time-dependent decrease in proliferating (BrdU-Iabeled) cells, arrested the cells in G1/0 phase, and differentially decreased the cyclin E and cyclin D1 expression at mRNA and protein levels. In the same tumors, apoptotic cells increased during the first 10 days of treatment, but their number remained unchanged with extension of the treatment to 20 days. Thus, we provide data that tamoxifen may differentially affect cell proliferation and apoptosis in mammary tumors and that the expression levels of cyclin D1 and cyclin E might also be considered potential intermediate biomarkers of response of mammary tumors to tamoxifen and possibly to other selective estrogen receptor modulators (SERMs). C1 Univ Illinois, Dept Surg Oncol, Chicago, IL 60612 USA. Columbia Univ, Herbert Irving Comprehens Canc Ctr, Dept Surg Oncol, New York, NY USA. Ohio State Univ, Dept Human Genet, Columbus, OH 43210 USA. Univ Alabama, Prevent Ctr, Birmingham, AL USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Christov, K (reprint author), Univ Illinois, Dept Surg Oncol, 840 S Wood St M-C 820, Chicago, IL 60612 USA. FU NCI NIH HHS [CN-55179] NR 33 TC 25 Z9 30 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2003 VL 77 IS 3 BP 253 EP 264 DI 10.1023/A:1021804121171 PG 12 WC Oncology SC Oncology GA 631MD UT WOS:000180170800007 PM 12602925 ER PT J AU Soars, MG Gelboin, HV Krausz, KW Riley, RJ AF Soars, MG Gelboin, HV Krausz, KW Riley, RJ TI A comparison of relative abundance, activity factor and inhibitory monoclonal antibody approaches in the characterization of human CYP enzymology SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE HLM monoclonal antibody; intrinsic clearance; reaction phenotyping; recombinant CYP ID HUMAN LIVER-MICROSOMES; EXPRESSED CYTOCHROMES P450; IN-VITRO; DRUG-METABOLISM; N-DEMETHYLATION; IDENTIFICATION; CYP2C19; 2C19; 3A4; BIOTRANSFORMATION AB Aims The objective of this study was to evaluate the potential uses of relative abundance, relative activity approaches and inhibitory monoclonal antibodies (mAbs) in the characterization of CYP enzymology in early drug discovery. Methods Intrinsic clearance estimates for the oxidation of ethoxyresorufin (a selective probe of CYP1A2 activity), tolbutamide (CYP2C9), S-mephenytoin (CYPC19), dextromethorphan (CYP2D6) and testosterone (CYP3A4) were used to determine relative activity factors (RAFs). CLint values were determined for the metabolism of 14 drugs in human liver microsomes (HLM) and for these major CYPs. The relative contribution of each individual CYP to the oxidation of each drug was then assessed using relative abundance and activity techniques in addition to inhibitory mAbs. Results Relative abundance and activity methods as well as inhibitory mAbs qualitatively assigned the same CYP isoform as predominantly responsible for the clearance of each drug by HLM. Metabolism catalysed by CYP1A2, 2C9, 2D6 and 3A4 was also predicted to be quantitatively similar using both abundance and activity techniques. However, the relative contribution of the polymorphic CYP2C19 appeared to be over-estimated approximately two-fold using recombinant CYP compared with that from the HLM and mAb approach. Conclusions All three methods investigated in this study appear suitable for use in the characterization of the CYP metabolism of new chemical entities produced during early drug discovery. C1 AstraZeneca Charnwood, Dept Phys & Metab Sci, Loughborough LE11 5RH, Leics, England. Natl Canc Inst, Mol Carcinogenesis Lab, NIH, Bethesda, MD USA. RP Riley, RJ (reprint author), AstraZeneca Charnwood, Dept Phys & Metab Sci, Bakewell Rd, Loughborough LE11 5RH, Leics, England. NR 29 TC 29 Z9 30 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD FEB PY 2003 VL 55 IS 2 BP 175 EP 181 DI 10.1046/j.1365-2125.2003.01721.x PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 644PR UT WOS:000180927700008 PM 12580989 ER PT J AU Uneda, S Hata, H Matsuno, F Nagasaki, A Harada, N Mitsuya, Y Matsuzaki, H Mitsuya, H AF Uneda, S Hata, H Matsuno, F Nagasaki, A Harada, N Mitsuya, Y Matsuzaki, H Mitsuya, H TI A nitric oxide synthase inhibitor, N-G-nitro-L-arginine-methyl-ester, exerts potent antiangiogenic effects on plasmacytoma in a newly established multiple myeloma severe combined immunodeficient mouse model SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE NOS inhibitor; multiple myeloma; angiogenesis; SCID mouse; myeloma animal model ID ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW ANGIOGENESIS; ANTITUMOR-ACTIVITY; PROGRESSION; CANCER; THALIDOMIDE; TAXOL; EXPRESSION; PACLITAXEL; MELPHALAN AB Angiogenesis is one of critical factors in sustaining the growth, invasion and metastasis of certain solid tumours and haematological malignancies such as multiple myeloma (MM). In the present study, we examined the anticancer potential of an inhibitor of nitric oxide synthase (NOS), N-G -nitro-l-arginine methyl ester (L-NAME), in a novel severe combined immunodeficient mouse model (KHM mouse) that harbours the highly sanguineous plasmacytoma cell line KHM-4, derived from a patient with highly chemoresistant MM. KHM mice were intraperitoneally administered with either L-NAME, doxorubicin, melphalan, or paclitaxel. A significant reduction in tumour sizes was noted in L-NAME-administered KHM mice while no significant reduction was observed in melphalan- or doxorubicin-administered mice. A profound decrease in angiogenesis was observed in tumour tissues from L-NAME- and paclitaxel-administered KHM mice. A marked decrease in human vascular endothelial cell growth factor (VEGF) levels was identified in tumour tissues from L-NAME-administered KHM mice, strongly suggesting that L-NAME suppressed VEGF production by tumour cells through its inhibition of NOS in tumour cells, resulting in reduced neovasculization in mice leading to the regression of tumour sizes. The present data represent the first observations that certain NOS inhibitors potentially serve as experimental agents for the treatment of chemoresistant MM and plasmacytoma. C1 Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 8608556, Japan. Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan. NCI, Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Hata, H (reprint author), Kumamoto Univ, Sch Med, Dept Internal Med 2, Honjo 1-1-1, Kumamoto 8608556, Japan. NR 41 TC 17 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2003 VL 120 IS 3 BP 396 EP 404 DI 10.1046/j.1365-2141.2003.04078.x PG 9 WC Hematology SC Hematology GA 643DP UT WOS:000180846900003 PM 12580953 ER PT J AU Trendelenburg, AU Gomeza, J Klebroff, W Zhou, HX Wess, J AF Trendelenburg, AU Gomeza, J Klebroff, W Zhou, HX Wess, J TI Heterogeneity of presynaptic muscarinic receptors mediating inhibition of sympathetic transmitter release: a study with M-2- and M-4-receptor-deficient mice SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE presynaptic muscarinic receptors; muscarinic receptor subtypes; sympathetic axon terminals; H-3-noradrenaline; M-2-knockout; M-4-knockout; mouse atria; mouse urinary bladder; mouse vas deferens; heterogeneity ID KNOCKOUT MICE; PHARMACOLOGICAL CHARACTERIZATION; NORADRENALINE RELEASE; ACETYLCHOLINE; ALPHA(2)-AUTORECEPTORS; MODULATION; SUBTYPES; ATRIA; HEART; CHOLINOCEPTORS AB I Presynaptic muscarinic receptors modulate sympathetic transmitter release. The goal of the present study was to identify the muscarinic receptor subtype(s) mediating inhibition of sympathetic transmitter release in mouse atria, urinary bladder and vas deferens. To address this question, electrically evoked noradrenaline release was assessed using tissue preparations from NMRI, M-2-and M-4-knockout, and the corresponding M-2- and M-4-wildtype mice, after preincubation with H-3-noradrenaline. 2 The muscarinic agonist carbachol decreased evoked tritium overflow (20 pulses/50 Hz) in each tissue and strain investigated. After deletion of the M-2-receptor the maximal inhibition by carbachol was significantly reduced (by 41-72%), but not abolished, in all tissues. After deletion of the M-4-receptor a moderate and significant reduction of the maximal inhibition by carbachol (by 28%) was observed only in the vas deferens. 3 Experiments with the muscarinic antagonists methoctramine and pirenzepine confirmed that the presynaptic muscarinic receptors were predominantly M-2 in atria and bladder and probably a mixture Of M-2 and M-4 in the vas deferens. 4 Experiments in the urinary bladder with the cholinesterase inhibitor physostigmine and the muscarinic antagonist ipratropium demonstrated that endogenously released acetylcholine predominantly acted through M-2-receptors to inhibit noradrenaline release. However, the results do not exclude a minor contribution Of M-4-receptors to this endogenous inhibition. 5 In conclusion, our results clearly indicate that the release-inhibiting muscarinic receptors on postganglionic sympathetic axons in mouse atria, bladder and vas deferens represent mixtures of M-2- and non-M-2-receptors. The non-M-2-receptors remain unknown in atria and the bladder, and may represent primarily M-4-receptors in the vas deferens. These results reveal an unexpected heterogeneity among the muscarinic receptors mediating inhibition of noradrenaline release. C1 Inst Expt & Klin Pharmakol & Toxikol, D-79104 Freiburg, Germany. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Trendelenburg, AU (reprint author), Novartis Ophthalm Res AG, WSJ-386-7-46,POB, CH-4002 Basel, Switzerland. NR 36 TC 23 Z9 27 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD FEB PY 2003 VL 138 IS 3 BP 469 EP 480 DI 10.1038/sj.bjp.0705053 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 646QJ UT WOS:000181045500008 PM 12569072 ER PT J AU Hurst, SA Mauron, A AF Hurst, SA Mauron, A TI Assisted suicide and euthanasia in Switzerland: allowing a role for non-physicians SO BRITISH MEDICAL JOURNAL LA English DT Article ID VOLUNTARY EUTHANASIA C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Geneva, Fac Med, Unite Rech & Enseignement Bioeth, Geneva, Switzerland. RP Hurst, SA (reprint author), NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 NR 20 TC 62 Z9 64 U1 0 U2 9 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD FEB 1 PY 2003 VL 326 IS 7383 BP 271 EP 273 DI 10.1136/bmj.326.7383.271 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 644FY UT WOS:000180908300027 PM 12560284 ER PT J AU Wood, BJ Abraham, J Hvizda, JL Alexander, HR Fojo, T AF Wood, BJ Abraham, J Hvizda, JL Alexander, HR Fojo, T TI Radiofrequency ablation of adrenal tumors and adrenocortical carcinoma metastases SO CANCER LA English DT Article DE adrenal metastases; radiofrequency ablation; adrenocortical carcinoma ID CORTICAL CARCINOMA; LIVER METASTASES; TISSUE ABLATION; ONCOLOGY-GROUP; MITOTANE; CANCER; EXPERIENCE; DISEASE AB BACKGROUND. The current study was performed to analyze the feasibility, safety, imaging appearance, and short-term efficacy of image-guided percutaneous radiofrequency ablation (RFA) of primary and metastatic adrenal neoplasms including adrenocortical carcinoma. METHODS. The procedure was performed using 36 treatment spheres on 15 adrenocortical. carcinoma primary or metastatic tumors in eight patients over 27 months. Tumors ranged from 15 to 90 mm in greatest dimension with a mean of 43 mm. All patients had unresectable tumors or were poor candidates for surgery. Mean follow-up was 10.3 months. RESULTS. All patients were discharged or were free of procedure-related medical care 6-48 hours after the procedures without major complications. All treatments resulted in presumptive coagulation necrosis by imaging criteria, which manifested as loss of previous contrast enhancement in ablated tissue. Eight of 15 (53%) posttreatment thermal lesions lost enhancement and stopped growing on latest follow-up computed tomographic scan. Three of 15 (20%) demonstrated interval growth and four did not change in size. Of these four lesions, two showed contrast enhancement. For smaller tumors with a mean greatest dimension less than or equal to 5 cm, 8 of 12 (67%) tumors were completely ablated, as defined by decreasing size and complete loss of contrast enhancement. Three of 15 (20%) tumors and related thermal lesions were found to have disappeared nearly completely on imaging. CONCLUSIONS. Percutaneous, image-guided RFA is a safe and well tolerated procedure for the treatment of unresectable primary or metastatic adrenocortical carcinoma. The procedure is effective for the short-term local control of small adrenal tumors, and is most effective for tumors less than 5 cm. The survival rate for patients with adrenocortical carcinoma improves when radical excision is performed in selected patients. Aggressive local disease control may potentially influence survival as well. However, further study is required to evaluate survival impact, document long-term efficacy, and to determine if RFA can obviate repeated surgical intervention in specific clinical scenarios. Cancer 2003;97:554- 60. Published 2003 by the American Cancer Society. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Ctr Clin, Bethesda, MD 20892 USA. W Virginia Univ, Mary Babb Randolph Canc Ctr, Sect Hematol Oncol, Morgantown, WV 26506 USA. NCI, Surg Branch, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1C-660, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 24 TC 140 Z9 149 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2003 VL 97 IS 3 BP 554 EP 560 DI 10.1002/cncr.11084 PG 7 WC Oncology SC Oncology GA 637WH UT WOS:000180536400004 PM 12548596 ER PT J AU Gurney, JG Kadan-Lottick, NS Packer, RJ Neglia, JP Sklar, CA Punyko, JA Stovall, M Yasui, Y Nicholson, HS Wolden, S McNeil, DE Mertens, AC Robison, LL AF Gurney, JG Kadan-Lottick, NS Packer, RJ Neglia, JP Sklar, CA Punyko, JA Stovall, M Yasui, Y Nicholson, HS Wolden, S McNeil, DE Mertens, AC Robison, LL TI Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors - Childhood Cancer Survivor Study SO CANCER LA English DT Article DE brain neoplasms; central nervous system neoplasms; epidemiology; treatment effects; surgery; radiation; chemotherapy; late effects; survivorship; children; adolescents; young adults; hypothyroidism; growth deficiency; stroke ID CENTRAL-NERVOUS-SYSTEM; THYROID-DYSFUNCTION; SEQUELAE; MEDULLOBLASTOMA; RADIOTHERAPY; DISEASE; RISK AB BACKGROUND. Survivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long-term effects of CBTs has been comprised of single-institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group. METHODS. As part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self-reported late effects were ascertained from a survey questionnaire of 1607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS. RESULTS. one or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late-onset (greater than or equal to 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% Cl] 9.7-21.0), growth hormone deficiency (RR = 277.8; 95% Cl 111.1-694.9), the need for medications to induce puberty (RR 86.1; 95% CI 31.1-238.2), and osteoporosis (RR = 24.7; 95% Cl 9.9-61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late-onset risk for stroke (RR = 42.8; 95% Cl 16.7-109.8), blood clots (RR = 5.7; 95% Cl 3.2-10.0), and angina-like symptoms (RR = 2.0; 95% Cl 1.5-2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy. CONCLUSIONS. Childhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow-up for potential toxicities are necessary because treatment-related complications may occur many years after therapy. Cancer 2003;97:663-73. (C) 2003 American Cancer Society. C1 Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA USA. Oregon Hlth Sci Univ, Div Pediat Hematol Oncol, Portland, OR USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Gurney, JG (reprint author), Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU NCI NIH HHS [U24 CA 55727] NR 23 TC 178 Z9 186 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2003 VL 97 IS 3 BP 663 EP 673 DI 10.1002/cncr.11094 PG 11 WC Oncology SC Oncology GA 637WH UT WOS:000180536400017 PM 12548609 ER PT J AU Mohla, S Weilbacher, KN Cher, ML Oyajobi, BO Van Poznak, C Clohisy, DR AF Mohla, S Weilbacher, KN Cher, ML Oyajobi, BO Van Poznak, C Clohisy, DR TI Third North American Symposium on Skeletal Complications of Malignancy - Summary of the Scientific Sessions SO CANCER LA English DT Article; Proceedings Paper CT 3rd North American Symposium on Skeletal Complications of Malignancy CY APR 25-27, 2002 CL BETHESDA, MARYLAND SP Paget Fdn DE prostate carcinoma; breast carcinoma; multiple myeloma; bone marrow, bone metastasis; bisphosphates; tumor microenvironment AB The current introduction summarizes the five scientific sessions (bone marrow microenvironment and animal models of bone metastasis; prostate carcinoma; multiple myeloma; breast carcinoma; and preclinical and clinical studies on me 4 tastasis: future directions) and provides an overview of the proceedings of the Third North American Symposium on Skeletal Complications of Malignancy, Bethesda, Maryland, April 25-27, 2002. (C) 2003 American Cancer Society. RP Mohla, S (reprint author), NCI, Tumor Biol & Metastasis Branch, Div Canc Biol, 6130 Execut Blvd,EPN 5038, Rockville, MD 20892 USA. NR 1 TC 5 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2003 VL 97 IS 3 SU S BP 719 EP 725 DI 10.1002/cncr.11136 PG 7 WC Oncology SC Oncology GA 640BK UT WOS:000180666300002 PM 12548568 ER PT J AU Slattery, ML Ballard-Barbash, R Edwards, S Caan, BJ Potter, JD AF Slattery, ML Ballard-Barbash, R Edwards, S Caan, BJ Potter, JD TI Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE colon cancer; estrogen; gender; IGF; IGF receptors; obesity; physical activity; sex steroids ID HUMAN BREAST-CANCER; GROWTH-FACTOR-I; RECEPTOR SUBSTRATE-1 EXPRESSION; HORMONE REPLACEMENT THERAPY; LARGE-BOWEL-CANCER; PHYSICAL-ACTIVITY; INSULIN; RISK; CELLS; WOMEN AB Objective: The association between body mass index (BMI) and colon cancer has been reported to be different for men and women. No prior literature has examined if estrogen influences these differences. Methods: Using data from an incident population-based case (n = 1972) and control (n = 2386) study of colon cancer we evaluated if estrogen modifies the association between BMI and risk of colon cancer. Results: Women who were estrogen-negative (postmenopausal women not taking hormone replacement therapy, HRT) were at increased risk of colon cancer regardless of indicator of estrogen status used (i.e. estrogen-negative compared to estrogen-positive women defined as either being premenopausal or postmenopausal women using HRT, OR 1.54, 95% CI 1.23-1.93; no recent exposure to estrogens compared to current or HRT use within the past 2 years, OR 1.58, 95% CI 1.24-2.00; postmenopausal women not currently using HRT compared to postmenopausal women taking HRT, OR 1.65, 95% Cl 1.29-2.12). BMI (kg/m(2)) was not associated with an increased risk of colon cancer among women who were estrogen-negative. However, women who were estrogen-positive experienced a greater than two-fold increase in colon cancer risk if they had a BMI of > 30 relative to those who had a BMI of <23 (for estrogen-positive, OR, 2.50, 95% CI 1.51-4.13; premenopausal, OR 2.19, 95% Cl 0.94-5.07; postmenopausal using HRT, OR 3.36, 95% CI 1.58-7.13). Among men the colon cancer risk associated with BMI decreased with advancing age. Physical activity modified the increased colon cancer risk associated with a large BMI. Conclusions: These data suggest the importance of estrogen in colon cancer etiology. Being estrogen-negative resulted in a significant increased risk of colon cancer. However, BMI significantly increased the risk of colon cancer among women who were estrogen-positive. We hypothesize that estrogen up-regulates IGF-I receptors and IRS-I levels in the colon, which in turn increases susceptibility to obesity-induced increased levels of insulin. We further hypothesize that androgens may have similar effects in men given the decline in colon cancer risk associated with BMI with advancing age. C1 Univ Utah, Hlth Res Ctr, Dept Family & Prevent Med, Salt Lake City, UT 84108 USA. NCI, Bethesda, MD 20892 USA. Kaiser Permanente Med Care Program, Oakland, CA 94611 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Slattery, ML (reprint author), Univ Utah, Hlth Res Ctr, Dept Family & Prevent Med, 375 Chipeta Way,Suite A, Salt Lake City, UT 84108 USA. OI Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [R01 CA048998-10, CA48998, N01-PC-67000, R01 CA048998] NR 45 TC 105 Z9 108 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2003 VL 14 IS 1 BP 75 EP 84 DI 10.1023/A:1022545017867 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 670KA UT WOS:000182405600010 PM 12708728 ER PT J AU Wright, ME Mayne, ST Swanson, CA Sinha, R Alavanja, MCR AF Wright, ME Mayne, ST Swanson, CA Sinha, R Alavanja, MCR TI Dietary carotenoids, vegetables, and lung cancer risk in women: the Missouri Women's Health Study (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE dietary carotenoids; lung cancer; vegetables; women ID BETA-CAROTENE; QUESTIONNAIRE; CONSUMPTION; EXPOSURE; COHORT; FRUIT; ACID AB Objective: To examine the effect of specific dietary carotenoids and their primary plant food sources on lung cancer risk in a population-based case-control study of women. Methods: Data were available for 587 incident primary lung cancer cases and 624 controls frequency matched to cases based on age. A modified version of the 100-item NCI-Block food-frequency questionnaire was used to obtain information concerning usual diet 2-3 years prior to interview. Results: In models adjusted for age, total calorie intake, pack-years of smoking, and education, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and total carotenoid intake were each associated with a significantly lower risk of lung cancer. Several vegetable groups were predictive of lower lung cancer risk, particularly the frequency of total vegetable intake. Individual and total carotenoids were no longer significantly associated with lower lung cancer risk in models adjusted for total vegetable intake. However, total vegetable intake remained significantly inversely associated with risk in models adjusted for total carotenoids. Conclusions: These results indicate that consumption of a wide variety of vegetables has a greater bearing on lung cancer risk in a population of smoking and nonsmoking women than intake of any specific carotenoid or total carotenoids. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Mayne, ST (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [N01-CP-2110] NR 24 TC 48 Z9 52 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2003 VL 14 IS 1 BP 85 EP 96 DI 10.1023/A:1022565601937 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 670KA UT WOS:000182405600011 PM 12708729 ER PT J AU Kunkel, TA AF Kunkel, TA TI Considering the cancer consequences of altered DNA polymerase function SO CANCER CELL LA English DT Review ID LESION-BYPASS; ERROR-PRONE; REPLICATION; REPAIR; EUKARYOTES; CELLS; ENDONUCLEASE; INSTABILITY; MUTAGENESIS; MUTATIONS AB Our appreciation of the DNA transactions that replicate and maintain a stable human genome is changing rapidly due to recent discoveries indicating that eukaryotic cells contain many more DNA polymerases than previously thought. This review describes emerging information on the properties and functions of human DNA polymerases, with emphasis on connections between DNA polymerase functions and cancer. C1 NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 30 TC 37 Z9 38 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2003 VL 3 IS 2 BP 105 EP 110 DI 10.1016/S1535-6108(03)00027-8 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 650AL UT WOS:000181240100004 PM 12620405 ER PT J AU Trotta, R Vignudelli, T Candini, O Intine, RV Pecorari, L Guerzoni, C Santilli, G Byrom, MW Goldoni, S Ford, LP Caligiuri, MA Maraia, RJ Perrotti, D Calabretta, B AF Trotta, R Vignudelli, T Candini, O Intine, RV Pecorari, L Guerzoni, C Santilli, G Byrom, MW Goldoni, S Ford, LP Caligiuri, MA Maraia, RJ Perrotti, D Calabretta, B TI BCR/ABL activates mdm2 rnRNA translation via the La antigen SO CANCER CELL LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; PROTEIN-KINASE-C; WILD-TYPE P53; ABL TYROSINE KINASE; RING-FINGER DOMAIN; BCR-ABL; HEMATOPOIETIC-CELLS; BLAST CRISIS AB In a BCR/ABL-expressing myeloid precursor cell line, p53 levels were markedly downmodulated. Expression of MDM2, the negative regulator of p53, was upregulated in a tyrosine kinase-dependent manner in growth factor-independent BCR/ABL-expressing cells, and in accelerated phase and blast crisis CML samples. Increased MDM2 expression was associated with enhanced mdm2 mRNA translation, which required the interaction of the La antigen with mdm2 5' UTR. Expression of MDM2 correlated with that of La and was suppressed by La siRNAs and by a dominant negative La mutant, which also enhanced the susceptibility to drug-induced apoptosis of BCR/ABL-transformed cells. By contrast, La overexpression led to increased MDM2 levels and enhanced resistance to apoptosis. Thus, La-dependent activation of mdm2 translation might represent an important molecular mechanism involved in BCR/ABL leukemogenesis. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Microbiol & Immunol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Univ Modena & Reggio Emilia, Dept Med Sci, I-41100 Modena, Italy. NICHD, NIH, Bethesda, MD 20892 USA. Ambion Inc, Res & Dev, Austin, TX 78744 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Canc & Leukemia Grp B, Chicago, IL USA. RP Perrotti, D (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Microbiol & Immunol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. RI Perrotti, Danilo/E-3852-2011 FU NCI NIH HHS [T32 CA 09662, U01 CA 31946] NR 69 TC 143 Z9 145 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2003 VL 3 IS 2 BP 145 EP 160 DI 10.1016/S1535-6108(03)00020-5 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 650AL UT WOS:000181240100008 PM 12620409 ER PT J AU Rosenwald, A Wright, G Wiestner, A Chan, WC Connors, JM Campo, E Gascoyne, RD Grogan, TM Muller-Hermelink, HK Smeland, EB Chiorazzi, M Giltnane, JM Hurt, EM Zhao, H Averett, L Henrickson, S Yang, LM Powell, J Wilson, WH Jaffe, ES Simon, R Klausner, RD Montserrat, E Bosch, F Greiner, TC Weisenburger, DD Sanger, WG Dave, BJ Lynch, JC Vose, J Armitage, JO Fisher, RI Miller, TP LeBlanc, M Ott, G Kvaloy, S Holte, H Delabie, J Staudt, LM AF Rosenwald, A Wright, G Wiestner, A Chan, WC Connors, JM Campo, E Gascoyne, RD Grogan, TM Muller-Hermelink, HK Smeland, EB Chiorazzi, M Giltnane, JM Hurt, EM Zhao, H Averett, L Henrickson, S Yang, LM Powell, J Wilson, WH Jaffe, ES Simon, R Klausner, RD Montserrat, E Bosch, F Greiner, TC Weisenburger, DD Sanger, WG Dave, BJ Lynch, JC Vose, J Armitage, JO Fisher, RI Miller, TP LeBlanc, M Ott, G Kvaloy, S Holte, H Delabie, J Staudt, LM TI The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma SO CANCER CELL LA English DT Article ID NON-HODGKINS-LYMPHOMAS; CYCLIN D1 EXPRESSION; AGGRESSIVE VARIANTS; MESSENGER-RNA; TUMOR-SUPPRESSOR; POOR-PROGNOSIS; INK4A LOCUS; P53 GENE; OVEREXPRESSION; P16(INK4A) AB We used gene expression profiling to establish a molecular diagnosis of mantle cell lymphoma (MCL), to elucidate its pathogenesis, and to predict the length of survival of these patients. An MCL gene expression signature defined a large subset of MCLs that expressed cyclin D1 and a novel subset that lacked cyclin D1 expression. A precise measurement of tumor cell proliferation, provided by the expression of proliferation signature genes, identified patient subsets that differed by more than 5 years in median survival. Differences in cyclin D1 mRNA abundance synergized with INK4a/ARF locus deletions to dictate tumor proliferation rate and survival. We propose a quantitative model of the aberrant cell cycle regulation in MCL that provides a rationale for the design of cell cycle inhibitor therapy in this malignancy. C1 NCI, Lymphoma Leukemia Mol Profiling Project, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Bioinformat & Mol Anal Sect, CBEL, CIT, Bethesda, MD 20892 USA. Univ Barcelona, Hosp Clin, Barcelona, Spain. Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Pediat, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE USA. Univ Arizona, Ctr Canc, Dept Pathol, Tucson, AZ USA. Univ Arizona, Ctr Canc, Dept Med, Tucson, AZ USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY USA. SW Oncol Grp, San Antonio, TX USA. British Columbia Canc Ctr, Vancouver, BC, Canada. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Norwegian Radium Hosp, Dept Oncol, Oslo, Norway. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Norwegian Radium Hosp, Dept Immunol, Oslo, Norway. RP Staudt, LM (reprint author), NCI, Lymphoma Leukemia Mol Profiling Project, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Giltnane, Jennifer/D-2584-2013; OI Delabie, Jan/0000-0001-5023-0689; Bosch, Francesc/0000-0001-9241-2886; Campo, elias/0000-0001-9850-9793 NR 57 TC 535 Z9 548 U1 4 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2003 VL 3 IS 2 BP 185 EP 197 DI 10.1016/S1535-6108(03)00028-X PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 650AL UT WOS:000181240100011 PM 12620412 ER PT J AU Brenner, AV Linet, MS Selker, RG Shapiro, WR Black, PM Fine, HA Inskip, PD AF Brenner, AV Linet, MS Selker, RG Shapiro, WR Black, PM Fine, HA Inskip, PD TI Polio vaccination and risk of brain tumors in adults: No apparent association SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SIMIAN-VIRUS-40; CANCER C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. W Pennsylvania Hosp, Div Neurosurg, Pittsburgh, PA USA. St Joseph Hosp, Barrow Neurol Inst, Phoenix, AZ USA. Med Ctr, Phoenix, AZ USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Neruooncol Branch, Bethesda, MD USA. RP Brenner, AV (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, 6120 Execut Blvd MSC 7362, Bethesda, MD 20892 USA. NR 8 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2003 VL 12 IS 2 BP 177 EP 178 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 644LG UT WOS:000180918800019 PM 12582033 ER PT J AU Cheng, YJ Chien, YC Hildesheim, A Hsu, MM Chen, IH Chuang, J Chang, J Ma, YL Luo, CT Hsu, WL Hsu, HHH Huang, H Chang, JF Chen, CJ Yang, CS AF Cheng, YJ Chien, YC Hildesheim, A Hsu, MM Chen, IH Chuang, J Chang, J Ma, YL Luo, CT Hsu, WL Hsu, HHH Huang, H Chang, JF Chen, CJ Yang, CS TI No association between genetic polymorphisms of CYP1A1, GSTM1, GSTT1, GSTP1, NAT2, and nasopharyngeal carcinoma in Taiwan SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CANCER; RISK; IDENTIFICATION; SUSCEPTIBILITY; BLADDER; CYP2E1 C1 Natl Taiwan Univ, Grad Inst Epidemiol, Coll Publ Hlth, Taipei 100, Taiwan. Natl Taiwan Univ, Grad Inst Microbiol, Taipei 100, Taiwan. Natl Taiwan Univ, Dept Otolaryngol, Coll Med, Taipei 100, Taiwan. Mackay Mem Hosp, Dept Otolaryngol, Taipei 100, Taiwan. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Chen, CJ (reprint author), Natl Taiwan Univ, Grad Inst Epidemiol, Coll Publ Hlth, 1 Jen Ai Rd,Sect 1, Taipei 100, Taiwan. RI Chen, Chien-Jen/C-6976-2008 NR 7 TC 31 Z9 32 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2003 VL 12 IS 2 BP 179 EP 180 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 644LG UT WOS:000180918800020 PM 12582034 ER PT J AU Kelley, MR Kow, YW Wilson, DM AF Kelley, MR Kow, YW Wilson, DM TI Disparity between DNA base excision repair in yeast and mammals: Translational implications SO CANCER RESEARCH LA English DT Article ID HUMAN APURINIC ENDONUCLEASE; HUMAN AP-ENDONUCLEASE; NUCLEAR REDOX FACTOR; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; POLYMERASE-BETA; APURINIC/APYRIMIDINIC ENDONUCLEASE; SCHIZOSACCHAROMYCES-POMBE; SUBSTRATE SPECIFICITIES; ABASIC ENDONUCLEASE AB One approach to the effective treatment of cancer requires the continued development of novel chemotherapeutic agents to kill tumor cells. Additionally, an element of cancer research has been devoted to understanding DNA repair pathways in hopes of defining the factors that confer resistance to anticancer drugs and developing strategies for modulating repair capacity as a means of overcoming resistance or enhancing sensitivity to cancer treatments. Historically, yeast, particularly Saccharomyces cerevisiae, has been used as a model system for DNA repair analyses. Additionally, it has been used to evaluate drug efficacy and selectivity, and to identify new targets for antitumor drugs. The usefulness of yeast for these types of analyses has been primarily because of it being considered to have well-conserved DNA repair processes among eukaryotes. However, as more information has accumulated in mammalian DNA repair, and particularly in DNA base excision repair (BER), a number of striking differences have emerged between yeast and mammalian (human) repair processes. The BER pathway is essential for the repair of damaged DNA induced by oxidizing and alkylating agents, which are the majority of chemotherapeutic drugs used currently in the clinic. The importance of this pathway in processing DNA damage makes its members potential targets for novel chemotherapeutic agents. However, because the BER process and its main players are remarkably divergent from S. cerevisiae to humans, it is worth keeping these differences in mind if yeast continues to be used as a model or primary system in the screening for potential new human therapeutics. C1 Herman B Wells Ctr Pediat Res, Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30303 USA. NIA, Lab Mol Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Kelley, MR (reprint author), Herman B Wells Ctr Pediat Res, Dept Pediat, Hematol Oncol Sect, 702 Barnhill Dr,Room 2600, Indianapolis, IN 46202 USA. FU NCI NIH HHS [CA90860, P01-CA75426, CA79056]; NIDDK NIH HHS [DK49218]; NIEHS NIH HHS [ES05865, P01-ES011163, ES03456]; NINDS NIH HHS [NS38506] NR 80 TC 24 Z9 24 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2003 VL 63 IS 3 BP 549 EP 554 PG 6 WC Oncology SC Oncology GA 640PT UT WOS:000180697700001 PM 12566294 ER PT J AU Reisman, DN Sciarrotta, J Wang, WD Funkhouser, WK Weissman, BE AF Reisman, DN Sciarrotta, J Wang, WD Funkhouser, WK Weissman, BE TI Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: Correlation with poor prognosis SO CANCER RESEARCH LA English DT Article ID MAMMALIAN SWI/SNF COMPLEXES; CHROMATIN REMODELING FACTOR; SWI-SNF COMPLEX; TUMOR SUPPRESSION; BREAST-CANCER; EXPRESSION; BRG-1; CYCLE; ACTIVATION; ARREST AB A role for the SWI/SNF complex in tumorigenesis based on its requirement for retinoblastoma induced growth arrest and p53-mediated transcription and the appearance of tumors in SWI/SNF-deficient mice. In addition, Western blot data have shown that the SWI/SNF ATPase sub-units cell, BRG1 and BRM (BRG1/BRM), are lost in similar to30% of human non-small lung cancer cell lines. To determine whether loss of expression of these proteins occurs in primary tumors, we examined their expression in 41 primary lung adenocarcinomas and 19 primary lung squamous carcinomas by immunchistochemistry. These analyses showed that 10% of tumors show a concomitant loss of BRG1 and BRM expression. Moreover, patients with BRG1/BRM-negative carcinomas, independent of stage, have a statistically significant decrease in survival compared with patients with BRG1/BRM. This report provides supportive evidence that BRG1 and BRM act as tumor suppressor proteins and implicates a role for their loss in the development of non-small cell lung cancers. C1 Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Weissman, BE (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA91048, T32CA09156] NR 27 TC 203 Z9 210 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2003 VL 63 IS 3 BP 560 EP 566 PG 7 WC Oncology SC Oncology GA 640PT UT WOS:000180697700003 PM 12566296 ER PT J AU Tseng, TL Shih, YP Huang, YC Wang, CK Chen, PH Chang, JG Yeh, KT Chen, YMA Buetow, KH AF Tseng, TL Shih, YP Huang, YC Wang, CK Chen, PH Chang, JG Yeh, KT Chen, YMA Buetow, KH TI Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer SO CANCER RESEARCH LA English DT Article ID GLYCINE-N-METHYLTRANSFERASE; MICROSATELLITE INSTABILITY; HEPATOCELLULAR-CARCINOMA; GENOMIC INSTABILITY; BINDING PROTEIN; CELL LINES; RAT-LIVER; EXPRESSION; RECEPTOR; POLYMORPHISMS AB Glycine N-methyltransferase (GNMT), a multifunctional protein involved in the maintenance of the genetic stability, is often down-regulated in hepatocellular carcinoma (HCC). Using genotypic characterization of GNMT in hepatoma cell lines and in a Taiwanese population with a high incidence of liver cancer we have investigated the role of this gene in the progression of liver cancer. Six novel polymorphisms, including two short tandem repeats, one 4-nucleotide insertion/deletion polymorphism, and three single nucleotide polymorphisms, in GNMT were identified in this study. The rates of loss of heterozygosity at the GNMT locus in pairs of normal and tumor tissue from the HCC patients were approximately 36-47%. In addition, the observed heterozygosity of GNMT decreases in tumor adjacent liver DNA from HCC patients compared with that observed in blood DNA from normal individuals and HCC patients. This may result from the early event of loss of heterozygosity within the GNMT gene in the liver tissues of HCC patients. However, in this study, we did not observe the association of polymorphic GNMT alleles as inherited risk factors for HCC. We also elucidated the functional impact of genetic markers in the GNMT promoter by performing luciferase reporter gene and gel mobility shift assays. The results indicate that two polymorphisms, short tandem repeat I and insertion/deletion polymorphism, in the promoter region could cause allelic specific effects on the transcriptional activity of GNMT. The risk genotypes of GNMT, which presumably have a lower expression level, as estimated from in vitro functional studies, are over-represented in tumor-adjacent tissues from HCC patients. In summary, our results suggest that GNMT alteration may be an early event in HCC development and that GNMT could be a new tumor susceptibility gene for HCC. C1 NCI, Lab Populat Genet, Ctr Canc Res, Bethesda, MD 20892 USA. Natl Yang Ming Univ, Inst Publ Hlth, Div Prevent Med, Taipei 112, Taiwan. Taipei Municipal Jen Ai Hosp, Dept Internal Med, Taipei 106, Taiwan. Yuans Gen Hosp, Dept Internal Med, Kaohsiung 802, Taiwan. China Med Coll Hosp, Dept Lab Med, Taichung, Taiwan. Changhua Christian Hosp, Dept Pathol, Changhua 500, Taiwan. RP Chen, YMA (reprint author), NCI, Lab Populat Genet, Ctr Canc Res, Bldg 41-D702,41 Lib Dr, Bethesda, MD 20892 USA. RI Chang, Jan-Gowth/C-9544-2009 NR 34 TC 53 Z9 56 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2003 VL 63 IS 3 BP 647 EP 654 PG 8 WC Oncology SC Oncology GA 640PT UT WOS:000180697700016 PM 12566309 ER PT J AU Wang, ZN Lo, HS Yang, H Gere, S Hu, Y Buetow, KH Lee, MP AF Wang, ZN Lo, HS Yang, H Gere, S Hu, Y Buetow, KH Lee, MP TI Computational analysis and experimental validation of tumor-associated alternative RNA splicing in human cancer SO CANCER RESEARCH LA English DT Article ID MESSENGER-RNAS; HUMAN GENES AB A genome-wide computational screen was performed to identify tumor-associated alternative RNA splicing isoforms. A BLAST algorithm was used to compare 11,014 genes from RefSeq with 3,471,822 human expressed sequence tag sequences. The screen identified 26,258 alternative splicing isoforms of which 845 were significantly associated with human cancer, and 54 were specifically associated with liver cancer. Furthermore, canonical GT-AG splice junctions were used significantly less frequently in the alternative splicing isoforms in tumors. Reverse transcription-PCR experiments confirmed association of the alternative splicing isoforms with tumors. These results suggest that alternative splicing may have potential as a diagnostic marker for cancer. C1 NCI, Lab Populat Genet, Gaithersburg, MD 20877 USA. RP Lee, MP (reprint author), NCI, Lab Populat Genet, Gaithersburg, MD 20877 USA. NR 14 TC 113 Z9 120 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2003 VL 63 IS 3 BP 655 EP 657 PG 3 WC Oncology SC Oncology GA 640PT UT WOS:000180697700017 PM 12566310 ER PT J AU Tomassetti, A Mangiarotti, F Mazzi, M Sforzini, S Miotti, S Galmozzi, E Elwood, PC Canevari, S AF Tomassetti, A Mangiarotti, F Mazzi, M Sforzini, S Miotti, S Galmozzi, E Elwood, PC Canevari, S TI The variant hepatocyte nuclear factor 1 activates the P1 promoter of the human alpha-Folate receptor gene in ovarian carcinoma SO CANCER RESEARCH LA English DT Article ID TISSUE-SPECIFIC PROMOTERS; BINDING-PROTEIN; MESSENGER-RNA; CELL-LINES; 5'-UNTRANSLATED REGION; SURFACE EPITHELIUM; IN-VITRO; KB CELLS; EXPRESSION; GROWTH AB The a folate receptor (alphaFR) is a membrane glycoprotein that binds folates, and mediates their uptake and that of antifolate drugs. aFR is absent on ovarian surface epithelium (OSE) but is detectable during early transforming events in this epithelium, with increasing expression levels in association with tumor progression. Analysis of transcriptional regulation of the aFR gene have revealed two promoter regions, P1 and P4, flanking exons 1 and 4, respectively, and a requirement for three SPI sites and an INR element for optimal P4 activity. Here, we focused on the P1 transcription regulation in ovarian carcinoma cells. RNase protection assay indicated that the 5'-untransiated region is heterogeneous because of different start sites and alternative splicing of exon 3. A core region of the P1 promoter was sufficient for maximal promoter activity in ovarian carcinoma cell lines but not in OSE cells or in alphaFR-nonexpressing cell lines. Deletion and mutation analysis of this core promoter identified a cis-regulatory element at position +27 to +33 of the untranslated exon 1, which is responsible for maximum P1 activity. This element formed an abundant DNA-protein complex with nuclear proteins from ovarian cancer cells but not from other cell lines or OSE cells. Competition experiments and supershift assays demonstrated binding of the P1 cis-regulatory element by a transcription factor involved in embryonic development, the variant hepatocyte nuclear factor-1 (vHNF1). Analysis of RNA from various cell lines and surgical specimens confirmed that vHNF1 is expressed in ovarian carcinomas. Thus, vHNF1 regulates tissue-specific transcription in ovarian carcinoma. C1 Ist Nazl Tumori, Unit Mol Therapies, Dept Expt Oncol, I-20133 Milan, Italy. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Tomassetti, A (reprint author), Ist Nazl Tumori, Unit Mol Therapies, Dept Expt Oncol, Via Venezian 1, I-20133 Milan, Italy. RI Tomassetti, Antonella/G-7906-2015 OI Tomassetti, Antonella/0000-0001-6772-9937 NR 38 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2003 VL 63 IS 3 BP 696 EP 704 PG 9 WC Oncology SC Oncology GA 640PT UT WOS:000180697700023 PM 12566316 ER PT J AU Krishnan, J Kirkin, V Steffen, A Hegen, M Weih, D Tomarev, S Wilting, J Sleeman, JP AF Krishnan, J Kirkin, V Steffen, A Hegen, M Weih, D Tomarev, S Wilting, J Sleeman, JP TI Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats SO CANCER RESEARCH LA English DT Article ID AVIAN CHORIOALLANTOIC MEMBRANE; FACTOR-C; IN-VIVO; TRANSGENIC MICE; FACTOR RECEPTOR-3; CARCINOMA-CELLS; NODE METASTASIS; BREAST-CANCER; LYMPHANGIOGENESIS; ANGIOGENESIS AB The presence of metastases in regional lymph nodes is a strong indicator of poor patient survival. A number of clinical and experimental studies suggest that tumor-induced lymphangiogenesis driven by vascular endothelial growth factor (VEGF)-C- and/or VEGF-D-induced activation of VEGF receptor (VEGFR)-3 may promote metastasis to regional lymph nodes. Here we show that constitutive VEGF-C and VEGF-D expression by tumor cells of diverse origin grown in tissue culture does not correlate with metastatic potential in vivo. However, tumors derived from cell lines that do not constitutively express VEGF-C or VEGF-D in tissue culture can nevertheless express one or both of these factors. We demonstrate that both tumor and stromal cells can contribute to this expression, suggesting that tumor cell-host interactions determine tumor expression of VEGF-C and VEGF-D. Using immunocompetent rat mammary tumor models, we show in two ways that this expression can promote metastasis via the lymphatics. Firstly, ectopic expression of a soluble VEGFR-3 receptor globulin protein in MT-450 tumor cells that are highly metastatic via the lymphatics blocked VEGF-C and VEGF-D activity and suppressed metastasis formation in both the regional lymph nodes and the lungs. Secondly, ectopic expression in the weakly metastatic NM-081 cell line of a mutant form of VEGF-C that is only able to activate VEGFR-3 strongly promoted metastasis of these cells to the regional lymph nodes and lung. These data show that expression of VEGF-C and VEGF-D in tissue culture does not reflect expression in vivo and that activation of VEGFR-3 in the absence of VEGFR-2 activation is sufficient to promote tumor-induced lymphangiogenesis and metastasis, and they support the notion that blockade of VEGFR-3 activation will be useful as a novel form of cancer therapy. C1 Forschungszentrum Karlsruhe, Inst Genet, POB 3640, D-76021 Karlsruhe, Germany. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Kinderklin & Poliklin Gottingen, D-37075 Gottingen, Germany. RP Forschungszentrum Karlsruhe, Inst Genet, POB 3640, D-76021 Karlsruhe, Germany. EM sleeman@itg.fzk.de RI Sleeman, Jonathan/H-2515-2013 NR 51 TC 145 Z9 183 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2003 VL 63 IS 3 BP 713 EP 722 PG 10 WC Oncology SC Oncology GA 640PT UT WOS:000180697700025 PM 12566318 ER PT J AU Araki, Y Okamura, S Hussain, SP Nagashima, M He, PJ Shiseki, M Miura, K Harris, CC AF Araki, Y Okamura, S Hussain, SP Nagashima, M He, PJ Shiseki, M Miura, K Harris, CC TI Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways SO CANCER RESEARCH LA English DT Article ID ADENOMATOUS POLYPOSIS COIL; PROSTAGLANDIN-H SYNTHASE-2; MESSENGER-RNA STABILITY; BETA-CATENIN MUTATIONS; COLON-CARCINOMA CELLS; EPITHELIAL-CELLS; COLORECTAL-CANCER; TRANSCRIPTIONAL ACTIVATION; HEPATOCELLULAR CARCINOMAS; ALTERED EXPRESSION AB Mutations in the adenomatous polyposis coli (APC) gene and K-ras occur in the majority of human colorectal cancers. Loss of functional APC protein activates the Wnt signal transduction pathway, allowing the nuclear accumulation of beta-catenin, which then binds to T-cell factor-4 (Tcf-4), causing increased transcriptional activation of downstream target genes. We investigated the hypothesis that the activation of the WNT pathway regulates cyclooxygenase-2 (COX-2). COX-2 was down-regulated after the induction of full-length APC in the HT29-APC cell line. We identified a Tcf-4-binding element (TBE) in the COX-2 promoter that specifically bound to Tcf-4 in an electrophoretic mobility shift assay. COX-2 promoter luciferase activity is down-regulated by APC in a promoter reporter construct containing the, TBE but not with mutant TBE. Mutant beta-catenin expression up-regulated the COX-2 promoter activity and the endogenous COX-2 mRNA expression in HuH7, hepatocellular carcinoma cell line, which is partially abrogated by cotransfection with a dominant-negative Tcf-4 expression vector. Although beta-catenin alone did not increase COX-2 protein to detectable levels in HuH7 cells, coexpression of both mutant beta-catenin and mutant K-ras increased COX-2 protein expression, which is consistent with the previous reports that K-ras can stabilize COX-2 mRNA. Taken together, our data support the hypothesis that COX-2 is down-regulated by APC and up-regulated by nuclear beta-catenin accumulation, and additionally implicate the Witt signal transduction pathway in colon and liver carcinogenesis. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,room 2C05,MSC 4255, Bethesda, MD 20892 USA. OI Miura, Koh/0000-0001-7303-9430 NR 56 TC 206 Z9 225 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2003 VL 63 IS 3 BP 728 EP 734 PG 7 WC Oncology SC Oncology GA 640PT UT WOS:000180697700027 PM 12566320 ER PT J AU Buters, J Quintanilla-Martinez, L Schober, W Soballa, VJ Hintermair, J Wolff, T Gonzalez, FJ Greim, H AF Buters, J Quintanilla-Martinez, L Schober, W Soballa, VJ Hintermair, J Wolff, T Gonzalez, FJ Greim, H TI CYP1B1 determines susceptibility to low doses of 7,12-dimethylbenz[a]anthracene-induced ovarian cancers in mice: correlation of CYP1B1-mediated DNA adducts with carcinogenicity SO CARCINOGENESIS LA English DT Article ID CHINESE-HAMSTER CELLS; POLYCYCLIC AROMATIC-HYDROCARBONS; METABOLIC-ACTIVATION; STABLE EXPRESSION; RAT-LIVER; EPITHELIAL-CELLS; AH RECEPTOR; BONE-MARROW; CYTOCHROME-P450; GENE AB We showed previously that CYP1B1-null mice developed 10 times less lymphomas than wild-type mice after receiving 7,12-dimethylbenz[a]anthracene (DMBA). In this study a 10-fold lower dose was applied to differentiate between toxicity induced lymphomas (200 mug/mouse/day) and tumor initiation (20 mug/day). DMBA adducts to DNA of organs of mice, or to DNA of V79 cells expressing single mice or human cytochrome P450 isoenzymes were also measured. Mice were dosed three cycles of 5 days/week with DMBA in corn oil orally. Histopathology was determined at intermittent death or I year after dosing. DMBA-DNA adducts were assayed by P-32-postlabeling. At 20 mug/day, wild-type mice developed ovary (71%, stromal cells derived), skin (36%), uterus (64%) and lung (14%) hyperplasias. At this dose the CYP1B1-null mice developed no lymphomas, 25% ovary (epithelial cells derived), 8% skin, 58% uterus and 33% lung tumors. Oil control mice (n = 35) developed only eight, mostly different, hyperplasias. Wild-type mice had more DMBA-DNA adducts than the CYP1B1-null mice. The differences were highest in thymus, spleen, ovaries and testes (5-7-fold). Additionally, one specific DMBA-DNA adduct was reduced in CYP1B1-null mice. V79-cells expressed mouse CYP1B1 was 35 times more active than mouse CYP1A1 in forming DMBA-DNA adducts. Human CYP1B1 was 2.5 times less active than mouse CYP1B1 but 2.3-fold more active than human CYP1A1. CYP1B1 is the dominant enzyme in metabolizing DMBA to carcinogenic metabolites at high and low doses in mice, leading to an increased tumor rate of especially the ovaries at low doses of DMBA. Wild-type mice had more DMBA-DNA adducts than CYP1B1-null mice. Additionally, a specific adduct was less present in the CYP1B1-null mice. Human CYP1B1 was less active than mouse CYP1B1, but more active than human CYP1A1 in forming DMBA-DNA adducts. Thus, we expect CYP1B1 to be an important DMBA activating enzyme in humans also. C1 TUM, Ctr Allergy & Environm, GSF, Div Environm Dermatol & Allergol, D-80802 Munich, Germany. GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Pathol, D-85764 Oberschleissheim, Germany. Tech Univ Munich, Inst Lebensmittelchem, D-85747 Garching, Germany. Degussa AG, Prod Toxikol, D-83303 Trostberg, Germany. GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Toxikol, D-85764 Oberschleissheim, Germany. NCI, Bethesda, MD 20892 USA. Tech Univ Munich, Inst Toxikol & Umwelthyg, D-80636 Munich, Germany. RP Buters, J (reprint author), TUM, Ctr Allergy & Environm, GSF, Div Environm Dermatol & Allergol, Biedersteinerstr 29, D-80802 Munich, Germany. RI Buters, Jeroen/G-5070-2011 NR 50 TC 69 Z9 73 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2003 VL 24 IS 2 BP 327 EP 334 DI 10.1093/carcin/24.2.327 PG 8 WC Oncology SC Oncology GA 651BD UT WOS:000181299600023 PM 12584184 ER PT J AU de Boer, RA Pinto, YM Suurmeijer, AJH Pokharel, S Scholtens, E Humler, M Saavedra, JM Boomsma, F van Gilst, WH van Veldhuisen, DJ AF de Boer, RA Pinto, YM Suurmeijer, AJH Pokharel, S Scholtens, E Humler, M Saavedra, JM Boomsma, F van Gilst, WH van Veldhuisen, DJ TI Increased expression of cardiac angiotensin II type 1 (AT(1)) receptors decreases myocardial microvessel density after experimental myocardial infarction SO CARDIOVASCULAR RESEARCH LA English DT Article DE angiotensin; growth factors; infarction; microcirculation; receptors; renin angiotensin system ID ENDOTHELIAL GROWTH-FACTOR; CONVERTING ENZYME-INHIBITION; BLOOD-PRESSURE; HEART-FAILURE; RAT; CELLS; CAPTOPRIL; ANGIOGENESIS; HYPERTROPHY; ACTIVATION AB Objective: To study the effects of increased levels of myocardial angiotensin II type I (AT,) receptor on microvascular growth following myocardial infarction (MI). Methods: MI was created in transgenic rats (TGR) with a cardioselective overexpression of the AT(1) receptor. We used Sprague-Dawley (SD) rats as controls. Some of the rats were treated with the selective AT(1) receptor blocker losartan (Los). Rats were sacrificed after 3 weeks. Results: MI caused left ventricular (LV) hypertrophy and LV dysfunction in both SD and TGR, which was prevented by AT, receptor blockade. Furthermore, MI decreased microvessel density in the non-infarcted myocardium (SD MI: 1653+/-37 /mm(2), p<0.01 vs. sham-operated controls), however, microvessel density decreased significantly more in TGR with MI (1298+/-33/mm(2) ,<0.01 vs. SD MI). AT(1) receptor blockade restored microvessel density (SD MI Los: 2046+/-195 /mm(2); TGR MI Los: 1742+47/mm(2); p<0.01 vs. untreated). The differences in microvessel density were still present after correction for LV hypertrophy. The increase in microvessel density after AT, receptor blockade was not accompanied by increased myocardial vascular endothelial growth factor (VEGF) levels. Microvessel density correlated with parameters of myocardial stretch, such as LV end-diastolic pressure (-0.681, P<0.001) and N-ANP (-0.424, P=0.01). Conclusions: Microvessel density after MI is decreased when the AT, receptor is overexpressed, and this is amenable to AT, receptor blockade. This suggests that efficacy of AT, receptor blockers post-MI may not only be due to attenuation of LV remodeling, but also to a stimulatory effect on angiogenesis. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved. C1 Univ Groningen Hosp, Thoraxctr, Dept Cardiol, NL-9713 GZ Groningen, Netherlands. Univ Groningen Hosp, Dept Clin Pharmacol, Groningen, Netherlands. Univ Groningen Hosp, Dept Pathol, Groningen, Netherlands. NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. Univ Hosp Dijkzigt, COEUR, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands. RP van Veldhuisen, DJ (reprint author), Univ Groningen Hosp, Thoraxctr, Dept Cardiol, Hanzeplein 1,POB 30-001,9700 RB, NL-9713 GZ Groningen, Netherlands. RI van Gilst, Wiek/C-3828-2008; van Veldhuisen, Dirk Jan/E-8967-2014 NR 42 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD FEB PY 2003 VL 57 IS 2 BP 434 EP 442 AR PII S0008-6363(02)00704-6 DI 10.1016/S0008-6363(02)00704-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647CR UT WOS:000181075100017 PM 12566116 ER PT J AU Nakamura, M Matsuo, T Stauffer, J Neckers, L Thiele, CJ AF Nakamura, M Matsuo, T Stauffer, J Neckers, L Thiele, CJ TI Retinoic acid decreases targeting of p27 for degradation via an N-myc-dependent decrease in p27 phosphorylation and an N-myc-independent decrease in Skp2 SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE N-my c; retinoics; p27 neuroblastoma; SKP2; CDK6; proteosome; ubiquitination ID KINASE INHIBITOR P27(KIP1); NEUROBLASTOMA CELL-LINE; INDUCED GROWTH ARREST; HUMAN NEURO-BLASTOMA; C-MYC; CDK INHIBITORS; DIFFERENTIATION; EXPRESSION; ACCUMULATION; CYCLE AB Poor prognosis neuroblastoma (NB) tumors are marked by amplification and overexpression of N-myc. Retinoic acid (RA) decreases N-myc levels and induces cell cycle arrest in vitro and increases event-free survival in advanced stage NB patients. In this study, we investigated the mechanism(s) by which RA regulates cell cycle and how N-myc affects NB cell cycle progression. Constitutive N-myc overexpression stimulates increases in cyclin E-dependent kinase activity and decreases in p27 resulting in increased DNA synthesis. N-myc regulates p27 levels through an increase in targeting of p27 to the proteasome via cyclin E kinase-dependent phosphorylation of p27 and its ubiquitination. N-myc also stimulates an increase in proteasome activity. In RA-treated cells in which N-myc levels decline as p27 levels increase, degradation of p27 is also decreased. However, RA does not affect the activity of proteasome. The decrease in the degradation of p27 in RA-treated cells is due in part to a decrease in the N-myc stimulated phosphorylation of p27. However, RA also decreases Skp2 levels thus impairing the ability of p27 to be ubiquitinated. Thus, RA induces both N-myc-dependent and -independent mechanisms to minimize the degradation of p27 and arrest NB cell growth. C1 NCI, Canc Res Ctr, Cell & Mol Biol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Cell & Canc Biol Branch, Canc Res Ctr, Rockville, MD 20850 USA. RP Thiele, CJ (reprint author), NCI, Canc Res Ctr, Cell & Mol Biol Sect, Pediat Oncol Branch, Bldg 10 Rm 13N240,10 Ctr Dr MSC-1928, Bethesda, MD 20892 USA. NR 41 TC 34 Z9 37 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 2003 VL 10 IS 2 BP 230 EP 239 DI 10.1038/sj.cdd.4401125 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 672CT UT WOS:000182503900010 PM 12700651 ER PT J AU O'Connell, K Caron, C Kopish, K Hurd, D Kemphues, K Li, Y White, J AF O'Connell, K Caron, C Kopish, K Hurd, D Kemphues, K Li, Y White, J TI Analysis of the C. elegans ZYG-1 kinase, a mitotic and meiotic regulator of centrosome duplication SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Meeting Abstract CT EMBO/EMBL Conference on Centrosomes and Spindle Pole Bodies CY SEP 13-17, 2002 CL HEIDELBERG, GERMANY C1 NIDDK, Lab Genet & Biochem, NIH, Bethesda, MD USA. Cornell Univ, Genet & Dev Sect, Ithaca, NY 14853 USA. Univ Wisconsin, Mol Biol Lab, Madison, WI 53706 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 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD FEB PY 2003 VL 54 IS 2 MA 81 BP 183 EP 183 PG 1 WC Cell Biology SC Cell Biology GA 642GJ UT WOS:000180795600087 ER PT J AU Park, JH Park, JS Ju, SK Lee, KB Park, YK Kang, MH Na, SY You, KH AF Park, JH Park, JS Ju, SK Lee, KB Park, YK Kang, MH Na, SY You, KH TI Clusterin mRNA expression in apoptotic and activated rat thymocytes SO CELL RESEARCH LA English DT Article DE clusterin; sgp-2; thymocytes; apoptosis; mRNA isoforms ID RETE TESTIS FLUID; CELL-DEATH; SULFATED GLYCOPROTEIN-2; VENTRAL PROSTATE; GENE-EXPRESSION; MESSENGER-RNA; HEAT-SHOCK; MOLECULAR-CLONING; PROTEIN; CHAPERONE AB Clusterin is a 75-80 kDa heterodimeric glycoprotein, that is produced in most tissues but which exact biological role is still not clear. Particularly, its role in protection or promotion of apoptosis is heavily disputed, since data supporting both views have been reported in several independent studies. To clarify this issue, and also to determine whether clusterin expression itself might be affected by apoptosis, in the present study, rat thymocytes were treated with dexamethasone, -a synthetic glucocorticoid that elicits apoptosis in thymocytes-, and clusterin mRNA expression was analyzed by semi-quantitative RT-PCR before and after induction of apoptosis. Interestingly, neither the treatment with dexamethasone in vitro nor triggering of apoptosis in vivo up- regulated clusterin expression, opposing the view that clusterin is involved in apoptotic processes. On the other hand, a new clusterin mRNA isoform was detected and isolated, whose expression was restricted to freshly isolated thymocytes. This novel isoform lacks the post-translational proteolytic cleavage site and is therefore predicted to encode a monomeric protein. The biological function under normal circumstances, however, will need further investigations for clarification. While apoptosis could not modulate clusterin expression, activation of thymocytes with concanavalin A and interleukin-2 resulted in up-regulation of clusterin mRNA level, indicating that clusterin expression is rather under the control of cell activation-mediated rather than apoptosis-induced signals. C1 Chungnam Natl Univ, Coll Nat Sci, Dept Biol, Taejon 305764, South Korea. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Hannam Univ, Dept Food & Nutr, Taejon 306791, South Korea. Univ Wurzburg, Inst Virol & Immunobiol, D-97078 Wurzburg, Germany. RP You, KH (reprint author), Chungnam Natl Univ, Coll Nat Sci, Dept Biol, 220 Gung Dong, Taejon 305764, South Korea. RI Park, Jung Hyun /B-5712-2015 OI Park, Jung Hyun /0000-0002-9547-9055 NR 30 TC 5 Z9 7 U1 0 U2 0 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD FEB PY 2003 VL 13 IS 1 BP 49 EP 58 DI 10.1038/sj.cr.7290150 PG 10 WC Cell Biology SC Cell Biology GA 673UB UT WOS:000182597600006 PM 12643349 ER PT J AU Botos, I Wlodawer, A AF Botos, I Wlodawer, A TI Cyanovirin-N: a sugar-binding antiviral protein with a new twist SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE cyanovirin-N; anti-HIV activity; 3D domain-swapping; gp120; protein folding; X-ray; NMR ID HIV-INACTIVATING PROTEIN; DOMAIN-SWAPPED DIMER; CIRCULAR PERMUTED VARIANT; DIPOLAR COUPLINGS; CRYSTAL-STRUCTURE; RELATIVE ORIENTATION; NATURAL-PRODUCTS; PROLINE RESIDUES; ENDONUCLEASE-I; GP120 AB Cyanovirin-N (CV-N), an 11-kDa protein from the cyanobacterium Nostoc ellipsosporum, is a highly potent virucidal agent that has generated interest as a lead natural product for the prevention and chemotherapy of human immunodeficiency virus infection. The antiviral activity of CV-N is mediated through specific, high-affinity interactions with the viral surface envelope glycoproteins. A number of structures of wild-type, mutant and sequence-shuffled CV-N have been solved by nuclear magnetic resonance and crystallography, showing that the protein exists as either a quasi-symmetric two-domain monomer or a domain-swapped dimer. Structures of several complexes of CV-N with oligosaccharides help in explaining the unique mode of high-affinity binding of these molecules to both forms of CV-N. C1 Natl Canc Inst, MCL, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), Natl Canc Inst, MCL, Bldg 536, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov NR 62 TC 32 Z9 41 U1 0 U2 3 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD FEB PY 2003 VL 60 IS 2 BP 277 EP 287 DI 10.1007/s000180300023 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 659FQ UT WOS:000181767000008 PM 12678493 ER PT J AU Inbaraj, JJ Motten, AG Chignell, CF AF Inbaraj, JJ Motten, AG Chignell, CF TI Photochemical and photobiological studies of tirapazamine (SR 4233) and related quinoxaline 1,4-di-N-oxide analogues SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID 3-AMINO-1,2,4-BENZOTRIAZINE 1,4-DIOXIDE TIRAPAZAMINE; N-OXIDE; SINGLET OXYGEN; DNA CLEAVAGE; AQUEOUS-SOLUTION; PLASMID DNA; REDUCTION; GUANINE; MECHANISM; RADICALS AB Tirapazamine, 3-amino-1,2,4-benzotriazine 1,4-di-N-oxide (TPZ; SR 4233), is currently undergoing phase II and III clinical trials as an antitumor agent. We have studied the photochemical properties of TPZ, and the related analogues 3-amino-2-quinoxalinecarbonitrile 1,4-di-N-oxide (TPZCN) and quinoxaline-1,4-di-N-oxide (quindoxin) with respect to their potential to photodamage DNA both oxidatively and reductively. We have found that TPZ, TPZCN, and quindoxin photosensitized the generation of singlet oxygen with quantum yields of 0.007, 0.19, and 0.02, respectively, in acetonitrile. Irradiation (lambda > 300 nm) of TPZ at pH 9.4 in the presence of a reducing agent, NADH, generated the corresponding nitroxide radical. At pH 7.4, photoirradiation of either TPZ or TPZCN in the presence of NADH in air saturated buffer gave the superoxide radical, which was trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO). In the absence of a reducing agent, singlet oxygen generated from TPZCN oxidized DMPO to 5,5-dimethyl-2-oxopyrrolin-1-oxyl (DMPOX). No spin adducts were detected during photoirradiation of TPZ, NADH, and DMPO in nitrogen-saturated buffer. However, when DMSO was also present, the DMPO/(CH3)-C-. adduct was observed, indicating the generation of the free hydroxyl radical. Both TPZ and TPZCN photooxidized reduced glutathione and azide to the glutathiyl and azidyl radicals, respectively. Under anaerobic conditions, NADH increased photoinduced strand breaks in pBR322 plasmid DNA caused by TPZ or TPZCN. For TPZ, the reactive species is probably the aforementioned nitroxide radical or the hydroxyl radical generated from its decomposition. In contrast, DNA damage by quindoxin was not affected by NADH, suggesting a different mechanism, possibly involving a photogenerated oxaziridine intermediate. These studies show that the photochemistry of TPZ, TPZCN, and quindoxin is complex and depends on the redox environment and whether oxygen is present. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 19 Z9 19 U1 3 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD FEB PY 2003 VL 16 IS 2 BP 164 EP 170 DI 10.1021/tx0256073 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 648CE UT WOS:000181131600008 PM 12588187 ER PT J AU Lee, YS Hodoscek, M Kador, PF Sugiyama, K AF Lee, YS Hodoscek, M Kador, PF Sugiyama, K TI Hydrogen bonding interactions between aldose reductase complexed with NADP(H) and inhibitor tolrestat studied by molecular dynamics simulations and binding assay SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT 11th International Workshop on Enzymology and Molecular Biology of Cabonyl Metabolism CY JUL 02-06, 2002 CL YSTAD, SWEDEN DE aldose reductase; cationic source; His 110; NADP(+) ID ACTIVE-SITE; DIABETIC COMPLICATIONS; CATALYTIC MECHANISM; REVEALS; STATE; MUTAGENESIS AB Molecular dynamics simulations and binding affinity studies have been carried out in order to probe the effect of the charge state of His110 and cofactor NADPH on the binding affinity of the potent inhibitor tolrestat to aldose reductase (ALR2) complexed with either NADPH or NADP(+). Molecular dynamics simulations of ALR2-NADP(+)-tolrestat indicate that the carboxylate group of tolrestat forms a hydrogen bond with Tyr48 and His110 of ALR2 regardless of the charge state of His110. In the case of ALR2-NADPH-tolrestat, the H-bonding pattern is significantly different from that of ALR2 -NADP(+)-tolrestat, in that Tyr48 does not H-bond to tolrestat. The binding affinity of tolrestat to ALR2 complexed with either NADPH or NADP(+) is comparable and pH-dependent. Based on the H-bonding interactions seen in computer simulations, it is proposed that the cationic moiety at the active site of ALR2-NADP(+) and ALR2-NADPH that interacts with the carboxylate of tolrestat is NADP(+) and His110, respectively. The residue that gives rise to the pH-dependent binding of tolrestat to ALR2-NADP+ and ALR2-NADPH has been identified as Tyr48 and His110, respectively. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Natl Inst Chem, Ljubljana, Slovenia. NEI, NIH, Bethesda, MD 20892 USA. RP Lee, YS (reprint author), NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. NR 27 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD FEB 1 PY 2003 VL 143 BP 307 EP 316 AR PII S0009-2797(02)00188-6 DI 10.1016/S0009-2797(02)00188-6 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 655KP UT WOS:000181551300036 PM 12604217 ER PT J AU Sato, S Secchi, EF Sakurai, S Ohta, N Fukase, S Lizak, MJ AF Sato, S Secchi, EF Sakurai, S Ohta, N Fukase, S Lizak, MJ TI NADPH-dependent reductases and polyol formation in human leukemia cell lines SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT 11th International Workshop on Enzymology and Molecular Biology of Cabonyl Metabolism CY JUL 02-06, 2002 CL YSTAD, SWEDEN DE aldose reductase; aldehyde reductase; leukemia; leukocyte; neutrophils; lymphocytes; polyol; NMR; 3-fluoro-3-deoxy-D-glucose ID LENS ALDOSE REDUCTASE; POLYMORPHONUCLEAR LEUKOCYTES; DIABETIC COMPLICATIONS; NEUTROPHIL PHAGOCYTOSIS; ALDEHYDE REDUCTASE; KIDNEY ALDOSE; INHIBITION; ADHESION; MELLITUS; PATHWAY AB Because of the limited availability of human tissues, leukemia cell lines are often utilized as the models for human leukocytes. In this study, we investigated the NADPH-dependent reductases and polyol pathway in commonly utilized human leukemia cell lines. The relative amounts of aldose and aldehyde reductases were estimated by separating two enzymes with chromatofocusing. The flux of glucose through the polyol pathway was examined by F-19-NMR using 3-fluoro-3-deoxy-D-glucose (3FG) as substrate. Sugar alcohol analysis was conducted by gas chromatography. In myelocytic leukemia cells, the major reductase was aldehyde reductase, and levels of aldose reductase were extremely low. Although lymphocytic cells also contained both aldose and aldehyde reductases, the levels of aldose reductase appeared to be higher in lymphocytic cells than myeolcytic cells. In two lymphocytic cells MOLT-4 and SKW6.4, aldose reductase is clearly dominant. When incubated in medium containing D-galactose, all cell lines quickly accumulated galactitol. There was correlation between galactitol levels and aldose reductase levels. The aldose reductase inhibitor FK 366 significantly reduced the formation of galactitol. F-19-NMR of the cells cultured with 3FG as substrate demonstrated the formation of 3-fluoro-3-dexoy-sorbitol in all the cell lines examined in this study. The relative amounts of sorbitol and fructose varied significantly among the cells. The data confirm that the polyol pathway is present in both myelocytic and lymphocytic leukemia cell lines. However, there is a large variation among the cell lines in the levels of enzymes and flux of glucose through the polyol pathway. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Oklahoma, Coll Med, Dept Med, Oklahoma City, OK 73190 USA. NEI, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Sato, S (reprint author), Univ Oklahoma, Coll Med, Dept Med, POB 26901,BSEB 331, Oklahoma City, OK 73190 USA. NR 35 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD FEB 1 PY 2003 VL 143 BP 363 EP 371 AR PII S0009-2797(02)00209-0 DI 10.1016/S0009-2797(02)00209-0 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 655KP UT WOS:000181551300042 PM 12604223 ER PT J AU Han, SW Tae, J Kim, JA Kim, DK Seo, GS Yun, KJ Choi, SC Kim, TH Nah, YH Lee, YM AF Han, SW Tae, J Kim, JA Kim, DK Seo, GS Yun, KJ Choi, SC Kim, TH Nah, YH Lee, YM TI The aqueous extract of Solanum melongena inhibits PAR2 agonist-induced inflammation SO CLINICA CHIMICA ACTA LA English DT Article DE Solanum melongena; anti-inflammatory; trypsin; tc-NH2; paw edema ID PROTEINASE-ACTIVATED RECEPTOR-2; MAST-CELL TRYPTASE; THROMBIN RECEPTOR; MOLECULAR-CLONING; (PAR(2))-ACTIVATING PEPTIDES; IN-VITRO; EXPRESSION; MECHANISM; EGGPLANT; TRYPSIN AB Background: Solanum melongena L. (Solanaceae) has antioxidant, analgesic, hypolipidemic and antiallergic activity. Methods: The anti-inflammatory effects of the water extract of the S. melongena (SMWE) were investigated in PAR2-mediated mouse paw edema. Paw edema was induced by injection of trypsin or trans-cinnamoyl-LIGRLO-NH2 (tc-NH2) into the hindpaw of mice. The SMWE (1, 5, 10, and 100 mg/kg) was orally administered 1 h before induction of inflammation. Results: At doses of 5, 10, and 100 mg/kg, the SMWE showed significant inhibition of both paw edema and vascular permeability. The SMWE (10 mg/kg) significantly also inhibited PAR2 agonist-induced myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-alpha expression in paw tissue. Conclusion: These results demonstrate that the SMWE inhibits PAR2 agonist-induced mouse paw edema. (C) 2002 Elsevier Science B.V All rights reserved. C1 Wonkwang Univ, Coll Pharm, Dept Oriental Pharm, Iksan 570749, Jeonbuk, South Korea. NIAID, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. Wonkwang Univ, Sch Med, Dept Internal Med, Iksan 570749, Jeonbuk, South Korea. Wonkwang Univ, Sch Med, Dept Pathol, Iksan 570749, Jeonbuk, South Korea. RP Lee, YM (reprint author), Wonkwang Univ, Coll Pharm, Dept Oriental Pharm, Iksan 570749, Jeonbuk, South Korea. NR 27 TC 21 Z9 22 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD FEB PY 2003 VL 328 IS 1-2 BP 39 EP 44 AR PII S0009-8981(02)00377-7 DI 10.1016/S0009-8981(02)00377-7 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 655ML UT WOS:000181556300004 PM 12559597 ER PT J AU Manal, K Davis, IM Galinat, B Stanhope, S AF Manal, K Davis, IM Galinat, B Stanhope, S TI The accuracy of estimating proximal tibial translation during natural cadence walking: bone vs. skin mounted targets SO CLINICAL BIOMECHANICS LA English DT Article DE soft tissue movement; error; knee; motion analysis; gait ID ANTERIOR CRUCIATE LIGAMENT; DEFICIENT KNEE; IN-VIVO; MARKERS; KINEMATICS; MOVEMENT; LAXITY; INJURY; MOTION AB Objective. To assess the efficacy of estimating proximal tibial translation using video-based motion capture and an array of surface-mounted targets ideal for tracking motion of the tibia. Design. Superficial and bone-anchored tracking targets were used to create two independent sets of data locating the proximal tibia in a global coordinate system. Background. Knowledge of the effect that soft tissue movement has on estimates of proximal tibial translation has not been reported to date. This basic information is necessary to establish construct validity for any study proposing to document tibial translation using standard video-based motion capture methods. Methods. A six camera motion capture system was used to collect surface-mounted and bone-anchored data for seven healthy adult subjects walking at a self-selected speed. The subjects walked along the positive Y-axis of the global reference system, with the positive Z-axis oriented vertically. Results. Average peak differences in the location of the proximal tibia calculated from the bone and surface-mounted targets were 7.1, 3.7 and 2.1 mm along the X, Y and Z axes of the global coordinate system respectively. Individual subject peak differences were as large as 14.1, 11.8 and 8.3 mm along the X, Y and Z axes. Conclusions. Estimates of tibial translation with a measurement resolution better than 3 mm are not likely using standard motion capture methods and tracking targets attached superficially to the lower leg. C1 Univ Delaware, Biomed Engn Res Ctr, Spencer Labs 126, Newark, DE 19716 USA. Joyner Sportsmed Inst, Harrisburg, PA USA. Delaware Orthopaed Ctr, Newark, DE USA. NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. RP Manal, K (reprint author), Univ Delaware, Biomed Engn Res Ctr, Spencer Labs 126, Newark, DE 19716 USA. NR 21 TC 38 Z9 38 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD FEB PY 2003 VL 18 IS 2 BP 126 EP 131 AR PII S0268-0033(02)00176-6 DI 10.1016/S0268-0033(02)00176-6 PG 6 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 653WY UT WOS:000181461100006 PM 12550811 ER PT J AU Messmann, RA Ullmann, CD Lahusen, T Kalehua, A Wasfy, J Melillo, G Ding, I Headlee, D Figg, WD Sausville, EA Senderowicz, AM AF Messmann, RA Ullmann, CD Lahusen, T Kalehua, A Wasfy, J Melillo, G Ding, I Headlee, D Figg, WD Sausville, EA Senderowicz, AM TI Flavopiridol-related proinflammatory syndrome is associated with induction of interleukin-6 SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-I TRIAL; DEPENDENT KINASE INHIBITOR; RECOMBINANT HUMAN INTERLEUKIN-6; HUMAN-BREAST-CARCINOMA; NF-KAPPA-B; INTRAVENOUS INTERLEUKIN-6; ANTITUMOR-ACTIVITY; GROWTH-INHIBITION; CELL-LINES; CYTOKINES AB Background: Flavopiridol is a flavonoid with antiproliferative effects mediated, in part, by inhibition of cyclin-dependent kinases. Clinical manifestations in a previous Phase I trial in patients with refractory malignancies treated with a 72-h flavopiridol infusion included a proinflammatory syndrome consisting of fever, fatigue, and "local" tumor pain with concomitant alterations in plasma acute-phase reactant proteins. Purpose: The aim of this study was to determine whether the proinflammatory syndrome observed in this trial was associated with modulation of plasma cytokines. Methods: Patients receiving flavopiridol (n = 76) had serial plasma samples drawn preinfusion and during the infusion for evaluation of interleukin (IL)-6, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, basicfibroblast growth factor, transforming growth factor-beta, and tumor necrosis factor-alpha levels by standard ELISA assays. The Wilcoxon signed rank test was used to test the significance of the difference between the baseline (time 0) plasma cytokine levels compared with the values of each subsequent data collection time points (8, 24, 48, and 72 h). Results: There was a significant and sustained increase in plasma IL-6 levels at all time points when compared with baseline values. Paired values were used in the statistical analysis. Median plasma (interquartile range) values of IL-6 were elevated from 15.5 (9-52) pg/ml at baseline to 23 (4-48) pg/ml (P < 0.01) at 8 h; from 15 (2-48) pg/ml at baseline to 46 (21-105) pg/ml (P < 0.001) at 24 h; from 16 (9-52) pg/ml at baseline to 61 (32-170) pg/ml (P < 0.001) at 48 h; and from 15.5 (6-48) pg/ml to 68 (40-200) pg/ml (P < 0.001) at 72 h. Significance was maintained even when adjusted for multiple comparisons. The relative increase in IL-6 concentration was dose-dependent. Moreover, IL-6 elevation had a direct correlation with flavopiridol peak plasma concentration, flavopiridol area under the curve, and plasma C-Reactive protein levels. A significant decrease in plasma granulocyte macrophage colony-stimulating factor occurred at the 8-h sampling point: 50 pg/ml (interquartile range 10-205 pg/ml, P < 0.01) when compared with baseline plasma levels and 71 pg/ml (interquartile range 5-152 pg/ml, P < 0.01). No changes in the other pro or anti-inflammatory cytokines were observed. Immunohistochemistry studies in bone marrow aspirates from a prospective group of patients in this trial demonstrated similar to4-fold induction of IL-6 (compared with baseline), mostly in non-T cells. Conclusion: Biochemical analysis of plasma in patients undergoing infusional flavopiridol found a significant dose-dependent induction of IL-6. IL-6 elevation could be a marker for the process leading to the appearance of the proinflammatory syndrome observed in patients treated with infusional flavopiridol. The mechanism(s) underlying IL-6 induction and its significance are still unknown but may influence strategies to modulate flavopiridol's clinical effects. C1 NIDCR, Oral & Pharyngeal Canc Branch, Mol Therapeut Unit, NIH, Bethesda, MD 20892 USA. NIA, Radiat Oncol Branch, Dev Therapeut Program, Bethesda, MD 20892 USA. NIA, Natl Canc Inst, Natl Aging Inst, Bethesda, MD 20892 USA. Univ Rochester, Dept Radiat Oncol, Rochester, NY 14627 USA. RP Senderowicz, AM (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, Mol Therapeut Unit, NIH, Bldg 30,Room 211,30 Convent Dr, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 55 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 2003 VL 9 IS 2 BP 562 EP 570 PG 9 WC Oncology SC Oncology GA 643AR UT WOS:000180840200005 PM 12576419 ER PT J AU Agrawal, M Abraham, J Balis, FM Edgerly, M Stein, WD Bates, S Fojo, T Chen, CC AF Agrawal, M Abraham, J Balis, FM Edgerly, M Stein, WD Bates, S Fojo, T Chen, CC TI Increased Tc-99m-sestamibi accumulation in normal liver and drug-resistant tumors after the administration of the glycoprotein inhibitor, XR9576 SO CLINICAL CANCER RESEARCH LA English DT Article ID PREDICTING CHEMOTHERAPEUTIC RESPONSE; BREAST-CANCER PATIENTS; CELL LUNG-CANCER; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; TC-99M SESTAMIBI; IN-VIVO; PSC 833; SOLID TUMORS; PHASE-I AB Tc-99m-sestamibi, a substrate of the multidrug transporter P-glycoprotein (Pgp), has been used as a functional imaging agent for the multidrug resistance-1 (MDR1) phenotype. In vitro, retention of Tc-99m-sestamibi by cells that over-express Pgp can be enhanced by the addition of Pgp inhibitors. XR9576 (Tariquidar) is a potent and selective noncompetitive inhibitor of Pgp that is active at 25-80 nM. A Phase I trial of XR9576 in combination with vinorelbine (Navelbine) was conducted in 26 patients with metastatic cancers. A Tc-99m-sestamibi scan was obtained at baseline followed 48-96 h later by a second scan 1-3 h after the administration of XR9576. Time activity curves and areas under the curves (AUCs) were obtained for tumor, liver, lung, and heart, and tissue:heart AUC ratios were calculated. XR9576 enhanced Tc-99m-sestamibi accumulation and retention in the liver of all but two patients with a mean change of +128%. Furthermore, in 13 of 17 patients with tumor masses visible by Tc-99m-sestamibi, the tumor:heart Tc-99m-sestamibi AUC(0-3 h) increased after the administration of XR9576, with increases of 36-263% seen in 8 patients. We conclude that in vivo administration of XR9576 inhibits Tc-99m-sestamibi efflux in both the normal liver and in drug resistant tumors. This study provides convincing evidence of the existence of XR9576-inhibitable Tc-99m-sestamibi efflux in a large fraction of drug resistant tumors. One can predict that efflux of Pgp substrates also occurs in these tumors. XR9576 provides an efficient way to inhibit this efflux and offers the potential to increase drug exposure in human cancer. C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. W Virginia Univ, Mary Babb Canc Ctr, Charleston, WV 25304 USA. Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Jerusalem, Israel. NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov NR 35 TC 100 Z9 104 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 2003 VL 9 IS 2 BP 650 EP 656 PG 7 WC Oncology SC Oncology GA 643AR UT WOS:000180840200017 PM 12576431 ER PT J AU Makower, D Rozenblit, A Kaufman, H Edelman, M Lane, ME Zwiebel, J Haynes, H Wadler, S AF Makower, D Rozenblit, A Kaufman, H Edelman, M Lane, ME Zwiebel, J Haynes, H Wadler, S TI Phase II clinical trial of intralesional administration of the oncolytic adenovirus ONYX-015 in patients with hepatobiliary tumors with correlative p53 studies SO CLINICAL CANCER RESEARCH LA English DT Article ID REPLICATION-SELECTIVE ADENOVIRUS; NECK-CANCER; HEPATOCELLULAR CARCINOMAS; ATTENUATED ADENOVIRUS; RECURRENT HEAD; HEPATITIS-B; CELLS; CHEMOTHERAPY; MUTATIONS; INFECTION AB Purpose: ONYX-015 is a genetically modified adenovirus with a deletion of the E1B early gene and is therefore designed to replicate preferentially in p53-mutated cells. A Phase II trial of intralesional ONYX-015 was conducted in patients with hepatobiliary tumors to determine the safety and efficacy of such a treatment. Experimental Design: All patients had biopsy-proven, measurable tumors of the liver, gall bladder, or bile ducts that were beyond the scope of surgical resection. Patients received intralesional injections of ONYX-015 at either 6 X 10(9) or 1 x 10(10) plaque-forming units/lesion up to a total dose of 3 x 10(10) plaque-forming units, and i.p. injections were allowed in patients with malignant ascites. The status of p53 was assessed by immunohistochemistry or Affymetrix GeneChip microarray analysis. Studies were conducted for viral shedding and for the presence of antiadenoviral antibodies before and after the injection of ONYX-015. Patients were assessed for response and toxicity. Results: Twenty patients were enrolled, and 19 patients were eligible. Half of the patients had primary bile duct carcinomas. Serious toxicities (> grade 2) were uncommon and included hepatic toxicity (three patients), anemia (one patient), infection (one patient), and cardiac toxicity (one patient, atrial fibrillation). Sixteen patients were evaluable for response. Among these evaluable patients, 1 of 16 (6.3%) had a partial response, 1 of 16 (6.3%) had prolonged disease stabilization (49 weeks), and 8 of 16 (50%) had a >50% reduction in tumor markers. Of the 19 eligible patients, 18 (94.7%) had specimens available for p53 analysis. Fifteen of these 18 patients (83.3%) had evidence of p53 mutation by one or both methods, although the methods correlated poorly. Viral shedding was confined to bile (two of two patients) and ascites (four of four patients). Pretreatment adenoviral antibodies were present in 14 of 14 patients and increased by 33.2% after ONYX-015 treatment. Conclusions: Intralesional treatment with ONYX-015 in patients with hepatobiliary tumors is safe and well tolerated, and some patients had evidence of an anticancer effect. The high incidence of p53 mutations in these tumors makes this a logical population in which to test this therapy but precludes definitive evaluation about the necessity of a p53 mutation for ONYX-015 clinical activity. C1 Cornell Univ, Weill Med Coll, Div Hematol Oncol, Dept Med, New York, NY 10021 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10463 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10463 USA. Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10463 USA. Albert Einstein Coll Med, Dept Surg, Bronx, NY 10463 USA. Albert Einstein Canc Ctr, Bronx, NY 10463 USA. RP Wadler, S (reprint author), Cornell Univ, Weill Med Coll, Div Hematol Oncol, Dept Med, C606,1300 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [CA 13330, N01-CM-07003-74] NR 40 TC 106 Z9 110 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 2003 VL 9 IS 2 BP 693 EP 702 PG 10 WC Oncology SC Oncology GA 643AR UT WOS:000180840200023 PM 12576437 ER PT J AU Bui, MHT Seligson, D Han, KR Pantuck, AJ Dorey, FJ Huang, Y Horvath, S Leibovich, BC Chopra, S Liao, SY Stanbridge, E Lerman, MI Palotie, A Figlin, RA Belldegrun, AS AF Bui, MHT Seligson, D Han, KR Pantuck, AJ Dorey, FJ Huang, Y Horvath, S Leibovich, BC Chopra, S Liao, SY Stanbridge, E Lerman, MI Palotie, A Figlin, RA Belldegrun, AS TI Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: Implications for prognosis and therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY G250; DIAGNOSTIC BIOMARKER; CANCER CELLS; MN ANTIGEN; EXPRESSION; HYPOXIA; PROTEIN; IDENTIFICATION; SPECIMENS; KIDNEY AB Purpose: Metastatic renal cell carcinoma (RCC) has a poor prognosis and an unpredictable course. To date, there are no molecular markers which can reliably predict RCC outcome. We investigated whether a novel kidney cancer marker, carbonic anhydrase IX (CAIX), is associated with progression and survival. Experimental Design: Immunohistochemical analysis using a CAIX monoclonal antibody was performed on tissue microarrays constructed from paraffin-embedded specimens from patients (N = 321) treated by nephrectomy for clear cell RCC. CAIX staining was correlated with response to treatment, clinical factors, pathologic features, and survival. Results: CAIX staining was present in 94% of clear cell RCCs. Survival tree analysis determined that a cutoff of 85% CAIX staining provided the most accurate prediction of survival. Low CAIX (less than or equal to85%) staining was an independent poor prognostic factor for survival for patients with metastatic RCC, with a hazard ratio of 3.10 (P < 0.001). CAIX significantly substratified patients with metastatic disease when analyzed by T stage, Fuhrman grade, nodal involvement, and performance status (P < 0.001, = 0.001, = 0.009, = 0.005, respectively). For patients with nonmetastatic RCC and at high risk for progression, low CAIX predicted a worse outcome similar to patients with metastatic disease (P = 0.058). Overall expression of CAIX decreased with development of metastasis; as demonstrated by the lower CAIX staining levels in metastatic lesions relative to matched primary tumor specimens (P = 0.036). Conclusions: On the basis of our data, CAIX is the most significant molecular marker described in kidney cancer to date. Decreased CAIX levels are independently associated with poor survival in advanced RCC. CAIX reflects significant changes in tumor biology, which should be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CAIX-targeted therapies. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biostat & Human Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. NCI, Bethesda, MD 20892 USA. RP Belldegrun, AS (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, 10833 Conte Ave,Room 66-118 CHS, Los Angeles, CA 90095 USA. NR 45 TC 428 Z9 447 U1 7 U2 22 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 2003 VL 9 IS 2 BP 802 EP 811 PG 10 WC Oncology SC Oncology GA 643AR UT WOS:000180840200039 PM 12576453 ER PT J AU Ouyang, XM Hejtmancik, JF Jacobson, SG Xia, XJ Li, A Du, LL Newton, V Kaiser, M Balkany, T Nance, WE Liu, XZ AF Ouyang, XM Hejtmancik, JF Jacobson, SG Xia, XJ Li, A Du, LL Newton, V Kaiser, M Balkany, T Nance, WE Liu, XZ TI USH1C: a rare cause of USH1 in a non-Acadian population and a founder effect of the Acadian allele SO CLINICAL GENETICS LA English DT Article DE Usher syndrome; harmonin; USH1C; Acadian population; founder effect ID SYNDROMIC RECESSIVE DEAFNESS; SYNDROME TYPE 1F; SYNDROME TYPE 1C; SYNDROME TYPE-I; HAPLOTYPE ANALYSIS; MUTATIONS; GENE; HYPERINSULINISM; CDH23; LOCUS AB Usher syndrome (USH) is characterized by the associated findings of hearing loss and retinitis pigmentosa (RP), leading to progressive loss of vision. Three forms of USH can be distinguished clinically. In the most severe form, USH1, profound congenital deafness is associated with vestibular dysfunction and RP. To determine the frequency of USH1C mutations as a cause for USH1, 128 probands with Usher syndrome type 1 including seven from Acadian and 121 from non-Acadian populations were systematically screened for mutations in USH1C using a combined single-strand conformational polymorphisms (SSCP)/heteroduplex and sequencing method. All seven Acadian USH1 patients were found to be homozygous for both the 216G>A mutation and the 9-repeat VNTR which characterizes the Acadian allele, confirming previous evidence for a founder effect by haplotype analysis. However, USH1C mutations were identified in only two non-Acadian USH1 probands (1.65%) including one from Pakistan who was homozygous for a 238-239insC mutation and one from Canada was also homozygous for the Acadian allele. The low prevalence of USH1C mutations in the present study suggests that the high prevalence of the 238-239insC in Germany may reflect a founder effect. Comparison of the affected haplotypes in the Canadian patient with the Acadian USH1 patients yielded evidence for a founder effect. Our data suggest that USH1C is a relatively rare form of USH1 in non-Acadian populations and that in addition to the 216G>A Acadian mutation, the 238-239insC mutation appears to be common in some populations. C1 Univ Miami, Dept Otolaryngol D48, Miami, FL 33136 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. Univ Manchester, Ctr Audiol, Manchester, Lancs, England. RP Liu, XZ (reprint author), Univ Miami, Dept Otolaryngol D48, 1666 NW 12th Ave, Miami, FL 33136 USA. FU NEI NIH HHS [EY-05627]; NIDCD NIH HHS [DC05575] NR 18 TC 15 Z9 15 U1 1 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD FEB PY 2003 VL 63 IS 2 BP 150 EP 153 DI 10.1046/j.0009-9163.2002.00004.x PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 652UB UT WOS:000181397800014 PM 12630964 ER PT J AU Abbott, KC Hshieh, P Cruess, D Agodoa, LYC Welch, PG Taylor, AJ Yuan, CM AF Abbott, KC Hshieh, P Cruess, D Agodoa, LYC Welch, PG Taylor, AJ Yuan, CM TI Hospitalized valvular heart disease in patients on renal transplant waiting list: incidence, clinical correlates and outcomes SO CLINICAL NEPHROLOGY LA English DT Article DE valvular heart disease; hospitalization; renal transplant; dialysis; end-stage renal disease; USRDS; aortic; mitral; surgery ID CARDIAC-VALVE CALCIFICATION; DIALYSIS PATIENTS; PRIMARY HYPERPARATHYROIDISM; METABOLISM; MORTALITY; ABNORMALITIES; REPLACEMENT; SURVIVAL; SURGERY; FAILURE AB Background: Patients with ESRD are at increased risk for heart valve calcification. It has not been established whether hospitalized valvular heart disease (VHD) is a substantial barrier to renal transplantation (RT) after transplant listing, or whether VHD progresses after RT. Methods: Using data from the USRDS, we studied 3 5,215 patients with ESRD enrolled on the renal transplant waiting list from July 1994 to June 1997. Cox non-proportional hazards regression models were used to calculate adjusted, time-dependent hazard ratios (HR) for RT and VHD. Results: In comparison to maintenance dialysis (2.2/1,000 person years), RT was independently associated with a lower hazard for hospitalization for VHD (0.7/1,000 person years, HR 0.28, 95% confidence interval 0.17 - 0.47). Renal transplant recipients had much lower rates of VHD after transplant than before (rate ratio (RR) 0.49, 95% Cl 0.47 - 0.52). Patients with VHD were significantly less likely to receive RT (adjusted rate for RT 0.38, 95% Cl 0.20 - 0.45) but patients who received valve replacement surgeries (VRS) were not affected (adjusted rate for RT 1.10, 95% Cl 0.52 - 2.32, not significant). Conclusions: VHD is an uncommon but serious barrier to RT after listing, while VRS is not a significant barrier to RT. Established VHD does not appear to worsen after RT. Clinicians should consider giving increased attention to the detection and treatment of VHD during the pre-transplant evaluation. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDK, NIH, Bethesda, MD USA. Walter Reed Army Med Ctr, Serv Cardiol, Washington, DC 20307 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 28 TC 8 Z9 8 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD FEB PY 2003 VL 59 IS 2 BP 79 EP 87 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 640CJ UT WOS:000180668900002 PM 12608550 ER PT J AU Lotze, M Kaethner, RJ Erb, M Cohen, LG Grodd, W Topka, H AF Lotze, M Kaethner, RJ Erb, M Cohen, LG Grodd, W Topka, H TI Comparison of representational maps using functional magnetic resonance imaging and transcranial magnetic stimulation SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE motor system; mapping; fMRI; TMS ID HUMAN MOTOR CORTEX; BRAIN-STIMULATION; MRI; FMRI; LOCALIZATION; ACTIVATION; MUSCLE AB Objective: Comparison of functional magnetic resonance imaging (fMRI) representational maps, that were generated during voluntary thumb abduction, hand dorsiflexion and foot elevation to amplitude maps of motor-evoked potentials (MEPs) elicited by single transcranial magnetic stimulation (TMS) administered to cortical motor representation areas of the muscles of the thenar eminence, extensor carpi radialis and tibialis anterior muscles. Methods: Stimulus locations that produced maximal motor-evoked potential amplitudes were compared to fMRI activation maxima in three-dimensional (3D)-space and in a 2D-projection using a novel technique that allowed fMRI activation sites to be projected onto the surface of the brain. Results and conclusions: When analyzing pooled data from all target muscles, the location of projected fMRI and TMS activation maxima on the cortical surface differed by an average 13.9 mm. The differences in 3D distances were particularly large for representation areas of lower leg muscles. 3D distances between fMRI activation maxima and highest MEP site in TMS correlated significantly with higher TMS thresholds. These observations strongly suggest that higher TMS excitation thresholds and lower MEP amplitudes are largely due to the absolute distance between the stimulation site and the excitable cortical tissue targeting this muscle. After the projection 4 out of 5 representation sites as evaluated by TMS were located anterior to the fMRI activation maxima, an observation which may due to the orientation of the magnetic field induced by the current in the coil. The representation sites as evaluated with both methods were specific for the type of movement: distances between representation maxima of the same movements were significantly smaller than those within different movements. Nevertheless, fMRI and TMS provide complementary information, which is discussed on the basis of the functional map observed with both methods. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Tubingen, Inst Med Psychol & Behav Biol, D-72074 Tubingen, Germany. Univ Tubingen, Dept Neuroradiol, CNS, Sect Expt NMR, Tubingen, Germany. Univ Tubingen, Dept Neurol, Tubingen, Germany. NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD USA. RP Lotze, M (reprint author), Univ Tubingen, Inst Med Psychol & Behav Biol, Gartenstr 29, D-72074 Tubingen, Germany. OI Erb, Michael/0000-0002-9311-4693 NR 26 TC 52 Z9 52 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD FEB PY 2003 VL 114 IS 2 BP 306 EP 312 DI 10.1016/S1388-2457(02)00380-2 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 647LJ UT WOS:000181094000016 PM 12559238 ER PT J AU Abernethy, D Urquidi-MacDonald, M Mascelli, M Frederick, B Freedman, J Fitzgerald, D Kleiman, N AF Abernethy, D Urquidi-MacDonald, M Mascelli, M Frederick, B Freedman, J Fitzgerald, D Kleiman, N TI Neural networks pattern recognition to predict abciximab pharmacodynamics using readily available patient characteristics. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 NIA, Baltimore, MD 21224 USA. Penn State Univ, University Pk, PA 16802 USA. Centocor Inc, Malvern, PA 19355 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Royal Coll Surgeons Ireland, Dublin 2, Ireland. Baylor Coll Med, Houston, TX 77030 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P51 EP P51 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100188 ER PT J AU Gordon, SM Wahl, SM Picco, C Dionne, RA AF Gordon, SM Wahl, SM Picco, C Dionne, RA TI Safety and tolerability and absorption of topical thalidomide. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 NIDCR, 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P55 EP P55 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100201 ER PT J AU Guo, X Ernst, A Grem, J AF Guo, X Ernst, A Grem, J TI Pharmacokinetics of capecitabine given in combination with oxaliplatin: A pilot study of adult cancer patients. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 NCI, 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P49 EP P49 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100179 ER PT J AU Kim, H Neubert, JK Iadarola, MJ Goldman, D Dionne, RA AF Kim, H Neubert, JK Iadarola, MJ Goldman, D Dionne, RA TI Evaluation of single nucleotide polymorphisms in genes related to the vanilloid receptor and cyclooxygenase-2 in human pain sensitivity. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 NIDCR, NIH, Bethesda, MD USA. NIAAA, NIH, Bethesda, MD 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P98 EP P98 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100358 ER PT J AU Mannes, A Neubert, J Polomano, RC Iadarola, MJ Hershey, MS AF Mannes, A Neubert, J Polomano, RC Iadarola, MJ Hershey, MS TI Precise percutaneous sciatic nerve injection with stimulator needle localization. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 NIH, Milton S Hershey Med 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P30 EP P30 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100108 ER PT J AU Medlock, MM Cantilena, L Haigney, M Riel, M Kahn, R Elkashef, A Chiang, CN AF Medlock, MM Cantilena, L Haigney, M Riel, M Kahn, R Elkashef, A Chiang, CN TI Cardiovascular effects of intravenous cocaine in human volunteers. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 NIDA, USUHS, 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P31 EP P31 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100110 ER PT J AU Neubert, JK Mannes, A Karai, L Iadarola, MJ Dionne, RA AF Neubert, JK Mannes, A Karai, L Iadarola, MJ Dionne, RA TI Percutaneous resiniferatoxin-induced incisional pain analgesia. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P30 EP P30 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100106 ER PT J AU Lipscomb, J Donaldson, MS AF Lipscomb, J Donaldson, MS TI Outcomes research at the national cancer institute: Measuring, understanding, and improving the outcomes of cancer care SO CLINICAL THERAPEUTICS LA English DT Article DE cancer care; outcomes research; national cancer institute ID QUALITY-OF-LIFE AB What is the National Cancer Institute (NCI) doing to enhance the state of the science for measuring and understanding patient-centered outcomes of cancer care and to make this information useful for improved decision making? The NCI has a new focus on research that describes, interprets, and predicts the impact of various influences, especially interventions, on end points that matter to decision makers. The research includes end points such as survival, health-related quality of life, satisfaction and patient experience, and economic burden. To further this work, NCI supports and conducts research to (1) identify valid, reliable, responsive, and feasible end-point measures; (2) collect high-quality evidence about the impact of interventions on the end points of interest; (3) improve our understanding of the effects of other factors that shape this interaction; and (4) expand our capacity to translate research findings into information that is useful to patients, clinical policy makers, payers, regulators, standard setters, and providers of cancer care. Copyright (C) 2003 Excerpta Medica, Inc. C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Outcomes Res Branch, Bethesda, MD 20892 USA. RP Lipscomb, J (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Outcomes Res Branch, 6130 Execut Blvd,MSC 7344,EPN Room 4005, Bethesda, MD 20892 USA. NR 26 TC 12 Z9 12 U1 2 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD FEB PY 2003 VL 25 IS 2 BP 699 EP 712 DI 10.1016/S0149-2918(03)80106-6 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 653KG UT WOS:000181433900023 PM 12749523 ER PT J AU McCray, AT AF McCray, AT TI An upper-level ontology for the biomedical domain SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Review DE ontologies; semantic networks; controlled vocabularies; Unified Medical Language System ID INFORMATION; KNOWLEDGE AB At the US National Library of Medicine we have developed the Unified Medical Language System (UMLS), whose goal it is to provide integrated access to a large number of biomedical resources by unifying the vocabularies that are used to access those resources. The UMLS currently interrelates some 60 controlled vocabularies in the biomedical domain. The UMLS coverage is quite extensive, including not only many concepts in clinical medicine, but also a large number of concepts applicable to the broad domain of the life sciences. In order to provide an overarching conceptual framework for all UMLS concepts, we developed an upper-level ontology, called the UMLS semantic network. The semantic network, through its 134 semantic types, provides a consistent categorization of all concepts represented in the UMLS. The 54 links between the semantic types provide the structure for the network and represent important relationships in the biomedical domain. Because of the growing number of information resources that contain genetic information, the UMLS coverage in this area is being expanded. We recently integrated the taxonomy of organisms developed by the NLM's National Center for Biotechnology Information, and we are currently working together with the developers of the Gene Ontology to integrate this resource, as well. As additional, standard, ontologies become publicly available, we expect to integrate these into the UMLS construct. Published in 2003 by John Wiley Sons, Ltd. C1 Natl Lib Med, Bethesda, MD 20209 USA. RP McCray, AT (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20209 USA. NR 11 TC 52 Z9 54 U1 2 U2 9 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PD FEB PY 2003 VL 4 IS 1 BP 80 EP 84 DI 10.1002/cfg.255 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 652RJ UT WOS:000181392000012 PM 18629109 ER PT J AU Smith, L Yeganova, L Wilbur, WJ AF Smith, L Yeganova, L Wilbur, WJ TI Hidden Markov models and optimized sequence alignments SO COMPUTATIONAL BIOLOGY AND CHEMISTRY LA English DT Article DE algorithm; optimization; gene synonyms; sequence alignment ID PROTEIN NAMES; GENE AB We present a formulation of the Needleman-Wunsch type algorithm for sequence alignment in which the mutation matrix is allowed to vary under the control of a hidden Markov process. The fully trainable model is applied to two problems in bioinformatics: the recognition of related gene/protein names and the alignment and scoring of homologous proteins. Crown Copyright (C) 2002 Published by Elsevier Science Ltd. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. RP Smith, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Rm 614D,Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 11 TC 2 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1476-9271 J9 COMPUT BIOL CHEM JI Comput. Biol. Chem. PD FEB PY 2003 VL 27 IS 1 BP 77 EP 84 AR PII S1476-9271(02)00096-8 DI 10.1016/S1476-9271(02)00096-8 PG 8 WC Biology; Computer Science, Interdisciplinary Applications SC Life Sciences & Biomedicine - Other Topics; Computer Science GA 686NL UT WOS:000183327800009 PM 12798042 ER PT J AU Proschan, MA Liu, Q Hunsberger, S AF Proschan, MA Liu, Q Hunsberger, S TI Practical midcourse sample size modification in clinical trials SO CONTROLLED CLINICAL TRIALS LA English DT Article DE two-stage design; adaptive design; conditional error function; effect size ID DESIGNS; VARIANCE AB Power calculations are very important in the planning of a well-designed clinical trial. Sometimes there is limited information available before the trial, making it highly desirable to adjust the sample size after seeing actual trial data. Indeed, there has been a recent proliferation of papers promising great flexibility in midcourse correction of sample size and other design features, such as choice of primary endpoint. We point out the difficulty in accurately estimating the treatment effect midway through a trial, and we encourage the use of a simple, conservative approach whereby sample size can be increased but not decreased from what was originally planned. We show how to compute the p value and confidence interval for this two-stage procedure. If the original sample size is maintained, analysis of the data is the same as for a fixed sample procedure. (C) 2003 Elsevier Science Inc. All rights reserved. C1 NHLBI, Bethesda, MD 20892 USA. J&J Pharmaceut Res & Dev, Raritan, NJ USA. NCI, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), 6701 Rockledge Dr,Room 8222,MSC 7938, Bethesda, MD 20892 USA. NR 16 TC 25 Z9 25 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 2003 VL 24 IS 1 BP 4 EP 15 AR PII S0197-2456(02)00240-4 DI 10.1016/S0197-2456(02)00240-4 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 639KX UT WOS:000180628600001 PM 12559638 ER PT J AU Lahiri, DK Farlow, MR Sambamurti, K Greig, NH Giacobini, E Schneider, LS AF Lahiri, DK Farlow, MR Sambamurti, K Greig, NH Giacobini, E Schneider, LS TI A critical analysis of new molecular targets and strategies for drug developments in Alzheimer's disease SO CURRENT DRUG TARGETS LA English DT Review DE Alzheimer's disease; acetylcholine; anticholinesterase; APP gene; beta-amyloid; cholinesterase; cholinergic agents; cholinomimetic drugs; dementia; NSAID; oxidative stress; phenserine; tau protein ID AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL; GAMMA-SECRETASE CLEAVAGE; C-TERMINAL FRAGMENT; A-BETA PEPTIDE; MESSENGER-RNA; APOLIPOPROTEIN-E; OXIDATIVE DAMAGE; IN-VIVO; CHOLINESTERASE-INHIBITORS AB Alzheimer's disease (AD), a progressive, degenerative disorder of the brain. is believed to be the most common cause of dementia amongst the elderly. AD is characterized by the presence of amyloid deposits and neurofibrillary tangles in the brain of afflicted individuals. AD is associated with a loss of the presynaptic markers of the cholinergic system in the brain areas related to memory and learning. AD appears to have a heterogeneous etiology with a large percentage termed sporadic AD arising from unknown causes and a smaller fraction of early onset familial AD (FAD) caused by mutations in one of several genes, such as the beta-amyloid precursor protein (APP) and presenilins (PS1, PS2). These proteins along with tau. secretases, such as beta-amyloid cleaving enzyme (BACE), and apolipoprotein E play important roles in the pathology of AD. On therapeutic fronts, there is significant research underway in the development of new inhibitors for BACE. PS-1 and gamma-secretase as targets for treatment of AD. There is also a remarkable advancement in understanding the function of cholinesterase (ChE) in the brain and the use of ChE-inhibitors in AD. A new generation of acetyl- and butyryl cholinesterase inhibitors is being studied and tested in human clinical trials for AD. The development of vaccination strategies, anti-inflammatory agents, cholesterol-lowering agents, anti-oxidants and hormone therapy are examples of new approaches for treating or slowing the progression of AD. In addition, nutritional, genetic and environmental factors highlight more effective preventive strategies for AD. Developments of early diagnostic tools and of quantitative markets are critical to better follow the Course of the disease and to evaluate different therapeutic strategies. In this review, we attempt to critically examine recent trends in AD research from molecular., genetic to clinical areas. We discuss various neurobiological mechanisms that provide the basis of new targets for AD drug development. All these current research efforts should lead to a deeper understanding of the pathobiochemical processes that Occur in the AD brain in order to effectively dianose and prevent their occurrence. C1 Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Inst Psychiat Res, Dept Neurol, Indianapolis, IN 46202 USA. Mayo Clin, Jacksonville, FL 32224 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Hosp Geneva, Dept Geriatr, Geneva, Switzerland. Univ So Calif, Dept Psychiat, Keck Sch Med, Los Angeles, CA 90089 USA. RP Lahiri, DK (reprint author), Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, 791 Union Dr,PR-313, Indianapolis, IN 46202 USA. EM dlahiri@iupui.edu FU NIA NIH HHS [AG18884, R01AG18379] NR 160 TC 143 Z9 147 U1 2 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD FEB PY 2003 VL 4 IS 2 BP 97 EP 112 DI 10.2174/1389450033346957 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 637DN UT WOS:000180496500001 PM 12558063 ER PT J AU Bogyo, M Hurley, JH AF Bogyo, M Hurley, JH TI Proteomics and genomics - Editorial overview SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Editorial Material C1 Celera Genomics, San Francisco, CA 94080 USA. NIDDKD, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), Celera Genomics, 180 Kimball Way, San Francisco, CA 94080 USA. NR 0 TC 10 Z9 11 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD FEB PY 2003 VL 7 IS 1 BP 2 EP 4 DI 10.1016/S1367-5931(02)00021-2 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 643PD UT WOS:000180868900001 ER PT J AU Anantharaman, V Aravind, L Koonin, EV AF Anantharaman, V Aravind, L Koonin, EV TI Emergence of diverse biochemical activities in evolutionarily conserved structural scaffolds of proteins SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID ESCHERICHIA-COLI PRIMASE; CRYSTAL-STRUCTURE; PHYLETIC DISTRIBUTION; CATALYTIC DOMAIN; PSI-BLAST; TOPOISOMERASES; NUCLEASES; SEQUENCE; GENOMICS; OXIDASE AB Comparative analysis of numerous protein structures that have become available in the past few years, combined with genome comparison, has yielded new insights into the evolution of enzymes and their functions. In addition to the well-known diversification of substrate specificities, enzymes with several widespread catalytic folds, particularly the TIM barrel, the RRM-like domain and the double-stranded beta-helix (cupin) domain, have been extensively explored in 'reaction space', resulting in the evolution of numerous, diverse catalytic activities supported by the same structural scaffold. Common protein folds differ widely in the diversity of catalyzed reactions. The biochemical plasticity of a fold seems to hinge on the presence of a generic, symmetrical substrate-binding pocket as opposed to highly specialized binding sites. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Anantharaman, V (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. OI Anantharaman, Vivek/0000-0001-8395-0009 NR 51 TC 92 Z9 95 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD FEB PY 2003 VL 7 IS 1 BP 12 EP 20 DI 10.1016/S0367-5931(02)00018-2 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 643PD UT WOS:000180868900003 PM 12547421 ER PT J AU Sechi, S Oda, Y AF Sechi, S Oda, Y TI Quantitative proteomics using mass spectrometry SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID RECEPTOR SIGNALING PATHWAYS; CODED AFFINITY TAGS; PROTEIN IDENTIFICATION; MESSENGER-RNA; GROWTH-FACTOR; PEPTIDES; EXPRESSION; DIFFERENTIATION; TOOL AB The use of stable isotopes as internal standards in mass spectrometry has opened a new era for quantitative proteomics. Depending on the point at which the label is introduced, most procedures can be classified as in vivo labeling, in vitro pre-digestion labeling or in vitro post-digestion labeling. In vivo labeling has been used for cells that can be grown in culture and has the advantage of being more accurate. The pre-digestion and post-digestion labeling procedures are suitable for all types of sample including human body fluids and biopsies. Several new mass spectrometric strategies mark significant achievements in determining relative protein concentrations and in quantifying post-translational modifications. However, further technology developments are needed for understanding the complexity of a dynamic system like the proteome. C1 NIDDKD, DHHS, NIH, Bethesda, MD 20892 USA. Eisai & Co Ltd, Lab Seeds Finding Technol, Tsukuba, Ibaraki 3002635, Japan. RP Sechi, S (reprint author), NIDDKD, DHHS, NIH, Bethesda, MD 20892 USA. NR 54 TC 72 Z9 79 U1 0 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD FEB PY 2003 VL 7 IS 1 BP 70 EP 77 DI 10.1016/S1367-5931(02)00010-8 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 643PD UT WOS:000180868900011 PM 12547429 ER PT J AU Sant, A Yewdell, J AF Sant, A Yewdell, J TI Antigen processing and recognition - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 Natl Inst Allergy & Infect Dis, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sant, A (reprint author), Univ Rochester, Sch Med, Dept Microbiol & Immunol, David H Smith Ctr Vaccine Biol & Immunol, 601 Elmwood Ave,Box 609, Rochester, NY 14642 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 4 TC 12 Z9 12 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 2003 VL 15 IS 1 BP 66 EP 68 DI 10.1016/S0952-7915(02)00020-1 PG 3 WC Immunology SC Immunology GA 631ZF UT WOS:000180197600011 PM 12495735 ER PT J AU Kreitman, RJ AF Kreitman, RJ TI Recombinant toxins for the treatment of cancer SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE CTCL; denileukin diftitox; diphtheria toxin; hairy cell leukemia; monoclonal antibody; Pseudomonas exotoxin ID PHASE-I TRIAL; SINGLE-CHAIN IMMUNOTOXIN; HAIRY-CELL LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; TRUNCATED PSEUDOMONAS EXOTOXIN; REFRACTORY HODGKINS LYMPHOMA; BONE-MARROW TRANSPLANTATION; INTERLEUKIN-2 FUSION TOXIN; ADVANCED SOLID TUMORS AB Recombinant toxins are proteins made by genetic engineering consisting of a toxin fused to a ligand which binds selectively to a target cell. Recombinant toxins used for cancer treatment generally contain either a growth factor or a recombinant fragment of a monoclonal antibody fused to a truncated bacterial toxin, derived either from Pseudomonas exotoxin or from diphtheria toxin. One recombinant toxin containing human interleukin (IL)-2 and truncated diphtheria toxin (DAB(389)-IL-2, denileukin diftitox or Ontak; Seragen Inc) is approved for clinical use in advanced stage cutaneous T-cell lymphoma. Recombinant toxins containing truncated Pseudomonas exotoxin and fragments of anti-CD22 and anti-CD25 monoclonal antibodies have induced remissions in chemotherapy-resistant hematological malignancies, particularly hairy cell leukemia, and are currently undergoing experimental testing. The number of approved recombinant toxins for the treatment of cancer is expected to increase in the coming years. C1 NIH, Div Canc Biol, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NIH, Div Canc Biol, 9000 Rockville, Bethesda, MD 20892 USA. NR 98 TC 56 Z9 64 U1 0 U2 7 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD FEB PY 2003 VL 5 IS 1 BP 44 EP 51 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 664AW UT WOS:000182040400007 PM 12669470 ER PT J AU Yang, W AF Yang, W TI Damage repair DNA polymerases Y SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID ESCHERICHIA-COLI; ERROR-PRONE; CRYSTAL-STRUCTURE; LESION-BYPASS; XERODERMA-PIGMENTOSUM; SULFOLOBUS-SOLFATARICUS; LARGE FRAGMENT; GENE ENCODES; MUTAGENESIS; REPLICATION AB The newly found Y-family DNA polymerases are characterized by low fidelity replication using an undamaged template and the ability to carry out translesion DNA synthesis. The crystal structures of three Y-family polymerases, alone or complexed with DNA and nucleotide substrate, reveal a conventional right-hand-like catalytic core consisting of finger, thumb and palm domains. The finger and thumb domains are unusually small resulting in an open and spacious active site, which can accommodate mismatched base pairs as well as various DNA lesions. Although devoid of a 3' -. 5' exonuclease activity, the Y-family polymerases possess a unique `little finger' domain that facilitates DNA association, catalytic efficiency and interactions with auxiliary factors. Expression of Y-family polymerases is often induced by DNA damage, and their recruitment to the replication fork is mediated by P-clamp, clamp loader, single-strand-DNA-binding protein and RecA in Escherichia coli, and by ubiquitin-modified proliferating cell nuclear antigen in yeast. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 51 TC 105 Z9 106 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 2003 VL 13 IS 1 BP 23 EP 30 DI 10.1016/S0959-440X(02)00003-9 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 648CY UT WOS:000181133300004 PM 12581656 ER PT J AU Sonenberg, N Dever, TE AF Sonenberg, N Dever, TE TI Eukaryotic translation initiation factors and regulators SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID POLY(A) BINDING-PROTEIN; POLY(A)-BINDING PROTEIN; MESSENGER-RNA; METHANOCOCCUS-JANNASCHII; CRYSTAL-STRUCTURES; TERMINAL DOMAIN; FACTOR IF3; CAP; ASSOCIATION; RESOLUTION AB Significant progress has been made over the past several years on structural studies of the eukaryotic translation initiation factors that facilitate the assembly of a translation-competent ribosome at the initiation codon of an mRNA. These structural studies have revealed the repeated use of a set of common structural folds, highlighted the evolutionary conservation of the translation apparatus, and provided insight into the mechanism and regulation of cellular and viral protein synthesis. C1 McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada. NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Sonenberg, N (reprint author), McGill Univ, Dept Biochem, 3655 Promenade Sir William Osler, Montreal, PQ H3G 1Y6, Canada. OI Dever, Thomas/0000-0001-7120-9678 NR 59 TC 224 Z9 230 U1 0 U2 13 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 2003 VL 13 IS 1 BP 56 EP 63 DI 10.1016/S0959-440X(03)00009-5 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 648CY UT WOS:000181133300008 PM 12581660 ER PT J AU Kort, EJ Jones, A Daumbach, M Hudson, EA Buckner, B Resau, JH AF Kort, EJ Jones, A Daumbach, M Hudson, EA Buckner, B Resau, JH TI Quantifying cell scattering: The blob algorithm revisited SO CYTOMETRY PART A LA English DT Article DE computer-assisted image analysis; cell scattering; hepatocyte growth factor receptor; blob algorithm ID HEPATOCYTE GROWTH-FACTOR; MET PROTOONCOGENE PRODUCT; BREAST-CANCER; OBJECT LOCATION; IMAGE-ANALYSIS; HUMAN TISSUES; EXPRESSION; RECEPTOR; REPRODUCIBILITY; IDENTIFICATION AB Background: A method to objectively quantify cell scattering would permit quantitative evaluation of therapies and compounds intended to affect this physiologic process, which has relevance to normal (e.g., development) and pathologic (e.g., metastasis) events. Methods: A grid-based modified blob analysis was performed on a set of images of Madin-Darby Canine Kidney (MDCK) cells to quantify the following parameters: the number of cellular clusters in each image, the size of the clusters in terms of pixel counts, and the number of cells in each cluster. These parameters were used as measures of cell scattering and were compared with subjective assessments of scattering made by three experienced examiners. Results: The quantitative parameters correlated strongly to subjective assessments. The algorithm displayed a different concept of "clustering" than the examiners and consistently identified more clusters than did the examiners. There was close agreement in the number of cells counted. All three quantitative parameters correlated strongly to the subjective scattering scores, as follows: cluster count (r(s) = -0.765 to -0.789, P < 0.0001), cluster size in pixels (r(s) = 0.838 to 0.845, P < 0.0001), and cluster size in cells (r(s) = 0.758 to 0.804, P < 0.0001). The parameters were continuous, providing greater resolving power than ordinal subjective scores. Conclusions: The findings confirmed that our algorithm reproduces the traditional classification of scattering with improved resolution, quantification, and objectivity. Cytometry Part A 51A:119-126, 2003. (C) 2003 Wiley-Liss, Inc. C1 Van Andel Res Inst, Grand Rapids, MI 49503 USA. NCI, ABL, BRP, FCRDC, Frederick, MD 21701 USA. RP Resau, JH (reprint author), Van Andel Res Inst, 333 Bostwick NE, Grand Rapids, MI 49503 USA. OI Kort, Eric/0000-0002-9966-7483 NR 34 TC 6 Z9 6 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 0196-4763 J9 CYTOM PART A JI Cytom. Part A PD FEB PY 2003 VL 51A IS 2 BP 119 EP 126 DI 10.1002/cyto.a.10010 PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 670TV UT WOS:000182426000007 PM 12541286 ER PT J AU Mukhopadhyay, M Teufel, A Yamashita, T Agulnick, AD Chen, L Downs, KM Schindler, A Grinberg, A Huang, SP Dorward, D Westphal, H AF Mukhopadhyay, M Teufel, A Yamashita, T Agulnick, AD Chen, L Downs, KM Schindler, A Grinberg, A Huang, SP Dorward, D Westphal, H TI Functional ablation of the mouse Ldb1 gene results in severe patterning defects during gastrulation SO DEVELOPMENT LA English DT Article DE Ldb1; Wnt inhibitor(s); Otx2; mouse; anterior-posterior axis ID PRIMORDIAL GERM-CELLS; ANTERIOR PRIMITIVE ENDODERM; BINDING-PROTEIN LDB1; WING MARGIN ENHANCER; LOOP-HELIX PROTEIN; LIM-DOMAIN; VISCERAL ENDODERM; HOMEODOMAIN PROTEINS; SPEMANN ORGANIZER; EMBRYONIC AXIS AB The LIM domain-binding protein 1 (Ldb1) is found in multi-protein complexes containing various combinations of LIM-homeodomain, LIM-only, bHLH, GATA and Otx transcription factors. These proteins exert key functions during embryogenesis. Here we show that targeted deletion of the Ldb1 gene in mice results in a pleiotropic phenotype. There is no heart anlage and head structures are truncated anterior to the hindbrain. In about 40% of the mutants, posterior axis duplication is observed. There are also severe defects in mesoderm-derived extraembryonic structures, 495 including the allantois, blood islands of the yolk sack, primordial germ cells and the amnion. Abnormal organizer gene expression during gastrulation may account for the observed axis defects in Ldb1 mutant embryos. The expression of several Wnt inhibitors is curtailed in the mutant, suggesting that Wnt pathways may be involved in axial patterning regulated by Ldb1. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Sch Med, Dept Anat, Madison, WI 53706 USA. NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Westphal, H (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD36847] NR 84 TC 94 Z9 94 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 2003 VL 130 IS 3 BP 495 EP 505 DI 10.1242/dev.00225 PG 11 WC Developmental Biology SC Developmental Biology GA 645KX UT WOS:000180975700007 PM 12490556 ER PT J AU Agarwal, P Wylie, JN Galceran, J Arkhitko, O Li, CL Deng, CX Grosschedl, R Bruneau, BG AF Agarwal, P Wylie, JN Galceran, J Arkhitko, O Li, CL Deng, CX Grosschedl, R Bruneau, BG TI Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo SO DEVELOPMENT LA English DT Article DE limb; mouse; T-box; Tbx5; Wnt; FGF; mouse ID HOLT-ORAM-SYNDROME; BHLH TRANSCRIPTION FACTOR; T-BOX GENES; VERTEBRATE LIMB; CHICK-EMBRYO; POLARIZING ACTIVITY; EXPRESSION; FGF8; SPECIFICATION; IDENTITY AB Transcriptional cascades responsible for initiating the formation of vertebrate embryonic structures such as limbs are not well established. Limb formation occurs as a result of interplay between fibroblast growth factor (FGF) and Wnt signaling. What initiates these signaling cascades and thus limb bud outgrowth at defined locations along the anteroposterior axis of the embryo is not known. The T-box transcription factor TBX5 is important for normal heart and limb formation, but its role in early limb development is not well defined. We report that mouse embryos lacking Tbx5 do not form forelimb buds, although the patterning of the lateral plate mesoderm into the limb field is intact. Tbx5 is not essential for an early establishment of forelimb versus hindlimb identity. In the absence of Tbx5, the FGF and Wnt regulatory loops required for limb bud outgrowth are not established, including initiation of Fgf10 expression. Tbx5 directly activates the Fgf10 gene via a conserved binding site, providing a simple and direct mechanism for limb bud initiation. Lefl/Tcf1-dependent Wnt signaling is not essential for initiation of Tbx5 or Fgf10 transcription, but is required in concert with Tbx5 for maintenance of normal levels of Fgf10 expression. We conclude that Tbx5 is not essential for the early establishment of the limb field in the lateral, plate mesoderm but is a primary and direct initiator of forelimb bud formation. These data suggest common pathways for the differentiation and growth of embryonic structures downstream of T-box genes. C1 Hosp Sick Children, Programme Cardiovasc Res, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Programme Dev Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada. Univ Munich, Gene Ctr, D-81377 Munich, Germany. Univ Munich, Inst Biochem, D-81377 Munich, Germany. NIDDKD, Genet Lab, Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Bruneau, BG (reprint author), Hosp Sick Children, Programme Cardiovasc Res, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Galceran, Juan/K-6744-2014; deng, chuxia/N-6713-2016; OI Galceran, Juan/0000-0002-5247-2726; Bruneau, Benoit/0000-0002-0804-7597 NR 74 TC 164 Z9 166 U1 0 U2 15 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 2003 VL 130 IS 3 BP 623 EP 633 DI 10.1242/dev.00191 PG 11 WC Developmental Biology SC Developmental Biology GA 645KX UT WOS:000180975700018 PM 12490567 ER PT J AU Brodigan, TM Liu, J Park, M Kipreos, ET Krause, M AF Brodigan, TM Liu, J Park, M Kipreos, ET Krause, M TI Cyclin E expression during development in Caenorhabditis elegans SO DEVELOPMENTAL BIOLOGY LA English DT Article DE cyclin; cye-1; cyclin-dependent kinase; expression ID PORPHOBILINOGEN DEAMINASE GENE; BIPARTITE REPRESSOR ELEMENT; CELL-CYCLE; C-ELEGANS; TRANSCRIPTION FACTOR; LIN-35 RB; DROSOPHILA EMBRYOGENESIS; VULVAL DEVELOPMENT; PHASE PROGRESSION; DOWN-REGULATION AB Our interest in the coordination of cell cycle control and differentiation has led us to investigate the Caenorhabditis elegans cye-1 gene encoding the G(1) cell cycle regulator cyclin E. We have studied the expression and function of cye-1 by using monoclonal antibodies directed against CYE-1 protein, cye-1::GFP reporter genes, and a cye-1 chromosomal deletion mutation. We show that a ubiquitous embryonic pattern of expression becomes restricted and dynamic during postembryonic development. Promoter analysis reveals a relatively small region of cis-acting sequences that are necessary for the complex pattern of expression of this gene. Our studies demonstrate that two other G(1) cell cycle genes, encoding cyclin D and CDK4/6, have similarly compact promoter requirements. This suggests that a relatively simple mechanism of regulation may underlie the dynamic developmental patterns of expression exhibited by these three G(1) cell cycle genes. Our analysis of a new cye-1 deletion allele confirms and extends previous studies of two point mutations in the gene. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA. RP Krause, M (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. OI Krause, Michael/0000-0001-6127-3940 FU NIGMS NIH HHS [R01 GM55297] NR 61 TC 34 Z9 38 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD FEB 1 PY 2003 VL 254 IS 1 BP 102 EP 115 DI 10.1016/S0012-1606(02)00032-5 PG 14 WC Developmental Biology SC Developmental Biology GA 641EJ UT WOS:000180731500008 PM 12606285 ER PT J AU Finkel, T AF Finkel, T TI Neutrophils with a license to kill: Permeabilized, not stirred SO DEVELOPMENTAL CELL LA English DT Editorial Material ID NADPH-OXIDASE ACTIVITY AB The neutrophil responds to invading microorganisms in part by assembling the NADPH oxidase complex and producing superoxide radicals. Relatively little is known about the intracellular assembly or activation of the oxidase, but Brown et al. in the January issue of Molecular Cell provide a useful strategy involving permeabilized neutrophils to tackle this question. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiovasc Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 10 TC 5 Z9 5 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD FEB PY 2003 VL 4 IS 2 BP 146 EP 148 DI 10.1016/S1534-5807(03)00023-6 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 645NN UT WOS:000180984600003 PM 12586056 ER PT J AU Chen, X Oh, SW Zheng, ZY Chen, HW Shin, HH Hou, SX AF Chen, X Oh, SW Zheng, ZY Chen, HW Shin, HH Hou, SX TI Cyclin D-Cdk4 and cyclin E-Cdk2 regulate the JAK/STAT signal transduction pathway in Drosophila SO DEVELOPMENTAL CELL LA English DT Article ID JAK-STAT PATHWAY; TRANSCRIPTION FACTOR; SEX-DETERMINATION; TYROSINE KINASE; S-PHASE; GENE; PROTEIN; PROGRESSION; RECEPTOR; LEUKEMIA AB The JAK/STAT signal transduction pathway regulates many developmental processes in Drosophila. However, the functional mechanism of this pathway is poorly understood. In this report, we identify the Drosophila cyclin-dependent kinase 4 (Cdk4), which exhibits embryonic mutant phenotypes identical to those in the Hopscotch/JAK kinase and stat92E/STAT mutations. Specific genetic interactions between Cdk4 and hop mutations suggest that Cdk4 functions downstream of the HOP tyrosine kinase. We further show that Cyclin D-Cdk4 (as well as Cyclin E-Cdk2) binds and regulates STAT92E protein stability. STAT92E regulates gene expression for various biological processes, including the endocycle S phase. These data suggest that Cyclin D-Cdk4 and Cyclin E-Cdk2 play more versatile roles in Drosophila development. C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, NIH, Frederick, MD 21702 USA. RP Hou, SX (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, NIH, Frederick, MD 21702 USA. RI Chen, Hua-Wei/A-8018-2011 NR 59 TC 30 Z9 31 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD FEB PY 2003 VL 4 IS 2 BP 179 EP 190 DI 10.1016/S1534-5807(03)00024-8 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 645NN UT WOS:000180984600009 PM 12586062 ER PT J AU Llorente, A Brouwers, P Charurat, M Magder, L Malee, K Mellins, C Ware, J Hittleman, J Mofenson, L Velez-Borras, J Adeniyi-Jones, S AF Llorente, A Brouwers, P Charurat, M Magder, L Malee, K Mellins, C Ware, J Hittleman, J Mofenson, L Velez-Borras, J Adeniyi-Jones, S TI Early neurodevelopmental markers predictive of mortality in infants infected with HIV-1 SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; IMMUNE-DEFICIENCY SYNDROME; TYPE-1 INFECTION; CLINICAL-TRIALS; CHILDREN; ENCEPHALOPATHY; IMPAIRMENT; SURVIVAL; LIFE; AGE AB One-hundred and fifty-seven vertically infected HIV-1 positive infants (85 males, 72 females) underwent longitudinal assessment to determine whether early neurodevelopmental markers are useful predictors of mortality in those infants who survive to at least 4 months of age. Survival analysis methods were used to estimate time to death for quartiles of 4-month scores (baseline) on the Bayley Scales of Infant Development (BSID). Cox proportional hazards progression was used to estimate relative hazard (RH, 95% CI) of death for BSID scores and potential confounders. Thirty infants with BSID scores at 4 months of age died during follow-up. Survival analysis revealed greater mortality rates in infants with BSID (Mental Developmental Index and Psychomotor Developmental Index) scores in the lower quartile(p=0.004,p=0.036). Unadjusted univariate analyses revealed increased mortality associated with baseline CD4(+) 29%, gestational age <37 weeks, smaller head circumference, advanced HIV and higher plasma viral load. BSID scores independently predicted mortality after adjusting for treatment, clinical category, gestational age, plasma viral load and CD4(+) percentage. C1 NIAID, Bethesda, MD 20892 USA. Univ Puerto Rico, Dept Pediat, San Juan, PR 00936 USA. NICHD, NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Div Infect Dis, Dept Pediat, Boston, MA USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Inst Human Virol, Baltimore, MD USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Llorente, A (reprint author), Washington Pediat Hosp, Neuropsychol Program, 1708 W Rogers Ave, Baltimore, MD 21209 USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [U01 AI 34840, N01 AI 85339, U01 AI 34841, U01 AI 34842, U01 AI 34856, U01 AI 34858]; NICHD NIH HHS [HD-3-6117]; PHS HHS [R0-1-llD-25714] NR 40 TC 21 Z9 23 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD FEB PY 2003 VL 45 IS 2 BP 76 EP 84 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 666LD UT WOS:000182178000002 PM 12578232 ER PT J AU Hsueh, WC St Jean, PL Mitchell, BD Pollin, TI Knowler, WC Ehm, MG Bell, CJ Sakul, H Wagner, MJ Burns, DK Shuldiner, AR AF Hsueh, WC St Jean, PL Mitchell, BD Pollin, TI Knowler, WC Ehm, MG Bell, CJ Sakul, H Wagner, MJ Burns, DK Shuldiner, AR TI Genome-wide and fine-mapping linkage studies of type 2 diabetes and glucose traits in the Old Order Amish - Evidence for a new diabetes locus on chromosome 14q11 and confirmation of a locus on chromosome 1q21-q24 SO DIABETES LA English DT Article ID MELLITUS GENETICS FUSION; PIMA-INDIANS; SUSCEPTIBILITY GENES; MEXICAN-AMERICANS; MAJOR-GENE; INDEPENDENT REPLICATION; CANDIDATE GENE; SCAN; SEARCH; PEDIGREES AB We conducted a genome scan using a 10-cM map to search for genes linked to type 2 diabetes in 691 individuals from a founder population, the Old Order Amish. We then saturated two regions on chromosomes 1 and 14 showing promising linkage signals with additional markers to produce a similar to2-cM map for fine mapping. Analyses of both discrete traits (type 2 diabetes and the composite trait of type 2 diabetes and/or impaired glucose homeostasis [IGH]), and quantitative traits (glucose levels during a 75-g oral glucose challenge, designated glucose 0-180 and HbA(1c)) were performed. We obtained significant evidence for linkage to type 2 diabetes in a novel region on chromosome 14q11 (logarithm of odds [LOD] for diabetes = 3.48, P = 0.00005). Furthermore, we observed evidence for the existence of a diabetes-related locus on chromosome 1q21-q24 (LOD for type 2 diabetes/IGH = 2.35, P = 0.0008), a region shown to be linked to diabetes in several other studies. Suggestive evidence for linkage to glucose traits was observed on three other regions: 14q11-q13 (telomeric to that above with LOD = 1.82-1.85 for glucose 150 and 180), 1p31 (LOD = 1.28-2.30 for type 2 diabetes and glucose 120-180), and 18p (LOD = 3.07, P = 0.000085 for HbA(1c) and LOD = 1.50 for glucose 0). In conclusion, our findings provide evidence that type 2 diabetes susceptibility genes reside on chromosomes 1, 14, and 18. C1 Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78284 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. NIDDK, NIH, Phoenix, AZ USA. Axys Pharmaceut, La Jolla, CA USA. Baltimore Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. RP Shuldiner, AR (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, 660 W Redwood St,Room 494, Baltimore, MD 21201 USA. OI Mitchell, Braxton/0000-0003-4920-4744 FU NIDDK NIH HHS [DK02673, DK54361] NR 51 TC 97 Z9 103 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2003 VL 52 IS 2 BP 550 EP 557 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 643YT UT WOS:000180891700045 PM 12540634 ER PT J AU Looker, HC Krakoff, J Knowler, WC Bennett, PH Klein, R Hanson, RL AF Looker, HC Krakoff, J Knowler, WC Bennett, PH Klein, R Hanson, RL TI Longitudinal studies of incidence and progression of diabetic retinopathy assessed by retinal photography in Pima Indians SO DIABETES CARE LA English DT Article ID RISK-FACTORS; PROLIFERATIVE RETINOPATHY; FUNDUS PHOTOGRAPHY; 4-YEAR INCIDENCE; BLOOD-PRESSURE; DIAGNOSIS; GLUCOSE; NIDDM; AGE; DURATION AB OBJECTIVE - To examine incidence and progression of retinopathy using retinal photographs in Pima Indians and to compare the results with those obtained when retinopathy is assessed by direct ophthalmoscopy. RESEARCH DESIGN AND METHODS - We undertook an analysis of examinations conducted between 1 April 1982 and 31 December 1990 in residents of the Gila River Community in central Arizona. Data were taken from 411 people with diabetes who had at least two examinations during this period. incidence and progression of retinopathy were evaluated by retinal photography and fundoscopy, and hazard rate ratios were calculated for various potential risk factors measured at baseline. RESULTS - Previously diagnosed retinopathy tended to progress, except in individuals with minimal nonproliferative retinopathy, among whom follow-up examinations were more likely to show no retinopathy. Diabetes duration (hazard rate ratio [HRR], 1.06 per year difference [P = 0.007]), hyperglycemia (HbA(1) HRR, 1.2 7 per 1% difference [P < 0.0001]), the type of treatment for diabetes (insulin use HRR, 3.06 [P = 0.0007], and oral hypoglycemic use HRR, 2.40 [P = 0.0034], compared with individuals on no pharmacotherapy), and macroalbuminuria (HRR 2.86, compared with individuals without macroalbuminuria [P = 0.0486]) were associated with the development of retinopathy. Although fundoscopy detected fewer cases of retinopathy, HRRs for most risk factors were similar when retinopathy was assessed by fundoscopy rather than retinal photography. CONCLUSIONS - Although retinopathy tends to worsen over time, some eyes show improvement, especially in patients with minimal nonproliferative retinopathy. As in other populations, glycemic control is the major modifiable risk factor for the development and progression of retinopathy. C1 NIDDKD, Diabet & Arthritis Epidemiol Sect, Phoenix, AZ USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. RP Looker, HC (reprint author), NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 24 TC 27 Z9 30 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2003 VL 26 IS 2 BP 320 EP 326 DI 10.2337/diacare.26.2.320 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UL UT WOS:000185505000011 PM 12547856 ER PT J AU Goodpaster, BH Krishnaswami, S Resnick, H Kelley, DE Haggerty, C Harris, TB Schwartz, AV Kritchevsky, S Newman, AB AF Goodpaster, BH Krishnaswami, S Resnick, H Kelley, DE Haggerty, C Harris, TB Schwartz, AV Kritchevsky, S Newman, AB TI Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women SO DIABETES CARE LA English DT Article ID NUTRITION EXAMINATION SURVEY; SUBCUTANEOUS ABDOMINAL FAT; 3RD NATIONAL-HEALTH; INSULIN-RESISTANCE; POSTMENOPAUSAL WOMEN; METABOLICALLY-OBESE; COMPUTED-TOMOGRAPHY; SENSITIVITY; MELLITUS; LEVEL AB OBJECTIVE - We examined whether regional adipose tissue distribution, specifically that of skeletal muscle fat and visceral abdominal fat aggregation, is characteristic of elderly individuals with hyperinsulinemia, type 2 diabetes, and impaired glucose, tolerance (IGT). RESEARCH DESIGN AND METHODS- A total of 2,964 elderly men and omen (mean age 73.6 years) were recruited for cross-sectional comparisons of diabetes or glucose tolerance, generalized obesity with dual-energy X-ray absorptiometry, and regional body fat distribution with computed tomography. RESULTS - Approximately one-third of men with type 2 diabetes and less than half of women with type 2 diabetes were obese (BMI greater than or equal to30 kg/m(2)). Despite similar amounts of subcutaneous thigh fat, intermuscular fat was higher in subjects with type 2 diabetes and IGT than in subjects with normal glucose tolerance (NGT) (11.2 +/- 9.4, 10.3 +/- 5.8, and 9.2 +/- 5.9 cm(2) for men; 12.1 +/- 6.1, 10.9 +/- 6.5, and 9.4 +/- 5.3 cm(2) for women; both P < 0.0001). Visceral abdominal fat was also higher in men and women with type 2 diabetes and IGT than in subjects with NGT (172 +/- 79, 163 +/- 72, and 145 +/- 66 cm(2) for men; 162 +/- 66, 141 +/- 60, and 116 +/- 54 cm for women; both P < 0.0001 across groups). Higher rates of intermuscular fat and Visceral abdominal fat were associated with higher fasting insulin in normal-weight (BMI <25 kg/m(2)) men (r = 0.24 for intermuscular fat, r = 0.37 for visceral abdominal fat, both P < 0.0001) and women (r = 0.20 for intermuscular fat, r = 0.40 for visceral abdominal fat, both P < 0.0001). These associations were not found in obese subjects. CONCLUSIONS - Elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes, if they possess an inordinate amount of muscle fat or visceral abdominal fat. C1 Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Medstar Res Inst, Dept Epidemiol, Hyattsville, MD USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Univ Tennessee, Memphis, TN USA. RP Goodpaster, BH (reprint author), Univ Pittsburgh, Med Ctr, Dept Med, 809 N MUH, Pittsburgh, PA 15213 USA. RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Haggerty, Catherine/0000-0002-9849-7865 FU NIA NIH HHS [K01-AG-00851, N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 24 TC 281 Z9 289 U1 2 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2003 VL 26 IS 2 BP 372 EP 379 DI 10.2337/diacare.26.2.372 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UL UT WOS:000185505000020 PM 12547865 ER PT J AU Lipson, SM Tortora, G Tempone, A Fedorko, DP Spitzer, ED AF Lipson, SM Tortora, G Tempone, A Fedorko, DP Spitzer, ED TI Rapid detection of Clostridium difficile in stool using the VIDAS(R) C-difficile Toxin A II assay SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID DIARRHEA; DIAGNOSIS; IMMUNOASSAYS; SPECIMENS; COLITIS AB A rapid laboratory diagnosis of Clostridium difficile-associated diarrhea (CDAD) is important in patient management and in the administration of appropriate therapeutic modalities. The VIDAS(R) C. difficile Toxin A II (CDA 2) assay (bioMerieux, Inc., Hazelwood, MO) was compared with the cell culture cytotoxicity assay (CCA) for the rapid detection of C. difficile in stool from patients in whom C. difficile infection was suspected. Thirty-eight consecutively collected CCA-positive stool specimens, and 33 CCA-negative stool specimens were tested by the CDA 2 assay. Where appropriate, discordant specimens were repeated and/or tested by isolation utilizing cyclosetine-cefoxitin-fructose agar (CCFA). Among 12 discordant stool specimens, 7 were VIDAS(R) E/cytotoxicity+, 2 were VIDASR equivocal (E)/cytotoxicity+, 2 were VIDAS(R) E/cytotoxicity-, and I was VIDAS(R)+/cytotoxicity-. One VIDASR E/cytotoxicity+ lacked sufficient stool to be repeated. From the single VIDAS(R)+/cytotoxicity- specimen, C. sordelli was isolated. Specimens that were equivocal by VIDASR, were omitted from incorporation into this study's test parameters. The sensitivity, specificity, positive and negative predictive values for the CDA 2 assay were 80.6, 96.8, 96.7, and 81.1%, respectively. The specimens which yielded false negative VIDASR results had low levels of toxin based on endpoint titrations using the cytotoxicity assay. Although the CDA 2 assay displayed a reduced sensitivity compared with the CCA, the automated assay is rapid (results promulgated within 2 h), with computer generated readings obviating visual interpretations. Recognition of the CDA 2 assay's limitations is important to addressing this test's clinical utility. (C) 2003 Elsevier Science Inc. All fights reserved. C1 SUNY Stony Brook, Clin Microbiol Lab, Dept Labs, Stony Brook, NY 11794 USA. NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Lipson, SM (reprint author), Virol Consultants Inc, 2364 E 74th St, Brooklyn, NY 11234 USA. NR 18 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD FEB PY 2003 VL 45 IS 2 BP 117 EP 121 AR PII S0732-8893(02)00520-5 DI 10.1016/S0732-8893(02)00520-5 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 653HT UT WOS:000181429700004 PM 12614982 ER PT J AU Vaupel, DB Tella, SR Huso, DL Mukhin, AG Baum, I Wagner, VO Horti, AG London, ED Koren, AO Kimes, AS AF Vaupel, DB Tella, SR Huso, DL Mukhin, AG Baum, I Wagner, VO Horti, AG London, ED Koren, AO Kimes, AS TI Pharmacology, toxicology, and radiation dosimetry evaluation of [I-123]5-I-a-85380, a radioligand for in vivo imaging of cerebral neuronal nicotinic acetylcholine receptors in humans SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE safety pharmacology; cardiovascular; electrocardiogram ID IN-VIVO; RADIOIODINATED ANALOG; ALZHEIMER BRAINS; BINDING-SITES; EPIBATIDINE; DOGS; ALPHA-4-BETA-2; 5-I-A-85380; POSTMORTEM; PARKINSONS AB [I-123]5-I-A-85380, which selectively binds to alpha4beta2 nicotinic acetylcholine receptors, may be a suitable single photon emission computed tomography (SPECT) ligand for imaging nicotinic receptors in the human brain. In a mutagenicity study, 5-I-A-85380 produced positive effects in one of five bacterial strains in the bacterial reverse mutation assay only with metabolic activation. The ED50 for 5-I-A-85380 to elicit tonic-clonic convulsions in mice, 7.1 mumol/kg, i.v., was five times that of nicotine (ED50 = 1.4 mumol/kg, i.v.). A 2-day acute toxicity study (0.03-150 nmol/kg, i.v.) and a 14-day chronic toxicity study (0.3-30 nmol/kg, s.c.) in mice revealed no evidence of gross pathology or histopathological changes. Biodistribution and dosimetry studies revealed that the urinary bladder wall and the thyroid gland were the critical organs with respect to radiation exposure. In unanesthetized rats, 5-I-A-85380 (5.2-174 nmol/kg, i.v.) and nicotine (20-400 nmol/kg, i.v.) produced similar increases in systolic and diastolic blood pressure, heart rate, and locomotor activity. Doses of 5-I-A-85380 that elevated blood pressure and heart rate by 10% ranged from 5-10 nmol/kg, i.v. The highest doses tested, which produced near maximal increases in blood pressure and heart rate, did not affect the PR, QRS, or QTc intervals of the electrocardiogram. Based on these preclinical data, initial SPECT imaging studies in humans (Fujita et al. [2002] Eur J Nucl Med 29:183-190) used a mass dose of 8.6 pmol/kg [I-123]5-1-A-8380, estimated to be 1/580th of the dose that elevates blood pressure and heart rate by 10%. Importantly, no clinical pharmacological effects were observed. C1 NIDA, IRP, Brain Imaging Ctr, Neuroimaging Res Branch, Baltimore, MD 21224 USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD USA. BioReliance Inc, Rockville, MD USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Vaupel, DB (reprint author), NIDA, IRP, Brain Imaging Ctr, Neuroimaging Res Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 44 TC 13 Z9 13 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD FEB PY 2003 VL 58 IS 2 BP 149 EP 168 DI 10.1002/ddr.10152 PG 20 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 668UX UT WOS:000182312500001 ER PT J AU Brown, AP Kirchner, DL Morrissey, RL Das, SR Fitzgerald, RL Crowell, JA Levine, BS AF Brown, AP Kirchner, DL Morrissey, RL Das, SR Fitzgerald, RL Crowell, JA Levine, BS TI Endocrine effects of dehydroepiandrosterone and its fluorinated analog, fluasterone, in rats SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE DHEA; androgens; estrogens; reproductive toxicology; steroid hormones; adrenal hormones ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; BREAST-CANCER; MAMMARY-GLAND; DHEA; CARCINOGENESIS; CHEMOPREVENTION; INHIBITION; ESTROGENS; SULFATE; RISK AB Cancer chemoprevention is the use of pharmacologic agents to inhibit the development of cancer. The adrenal steroid dehydroepiandrosterone (DHEA) has demonstrated chemopreventive efficacy in animal models of tumorigenesis. However, due to DHEA's undesirable hormonal actions, the fluorinated analog fluasterone (fI-DHEA), which also has chemopreventive characteristics, was synthesized as a potential alternate agent. It is not known whether fI-DHEA has hormonal actions. The endocrinologic effects of DHEA and fI-DHEA in adult male and female Fischer 344 rats were examined following 28 days of daily oral treatment. Initial doses tested were 30 and 300mg/kg/day for each drug (n = 12/sex/group), which are equivalent to 104 and 1,042 mumoles/kg/day DHEA, and 103 and 1,034 mumoles/kg/day fI-DHEA. However, due to weight loss at the high dose, doses were lowered to 150 mg/kg/day for each drug (521 and 517 mumoles/kg/day DHEA and fI-DHEA, respectively). Administration of DHEA resulted in dose-dependent increases in plasma DHEA and DHEA-S 1 h after dosing in week 4. DHEA produced an estrogenic effect in female rats expressed as decreased plasma FSH and LH, inhibition of ovulation, prolonged estrus, and increased uterine estrogen receptors. DHEA also increased plasma levels of androstenedione in males and females. Administration of fl-DHEA increased the estrus cycle length due to a prolonged diestrus II phase and decreased the weights of the uterus, prostate, seminal vesicles, and testes. In addition, fl-DHEA decreased plasma FSH, LH, and tissue estradiol, and increased plasma dihydrotestosterone levels in both sexes. These results indicate that fl-DHEA is hormonally active and additional studies are warranted to further describe its endocrinologic effects. (C) 2003 Wiley-Liss, Inc. C1 Univ Illinois, Toxicol Res Lab, Chicago, IL USA. Pathol Associates Int, Chicago, IL USA. Ani Lyt Inc, Gaithersburg, MD USA. Vet Affairs Med Ctr 113, San Diego, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Levine, BS (reprint author), Vertex Pharmaceut Inc, Dept Toxicol, DABT, 130 Waverly St, Cambridge, MA 02139 USA. NR 31 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD FEB PY 2003 VL 58 IS 2 BP 169 EP 178 DI 10.1002/ddr.10156 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 668UX UT WOS:000182312500002 ER PT J AU Barrett, JC Kawasaki, ES AF Barrett, JC Kawasaki, ES TI Microarrays: the use of oligonucleotides and cDNA for the analysis of gene expression SO DRUG DISCOVERY TODAY LA English DT Review ID SIMPLEX-VIRUS TYPE-1; DNA MICROARRAYS; MESSENGER-RNA; PROTEIN MICROARRAYS; SERIAL ANALYSIS; DRAFT SEQUENCE; ARRAYS; DESIGN; GENOME; SENSITIVITY AB Completion of the human genome sequence has made it possible to study the expression of the entire human gene complement (>30,000 estimated genes). Aiding in this remarkable feat, DNA microarrays have become the main technological workhorse for gene expression studies. To date, detection platforms for most microarrays have relied on short (25 base) oligonucleotides synthesized in situ, or longer, highly variable length DNAs from PCR amplification of cDNA libraries. A third choice, long (50-80 base) oligonucleotide arrays, is now available and might eventually eliminate the use of cDNA arrays. The technology has advanced to such a point that researchers now demand microarrays that are cost-effective and have flexibility and quality assurance. Short-and long-oligonucleotide technologies offer such advantages, and could possibly become the major competing platform in the near future. C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Gaithersburg, MD 20877 USA. RP NCI, Ctr Canc Res, 31 Ctr Dr,MSC-2440, Bethesda, MD 20892 USA. EM kawasake@mail.nih.gov NR 76 TC 78 Z9 85 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 EI 1878-5832 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD FEB 1 PY 2003 VL 8 IS 3 BP 134 EP 141 AR PII S1359-6446(02)02578-3 DI 10.1016/S1359-6446(02)02578-3 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 640JB UT WOS:000180684300011 PM 12568783 ER PT J AU Schofield, DJ Emerson, SU Purcell, RH AF Schofield, DJ Emerson, SU Purcell, RH TI Four chimpanzee monoclonal antibodies that neutralize hepatitis A virus SO DRUGS OF THE FUTURE LA English DT Article ID PHAGE DISPLAY LIBRARIES; A VIRUS; CAPSID PROTEIN; IDENTIFICATION; REPERTOIRE; SEGMENTS; SURFACE; FAILURE; SITE AB Chimpanzee immunoglobulins are virtually identical to human immunoglobulins and thus may have clinically useful applications. In a recent manuscript we described 4 chimpanzee monoclonal antibodies (MAbs) that neutralized hepatitis A virus (HAV) (1). The MAbs were isolated from a combinatorial cIDNA library of chimpanzee gamma1/kappa antibody genes using bacteriophage displaying Fab fragments on their surfaces. Three of the MAbs recognized the same or overlapping epitopes on the HAV capsid, whereas the fourth recognized a different, nonoverlapping epitope on the capsid. All 4 MAbs neutralized the homologous HAV strain, HM-175, in a radioimmunofocus assay and 2 of the 4 MAbs neutralized a heterologous simian HAV strain, AGM-27. From these data, we conclude that the MAbs must recognize at least 3 epitopes on the HAV capsid. Competition assays performed with neutralizing murine MAbs suggested that 3 of the chimpanzee MAbs recognized epitopes on the HAV capsid which have not been defined previously. It is hoped that these MAbs may be used directly in passive immunoprophylaxis to prevent hepatitis A in susceptible populations, e.g., travelers to regions where HAV is endemic or at risk individuals where epidemics are occurring. C1 NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bldg 50 Rm 6537,50 S Dr MSC-8008, Bethesda, MD 20892 USA. NR 33 TC 0 Z9 1 U1 1 U2 1 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD FEB PY 2003 VL 28 IS 2 BP 137 EP 142 DI 10.1358/dof.2003.028.02.856927 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 667XA UT WOS:000182259100004 ER PT J AU Miller, JL Sonies, BC Macedonia, C AF Miller, JL Sonies, BC Macedonia, C TI Emergence of oropharyngeal, laryngeal and swallowing activity in the developing fetal upper aerodigestive tract: an ultrasound evaluation SO EARLY HUMAN DEVELOPMENT LA English DT Article DE fetal development; upper aerodigestive growth; fetal swallowing; fetal respiration ID BRACHMANN-DELANGE-SYNDROME; PRENATAL-DIAGNOSIS; BIRTH-WEIGHT; UPPER AIRWAY; INFANTS; GROWTH; GESTATION; DIAMETER; BEHAVIOR; FLUID AB The developing fetal upper aerodigestive system provides the structural support for respiratory and ingestive functions necessary to sustain life at birth. This study investigated prenatal development of upper aerodigestive anatomy and the association of emerging functions as predictors of postnatal feeding skills. Biometric measures of oral, lingual, pharyngeal and laryngeal structures were obtained in fetuses 15-38 weeks gestational age using a four-plane sonographic technique. Accompanying ingestive behaviors were tallied across development. The data from 62 healthy controls were compared to seven cases at risk for postnatal feeding and swallowing dysfunction (Type 11 Arnold Chiari Malformation, trisomy 18, polyhydramnios, intrauterine growth restriction, Brachmann-de Lange Syndrome). Significant (p < 0.001) linear regressions occurred in pharyngeal and lingual growth across gestation while ingestive behavior such as suckling emerged in a sequence of basic to complex movement patterns. Jaw and lip movements progressed from simple mouth opening to repetitive open-close movements important for postnatal suckling. Lingual movements increased in complexity from simple forward thrusting and cupping to anterior-posterior motions necessary for successful suckling at term. Laryngeal movements varied from shallow flutter-like movements along the lumen to more complex and complete adduction-abduction patterns. Fetal swallowing primarily occurred in the presence of concomitant oral-facial stimulatory activity. Significant variations (p < 0.01) in the form and function of the ingestive system occurred in comparisons of gestational age-matched controls to at-risk cases. We postulate that prenatal developmental indices of emerging aerodigestive skills may guide postnatal decisions for feeding readiness and, ultimately, advance the care of the premature, medically fragile neonate. Published by Elsevier Science Ireland Ltd. C1 NIH, Dept Rehabil Med, Phys Disabil Branch, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD USA. RP Miller, JL (reprint author), NIH, Dept Rehabil Med, Phys Disabil Branch, Warren G Magnuson Clin Ctr, 9000 Rockville Pike,Room S6235,Bldg 10, Bethesda, MD 20892 USA. EM jmiller@cc.nih.gov FU ODCDC CDC HHS [00-CC-081] NR 56 TC 46 Z9 52 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD FEB PY 2003 VL 71 IS 1 BP 61 EP 87 AR PII S0378-3782(02)00110-X DI 10.1016/S0378-3782(02)00110-X PG 27 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 659ML UT WOS:000181780400007 PM 12614951 ER PT J AU Skelton, TN Andrew, ME Arnett, DK Burchfiel, CM Garrison, RJ Samdarshi, TE Taylor, HA Hutchinson, RG AF Skelton, TN Andrew, ME Arnett, DK Burchfiel, CM Garrison, RJ Samdarshi, TE Taylor, HA Hutchinson, RG TI Echocardiographic left ventricular mass in African-Americans - The Jackson Cohort of the Atherosclerosis Risk in Communities Study SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE African-American; left ventricular mass; echocardiography; left uentricular hypertrophy ID CORONARY-ARTERY DISEASE; HEART-DISEASE; ESSENTIAL-HYPERTENSION; RACIAL-DIFFERENCES; ETHNIC-DIFFERENCES; MILD HYPERTENSION; ELDERLY COHORT; WALL THICKNESS; WHITE PATIENTS; YOUNG-ADULTS AB Characterization of target organ damage from hypertension is of particular interest in African Americans, and evidence from electrocardiographic studies suggests that left ventricular hypertrophy is a frequent clinical finding of considerable prognostic importance. Echocardiographic studies may permit more precise characterization of the pathologic impact of hypertension on cardiac structure and function. The objective of this study is to characterize left ventricular (LV) structure including measures of wall thickness, septal thickness, internal dimension, and mass in a middle-aged sample of African-Americans using echocardiography. This study is a cohort (cross-sectional) study in which 2445 middle-aged African-American study participants from a population-based sample initially enrolled by the Atherosclerosis Risk in Communities, Jackson, Mississippi Examination Center in 1987-1989 underwent an M-mode echocardiograpic examination at their third or fourth clinic visit in 1993-1996. Measures of LV mass, even where indexed by size were conspicuously greater in men compared to women, and men exhibited a demonstrably steeper gradient of LV mass across the rather restricted age range of the study. However, when gender specific thresholds for LV hypertrophy were utilized, African-American men appear to have lower prevalence of LV hypertrophy than women. The lowest prevalence of LV hypertrophy was observed in African-American men who did not have hypertension (28.4%). The findings confirm previous suggestions from electrocardiographic investigations that cardiac hypertrophy is common, if not epidemic in middle-aged African-American men and women whether or not they have hypertension. C1 Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Univ Minnesota, Minneapolis, MN USA. NHLBI, Jackson, MS USA. Jackson State Univ, Jackson, MS USA. RP Garrison, RJ (reprint author), Jackson Med Mall,Suite 701,350 W Woodrow Wilson, Jackson, MS 39213 USA. FU NHLBI NIH HHS [N01 HC 955016, N01 HC 955015, N01 HC 955018, N01 HC 955021, N01 HC 95170, N01 HC 955019, N01 HC 955020, N01 HC 95172, N01 HC 95171, N01 HC 955022] NR 43 TC 28 Z9 29 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD FEB PY 2003 VL 20 IS 2 BP 111 EP 120 DI 10.1046/j.1540-8175.2003.03000.x PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 656MB UT WOS:000181610600001 PM 12848675 ER PT J AU Karev, GP AF Karev, GP TI Inhomogeneous models of tree stand self-thinning SO ECOLOGICAL MODELLING LA English DT Article DE self-thinning; inhomogeneous population dynamics; distributed Malthusian parameter ID ECOLOGICAL FIELD-THEORY; POPULATION-DYNAMICS; RULE; COMPETITION; SIMULATION AB It is shown that some rather different formulas of forest stand self-thinning can be considered as solutions of unique inhomogeneous Malthus extinction model with corresponding initial distributions of the mortality rate of trees. The results allow hypothesising that the distribution of mortality rate is specific for different tree species Developed theory suggests new methods to improve existing and to derive new self-thinning formulas using appropriate distributions of Malthusian parameter. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Russian Acad Sci, Ctr Forest Ecol & Prod, Moscow 117418, Russia. RP Karev, GP (reprint author), 3014 Homewood Pkwy, Kensington, MD 20895 USA. NR 37 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3800 J9 ECOL MODEL JI Ecol. Model. PD FEB 1 PY 2003 VL 160 IS 1-2 BP 23 EP 37 AR PII S0304-3800(02)00287-9 DI 10.1016/S0304-3800(02)00287-9 PG 15 WC Ecology SC Environmental Sciences & Ecology GA 641GB UT WOS:000180735900003 ER PT J AU Trindade, GD da Fonseca, FG Marques, JT Nogueira, ML Mendes, LCN Borges, AS Peiro, JR Pituco, EM Bonjardim, CA Ferreira, PCP Kroon, EG AF Trindade, GD da Fonseca, FG Marques, JT Nogueira, ML Mendes, LCN Borges, AS Peiro, JR Pituco, EM Bonjardim, CA Ferreira, PCP Kroon, EG TI Aracatuba virus: A vaccinialike m virus associated with infection in humans and cattle SO EMERGING INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; RIO-DE-JANEIRO; MOLECULAR CHARACTERIZATION; POXVIRUS; ORTHOPOXVIRUS; STATE; DIFFERENTIATION; BEAN-58058; SMALLPOX; PROTEIN AB We describe a vaccinialike virus, Aragatuba virus, associated with a cowpoxlike outbreak in a dairy herd and a related case of human infection. Diagnosis was based on virus growth characteristics, electron microscopy, and molecular biology techniques. Molecular characterization of the virus was done by using polymerase chain reaction amplification, cloning, an DNA sequencing of conserved orthopoxvirus genes such as the vaccinia growth factor (VGF), thymidine kinase (TK), and hemagglutinin. We used VGF-homologous and TK gene nucleoticle sequences to construct a phylogenetic tree for comparison with other poxviruses. Gene sequences showed 99% homology with vaccinia virus genes and were clustered together with the isolated virus in the phylogenetic tree. Aragatuba virus is very similar to Cantagalo virus, showing the same signature deletion in the gene. Aragatuba virus could be a novel vaccinialike virus or could represent the spread of Cantagalo virus. C1 Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Virus Lab, BR-31270901 Belo Horizonte, MG, Brazil. NIH, Bethesda, MD 20892 USA. Univ Estadual Paulista, Sao Paulo, Brazil. Inst Biol, Sao Paulo, Brazil. RP Kroon, EG (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Virus Lab, Av Antonio Carlos 6627,Caixa Postal 486, BR-31270901 Belo Horizonte, MG, Brazil. RI Nogueira, Mauricio/B-7599-2012; Mendes, Luiz Claudio/B-8095-2012; Peiro, Juliana/C-4880-2012; Marques, Joao/F-7683-2012; Pituco, Edviges/J-2424-2012; Borges, Alexandre/B-5506-2013; Bonjardim, Claudio/J-2601-2014; OI Nogueira, Mauricio/0000-0003-1102-2419; Mendes, Luiz Claudio/0000-0002-7696-6018; Marques, Joao/0000-0002-3457-3320; Pituco, Edviges Maristela/0000-0003-1469-9257 NR 30 TC 75 Z9 78 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2003 VL 9 IS 2 BP 155 EP 160 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 646KR UT WOS:000181034600002 PM 12603984 ER PT J AU Tomic, M Andric, SA Stojilkovic, SS AF Tomic, M Andric, SA Stojilkovic, SS TI Dependence of prolactin release on coupling between Ca2+ mobilization and voltage-gated Ca2+ influx pathways in rat lactotrophs SO ENDOCRINE LA English DT Article DE endothelin-A; thyrotropin-releasing hormone; calcium; prolactin; voltage-gated calcium channels; inward rectifier potassium channels ID ANTERIOR-PITUITARY-CELLS; HORMONE SECRETION; CALCIUM INFLUX; THYROTROPIN; ENDOTHELIN; RECEPTORS; CHANNELS; K+; SOMATOSTATIN; EXPRESSION AB Two Ca2+-mobilizing receptors expressed in lactotrophs, endothelin-A (ETA) and thyrotropin-releasing hormone (TRH), induce a rapid Ca2+ release from intracellular stores and prolactin (PRL) secretion but differ in their actions during the sustained stimulation; TRH facilitates and ET-1 inhibits voltage-gated calcium influx (VGCI) and PRL secretion. In pertussis toxin (PTX)-treated cells, ET-1-induced inhibition of VGCI was abolished and the pattern of Ca2+ signaling was highly comparable with that observed in TRH-stimulated cells. The addition of Cs+, a relatively specific blocker of inward rectifier K+ channels, mimicked the effect of PTX on the pattern of ET-1-induced sustained Ca2+ signaling, but only in about 50% of cells, and did not affect agonist-induced inhibition of PRL secretion. Extracellullar Cs+ was also ineffective in altering the TRH-induced facilitation of VGCI and PRL secretion. Furthermore, apamin and paxilline, specific blockers of Ca2+-activated SK- and BK-type K+ channels, respectively; E-4031, a blocker of ether a-go-go K+ channel; and linopirdine, a blocker of M-type K+ channel, did not affect the agonist-specific patterns of calcium signaling and PRL secretion. These results suggest that ET-1 inhibits VGCI through activation of Cs+-sensitive channels, presumably the G(i/o)-controlled inward rectifier K+ channels, and that this agonist also inhibits PRL release, but downstream of Ca2+ influx. Further studies are required to identify the mechanism of sustained TRH-induced facilitation of VGCI and PRL secretion. C1 NICHHD, ERRB, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHHD, ERRB, Sect Cellular Signaling, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. RI Tomic, Melanija/C-3371-2016 NR 34 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD FEB-MAR PY 2003 VL 20 IS 1-2 BP 45 EP 52 DI 10.1385/ENDO:20:1-2:45 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 671UZ UT WOS:000182483600006 PM 12668867 ER PT J AU Heiman, ML Tinsley, FC Mattison, JA Hauck, S Bartke, A AF Heiman, ML Tinsley, FC Mattison, JA Hauck, S Bartke, A TI Body composition of prolactin-, growth hormone-, and thyrotropin-deficient Ames dwarf mice SO ENDOCRINE LA English DT Article DE fat content; bone mineral density; dual X-ray absorptiometry; growth hormone ID CALORIC RESTRICTION; TESTICULAR FUNCTION; LIFE-SPAN; PITUITARY; GENE; TISSUE; MOUSE; BONE; HYPERPROLACTINEMIA; GLUCOSE AB Ames dwarf mice have primary deficiency of prolactin (PRL), growth hormone (GH), and thyroid-stimulating hormone (TSH), and live considerably longer than normal animals from the same line. In view of the documented effects of GH, PRL, and thyroid hormones on lean and fat body mass and skeletal growth, and the suspected relationship of body size and composition to life expectancy, it was of interest to examine age-related changes in body composition of Ames dwarf mice. Lean mass, fat mass, bone area, and bone mineral content (BMC) were determined in dwarf and normal mice at the ages of 2, 4.5-6, and 18 mo using dual X-ray absorptiometry. In addition to the expected significant declines in lean mass, bone area, and BMC, dwarf mice exhibited attenuation of the age-related increase in bone mineral density and delayed or attenuated increase in percentage of body fat. Percentage of body fat was lower in adult dwarfs than in the corresponding normal controls. Patterns of age-related changes in body composition in Ames dwarf mice are consistent with the recent report of age-related changes in body composition in PRL receptor knockout mice. We suspect that reduction in relative adiposity may contribute to the previously reported increase in insulin sensitivity of Ames dwarf mice and thus may be a factor in delayed aging and increased longevity of these animals. C1 So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. Lilly Res Labs, Corp Ctr, Indianapolis, IN USA. NIA, Poolesville, MD USA. RP Bartke, A (reprint author), So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X FU NIA NIH HHS [AG19899] NR 40 TC 37 Z9 37 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD FEB-MAR PY 2003 VL 20 IS 1-2 BP 149 EP 154 DI 10.1385/ENDO:20:1-2:149 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 671UZ UT WOS:000182483600019 PM 12668880 ER PT J AU Lovekamp-Swan, T Davis, BJ AF Lovekamp-Swan, T Davis, BJ TI Mechanisms of phthalate ester toxicity in the female reproductive system SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review ID PROLIFERATOR-ACTIVATED RECEPTORS; FOLLICLE-STIMULATING-HORMONE; ACID-BINDING PROTEIN; RAT GRANULOSA-CELLS; PPAR-GAMMA; MONO(2-ETHYLHEXYL) PHTHALATE; DI(2-ETHYLHEXYL) PHTHALATE; PEROXISOME PROLIFERATORS; DIETHYLHEXYL PHTHALATE; SEXUAL-DIFFERENTIATION AB Phthalates are high-production-volume synthetic chemicals with ubiquitous human exposures because of their use in plastics and other common consumer products. Recent epiderniologic evidence suggests that women have a unique exposure profile to phthalates, which raises concern about the potential health hazards posed by such exposures. Research in our laboratory examines how phthalates interact with the female reproductive system in animal models to provide insights into the potential health effects of these chemicals in women. Here we review our work and the work of others studying these mechanisms and propose a model for the ovarian action of di-(2-ethylhexyl) phthalate (DEHP). In vivo, DEHP (2 g/kg) causes decreased serum estradiol levels, prolonged estrous cycles, and no ovulations in adult, cycling rats. In vitro, monoethylhexyl phthalate (MEHP; the active metabolite of DEHP) decreases granulosa cell aromatase RNA message and protein levels in a dose-dependent manner. MEHP is unique among the phthalates in its suppression of aromatase and in its ability to activate peroxisome proliferator-activated receptors (PPARs). We hypothesize that MEHP activates the PPARs to suppress aromatase in the granulosa cell. MEHP-, PPARalpha, and PPARgamma-specific ligands all similarly decreased estradiol production and RNA message levels of aromatase in vitro. Our model shows that MEHP acts on the granulosa cell by decreasing cAMP stimulated by follicle stimulating hormone and by activating the PPARs, which leads to decreased aromatase transcription. Thus, the environmental contaminant DEHP, through its metabolite MEHP, acts through a receptor-mediated signaling pathway to suppress estradiol production in the ovary, leading to anovulation. C1 NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Davis, BJ (reprint author), NIEHS, Lab Womens Hlth, POB 12233,MD A2-01, Res Triangle Pk, NC 27709 USA. NR 62 TC 261 Z9 278 U1 6 U2 77 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2003 VL 111 IS 2 BP 139 EP 145 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 645EN UT WOS:000180963400023 PM 12573895 ER PT J AU Cantor, KP Strickland, PT Brock, JW Bush, D Helzlsouer, K Needham, LL Zahm, SH Comstock, GW Rothman, N AF Cantor, KP Strickland, PT Brock, JW Bush, D Helzlsouer, K Needham, LL Zahm, SH Comstock, GW Rothman, N TI Risk of non-Hodgkin's lymphoma and prediagnostic serum organochlorines: beta-hexachlorocyclohexane, chlordane/heptachlor-related compounds, dieldrin, and hexachlorobenzene SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE chlordane; dieldrin; heptachlor; hexachlorobenzene; hexachlorocyclohexane; lindane; non-Hodgkin's lymphoma; organochlorine ID PESTICIDE MANUFACTURING PLANTS; ADIPOSE-TISSUE; POLYCHLORINATED-BIPHENYLS; CHLORINATED HYDROCARBONS; APLASTIC-ANEMIA; BONE-MARROW; MORTALITY; EXPOSURE; LEUKEMIA; CANCER AB Increases in non-Hodgkin's lymphoma (NHL) incidence and mortality rates during the past few decades remain largely unexplained. Studies suggest that organochlorine pesticides may contribute to an increased risk of NHL. In 1974, serum samples were obtained from 25,802 participants in the Campaign Against Cancer and Stroke in Washington County, Maryland (USA), and cryopreserved for future study. We measured prediagnostic levels of chlordane, lindane (gamma-hexachlorocyclohexane), beta-hexachlorocyclohexane, transnonachlor, heptachlor, heptachlor epoxide, oxychlordane, dieldrin, and hexachlorobenzene in serum samples of 74 cases of NHL and 147 matched controls. Previously, we found an association between NHL and serum levels of total PCBs (polychlorinated biphenyls), but not DDT (dichlorodiphenyttrichloroethane) and related compounds. In this instance, there was no evidence of an association between NHL risk and serum levels of any of the individual lipid- and recovery-corrected organochlorines that we evaluated, nor of the summed chlordane-related compounds (transnonachlor, heptachlor, heptachlor epoxide, oxychlordane). These findings do not support the hypothesis that the organochlorine compounds included in this study are strongly linked to the development of NHL. The possibaity of a weak association cannot be excluded by these data. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Cantor, KP (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-8106, Bethesda, MD 20892 USA. RI Needham, Larry/E-4930-2011; Zahm, Shelia/B-5025-2015 FU NCI NIH HHS [CA60754]; NHLBI NIH HHS [HL21670] NR 38 TC 31 Z9 33 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2003 VL 111 IS 2 BP 179 EP 183 DI 10.1289/ehp.4347 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 645EN UT WOS:000180963400030 PM 12573902 ER PT J AU Dimmock, JR Padmanilayam, MP Zello, GA Nienaber, KH Allen, TM Santos, CL De Clercq, E Balzarini, J Manavathu, EK Stables, JP AF Dimmock, JR Padmanilayam, MP Zello, GA Nienaber, KH Allen, TM Santos, CL De Clercq, E Balzarini, J Manavathu, EK Stables, JP TI Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE alpha,beta-unsaturated ketones; cytotoxicity; structure-activity relationships; bioscreens ID CONJUGATED STYRYL KETONE; MANNICH-BASES; INHIBITION; INVITRO AB A series of 2,6-bis(arylidene)cycloalkanones (1) and related compounds containing one or two substituents at the four position of the cyclohexyl ring were prepared and shown to display cytotoxic activity towards murine P388 and L1210 cells as ell as human Molt 4/C8 and CEM T-lymphoctes. In some of the series of compounds. positive e correlations were noted between the potencies of the enones and the magnitude of the Hammett c values of the aryl substituents. Four representatives compounds were cytotoxic to a number of human tumours in vitro. particularly towards colon cancer and leukemic cells. A noteworthy feature of the compounds prepared in this study is that. in general, they were well tolerated when administered to rodents. A number of lead molecules emerged from this investigation as well as guidelines for future expansion of these series of compounds. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. Univ Saskatchewan, Dept Biochem, Saskatoon, SK S7N 5E5, Canada. Univ Alberta, Dept Pharmacol, Edmonton, AB T6G 2H7, Canada. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. Wayne State Univ, Dept Med, Detroit, MI 48201 USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. RP Dimmock, JR (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, 110 Sci Pl, Saskatoon, SK S7N 5C9, Canada. EM dimmock@skyway.usask.ca NR 36 TC 62 Z9 62 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD FEB PY 2003 VL 38 IS 2 BP 169 EP 177 DI 10.1016/S0223-5234(02)01444-7 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 662AY UT WOS:000181924500004 PM 12620661 ER PT J AU Zapata, A Chefer, VI Ator, R Shippenberg, TS Rocha, BA AF Zapata, A Chefer, VI Ator, R Shippenberg, TS Rocha, BA TI Behavioural sensitization and enhanced dopamine response in the nucleus accumbens after intravenous cocaine self-administration in mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE contingent; microdialysis; psychostimulant; withdrawal ID EXTRACELLULAR DOPAMINE; INTRACEREBRAL DIALYSIS; INDEPENDENT COCAINE; AMPHETAMINE; RELEASE; RATS; MICRODIALYSIS; SENSITIVITY; ABSTINENCE; EXPRESSION AB The behavioural effects of cocaine are enhanced in animals with a prior history of repeated cocaine administration. This phenomenon, referred to as sensitization, is also associated with an increase in cocaine-evoked extracellular dopamine levels in the nucleus accumbens. Behavioural and neurochemical sensitization has been demonstrated in rats with a prior history of cocaine self-administration and in those that had received experimenter-administered cocaine. Although it is clear that the repeated non-contingent administration also results in behavioural sensitization in the mouse, the issue of whether behavioural and neurochemical sensitization also occur in this species following intravenous cocaine self-administration has not been assessed. The present study used the technique of in vivo microdialysis in conjunction with operant self-administration to characterize cocaine-evoked locomotor activity and dopamine levels in the nucleus accumbens in mice with a prior history of intravenous cocaine self-administration or those that had received yoked infusions of cocaine. Mice that had received contingent or non-contingent infusions of cocaine exhibited an enhanced behavioural response to cocaine and increased cocaine-evoked dopamine levels in the nucleus accumbens. There was no difference between groups in the magnitude of this effect. Prior exposure to cocaine did not modify baseline dopamine levels in the nucleus accumbens. These data demonstrate that mice with previous cocaine self-administration experience show an enhanced behavioural and dopamine response to cocaine in the nucleus accumbens. Furthermore, control over cocaine infusion does not significantly alter the magnitude of the sensitized behavioural and presynaptic dopamine responses observed in response to a challenge dose of cocaine. C1 NIDA, Integrat Neurosci Sect, Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD USA. Univ Maryland, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD USA. RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Sect, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [R29 DA 12579] NR 37 TC 44 Z9 46 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2003 VL 17 IS 3 BP 590 EP 596 DI 10.1046/j.1460-9568.2003.02491.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 644CD UT WOS:000180899600016 PM 12581176 ER PT J AU Windels, F Kiyatkin, EA AF Windels, F Kiyatkin, EA TI Modulatory action of acetylcholine on striatal neurons: microiontophoretic study in awake, unrestrained rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE oxotremorine M; nicotine; neuromodulation; nicotinic and muscarinic receptors; presynaptic regulation of dopamine and glutamate release; single-unit recording and iontophoresis ID FREELY MOVING RATS; BASAL GANGLIA; NICOTINIC RECEPTOR; NUCLEUS-ACCUMBENS; DOPAMINE; EXCITATION; GLUTAMATE; RELEASE; BRAIN; TRANSMISSION AB Cholinergic interneurons innervate virtually all medium spiny striatal cells, but the relevance of this input in regulating the activity and afferent responsiveness of these cells remains unclear. Studies in anaesthetized animals and slice preparations have shown that iontophoretic acetylcholine (ACh) either weakly excites or inhibits striatal neurons. These differential responses may reflect cholinergic receptor heterogeneity but may be also related to the different activity states of recorded units and different afferent inputs specific in each preparation. Single-unit recording was combined with iontophoresis in awake, unrestrained rats to examine the effects of ACh and selective muscarinic (oxotremorine M or Oxo-M) and nicotinic agonists (nicotine or NIC) on dorsal and ventral striatal neurons. These effects were tested on naturally silent, spontaneously active and glutamate-stimulated units. We found that iontophoretic ACh primarily inhibited spontaneously active and glutamate-stimulated units; the direction of the ACh response, however, was dependent on the firing rate. The effects of ACh were generally mimicked by Oxo-M and, surprisingly, by NIC, which is known to excite units in most central structures, including striatal neurons in anaesthetized preparation. Given that NIC receptors are absent on striatal cells but located primarily on dopamine terminals, we assessed the effects of NIC after complete blockade of dopamine receptors induced by systemic administration of a mixture of D1 and D2 antagonists. During dopamine receptor blockade the number of NIC-induced inhibitions dramatically decreased and NIC had mainly excitatory effects on striatal neurons. Thus, our data suggest that under physiologically relevant conditions ACh acts as a state-dependent neuromodulator, and its action involves not only postsynaptic but also presynaptic cholinoreceptors located on dopamine- and glutamate-containing terminals. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Windels, Francois/G-5432-2010 NR 33 TC 18 Z9 19 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2003 VL 17 IS 3 BP 613 EP 622 DI 10.1046/j.1460-9568.2003.02492.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 644CD UT WOS:000180899600019 PM 12581179 ER PT J AU Bussey, TJ Saksida, LM Murray, EA AF Bussey, TJ Saksida, LM Murray, EA TI Impairments in visual discrimination after perirhinal cortex lesions: testing 'declarative' vs. 'perceptual-mnemonic' views of perirhinal cortex function SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE discrimination learning; inferotemporal cortex; learning; object recognition; rhesus macaque monkey; ventral visual stream ID RHINAL CORTEX; RECOGNITION MEMORY; HIPPOCAMPAL-LESIONS; NEUROTOXIC LESIONS; RHESUS-MONKEYS; ABLATION; IDENTIFICATION; RAT AB Two experiments tested the predictions of 'declarative' vs. 'perceptual-mnemonic' views of perirhinal cortex function. The former view predicts that perirhinal cortex lesions should impair rapidly learned, but not more slowly learned, visual discriminations, whereas the latter view predicts that impairments should be related not to speed of learning but to perceptual factors. It was found that monkeys with perirhinal cortex lesions were impaired in the acquisition and performance of slowly learned, perceptually difficult greyscale picture discriminations, but were not impaired in the acquisition of rapidly learned, perceptually easier discriminations. In addition, these same monkeys were not impaired in the acquisition or performance of difficult colour or size discriminations, indicating that the observed pattern of impairments was not due to ceiling effects or difficulty per se. These findings, taken together, are consistent with the 'perceptual-mnemonic' view that the perirhinal cortex is involved in both perception and memory, but are not consistent with the 'declarative' view that the perirhinal cortex is important exclusively for declarative memory, having little or no role in perception. Moreover, the results are consistent with the more specific proposal that the perirhinal cortex contributes to the solution of complex visual discriminations with a high degree of 'feature ambiguity', a property of visual discrimination problems that can emerge when features of an object are rewarded when part of one object, but not when part of another. These and other recent findings suggest the need for a revision of prevailing views regarding the neural organization of perception and memory. C1 NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Bussey, TJ (reprint author), Univ Cambridge, Dept Expt Psychol, Downing St, Cambridge CB1 2EB, England. RI Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016; OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642 NR 29 TC 147 Z9 147 U1 2 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2003 VL 17 IS 3 BP 649 EP 660 DI 10.1046/j.1460-9568.2003.02475.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 644CD UT WOS:000180899600023 PM 12581183 ER PT J AU Strausbaugh, HJ Green, PG Dallman, MF Levine, JD AF Strausbaugh, HJ Green, PG Dallman, MF Levine, JD TI Repeated, non-habituating stress suppresses inflammatory plasma extravasation by a novel, sympathoadrenal dependent mechanism SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE ether stress; rat; repeated stress; sound stress; stressor intensity ID CORTICOTROPIN-RELEASING FACTOR; ADJUVANT-INDUCED ARTHRITIS; DISEASE-ACTIVITY; MAST-CELLS; C-FOS; PARAVENTRICULAR NUCLEUS; RHEUMATOID-ARTHRITIS; ULCERATIVE-COLITIS; IMMUNE-RESPONSES; JOINT INJURY AB The mechanism by which chronic stress affects the course of inflammatory diseases is still not well understood. We have evaluated the effect of two types of nonhabituating stress on a major component of the inflammatory response, synovial plasma extravasation, induced by perfusion of the potent inflammatory mediator, bradykinin and evaluated the underlying neuroendocrine mechanism in the rat. Chronic intermittent noise or ether stress induced profound inhibition of bradykinin-induced plasma extravasation, which is associated with increased adjuvant-arthritis severity. This inhibition, however, took 24 h to fully develop after the last exposure to stress and persisted for at least 48 h. The inhibition could be reversed by an additional exposure to the stressor, just prior to measuring the inflammatory response, suggesting that the delay is due to stress-induced release of a factor that acutely masks the inhibition of the inflammatory response. This novel, unexpected feature of the effect of nonhabituating stress on inflammation may help explain variability in effects of stress in patients with inflammatory disease. The effect of nonhabituating stress on inflammation was dependent on the sympathoadrenal axis with no detectable contribution by the hypothalamic-pituitary-adrenal axis. C1 Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH Pain Ctr, 521 Parnassus Ave, San Francisco, CA 94143 USA. RI Green, Paul/C-5943-2011 FU NIAMS NIH HHS [AR32634]; NIDDK NIH HHS [DK28172] NR 55 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2003 VL 17 IS 4 BP 805 EP 812 DI 10.1046/j.1460-9568.2003.02493.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 649VY UT WOS:000181229700014 PM 12603270 ER PT J AU Khasar, SG Green, PG Miao, FJP Levine, JD AF Khasar, SG Green, PG Miao, FJP Levine, JD TI Vagal modulation of nociception is mediated by adrenomedullary epinephrine in the rat SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE beta-adrenergic receptor; catecholamines; hyperalgesia; nociception ID VAGUS NERVE-STIMULATION; CYCLASE-ACTIVATING POLYPEPTIDE; POSTTRAUMATIC-STRESS-DISORDER; INDUCED PLASMA EXTRAVASATION; EXPERIMENTALLY-INDUCED PAIN; PACAP RECEPTOR EXPRESSION; ADRENAL CHROMAFFIN CELLS; MECHANICAL HYPERALGESIA; NORADRENALINE HYPERALGESIA; SYMPATHOADRENAL ACTIVITY AB Vagal afferent activity modulates mechanical nociceptive threshold and inflammatory mediator-induced hyperalgesia, effects that are mediated by the adrenal medulla. To evaluate the role of epinephrine, the major hormone released from the adrenal medulla, the beta(2) -adrenergic receptor antagonist ICI 118,551 was chronically administered to vagotomized rats and epinephrine to normal rats. In vagotomized rats, chronic administration of ICI 118,551 markedly attenuated vagotomy-induced enhancement of bradykinin hyperalgesia but had no effect on nociceptive threshold. In normal rats, chronic epinephrine had the opposite effect, enhancing bradykinin hyperalgesia. Like vagotomy-, epinephrine-induced enhancement of hyperalgesia developed slowly, taking 14 days to reach its peak. Vagotomy induced a chronic elevation in plasma concentrations of epinephrine. We suggest that ongoing activity in vagal afferents inhibits the release of epinephrine from the adrenal medulla. Chronically elevated levels of epinephrine, occurring after vagotomy, desensitize peripheral beta(2) -adrenergic receptors and lead to enhancement of bradykinin hyperalgesia. The ability of prolonged elevated plasma levels of epinephrine to sensitize bradykinin receptors could contribute to chronic generalized pain syndromes. C1 Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94143 USA. RI Green, Paul/C-5943-2011 FU NINR NIH HHS [NR004880] NR 59 TC 54 Z9 55 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2003 VL 17 IS 4 BP 909 EP 915 DI 10.1046/j.1460-9568.2003.02503.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 649VY UT WOS:000181229700027 PM 12603283 ER PT J AU Aley, KO Levine, JD AF Aley, KO Levine, JD TI Contribution of 5-and 12-lipoxygenase products to mechanical hyperalgesia induced by prostaglandin E-2 and epinephrine in the rat SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE arachidonic acid; epinephrine; hyperalgesia; lipoxygenase; prostaglandin; protein kinases ID PROTEIN-KINASE-C; TUMOR-NECROSIS-FACTOR; ARACHIDONIC-ACID; NOCICEPTOR SENSITIZATION; CYCLIC-AMP; IN-VITRO; ACTIVATION; CELLS; 5-LIPOXYGENASE; NEURONS AB We evaluated the role of lipoxygenase products of arachidonic acid metabolism in mechanical hyperalgesia induced by epinephrine, an agent that directly sensitizes nociceptors to produce mechanical hyperalgesia via three second messenger signaling pathways, protein kinase A (PKA), protein kinase C epsilon (PKCepsilon), and mitogen activated protein kinase (MAPK). Epinephrine hyperalgesia and that induced by a selective activator of MCE, ERACK, were inhibited by nordihydroguaretic acid (NDGA, non-selective lipoxygenase inhibitor), baicalein (BAIC, 12-lipoxygenase inhibitor) and 5, 6-dehydroarachidonic acid (5, 6-dhAA, 5-lipoxygenase inhibitor). NDGA and 5, 6-dhAA inhibited the hyperalgesia associated with activation of the protein kinase A pathway, elicited by the direct-acting hyperalgesic agent prostaglandin E-2 or by the catalytic subunit of protein kinase A. The hyperalgesia produced by active MAPK was not blocked by any of the lipoxygenase inhibitors. Injection of 5- and 12-lipoxygenase produced hyperalgesia that was not antagonized by inhibitors of PKA, PKCE or MAPK. These findings suggest that: (1) lipoxygenase products of arachidonic acid function as second messengers in the peripheral hyperalgesia induced by agents that act directly on primary afferent nociceptors (epinephrine and prostaglandin EA (2) products of the 5-lipoxygenase and 12-lipoxygenase pathway are involved in this function, and (3) these lipoxygenase products contribute to hyperalgesia at or downstream of protein kinase A and PKCe. C1 Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94143 USA. RP Aley, KO (reprint author), Univ Calif San Francisco, NIH Pain Ctr, Box 0440,Room C522,521 Parnassus Ave, San Francisco, CA 94143 USA. NR 38 TC 9 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD FEB PY 2003 VL 148 IS 4 BP 482 EP 487 DI 10.1007/s00221-002-1323-2 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 652QV UT WOS:000181390600007 ER PT J AU Sawaki, L Werhahn, KJ Barco, R Kopylev, L Cohen, LG AF Sawaki, L Werhahn, KJ Barco, R Kopylev, L Cohen, LG TI Effect of an alpha(1)-adrenergic blocker on plasticity elicited by motor training SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE plasticity; motor training; transcranial magnetic stimulation; learning; stroke ID USE-DEPENDENT PLASTICITY; LONG-TERM POTENTIATION; FUNCTIONAL RECOVERY; CORTEX; NOREPINEPHRINE; AMPHETAMINE; DAMAGE AB Recovery of motor function elicited by motor training after cortical lesions in rats is enhanced by norepinephrine (neurotransmitter mediating alpha(1)-adrenergic function) and downregulated by alpha(1)-adrenergic antagonists. In spite of this, alpha(1)-adrenergic antagonists are used to treat elderly patients with hypertension and prostate hyperplasia in stroke settings. The purpose of this study was to determine the effects of a single oral dose of the alpha(1)-adrenergic antagonist prazosin on training-dependent plasticity in intact humans, a function thought to contribute to recovery of motor function after cortical lesions. We report that prazosin decreased the ability of motor training to elicit training-dependent plasticity relative to a drug-free condition. These data suggest caution when using alpha(1)-adrenergic blockers in rehabilitative clinical settings following brain lesions. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, 10 Ctr DrmNSC 1428, Bethesda, MD 20892 USA. NR 15 TC 25 Z9 26 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD FEB PY 2003 VL 148 IS 4 BP 504 EP 508 DI 10.1007/s00221-002-1328-x PG 5 WC Neurosciences SC Neurosciences & Neurology GA 652QV UT WOS:000181390600010 PM 12582834 ER PT J AU Leitner, WW AF Leitner, WW TI Myth, menace or medical blessing? The clinical potential and problems of genetic vaccines SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Editorial Material ID HEMATOPOIETIC NECROSIS VIRUS; DNA VACCINATION; RAINBOW-TROUT; BACTERIAL-DNA; VECTORS; INDUCTION; CANCER; CELLS C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Leitner, WW (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 NR 23 TC 3 Z9 3 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD FEB PY 2003 VL 3 IS 1 BP 1 EP 4 PG 4 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 650LU UT WOS:000181266000001 PM 12718726 ER PT J AU Zhang, PS Chan, SL Fu, WM Mendoza, M Mattson, MP AF Zhang, PS Chan, SL Fu, WM Mendoza, M Mattson, MP TI TERT suppresses apoptotis at a premitochondrial step by a mechanism requiring reverse transcriptase activity and 14-3-3 protein binding ability SO FASEB JOURNAL LA English DT Article DE cancer; cytochrome c; etoposide; mitochondria; site-directed mutagenesis ID INDUCED CELL-DEATH; HUMAN TUMOR-CELLS; TELOMERASE ACTIVITY; DNA-DAMAGE; CANCER-CELLS; HELA-CELLS; LIFE-SPAN; 14-3-3-PROTEINS; STAUROSPORINE; PROLIFERATION AB The catalytic subunit of telomerase (TERT) is a reverse transcriptase (RT) that adds a six-base DNA repeat onto chromosome ends and prevents their shortening during successive cell divisions. Telomerase is associated with cell immortality and cancer, which may by related to the ability of TERT to prevent apoptosis by stabilizing telomeres. However, fundamental information concerning the antiapoptotic function of TERT is lacking, including whether RT activity and/or nuclear localization are required and where telomerase acts to suppress the cell death process. Here, we show that overexpression of wild-type human TERT in HeLa cells, and in a cells lacking TERT but containing the telomerase RNA template, increases their resistance to apoptosis induced by the DNA damaging agent etoposide or the bacterial alkaloid staurosporine. In contrast, TERT mutants with disruptions of either the RT domain or a 14-3-3 binding domain fail to protect cells against apoptosis, and overexpression of TERT in cells lacking the telomerase RNA template is also ineffective in preventing apoptosis. Additional findings show that TERT suppresses apoptosis at an early step before release of cytochrome c and apoptosis-inducing factor from mitochondria. We conclude that both RT activity and 14-3-3 protein binding ability are required for the antiapoptotic function of TERT in tumor cells and that TERT can suppress a nuclear signal(s) that is an essential component of apoptotic cascades triggered by diverse stimuli. 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, GRC 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 51 TC 61 Z9 74 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 2003 VL 17 IS 2 BP 767 EP + DI 10.1096/fj.02-0603fje PG 20 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 653VC UT WOS:000181456900009 PM 12594176 ER PT J AU Meky, FA Turner, PC Ashcroft, AE Miller, JD Qiao, YL Roth, MJ Wild, CP AF Meky, FA Turner, PC Ashcroft, AE Miller, JD Qiao, YL Roth, MJ Wild, CP TI Development of a urinary biomarker of human exposure to deoxynivalenol SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE deoxynivalenol; biomarkers; human exposure ID ESOPHAGEAL CANCER; C-14-LABELED DEOXYNIVALENOL; MYCOTOXINS TRICHOTHECENES; FUSARIUM MYCOTOXINS; NATURAL OCCURRENCE; HIGH-RISK; ZEARALENONE; EXCRETION; WHEAT; CHINA AB Deoxynivalenol (DON) is a mycotoxin frequently found as a contaminant of cereal crops and may be etiologically associated with adverse health effects in developing countries where considerable quantities of contaminated crops are consumed. We investigated the metabolism of DON in rats as a basis to establish methodology for a candidate biomarker of human exposure to this toxin and tested this methodology on urine samples from a potentially highly exposed population. Sprague-Dawley rats received a single dose of [C-14]DON (5.0+/-0.1 mg/kg body weight, 5.5+/-0.1 muCi/kg) and the distribution of DON in body fluids was investigated over 72 h. DON and its metabolites were detectable in the plasma of rats with the highest levels at 8 h, at which time approximately 9% was bound to plasma protein. A total of 37% of the administered DON was excreted in the urine and DON-glucuronide was implicated as the major urinary metabolite based on reverse-phase HPLC analysis of beta-glucuronidase- and sulphatase-treated samples. An immunoaffinity column (IAC)-HPLC method was subsequently developed to measure urinary metabolites, with a view to establishing a urine-based human biomarker. Urine samples were collected from female inhabitants of Linxian County, China, a high risk region for oesophageal cancer (OC) and an area of potentially high DON exposure, and Gejiu, a low risk region in China. DON was detected in all 15 samples following beta-glucuronidase treatment and IAC enrichment with the identity of DON being confirmed by mass spectrometry. The mean levels of DON from the suspected high and low exposure regions of China were 37 ng/ml (range 14-94 ng/ml) and 12 ng/ml (range 4-18 ng/ml), respectively. This is estimated to correspond to daily exposures of 1.1-7.4 mug/kg/day and 0.3-1.4 mug/kg/day, respectively. This is the first reported measurement of a urinary biomarker for DON in both animals and humans and should facilitate epidemiological studies of disease associations with this mycotoxin. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Leeds, Mol Epidemiol Unit, Epidemiol & Hlth Serv Res, Sch Med, Leeds LS2 9JT, W Yorkshire, England. Univ Leeds, Dept Biochem & Mol Biol, Leeds LS2 9JT, W Yorkshire, England. Carleton Univ, Dept Chem, Ottawa, ON K1S 5B6, Canada. Chinese Acad Med Sci, Dept Epidemiol, Inst Canc, Beijing 100021, Peoples R China. NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wild, CP (reprint author), Univ Leeds, Mol Epidemiol Unit, Epidemiol & Hlth Serv Res, Sch Med, Leeds LS2 9JT, W Yorkshire, England. RI Turner, Paul/A-6152-2011; Qiao, You-Lin/B-4139-2012; Turner, Paul/B-8131-2013 OI Qiao, You-Lin/0000-0001-6380-0871; FU NIEHS NIH HHS [ES 06052] NR 26 TC 112 Z9 115 U1 4 U2 51 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD FEB PY 2003 VL 41 IS 2 BP 265 EP 273 AR PII S0278-6915(02)00228-4 DI 10.1016/S0278-6915(02)00228-4 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 635XN UT WOS:000180425600008 PM 12480302 ER PT J AU Promrat, K McDermott, DH Gonzalez, CM Kleiner, DE Koziol, DE Lessie, M Merrell, M Soza, A Heller, T Ghany, M Park, Y Alter, HJ Hoofnagle, JH Murphy, PM Liang, TJ AF Promrat, K McDermott, DH Gonzalez, CM Kleiner, DE Koziol, DE Lessie, M Merrell, M Soza, A Heller, T Ghany, M Park, Y Alter, HJ Hoofnagle, JH Murphy, PM Liang, TJ TI Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C SO GASTROENTEROLOGY LA English DT Article ID HIV-1 DISEASE PROGRESSION; PROMOTER POLYMORPHISM; GENETIC RESTRICTION; INFECTION; CCR5; AIDS; RISK; MUTATION; RANTES; LIVER AB Background & Aims: CCR5Delta32, a 32-base pair deletion of the CC chemokine receptor (CCR) 5 gene, is associated with slowed human immunodeficiency virus disease progression in heterozygotes and protection against infection in homozygotes. A recent study found a higher than expected frequency of CCR5Delta32/Delta32 in patients with hepatitis C virus infection. The roles of other disease-associated chemokine system polymorphisms have not been evaluated in hepatitis C virus infection. Methods: Six chemokine system polymorphisms (CCR5Delta32, CCR5 promoter 59029-G/A, CCR2 -641, RANTES [regulated upon activation, normal T cells expressed and secreted] -403 -G/A, and -28 -C/G and stromal derived factor 1-3'A) were studied in 417 patients with liver diseases (339 with hepatitis C) and 2380 blood donors. The clinical parameters of hepatitis C virus infection were compared between carriers and noncarriers of each genetic variant. Results: The frequency of CCR5Delta32 homozygosity was 0.8% in whites with hepatitis C virus and 1.1% in controls (P = 0.75). The CCR5Delta32 allele was not associated with any of the clinical parameters of hepatitis C virus infection. Hepatitis C virus-seropositive whites with the RANTES -403 -A allele were less likely to have severe hepatic inflammation compared with those without (odds ratio, 0.34; P = 0.03). In multivariate analysis, the CCR5 promoter 59029 -A allele was marginally associated with a sustained response to interferon therapy (odds ratio, 3.07; P = 0.048). Conclusions: In this cohort, the frequency of CCR5Delta32 homozygosity in patients with hepatitis C was similar to controls. The high prevalence of CCR5Delta32 homozygosity in the hepatitis C virus patients of the earlier study likely reflects resistance to human immunodeficiency virus infection in hemophiliacs rather than a susceptibility to hepatitis C virus infection. Expression of CCR5 and RANTES may be important in the modulation of hepatic inflammation and response to interferon therapy in chronic hepatitis C. C1 NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Promrat, K (reprint author), NIDDKD, Liver Dis Sect, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. RI Soza, Alejandro/C-2907-2009; OI McDermott, David/0000-0001-6978-0867; Kleiner, David/0000-0003-3442-4453 NR 34 TC 95 Z9 102 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2003 VL 124 IS 2 BP 352 EP 360 DI 10.1053/gast.2003.50061 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 641EP UT WOS:000180732100012 PM 12557141 ER PT J AU Wu, SG Morin, PJ Maouyo, D Sears, CL AF Wu, SG Morin, PJ Maouyo, D Sears, CL TI Bacteroides fragilis enterotoxin induces c-myc expression and cellular proliferation SO GASTROENTEROLOGY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; APC TUMOR-SUPPRESSOR; BETA-CATENIN; E-CADHERIN; DIARRHEAL DISEASE; IN-VITRO; NUCLEAR EXPORT; GAMMA-CATENIN; CANCER; TOXIN AB Background & Aims: Enterotoxigenic Bacteroides fragilis that secrete a zinc-dependent metalloprotease toxin termed the B. fragilis toxin (BFT) have been associated with acute diarrheal disease. BFT rapidly cleaves the extracellular domain of E-cadherin, leading to the complete degradation of the E-cadherin protein. E-cadherin is the primary intercellular adhesion protein of the zonula adherens, and its cytoplasmic domain associates with the nuclear signaling protein beta-catenin. The goal of this study was to examine if BFT triggers beta-catenin nuclear signaling in intestinal epithelial cells. Methods: Cell biologic and biochemical techniques were combined to address beta-catenin nuclear signaling stimulated by BFT. Results: Loss of membrane-associated E-cadherin after BFT treatment of human colonic epithelial cells (HT29/C1 clone) triggers beta-catenin nuclear localization within 3 hours. Subsequently, c-myc transcription and translation are induced and persistent cellular proliferation ensues, mediated in part by beta-catenin/T-cell factor-dependent transcriptional activation. Cellular proliferation is stimulated by as little as 5 x 10(-10) mol/L BFT. Conclusions: To our knowledge, BFT is the first bacterial toxin reported to activate T-cell factor-dependent beta-catenin nuclear signaling in intestinal epithelial cells. These results suggest that genetic evolution of this common colonic commensal has rendered an organism with the potential to contribute to oncogenic transformation in the colon. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21205 USA. NIA, Baltimore, MD 21224 USA. RP Sears, CL (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, 720 Rutland Ave,Ross Bldg, Room 1167, Baltimore, MD 21205 USA. FU NIDDK NIH HHS [R01 DK 45496] NR 50 TC 78 Z9 81 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2003 VL 124 IS 2 BP 392 EP 400 DI 10.1053/gast.2003.50047 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 641EP UT WOS:000180732100016 PM 12557145 ER PT J AU Nan, X Peng, B Hahn, TW Richardson, E Lizonova, A Kovesdi, I Robert-Guroff, M AF Nan, X Peng, B Hahn, TW Richardson, E Lizonova, A Kovesdi, I Robert-Guroff, M TI Development of an Ad7 cosmid system and generation of an Ad7 Delta E1 Delta E3HIV(MN) env/rev recombinant virus SO GENE THERAPY LA English DT Article DE Ad7 recombinants; HIV; cosmid system ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN ADENOVIRUS TYPE-5; CELLULAR IMMUNE-RESPONSES; MEDIATED GENE-TRANSFER; TRANSFER IN-VIVO; NEUTRALIZING ANTIBODIES; NUCLEOTIDE-SEQUENCES; PROTECTIVE IMMUNITY; NUCLEAR EXPORT; SUBGROUP-A AB A strategy to circumvent immune responses to adenovirus (Ad) resulting from natural infection or repeated vector administrations involves sequential use of vectors from different Ad serotypes. To further develop an Ad-HIV recombinant AIDS vaccine approach, a replication-defective recombinant Ad from a non-subgroup C virus was required. Using a cosmid system, we generated an AdDeltaE1JDeltaE3HI(MN) env/rev recombinant virus and compared expression of the inserted HIV genes with a similarly constructed replication-competent Ad7DeltaE1DeltaE3HIV(MN)env/rev recombinant. Ad7DeltaE1DeltaE3HIV(MN)env/rev expressed both HIV env and rev gene products. The envelope protein was correctly processed and functional, mediating syncytia formation of Ad7DeltaE1DeltaE3HIV(MN) env/rev-infected cells and CD4(+) T lymphocytes. AdDeltaE1DeltaE3H1V(MN)env/rev could be amplified on 293-ORF6 cells, containing the E4 ORF6 gene, shown earlier to support production of an Ad7 vector lacking the E1a gene. The utility of this cell line is now extended to the production of replication-defective Ad7 recombinants lacking E1a, E1b, and protein IX genes. Sequential immunizations with Ad-HIV recombinants based in different Ad serotypes have been shown to effectively elicit both humoral and cellular HIV-specific immune responses. The recombinant Ad7DeltaE1DeltaE3HlV(MN)env/rev will be useful in such AIDS vaccine strategies. Further, these studies have created new cosmid vectors that can be applied to generation of single- or double-deleted Ad7 recombinants with foreign genes inserted into the El and/or E3 regions. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. GenVec, Gaithersburg, MD USA. RP Robert-Guroff, M (reprint author), NCI, Basic Res Lab, 41 Lib Dr MSC 5055,Bldg 41 Room D804, Bethesda, MD 20892 USA. OI Kovesdi, Imre/0000-0002-0322-3969 NR 65 TC 17 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD FEB PY 2003 VL 10 IS 4 BP 326 EP 336 DI 10.1038/sj.gt.3301903 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 643UF UT WOS:000180878300005 PM 12595891 ER PT J AU Sreenath, TL Cho, A Thyagarajan, T Kulkarni, AB AF Sreenath, TL Cho, A Thyagarajan, T Kulkarni, AB TI Odontoblast-specific expression of Cre recombinase successfully deletes gene segments flanked by loxP sites in mouse teeth SO GENESIS LA English DT Article DE dentin sialophosphoprotein (dspp); promoter; dentinogenesis; Cre recombinase; homologous recombination; ROSA26 reporter (R26R); beta-galactosidase; odontoblasts; dentin; transgenic mouse ID DENTIN SIALOPHOSPHOPROTEIN GENE; TOOTH MORPHOGENESIS; MOLECULAR MECHANISMS; RNA EXPRESSION; MICE; CELL; TGF-BETA-1; GENOME; PROMOTER AB Embryonic or neonatal lethality of mice with targeted disruption of critical genes preclude them from further characterization of specific roles of these genes during postnatal development and aging. In order to study the molecular roles of such genes in teeth, we generated transgenic mouse lines expressing bacteriophage Cre recombinase under the control of the mouse dentin sialophosphoprotein (dspp) gene promoter. The expression of Cre recombinase protein was mainly detected in the nucleus of the odontoblasts. The efficiency of Cre activity was analyzed by crossing the Dspp-Cre mice with ROSA26 reporter (R26R) mice. The offspring with both genotypes have shown specific deletion of intervening sequences flanked by IoxP sites upstream of the reporter gene, thereby facilitating the expression of the beta-galactosidase (beta-gal) gene in the teeth. The activity of beta-gal was initially observed in the odontoblasts of 1-day-old mice and increased with tooth development. Almost all of the odontoblasts have shown lacZ activity by 3 weeks of age. We could not detect Cre recombinase activity in any other cells, including ameloblasts. These studies indicate that the Dspp-Cre transgenic mice will be valuable to generate odontoblast-specific gene knockout mice so as to gain insight into the molecular roles of critical genes in the odontoblasts during dentinogenesis. Published 2003 Wiley-Liss, lnc. C1 NIDCR, Funct Genome Unit, NIH, Bethesda, MD 20892 USA. NIDCR, Gene Targeting Facil, NIH, Bethesda, MD 20892 USA. RP Sreenath, TL (reprint author), NIDCR, Funct Genome Unit, NIH, Bldg 30,Rm 527,30 Convent Dr, Bethesda, MD 20892 USA. NR 29 TC 10 Z9 10 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 1526-954X J9 GENESIS JI Genesis PD FEB PY 2003 VL 35 IS 2 BP 94 EP 99 DI 10.1002/gene.10170 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 651RL UT WOS:000181334700003 PM 12533791 ER PT J AU Yang, HP Kondrashov, AS AF Yang, HP Kondrashov, AS TI Cyclical dynamics under constant selection against in haploid and diploid populations with facultative mutations selfing SO GENETICAL RESEARCH LA English DT Article ID INBREEDING DEPRESSION; RATES; EVOLUTION; FERN; SYSTEMS; MODELS; PLANTS; LOAD AB We have found that constant selection against mutations can cause cyclical dynamics in a population with facultative selfing. When this happens, the distribution of the number of deleterious mutations per genotype fluctuates with the period similar to 1/s(He) generations, where s(He) is the coefficient of selection against a heterozygous mutation. The amplitude of oscillations of the mean population fitness often exceeds an order of magnitude. Cyclical dynamics can occur under intermediate selfing rates if selection against heterozygous mutations is weak and selection against homozygous mutations is much stronger. Cycling is possible without epistasis or with diminishing-returns epistasis, but not with synergistic epistasis. Under multiplicative selection, cycling might happen if the haploid mutation rate exceeds 1.9 in the case of selfing of haploids, and if this diploid mutation rate exceeds 4.5 in the case of selfing of diploids. We propose a heuristic explanation for cycling under facultative selfing and discuss its possible relevance. C1 Cornell Univ, Dept Ecol & Evolutionary Biol, Ithaca, NY 14853 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Yang, HP (reprint author), Univ Calif Davis, Sect Evolut & Ecol, Storer Hall,1 Shields Ave, Davis, CA 95616 USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0016-6723 J9 GENET RES JI Genet. Res. PD FEB PY 2003 VL 81 IS 1 BP 1 EP 6 DI 10.1017/S0016672302005979 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 668BA UT WOS:000182269400001 PM 12693677 ER PT J AU Jones, GW Masison, DC AF Jones, GW Masison, DC TI Saccharomyces cerevisiae Hsp70 mutations affect [PSI+] pirion propagation and cell growth differently and implicate Hsp40 and tetratricopeptide repeat cochaperones in impairment of [PSI+] SO GENETICS LA English DT Article ID MOLECULAR CHAPERONE DNAK; SHOCK COGNATE PROTEIN; PRION-LIKE FACTOR; SUBSTRATE-BINDING; YEAST PRIONS; ANTAGONISTIC INTERACTIONS; FUNCTIONAL-PROPERTIES; CYTOSOLIC HSP70; URE3 PRION; IN-VIVO AB We previously described an Hsp70 mutant (Ssa1-21p), altered in a conserved residue (L483W), that dominantly impairs yeast [PSI+] prion propagation without affecting growth. We generated new SSA1 mutations that impaired [PSI+] propagation and second-site mutations in SSA1-21 that restored normal propagation. Effects of mutations on growth did not correlate with [PSI+] I phenotype, revealing differences in Hsp70 function required for growth and [PSI] propagation and suggesting that Hsp70 interacts differently with [PSI] prion aggregates than with other cellular substrates. Complementary suppression of altered activity between forward and suppressing mutations suggests that mutations that impair [PSI+] affect a similar Hsp70 function and that suppressing mutations similarly overcome this effect. All new mutations that impaired [PSI+] propagation were located in the ATPase domain. Locations and homology of several suppressing substitutions suggest that they weaken Hsp70's substrate-trapping conformation, implying that impairment of [PSI+] by forward mutations is due to altered ability of the ATPase domain to regulate substrate binding. Other suppressing mutations are in residues important for interactions with Hsp40 or TPR-containing cochaperones, suggesting that such interactions are necessary for the impairment of [PSI+] propagation caused by mutant Ssalp. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Masison, DC (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 407,8 Ctr Dr, Bethesda, MD 20892 USA. NR 58 TC 69 Z9 72 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2003 VL 163 IS 2 BP 495 EP 506 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 653CG UT WOS:000181417200005 PM 12618389 ER PT J AU Hoffmann, ER Shcherbakova, PV Kunkel, TA Borts, RH AF Hoffmann, ER Shcherbakova, PV Kunkel, TA Borts, RH TI MLH1 mutations differentially affect meiotic functions in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID DNA MISMATCH-REPAIR; CROSSING-OVER; MUTS HOMOLOG; CONDITIONAL MUTATIONS; BUDDING YEAST; ATP BINDING; GENE; MEIOSIS; RECOMBINATION; PROTEIN AB To test whether missense mutations in the cancer susceptibility gene MLH1 adversely affect meiosis, we examined 14 yeast MLH1 mutations for effects on meiotic DNA transactions and gamete viability in the yeast Saccharomyces cerevisiae. Mutations analogous to those associated with hereditary nonpolyposis colorectal cancer (HNPCC) or those that reduce Mlh1p interactions with ATP or DNA all impair replicativc mismatch repair as measured by increased mutation rates. However, their effects on meiotic heteroduplex repair, crossing over, chromosome segregation, and gametogenesis vary from complete loss of meiotic functions to no meiotic defect, and mutants defective in one meiotic process are not necessarily defective in others. DNA binding and ATP binding but not ATP hydrolysis are required for meiotic crossing over. The results reveal clear separation of different Mlh1p functions in mitosis and meiosis, and they suggest that some, but not all, MLH1 mutations may be a source of human infertility. C1 Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. Univ Oxford, Dept Biochem, Oxford OX1 3Q, England. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Borts, RH (reprint author), Univ Leicester, Dept Genet, Univ Rd, Leicester LE1 7RH, Leics, England. NR 60 TC 31 Z9 32 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2003 VL 163 IS 2 BP 515 EP 526 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 653CG UT WOS:000181417200007 PM 12618391 ER PT J AU Klar, AJS AF Klar, AJS TI Response to Millar et al. critique of chromosome 1;11 translocation causing psychosis SO GENETICS LA English DT Letter ID AFFECTIVE-DISORDERS; SCHIZOPHRENIA C1 NCI, Gene Regulat & Chromosome Lab, Frederick, MD 21702 USA. RP Klar, AJS (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, POB B,Bldg 539, Ft Detrick, MD 21702 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2003 VL 163 IS 2 BP 837 EP 838 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 653CG UT WOS:000181417200035 ER PT J AU Woram, RA Gharbi, K Sakamoto, T Hoyheim, B Holm, LE Naish, K McGowan, C Ferguson, MM Phillips, RB Stein, J Guyomard, R Cairney, M Taggart, JB Powell, R Davidson, W Danzmann, RG AF Woram, RA Gharbi, K Sakamoto, T Hoyheim, B Holm, LE Naish, K McGowan, C Ferguson, MM Phillips, RB Stein, J Guyomard, R Cairney, M Taggart, JB Powell, R Davidson, W Danzmann, RG TI Comparative genome analysis of the primary sex-determining locus in salmonid fishes SO GENOME RESEARCH LA English DT Article ID TROUT ONCORHYNCHUS-MYKISS; FLY MEGASELIA-SCALARIS; GROWTH-HORMONE GENES; VNTR DNA LOCI; RAINBOW-TROUT; Y-CHROMOSOME; BROWN TROUT; TRUTTA-L; SALVELINUS-NAMAYCUSH; DETERMINING REGION AB We compared the Y-chromosome linkage maps for four salmonid species (Arctic charr, Salvelinus alpinus, Atlantic salmon, Salmo salar, brown trout, Salmo trutta; and rainbow trout, Oncorhynchus mykiss) and a putative Y-linked marker from lake trout (Salvelinus namaycush). These species represent the three major genera within the subfamily Salmoninae of the Salmonidae. The data clearly demonstrate that different Y-chromosomes have evolved in each of the species. Arrangements of markers proximal to the sex-determining locus are preserved on homologous, but different, autosomal linkage groups across the four species studied in detail. This indicates that a small region of DNA has been involved in the rearrangement of the sex-determining region. Placement of the sex-determining region appears telomeric in brown trout, Atlantic salmon, and Arctic charr, whereas an intercalary location for SEX may exist in rainbow trout. Three hypotheses are proposed to account for the relocation: translocation of a small chromosome arm; transposition of the sex-determining gene; or differential activation of a primary sex-determining gene region among the species. C1 Univ Guelph, Dept Zool, Guelph, ON N1G 2W1, Canada. INRA, Lab Fish Genet, F-78352 Jouy En Josas, France. Tokyo Univ Fisheries, Tokyo 1088477, Japan. Norwegian Sch Vet Sci, Oslo, Norway. Danish Inst Agr Sci, DK-8830 Tjele, Denmark. Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98105 USA. Simon Fraser Univ, Fac Sci, Burnaby, BC V5A 1S6, Canada. Univ Wisconsin, NIEHS, Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53204 USA. Univ Stirling, Inst Aquaculture, Stirling FK9 4LA, Scotland. Natl Univ Ireland Univ Coll Galway, Dept Microbiol, Galway, Ireland. RP Danzmann, RG (reprint author), Univ Guelph, Dept Zool, Guelph, ON N1G 2W1, Canada. RI Holm, Lars-Erik/A-4678-2013; Naish, Kerry/F-5768-2014; Gharbi, Karim/C-5771-2012; SAKAMOTO, Takashi/O-1949-2014; OI Holm, Lars-Erik/0000-0002-5312-3579; Naish, Kerry/0000-0002-3275-8778; Gharbi, Karim/0000-0003-1092-4488; SAKAMOTO, Takashi/0000-0002-8399-851X; Taggart, John/0000-0002-3843-9663 NR 70 TC 145 Z9 152 U1 1 U2 25 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD FEB PY 2003 VL 13 IS 2 BP 272 EP 280 DI 10.1101/gr.578503 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 642TY UT WOS:000180821900014 PM 12566405 ER PT J AU Vogel, W Grunebach, F Messam, CA Kanz, L Brugger, W Buhring, HJ AF Vogel, W Grunebach, F Messam, CA Kanz, L Brugger, W Buhring, HJ TI Heterogeneity among human bone marrow-derived mesenchymal stem cells and neural progenitor cells SO HAEMATOLOGICA LA English DT Article DE mesenchymal stem cells; heterogeneity; phenotypes ID CENTRAL-NERVOUS-SYSTEM; INTERMEDIATE FILAMENT PROTEIN; STROMAL CELLS; ADULT MICE; IN-VITRO; DIFFERENTIATE; MULTIPOTENT; MUSCLE; NESTIN; BRAIN AB Background and Objectives. Mesenchymal stem cells (MSC) and neural progenitor cells (NPC) are pluripotent cells. The former can give rise to myocytes, chondrocytes, adipocytes, and osteogenic cells, while the latter can give rise to astrocytes, neurons, and oligodendrocytes. The aim of this study was to analyze and compare the antigen expression patterns of MSC and NPC. Design and Methods. Human bone marrow-derived MSC and NPC were analyzed. by flow cytometry and immunocytochemistry using a variety of unique monoclonal antibodies (57D2, W4A5, W8B2) generated in our laboratory. In addition, the expression profile of CD antigens and intracellular differentiation markers was analyzed. Results. We show for the first time that CD10(+), CD13(+), CD61(+), CD90(+), CD105 (endoglin)(+), CD45(-), CD34(-), and CD133(-) MSC also expressed CD109, CD140b (PDGFRB), CD 164, and CD 172a (SIRPalpha). In addition, we found heterogeneity of MSC as demonstrated by the preferential expression of nestin and W8B2 antigen on distinct MSC subpopulations. Morphologically, these populations comprised small single cells and larger cells with polygonal appearance. NPC expressed high levels of CD56, CD90 and nestin and moderate levels of CD15, W4A5, and 57D2 antigens. In contrast, CD133 and CD172 were found only on NPC subpopulations. Interpretation and Conclusions. Our data demonstrate nestin expression in most NPC as well as in immature MSC subpopulations. MSC and NPC subpopulations can now be distinguished using our novel antibodies W8B2, 57D2, and W4A5. C1 Univ Tubingen, Dept Internal Med 2, Div Hematol Oncol Immunol & Rheumatol, D-72076 Tubingen, Germany. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Buhring, HJ (reprint author), Univ Tubingen, Dept Internal Med 2, Div Hematol & Oncol, Otfried Muller Str 10, D-72076 Tubingen, Germany. NR 37 TC 154 Z9 166 U1 1 U2 5 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD FEB PY 2003 VL 88 IS 2 BP 126 EP 133 PG 8 WC Hematology SC Hematology GA 646LZ UT WOS:000181037700005 PM 12604402 ER PT J AU Liu, J Li, CX Waalkes, MP Clark, J Myers, P Saavedra, JE Keefer, LK AF Liu, J Li, CX Waalkes, MP Clark, J Myers, P Saavedra, JE Keefer, LK TI The nitric oxide donor, V-PYRRO/NO, protects against acetaminophen-induced hepatotoxicity in mice SO HEPATOLOGY LA English DT Article ID DNA-BINDING ACTIVITY; HEPATIC-NECROSIS; LIVER-INJURY; IN-VIVO; APOPTOSIS; TOXICITY; MECHANISMS; ADDUCTS; RAT AB The liver-selective nitric oxide (NO) donor, O-2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V PYRRO/NO), is metabolized by P-450 enzymes to release NO in the liver, and is shown to protect the liver from tumor necrosis factor a (TNF-alpha)-induced apoptosis and D-glactosamine/endotoxin-induced hepatotoxicity. This study was undertaken to examine the effects of V PYRRO/NO on acetaminophen-induced hepatotoxicity in mice. Mice were given V PYRRO/NO via osmotic pumps (1.8-5.4 mg/ml,, 8 muL/h) 4 to 16 hours before a hepatotoxic dose of acetaminophen (600 mg/kg, intraperitoneally [ip]). V PYRRO/NO administration dramatically reduced acetaminophen-induced hepatotoxicity in a dose- and time-dependent manner, as evidenced by reduced serum alanine aminotransferase (ALT) activity, reduced hepatic congestion, apoptosis, and improved hepatocellular pathology. The protection afforded by V PYRRO/NO does not appear to be caused by a decrease in the formation of toxic acetaminophen metabolites, which consumes glutathione (GSH), because V PYRRO/NO did not alter acetaminophen-induced hepatic GSH depletion. Acetaminophen-induced lipid peroxidation, as determined by the concentrations of 4-hydroxyalkenals (4-HNE) and malondialdehyde (MDA), was reduced significantly by V PYRRO/NO treatment. Although pretreatment was most effective, administration of V PYRRO/NO simultaneously with acetaminophen also was able to reduce acetaminophen hepatotoxicity. Genomic analysis of the liver samples 10 hours after acetaminophen intoxication showed the enhanced expression of genes associated with stress/oxidative stress, apoptosis/cell death, and DNA damage/repair. Acetaminophen-induced alterations in gene expression were attenuated significantly by V PYRRO/NO. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western-blot analysis confirmed microarray results. In conclusion, V PYRRO/NO is effective in blocking acetaminophen -induced hepatotoxicity in mice. This protection may involve the reduction of oxidative stress, the inhibition of apoptosis, and possibly the maintenance of hepatic vasculature to prevent congestion. C1 NIEHS, Inorgan Carcinogensis Sect, Lab Comparat Carcinogenesis, NCI, Res Triangle Pk, NC 27709 USA. NIEHS, Comparat Med Branch, Res Triangle Pk, NC USA. NCI, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD USA. RP Liu, J (reprint author), NIEHS, Inorgan Carcinogensis Sect, Lab Comparat Carcinogenesis, NCI, Mail Drop F0-09, 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 38 TC 62 Z9 63 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2003 VL 37 IS 2 BP 324 EP 333 DI 10.1053/jhep.2003.50063 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 640FQ UT WOS:000180678000013 PM 12540782 ER PT J AU Jiao, XM Wang, RYH Feng, ZM Alter, HJ Shih, JWK AF Jiao, XM Wang, RYH Feng, ZM Alter, HJ Shih, JWK TI Modulation of cellular immune response against hepatitis C virus nonstructural protein 3 by cationic liposome encapsulated DNA immunization SO HEPATOLOGY LA English DT Article ID BACTERIAL-DNA; PLASMID DNA; CPG MOTIFS; GENE-TRANSFER; ACTIVATION; INFECTION; VACCINE; INDUCTION; MURINE; CELLS AB A vaccine strategy directed to increase Th1 cellular immune responses, particularly to hepatitis C virus (HCV) nonstructural protein 3 (NS3), has considerable potential to overcome the infection with HCV. DNA vaccination can induce both humoral and cellular immune responses, but it became apparent that the cellular uptake of naked DNA injected into muscle was not very efficient, as much of the DNA is degraded by interstitial nucleases before it reaches the nucleus for transcription. In this paper, cationic liposomes composed of different cationic lipids, such as dimethyl-dioctadecylammonium bromide (DDAB), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), or 1,2-dioleoyl-sn-glycerol-3-ethylphosphocholine (DOEPC), were used to improve DNA immunization in mice, and their efficiencies were compared. It was found that cationic liposome-mediated DNA immunization induced stronger HCV NS3-specific immune responses than immunization with naked DNA alone. Cationic liposomes composed of DDAB and equimolar of a neutral lipid, egg yolk phosphatidylcholine (EPC), induced the strongest antigen-specific Th1 type immune responses among the cationic liposome investigated, whereas the liposomes composed of 2 cationic lipids, DDAB and DOEPC, induced an antigen-specific Th2 type immune response. All cationic liposomes used in this study triggered high-level, nonspecific IL-12 production in mice, a feature important for the development of maximum Th1 immune responses. In conclusion, the cationic liposome-mediated gene delivery is a viable HCV vaccine strategy that should be further tested in the chimpanzee model. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Shih, JWK (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 51 TC 37 Z9 41 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2003 VL 37 IS 2 BP 452 EP 460 DI 10.1053/jhep.2003.50051 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 640FQ UT WOS:000180678000027 PM 12540796 ER PT J AU de Brouwer, APM Pennings, RJE Roeters, M Van Hauwe, P Astuto, LM Hoefsloot, LH Huygen, PLM van den Helm, B Deutman, AF Bork, JM Kimberling, WJ Cremers, FPM Cremers, CWRJ Kremer, H AF de Brouwer, APM Pennings, RJE Roeters, M Van Hauwe, P Astuto, LM Hoefsloot, LH Huygen, PLM van den Helm, B Deutman, AF Bork, JM Kimberling, WJ Cremers, FPM Cremers, CWRJ Kremer, H TI Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2 cause hearing loss in one family SO HUMAN GENETICS LA English DT Article ID AUTOSOMAL RECESSIVE DEAFNESS; SYNDROME TYPE 1D; E-CADHERIN; SENSORINEURAL DEAFNESS; CONNEXIN-26 MUTATIONS; PHYLOGENETIC ANALYSIS; PROTEIN STRUCTURES; AUDITORY FUNCTION; GENE; SUPERFAMILY AB We have ascertained a multi-generation family with apparent autosomal recessive non-syndromic childhood hearing loss (DFNB). Failure to demonstrate linkage in a genome-wide scan with 300 polymorphic markers has suggested genetic heterogeneity for the hearing loss in this family. This heterogeneity could be demonstrated by analysis of candidate loci and genes for DFNB. Patients in one branch of the family (branch C) are homozygous for the 35delG mutation in the GJB2 gene (DFNB 1). Patients in two other branches (A and B) carry two new mutations in the cadherin 23 (CDH23) gene (DFNB 12). A homozygous CDH23 c.6442G-->A (D2148N) mutation is present in branch A. Patients in branch B are compound heterozygous for this mutation and the c.402IG-->A (D1341N) mutation. The substituted aspartic acid residues are highly conserved and are part of the calcium-binding sites of the extracellular cadherin (EC) domains. Molecular modeling of the mutated EC domains of CDH23 based on the structure of E-cadherin indicates that calcium-binding is impaired. In addition, other aspartic and glutamic acid residue substitutions in the highly conserved calcium-binding sites reported to cause DFNB12 are also likely to result in a decreased affinity for calcium. Since calcium provides rigidity to the elongated structure of cadherin molecules enabling homophilic lateral interaction, these mutations are likely to impair interactions of CDH23 molecules either with CDH23 or with other proteins. DFNB12 is the first human disorder that can be attributed to inherited missense mutations in the highly conserved residues of the extracellular calcium-binding domain of a cadherin. C1 Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen, Ctr Mol & Biomol Informat, NL-6500 HC Nijmegen, Netherlands. Boys Town Natl Res Hosp, Gene Marker Lab, Omaha, NE 68131 USA. Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA. RP Kremer, H (reprint author), Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, POB 9101, NL-6500 HB Nijmegen, Netherlands. RI Kremer, Hannie/F-5126-2010; Pennings, Ronald/J-6651-2012; Cremers, Frans/A-5625-2014; Cremers, C.W.R.J./L-4254-2015; Huygen, P.L.M./L-4401-2015; de Brouwer, Arjan/P-5949-2015 OI Kremer, Hannie/0000-0002-0841-8693; FU NIDCD NIH HHS [P01DC01813] NR 67 TC 24 Z9 26 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 2003 VL 112 IS 2 BP 156 EP 163 DI 10.1007/s00439-002-0833-0 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 643UE UT WOS:000180878200008 PM 12522556 ER PT J AU Polakova, K Bennink, JR Yewdell, JW Bystricka, M Bandzuchova, E Russ, G AF Polakova, K Bennink, JR Yewdell, JW Bystricka, M Bandzuchova, E Russ, G TI Mild acid treatment induces cross-reactivity of 4H84 monoclonal antibody specific to nonclassical HLA-G antigen with classical HLA class I molecules SO HUMAN IMMUNOLOGY LA English DT Article DE HLA class I; HLA-G; heavy chain; leukemia cell lines; mAb 4H84 ID HEAVY-CHAINS; PROTEIN EXPRESSION; CELL-LINES; T-CELL; MELANOMA; BETA-2-MICROGLOBULIN; TRANSCRIPTION; DISSOCIATION; SURFACE; TP25.99 AB Mild acid treatment by releasing beta(2)m and antigenic peptides leaves human leukocyte antigen (HLA) class I free heavy chains attached to the cell surface. Acid treatment thus allows detection of the cell surface class 1 antigens by monoclonal antibodies (mAbs) specific to HLA-free heavy chains. We found that acid treatment also enables detection of the cell surface non-classical HLA-G class I antigen with mAbs specific for HLA-G free heavy chains, including 4H84 mAb recognizing all isoforms. Furthermore, we found that 4H84 mAb, but not other mAbs specific to HLA-G free heavy chains, binds to the surface of 8 out of 16 acid-treated leukemia cell lines. Nevertheless, HLA-G antigen is not present in any of these leukemia cells. This was demonstrated by failure to detect any antigen with 4H84 mAb in immunoblotting as well as by inability to detect HLA-G mRNA by RT-PCR. The antigen recognized by 4H84 mAb in some acid treated leukemia cells was identified by immunoprecipitation as a 45 kDa protein. A number of observations indicate that 45 kDa proteins are none other than classical class I heavy chains. Acid treatment thus induces the ability of the 41184 mAb to recognize some classical HLA class I molecules. Remarkably, 41184 determinant on HLA-G is linear but corresponding determinant present on some partially folded classical HLA class I free heavy chains is conformational. In view of the unexpected cross-reactivity, detection of HLA-G with this mAb must be carefully evaluated to avoid false detection. (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Science Inc. C1 Slovak Acad Sci, Inst Virol, Bratislava 84245, Slovakia. Slovak Acad Sci, Canc Res Inst, Bratislava, Slovakia. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Inst Prevent & Clin Med, Bratislava, Slovakia. RP Russ, G (reprint author), Slovak Acad Sci, Inst Virol, Dubravaska Cesta 9, Bratislava 84245, Slovakia. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 31 TC 20 Z9 20 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD FEB PY 2003 VL 64 IS 2 BP 256 EP 264 AR PII S0198-8859(02)00777-2 DI 10.1016/S0198-8859(02)00777-2 PG 9 WC Immunology SC Immunology GA 643ZR UT WOS:000180893900008 PM 12559628 ER PT J AU Martinez, A Pio, R Zipfel, PF Cuttitta, F AF Martinez, A Pio, R Zipfel, PF Cuttitta, F TI Mapping of the adrenomedullin-binding domains in human complement factor H SO HYPERTENSION RESEARCH LA English DT Article; Proceedings Paper CT 3rd International Symposium on Adrenomedullin and PAMP CY NOV 21, 2002 CL OSAKA, JAPAN DE adrenomedullin; complement factor H; FHL-1; binding assay; recombinant proteins ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; SHORT CONSENSUS REPEAT; HUMAN PLASMA; PROTEIN; C3B; IDENTIFICATION; PATHWAY; SITES AB Adrenomedullin (AM) is a multifunctional peptide involved in roles as varied as blood pressure regulation, growth, neurotransmission, and inflammation control, among others. We previously identified complement factor H as a serum binding protein for AM and showed that factor H regulates AM functions and vice versa. Here we searched for the specific binding sites for AM by using recombinant fragments of factor H and a non-radioactive binding assay with fluorescein-tagged AM. By this methodology, two specific binding sites for AM were found in factor H. One of them shows a high affinity for AM and is located at the carboxy terminal end of factor H, comprising short consensus repeats (SCR) 15-20. Smaller fragments of this region did not bind to AM efficiently, suggesting that the high affinity binding site of factor H requires a complex three-dimensional structure to recognize AM. Another binding site with lower affinity for AM was found in the middle of the factor H molecule, at SCR 8-11. Antibodies against factor H prevented AM binding altogether, but the main binding partner of factor H, C3b, did not, indicating that C3b and AM bind to different regions of factor H. These structure-function data support previous biochemical observations. Our understanding of the binding between AM and factor H may help in the development of new treatments for diseases in which these molecules play active roles. C1 NCI, Cell & Canc Biol Branch, Vasc Biol Fac, NIH, Bethesda, MD 20892 USA. Univ Navarra, CIMA, Carcinogenesis Unit, E-31080 Pamplona, Spain. Univ Navarra, Dept Biochem, E-31080 Pamplona, Spain. Hans Knoell Inst Nat Prod Res, Jena, Germany. RP Martinez, A (reprint author), NCI, Cell & Canc Biol Branch, Vasc Biol Fac, NIH, Bldg 10,Room 13N262, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013; Pio, Ruben/F-5353-2017 OI Martinez, Alfredo/0000-0003-4882-4044; Pio, Ruben/0000-0002-6831-6111 NR 26 TC 13 Z9 15 U1 0 U2 2 PU JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE PI TOYONAKA PA OSAKA, 14TH FL, SENRI LIFE SCI CENTER BLDG, 4-2 SHINSENRI- HIGASHI-MACHI 1 CHOME, TOYONAKA, 565-0082, JAPAN SN 0916-9636 J9 HYPERTENS RES JI Hypertens. Res. PD FEB PY 2003 VL 26 SU S BP S55 EP S59 DI 10.1291/hypres.26.S55 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 651TC UT WOS:000181337300009 PM 12630812 ER PT J AU Hayes, SM Shores, EW Love, PE AF Hayes, SM Shores, EW Love, PE TI An architectural perspective on signaling by the pre-, alpha beta and gamma delta T cell receptors SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ANTIGEN RECEPTOR; POSITIVE SELECTION; LYMPHOCYTES-T; TCR COMPLEX; THYMOCYTE SELECTION; IMMATURE THYMOCYTES; THYMUS DEVELOPMENT; CD3 COMPLEX; MUTANT MICE; ZETA-CHAIN AB The T cell antigen receptor (TCR) is a multimeric complex composed of an antigen-binding clonotypic heterodimer and a signal transducing complex consisting of the CD3 dimers (CD3gammaepsilon and CD3deltaepsilon) and a TCR-zeta homodimer. In all jawed vertebrates there are two T cell lineages, alphabeta and gammadelta, distinguished by the clonotypic subunits contained within their TCRs (TCR-alpha and -beta or TCR-gamma and -delta, respectively). A third receptor complex, the preTCR, is only expressed on immature T cells. The preTCR, which contains the invariant pre-Talpha (pTalpha) chain in lieu of TCR-alpha, plays a critical role in the early development of alphabeta lineage cells. The subunit composition of the signal transducing complexes of the pre-, alphabeta- and gammadeltaTCRs was previously thought to be identical. However, recent data demonstrate that there are significant differences in the signal transducing complexes of these three TCRs. For example, alphabetaTCRs contain both CD3gammaepsilon and CD3deltaepsilon dimers, whereas gammadeltaTCRs contain only CD3gammaepsilon dimers. Moreover, preTCR function appears to be unaffected in the absence of CD3delta, suggesting that CD3deltaepsilon dimers are dispensable for pre-TCR assembly. In this review, we summarize current data relating to the subunit composition of the pre-, alphabeta- and gammadeltaTCRs and discuss how these structural differences may impact receptor signaling and alphabeta/gammadelta lineage determination. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, MSC 2780,Bldg 6B,Room 2B-210,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 60 TC 51 Z9 51 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2003 VL 191 IS 1 BP 28 EP 37 DI 10.1034/j.1600-065X.2003.00011.x PG 10 WC Immunology SC Immunology GA 652GY UT WOS:000181372500003 PM 12614349 ER PT J AU Stefanova, I Dorfman, JR Tsukamoto, M Germain, RN AF Stefanova, I Dorfman, JR Tsukamoto, M Germain, RN TI On the role of self-recognition in T cell responses to foreign antigen SO IMMUNOLOGICAL REVIEWS LA English DT Review ID PEPTIDE-MHC COMPLEXES; RECEPTOR SIGNAL-TRANSDUCTION; TYROSINE KINASE P56(LCK); CLASS-II MOLECULES; N-TERMINAL REGION; HOMEOSTATIC PROLIFERATION; ZETA-PHOSPHORYLATION; NEGATIVE SELECTION; TCR ANTAGONISM; IMMUNE-SYSTEM AB The key role of the thymus in shaping the peripheral T cell receptor (TCR) repertoire has been appreciated for nearly a quarter of a century. For most of that time, a single model has dominated thinking about the physiological role of the positive selection process mediated by TCR recognition of self-peptides and major histocompatibility complex (MHC) molecules. This developmental filter was believed to populate secondary lymphoid tissues with T cells bearing receptors best able to recognize unknown foreign peptides associated with the particular allelic forms of the MHC molecules present in an individual. More recently, self-recognition has been suggested to regulate the viability of naive T cells. Here we focus on new results indicating that a critical contribution of positive selection to host defense is insuring that each peripheral T cell can use self-recognition to (i) enhance TCR signaling sensitivity upon foreign antigen recognition and (ii) augment the clonal expansion that accompanies limiting foreign antigen display at early points in an infectious process. We also detail new insights into the intracellular signaling circuitry that underlies the effective discrimination between low- and high-quality ligands of the TCR and speculate on how this design might facilitate an additional contribution of self-recognition to T cell activation in the presence of foreign stimuli. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Kenya Govt Med Res Ctr, Wellcome Trust Res Labs, Kilifi, Kenya. Tokyo Metropolitan Komagome Hosp, Transfus Serv, Bunkyo Ku, Tokyo 1138677, Japan. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bldg 10,Rm 11 N311 10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA. RI Dorfman, Jeffrey/B-4854-2011 OI Dorfman, Jeffrey/0000-0001-9938-8911 NR 85 TC 44 Z9 44 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2003 VL 191 IS 1 BP 97 EP 106 DI 10.1034/j.1600-065X.2003.00006.x PG 10 WC Immunology SC Immunology GA 652GY UT WOS:000181372500008 PM 12614354 ER PT J AU Fuller, CL Braciale, VL Samelson, LE AF Fuller, CL Braciale, VL Samelson, LE TI All roads lead to actin: the intimate relationship between TCR signaling and the cytoskeleton SO IMMUNOLOGICAL REVIEWS LA English DT Review ID WISKOTT-ALDRICH-SYNDROME; T-CELL RECEPTOR; PROTEIN-TYROSINE KINASE; MICROTUBULE-ORGANIZING CENTER; ANTIGEN-PRESENTING CELLS; SUPRAMOLECULAR ACTIVATION CLUSTERS; SRC HOMOLOGY-3 DOMAINS; WASP-FAMILY PROTEINS; TOXIC LYMPHOCYTES-T; SPLENIC B-CELLS AB Regardless of cell type, the regulation of the actin cytoskeleton is tightly linked to vital biological properties such as polarity, motility, cell-cell contact, exocytosis and proliferation. In the immune system, where rapid and efficient response to antigen-provoked stimuli is crucial, an overwhelming amount of data implicate the actin cytoskeleton and its regulators as central to immune function. Increasingly, the cytoskeleton is considered an essential amplification step in T cell receptor (TCR)-, costimulatory-, and integrin-mediated signaling. Advances in genetic manipulation and confocal imaging have led to a keener appreciation of the importance of TCR signal integration by the actin cytoskeleton. This review outlines recent advances in elucidating the regulation of T cell function through the actin cytoskeleton. We also examine intriguing parallels between the immune system and other models of cytoskeletal regulation. C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77550 USA. RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Bldg 37,Room 1E24, Bethesda, MD 20892 USA. NR 174 TC 53 Z9 55 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2003 VL 191 IS 1 BP 220 EP 235 DI 10.1034/j.1600-065X.2003.00004.x PG 16 WC Immunology SC Immunology GA 652GY UT WOS:000181372500017 PM 12614363 ER PT J AU Lobos, E Nutman, TB Hothersall, JS Moncada, S AF Lobos, E Nutman, TB Hothersall, JS Moncada, S TI Elevated immunoglobulin E against recombinant Brugia malayi gamma-glutamyl transpeptidase in patients with Bancroftian filariasis: Association with tropical pulmonary eosinophilia or putative immunity SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN LYMPHATIC FILARIASIS; IGE RESPONSES; WUCHERERIA-BANCROFTI; SCHISTOSOMA-MANSONI; IGG4 SUBCLASS; ASCARIS-SUUM; T-HELPER; ANTIBODY; INFECTION; RESISTANCE AB A major allergen of the lymphatic filarial nematode Brugia malayi, a homologue of gamma-glutamyl transpeptidase (gamma-GT), is involved in the pathology of tropical pulmonary eosinophilia (TPE) through its potent allergenicity and the induction of antibodies against the host pulmonary epithelium. To investigate the immunoglobulin G (IgG) subclass and IgE responses to recombinant B. malayi gamma-GT, we analyzed the results obtained from 51 patients with differing clinical manifestations of bancroftian filariasis. gamma-GT-specific IgG1, rather than IgG4, was the predominant IgG subclass, particularly in patients with TPE (geomean, 6,321 ng/ml; range, 78 to 354,867 ng/ml) and was 75 times higher than in patients with elephantiasis (CP) (P < 0.003) and 185 times higher than in endemic normal individuals (ENL) (P < 0.010). IgG2 responses were low and IgG3 was almost absent, with no significant differences among the groups. gamma-GT-specific IgG4 responses were significantly elevated in those with subclinical microfilaremia (MF) compared to the CP and ENL groups and correlated with the presence of circulating filarial antigen (CAg). More significantly, gamma-GT-specific IgE antibody levels were strikingly elevated in patients with TPE (geomean, 681 ng/ml; range, 61 to 23,841 ng/ml) and in the ENL group (geomean, 106 ng/ml; range, 13 to 1,405 ng/ml) whereas the gamma-GT-specific IgE level was 44 and 61 times lower in those with MF and CP, respectively (P < 0.001). Elevated gamma-GT-specific IgE/IgG4 ratios were demonstrated in patients with TPE (ratio, 45) and ENL (ratio, 107). Because expression of gamma-GT in Brugia infective third-stage larvae (L3) was demonstrated by immunoblot analysis, the elevated gamma-GT-specific IgE antibodies appear to be associated not only with pulmonary pathology but also with possible resistance to infection in lymphatic filariasis. C1 UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England. UCL, Inst Urol & Nephrol, London WC1E 6BT, England. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Lobos, E (reprint author), Univ Leipzig, Inst Anat, Liebigstr 13, D-04103 Leipzig, Germany. EM lobe@medizin.uni-leipzig.de NR 55 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2003 VL 71 IS 2 BP 747 EP 753 DI 10.1128/IAI.71.2.747-753.2003 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 639PZ UT WOS:000180639600022 PM 12540554 ER PT J AU Minnick, MF Sappington, KN Smitherman, LS Andersson, SGE Karlberg, O Carroll, JA AF Minnick, MF Sappington, KN Smitherman, LS Andersson, SGE Karlberg, O Carroll, JA TI Five-member gene family of Bartonella quintana SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; ROCHALIMAEA-QUINTANA; SEQUENCE; BACILLIFORMIS; EXPRESSION; ALIGNMENT; INFECTION; INVASION; BRUCELLA; SYSTEM AB Bartonella quintana, the agent of trench fever and an etiologic agent of bacillary angiomatosis, has an extraordinarily high hemin requirement for growth compared to other bacterial pathogens. We previously identified the major hemin receptor of the pathogen as a 30-kDa surface protein, termed HbpA. This report describes four additional homologues that share approximately 48% amino acid sequence identity with hbpA. Three of the genes form a paralagous cluster, termed hbpCAB, whereas the other members, hbpD and hbpE, are unlinked. Secondary structure predictions and other evidence suggest that Hbp family members are beta-barrels located in the outer membrane and contain eight transmembrane domains plus four extracellular loops. Homologs from a variety of gram-negative pathogens were identified, including Bartonella henselae Pap31, Brucella Omp31, Agrobacterium tumefaciens Omp25, and neisserial opacity proteins (Opa). Family members expressed in vitro-synthesized proteins ranging from ca. 26.5 to 35.1 kDa, with the exception of HbpB, an similar to55.9-kDa protein whose respective gene has been disrupted by a similar to510 GC-rich element containing variable-number tandem repeats. Transcription analysis by quantitative reverse transcriptase-PCR (RT-PCR) indicates that all family members are expressed under normal culture conditions, with hbpD and hbpB transcripts being the most abundant and the rarest, respectively. Mutagenesis of hbpA by allelic exchange produced a strain that exhibited an enhanced hemin-binding phenotype relative to the parental strain, and analysis by quantitative RT-PCR showed elevated transcript levels for the other hbp family members, suggesting that compensatory expression occurs. C1 Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. Uppsala Univ, Evolutionary Biol Ctr, Dept Mol Evolut, Uppsala, Sweden. NIAID, Microscopy Branch, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. EM minnick@selwav.umt.edu FU NIAID NIH HHS [R15 AI045534, R15 AI045534-01] NR 32 TC 36 Z9 38 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2003 VL 71 IS 2 BP 814 EP 821 DI 10.1128/IAI.71.2.814-821.2003 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 639PZ UT WOS:000180639600029 PM 12540561 ER PT J AU Scidmore, MA Fischer, ER Hackstadt, T AF Scidmore, MA Fischer, ER Hackstadt, T TI Restricted fusion of Chlamydia trachomatis vesicles with endocytic compartments during the initial stages of infection SO INFECTION AND IMMUNITY LA English DT Article ID ELECTRON-MICROSCOPY; INTRACELLULAR PATHOGENS; PHAGOLYSOSOME FUSION; CONTAINING VACUOLES; EPITHELIAL-CELLS; INCLUSION; PSITTACI; PATHWAY; TRAFFICKING; MEMBRANE AB The chlamydial inclusion occupies a unique niche within the eukaryotic cell that does not interact with endocytic compartments but instead is fusogenic with a subset of sphingomyelin-containing exocytic vesicles. The Chlamydia trachomatis inclusion acquires these distinctive properties by as early as 2 h postinfection as demonstrated by the ability to acquire sphingomyelin, endogenously synthesized from 6{N-[(7-nitrobenzo-2-oxa-1,3-diazol-4-yl) amino] caproyisphingosine} (C-6-NBD-ceramide). The molecular mechanisms involved in transformation of the properties and cellular interactions of the inclusion are unknown except that they require early chlamydial transcription and translation. Although the properties of the inclusion are established by 2 h postinfection, the degree of interaction with endocytic pathways during the brief interval before fusogenicity with an exocytic pathway is established is unknown. Using a combination of confocal and electron microscopy to localize endocytic and lysosomal markers in C. trachomatis infected cells during the early stages of infection, we demonstrate a lack of these markers within the inclusion membrane or lumen of the inclusion to conclude that the nascent chlamydial inclusion is minimally interactive with endosomal compartments during this interval early in infection. Even when prevented from modifying the properties of the inclusion by incubation in the presence of protein synthesis inhibitors, vesicles containing elementary bodies are very slow to acquire lysosomal characteristics. These results imply a two-stage mechanism for chlamydial avoidance of lysosomal fusion: (i) an initial phase of delayed maturation to lysosomes due to an intrinsic property of elementary bodies and (ii) an active modification of the vesicular interactions of the inclusion requiring chlamydial protein synthesis. C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Host Parasite Interact, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Microscopy Branch, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Host Parasite Interact, Hamilton, MT 59840 USA. NR 36 TC 93 Z9 98 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2003 VL 71 IS 2 BP 973 EP 984 DI 10.1128/IAI.71.2.973-984.2003 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 639PZ UT WOS:000180639600048 PM 12540580 ER PT J AU Cugini, C Medrano, M Schwan, TG Coburn, J AF Cugini, C Medrano, M Schwan, TG Coburn, J TI Regulation of expression of the Borrelia burgdorferi beta 3-chain integrin ligand, P66, in ticks and in culture SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-SURFACE-PROTEIN; LYME-DISEASE SPIROCHETE; IXODES-SCAPULARIS; GENE-EXPRESSION; OMS66 P66; EPITOPES; PATTERNS AB Borrelia burgdorferi is maintained in an infection cycle between mammalian and arthropod hosts. Appropriate gene expression by B. burgdorferi at different stages of this cycle is probably essential for transmission and establishment of infection. The B. burgdorferi beta(3) integrin ligand P66 is expressed by the bacteria in mammals, laboratory culture, and engorged but not unfed ticks. No in vitro culture conditions in which P66 expression reflected that in the unfed tick were found, suggesting that there are aspects of B. burgdorferi-tick interaction that remain unexplored. C1 Tufts New England Med Ctr, Div Geog Med & Infect Dis, Dept Med, Boston, MA USA. Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. NIAID, Lab Human Bacterial Pathogensis, Rocky Mt Labs, Hamilton, MT USA. RP Coburn, J (reprint author), Tufts New England Med Ctr, Div Geog Med & Infect Dis, Dept Med, NEMC Box 41,750 Washington St, Boston, MA USA. FU NIAID NIH HHS [T32-AI-07422, T32 AI007422]; NIDDK NIH HHS [1 P30DK39428]; PHS HHS [40938] NR 26 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2003 VL 71 IS 2 BP 1001 EP 1007 DI 10.1128/IAI.71.2.1001-1007.2003 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 639PZ UT WOS:000180639600052 PM 12540584 ER PT J AU Ramalho-Ortigao, JM Kamhawi, S Rowton, ED Ribeiro, JMC Valenzuela, JG AF Ramalho-Ortigao, JM Kamhawi, S Rowton, ED Ribeiro, JMC Valenzuela, JG TI Cloning and characterization of trypsin- and chymotrypsin-like proteases from the midgut of the sand fly vector Phlebotomus papatasi SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE sand flies; midgut trypsin and chymotrypsin-like proteases; RT-PCR ID ANOPHELES-GAMBIAE; AEDES-AEGYPTI; MOLECULAR CHARACTERIZATION; BLOODMEAL DIGESTION; MALARIA MOSQUITO; LEISHMANIA; GENES; TRANSCRIPTION; COMPETENCE; EXPRESSION AB Trypsin and chymotrypsin serine proteases are the main digestive proteases in Diptera midguts and are also involved in many aspects of the vector-parasite relationship. In sand flies, these proteases have been shown to be a potential barrier to Leishmania growth and development within the midgut. Here we describe the sequence and partial characterization of six Phlebotomus papatasi midgut serine proteases: two chymotrypsin-like (Ppchym1 and Ppchym2) and four trypsin-like (Pptryp1-Pptryp4). All six enzymes show structural features typical to each type, including the histidine, aspartic acid, and serine (H/D/S) catalytic triad, six conserved cysteine residues, and other amino acid residues involved in substrate specificity. They also show a high degree of homology (4060% identical residues) with their counterparts from other insect vectors, such as Anopheles gambiae and Aedes aegypti. The mRNA expression profiles of these six proteases vary considerably: two trypsin-like proteases (Pptryp1 and Pptryp2) are downregulated and one (Pptryp4) upregulated upon blood feeding. The two chymotrypsin-like enzymes display expression behavior similar to that of the early and late trypsins from Ae. aegypti. Published by Elsevier Science Ltd. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Intracellular Parasite Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Entomol, Silver Spring, MD 20910 USA. RP Valenzuela, JG (reprint author), NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, 4 Ctr Dr,Bldg 4,Rm 126,MSC 0425, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-4474-2012; Ramalho-Ortigao, Marcelo/E-8225-2011; Rowton, Edgar/A-1975-2011; OI Rowton, Edgar/0000-0002-1979-1485; Ribeiro, Jose/0000-0002-9107-0818 NR 27 TC 42 Z9 44 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD FEB PY 2003 VL 33 IS 2 BP 163 EP 171 DI 10.1016/S0965-1748(02)00187-X PG 9 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 641XK UT WOS:000180772200004 PM 12535675 ER PT J AU Taioli, E Gaspari, L Benhamou, S Boffeta, P Brockmoller, J Butkiewicz, D Cascorbi, I Clapper, ML Dolzan, V Haugen, A Hirvonen, A Husgafvel-Pursiainen, K Kalina, I Kremers, P Le Marchand, L London, S Rannug, A Romkes, M Schoket, B Seidegard, J Strange, RC Stucker, I To-Figueras, J Garte, S AF Taioli, E Gaspari, L Benhamou, S Boffeta, P Brockmoller, J Butkiewicz, D Cascorbi, I Clapper, ML Dolzan, V Haugen, A Hirvonen, A Husgafvel-Pursiainen, K Kalina, I Kremers, P Le Marchand, L London, S Rannug, A Romkes, M Schoket, B Seidegard, J Strange, RC Stucker, I To-Figueras, J Garte, S TI Polymorphisms in CYP1A1, GSTM1, GSTT1 and lung cancer below the age of 45 years SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID GENETIC SUSCEPTIBILITY; RISK; CARCINOGENS AB Background A genetic component of early-onset lung cancer has been suggested. The role of metabolic gene polymorphisms has never been studied in young lung cancer cases. Phase 1 and Phase 2 gene polymorphisms are involved in tobacco carcinogens' metabolism and therefore in lung cancer risk. Methods The effect of metabolic gene polymorphisms on lung cancer at young ages was studied by pooling data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database. All primary lung cancer cases of both sexes who were Caucasian and less than or equal to45 years of age at diagnosis, and the corresponding controls were selected. We obtained 261 cases and 1452 controls. Results There was a marginally significant association between lung cancer and GST1 null genotype (OR = 1.2; 95% Cl: 1.0-1.6), and a significant association between lung cancer and the homozygous CYP1A1 Msp1 variant allele (CYP1A1*2A and *2B) genotype (OR = 4.7 95% Cl: 1.2-19.0). When data were stratified by smoking status, the association between CYP1A1 genotype and lung cancer was confined to never smokers. Conclusions These results suggest that metabolic genetic factors play a role in lung cancer developing at young ages. C1 Osped Maggiore, IRCCS, Mol & Genet Epidemiol Unit, Milan, Italy. INSERM, Villejuif, France. Geneva Canc Registry, Geneva, Switzerland. IARC, Lyon, France. Univ Gottingen, Inst Clin Pharmacol, D-3400 Gottingen, Germany. Inst Clin Pharmacol, Gliwice, Poland. Univ Greifswald, Greifswald, Germany. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Ljubljana, Ljubljana 61000, Slovenia. Natl Inst Occupat Hlth, Oslo, Norway. Finnish Inst Occupat Hlth, Helsinki, Finland. Safarik Univ, Kosice, Slovakia. Inst Pathol, Liege, Belgium. Univ Hawaii, Honolulu, HI 96822 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Karolinska Inst, Stockholm, Sweden. Univ Pittsburgh, Pittsburgh, PA USA. Natl Inst Environm Hlth, Budapest, Hungary. Lund Univ, Lund, Sweden. Keele Univ, Keele, Staffs, England. Hosp Clin Barcelona, Barcelona, Spain. UMDNJ, EOHSI, Piscataway, NJ USA. Genet Res Inst Milano, Milan, Italy. RP Taioli, E (reprint author), Osped Maggiore, IRCCS, Mol & Genet Epidemiol Unit, Milan, Italy. RI Cascorbi, Ingolf/A-4519-2009; Benhamou, Simone/K-6554-2015; OI Garte, Seymour/0000-0003-3284-5975; London, Stephanie/0000-0003-4911-5290 NR 17 TC 81 Z9 86 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 2003 VL 32 IS 1 BP 60 EP 63 DI 10.1093/ije/dyg001 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 669FM UT WOS:000182341300012 PM 12690010 ER PT J AU Ndebele, K Tchounwou, PB McMurray, RW AF Ndebele, K Tchounwou, PB McMurray, RW TI Effects of xenoestrogens on T lymphocytes: Modulation of bcl-2, p53, and apoptosis SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE xenoestrogens; coumestrol; bisphenol A; DDT; TCDD; T lymphocytes; cell cycle ID ENDOCRINE-ACTIVE COMPOUNDS; DOSE-RESPONSE ASSESSMENT; ESTROGEN-RECEPTOR-ALPHA; ENVIRONMENTAL ESTROGENS; CELL-CYCLE; SEX STEROIDS; BISPHENOL-A; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; THYMIC ATROPHY; ACTIVATION AB Endogenous estrogens have significant immunomodulatory effects characterized as suppression of cell mediated immunity and stimulation of humoral immunity. Xenoestrogens are environmental estrogens that have endocrine impact, acting as estrogen agonists and antagonists but whose immune effects are not well characterized. Using CD4(+) Jurkat T cells as a model, the effects of representative xenoestrogens on T proliferation, cell cycle, and apoptosis were examined. Coumestrol ( CM), a phytoestrogen, and tetrachlorodioxin (TCDD) in concentrations of 10(-4) to 10(-6)M significantly inhibited Jurkat T cell lymphoproliferation, whereas bisphenol A (BPA) and DDT had minimal effect, but did antagonize 17-beta-estrtadiol induced effects. Xenoestrogens, especially CM, produced accumulation of Jurkat T cells in G(2)/M phase, and subsequently induced apoptosis, particularly CM (% apoptotic cells = 30 +/- 12 vs. control = 5 +/- 2). These changes were associated with DNA fragmentation. BPA and DDT also induced DNA fragmentation but not significant DNA hypoploidy. Xenoestrogen - CM, BPA, DDT, and TCDD - exposure suppressed bcl-2 protein and mRNA transcript levels but augmented p53 protein and mRNA transcripts. Human purified peripheral blood lymphocytes responded with similar significant cell cycle changes (G(0)/G(1) exodus and G(2)/M accumulation) for CM, BPA, and DDT exposure. These preliminary data, taken together, suggest that xenoestrogens have direct, compound-specific T lymphocyte effects that enhance our understanding of environmental modulation of immune and autoimmune responses. C1 Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, Jackson, MS 39217 USA. Univ Mississippi, Sch Med, Div Rheumatol & Mol Immunol, Jackson, MS 39216 USA. RP McMurray, RW (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu; Robert.McMurray@med.va.gov NR 59 TC 5 Z9 5 U1 0 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD FEB PY 2003 VL 4 IS 2 BP 45 EP 61 DI 10.3390/i4020045 PG 17 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 751YA UT WOS:000187117000003 ER PT J AU Mulert, C Gallinat, J Dorn, H Herrmann, WM Winterer, G AF Mulert, C Gallinat, J Dorn, H Herrmann, WM Winterer, G TI The relationship between reaction time, error rate and anterior cingulate cortex activity SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE cognitive control; attention; reaction time; error rate; anterior cingulate cortex; event-related potential ID ELECTRICAL TOMOGRAPHY; SCHIZOPHRENIA; BRAIN; ACTIVATION; TASK; EEG; INTERFERENCE; NEGATIVITY; ATTENTION; RESONANCE AB Current concepts of cognitive control suggest that the anterior cingulate cortex (ACC) is involved in performance monitoring. This idea is supported by the finding that increased ACC activity is found in situations in which errors are likely to occur, even if none are actually made. In addition, recent results suggest that increased ACC activity is negatively correlated with reaction time. We have now compared the error rates and the ACC activity of healthy subjects with short (n = 19) vs. long reaction times (n = 17) in an auditory choice reaction paradigm and analysed the current density differences in the ACC in the time range of the NI component with low resolution electromagnetic tomography. Subjects with short reaction times showed significantly more ACC activation (Brodmann Area 24) and an increased error rate. This finding suggests that increased ACC activity is associated with a gain in reaction speed at the expense of correctness and is discussed in the context of current concepts about the role of the ACC in cognitive functions. (C) 2002 Elsevier Science B.V. All rights reserved. C1 LMU, Dept Psychiat, Lab Clin Neurophysiol, D-80336 Munich, Germany. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Mulert, C (reprint author), LMU, Dept Psychiat, Lab Clin Neurophysiol, Nussbaumstr 7, D-80336 Munich, Germany. RI Mulert, Christoph/F-2576-2012 NR 38 TC 40 Z9 42 U1 4 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD FEB PY 2003 VL 47 IS 2 BP 175 EP 183 AR PII S0167-8760(02)00125-3 DI 10.1016/S0167-8760(02)00125-3 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 647QX UT WOS:000181106400007 PM 12568947 ER PT J AU Goel, S Wadler, S Hoffman, A Volterra, F Baker, C Nazario, E Ivy, P Silverman, A Mani, S AF Goel, S Wadler, S Hoffman, A Volterra, F Baker, C Nazario, E Ivy, P Silverman, A Mani, S TI A phase II study of rebeccamycin analog NSC 655649 in patients with metastatic colorectal cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE rebeccamycin analog; phase II; colorectal cancer ID TOPOISOMERASE-I; SOLID TUMORS; DNA; DERIVATIVES; NSC-655649; SEQUENCES; CLEAVAGE AB The analog, rebeccamycin tartrate salt (NSC 655649, Cancer Therapy Evaluation Program, National Cancer Institute) has broad preclinical anti-neoplastic activity. Preliminary data from phase I study demonstrated antitumor activity in colorectal carcinoma. This phase II trial evaluates its efficacy in patients with minimally treated metastatic colorectal cancer. Eligibility included Karnofsky performance status greater than or equal to70%, age greater than or equal to18 years and bidimensionally measurable disease. Thirteen patients were treated with NSC 655649 at 500 mg/m(2) by central venous catheter once every 3 weeks by bolus injection. Thirty-four cycles (median [range] 2 [1-6]) of therapy were administered. Twelve patients are eligible for response assessment. No major objective responses were seen using the RECIST criteria; however stable disease was observed in three patients with mean duration of 15 weeks. The median time to progression was 8 weeks. There was no toxic death. Four patients received only one cycle of treatment, and three had disease progression. Toxicities were tolerable and hematologic toxicity was the most common. The median (range) granulocyte and platelet nadir counts were 2043/mu1 (116-16,374/mul) and 276x10(3)/mul (5-769), respectively. Non-hematologic toxicities were moderate, including generalized weakness/fatigue, nausea/vomiting, diarrhea and anorexia. One patient required dose reduction; three patients required dose delays. NSC 655649 at this dose and schedule is inactive against advanced previously minimally treated metastatic colorectal cancer and further study of this drug as a single agent in this disease using an every three-week schedule is not warranted. C1 Montefiore Med Ctr, Dept Oncol, Weiler Div, Bronx, NY 10461 USA. Albert Einstein Canc Ctr, Bronx, NY 10461 USA. Cornell Univ, Div Hematol Oncol, Weill Med Coll, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. RP Mani, S (reprint author), Montefiore Med Ctr, Dept Oncol, Weiler Div, Room 2S-49,1825 Eastchester Rd, Bronx, NY 10461 USA. FU NCI NIH HHS [N01-CM-07003-74, P30CA 13330] NR 16 TC 14 Z9 14 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2003 VL 21 IS 1 BP 103 EP 107 DI 10.1023/A:1022980613420 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 660FJ UT WOS:000181822900011 PM 12795535 ER PT J AU Organisciak, DT Darrow, RA Barsalou, L Kutty, RK Wiggert, B AF Organisciak, DT Darrow, RA Barsalou, L Kutty, RK Wiggert, B TI Susceptibility to retinal light damage in transgenic rats with rhodopsin mutations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DOMINANT RETINITIS-PIGMENTOSA; PHOTORECEPTOR DEGENERATION; MICE; APOPTOSIS; GENE; ACTIVATION; LOCALIZATION; EXPRESSION; CASPASE-3; INCREASES AB PURPOSE. To determine relative light induced retinal damage susceptibility in transgenic rats expressing mutations in the N- or C-terminal region of rhodopsin. METHODS. Heterozygous transgenic rats, including P23H sublines 2 and 3 and S334ter, sublines 4 and 9, were reared in dim cyclic light or in darkness before visible light exposure starting at various times of the day or night. Before exposure to light, some rats were given the synthetic antioxidant dimethylthiourea (DMTU). At various times after intense fight treatment, rats were killed for determinations of rhodopsin and retinal DNA recovery, DNA fragmentation patterns, and Northern blot analysis of retinal heme oxygenase (HO)-1 and interphotoreceptor retinol binding protein (IRBP). Rod outer segments (ROSS) were isolated for Western blot analysis of rhodopsin using N- and C- terminal-specific monoclonal antibodies. RESULTS. All rats incurred greater photoreceptor cell damage from exposure to light starting at 1 AM than from exposure at 5 PM. Among cyclic-fight-reared rats, P23H line 3 animals were more susceptible to light-induced damage than P23H line 2 animals. S334ter rats exhibited retinal light damage profiles similar to those in normal rats. Dark-rearing potentiated retinal damage by light. However, dark rearing alone prolonged photoreceptor cell life in P23H rats, but had no such effect in S334ter animals. DMTU pretreatment was effective in preventing or reducing light-induced retinal damage in all transgenic rats. S334ter rat ROSs contained the truncated form of rhodopsin. Intense fight exposure resulted in DNA ladders typical of apoptotic cell death and the simultaneous induction of retinal HO-1 mRNA and reduced expression of IRBP. CONCLUSIONS. Light-induced retinal damage in transgenic rats depends on the time of day of exposure to light, prior light-or dark-rearing environment, and the relative level of transgene expression. Retinal light damage leads to apoptotic visual cell loss and appears to result from oxidative stress. These results suggest that reduced environmental lighting and/or antioxidant treatment may delay retinal degenerations arising from rhodopsin mutations. C1 Wright State Univ, Sch Med, Dept Biochem & Mol Biol, Petticrew Res Lab, Dayton, OH 45435 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Organisciak, DT (reprint author), Wright State Univ, Sch Med, Dept Biochem & Mol Biol, Petticrew Res Lab, 3640 Colonel Glenn Highway, Dayton, OH 45435 USA. FU NEI NIH HHS [EY-01959] NR 34 TC 61 Z9 64 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2003 VL 44 IS 2 BP 486 EP 492 DI 10.1167/iovs.02-0708 PG 7 WC Ophthalmology SC Ophthalmology GA 645GA UT WOS:000180966800005 PM 12556372 ER PT J AU Gottsch, JD Bowers, AL Margulies, EH Seitzman, GD Kim, SW Saha, S Jun, AS Stark, WJ Liu, SH AF Gottsch, JD Bowers, AL Margulies, EH Seitzman, GD Kim, SW Saha, S Jun, AS Stark, WJ Liu, SH TI Serial analysis of gene expression in the corneal endothelium of Fuchs' dystrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MITOCHONDRIAL-DNA; CELL-DEATH; APOPTOSIS; PROFILES; DENSITY; SAGE AB PURPOSE. To compare the gene expression profiles of normal human corneal endothelium with Fuchs' corneal endothelium, by using serial analysis of gene expression (SAGE). METHODS. Three pairs of normal human corneas were obtained from eye banks. Thirteen bisected Fuchs' corneal buttons were processed at the time of corneal transplantation. The endothelia of normal and Fuchs'-affected corneas were stripped, and total RNA was isolated. Serial analysis of gene expression (SAGE) was performed to identify and quantify gene transcripts. Genes over- and underexpressed by Fuchs' endothelium were limited to P < 0.01 by the method of Audic and Claverie. RESULTS. A total of 19,136 tags were identified with 9,530 from normal and 9,606 from Fuchs' endothelium. The expression of IS transcripts was upregulated, and 36 transcripts were down-regulated ut Fuchs' endothelium compared with normal tissue. Upregulated transcripts included serum amyloid A1 and A2, metallothionein, and apolipoprotein D. Of the downregulated transcripts, 26 matched known genes, 3 matched expressed sequence tags (ESTs), and 7 were unknown to current databases. One downregulated transcript involved a newly reported bicarbonate transporter. Decreased transcripts related to antioxidants and proteins conferring protection against toxic stress were noted in Fuchs' versus normal endothelium including nuclear ferritin, glutathione S-transferase-v and heat shock 70-kDa protein. Nine different SAGE tags matching mitochondrial sequences accounted for 25% of the ESTs that were decreased in Fuchs' endothelium. CONCLUSIONS. SAGE analysis comparing normal to Fuchs' endothelium demonstrates diminished expression of mitochondrial, pump function, and antiapoptotic cell defense genes. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Mol Genet Lab, Baltimore, MD 21205 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Wilmer Eye Inst, Ctr Corneal Genet, Cornea & External Dis Serv, Baltimore, MD USA. RP Gottsch, JD (reprint author), Johns Hopkins Univ Hosp, Wilmer Eye Inst, 600 N Wolfe St,Maumenee 321, Baltimore, MD 21287 USA. NR 33 TC 50 Z9 53 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2003 VL 44 IS 2 BP 594 EP 599 DI 10.1167/iovs.02-0300 PG 6 WC Ophthalmology SC Ophthalmology GA 645GA UT WOS:000180966800021 PM 12556388 ER PT J AU Wang, F Rendahl, KG Manning, WC Quiroz, D Coyne, M Miller, SS AF Wang, F Rendahl, KG Manning, WC Quiroz, D Coyne, M Miller, SS TI AAV-mediated expression of vascular endothelial growth factor induces choroidal neovascularization in rat SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; PIGMENT EPITHELIAL-CELLS; BLOOD-RETINAL BARRIER; MACULAR DEGENERATION; GENE-TRANSFER; IN-VIVO; SUBRETINAL NEOVASCULARIZATION; TRANSGENIC MICE; HEMOPHILIA-B; VIRAL VECTOR AB PURPOSE. To develop a small-animal model of choroidal neovascularization (CNV) by injecting adeno-associated virus (AAV)-VEGF into the subretinal space (SRS) of rats. METHODS. An adeno-associated viral vector encoding human VEGF,6, was injected into the subretinal space (SRS) of Sprague-Dawley or Long Evans rats. Expression of VEGF was identified by RT-PCR and immunohistochemistry. Physiological and pathologic changes in the retina and choroid were evaluated by electroretinography, fluorescein angiography, light microscopy, and three-dimensional reconstruction of serial sections. RESULTS. Green fluorescent protein (GFP) and VEGF were expressed for at least 20 months in the retina and retinal pigment epithelium (RPE). Histologic sections showed extensive subretinal neovascularization, degenerating photoreceptors, and proliferating RPE at 5 weeks to 20 months after injection of AAV-VEGF. At 2 to 12 months after injection, leaking blood vessels were detected by fluorescein angiography. Electroretinogram a- and b-wave amplitudes were significantly decreased during this time. Three-dimensional reconstruction of serial sections demonstrated that choroidal blood vessels penetrated Bruch's membrane, one of them splitting into three branches in the SRS. In the current model, CNV was produced in 95% of the animals tested (19/20). It persisted for more than 20 months, a necessary requirement for modeling the development of CNV in age-related macular degeneration (AMD). CONCLUSIONS. In this study, a highly reproducible animal model of long-lasting CNV was developed. This model is being used to test antiangiogenic molecules to reduce or inhibit CNV and could be extended to primates. C1 Univ Calif Berkeley, Sch Optometry, Berkeley, CA USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Chiron Corp, Gene Therapy Grp, Emeryville, CA USA. RP Miller, SS (reprint author), NEI, NIH, Bldg 31,Rm 6A20,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY02205, EY03176] NR 66 TC 58 Z9 65 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2003 VL 44 IS 2 BP 781 EP 790 DI 10.1167/iovs.02-0281 PG 10 WC Ophthalmology SC Ophthalmology GA 645GA UT WOS:000180966800047 PM 12556414 ER PT J AU Wang, FS Hong, WG Cao, YZ Liu, MX Jin, L Hu, LP Wang, Z Feng, TJ Hou, J Zhang, B Shi, M Xu, DP Lei, ZY Wang, B Liu, ZD Ye, JJ Peng, L Qiu, Y Winkler, C AF Wang, FS Hong, WG Cao, YZ Liu, MX Jin, L Hu, LP Wang, Z Feng, TJ Hou, J Zhang, B Shi, M Xu, DP Lei, ZY Wang, B Liu, ZD Ye, JJ Peng, L Qiu, Y Winkler, C TI Population survey of CCR5 Delta 32, CCR5 m303, CCR2b 64I, and SDF1 3 ' A allele frequencies in indigenous Chinese healthy individuals, and in HIV-1-infected and HIV-1-uninfected individuals in HIV-1 risk groups SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE coreceptors; SDF-1; CCR2; CCR5; HIV-1; allele frequency ID CHEMOKINE GENE VARIANT; DISEASE PROGRESSION; AIDS PROGRESSION; RECEPTOR; CCR2-641; POLYMORPHISMS; TRANSMISSION; INFECTION; GENOTYPES; THERAPY AB The aim of this study is to determine in indigenous Chinese ethnic groups the frequencies of the chemokine (SDFI 3'A) and chemokine receptors (CCR5 Delta32, CCR5 m303, and CCR2b 641) HIV-1/AIDS restriction alleles. The study includes two cohorts; the first comprised 3165 indigenous healthy subjects representing eight ethnic groups: Han (n = 1406), Uygur (n = 316), Mongolia (n = 134), Hui (n = 386), Tibetan (n = 330), Zhuang (n = 378), Dai (n = 101), and Jingbo (n = 114). The second cohort consisted of 330 HIV-1-infected (86 subjects infected by sexual transmission and 198 subjects infected by HIV-1-contaminated blood or by sharing injection equipment; the remaining 46 subjects said nothing about HIV-1 transmission) and 474 HIV-1-uninfected Han Chinese belonging to one of two HIV-1 high-risk groups: intravenous drug users (n = 215) and individuals with sexually transmitted diseases (n = 259). Genotypes for the four genes were obtained using PCR (CCR5 Delta32) or PCR-restriction fragment length polymorphism. Randomly selected amplified PCR products were further confirmed by direct DNA sequencing. The variant allele frequencies were determined to be 0% to 3.48% for CCR5 Delta32, 0% for CCR5 m303, 16.23% to 28.79% for CCR2b 641, and 17.70% to 27.76% for SDFI 3'A in Chinese healthy individuals from eight ethnic groups. These findings show that allele frequencies differ among the eight Chinese ethnic groups for CCR5 Delta32, CCR2b 641, and SDFI 3'A and that the CCR5 m303 and CCR5 Delta32 mutant alleles were absent or infrequent in Chinese, which may be helpful for studies of specific anti-HIV-1 vaccine trials and coreceptor inhibitor drug targets in Chinese populations. Furthermore, we observed no significant differences in allele or genotypic frequencies between HIV-1-infected and HIV-1-uninfected groups from the Han ethnic group. Our finding is the first reporting that there is likely no effect of the examined polymorphisms in our study on HIV-1 transmission in the Chinese Han population, However, the genetic effects of these and other AIDS-modifying polymorphisms on the pathogenesis and clinical outcome of HIV-1/AIDS diseases is under investigation in Chinese populations. C1 Beijing Hosp Infect Dis, Beijing Inst Infect Dis, Div Biol Engn, Beijing, Peoples R China. Natl Ctr AIDS Prevent & Control, Beijing, Peoples R China. Inst Med Informat, Div Med Stat, Beijing, Peoples R China. Hlth & Antiepidem Ctr Henan Province, Zhengzhou, Peoples R China. Shenzhen Hlth & Antiepidem Stn, Shenzhen, Guangdong Prov, Peoples R China. Hlth & Antiepidem Ctr Xin Jiang Autonomous Reg, Mulomuqi, Peoples R China. Sci & Technol Inst Family Planning, Kunming, Yunnan Province, Peoples R China. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Wang, FS (reprint author), Beijing Inst Infect Dis, Div Biol Engn, 26 Feng Tai Rd, Beijing 100039, Peoples R China. NR 33 TC 36 Z9 48 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB PY 2003 VL 32 IS 2 BP 124 EP 130 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 643BU UT WOS:000180842700002 PM 12571520 ER PT J AU Coletti, AS Heagerty, P Sheon, AR Gross, M Koblin, BA Metzger, DS Seage, GR AF Coletti, AS Heagerty, P Sheon, AR Gross, M Koblin, BA Metzger, DS Seage, GR CA HIVNET VPS Protocol Team TI Randomized, controlled evaluation of a prototype informed consent process for HIV vaccine efficacy trials SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE informed consent; HIV; HIV vaccines; randomized trial; high-risk populations ID PREVENTING DISCRIMINATION; CLINICAL-TRIALS; VOLUNTEERS; CANCER; PARTICIPANTS; RISK AB Procedures must be developed to ensure that valid informed consent is obtained from participants in HIV vaccine efficacy trials. A prototype informed consent process was evaluated among 4,892 persons at high risk for HIV infection in the HIV Network for Prevention Trials Vaccine Preparedness Study (VPS), a prospective cohort study of HIV seroincidence in eight U.S. metropolitan areas. Twenty percent of VPS participants were selected at random to undergo the prototype informed consent process at VPS month 3. Participants' knowledge of 10 key HIV vaccine trial concepts and willingness to participate in HIV vaccine efficacy trials were assessed and compared at baseline and semiannually thereafter for 18 months. Knowledge of HIV vaccine trial concepts was low at baseline. Participation in the prototype process was associated with substantial and sustained increases in knowledge (relative risks for the 10 items, 1.04-2.26), which were of similar magnitude across HIV risk groups, race/ethnicity, and educational levels. It is recommended that the prototype informed consent process be adopted for future HIV vaccine efficacy trials as well as for clinical trials in other research areas. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Family Hlth Int, Res Triangle Pk, NC 27709 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NIAID, Washington, DC USA. New York Blood Ctr, New York, NY 10021 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Seage, GR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [N01-AI-45200, N01-AI-35176] NR 43 TC 43 Z9 43 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB PY 2003 VL 32 IS 2 BP 161 EP 169 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 643BU UT WOS:000180842700008 PM 12571526 ER PT J AU Bardeguez, AD Shapiro, DE Mofenson, LM Coombs, R Frenkel, LM Fowler, MG Huang, S Sperling, RS Cunningham, B Gandia, J Maupin, R Zorrilla, CD Jones, T O'Sullivan, MJ AF Bardeguez, AD Shapiro, DE Mofenson, LM Coombs, R Frenkel, LM Fowler, MG Huang, S Sperling, RS Cunningham, B Gandia, J Maupin, R Zorrilla, CD Jones, T O'Sullivan, MJ CA Pediat AIDS Clinical Trials Grp 28 TI Effect of cessation of zidovudine prophylaxis to reduce vertical transmission on maternal HIV disease progression and survival SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE women; PACTG 076 protocol; genotypic resistance; disease progression; antiretroviral therapy; ZDV chemoprophylaxis; perinatal transmission ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOTHER-TO-INFANT; TYPE-1 RNA; VIRAL LOAD; INFECTED WOMEN; RESISTANCE; AIDS; MUTATIONS; THERAPY; PLASMA AB Zidovudine prophylaxis is recommended to reduce perinatal HIV-1 transmission, but there are limited data on long-term effects on women's health. Pediatrics AIDS Clinical Trials Group (PACTG) 288 was a prospective observational study among US women randomized to zidovudine or placebo in PACTG 076 that was designed to evaluate and compare postpartum clinical, immune, and viral parameters between randomized treatment arms. Forty-eight percent (226/474) of eligible women enrolled in the study (mean follow-up of 4.1 years). Progression and time to AIDS or death were similar in both groups, observed in 21 (19%) zidovudine group women and 29 (25%) placebo group women (RR = 0.73, 90% CI: 0.46-1.17). No significant differences in CD4(+) lymphocyte count or HIV RNA levels were detected. Genotypic zidovudine resistance was detected in 10% of 156 women (9% of zidovudine group women and 11% of placebo group women). Based on our data, ZDV monotherapy could be considered as chemoprophylaxis to reduce perinatal HIV transmission for minimally symptomatic HIV-infected pregnant women with a low viral load and normal CD4(+) cell count who do not want to receive highly active antiretroviral therapy because of concern about potential side effects or who wish to reduce fetal exposure to multiple drugs during pregnancy. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet Gynecol & Womens Hlth, MSB, Newark, NJ 07103 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NICHHD, Rockville, MD USA. Univ Washington, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Mt Sinai Sch Med, New York, NY USA. Merck Pharmaceut Co, Whitehouse Stn, NJ USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. San Juan City Hosp, San Juan, PR USA. Louisiana State Univ Hlth Sci, New Orleans, LA USA. Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Univ Miami, Sch Med, Miami, FL 33152 USA. RP Bardeguez, AD (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet Gynecol & Womens Hlth, MSB, E-506,185 S Orange Ave, Newark, NJ 07103 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 28 TC 23 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB PY 2003 VL 32 IS 2 BP 170 EP 181 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 643BU UT WOS:000180842700009 PM 12571527 ER PT J AU Chulada, PC Arbes, SJ Dunson, D Zeldin, DC AF Chulada, PC Arbes, SJ Dunson, D Zeldin, DC TI Breast-feeding and the prevalence of asthma and wheeze in children: Analyses from the Third National Health and Nutrition Examination Survey, 1988-1994 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; recurrent wheeze; breast-feeding; atopy; environmental tobacco smoke; National Health and Nutrition Examination; Survey III ID ENVIRONMENTAL TOBACCO-SMOKE; DAY-CARE ATTENDANCE; CHILDHOOD ASTHMA; MATERNAL SMOKING; PARENTAL SMOKING; YOUNG-CHILDREN; LUNG-FUNCTION; 1ST YEAR; LIFE; ASSOCIATION AB Background: Asthma prevalence has increased dramatically in recent years, especially among children. Breast-feeding might protect children against asthma and related conditions (recurrent wheeze), and this protective effect might depend on the duration and exclusivity of the breast-feeding regimen. Objective: We sought to determine whether there is an association between breast-feeding and asthma, recurrent wheeze, or both in children up to 72 months of age and whether the duration and exclusivity of breast-feeding affect this association. Methods: Data were from the third National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey conducted from 1988 to 1994. We tested for significant associations between breast-feeding and physician-diagnosed asthma and recurrent wheeze (>3 episodes in the past 12 months) before and after adjusting for potential confounders. Results: Crude analyses showed that breast-feeding was associated with significantly reduced risks for asthma and recurrent wheeze in children 2 to 71 months of age, but after adjusting for potential confounders, these overall protective associations attenuated and were no longer statistically significant. However, 2 new and important associations were revealed after adjusting for confounders: (1) compared with never breast-fed children, ever breast-fed children had significantly reduced odds of being diagnosed with asthma and of having recurrent wheeze before 24 months of age, and (2) among children 2 to 71 months of age who had been exposed to environmental tobacco smoke, those who had ever been breast-fed had significantly reduced risks of asthma and wheeze compared with those who had never been breast-fed. Conclusions: Breast-feeding might delay the onset of or actively protect children less than 24 months of age against asthma and recurrent wheeze. Breast-feeding might reduce the prevalence of asthma and recurrent wheeze in children exposed to environmental tobacco smoke. (J Allergy Clin Immunol 2003;111:328-36.). C1 NIEHS, Off Clin Res, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Chulada, PC (reprint author), NIEHS, Off Clin Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 43 TC 66 Z9 72 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2003 VL 111 IS 2 BP 328 EP 336 DI 10.1067/mai.2003.127 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 644WF UT WOS:000180942700017 PM 12589353 ER PT J AU Jirapongsananuruk, O Malech, HL Kuhns, DB Niemela, JE Brown, MR Anderson-Cohen, M Fleisher, TA AF Jirapongsananuruk, O Malech, HL Kuhns, DB Niemela, JE Brown, MR Anderson-Cohen, M Fleisher, TA TI Diagnostic paradigm for evaluation of male patients with chronic granulomatous disease, based on the dihydrorhodamine 123 assay SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE chronic granulomatous disease; CGD; CYBB; diydrorhodamine assay; DHR; gp91(phox); immune deficiency; mutation analysis; phagocyte defect ID RESPIRATORY BURST; MUTATIONS AB Background: Chronic granulomatous disease (CGD) is a phagocyte disorder caused by mutations in nicotinamide dinucleotide phosphate (NADPH) oxidase subunits. The dihydrorhodamine 123 (DHR) assay is an effective test for CGD that for most patients also might help to differentiate between the 2 most common forms, X-linked (X) gp91(phox) defect CGD and autosomal recessive (AR) p47(phox) defect CGD. However, some male patients with X-CGD have DHR patterns that overlap the AR-CGD pattern. Objective: The purpose of this investigation was to develop a diagnostic paradigm to delineate male patients with X-CGD expressing a DHR pattern suggestive of p47(phox) deficiency. Methods: The DHR assay measured change in fluorescence of DHR-loaded granulocytes after phorbol myristate acetate (PMA) stimulation. Western blot analysis measured the presence of NADPH oxidase subunits gp91(phox), p47(phox), p67(phox), and p22(phox). CYBB exonic sequencing was performed on PCR-amplified genomic DNA through use of intronic flanking primers. Ferricytochrome-c assay evaluated specific superoxide production by PMA-stimulated granulocytes. Results: Although 83% of patients with X-CGD have virtually no neutrophil DHR activity, we found that 17% of patients, proven to have X-CGD by other criteria, have modest DHR activity that is most consistent with p47(phox) deficiency. We describe a diagnostic paradigm to deal with such patients, and we present 2 cases, along with results of additional studies, including carrier evaluation, protein assessment, and mutation analysis, that are useful in establishing the genotype under these circumstances. DHR assays from the 2 patients described showed a fluorescence shift most characteristic of p47(phox)-AR-CGD; however, each of the patients' mothers showed mosaicism with a bimodal DHR pattern. Patient 1 had some gp91(phox) protein with a Y41D mutation and modest superoxide activity. Patient 2 had a normal level of gp91(phox) protein with a C537R mutation without detectable superoxide activity, as determined by ferricytochrome-c assay, despite the modest DHR activity. Conclusions: Evaluation of male patients with CGD with modest DHR activity should initially include evaluation of potential female carriers for mosaicism with the use of the DHR assay. In circumstances in which this is uninformative, patients should be referred to centers capable of additional testing, including Western blot analysis and CYBB mutation analysis, to clarify the disease genotype. C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Clin Serv Program, Frederick, MD 21701 USA. RP Fleisher, TA (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bldg 10,Room 2C-306,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. OI Niemela, Julie/0000-0003-4197-3792; Malech, Harry/0000-0001-5874-5775 NR 13 TC 45 Z9 53 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 FEB PY 2003 VL 111 IS 2 BP 374 EP 379 DI 10.1067/mai.2003.58 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 644WF UT WOS:000180942700023 PM 12589359 ER PT J AU Arbes, SJ Cohn, RD Yin, M Muilenberg, ML Burge, HA Friedman, W Zeldin, DC AF Arbes, SJ Cohn, RD Yin, M Muilenberg, ML Burge, HA Friedman, W Zeldin, DC TI House dust mite allergen in US beds: Results from the first National Survey of Lead and Allergens in Housing SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT 97th International Conference of the American-Thoracic-Society CY MAY 18-23, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Thorac Soc DE house dust mite allergen; indoor allergens; surveys; epidemiology ID REDUCING RELATIVE-HUMIDITY; DER-P-I; INDOOR ALLERGENS; RISK FACTOR; AVOIDANCE MEASURES; SEASONAL-VARIATION; ASTHMATIC-PATIENTS; CHILDHOOD ASTHMA; GRASS-POLLEN; EXPOSURE AB Background: Although exposure to house dust mite allergen is a major risk factor for allergic sensitization and asthma, nationwide estimates of dust mite allergen levels in US homes have not been reported. Objective: The purpose of this study was to estimate the prevalence of dust mite allergen in beds of US homes and to identify predictors of dust mite allergen concentration. Methods: Data were obtained from the first National Survey of Lead and Allergens in Housing, a cross-sectional survey of 831 permanently occupied noninstitutional housing units that permitted resident children. Dust mite allergen concentration (Der f 1 plus Der p 1) was determined from a dust sample collected from a bed. The percentages of homes with concentrations at or greater than detection, 2.0 mug/g bed dust, and 10.0 mug/g bed dust were estimated. Independent predictors of allergen concentration were assessed with multivariable linear regression. Results: The percentages of US homes with dust mite allergen concentrations at or greater than detection, 2.0 mug/g, and 10.0 mug/g were 84.2% (SE, 1.73), 46.2% (SE, 2.0), and 24.2% (SE, 2.1), respectively. Independent predictors of higher levels were older homes, non-West census regions, single-family homes, no resident children, lower household income, heating sources other than forced air, musty or mildew odor, and higher bedroom humidity. Conclusion: Most US homes have detectable levels of dust mite allergen in a bed. Levels previously associated with allergic sensitization and asthma are common in US bedrooms. Predictors can be used to identify conditions under which homes are more likely to have increased dust mite allergen levels. C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Analyt Sci, Durham, NC USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. US Dept Housing & Urban Dev, Off Healthy Homes & Lead Hazard Control, Washington, DC USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, 111 Alexander Dr,Mail Drop D2-01, Res Triangle Pk, NC 27709 USA. NR 49 TC 74 Z9 78 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 FEB PY 2003 VL 111 IS 2 BP 408 EP 414 DI 10.1067/mai.2003.16 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 644WF UT WOS:000180942700028 PM 12589364 ER PT J AU Pechhold, K Karges, W Blum, C Boehm, BO Harlan, DM AF Pechhold, K Karges, W Blum, C Boehm, BO Harlan, DM TI Beta cell-specific CD80 (B7-1) expression disrupts tissue protection from autoantigen-specific CTL-mediated diabetes SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE autoimmune diabetes; costimulatory molecules; genetic immunization; intracytoplasmic cytokine staining; islet-infiltrating lymphocytes ID MHC CLASS-I; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; ANTIGEN-PRESENTING CELLS; CYTOTOXIC T-LYMPHOCYTES; NECROSIS-FACTOR-ALPHA; TRANSGENIC MICE; INFLAMMATORY CYTOKINES; COSTIMULATOR B7-1; VIRAL-INFECTION; DENDRITIC CELLS AB T cell responses toward pancreatic beta cell autoantigens arise spontaneously or on immunization in many mouse strains, yet sustained islet infiltration and progressive diabetes rarely ensues. Most mouse diabetes models overcome the innocuous coexistence of anti-islet specific T cells and endogenous islets via incompletely understood mechanisms (e.g. the spontaneous disease onset of the non-obese diabetic mouse) or depend on overwhelming numbers of peripheral islet-specific T cells. We report that insulin promoter murine CD80 (RIP-CD80) transgenic mice are extraordinarily susceptible to autoantigen-induced diabetes, while spontaneous disease is rare. Autoimmunity to the pancreatic beta cell-expressed glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV) was elicited by a single injection of syngeneic fibroblastoid cell lines (FCL) loaded with the immunodominant LCMV-GP peptide, gp33. While both RIP-GP(+) and RIP-CD80(+)GP(+) mice mounted moderate CD4-independent CTL responses, only CD80(+)GP(+) mice developed severe insulitis and diabetes due to islet-infiltration of activated, gp33-specific, CD8(+) T cells. Strikingly, DNA immunization using plasmids encoding LCMV-GP or murine preproinsulin also efficiently induced Ag-specific RIP-CD80-dependent diabetes. We conclude that aberrant CD80-expression in a peripheral tissue disrupts that tissue's natural resistance to CD8 T cell-mediated autoimmune destruction. This rodent model thus represents a novel approach to identify beta cell-derived autoantigenic determinants involved in the pathogenesis of autoimmune diabetes, and may also serve as a prototype approach to uncover relevant autoantigens leading to a variety of organ-specific autoimmune disorders. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Transplantat & Autoimmun Branch, NNMC, AFRRI, Bethesda, MD 20889 USA. Univ Ulm, Dept Internal Med 1, D-7900 Ulm, Germany. RP Pechhold, K (reprint author), NIDDK, Transplantat & Autoimmun Branch, NNMC, AFRRI, NNMC AFRRI Bldg 46,Room 2417,8901 Wisconsin Ave, Bethesda, MD 20889 USA. RI Boehm, Bernhard/F-8750-2015 NR 61 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD FEB PY 2003 VL 20 IS 1 BP 1 EP 13 DI 10.1016/S0896-8411(02)00105-1 PG 13 WC Immunology SC Immunology GA 650ZB UT WOS:000181293800001 PM 12604308 ER PT J AU Schwan, TG Battisti, JM Porcella, SF Raffel, SJ Schrumpf, ME Fischer, ER Carroll, JA Stewart, PE Rosa, P Somerville, GA AF Schwan, TG Battisti, JM Porcella, SF Raffel, SJ Schrumpf, ME Fischer, ER Carroll, JA Stewart, PE Rosa, P Somerville, GA TI Glycerol-3-phosphate acquisition in spirochetes: Distribution and biological activity of glycerophosphodiester phosphodiesterase (GlpQ) among Borrelia species SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; MICE PEROMYSCUS-LEUCOPUS; BORNE RELAPSING FEVER; MIYAMOTOI SP-NOV; HAEMOPHILUS-INFLUENZAE; BOOPHILUS-MICROPLUS; BURGDORFERI; TICK; TREPONEMA; AGENT AB Relapsing-fever spirochetes achieve high cell densities (>10(8)/ml) in their host's blue, while Lye disease spirochetes do not (<10(5)/ml). This striking contrast in pathogenicity of these two groups of bacteria suggests a fundamental difference in their ability tat either exploit or survive in blood. Borrelia hermsii, a tick-borne relapsing-fever spirochete, contains orthologs to glpQ and glpT, genes that encode glycerophosphodiester phosphodiesterase (GlpQ) and glycerol-3-phosphate transporter (GlpT), respectively. In other bacteria, GlpQ hydrolyzes deacylated phospholipids to glycerol-3-phosphate (GP) while GlpT transports G3P into the cytoplasm. Enzyme assays on 17 isolates of borreliae demonstrated GlpQ activity relapsing-fever spirochetes but not in Lyme disease spirochetes. Southern blots demonstrated glpQ and glpT in all relapsing-fever spirochetes but not in the ye disease group. A Lye disease spirochete, Borrelia burgdorferi, that was transformed with a shuttle rector containing glpTQ front B. hermsii produced active enzyme, which demonstrated the association of glpQ with the hydrolysis of phospholipids. Sequence analysis of B. hermsii identified glpF, glpK, ana glpA, which encode the glycerol facilitator, glycerol kinase, and glycerol-3-phosphate dehydrogenase, respectively, all of which are present in B. burgdorferi. All spirochetes mined had gpsA, which encodes the enzyme that reduces dihydroxyacetone phosphate (DHAP) to G3P. Consequently, three pathways for the acquisition of G3P exist among borreliae. (I) hydrolysis of deacylated phospholipids, (ii) reduction of DID, and (ill) uptake and phosphorylation of glycerol. The unique ability of relapsing-fever spirochetes to hydrolyze phospolipids may contribute to their higher cell densities in blood than those of Lyme disease spirochetes. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Microscopy Branch, NIH, Hamilton, MT 59840 USA. RP Schwan, TG (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. RI Somerville, Greg/B-1326-2013 OI Somerville, Greg/0000-0002-0991-8737 NR 50 TC 38 Z9 39 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2003 VL 185 IS 4 BP 1346 EP 1356 DI 10.1128/JB.185.4.1346-1356.2003 PG 11 WC Microbiology SC Microbiology GA 645GB UT WOS:000180966900026 PM 12562805 ER PT J AU Ouatas, T Salerno, M Palmieri, D Steeg, PS AF Ouatas, T Salerno, M Palmieri, D Steeg, PS TI Basic and translational advances in cancer metastasis: Nm23 SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Nm23; metastasis; suppressor; breast ID NUCLEOSIDE-DIPHOSPHATE KINASE; HUMAN BREAST-CARCINOMA; MEDIATED SIGNAL-TRANSDUCTION; SUPPRESSOR GENE-EXPRESSION; SQUAMOUS-CELL CARCINOMA; TUMOR-METASTASIS; PHOSPHOTRANSFERASE ACTIVITY; DROSOPHILA DEVELOPMENT; ADENOCARCINOMA CELLS; ENZYMATIC-ACTIVITY AB Cancer metastasis is a significant contributor to breast cancer patient morbidity and mortality. To develop new anti-metastatic therapies, we need to understand the biological and biochemical mechanisms of metastasis. Toward these efforts, we and others have studied metastasis suppressor genes, which halt metastasis in vivo without affecting primary tumor growth. The first metastasis suppressor gene confirmed was nm23, also known as NDP kinase. Using in vitro assays, nm23 overexpression resulted in reduced anchorage-independent colonization in response to TGF-beta, reduced invasion and motility in response to multiple factors, and increased differentiation. We hypothesize that the mechanism of action of Nm23 in metastasis suppression involves diminished signal transduction, downstream of a particular receptor. We hypothesize that a histidine protein kinase activity of Nm23 underlies its suppression of metastasis, and identify candidate substrates. This review also discusses therapeutic options on the basis of reexpression of metastasis suppressors. C1 NCI, Womens Canc Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Ouatas, T (reprint author), NCI, Womens Canc Sect, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. RI Palmieri, Diane/B-4258-2015 NR 69 TC 85 Z9 87 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD FEB PY 2003 VL 35 IS 1 BP 73 EP 79 DI 10.1023/A:1023497924277 PG 7 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 668WU UT WOS:000182318800010 PM 12848344 ER PT J AU Reddi, AH Roodman, D Freeman, C Mohla, S AF Reddi, AH Roodman, D Freeman, C Mohla, S TI Mechanisms of tumor metastasis to the bone: Challenges and opportunities SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Review DE prostate; breast; myeloma; bone morphogenetic proteins; parathyroid hormone ID PROSTATE-CANCER; CELL-SURVIVAL; IN-VITRO; GROWTH; DIFFERENTIATION; DESTRUCTION; EXPRESSION; INVASION; BIOLOGY; MODEL AB In human cancers, bone is a common site for metastasis. It is well known that metastasis is the cause of morbidity and mortality in patients with cancer. Both breast and prostate carcinomas have a propensity to metastasize to bone. In general, metastatic breast cancers result in osteolytic lesions. On the other hand, prostate cancer metastases are osteoblastic and result in osteosclerosis. Thus, bone formation and bone resorption are at the crux of the cancer metastasis problem. For example, in the prostate, there is a vicious cycle of metastasis to bone (Fig. 1). Metastases to bone causes excruciating bone pain, pathological fractures, and eventually death, and therefore is a serious challenge to both bone biologists and cancer cell biologists. The stromal-epithelial interactions in breast and prostate are critical in initiation of carcinogenesis and the progression of the metastatic cascade to bone (Fig. 2). Over a hundred years ago, Stephen Paget enunciated the seed and soil hypothesis in which seeds of metastatic cancer cells of breast preferentially settle in the soil of bone matrix. Thus, the prostate/breast cancer bone interface and continuum has continuously presented challenges and opportunities and were discussed at a recent workshop. C1 Univ Calif Davis, Sch Med, Ctr Tissue Regenerat & Repair, Sacramento, CA 95817 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NCI, Div Canc Biol, NIH, Bethesda, MD 20892 USA. RP Reddi, AH (reprint author), Univ Calif Davis, Sch Med, Ctr Tissue Regenerat & Repair, 4635 2nd Ave,Res Bldg 1,Room 200, Sacramento, CA 95817 USA. NR 30 TC 68 Z9 70 U1 0 U2 5 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2003 VL 18 IS 2 BP 190 EP 194 DI 10.1359/jbmr.2003.18.2.190 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 637ZU UT WOS:000180544200003 PM 12568395 ER PT J AU Marini, JC Hopkins, E Glorieux, FH Chrousos, GP Reynolds, JC Gundberg, CM Reing, CM AF Marini, JC Hopkins, E Glorieux, FH Chrousos, GP Reynolds, JC Gundberg, CM Reing, CM TI Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: High predictive value of the carboxyterminal propeptide of type I procollagen SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteogenesis imperfecta; growth hormone; histomorphometry; DXA; carboxyterminal propeptide ID HEALTHY-CHILDREN; TURNER-SYNDROME; HISTOMORPHOMETRY; HETEROGENEITY; OSTEOCALCIN; THERAPY; STATURE; HEIGHT; AXIS AB Extreme short stature is a cardinal feature of severe osteogenesis imperfecta (OI), types III and IV. We conducted a treatment trial of growth hormone in children with OI and followed linear growth velocity, bone metabolism markers, histomorphometrics, and vertebral bone density. Twenty-six children with types III and IV OI, ages 4.5-12 years, were treated with recombinant growth hormone (rGH), 0.1-0.2 IU/kg per day for 6 days/week, for at least 1 year. Length, insulin-like growth factor (IGF-I), insulin-like growth factor binding protein (IGFBP-3), bone metabolic markers, and vertebral bone density by DXA were evaluated at 6-month intervals. An iliac crest biopsy was obtained at baseline and 12 months. Approximately one-half of the treated OI children sustained a 50% or more increase in linear growth over their baseline growth rate. Most responders (10 of 14) had moderate type IV OI. All participants had positive IGF-I, IGFBP-3, osteocalcin, and bone-specific alkaline phosphatase responses. Only the linear growth responders had a significant increase in vertebral DXA z-score and a significant decrease in long bone fractures. After 1 year of treatment, responders' iliac crest biopsy showed significant increases in cancellous bone volume, trabecular number, and bone formation rate. Responders were distinguished from nonresponders by higher baseline carboxyterminal propeptide (PICP) values (p < 0.05), suggesting they have in intrinsically higher capacity for collagen production. The results show that growth hormone can cause a sustained increase in the linear growth rate of children with OI, despite the abnormal collagen in their bone matrix. In the first year of treatment, growth responders achieve increased bone formation rate and density, and decreased fracture rates. The baseline plasma concentration of PICP was an excellent predictor of positive response. C1 NICHD, Sect Connect Tissue Disorders, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. NIH, Nucl Med Dept, Ctr Clin, Bethesda, MD 20892 USA. Yale Univ, Dept Orthopaed, New Haven, CT USA. Fairfax Hosp, INOVA, Dept Orthoped Surg, Fairfax, VA USA. RP Marini, JC (reprint author), NICHD, Sect Connect Tissue Disorders, Heritable Disorders Branch, NIH, Bldg 10,Rm 9S241,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2003 VL 18 IS 2 BP 237 EP 243 DI 10.1359/jbmr.2003.18.2.237 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 637ZU UT WOS:000180544200009 PM 12568401 ER PT J AU Xing, LP Carlson, L Story, B Tai, ZX Keng, P Siebenlist, U Boyce, BF AF Xing, LP Carlson, L Story, B Tai, ZX Keng, P Siebenlist, U Boyce, BF TI Expression of either NF-kB p50 or p52 in osteoclast precursors is required for IL-1-induced bone resorption SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE interleukin 1; NF-KB; osteoclast; bone resorption; cytokine ID TUMOR-NECROSIS-FACTOR; KAPPA-B; TRANSCRIPTION FACTOR; EMBRYONIC LETHALITY; SURVIVAL FACTOR; MESSENGER-RNA; MICE LACKING; IN-VIVO; CELLS; INTERLEUKIN-1 AB Interleukin (IL)-1 is implicated in postmenopausal- and inflammation-mediated bone loss. Its expression is regulated by NF-kappaB and vice versa. To examine the role of NF-kappaB p50 and p52 (they are required for osteoclast formation during embryonic development) in IL-1-induced resorption, we used various NF-kappaB knockout (KO) mice, including p50(-/-) and p52(-/-) single KO, p50(-/-) and p52(+/-) (3/4KO), and p50(-/-) and p52(-/-) double KO (dKO) mice. IL-1 increased blood calcium and bone resorption in wild-type (wt), p50, and p52 single KO mice, but not in 3/4KO or dKO mice. Osteoclast formation was impaired in bone marrow cultures from 3/4KO compared with single KO and wt mice treated with IL-1. IL-1 receptor expression was similar in colony forming unit-granulocyte macrophage (CFU-GM) colony cells from wt and dKO mice. However, IL-1 promoted CFU-GM colony formation and survival as well as the formation, activity, and survival of osteoclasts generated from these colonies from wt mouse splenocytes, but not from dKO splenocytes. No difference in expression of the osteoclast regulatory cytokines, RANKL, and OPG, was observed in osteoblasts from wt and dKO mice. Thus, expression of either NF-kappaB p50 or p52 is required in osteoclasts and their precursors, rather than osteoblasts, for IL-1-mediated bone resorption. C1 Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Rochester, Med Ctr, Ctr Canc, Rochester, NY 14642 USA. RP Boyce, BF (reprint author), Univ Rochester, Med Ctr, Dept Pathol, Box 626,601 Elmwood Ave, Rochester, NY 14642 USA. FU NIAMS NIH HHS [AR43510] NR 46 TC 36 Z9 45 U1 2 U2 3 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2003 VL 18 IS 2 BP 260 EP 269 DI 10.1359/jbmr.2003.18.2.260 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 637ZU UT WOS:000180544200011 PM 12568403 ER PT J AU Lader, E Egan, D Hunsberger, S Garg, R Czajkowski, S McSherry, F AF Lader, E Egan, D Hunsberger, S Garg, R Czajkowski, S McSherry, F TI The effect of digoxin on the quality of life in patients with heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE exercise tolerance; 6-minute walk test; DIG trial ID OF-LIFE; EXERCISE CAPACITY; TRIAL; PLACEBO; WITHDRAWAL; ENALAPRIL AB Background: The Digitalis Investigation Group (DIG) trial was a randomized double-blind placebo-controlled study that examined the effect of digoxin on mortality in 7,788 patients with heart failure and sinus rhythm. A prespecified substudy evaluated the effect of digoxin therapy on health-related quality of life (HQOL) in a subset of these patients. Methods: Patients in the DIG trial had clinical heart failure and were randomized to either digoxin or placebo in addition to their baseline diuretic and angiotensin-converting enzyme therapy (n = 7,788). The patients in this substudy had HQCL measured using a self-administered questionnaire employing scales that measured general health, physical functioning, depression, anger, anxiety, life satisfaction, and disease specific measures. A subjective assessment by the investigator and a 6-minute walk test evaluated functional status. HQOL was measured at baseline and at the 4- and 12-month follow-up visits. Results: The baseline characteristics of the patients in the quality of life substudy (n = 589) were comparable to the remaining patients in the study (n = 7,199) by age and other clinical measures, including history of prior myocardial infarction or etiology of heart failure; heart failure was of shorter duration and the ejection fraction was slightly better than in the main trial. Within the substudy, patients receiving digoxin (n = 298) or placebo (n = 291) were also similar in baseline characteristics. There was no statistically significant difference in any HQOL measure between the digoxin and the placebo groups at baseline. At the 4-month visit, only perceived health was improved in the digoxin group. At 12 months, there was no statistically significant difference in perceived health, physical functioning, Minnesota Living with Heart Failure, depression, anxiety, anger, Ladder of Life, or the 6-minute walk between the digoxin and placebo groups. Conclusion: In this subset of the DIG population, digoxin therapy had no effect on the HQOL in patients with heart failure in sinus rhythm. C1 NYU, Sch Med, New York, NY USA. NHLBI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Perry Point VA Med Ctr, Perry Point, MD USA. RP Lader, E (reprint author), Cooperat Studies Program Coordinating Ctr, POB 1010, Perry Point, MD 21902 USA. NR 38 TC 29 Z9 30 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD FEB PY 2003 VL 9 IS 1 BP 4 EP 12 DI 10.1054/jcaf.2003.7 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 652HL UT WOS:000181373700002 PM 12612867 ER PT J AU Fishman, PH Orlandi, PA AF Fishman, PH Orlandi, PA TI Cholera toxin internalization and intoxication SO JOURNAL OF CELL SCIENCE LA English DT Letter ID GPI-ANCHORED PROTEINS; PLASMA-MEMBRANE; CELL-SURFACE; CAVEOLAE; ACTIVATION; MECHANISM; DOMAINS; DYNAMIN C1 NIH, Bethesda, MD 20892 USA. US FDA, Washington, DC 20204 USA. RP Fishman, PH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 13 TC 6 Z9 7 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB 1 PY 2003 VL 116 IS 3 BP 431 EP 432 DI 10.1242/jcs.00199 PG 2 WC Cell Biology SC Cell Biology GA 645VC UT WOS:000180999400001 PM 12508102 ER PT J AU Carson, RE Wu, YJ Lang, LX Ma, Y Der, MG Herscovitch, P Eckelman, WC AF Carson, RE Wu, YJ Lang, LX Ma, Y Der, MG Herscovitch, P Eckelman, WC TI Brain uptake of the acid metabolites of F-18-labeled WAY 100635 analogs SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE acid; metabolite; compartment modeling; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; INJECTION PET DATA; F-18 ALTANSERIN; RADIOLABELED METABOLITES; RADIOACTIVE METABOLITES; SKELETAL KINETICS; QUANTITATION; BINDING; BOLUS; WAY-100635 AB The 5-HT1A ligands [F-18]FPWAY and [F-18]FCWAY are metabolized in vivo to [F-18]fluorobenzoic acid (FB) and [F-18]fluorocyclohexanecarboxylic acid (FC), respectively. To quantify the penetration of these acids into the brain, dynamic positron emission tomography studies were performed in rhesus monkeys with [F-18]FB and [F-18]FC. High-performance liquid chromatography analysis of arterial blood samples showed no metabolites for [F-18]FB, whereas [F-18]FC was rapidly metabolized to [F-18]fluoride. A model with one tissue compartment and vascular radioactivity was used to analyze gray matter time-activity curves. For [F-18]FC, an additional term was added to account for [F-18]fluoride skull spillover into the brain; this term accounted for 70% to 90% of the measured radioactivity concentration at 90 minutes. For [F-18]FB, mean gray matter parameters were as follows: K-1, 10 +/- 3 muL . min(-1) . mL(-1); distribution volume V, 0.052 +/- 0.006 (mL/mL). For [F-18]FC, the values were as follows: K-1, 15 +/- 4 muL . min(-1) . mL(-1); V, 0.29 +/- 0.06 mL/mL. The V values were consistent with a physiologic model that included brain-to-blood pH difference and the plasma free fraction of the acid. Simulations based on [F-18]FCWAY human data showed that [F-18]FC uptake produces significant biases in V estimates in regions with low specific binding. These results can be used to correct the tissue [F-18]FCWAY time-activity data for brain uptake of [F-18]FC using the measured [F-18]FC input function. C1 NIH, PET Dept, WG Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Carson, RE (reprint author), NIH, PET Dept, WG Magnuson Clin Ctr, Bldg 10,Room 1C-401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 37 TC 34 Z9 34 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 2003 VL 23 IS 2 BP 249 EP 260 DI 10.1097/01.WCB.0000046145.31247.7A PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 643ZQ UT WOS:000180893800012 PM 12571456 ER PT J AU Dagdug, L Berezhkovskii, A Bezrukov, SM Weiss, GH AF Dagdug, L Berezhkovskii, A Bezrukov, SM Weiss, GH TI Diffusion-controlled reactions with a binding site hidden in a channel SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID LIGAND-BINDING; RECEPTORS AB The rate of a diffusion-controlled reaction with a buried binding site is smaller than the rate for the same site on the surface. We study the slowdown of the reaction rate when the site is hidden in a pore that connects two bulk media. On the assumption that the pore is cylindrical we derive an expression for the Laplace transform of the rate coefficient from which we infer the long-time limit of the reaction rate. This provides information on how the reaction rate depends on the channel radius, the location of the site, and the diffusion constant in the pore, which is allowed to differ from that in the bulk. The validity of approximations was checked by simulations that indicated excellent agreement between the analytical and and numerical results. (C) 2003 American Institute of Physics. C1 Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. Karpov Inst Phys Chem, Moscow 103064, Russia. RP Dagdug, L (reprint author), Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. NR 19 TC 10 Z9 10 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD FEB 1 PY 2003 VL 118 IS 5 BP 2367 EP 2373 DI 10.1063/1.1533061 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 638PR UT WOS:000180579900039 ER PT J AU Eisenhofer, G AF Eisenhofer, G TI Editorial: Biochemical diagnosis of pheochromocytoma - Is it time to switch to plasma-free metanephrines? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CATECHOLAMINE C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Eisenhofer, G (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 10,Room 6N252, Bethesda, MD 20892 USA. EM graeme@catecholamine.org NR 14 TC 36 Z9 36 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2003 VL 88 IS 2 BP 550 EP 552 DI 10.1210/jc.2002-021913 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 644JZ UT WOS:000180915300008 PM 12574178 ER PT J AU Gourgiotis, L Sarlis, NJ Reynolds, JC Vanwaes, C Merino, MJ Pacak, K AF Gourgiotis, L Sarlis, NJ Reynolds, JC Vanwaes, C Merino, MJ Pacak, K TI Localization of medullary thyroid carcinoma metastasis in a multiple endocrine neoplasia type 2A patient by 6-[F-18]-fluorodopamine positron emission tomography SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NEUROENDOCRINE TUMORS; PHEOCHROMOCYTOMA; CANCER; IMMUNOSCINTIGRAPHY; SCINTIGRAPHY; MIBG AB 6-[F-18]fluorodopamine, a substrate for the norepinephrine transporter, has been used as a tumor-seeking tracer in positron emission tomography (PET) to localize pheochromocytomas and other chromaffin tumors. Here, we report the case of a 42-yr-old woman with multiple endocrine neoplasia type 2A, in whom biopsy-proven recurrent medullary thyroid cancer (MTC) was detected by 6-[F-18]fluorodopamine PET scanning. The patient had previously undergone bilateral adrenalectomy for pheochromocytoma, total thyroidectomy, and extirpation of a parapharyngeal MTC metastatic deposit. An increase in plasma calcitonin 5 yr after her initial presentation was further investigated, leading to the discovery of a mass in the left parapharyngeal space. Levels of serum and urine catecholamines and metanephrines were normal. To exclude a hormonally silent pheochromocytoma metastasis, 6-[F-18]fluorodopamine PET was performed. The study showed a focus of radionuclide accumulation corresponding to the parapharyngeal mass. After resection of the latter, pathology confirmed metastatic MTC. To our knowledge, this is the first case of metastatic, histologically proven MTC, which was unequivocally detected by 6-[F-18]fluorodopamine PET scanning. Because norepinephrine transporter systems have been previously found in MTC, it is conceivable that 6-[F-18]fluorodopamine PET scanning can be used for the diagnostic localization of this tumor and its metastatic deposits because total and early resection is beneficial to the outcome of the patient. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. Natl Inst Commun Disorders & Deafness, Off Clin Director, Bethesda, MD 20892 USA. NICHD, Pathol Lab, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM karel@mail.nih.gov NR 23 TC 35 Z9 34 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 FEB PY 2003 VL 88 IS 2 BP 637 EP 641 DI 10.1210/jc.2002-021354 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 644JZ UT WOS:000180915300023 PM 12574193 ER PT J AU Woods, GL Williams-Bouyer, N Wallace, RJ Brown-Elliott, BA Witebsky, FG Conville, PS Plaunt, M Hall, G Aralar, P Inderlied, C AF Woods, GL Williams-Bouyer, N Wallace, RJ Brown-Elliott, BA Witebsky, FG Conville, PS Plaunt, M Hall, G Aralar, P Inderlied, C TI Multisite reproducibility of results obtained by two broth dilution methods for susceptibility testing of Mycobacterium avium complex SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LUNG-DISEASE; NONTUBERCULOUS MYCOBACTERIA; AIDS PATIENTS; DOUBLE-BLIND; CLARITHROMYCIN; AZITHROMYCIN; REGIMENS; PROPHYLAXIS; INFECTIONS AB A multicenter study was conducted to assess the interlaboratory reproducibility of susceptibility testing of Mycobacterium avium complex (MAC) by broth microdilution using two different media (cation-adjusted Mueller-Hinton broth with 5% oleic acid-albumin-dextrose-catalase and 7H9 broth with casein) and by macrodilution using the BACTEC 460TB and 12B media at pH 6.8 and 7.3 to 7.4. Ten well-characterized strains of MAC (four macrolide susceptible, six macrolide resistant) were tested against clarithromycin and azithromycin (the latter only by BACTEC 460TB, pH 6.8). At each site, strains were tested against clarithromycin three times on each of three separate days (nine testing events per isolate) by using a common lot of microdilution trays and BACTEC 12B medium, pH 6.8; strains were tested once on three separate days against clarithromycin in 12B medium at pH 7.3 to 7.4 and against azithromycin. Agreement among MICs (i.e., mode 1 twofold dilution) was 100% for all strains and both drugs when BACTEC 460TB was used, regardless of the pH of the medium, but varied when microdilution with either medium was used, particularly with susceptible strains. Agreement based on interpretive category, with NCCLS-recommended breakpoints, was 100% for all strains with the BACTEC 460TB method (both drugs and both pH values) and with microdilution using 7H9 broth. With microdilution and Mueller-Hinton broth, agreement by interpretive category was 100% for eight isolates and >90% for two; errors occurred only in laboratories where personnel had minimal experience with this technique. MAC susceptibility testing may be performed by broth macrodilution or microdilution at either pH, with NCCLS-recommended interpretive breakpoints. However, because visual interpretation of broth microdilution end points is subjective, it is more prone to reader error; therefore, this method requires greater expertise than the BACTEC 460TB. Both techniques require appropriate validation and continued documentation of proficiency. C1 Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA. Univ Texas Hlth Ctr, Dept Microbiol, Tyler, TX 75710 USA. NIH, Microbiol Serv, Dept Lab Med, WG Magnuson Clin Ctr, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Microbiol, Cleveland, OH 44195 USA. StatProbe, Ann Arbor, MI 48108 USA. Childrens Hosp, Dept Pathol, Los Angeles, CA 90027 USA. RP Woods, GL (reprint author), Merck & Co Inc, 10 Sentry Pkwy,BL3-4, Blue Bell, PA 19422 USA. NR 25 TC 16 Z9 19 U1 0 U2 2 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 FEB PY 2003 VL 41 IS 2 BP 627 EP 631 DI 10.1128/JCM.41.2.627-631.2003 PG 5 WC Microbiology SC Microbiology GA 643YM UT WOS:000180891200018 PM 12574258 ER PT J AU Roilides, E Farmaki, E Evdoridou, J Francesconi, A Kasai, M Filioti, J Tsivitanidou, M Sofianou, D Kremenopoulos, G Walsh, TJ AF Roilides, E Farmaki, E Evdoridou, J Francesconi, A Kasai, M Filioti, J Tsivitanidou, M Sofianou, D Kremenopoulos, G Walsh, TJ TI Candida tropicalis in a neonatal intensive care unit: Epidemiologic and molecular analysis of an outbreak of infection with an uncommon neonatal pathogen SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BLOOD-STREAM INFECTIONS; IMMUNOCOMPROMISED PATIENTS; PARAPSILOSIS FUNGEMIA; ALBICANS; SURVEILLANCE; CHILDREN; FEATURES AB From June to July 1998, two episodes of Candida tropicalis fungemia occurred in the Aristotle University neonatal intensive care unit (ICU). To investigate this uncommon event, a prospective study of fungal colonization and infection was conducted. From December 1998 to December 1999, surveillance cultures of the oral cavities and perinea of the 593 of the 781 neonates admitted to the neonatal ICU who were expected to stay for >7 days were performed. Potential environmental reservoirs and possible risk factors for acquisition of C. tropicalis were searched for. Molecular epidemiologic studies by two methods of restriction fragment length polymorphism analysis and two methods of random amplified polymorphic DNA analysis were performed. Seventy-two neonates were colonized by yeasts (12.1%), of which 30 were colonized by Candida albicans, 17 were colonized by C. tropicalis, and 5 were colonized by Candida parapsilosis. From December 1998 to December 1999, 10 cases of fungemia occurred; 6 were due to C. parapsilosis, 2 were due to C. tropicalis, 1 was due to Candida glabrata, and 1 was due to Trichosporon asahii (12.8/1,000 admissions). Fungemia occurred more frequently in colonized than in noncolonized neonates (P < 0.0001). Genetic analysis of 11 colonization isolates and the two late blood isolates of C. tropicalis demonstrated two genotypes. One blood isolate and nine colonization isolates belonged to a single type. The fungemia/colonization ratio of C. parapsilosis (3/5) was greater than that of C. tropicalis (2/17, P = 0.05), other non-C. albicans Candida spp. (1/11, P = 0.02), or C. albicans (0/27, P = 0.05). Extensive environmental cultures revealed no common source of C. tropicalis or C. parapsilosis. There was neither prophylactic use of azoles nor other risk factors found for acquisition of C. tropicalis except for total parenteral nutrition. A substantial risk of colonization by non-C. albicans Candida spp. in the neonatal ICU may lead to a preponderance of C. tropicalis as a significant cause of neonatal fungemia. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Dept Pediat 3, Thessaloniki 54642, Greece. Aristotle Univ Thessaloniki, Neonatol Dept 1, Thessaloniki 54642, Greece. Hippokratio Gen Hosp, Dept Microbiol, Thessaloniki 54642, Greece. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 34 TC 46 Z9 50 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 2003 VL 41 IS 2 BP 735 EP 741 DI 10.1128/JCM.41.2.735-741.2003 PG 7 WC Microbiology SC Microbiology GA 643YM UT WOS:000180891200035 PM 12574275 ER PT J AU Dignam, JJ Ye, YR Colangelo, L Smith, R Mamounas, EP Wieand, HS Wolmark, N AF Dignam, JJ Ye, YR Colangelo, L Smith, R Mamounas, EP Wieand, HS Wolmark, N TI Prognosis after rectal cancer in blacks and whites participating in adjuvant therapy randomized trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CONSERVING SURGERY; COLORECTAL-CANCER; LOCAL RECURRENCE; MEDICARE BENEFICIARIES; SOCIOECONOMIC-FACTORS; RACIAL-DIFFERENCES; CARCINOMA PATIENTS; AFRICAN-AMERICANS; RADIATION-THERAPY; COLON-CARCINOMA AB Purpose: National health statistics indicate that blacks have lower survival rates from colorectal cancer than do whites. This disparity has been attributed to differences in stage at diagnosis and other disease features, extent and quality of treatment, and socioeconomic factors. We evaluated outcomes for blacks and whites with rectal cancer who participated in randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP). The randomized trial setting enhances uniformity in disease stage and treatment plan among all participants. Patients and Methods: The study included black (N = 104) or white (N = 1,070) patients from two serially conducted NSABP randomized trials for operable rectal cancer. Recurrence-free survival and survival were compared using statistical modeling to account for differences in patient and disease characteristics between the groups. Results: Blacks and whites had largely similar disease features at diagnosis. After adjustment for patient and tumor prognostic covariates, the black/white recurrence hazard ratio (HR) was 1.25 (95% confidence interval [CI], 0.94 to 1.66). The mortality HR was somewhat larger at 1.45 (95% CI = 1.09 to 1.93). Outcomes were improved for both groups in the more recent trial, which employed systemic adjuvant chemotherapy in all treatment arms. Conclusion: Recurrence-free survival was modestly less favorable for blacks, whereas overall survival was more disparate. Outcomes between groups were more comparable than those noted in national health statistics surveys and other studies. Adequate treatment access and the identification of new prognostic factors that can identify patients at high risk of recurrence are needed to ensure optimal outcomes for rectal cancer patients of all racial/ethnic backgrounds. (C) 2003 by American Society of Clinical Oncology. C1 Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Univ Pittsburgh, NSABP, Ctr Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA USA. NSABP, Operat Ctr, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Aultman Hosp, Ctr Canc, Canton, OH USA. RP Dignam, JJ (reprint author), Univ Chicago, Dept Hlth Studies, 5841 S Maryland Ave MC2007, Chicago, IL 60637 USA. FU NCI NIH HHS [P30-CA-14599, U10-CA-12027, U10-CA-69651] NR 67 TC 32 Z9 34 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2003 VL 21 IS 3 BP 413 EP 420 DI 10.1200/JCO.2003.02.004 PG 8 WC Oncology SC Oncology GA 644QT UT WOS:000180930900007 PM 12560428 ER PT J AU Capparelli, EV Englund, JA Connor, JD Spector, SA McKinney, RE Palumbo, P Baker, CJ AF Capparelli, EV Englund, JA Connor, JD Spector, SA McKinney, RE Palumbo, P Baker, CJ CA PACTG 152 Team TI Population pharmacokinetics and pharmacodynamics of zidovudine in HIV-infected infants and children SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL PHARMACOKINETICS; EFFICACY; TOXICITY; THERAPY; WOMEN; AIDS AB The purpose of this study was to assess the population pharmacokinetics (PK) and pharmacodynamics (PD) of zidovudine (ZDV) in infants and children. This evaluation includes 394 subjects who participated in Pediatric AIDS Clinical Trials Group (PACTG) Study 152 and received either ZDV alone or in combination with didanosine. The most significant PK covariate was age, with infants < 2 years of age having reduced size-adjusted clearance. ZDV exposure was weakly related to maximal reduction in immune complex-dissociated (ICD) p24 antigen but not to reduction at 6 months. Mild chronic anemia occurred in 7.6% of subjects with ZDV average concentration < 1.3 muM (350 ng/mL) versus in 23.4% subjects with higher ZDV concentrations (p < 0.001). There was a direct linear relationship between hemoglobin and ZDV levels. It was concluded that ZDV oral clearance is reduced in infants compared to older children. This lower clearance leads to higher ZDV exposure in infants and contributes to increased hematologic toxicity (C)2003 the American College of Clinical Pharmacology. C1 Univ Calif San Diego, Sch Med, Pediat Pharmacol Res Unit, La Jolla, CA 92093 USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Baylor Coll Med, Houston, TX 77030 USA. NIAID, NICHD, Bethesda, MD 20892 USA. RP Capparelli, EV (reprint author), Univ Calif San Diego, Sch Med, Pediat Pharmacol Res Unit, 9500 Gilman Dr 0979, La Jolla, CA 92093 USA. NR 26 TC 32 Z9 33 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD FEB PY 2003 VL 43 IS 2 BP 133 EP 140 DI 10.1177/0091270002239821 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 638TT UT WOS:000180587600005 PM 12616665 ER PT J AU Frazier, JA Cohen, LG Jacobsen, L Grothe, D Flood, J Baldessarini, RJ Piscitelli, S Kim, GS Rapoport, JL AF Frazier, JA Cohen, LG Jacobsen, L Grothe, D Flood, J Baldessarini, RJ Piscitelli, S Kim, GS Rapoport, JL TI Clozapine pharmacokinetics in children and adolescents with childhood-onset schizophrenia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID MULTIPLE-DOSE PHARMACOKINETICS; PLASMA CLOZAPINE; CAFFEINE TEST; METABOLISM; SERUM; NORCLOZAPINE; CYP1A2 AB Clozapine (CLZ) dose-related adverse effects may be more common in children than adults, perhaps reflecting developmental pharmacokinetic (PK) differences. However, no pediatric CLZ PK data are available. Accordingly, we studied CLZ and its metabolites, norclozapine (NOR), and clozapine-N-oxide (NOX) in six youth, ages 9-16 years, with childhood onset schizophrenia (COS). At the time of the PK study, mean CLZ dose was 200 mg (3.4 mg/kg). Serum was collected during week 6 on CLZ before and 0.5-8 h after a morning dose. Serum concentrations were assayed by liquid chromatography/UV-detection. Mean concentration, area-under-the-curve (AUC), and clearance were calculated. CLZ clearance averaged 1.7 L/kg-h. NOR concentrations (410) exceeded CLZ (289) and NOX (63 ng/ml) and AUC(0-8h) of NOR (3,356) > CLZ (2,359) > NOX (559 ng/ml-h) [53, 38, and 9% of total analytes, respectively]. In adults, NOR serum concentrations on average are 10-25%.< CLZ, differing significantly from our sample. Dose normalized concentrations of CLZ (mg/kg-d) did not vary with age and were similar to reported adult values. Clinical improvement seen in. 5/6 patients correlated with serum CLZ concentrations. In addition, clinical response and total number of side effects correlated with NOR concentrations. NOR (a neuropharmacologically active metabolite) and free CLZ may contribute to the effectiveness and adverse effects in youth. C1 McLean Hosp, Pediat Psychot Disorders Program, Child Outpatient Serv, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Belmont, MA USA. Massachusetts Gen Hosp, Joint Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. NIH, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. NIH, Dept Pharm, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Clin Chem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Program Neurosci, Cambridge, MA 02138 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Frazier, JA (reprint author), McLean Hosp, Pediat Psychot Disorders Program, Child Outpatient Serv, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-34006, MH-47370]; PHS HHS [M-01573] NR 27 TC 43 Z9 44 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2003 VL 23 IS 1 BP 87 EP 91 DI 10.1097/00004714-200302000-00012 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 641UJ UT WOS:000180765000012 PM 12544379 ER PT J AU Wood, JN Romero, SG Makale, M Grafman, J AF Wood, JN Romero, SG Makale, M Grafman, J TI Category-specific representations of social and nonsocial knowledge in the human prefrontal cortex SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EVENT-RELATED FMRI; BRAIN ACTIVATION; FUNCTIONAL MRI; SEMANTIC CATEGORY; FRONTAL-CORTEX; PET; RETRIEVAL; MEMORY; WORD; LANGUAGE AB Complex social behavior and the relatively large size of the prefrontal cortex are arguably two of the characteristics that distinguish humans from other animals. Grafman presented a framework concerning how the prefrontal cortex (PFC) controls complex behavior using stored structured event complexes (SECs). We report behavioral and imaging data from a modified go/no-go paradigm in which subjects had to classify words (semantic) and phrases (SEC) according to category. In experimental trials, subjects classified items according to social or nonsocial activity; in control trials, they classified items according to font. Subjects were faster to classify social than nonsocial semantic items, with the reverse pattern evident for the social and nonsocial SEC items. In addition, the conditions were associated with different patterns of PFC activation. These results suggest that there are different psychological and neural substrates for social and nonsocial semantic and SEC representations. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Room 5C205,Bldg 10,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 70 TC 34 Z9 34 U1 5 U2 7 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD FEB PY 2003 VL 15 IS 2 BP 236 EP 248 DI 10.1162/089892903321208178 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 653TJ UT WOS:000181452900008 PM 12676061 ER PT J AU Lewis, PJ de Jonge, M Daeyaert, F Koymans, L Vinkers, M Heeres, J Janssen, PAJ Arnold, E Das, K Clark, AD Hughes, SH Boyer, PL de Bethune, MP Pauwels, R Andries, K Kukla, M Ludovici, D De Corte, B Kavash, R Ho, C AF Lewis, PJ de Jonge, M Daeyaert, F Koymans, L Vinkers, M Heeres, J Janssen, PAJ Arnold, E Das, K Clark, AD Hughes, SH Boyer, PL de Bethune, MP Pauwels, R Andries, K Kukla, M Ludovici, D De Corte, B Kavash, R Ho, C TI On the detection of multiple-binding modes of ligands to proteins, from biological, structural, and modeling data SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE molecular modeling; virology; HIV; X-ray crystallography; drug design; statistical analysis; PLS ID HIV DRUG CANDIDATES; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURES; EVOLUTION; INHIBITORS; ANALOGS/; SERIES AB There are several indications that a given compound or a set of related compounds can bind in different modes to a specific binding site of a protein. This is especially evident from X-ray crystallographic structures of ligand-protein complexes. The availability of multiple binding modes of a ligand in a binding site may present an advantage in drug design when simultaneously optimizing several criteria. In the case of the design of anti-HIV compounds we observed that the more active compounds that are also resilient against mutation of the non-nucleoside binding site of HIV1-reverse transcriptase make use of more binding modes than the less active and resilient compounds. C1 Janssen Pharmaceut NV, J&JPRD, Ctr Mol Design, Vosselaar, Belgium. Rutgers State Univ, Ctr Biotechnol & Med, Piscataway, NJ 08855 USA. Rutgers State Univ, Dept Chem & Biol Chem, Piscataway, NJ 08855 USA. NCI, NIH, HIV Drug Resistance Program, Frederick, MD 21701 USA. Tibotec Virco, Mechelen, Belgium. Janssen Pharmaceut NV, J&JPRD, Dept Virol, Beerse, Belgium. J&JPRD, Dept Chem, Spring House, PA USA. RP Lewis, PJ (reprint author), Janssen Pharmaceut NV, J&JPRD, Ctr Mol Design, Vosselaar, Belgium. RI de Jonge, Marc/B-3391-2010 OI de Jonge, Marc/0000-0003-3225-8172 NR 16 TC 36 Z9 40 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD FEB PY 2003 VL 17 IS 2 BP 129 EP 134 DI 10.1023/A:1025313705564 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA 711ZE UT WOS:000184770300005 PM 13677481 ER PT J AU Karibe, H Goddard, G Gear, RW AF Karibe, H Goddard, G Gear, RW TI Sex differences in masticatory muscle pain after chewing SO JOURNAL OF DENTAL RESEARCH LA English DT Article; Proceedings Paper CT IADR 2001 Meeting CY JUN, 2001 CL CHIBA, JAPAN SP IADR DE muscle pain; exercise; chewing; sex differences; mastication; TMD ID TEMPOROMANDIBULAR DISORDERS; ADOLESCENT GIRLS; ORAL HABITS; SYMPTOMS; ASSOCIATION; SIGNS AB Neither the etiology of muscle-related temporomandibular disorders (TMD) not reason for the disproportionate number of women suffering from these disorders is well-established. We tested the hypothesis that physiologically relevant exercise (i.e., chewing bubble gum for 6 min) increases masticatory muscle pain in patients, but not in asymptomatic control subjects, and that female patients experience a significantly greater increase than males. Chewing increased pain in both female and mate patients and, unexpectedly, also in female control subjects. One hour after chewing, the pain remained above pretest levels for female patients but not for the other groups. Thus, sex differences in chewing-induced pain were found in control subjects but not as hypothesized in patients. Because chewing-induced masticatory muscle pain was significantly greater in female control subjects than in males, and persisted longer in female patients than in males, these results suggest greater susceptibility in women. C1 Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, NIH, Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, NIH, Ctr Orofacial Pain, San Francisco, CA 94143 USA. RP Gear, RW (reprint author), Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, NIH, Pain Ctr, Box 0440, San Francisco, CA 94143 USA. NR 22 TC 42 Z9 43 U1 0 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2003 VL 82 IS 2 BP 112 EP 116 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 640DP UT WOS:000180672500007 PM 12562883 ER PT J AU Nowjack-Raymer, RE Sheiham, A AF Nowjack-Raymer, RE Sheiham, A TI Association of edentulism and diet and nutrition in US adults SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dentures; health disparities; nutrition; NHANES III; Healthy People 2010 ID IMPLANT-SUPPORTED OVERDENTURES; NUTRIENT INTAKE; CONVENTIONAL DENTURES; DIABETIC-PATIENTS; DENTAL STATUS; POPULATION; EFFICACY; PEOPLE; SWEDEN; IMPACT AB Dental status and its relationship to diet and nutritional status have been little explored. In this study of a representative sample of the US civilian, non-institutionalized population (NHANES III), we predicted that the intake of nutritious foods, dietary fiber, and levels of biochemical analytes would be lower, even after adjusting for potential social and behavioral factors, among those who were edentulous and wore complete dentures than for those who had all their natural teeth. Multivariate analyses indicated that intake of carrots and tossed salads among denture-wearers was, respectively, 2.1 and 1.5 times less than for the fully dentate (p < 0.0001), and dietary fiber intake was 1.2 times less (p < 0.05). Serum levels of beta carotene (9.8 mug/dL), folate (4.7 ng/dL), and vitamin C (0.87 mg/dL) were also lower among denture-wearers (p < 0.05). Intakes of some nutrient-rich foods and beta carotene, folate, and vitamin C serum levels were significantly lower in denture-wearers. C1 Natl Inst Dent & Craniofacial Res, Div Populat & Hlth Promot Sci, Bethesda, MD 20892 USA. UCL, Sch Med, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England. RP Nowjack-Raymer, RE (reprint author), Natl Inst Dent & Craniofacial Res, Div Populat & Hlth Promot Sci, 45 Ctr Dr,Room 4AS-43J, Bethesda, MD 20892 USA. EM Ruth.Nowjack-Raymer@nih.gov NR 27 TC 133 Z9 139 U1 4 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2003 VL 82 IS 2 BP 123 EP 126 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 640DP UT WOS:000180672500009 PM 12562885 ER PT J AU Dworkin, PH AF Dworkin, PH TI Families matter-even for kids in child care SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material ID LIFE C1 Univ Calif Irvine, Irvine, CA 92717 USA. Univ London Birkbeck Coll, London WC1E 7HX, England. Univ Washington, Seattle, WA 98195 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ N Carolina, Chapel Hill, NC USA. NICHD, Bethesda, MD USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Texas, Austin, TX 78712 USA. St Josephs Univ, Philadelphia, PA 19131 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Wellesley Coll, Wellesley, MA 02181 USA. Harvard Univ, Cambridge, MA 02138 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ N Carolina, Greensboro, NC 27412 USA. Univ Texas, Dallas, TX 75230 USA. Georgetown Univ, Washington, DC 20057 USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Wisconsin, Madison, WI USA. Temple Univ, Philadelphia, PA 19122 USA. RP Dworkin, PH (reprint author), Univ Calif Irvine, Irvine, CA 92717 USA. NR 38 TC 9 Z9 9 U1 8 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD FEB PY 2003 VL 24 IS 1 BP 58 EP 62 PG 5 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 645UF UT WOS:000180997200010 ER PT J AU Jaber, L Swaim, WD Dionne, RA AF Jaber, L Swaim, WD Dionne, RA TI Immunohistochemical localization of mu-opioid receptors in human dental pulp SO JOURNAL OF ENDODONTICS LA English DT Article ID PERIPHERAL MORPHINE ANALGESIA; INFLAMED TISSUE; INFLAMMATION; MECHANISMS; RAT; MICROENVIRONMENT; EXPRESSION; NERVE AB Studies in both animal and clinical models suggest that opioids exert their analgesic effects not only through activation of receptors in the CNS but also through interaction with peripheral opioid receptors. This study evaluated the presence and distribution of mu-opioid receptors in human dental pulp' Human third molars indicated for extraction were removed, fixed in 4% paraformaldehyde and 0.2% picric acid, and decalcified in 10% EDTA and 7.5% polyvinylpyrrolidone. The teeth were cut using a cryostat, and the avidin-biotin peroxidase immunohistochemistry technique was used. Immunostaining for mu-opioid receptors was detected along the nerve bundle of the radicular as well as coronal dental pulp. Positive immunostaining was also observed in the individual nerve fibers in the coronal region. This demonstration of opiate receptors on pulpal nerve fibers suggests a peripheral site in the dental pulp where endogenous or exogenous opioids can interact with mu-opioid receptors. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Dionne, RA (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, 10 Ctr Dr,Room 1N-117, Bethesda, MD 20892 USA. NR 20 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD FEB PY 2003 VL 29 IS 2 BP 108 EP 110 DI 10.1097/00004770-200302000-00005 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 642XW UT WOS:000180833000005 PM 12597708 ER PT J AU Seibel, BA Walsh, PJ AF Seibel, BA Walsh, PJ TI Biological impacts of deep-sea carbon dioxide injection inferred from indices of physiological performance SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE carbon dioxide; global warming; deep sea; hypercapnia; acid-base balance; sequestration; cephalopoda; metabolism ID ACID-BASE REGULATION; ARTEMIA-FRANCISCANA EMBRYOS; SANTA-BARBARA BASIN; LOW-OXYGEN LEVELS; FRESH-WATER FISH; FOSSIL-FUEL CO2; ENVIRONMENTAL HYPERCAPNIA; BUFFERING CAPACITY; RIFTIA-PACHYPTILA; PROTEIN-SYNTHESIS AB A recent proposal to store anthropogenic carbon dioxide in the deep ocean is assessed here with regard to the impacts on deep-living fauna. The stability of the deepsea has allowed the evolution of species ill-equipped to withstand rapid environmental changes. Low metabolic rates of most deep-sea species are correlated with low capacities for pH buffering and low concentrations of ion-transport proteins. Changes in seawater carbon dioxide partial pressure (Pco(2)) may thus lead to large cellular Pco(2) and pH changes. Oxygen transport proteins of deepsea animals are also highly sensitive to changes in pH. Acidosis leads to metabolic suppression, reduced protein synthesis, respiratory stress, reduced metabolic scope and, ultimately, death. Deep-sea CO2 injection as a means of controlling atmospheric CO2 levels should be assessed with careful consideration of potential biological impacts. In order to properly evaluate the risks within a relevant timeframe, a much more aggressive approach to research is warranted. C1 Monterey Bay Aquarium Res Inst, Moss Landing, CA 95039 USA. Univ Miami, NIEHS, Marine & Freshwater Biomed Sci Ctr, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33149 USA. RP Seibel, BA (reprint author), Monterey Bay Aquarium Res Inst, 7700 Sandholdt Rd, Moss Landing, CA 95039 USA. EM bseibel@mbari.org FU NIEHS NIH HHS [ES05705] NR 91 TC 106 Z9 111 U1 4 U2 33 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 EI 1477-9145 J9 J EXP BIOL JI J. Exp. Biol. PD FEB PY 2003 VL 206 IS 4 BP 641 EP 650 DI 10.1242/jeb.00141 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 648YJ UT WOS:000181179100001 PM 12517981 ER PT J AU Nomiyama, K Shibuya, T Kataoka, C Aoki, Y AF Nomiyama, K Shibuya, T Kataoka, C Aoki, Y TI When lymphoma and heart failure cross paths SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Letter ID THERAPY C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Hamanoumachi Hosp, Dept Med, Fukuoka, Japan. Fukuoka Red Cross Hosp, Dept Cardiovasc Med, Fukuoka, Japan. RP Aoki, Y (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,12N226, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. Hematother. Stem Cell Res. PD FEB PY 2003 VL 12 IS 1 BP 7 EP 8 DI 10.1089/152581603321210073 PG 2 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 655AV UT WOS:000181529900002 PM 12662430 ER PT J AU Matkowskyj, KA Cox, R Jensen, RT Benya, RV AF Matkowskyj, KA Cox, R Jensen, RT Benya, RV TI Quantitative immunohistochemistry by measuring cumulative signal strength accurately measures receptor number SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE bombesin; gastrin-releasing peptide; archived tissues; receptor number ID GASTRIN-RELEASING PEPTIDE; IMAGE-ANALYSIS; BOMBESIN RECEPTORS; COLON-CANCER; EXPRESSION; PHOTOSHOP; QUANTIFICATION AB We previously demonstrated that quantitative immunohistochemistry (Q-IHC) performed by measuring the cumulative signal strength of the digital file encoding an image can be used to determine the absolute amount of chromogen present per pixel. We now show that Q-IHC so performed can be used to accurately determine the amount of peptide hormone receptor of interest in archived tissues. To do this we transfected Balb 3T3 fibroblasts with the cDNA encoding the human receptor for gastrin-releasing peptide (GRP), and selected six cell lines stably expressing between 10(2) and 10(6) receptors/cell. These cell lines were fixed in formalin, embedded in paraffin, and treated with antipeptide antibodies against the GRP receptor, followed by DAB chromogen to identify bound antibody. Images were acquired using a 4.9 million pixel digital scanning 24-bit RGB camera, saved in TIFF format, and used for subsequent analysis. Q-IHC was performed after digitally dissecting out the relevant portion of the image for analysis, and processing using a program written in C (available at http://www.uic.edu/com/dom/gastro/Freedownloads.html). Under the conditions defined here, chromogen quantity as determined by Q-IHC tightly correlated with GRP receptor number (r(2)=0.867) in these cell lines. Using the conversion factor identified as a result of these studies, we then determined GRP receptor number on eight randomly selected, archived human colon cancers. Overall GRP receptor expression in colon cancer depended on the degree to which cells within any particular tumor were differentiated, with well-differentiated cells expressing the greatest numbers of receptors (similar to55,000 +/- 10,000 sites/cell). These studies indicate that Q-IHC can be used to determine receptor quantity in archived tissues and other samples of limited quantity. C1 Univ Illinois, Dept Med, Chicago, IL 60612 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. Univ Illinois, Dept Biochem & Mol Genet, Bioinformat Grp, Chicago, IL USA. Vet Adm Med Ctr, Chicago, IL USA. RP Benya, RV (reprint author), Univ Illinois, Dept Med, 840 S Wood St M-C 716, Chicago, IL 60612 USA. FU NIDDK NIH HHS [DK51168, DK54777] NR 20 TC 69 Z9 74 U1 1 U2 3 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD FEB PY 2003 VL 51 IS 2 BP 205 EP 214 PG 10 WC Cell Biology SC Cell Biology GA 639LT UT WOS:000180631000009 PM 12533529 ER PT J AU Hiltbold, EM Poloso, NJ Roche, PA AF Hiltbold, EM Poloso, NJ Roche, PA TI MHC class II-peptide complexes and APC lipid rafts accumulate at the immunological synapse SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; GPI-ANCHORED PROTEINS; PLASMA-MEMBRANE; MONOCLONAL-ANTIBODIES; ANTIGEN PRESENTATION; CHOLESTEROL; RECEPTOR; SURFACE; MOLECULES; DYNAMICS AB Activation of CD4(+) Th cells requires their cognate interaction with APCs bearing specific relevant MHC class II-peptide complexes. This cognate interaction culminates in the formation of an immunological synapse that contains the various proteins and lipids required for efficient T cell activation. We now show that APC lipid raft membrane microdomains contain specific class II-peptide complexes and serve as platforms that deliver these raft-associated class 11 molecules to the immunological synapse. APC rafts are required for T cell:APC conjugate formation and T cell activation at low densities of relevant class II-peptide complexes, a requirement that can be overcome at high class II-peptide density. Analysis of confocal microscopy images revealed that over time APC lipid rafts, raft-associated relevant class II-peptide complexes, and even immunologically irrelevant class 11 molecules accumulate at the immunological synapse. As the immunological synapse matures, relevant class II-peptide complexes are sorted to a central region of the interface, while irrelevant class II molecules are excluded from this site. We propose that T cell activation is facilitated by recruitment of MHC class II-peptide complexes to the immunological synapse by virtue of their constitutive association with lipid raft microdomains. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 44 TC 96 Z9 99 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2003 VL 170 IS 3 BP 1329 EP 1338 PG 10 WC Immunology SC Immunology GA 639XM UT WOS:000180655500027 PM 12538693 ER PT J AU Fitzgerald, JC Gao, GP Reyes-Sandoval, A Pavlakis, GN Xiang, ZQ Wlazlo, AP Giles-Davis, W Wilson, JM Ertl, HCJ AF Fitzgerald, JC Gao, GP Reyes-Sandoval, A Pavlakis, GN Xiang, ZQ Wlazlo, AP Giles-Davis, W Wilson, JM Ertl, HCJ TI A simian replication-defective vaccine to HIV-1 gag SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; IMMUNE-RESPONSES; RHESUS-MONKEYS; RECOMBINANT ADENOVIRUS; DNA VACCINES; VIRUS; IMMUNODEFICIENCY; INFECTION; CELLS; PREVENTION AB In animal models, El-deleted human adenoviral recombinants of the serotype 5 (AdHu5) have shown high efficacy as vaccine carriers for different Ags including those of HIV-1. Humans are infected by common serotypes of human adenovirus such as AdHu5 early in life and a significant percentage has high levels of neutralizing Abs to these serotypes, which will very likely impair the efficacy of recombinant vaccines based on the homologous virus. To circumvent this problem, a novel replication-defective adenoviral vaccine carrier based on an El-deleted recombinant of the chimpanzee adenovirus 68 (AdC68) was developed. An AdC68 construct expressing a codon-optimized, truncated form of gag of HIV-1 induces CD8(+) T cells to gag in mice which at the height of the immune response encompass nearly 20% of the entire splenic CD8(+) T cell population. The vaccine-induced immune response provides protection to challenge with a vaccinia gag recombinant virus. Induction of transgene-specific CD8(+) T cells and protection against viral challenge elicited by the AdC68 vaccines is not strongly inhibited in animals preimmune to AdHu5 virus. However, the response elicited by the AdHu5 vaccine is greatly attenuated in AdHu5 preimmune animals. C1 Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. NCI, Ctr Canc Res, Frederick, MD 21701 USA. Inst Politecn Nacl, Ctr Invest Ciencia Aplicada & Tecnol Avanzada, Mexico City, DF, Mexico. RP Ertl, HCJ (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. RI Reyes-Sandoval, Arturo/B-4264-2011; Wilson, James/F-9220-2011 OI Wilson, James/0000-0002-9630-3131 NR 27 TC 161 Z9 162 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 FEB 1 PY 2003 VL 170 IS 3 BP 1416 EP 1422 PG 7 WC Immunology SC Immunology GA 639XM UT WOS:000180655500036 PM 12538702 ER PT J AU Touloukian, CE Leitner, WW Schnur, RE Robbins, PF Li, Y Southwood, S Sette, A Rosenberg, SA Restifo, NP AF Touloukian, CE Leitner, WW Schnur, RE Robbins, PF Li, Y Southwood, S Sette, A Rosenberg, SA Restifo, NP TI Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID OCULAR ALBINISM TYPE-1; INFILTRATING LYMPHOCYTES; IN-VIVO; GENE; IDENTIFICATION; MICE; IMMUNOTHERAPY; AUTOIMMUNITY; MECHANISMS; DELETIONS AB Antitumor T cells often recognize targets that are nonmutated "self" tissue differentiation Ags, but the relative impact of Ag expression by normal and transformed tissue for a human self/tumor Ag has not been studied. To examine the influence of self-tolerance mechanisms on the function of self/tumor-specific T cell responses in humans, we sought to identify an Ag that was expressed, processed, and presented in an MHC-restricted fashion by tumor cells, but for which there was the human equivalent of a "knockout." In this study, we report the first immunological characterization of a melanoma/melanocyte differentiation Ag, called OA1, which meets these criteria. This Ag, an X chromosome-encoded melanoma/melanocyte differentiation Ag, was completely deleted in a male patient. Using a newly identified HLA-A*2402-restricted epitope (LYSACFWWL) to study T cell tolerance, we found that OA1-specific T cell reactivity was more than five SD higher in the knockout patient that in normal controls. These data provide compelling evidence for T cell tolerance to OA1 in humans. Most surprisingly, we found elevated levels of OA1-specific T cells in patients with metastatic malignant melanoma, indicating that the tumor-bearing state partially reversed tolerance observed in normal (non-"knockout") individuals. Taken together, these findings indicated that tolerance can exist for self/tumor Ags in humans, and that this tolerance could be partially abrogated by the growth of the tumor, increasing the reactivity of tumor Ag-specific T cells. Thus, the tumor-bearing state reverses, in part, the tolerance of T cells that results from the normal expression of tissue differentiation Ags. The Journal of Immunology, 2003, 170: 1579-1585. C1 NCI, NIH, Bethesda, MD 20892 USA. Robert Wood Johnson Med Sch, Div Genet, Cooper Hlth Syst, Camden, NJ 08103 USA. Epimmune, San Diego, CA 92121 USA. RP Restifo, NP (reprint author), NCI, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Leitner, Wolfgang/F-5741-2011; OI Leitner, Wolfgang/0000-0003-3125-5922; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 37 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2003 VL 170 IS 3 BP 1579 EP 1585 PG 7 WC Immunology SC Immunology GA 639XM UT WOS:000180655500057 PM 12538723 ER PT J AU Tuomala, RE O'Driscoll, PT Bremer, JW Jennings, C Xu, C Read, JS Matzen, E Landay, A Zorrilla, C Blattner, W Charurat, M Anderson, DJ AF Tuomala, RE O'Driscoll, PT Bremer, JW Jennings, C Xu, C Read, JS Matzen, E Landay, A Zorrilla, C Blattner, W Charurat, M Anderson, DJ CA Woman Infants Transmission Study TI Cell-associated genital tract virus and vertical transmission of human immunodeficiency virus type 1 in antiretroviral-experienced women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MOTHER-TO-CHILD; PERINATAL HIV-1 TRANSMISSION; MATERNAL-INFANT TRANSMISSION; VITAMIN-A-DEFICIENCY; RISK-FACTORS; CERVICOVAGINAL SECRETIONS; HISTOLOGIC CHORIOAMNIONITIS; ZIDOVUDINE PROPHYLAXIS; VAGINAL SECRETIONS; CIGARETTE-SMOKING AB To determine the association between genital tract shedding of human immunodeficiency virus (HIV) type 1 and vertical transmission, a case-control substudy was conducted within the Women and Infants Transmission Study. Antenatal cervicovaginal lavage specimens were assessed for HIV-1 RNA in the supernatant and HIV-1 RNA and DNA in cell pellets. Multivariate analyses compared 26 women who transmitted HIV to their infants with 52 women who did not; 33% received combination antiretroviral therapy, and 65% received monotherapy. Adjusted odds ratios (ORs) for the presence (OR, 3.42; 95% confidence interval [CI], 0.76-15.4; P = .11) and titer (OR, 1.66; 95% CI, 0.93-2.99; P = .09) of HIV-1 DNA suggested that there is an independent association with vertical transmission. When analyses were restricted to vaginal and nonelective cesarean deliveries, each one-log increase in mean titer of HIV-1 DNA was associated with a significantly higher risk of transmission (OR, 2.28; 95% CI, 1.09-4.78; P = .03). The cell-associated genital tract compartment is important in the pathophysiology and prevention of vertical HIV-1 transmission. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Brigham & Womens Hosp, Fearing Lab, Boston, MA 02115 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Inst Human Virol, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. Rush Med Coll, Chicago, IL 60612 USA. Univ Puerto Rico, Sch Med, Dept Obstet & Gynecol, San Juan, PR 00936 USA. RP Tuomala, RE (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St,ASB1-3, Boston, MA 02115 USA. FU NCRR NIH HHS [RR00188, RR00645]; NIAID NIH HHS [1 U01 AI 50274, U01 AI 34858, AI 39042, N01 AI 85339, U01 AI 34841]; NICHD NIH HHS [HD-36117, U01 HD 41983]; NIDA NIH HHS [9U01 DA15054, U01 DA 15053] NR 67 TC 61 Z9 64 U1 0 U2 2 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 FEB 1 PY 2003 VL 187 IS 3 BP 375 EP 384 DI 10.1086/367706 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 639NU UT WOS:000180636800005 PM 12552421 ER PT J AU Raghunath, M Hennies, HC Ahvazi, B Vogel, M Reis, A Steinert, PM Traupe, H AF Raghunath, M Hennies, HC Ahvazi, B Vogel, M Reis, A Steinert, PM Traupe, H TI Self-healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE collodion baby; genetics; lamellar desquamation; newborn; skin; transglutaminase 1 ID RECESSIVE LAMELLAR ICHTHYOSIS; FACTOR-XIII; GENE AB Spontaneous healing with no or only very mild ichthyosis distinguishes the "self-healing collodion baby" from other congenital ichthyoses. In two self-healing collodion baby siblings with markedly diminished epidermal transglutaminase 1 activity we found the compound heterozygous transglutaminase 1 mutations G278R and D490G. Molecular modeling and biochemical assays of mutant proteins under elevated hydrostatic pressure suggest significantly reduced activity in G278R and a chelation of water molecules in D490G that locks the mutated enzyme in an inactive trans conformation in utero . After birth these water molecules are removed and the enzyme is predicted to isomerize back to a partially active cis form, explaining the dramatic improvement of this skin condition. C1 Univ Hosp, Dept Dermatol, Munster, Germany. Max Delbruck Ctr Mol Med, Gene Mapping Ctr, Berlin, Germany. NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany. RP Traupe, H (reprint author), Univ Munster, Dept Dermatol, Von Esmarch Str 58, D-48149 Munster, Germany. RI Raghunath, Michael/E-6483-2010; Reis, Andre/D-2309-2009 OI Raghunath, Michael/0000-0002-2138-6614; Reis, Andre/0000-0002-6301-6363 NR 28 TC 53 Z9 58 U1 0 U2 2 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 FEB PY 2003 VL 120 IS 2 BP 224 EP 228 DI 10.1046/j.1523-1747.2003.12032.x PG 5 WC Dermatology SC Dermatology GA 639AU UT WOS:000180606100011 PM 12542526 ER PT J AU Fu, X Wei, Q Adelstein, R AF Fu, X Wei, Q Adelstein, R TI GFP-tagged analysis of mammalian cells SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 20 BP S95 EP S95 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600026 ER PT J AU Hashimoto, K Graham, BS Geraci, M FitzGerald, G Goleniewska, K O'Neal, JF Morrow, JD Peebles, RS AF Hashimoto, K Graham, BS Geraci, M FitzGerald, G Goleniewska, K O'Neal, JF Morrow, JD Peebles, RS TI Signaling through the PGI(2) receptor protects against RSV-induced illness. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NIH, VRC, Viral Pathogenesis Lab & Clin Core Trial, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 267 BP S303 EP S303 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600796 ER PT J AU Miller, FG AF Miller, FG TI Clinical research with healthy volunteers: An ethical framework SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Federation-for-Medical-Research CY APR, 2002 CL BALTIMORE, MARYLAND SP Amer Federat Med Res DE ethics; healthy volunteers AB Clinical research involving healthy volunteers is important for advancing medical knowledge but raises a variety of ethical issues, many of which stem from the fact that such studies pose risks to research participants without the prospect of medical benefits to them. Ethical issues in research with healthy volunteers are identified and analyzed with the help of an ethical framework consisting of seven ethical requirements for clinical research. These ethical requirements include (1) scientific or social value; (2) scientific validity; (3) fair subject selection; (4) favorable risk-to-benefit ratio; (5) independent review; (6) informed consent; and (7) respect for enrolled subjects. C1 NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 13 TC 3 Z9 3 U1 0 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 BP S2 EP S5 PG 4 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600002 PM 12664947 ER PT J AU Nadig, JD Ianosi-Irimie, M Whitbred, J Vu, H Fedorova, O Agalakova, N Bagrov, AY Puschett, JB AF Nadig, JD Ianosi-Irimie, M Whitbred, J Vu, H Fedorova, O Agalakova, N Bagrov, AY Puschett, JB TI Effects of chronic volume expansion on circulating humoral factors. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 93 BP S271 EP S272 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600621 ER PT J AU Nguyen, V Sadler, GR Shi, M Gilpin, E Cruz, LC Blas, LA Acfalle, B Blas, T Acfalle, R AF Nguyen, V Sadler, GR Shi, M Gilpin, E Cruz, LC Blas, LA Acfalle, B Blas, T Acfalle, R TI Cancer risk factor assessment among Chamorro women. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Pacific Islander Canc Control Network, La Jolla, CA 92093 USA. NCI, CURE, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 294 BP S142 EP S142 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600300 ER PT J AU Shikuma, KM Kamemoto, L Shikuma, C Gerschenson, M Shiramizu, B AF Shikuma, KM Kamemoto, L Shikuma, C Gerschenson, M Shiramizu, B TI Quantitative real-time PCR analysis for mitochondrial DNA toxicity in HIV-infected women receiving HAART during pregnancy SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ So Calif, Los Angeles, CA 90089 USA. Univ Hawaii, Honolulu, HI 96822 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 397 BP S161 EP S161 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600403 ER PT J AU Vasquez, NL Dyer, KD Rosenberg, HF AF Vasquez, NL Dyer, KD Rosenberg, HF TI The enzymatic characterization of mouse eosinophil associated ribonuclease 1 (Ear-1). SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 NIH Acad, Bethesda, MD USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 314 BP S146 EP S146 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600320 ER PT J AU Kobayashi, SD Voyich, JM Somerville, GA Braughton, KR Malech, HL Musser, JM DeLeo, FR AF Kobayashi, SD Voyich, JM Somerville, GA Braughton, KR Malech, HL Musser, JM DeLeo, FR TI An apoptosis-differentiation program in human polymorphonuclear leukocytes facilitates resolution of inflammation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE microarray; neutrophil; metabolism; phagocytosis ID NEUTROPHIL APOPTOSIS; HEME OXYGENASE; ANTIOXIDANT; GLYCOLYSIS AB Human polymorphonuclear leukocytes (PMNs) are an essential part of innate immunity and contribute significantly to inflammation. Although much is understood about the inflammatory response, the molecular basis for termination of inflammation in humans is largely undefined. We used human oligonucleotide microarrays to identify genes differentially regulated during the onset of apoptosis occurring after PMN phagocytosis. Genes encoding proteins that regulate cell metabolism and vesicle trafficking comprised 198 (98 genes induced, 100 genes repressed) of 867 differentially expressed genes. We discovered that complex cellular pathways involving glutathione and thioredoxin detoxification systems, heme catabolism, ubiquitin-proteasome degradation, purine nucleotide metabolism, and nuclear import were regulated at the level of gene expression during the initial stages of PMN apoptosis. Eleven genes encoding key regulators of glycolysis, the hexose monophosphate shunt, the glycerol-phosphate shuttle, and oxidative phosphorylation were induced. Increased levels of cellular reduced glutathione and gamma-glutamyltransferase and glycolytic activity confirmed that several of these metabolic pathways were up-regulated. In contrast, seven genes encoding critical enzymes involved in fatty acid beta-oxidation, which can generate toxic lipid peroxides, were down-regulated. Our results indicate that energy metabolism and oxidative stress-response pathways are gene-regulated during PMN apoptosis. We propose that changes in PMN gene expression leading to programmed cell death are part of an apoptosis-differentiation program, a final stage of transcriptionally regulated PMN maturation that is accelerated significantly by phagocytosis. These findings provide new insight into the molecular events that contribute to the resolution of inflammation in humans. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. RI Somerville, Greg/B-1326-2013; OI Somerville, Greg/0000-0002-0991-8737; Malech, Harry/0000-0001-5874-5775; DeLeo, Frank/0000-0003-3150-2516 NR 26 TC 52 Z9 53 U1 0 U2 2 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 FEB PY 2003 VL 73 IS 2 BP 315 EP 322 DI 10.1189/jlb.1002481 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 641RP UT WOS:000180759900013 PM 12554809 ER PT J AU Basso, F Freeman, L Knapper, CL Remaley, A Stonik, J Neufeld, EB Tansey, T Amar, MJA Fruchart-Najib, J Duverger, N Santamarina-Fojo, S Brewer, HB AF Basso, F Freeman, L Knapper, CL Remaley, A Stonik, J Neufeld, EB Tansey, T Amar, MJA Fruchart-Najib, J Duverger, N Santamarina-Fojo, S Brewer, HB TI Role of the hepatic ABCA1 transporter in modulating intrahepatic cholesterol and plasma HDL cholesterol concentrations SO JOURNAL OF LIPID RESEARCH LA English DT Article DE reverse cholesterol transport; lipoprotein; cholesterol; Tangier disease ID BINDING CASSETTE TRANSPORTER-1; DENSITY-LIPOPROTEIN CHOLESTEROL; TANGIER-DISEASE; TRANSGENIC MICE; X-RECEPTOR; GENE; EFFLUX; ATHEROSCLEROSIS; DEFICIENCY; MUTATIONS AB The current model for reverse cholesterol transport proposes that HDL transports excess cholesterol derived primarily from peripheral cells to the liver for removal. However, recent studies in ABCA1 transgenic mice suggest that the liver itself may be a major source of HDL cholesterol (HDL-C). To directly investigate the hepatic contribution to plasma HDL-C levels, we generated an adenovirus (rABCA1-GFP-AdV) that targets expression of mouse ABCA1-GF'P in vivo to the liver. Compared with mice injected with control AdV, infusion of rABCA1-GFP-AdV into C57B1/6 mice resulted in increased expression of mouse ABCA1 mRNA and protein in the liver. ApoA-I-dependent cholesterol efflux was increased 2.6-fold in primary hepatocytes isolated I day after rABCA1-GFP-AdV infusion. Hepatic ABCAI expression in C57B1/6 mice (n = 15) raised baseline levels of TC, PL, FC, HDL-C, apoE, and apoA-I by 150-300% (P < 0.05 all). ABCA1 expression led to significant compensatory changes in expression of genes that increase hepatic cholesterol, including HMG-CoA reductase (3.5-fold), LDLr (2.1-fold), and LRP (5-fold) in the liver. These combined results demonstrate that ABCA1 plays a key role in hepatic cholesterol efflux, inducing pathways that modulate cholesterol homeostasis in the liver, and establish the liver as a major source of plasma HDI-C. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20862 USA. Aventis Pharma, Vitry Sur Seine, France. Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France. RP Basso, F (reprint author), NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20862 USA. NR 35 TC 151 Z9 154 U1 0 U2 3 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 FEB PY 2003 VL 44 IS 2 BP 296 EP 302 DI 10.1194/jlr.M200414-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 650CZ UT WOS:000181246000007 PM 12576511 ER PT J AU Galban, CJ Spencer, RGS AF Galban, CJ Spencer, RGS TI Long repetition time experiments for measurement of concentrations in systems with chemical exchange and undergoing temporal variation-comparison of methods with and without correction for saturation SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID LATTICE RELAXATION-TIMES; MAGNETIC-RESONANCE SPECTROSCOPY; ONE-PULSE EXPERIMENT; P-31 MRS DATA; IN-VIVO NMR; PITFALLS AB The purpose of this paper is to compare two methods for quantifying metabolite concentrations using the one-pulse experiment for a sample undergoing chemical exchange and subject to an intervention or other temporal variation. The methods, LATR-C (Long Acquisition TR (interpulse delay); Corrected for partial saturation) and LATR-NC (Long Acquisition TR; Not Corrected), are compared in terms of signal-to-noise ratio, SNR, per unit time and quantitation errors. Parameters relevant to the isolated perfused rat heart are used as a specific application, although the results are general. We assume throughout that spin-lattice relaxation times, T-1, do not change. For a given flip angle, theta, TR's are calculated which result in maximal SNR per unit time under 10%, 5%, and 1% constraints on quantitation errors. Additional simulations were performed to demonstrate explicitly the dependence of the quantitation errors on TR for a fixed theta. We find (i) if the allowed error is large, and when both metabolite concentrations and rate constants vary, LATR-C permits use of shorter TR, and hence yields greater SNR per unit time, than LATR-NC (ii) for small allowed error, the two methods give similar TR's and SNR per unit time, so that the simpler LATR-NC experiment may be preferred; (iii) large values of theta result in similar constrained TR's and hence SNR per unit time for the two methods; (iv) the ratio of concentrations of metabolites with similar T-1 exhibit similar errors for the two methods. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIA, NIH, Baltimore, MD 21224 USA. RP Spencer, RGS (reprint author), NIA, NIH, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD FEB PY 2003 VL 160 IS 2 BP 126 EP 130 DI 10.1016/S1090-7807(02)00104-0 PG 5 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 656YL UT WOS:000181638600007 PM 12615153 ER PT J AU Rebmann, AJ Sheehan, FT AF Rebmann, AJ Sheehan, FT TI Precise 3D skeletal kinematics using fast phase contrast magnetic resonance imaging SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine (ISMRM) CY 2001 CL GLASGOW, SCOTLAND SP Int Soc Magnet Resonance Med DE musculoskeltal; dynamic MRI; patella; femur tibia; knee ID PATELLOFEMORAL JOINT; KNEE EXTENSION; TRACKING; MOTION; PATELLA; MRI; CT AB Purpose: To examine the precision of cine phase contrast (PC) magnetic resonance imaging (MRI) techniques as applied to the quantification of three-dimensions knee joint kinematics. Materials and Methods: The knee joints of eight healthy volunteers were studied using three different dynamic, PC MRI protocols: cine-PC (one average), cine-PC (two averages), and cine-PC with segmented phase encoding (fast PC). Results: Fast-PC has comparable precision, shorter scan times, and improved subject interexam variability (SIEV) compared to cine-PC (two averages). Further, cine-PC (one average) has low precision and high SIEV, making fast-PC the preferred method of data acquisition. Specifically, the precision of fast-PC MRI in measuring knee joint kinematics ranged from 0.22degrees-1.16degrees. Conclusion: A cine-PC MRI technique utilizing segmented phase encoding (fast-PC MRI) acquires dynamic data at a faster rate than other PC imaging protocols, without compromising data precision. Being able to acquire precise 3D kinematics with shorter imaging times is critical if we are to use this technique to advance ongoing research in musculoskeletal kinematics. C1 Catholic Univ Amer, Washington, DC 20064 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. RP Sheehan, FT (reprint author), Catholic Univ Amer, Washington, DC 20064 USA. RI sheehan, frances/B-6962-2009 NR 26 TC 34 Z9 36 U1 1 U2 2 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 FEB PY 2003 VL 17 IS 2 BP 206 EP 213 DI 10.1002/jmri.10253 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 670JE UT WOS:000182403400008 PM 12541228 ER PT J AU Keller, PA Lipkus, IM Rimer, BK AF Keller, PA Lipkus, IM Rimer, BK TI Affect, framing, and persuasion SO JOURNAL OF MARKETING RESEARCH LA English DT Article ID POSITIVE AFFECT; SELF-REGULATION; BREAST-CANCER; RISK-TAKING; BEHAVIOR; MOOD; ELABORATION; ENVIRONMENT; COMMERCIALS; DEPRESSION AB The authors conduct two experiments that indicate that the effectiveness of loss- versus gain-framed messages depends on the affective state of the message recipient. In Experiment 1, the authors find that participants induced with a positive mood are more persuaded by the loss-framed message, whereas participants induced with a negative mood are more persuaded by the gain-framed message. In addition, the authors observe that participants in a positive mood have higher risk estimates and lower costs in response to the loss frame than the gain frame, whereas the reverse is true for participants in a negative mood. The authors replicate these effects in Experiment 2 in which they measure rather than induce the participants' affective state. C1 Dartmouth Coll, Tuck Sch Business, Hanover, NH 03755 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Natl Canc Inst, Bethesda, MD 20892 USA. RP Keller, PA (reprint author), Dartmouth Coll, Tuck Sch Business, Hanover, NH 03755 USA. NR 47 TC 46 Z9 48 U1 3 U2 27 PU AMER MARKETING ASSOC PI CHICAGO PA 311S WACKER DR, STE 5800, CHICAGO, IL 60606-6629 USA SN 0022-2437 J9 J MARKETING RES JI J. Mark. Res. PD FEB PY 2003 VL 40 IS 1 BP 54 EP 64 DI 10.1509/jmkr.40.1.54.19133 PG 11 WC Business SC Business & Economics GA 648UX UT WOS:000181170000005 ER PT J AU Praetorius, HA Frokiaer, J Nielsen, S Spring, KR AF Praetorius, HA Frokiaer, J Nielsen, S Spring, KR TI Bending the primary cilium opens Ca2+-sensitive intermediate-conductance K+ channels in MDCK cells SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE DiBAC(4)(3); Ca2+; fluo-4; flow; Ba2+; charybdotoxin ID CORTICAL COLLECTING DUCT; EPITHELIAL-CELLS; APICAL MEMBRANE; KIDNEY; RAT; SECRETION; TUBULE; ACTIVATION; TRANSPORT; VOLTAGE AB Increasing tubular fluid flow rate has previously been shown to induce K+ secretion in mammalian cortical collecting duct. The mechanism responsible was examined in the present study using MDCK cells as a model. The change in membrane potential difference (Em) of MDCK cells was measured with a fluorescent voltage-sensitive dye, Di-BAC(4)(3), when the cell's primary cilium was continuously bent with a micropipette or by the flow of perfusate. Bending the cilium produced a hyperpolarization of the membrane that lagged behind the increase in intracellular Ca2+ concentration by an average of 36 seconds. Gd3+, an inhibitor of the flow-induced Ca2+ increase, prevented the hyperpolarization. Blocking K+ channels with Ba2+ reduced the flow-induced hyperpolarization, implying that it resulted from activation of Ca2+ -sensitive K+ channels. Further studies demonstrated that the hyperpolarization was diminished by the blocker of Ca2+-activated K channels, charybdotoxin, whereas iberiotoxin or apamin had no effect, results consistent with the activation of intermediate-conductance Ca2+-sensitive K+ channels. RT-PCR analysis and sequencing confirmed the presence of intermediate-conductance K+ channels in MDCK cells. We conclude that the increase in intracellular Ca2+ associated with bending of the primary cilium is the cause of the hyperpolarization and increased K+ conductance in MDCK cells. C1 Aarhus Univ, Water & Salt Res Ctr, Aarhus, Denmark. Aarhus Univ, Inst Expt Clin Res, Aarhus, Denmark. Aarhus Univ, Inst Anat, Aarhus, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Praetorius, HA (reprint author), Aarhus Univ, Water & Salt Res Ctr, Aarhus, Denmark. NR 28 TC 90 Z9 91 U1 0 U2 7 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD FEB 1 PY 2003 VL 191 IS 3 BP 193 EP 200 DI 10.1007/s00232-002-1055-z PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 642NP UT WOS:000180810700004 PM 12571753 ER PT J AU Yuan, BZ Zhou, XL Zimonjic, DB Durkin, ME Popescu, NC AF Yuan, BZ Zhou, XL Zimonjic, DB Durkin, ME Popescu, NC TI Amplification and overexpression of the EMS 1 oncogene, a possible prognostic marker, in human hepatocellular carcinoma SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; SQUAMOUS-CELL CARCINOMAS; BREAST-CANCER CELLS; 11Q13 AMPLIFICATION; CONSISTENT PATTERN; CONTACT SITES; CYCLIN D1; GENE; CORTACTIN; ABERRATIONS AB DNA amplification in cancer cells frequently involves oncogenes whose increased expression confers a selective advantage on tumor cell growth. in an attempt to identify novel oncogenes involved in hepatocarcinogenesis, representational difference analysis (RDA) was performed using DNA from a primary human hepatocellular carcinoma (HCC) that showed high-level DNA amplifications on chromosomes 1p32 and 11q13 by comparative genomic hybridization. Ten amplification fragments were isolated by RDA, and when used to probe Southern blots of tumor DNA, there was a 5- to 50-fold increase in hybridization intensity relative to normal DNA. The sequence of one amplification product matched that of the EMS1 oncogene, which is located on chromosome 11q13 and is amplified in other cancers. We detected EMS I amplification in 3 of 17 primary HCC. Overexpression of EMS1 mRNA was observed in 12 of 14 HCC cell lines in the absence of gene amplification or an increased copy-number of the gene. The EMS1 gene encodes cortactin, a cortical actin-associated protein that is a substrate for Src kinase and is involved in cytoskeleton organization. Alterations of the EMS1 gene that lead to overexpression of cortactin may be associated with tumor development in HCC. EMS1 amplification and overexpresion is indicative of unfavorable prognosis in several cancers and may have similar prognostic implications in liver cancer. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bldg 37,Room 4128B,37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA. NR 30 TC 44 Z9 52 U1 1 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD FEB PY 2003 VL 5 IS 1 BP 48 EP 53 DI 10.1016/S1525-1578(10)60451-5 PG 6 WC Pathology SC Pathology GA 639LU UT WOS:000180631100009 PM 12552080 ER PT J AU Trott, JF Hovey, RC Koduri, S Vonderhaar, BK AF Trott, JF Hovey, RC Koduri, S Vonderhaar, BK TI Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; CHINESE-HAMSTER OVARY; BREAST-CANCER CELLS; GM-CSF RECEPTOR; SIGNAL-TRANSDUCTION; PLASMA PROLACTIN; PRL RECEPTOR; SHORT FORMS; PROMOTER UTILIZATION; EXPRESSION AB Endocrine and autocrine prolactin (PRL) exerts effects on normal breast and breast cancer cells, and high serum PRL is a poor prognostic factor for colorectal cancer. Here we tested the hypothesis that short isoforms of the PRL receptor (PRLR) in human tissue regulate the actions of PRL in cancer. Using 3' RACE we isolated five splice variants of the human PRLR (hPRLR), three of which encode the complete extracellular binding domain. Two of these isoforms, short form 1a (SF1a) and short form 1b (SF1b), possess unique intracellular domains encoded by splicing to exon 11 from exons 10 and 9 respectively. A third novel isoform (Delta7/11) reflects alternative splicing from exon 7 to exon 11 and encodes a secreted soluble PRL-binding protein. Additional splice variants of SF1b and Delta7/11 that lacked exon 4 (Delta4-SF1b and A4-Delta7/11) were also identified. Functional analyses indicated that hPRLR-SF1b is a strong dominant-negative to the differentiative function of the PRLR long form while hPRLR-SF1a is a weaker dominant-negative. Differential abundance of SF1a, SF1b and Delta7/11 expression was detected in normal breast, colon, placenta, kidney, liver, ovary and pancreas, and breast and colon tumors. Taken together, these data indicate the presence of multiple isoforms of the hPRLR that may function to modulate the endocrine and autocrine effects of PRL in normal human tissue and cancer. C1 NCI, Mol & Cellular Endocrinol Sect, Bethesda, MD 20892 USA. RP Vonderhaar, BK (reprint author), NCI, Mol & Cellular Endocrinol Sect, 5B47-10 Ctr Dr, Bethesda, MD 20892 USA. NR 49 TC 77 Z9 84 U1 0 U2 2 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD FEB PY 2003 VL 30 IS 1 BP 31 EP 47 DI 10.1677/jme.0.0300031 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 650WR UT WOS:000181287000003 PM 12580759 ER PT J AU Patel, M McCully, C Godwin, K Balis, FM AF Patel, M McCully, C Godwin, K Balis, FM TI Plasma and cerebrospinal fluid pharmacokinetics of intravenous temozolomide in non-human primates SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE temozolomide; pharmacokinetics; cerebrospinal fluid; blood-brain barrier; brain tumors ID PHASE-I; ANTITUMOR IMIDAZOTETRAZINES; MALIGNANCIES; TRIAL AB Temozolomide is a prodrug that undergoes spontaneous chemical degradation at physiologic pH to form the highly reactive alkylating agent, methyl-triazenyl imidazole carboxamide ( MTIC). In clinical trials, temozolomide has activity in gliomas and is approved for recurrent anaplastic astrocytoma. We, therefore, studied the penetration of temozolomide into the cerebrospinal fluid (CSF) as a surrogate for blood-brain barrier penetration in a non-human primate model. Three Rhesus monkeys with indwelling Ommaya reservoirs received 7.5 mg/kg (150 mg/m(2)) of temozolomide as a 1 h intravenous infusion. Frequent blood and CSF samples were obtained over 24 h, plasma was immediately separated by centrifugation at 4degreesC, and plasma and CSF samples were acidified with HCl. Temozolomide concentration in plasma and CSF was measured by reverse-phase high-pressure liquid chromatography. Plasma temozolomide concentration peaked 0.5 h after the end of the infusion and was 104 +/- 3 muM. The mean peak CSF temozolomide concentration was 26 +/- 4 muM at 2.5 h. The mean areas under the temozolomide concentration-time curves in plasma and CSF were 392 +/- 18 and 126 +/- 18 muM h, respectively, and the CSF : plasma ratio was 0.33 +/- 0.06. Clearance of temozolomide was 0.116 +/- 0.004 l/kg/h, and the volume of distribution at steady state was 0.254 +/- 0.033 l/kg. In this non-human primate model, temozolomide penetrated readily across the blood-brain barrier. These findings are consistent with the activity of temozolomide in brain tumors. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Balis, FM (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10,Rm 13C103,10 Ctr Dr,MSC 1920, Bethesda, MD 20892 USA. NR 17 TC 69 Z9 73 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD FEB PY 2003 VL 61 IS 3 BP 203 EP 207 DI 10.1023/A:1022592913323 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 649JL UT WOS:000181204400003 PM 12675312 ER PT J AU Mattson, MP Duan, WZ Guo, ZH AF Mattson, MP Duan, WZ Guo, ZH TI Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE Alzheimer's disease; brain-derived neurotrophic factor (BDNF); caloric restriction; chaperone; neurogenesis stem cells ID PROTECTS HIPPOCAMPAL-NEURONS; CORTICAL SYNAPTIC TERMINALS; AMYLOID PRECURSOR PROTEIN; LONG-TERM POTENTIATION; RAT DENTATE GYRUS; DIETARY RESTRICTION; NEUROTROPHIC FACTOR; NEURODEGENERATIVE DISORDERS; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE AB Although all cells in the body require energy to survive and function properly, excessive calorie intake over long time periods can compromise cell function and promote disorders such as cardiovascular disease, type-2 diabetes and cancers. Accordingly, dietary restriction (DR; either caloric restriction or intermittent fasting, with maintained vitamin and mineral intake) can extend lifespan and can increase disease resistance. Recent studies have shown that DR can have profound effects on brain function and vulnerability to injury and disease. DR can protect neurons against degeneration in animal models of Alzheimer's, Parkinson's and Huntington's diseases and stroke. Moreover, DR can stimulate the production of new neurons from stem cells (neurogenesis) and can enhance synaptic plasticity, which may increase the ability of the brain to resist aging and restore function following injury. Interestingly, increasing the time interval between meals can have beneficial effects on the brain and overall health of mice that are independent of cummulative calorie intake. The beneficial effects of DR, particularly those of intermittent fasting, appear to be the result of a cellular stress response that stimulates the production of proteins that enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic factors such as brain-derived neurotrophic factor (BDNF), protein chaperones such as heat-shock proteins, and mitochondrial uncoupling proteins. Some beneficial effects of DR can be achieved by administering hormones that suppress appetite (leptin and ciliary neurotrophic factor) or by supplementing the diet with 2-deoxy-d-glucose, which may act as a calorie restriction mimetic. The profound influences of the quantity and timing of food intake on neuronal function and vulnerability to disease have revealed novel molecular and cellular mechanisms whereby diet affects the nervous system, and are leading to novel preventative and therapeutic approaches for neurodegenerative disorders. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 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 121 TC 165 Z9 172 U1 4 U2 25 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 FEB PY 2003 VL 84 IS 3 BP 417 EP 431 DI 10.1046/j.1471-4159.2003.01586.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 635UF UT WOS:000180417200001 PM 12558961 ER PT J AU Chen, RW Qin, ZH Ren, M Kanai, H Chalecka-Franaszek, E Leeds, P Chuang, DM AF Chen, RW Qin, ZH Ren, M Kanai, H Chalecka-Franaszek, E Leeds, P Chuang, DM TI Regulation of c-Jun N-terminal kinase, p38 kinase and AP-1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AP-1; excitotoxicity; JNK; lithium neuroprotection; p38; p53 phosphorylation ID ACTIVATED PROTEIN-KINASE; NEUROBLASTOMA SH-SY5Y CELLS; CNS IN-VIVO; HUMAN P53; SIGNAL-TRANSDUCTION; INDUCED APOPTOSIS; KAPPA-B; INDUCED INHIBITION; NERVOUS-SYSTEM; RAT-BRAIN AB In rat cerebellar granule cells, glutamate induced rapid activation of c-Jun N-terminal kinase (JNK) and p38 kinase to phosphorylate c-Jun (at Ser63) and p53 (at Ser15), respectively, and a subsequent marked increase in activator protein-1 (AP-1) binding that preceded apoptotic death. These glutamate-induced effects and apoptosis could largely be prevented by long-term (7 days) pretreatment with 0.5-2 mM lithium, an antibipolar drug. Glutamate's actions could also be prevented by known blockers of this pathway, MK-801 (an NMDA receptor blocker), SB 203580 (a p38 kinase inhibitor) and curcumin (an AP-1 binding inhibitor). The concentration- and time-dependent suppression of glutamate's effects by lithium and curcumin correlated well with their neuroprotective effects. These results suggest a prominent role of JNK and p38, as well as their downstream AP-1 binding activation and p53 phosphorylation in mediating glutamate excitotoxicity. Moreover, the neuroprotective effects of lithium are mediated, at least in part, by suppressing NMDA receptor-mediated activation of the mitogen-activated protein kinase pathway. C1 NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bldg 10-Rm 4C206,10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA. NR 60 TC 83 Z9 104 U1 0 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 FEB PY 2003 VL 84 IS 3 BP 566 EP 575 DI 10.1046/j.1471-4159.2003.01548.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 635UF UT WOS:000180417200016 PM 12558976 ER PT J AU Le, YZ Gagneten, S Larson, T Santha, E Dobi, A von Agoston, D Sauer, B AF Le, YZ Gagneten, S Larson, T Santha, E Dobi, A von Agoston, D Sauer, B TI Far-upstream elements are dispensable for tissue-specific proenkephalin expression using a Cre-mediated knock-in strategy SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Cre/lox; enkephalin; ES cells; knock-in; transcriptional regulation; transgenic mice ID EMBRYONIC STEM-CELLS; TRANSGENIC MICE; GENE-EXPRESSION; RAT-HEART; TARGETED MUTATION; FUSION GENE; BRAIN; PROMOTER; SYSTEM; DIFFERENTIATION AB Several cis -regulatory DNA elements are present in the 5' upstream regulatory region of the enkephalin gene (ENK) promoter. To determine their role in conferring organ-specificity of ENK expression in mice and to circumvent the position effects from random gene insertion that are known to often frustrate such analysis in transgenic mice, we used a Cre-mediated gene knock-in strategy to target reporter constructs to a 'safe haven' loxP -tagged locus in the hypoxanthine phosphoribosyltransferase (HPRT)gene. Here we report reliable and reproducible reporter gene expression under the control of the 5' upstream regulatory region of the mouse ENK gene in gene-modified mice using this Cre-mediated knock-in strategy. Comparison of two 5'ENK regulatory regions (one with and the other without known cis -regulatory DNA elements) in the resulting adult mice showed that conserved far-upstream cis -regulatory DNA elements are dispensable for correct organ-specific gene expression. Thus the proximal 1.4 kb of the murine ENK promoter region is sufficient for organ-specificity of ENK gene expression when targeted to a safe-haven genomic locus. These results suggest that conservation of the far-upstream DNA elements serves more subtle roles, such as the developmental or cell-specific expression of the ENK gene. C1 Stowers Inst Med Res, Kansas City, MO 64110 USA. NIDDKD, Biochem & Metab Lab, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Dev Biol Program, Oklahoma City, OK 73104 USA. NICHD, LDN, NIH, Bethesda, MD USA. USU, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD USA. RP Sauer, B (reprint author), Stowers Inst Med Res, 1000 E 50th St, Kansas City, MO 64110 USA. NR 40 TC 17 Z9 17 U1 0 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 FEB PY 2003 VL 84 IS 4 BP 689 EP 697 DI 10.1046/j.0022-3042.2003.01573.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 641JV UT WOS:000180742400007 PM 12562513 ER PT J AU Gary, DS Milhavet, O Camandola, S Mattson, MP AF Gary, DS Milhavet, O Camandola, S Mattson, MP TI Essential role for integrin linked kinase in Akt-mediated integrin survival signaling in hippocampal neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Akt kinase; apoptosis; excitotoxicity; glutamate; laminin; PI3 kinase ID LONG-TERM POTENTIATION; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; NEURITE OUTGROWTH; CELL-ADHESION; SYMPATHETIC NEURONS; GENE-EXPRESSION; UP-REGULATION; CANCER CELLS; APOPTOSIS AB Activation of integrin receptors in neurons can promote cell survival and synaptic plasticity, but the underlying signal transduction pathway(s) is unknown. We report that integrin signaling prevents apoptosis of embryonic hippocampal neurons by a mechanism involving integrin-linked kinase (ILK) that activates Akt kinase. Activation of integrins using a peptide containing the amino acid sequence EIKLLIS derived from the alpha chain of laminin protected hippocampal neurons from apoptosis induced by glutamate or staurosporine, and increased Akt activity in a beta(1) integrin-dependent manner. Transfection of neurons with a plasmid encoding dominant negative Akt blocked the protective effect of the integrin-activating peptide, as did a chemical inhibitor of Akt. Although inhibitors of phosphoinositide-3 (PI3) kinase blocked the protective effect of the peptide, we found no increase in PI3 kinase activity following integrin stimulation suggesting that PI3 kinase was necessary for Akt activity but was not sufficient for the increase in Akt activity following integrin activation. Instead, we show a requirement for ILK in integrin receptor-induced Akt activation. ILK was activated following integrin stimulation and dominant negative ILK blocked integrin-mediated Akt activation and cell survival. Activation of ILK and Akt were also required for neuroprotection by substrate-associated laminin. These results establish a novel pathway that signals cell survival in neurons in response to integrin receptor activation. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 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 53 TC 63 Z9 65 U1 0 U2 0 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 FEB PY 2003 VL 84 IS 4 BP 878 EP 890 DI 10.1046/j.0022-3042.2003.01579.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 641JV UT WOS:000180742400024 PM 12562530 ER PT J AU Grinevich, V Ma, XM Jirikowski, G Verbalis, J Aguilera, G AF Grinevich, V Ma, XM Jirikowski, G Verbalis, J Aguilera, G TI Lipopolysaccharide endotoxin potentiates the effect of osmotic stimulation on vasopressin synthesis and secretion in the rat hypothalamus SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE lipopolysaccharide; osmotic stimulation; vasopressin; hypothalamic supraoptic and paraventricular nuclei ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; ARGININE-VASOPRESSIN; GENE-TRANSCRIPTION; SUPRAOPTIC NUCLEI; MAGNOCELLULAR VASOPRESSIN; MEMBRANE DEPOLARIZATION; HETERONUCLEAR RNA; MESSENGER-RNAS; TNF-ALPHA AB Vasopressin secreted by magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei is essential for water balance. In this study, we examined magnocellular neurone responses to osmotic stimulation in vehicle-injected controls or rats receiving an intraperitoneal (i.p.) injection of 250 mug/100 g of lipopolysaccharide (LPS), 3 h or 6 h earlier. LPS injection had no effect on plasma vasopressin concentrations in control rats but it caused marked and transient potentiation of the responses to a single i.p. injection of hypertonic saline (five- and two-fold, 3 and 6 h after LPS, respectively). The enhancement of plasma vasopressin responses was independent of plasma sodium concentrations or changes in blood pressure. Basal vasopressin mRNA expression in the paraventricular and supraoptic nuclei decreased slightly 6 h after LPS injection, without changes in vasopressin transcription as indicated by vasopressin heteronuclear (hn) RNA levels. Parvocellular neurones showed expected increases in vasopressin hnRNA expression following LPS injection and a further increase after i.p. hypertonic saline injection (due to the painful component). In contrast to magnocellular vasopressin mRNA expression, the effects of LPS and hypertonic saline injections in parvocellular neurones were additive and not synergistic. Light microscopic immunohistochemical examination revealed an increase in size of vasopressin but not oxytocin axonal terminals in the neural lobe 3 h after LPS injection. Osmotic stimulation caused marked depletion of vasopressin immunoreactivity in axonal terminals of the neural lobe in both control and LPS-pretreated rats. The changes in vasopressin axon terminals were accompanied by induction of interleukin (IL)-1beta and IL-6 in the posterior pituitary. The data show that endotoxemia causes morphological and functional alterations of the hypothalamic neurohypophyseal system, resulting in facilitation rather than inhibition of vasopressin synthesis, and secretion in response to osmotic stimulation. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Klinikum Univ Jena, Inst Anat 2, Jena, Germany. Georgetown Univ, Dept Endocrinol, Washington, DC USA. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bldg 10 Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 47 TC 18 Z9 19 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD FEB PY 2003 VL 15 IS 2 BP 141 EP 149 DI 10.1046/j.1365-2826.2003.00967.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 636VV UT WOS:000180478700005 PM 12535156 ER PT J AU Wei, RT Listwak, SJ Sternberg, EM AF Wei, RT Listwak, SJ Sternberg, EM TI Lewis hypothalamic cells constitutively and upon stimulation express higher levels of mRNA for pro-inflammatory cytokines and related molecules: comparison with inflammatory resistant Fischer rat hypothalamic cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE LEW/N; F344/N; hypothalamic cultures; cytokine; homeostasis ID TUMOR-NECROSIS-FACTOR; LIPOPOLYSACCHARIDE-BINDING PROTEIN; MESSENGER-RNA EXPRESSION; PITUITARY-ADRENAL AXIS; CENTRAL-NERVOUS-SYSTEM; LPS-INDUCED ANOREXIA; RECEPTOR-TYPE-I; SUSCEPTIBLE LEWIS; FACTOR-ALPHA; QUANTITATIVE PCR AB Endogenous hypothalamic pro-inflammatory cytokines modulate the hypothalamic-pituitary-adrenal (HPA) axis responses. To investigate whether hypothalamic IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) are associated with differential inflammatory susceptibilities between Lewis (LEW/N) and Fischer (F344/N) rats, mRNA levels of pro-inflammatory cytokines and related molecules in hypothalamic cell cultures of both strains were quantified by real-time polymerase chain reaction (PCR). In addition to IL-1beta, IL-6, TNF-alpha, and their receptors, LEW/N hypothalamic cells also transcribed more anti-inflammatory molecules, IL-1RII, IL-1RA, and transforming growth factor (TGFbeta1), than F334/N cells. Our findings suggest that a balance exists between transcripts for endogenous pro- and antiinflammatory molecules in LEW/N rats that may allow them, under basal conditions, to maintain hypothalamic homeostasis and health. However, under stimulated conditions, this balance may be more easily perturbed toward chronic inflammation. Published by Elsevier Science B.V. C1 NIMH, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Integrat Neural Immune Program, NIH, 36 Convent Dr,Rm 1A23, Bethesda, MD 20892 USA. NR 38 TC 23 Z9 23 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 FEB PY 2003 VL 135 IS 1-2 BP 10 EP 28 AR PII S0165-5728(02)00429-0 DI 10.1016/S0165-5728(02)00429-0 PG 19 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 651XW UT WOS:000181349500002 PM 12576220 ER PT J AU Hu, SB Zhao, ZS Yhap, C Grinberg, A Huang, SP Westphal, H Gold, P AF Hu, SB Zhao, ZS Yhap, C Grinberg, A Huang, SP Westphal, H Gold, P TI Vasopressin receptor 1a-mediated negative regulation of B cell receptor signaling SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE V1a; knockout; B cell receptor (BCR); T cell; immunoglobulin ID CORTICOTROPIN-RELEASING HORMONE; ARGININE-VASOPRESSIN; IMMUNE-SYSTEM; B-1 CELLS; INFLAMMATORY DISEASE; RAT THYMUS; EXPRESSION; SPLEEN; AUTOIMMUNITY; LYMPHOCYTES AB We report here a study of T and B cell development and function in mice with disruption of the vasopressin receptor I a (v I a) gene. Loss of the v I a receptor caused a shift from IgM(high)/IgD(high) to the more mature IgM(low)/IgD(high) B cells, a significantly greater extent of splenic B cells proliferation in response to anti-IgM stimulation, and enhanced IgG1 and IgG2b production in response to immune challenge with T-dependent antigen. B-1 cells were increased in v1a(-/-) mice. In contrast, T cell differentiation and activation were normal in v1a(-/-) mice. Our data identify a novel function for v I a in the periphery as a negative regulator of B cell receptor (BCR) signaling. These data suggest that in addition to its other stress-related effects, vasopressin may also serve as a counter-regulatory restraint upon the immune system during fight or flight situations. Published by Elsevier Science B.V. C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Hu, SB (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, 10 Ctr Dr,10-2D46, Bethesda, MD 20892 USA. NR 61 TC 31 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB PY 2003 VL 135 IS 1-2 BP 72 EP 81 DI 10.1016/S0165-5728(02)00442-3 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 651XW UT WOS:000181349500008 PM 12576226 ER PT J AU Hanakawa, T Immisch, I Toma, K Dimyan, MA Van Gelderen, P Hallett, M AF Hanakawa, T Immisch, I Toma, K Dimyan, MA Van Gelderen, P Hallett, M TI Functional properties of brain areas associated with motor execution and imagery SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; IMAGINED HAND MOVEMENTS; FINGER MOVEMENTS; CORTICOSPINAL PROJECTIONS; TOPOGRAPHIC ORGANIZATION; MENTAL REPRESENTATION; PARIETAL CORTEX; FRONTAL-LOBE; ACTIVATION; PET AB Imagining motor acts is a cognitive task that engages parts of the executive motor system. While motor imagery has been intensively studied using neuroimaging techniques, most studies lack behavioral observations. Here, we used functional MRI to compare the functional neuroanatomy of motor execution and imagery using a task that objectively assesses imagery performance. With surface electromyographic monitoring within a scanner, 10 healthy subjects performed sequential finger-tapping movements according to visually presented number stimuli in either a movement or an imagery mode of performance. We also examined effects of varied and fixed stimulus types that differ in stimulus dependency of the task. Statistical parametric mapping revealed movement-predominant activity, imagery-predominant activity, and activity common to both movement and imagery modes of performance (movement-and-imagery activity). The movement-predominant activity included the primary sensory and motor areas, parietal operculum, and anterior cerebellum that had little imagery-related activity (-0.1 similar to 0.1%), and the caudal premotor areas and area 5 that had mild-to-moderate imagery-related activity (0.2 similar to 0.7%). Many frontoparietal areas and posterior cerebellum demonstrated movement-and-imagery activity. Imagery-predominant areas included the precentral sulcus at the level of middle frontal gyrus and the posterior superior parietal cortex/precuneus. Moreover, activity of the superior precentral sulcus and intraparietal sulcus areas, predominantly on the left, was associated with accuracy of the imagery task performance. Activity of the inferior precentral sulcus (area 6/44) showed stimulus-type effect particularly for the imagery mode. A time-course analysis of activity suggested a functional gradient, which was characterized by a more "executive" or more "imaginative" property in many areas related to movement and/or imagery. The results from the present study provide new insights into the functional neuroanatomy of motor imagery, including the effects of imagery performance and stimulus-dependency on brain activity. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr, Bethesda, MD 20892 USA. RI Dimyan, Michael/B-1715-2012; OI Dimyan, Michael/0000-0002-9715-9741 NR 65 TC 306 Z9 318 U1 6 U2 29 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2003 VL 89 IS 2 BP 989 EP 1002 DI 10.1152/jn.00132.2002 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 642WD UT WOS:000180827700036 PM 12574475 ER PT J AU Song, HT Nie, LP Rodriguez-Contreras, A Sheng, ZH Yamoah, EN AF Song, HT Nie, LP Rodriguez-Contreras, A Sheng, ZH Yamoah, EN TI Functional interaction of auxiliary subunits and synaptic proteins with Ca(v)1.3 may impart hair cell Ca2+ current properties SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; PRESYNAPTIC CALCIUM CHANNELS; TRANSMITTER RELEASE; ALPHA(1D) SUBUNIT; CHICKENS COCHLEA; KINETIC-ANALYSIS; ACTIVE ZONES; SYNTAXIN; FROG; ALPHA-1-SUBUNIT AB We assessed the functional determinants of the properties of L-type Ca2+ currents in hair cells by co-expressing the pore-forming Ca(V)1.3alpha(1) subunit with the auxiliary subunits beta(1A) and/or alpha(2delta). Because Ca2+ channels in hair cells are poised to interact with synaptic proteins, we also co-expressed the Ca(V)1.3alpha(1) subunit with syntaxin, vesicle-associated membrane protein (VAMP), and synaptosome associated protein of 25 kDa (SNAP25). Expression of the Ca(V)1.3alpha(1) subunit in human embryonic kidney cells (HEK 293) produced a dihydropyridine (DHP)-sensitive Ca2+ current (peak current density -2.0 +/- 0.2 pA/pF; n = 11). Co-expression with beta(1A) and alpha(2delta) subunits enhanced the magnitude of the current (peak current density: Ca(V)1.3alpha(1) + beta(1A) = -4.3 +/- 0.8 pA/pF, n = 10; Ca(V)1.3alpha(1) + beta(1A) + alpha(2delta) = -4.1 +/- 0.6 pA/pF, n = 9) and produced a leftward shift of approximately 9 mV in the voltage-dependent activation of the currents. Furthermore, co-expression of Ca(V)1.3alpha(1) with syntaxin/ VAMP/SNAP resulted in at least a twofold increase in the peak current density (-4.7 +/- 0.2 pA/pF; n = 11) and reduced the extent of inactivation of the Ca2+ currents. Botulinum toxin, an inhibitor of syntaxin, accelerated the inactivation profile of Ca2+ currents in hair cells. Immunocytochemical data also indicated that the Ca2+ channels and syntaxin are co-localized in hair cells, suggesting there is functional interaction of the Ca(V)1.3alpha(1) with auxiliary subunits and synaptic proteins, that may contribute to the distinct properties of the DHP-sensitive channels in hair cells. C1 Univ Calif Davis, Ctr Neurosci, Dept Otolaryngol, Davis, CA 95616 USA. Beijing Hosp, Dept Otolaryngol, Beijing 10000, Peoples R China. NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. RP Yamoah, EN (reprint author), Univ Calif Davis, Ctr Neurosci, Dept Otolaryngol, 1544 Newton Ct, Davis, CA 95616 USA. FU NIDCD NIH HHS [DC-03828] NR 43 TC 25 Z9 28 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2003 VL 89 IS 2 BP 1143 EP 1149 DI 10.1152/jn.00482.2002 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 642WD UT WOS:000180827700048 PM 12574487 ER PT J AU Grimm, JW Lu, L Hayashi, T Hope, BT Su, TP Shaham, Y AF Grimm, JW Lu, L Hayashi, T Hope, BT Su, TP Shaham, Y TI Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: Implications for incubation of cocaine craving SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amygdala; extinction; nucleus accumbens; reinstatement; relapse; ventral tegmental area ID NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION; NEURONAL PLASTICITY; CONDITIONED REWARD; DENDRITIC SPINES; ADDICTION; AMPHETAMINE; NEUROBIOLOGY; PERSISTENCE; EXPRESSION AB Using a rat model of drug craving, we found that the responsiveness to cocaine cues progressively increases or incubates over the first 60 d of cocaine withdrawal. Here we studied whether alterations in brain-derived neurotrophic factor (BDNF) protein levels within the mesolimbic dopamine system are associated with this incubation phenomenon. BDNF is involved in synaptic plasticity and was found to enhance responding for cues associated with natural rewards. Rats were trained to press a lever to receive intravenous cocaine or oral sucrose for 6 hr/d for 10 d; each earned reward was paired with a tone-light cue. Resumption of lever-pressing behavior was then assessed on days 1, 30, or 90 of reward withdrawal. First, resistance to extinction was assessed during 6 hr in which lever presses were not reinforced and the cue was absent. Second, cue-induced reinstatement was assessed after extinction during 1 hr in which responding led to cue presentations. Other rats were killed without testing on days 1, 30, and 90 of reward withdrawal, and BDNF and nerve growth factor (NGF) protein levels were measured in the ventral tegmental area (VTA), accumbens, and amygdala. Lever pressing during extinction and cue-induced reinstatement tests of cocaine craving progressively increased after cocaine withdrawal. Time-dependent changes also were observed during the tests for sucrose craving, with maximal responding on day 30. BDNF, but not NGF, levels in the VTA, accumbens, and amygdala progressively increased after cocaine, but not sucrose, withdrawal. Time-dependent increases in BDNF levels may lead to synaptic modifications that underlie enhanced responsiveness to cocaine cues after prolonged withdrawal periods. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,US DHHS, Baltimore, MD 21224 USA. NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH,US DHHS, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,US DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hayashi, Teruo/A-9690-2008; Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; NR 34 TC 354 Z9 369 U1 4 U2 19 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 FEB 1 PY 2003 VL 23 IS 3 BP 742 EP 747 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 643MQ UT WOS:000180865400004 PM 12574402 ER PT J AU Hu, GH Lyeth, BG Zhao, XR Mitchell, JB Watson, JC AF Hu, GH Lyeth, BG Zhao, XR Mitchell, JB Watson, JC TI Neuroprotection by the stable nitroxide, 3-carbamoyl-proxyl during reperfusion in a rat model of transient focal ischemia SO JOURNAL OF NEUROSURGERY LA English DT Article DE cerebral ischemia; reperfusion damage; 3-carbamoyl-proxyl; nitroxide; rat ID SUPEROXIDE-DISMUTASE MIMICS; CEREBRAL-ISCHEMIA; NITRIC-OXIDE; ACUTE STROKE; IN-VIVO; TRIAL; ANTAGONIST; DAMAGE; INJURY; MECHANISM AB Object. Nitroxides mimic superoxide dismutase (SOD) biochemically and may prevent free radical oxidative injury in settings in which endogenous SOD is overwhelmed. The authors have previously shown the efficacy of a nitroxide, Tempol, in reducing stroke infarct size. Of the nitroxides, 3-carbamoyl-proxyl (3-CP) is especially promising for clinical use, because it does not cause hypotension in animals. Its efficacy in brain ischemia, however, is untested. The goal of this study was to ascertain whether 3-CP would reduce brain damage in a rat ischemia-reperfusion model. Methods. The authors performed a blinded, dose-response study of the effect of different amounts of 3-CP (1, 10, and 100 mg/kg) on infarct size at 24 hours after focal ischemia and reperfusion. The 3-CP was given intravenously during reperfusion, which followed I hour of reversible ischemia induced by a thread placed intraluminally in the middle cerebral artery of rats. Brain infarcts, measured with 2,3,5-triphenyltetrazolium chloride staining in six 3-CP groups, were compared with those measured in controls (animals given an equal volume of saline). Edema-corrected infarct sizes (mean +/- standard deviation) were as follows: 146 +/- 64 mm(3) in controls; 107 +/- 18 mm(3) in rats given 1 mg/kg 3-CP; 40 +/- 20 mm(3) in those given 10 mg/kg 3-CP; and 44 +/- 17 mm(3) in those given 100 mg/kg 3-CP. A statistically significant reduction in infarct size was achieved in the 10- and 100-mg/kg 3-CP-treated groups (p < 0.01). A reduction in infarct size was also seen in the 1 mg/kg 3-CP-treated group, but this did not reach statistical significance. The authors observed no effects of 3-CP on blood pressure or brain temperature. Conclusions. Given at reperfusion, 3-CP significantly decreases brain infarct size at doses of 10 and 100 mg/kg without causing hypotension. The authors found that 3-CP is well suited for further laboratory and clinical use in brain ischemia and reperfusion. C1 Univ Calif Davis, Dept Neurol Surg, Sacramento, CA 95817 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Watson, JC (reprint author), Univ Calif Davis, Dept Neurosurg, 4860 Y St,Suite 3740, Sacramento, CA 95817 USA. FU NINDS NIH HHS [NS29995] NR 27 TC 9 Z9 9 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2003 VL 98 IS 2 BP 393 EP 396 DI 10.3171/jns.2003.98.2.0393 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 643RB UT WOS:000180873300020 PM 12593628 ER PT J AU Gemmill, ME Eskay, RL Hall, NL Douglass, LW Castonguay, TW AF Gemmill, ME Eskay, RL Hall, NL Douglass, LW Castonguay, TW TI Leptin suppresses food intake and body weight in corticosterone-replaced adrenalectomized rats SO JOURNAL OF NUTRITION 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 adrenalectomy; corticosterone; leptin; food intake; body weight; hypothalamus ID GENE-EXPRESSION; MICE; OB; GLUCOCORTICOIDS; DEXAMETHASONE; ADIPOCYTES; BRAIN; SIZE; RNA AB Intracerebroventricular (ICV) injections of leptin decrease food intake and body weight while increasing energy expenditure. Some of these effects are reportedly enhanced in bilaterally adrenal ectomized (ADX) rats. The purpose of the present experiment was to establish the time course of the suppression in body weight and food intake after an ICV injection of leptin. We wanted to establish the effect of varying doses of corticosterone (CORT) on body weight and food intake suppression by using separate groups of ADX, ADX and corticosterone-treated and sham-operated Sprague-Dawley rats. All rats were implanted with cholesterol pellets that varied in CORT content. During the same surgical session, all rats were fitted with a cannula in the lateral ventricle. After recovering from surgery, each rat was administered a 5-mug ICV injection of leptin. ADX rats that were treated with CORT replacement lost more (P < 0.05) weight and took longer (P < 0.05) to return to baseline body weight than sham-operated controls. Leptin injection decreased food consumption to a greater extent (P < 0.05) in the ADX groups treated with CORT than in the sham-operated controls. Plasma insulin increased in a dose-dependent manner in the ADX rats as a function of CORT replacement. The higher of the two CORT replacement doses used in this experiment restored circulating CORT to levels observed in sham-operated controls. Contrary to earlier reports, physiological doses of CORT appear to enhance leptin-induced weight loss. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NIAAA, NIH, Bethesda, MD 20892 USA. RP Castonguay, TW (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. OI Castonguay, Thomas/0000-0003-1176-5095 NR 27 TC 3 Z9 3 U1 1 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2003 VL 133 IS 2 BP 504 EP 509 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 643RW UT WOS:000180875100027 PM 12566491 ER PT J AU Dwyer, J Picciano, MF Raiten, DJ AF Dwyer, J Picciano, MF Raiten, DJ TI Future directions for the integrated CSFII-NHANES: What we eat in America-NHANES SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Future Directions for the Integrated CSFII-NHANES: What We Eat in America-NHANES CY JUN 20-21, 2002 CL ROCKVILLE, MARYLAND DE What We Eat in America-NHANES; nutritional status; Office of Dietary Supplements; National Institutes of Health; Agricultural Research Service; US Department of Agriculture AB The history of the integration of the dietary data collection from the National Health and Nutrition Examination Survey (NHANES) and the Continuing Survey of Food Intakes by Individuals (CSFII) is reviewed. The purposes and process of the workshop are presented. The three key topics of the workshop are summarized. The key roles of cosponsors and participants are acknowledged. C1 US Dept Hlth & Human Serv, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. US Dept Hlth & Human Serv, Off Prevent Res & Int Programs, NIH, Bethesda, MD 20892 USA. USDA ARS, Washington, DC 20250 USA. RP Picciano, MF (reprint author), US Dept Hlth & Human Serv, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. NR 2 TC 30 Z9 30 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2003 VL 133 IS 2 BP 576S EP 581S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 643RW UT WOS:000180875100043 PM 12566506 ER PT J AU Dwyer, J Picciano, MF Raiten, DJ AF Dwyer, J Picciano, MF Raiten, DJ CA Steering Comm TI Collection of food and dietary supplement intake data: What We Eat in America-NHANES SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Future Directions for the Integrated CSFII-NHANES: What We Eat in America-NHANES CY JUN 20-21, 2002 CL ROCKVILLE, MARYLAND DE food intake; supplement intake; survey methodology; dietary recall; data capture AB This paper describes the collection process for the integrated dietary component of the National Health and Nutrition Examination Survey(NHANES) 2002 (entitled What We Eat in America-NHANES), referred to here as the integrated survey. The dietary components of previous NHANES cycles and the Continuing Survey of Food Intake in Individuals (CSFII) are also described. The collection process for foods in the integrated survey consists of an in-person 24-h recall using a computerized 5-step method and a second nonconsecutive 24-h recall via telephone. A food frequency questionnaire is being pilot-tested to provide information on the propensity to consume certain foods. Dietary supplement intakes over the past 30 d are assessed for all persons during the household interview. Other diet-related data are also obtained. Strengths of the integrated survey include information on food and supplement intakes in a representative sample of the civilian noninstitutionalized population of the United States that can be linked to anthropometric, biochemical, clinical and disease history information in NHANES. After reviewing the current state of the art on dietary and dietary supplement data collection, discussion groups consisting of members of key stakeholder community concluded that, although the most advanced methods for dietary data collection available are being used, the differences between how information on food and dietary supplement intakes is collected make it challenging to combine data describing nutrients from both sources to obtain estimates of total nutrient intakes. The discussion groups concluded that more research is needed on these issues and provided key recommendations for future efforts in this important area of public health surveillance. C1 US Dept Health & Human Serv, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. US Dept Health & Human Serv, Off Prevent Res & Int Programs, NIH, Bethesda, MD 20892 USA. USDA ARS, Washington, DC 20250 USA. RP Picciano, MF (reprint author), US Dept Health & Human Serv, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. NR 10 TC 56 Z9 57 U1 0 U2 7 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2003 VL 133 IS 2 BP 590S EP 600S PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 643RW UT WOS:000180875100046 PM 12566509 ER PT J AU Dwyer, J Picciano, MF Raiten, DJ AF Dwyer, J Picciano, MF Raiten, DJ CA Steering Comm TI Estimation of usual intakes: What We Eat in America-NHANES SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Future Directions for the Integrated CSFII-NHANES: What We Eat in America-NHANES CY JUN 20-21, 2002 CL ROCKVILLE, MARYLAND DE ISU method; IOM method; total nutrient intake; food intake; dietary supplement intake ID DOUBLY-LABELED WATER; FOOD-FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; TOTAL-ENERGY EXPENDITURE; BODY-MASS INDEX; DIETARY MEASUREMENTS; URINARY NITROGEN; NATIONAL-HEALTH; SUPPLEMENT USE; WOMEN AB Usual intakes of nutrients are reliable indicators for making associations between diet and health or disease risks. Estimates of consumption of specific foods and food groups are also important for evaluating the progress in meeting key objectives in such national public health initiatives as Healthy People 2010. Reliable and valid estimates of intakes of particular foods, food ingredients, dietary supplements and other bioactive substances are also needed for dietary assessment and regulatory purposes. The ability to generate useful estimates of these constituents often requires much larger sample sizes than are needed for estimating nutrient intakes. Statistical methods recommended by the National Academy of Sciences are described that provide estimates of distributions of usual nutrient intakes and permit dietary assessment and planning at the population level. Statistical and modeling approaches for estimating intakes of foods, dietary supplements and other bioactive substances are also summarized. Based on the deliberations of discussion groups consisting of members of key stakeholder groups involved in the planning, implementation and utilization of national survey data, a high priority was placed on the need for more research to determine the best approaches for applying these methods to dietary data in the integrated What We Eat in America-National Health and Nutrition Examination Survey (NHANES). C1 US Dept Hlth & Human Serv, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. US Dept Hlth & Human Serv, Off Prevent Res & Int Programs, NIH, Bethesda, MD 20892 USA. USDA ARS, Washington, DC 20250 USA. RP Picciano, MF (reprint author), US Dept Hlth & Human Serv, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. NR 47 TC 34 Z9 36 U1 1 U2 12 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2003 VL 133 IS 2 BP 609S EP 623S PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 643RW UT WOS:000180875100048 PM 12566511 ER PT J AU Dwyer, J Picciano, MF Raiten, DJ AF Dwyer, J Picciano, MF Raiten, DJ CA Steering Comm TI Food and dietary supplement databases for What We Eat in America-NHANES SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Future Directions for the Integrated CSFII-NHANES: What We Eat in America-NHANES CY JUN 20-21, 2002 CL ROCKVILLE, MARYLAND DE database; food composition; dietary supplement composition; chemical analysis; label database AB Relative strengths and potential approaches for improvement of food and dietary supplement databases used for tabulating intakes from the dietary component of the What We Eat in America-National Health and Nutrition Examination Survey (NHANES) are discussed. The U.S. Department of Agriculture's Nutrient Data Laboratory develops and maintains the Nutrient Databank System (NDBS) and many nutrient-specific and population-specific databases. NDBS contains data for similar to8000 foods and similar to115 components; tables for compounds of special interest are also available. Nutrient databases need constant revision because of a constantly changing food supply. The completeness of analytical data varies from nutrient to nutrient. The National Center for Health Statistics developed and maintains a database of dietary supplements based on label information. To date, no verification of ingredients has been undertaken. The development of a dietary supplement database containing analytical values would require extensive resources but would be valuable. Databases for vitamin and mineral supplements are compatible with food databases. Databases for botanicals and other supplements include nonnutrient constituents that may not be documented in food composition databases. Gaps in food and dietary supplement composition data exist because of limited resources, changing availability of foods and products and the advent of new compounds of health interest. More data are needed on nutrients and other bioactive constituents in foods and dietary supplements. Analytical methods do not exist for all ingredients or active constituents in foods and dietary supplements. Research needs for further development of meaningful food and dietary supplement databases are similar. C1 US Dept Hlth & Human Serv, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. US Dept Hlth & Human Serv, Off Prevent Res & Int Programs, NIH, Bethesda, MD 20892 USA. USDA ARS, Washington, DC 20250 USA. RP Picciano, MF (reprint author), US Dept Hlth & Human Serv, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. NR 19 TC 24 Z9 25 U1 0 U2 4 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2003 VL 133 IS 2 BP 624S EP 634S PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 643RW UT WOS:000180875100049 PM 12566512 ER PT J AU Miller, FG Wendler, D Wilfond, B AF Miller, FG Wendler, D Wilfond, B TI When do the federal regulations allow placebo-controlled trials in children? SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID MODERATE ASTHMA; EFFICACY; PHARMACOTHERAPY; BECLOMETHASONE; DEPRESSION; POWERLESS; SAFETY C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 23 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 2003 VL 142 IS 2 BP 102 EP 107 DI 10.1067/mpd.2003.43 PG 6 WC Pediatrics SC Pediatrics GA 648HH UT WOS:000181144400007 PM 12584527 ER PT J AU Sarntinoranont, M Iadarola, MJ Morrison, PF AF Sarntinoranont, M Iadarola, MJ Morrison, PF TI A kinetic analysis of substance P trafficking SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE substance-P; trafficking; kinetics; mathematical model ID RAT SPINAL-CORD; RECEPTOR-MEDIATED ENDOCYTOSIS; PROTEASE-ACTIVATED RECEPTOR-1; NK1 RECEPTOR; INDUCED INTERNALIZATION; RECYCLING RECEPTORS; FUSION PROTEIN; BINDING-SITES; NK-1 RECEPTOR; IN-VITRO AB The potential for administering substance P (SP) nocitoxins for the treatment of chronic pain has been identified. To characterize treatment protocols for the spinal cord or elsewhere, binding/internalization of these compounds at the cellular targets must be understood quantitatively. Thus, a kinetic model of SP binding and intracellular trafficking has been developed from data. The eight differential equation model describes surface binding between SP and neurokinin 1 receptor, clathrin-mediated endocytosis followed by spatial translation to a perinuclear endosome where SP is sorted from its receptor, SP degradation in late endosomes/early lysosomes, and return of sorted receptor to plasma membrane via recycling endosomes. With suitably optimized parameters, the model accounts for the kinetics of total, membrane-associated, and internalized SP in cells continuously exposed to SP, as well as the fractions of internalized SP remaining intact at 30 and 60 min. Simultaneously, the model accounts for the kinetics of internalization and receptor recycling after SP preloading of membrane and subsequent exposure to SP-free media. Rate constants (min(-1)) are: 0.034 +/- 0.004 (receptor off-rate), 0.15 +/- 0.03 (internalization), 0.048 +/- 0.003 (exit from sorting endosome), 0.062 +/- 0.008 (exit of labeled SP amino acids from prelysosome), and 0.029 +/- 0.004 (receptor return from recycling endosome to plasma membrane). The SP kinetics resemble those of transferrin and its receptor at the internalization step, but are several-fold slower in the sorting and recycling steps. (C) 2003 Wiley-Liss, Inc. C1 NIH, Div Bioengn & Phys Sci ORS OD, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Morrison, PF (reprint author), NIH, Div Bioengn & Phys Sci ORS OD, Bldg 10, Bethesda, MD 20892 USA. NR 51 TC 8 Z9 8 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD FEB PY 2003 VL 92 IS 2 BP 232 EP 243 DI 10.1002/jps.10280 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 640XD UT WOS:000180713200003 PM 12532372 ER PT J AU Yu, AM Granvil, CP Haining, RL Krausz, KW Corchero, J Kupfer, A Idle, JR Gonzalez, FJ AF Yu, AM Granvil, CP Haining, RL Krausz, KW Corchero, J Kupfer, A Idle, JR Gonzalez, FJ TI The relative contribution of monoamine oxidase and cytochrome P450 Isozymes to the metabolic deamination of the trace amine tryptamine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MESSENGER-RNA; REGIONAL DISTRIBUTION; HUMAN BRAIN; DEBRISOQUINE; CYP2D6; OXIDATION; HYDROXYLATION; SUBSTRATE; 2D6; PERSONALITY AB Tryptamine is a trace amine in mammalian central nervous system that interacts with the trace amine TA(2) receptor and is now thought to function as a neurotransmitter or neuromodulator. It had been reported that deamination of tryptamine to tryptophol was mediated by CYP2D6, a cytochrome P450 that is expressed in human brain, suggesting that tryptamine may be an endogenous substrate for this polymorphic enzyme. We were unable to confirm this report and have reinvestigated tryptamine metabolism in human liver microsomes (HLM) and in microsomes expressing recombinant human cytochrome P450 and monoamine oxidase (MAO) isozymes. Tryptamine was oxidized to indole-3-acetaldehyde by HLM and recombinant human MAO-A in the absence of NADPH, and indole-3-acetaldehyde was further reduced to tryptophol by aldehyde reductase in HLM in the presence of NADPH. Steady-state kinetic parameters were estimated for each reaction step by HLM and MAO-A. The CYP2D6 substrates bufuralol and debrisoquine showed strong inhibition of both tryptophol production from tryptamine in HLM and the formation of indole-3-acetaldehyde from tryptamine catalyzed by recombinant MAO-A. Anti-CYP2D6 monoclonal antibody did not inhibit these reactions. Pargyline, a nonselective MAO inhibitor, did not show cross inhibition to debrisoquine 4-hydroxylation and dextromethorphan O-demethylation by HLM and recombinant CYP2D6 enzyme. This is the first unequivocal report of the selective conversion of tryptamine to tryptophol by MAO-A. CYP2D6 does not contribute to this reaction. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. Univ Bern, Dept Clin Pharmacol, Bern, Switzerland. Norwegian Univ Sci & Technol, Inst Canc Res & Mol Biol, N-7034 Trondheim, Norway. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 3E24, Bethesda, MD 20892 USA. NR 30 TC 31 Z9 31 U1 0 U2 6 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 FEB PY 2003 VL 304 IS 2 BP 539 EP 546 DI 10.1124/jpet.102.043786 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 637RL UT WOS:000180526600008 PM 12538805 ER PT J AU Landon, LA Peletskaya, EN Glinsky, VV Karasseva, N Quinn, TP Deutscher, SL AF Landon, LA Peletskaya, EN Glinsky, VV Karasseva, N Quinn, TP Deutscher, SL TI Combinatorial evolution of high-affinity peptides that bind to the Thomsen-Friedenreich carcinoma antigen SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE bacteriophage display; affinity maturation; carcinoma antigen; peptide; glycoepitope; fluorescence quenching; confocal microscopy ID HUMAN BREAST-CARCINOMA; RESISTANT MCF-7 CELLS; STRANDED DNA FAB; HOMOTYPIC AGGREGATION; MELANOMA-CELLS; COLORECTAL-CARCINOMA; ADHESION PROPERTIES; DISPLAY LIBRARIES; IMAGE-ANALYSIS; MICROSCOPY AB Thomsen-Friedenreich (TF) antigen occurs on approximately 90% of human carcinomas, is likely involved in carcinoma cell homotypic aggregation, and has clinical value as a prognostic indicator and marker of metastasized cells. Previously, we isolated anti-TF antigen peptides from bacteriophage display libraries. These bound to TF antigen on carcinoma cells but were of low affinity and solubility. We hypothesized that peptide amino acid sequence changes would result in increased affinity and solubility, which would translate into improved carcinoma cell binding and increased inhibition of aggregation. The new peptides were more soluble and exhibited up to fivefold increase in affinity (K-d congruent to 60 nM). They bound cultured human breast and prostate carcinoma cells at low concentrations, whereas the earlier peptides did not. Moreover, the new peptides were potent inhibitors of homotypic aggregation. The maturated peptides will have expanded applications in basic studies of the TF antigen and particular utility as clinical carcinoma-targeting agents. C1 Univ Missouri, Dept Biochem, Columbia, MO 65212 USA. NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21702 USA. Univ Missouri, Dept Hlth Profess, Columbia, MO 65211 USA. Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO 65201 USA. RP Deutscher, SL (reprint author), Univ Missouri, Dept Biochem, M121 Med Sci Bldg, Columbia, MO 65212 USA. NR 57 TC 24 Z9 24 U1 1 U2 7 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD FEB PY 2003 VL 22 IS 2 BP 193 EP 204 DI 10.1023/A:1023483232397 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 671BE UT WOS:000182444400010 PM 12760424 ER PT J AU Fraser, PA Ding, WZ Mohseni, M Treadwell, EL Dooley, MA St Clair, EW Gilkeson, GS Cooper, GS AF Fraser, PA Ding, WZ Mohseni, M Treadwell, EL Dooley, MA St Clair, EW Gilkeson, GS Cooper, GS TI Glutathione S-Transferase M null homozygosity and risk of systemic lupus erythematosus associated with sun exposure: A possible gene-environment interaction for autoimmunity SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; autoimmune disease; glutathione S-transferase; metabolism; ultraviolet radiation ID CULTURED HUMAN-LYMPHOCYTES; INDUCED DNA-DAMAGE; REVISED CRITERIA; IN-VITRO; T-CELLS; POLYMORPHISMS; CANCER; UV; P1; CLASSIFICATION AB Objective. Multiple genetic factors modulate predisposition to systemic lupus erythematosus (SLE). The glutathione S-transferase (GST) genes GSTM1, GSTT1, and GSTP1 catalyze metabolic pathways for the excretion of reactive oxygen species that may be generated by cellular oxidative stress induced by ultraviolet radiation in sunlight. We hypothesized that risk of SLE associated with occupational sun exposure is modulated by GSTM1, GSTT1, and GSTP1 genotypes. Methods. DNA samples and occupational history were collected from 243 cases and 298 controls in the Carolina Lupus Study, a population based case-control study of patients with recently diagnosed SLE. Results. There was no independent association between SLE and presence of the homozygous null GSTM1 or GSTT1 genotype, the homozygous Val/Val or heterozygous Val/Ile GSTP1 genotype, or occupational sunlight exposure. The prevalence of Ro autoantibodies was significantly increased among Caucasians with the GSTM1 null genotype (OR 2.6, 95% CI 1.0, 6.8), but was somewhat weaker among African-Americans (OR 1.5, 95% CI 0.7, 3.5). In the combined analysis of occupational sunlight exposure and GSTM1 genotype, the effect of sun exposure among Caucasians varied depending on GSTM1 genotype. There was a 3-fold increased risk (OR 3.1, 95% CI 0.9, 10.8) of SLE associated with 24 or more months' occupational sun exposure among Caucasians with the GSTM1 null genotype, but sun exposure was not associated with risk among GSTM1 positive Caucasians (OR 0.6, 95% CI 0.3, 1.5). The interaction was statistically significant (p = 0.028). Conclusion. Our results suggest that GSTM1 homozygous null genotype may modify the effect of occupational sun exposure on the risk of SLE in caucasians. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC USA. Univ N Carolina, Div Rheumatol, Chapel Hill, 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. NIEHS, Epidemiol Branch, Durham, NC USA. RP Fraser, PA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES10295] NR 37 TC 31 Z9 32 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 2003 VL 30 IS 2 BP 276 EP 282 PG 7 WC Rheumatology SC Rheumatology GA 640VY UT WOS:000180709700012 PM 12563680 ER PT J AU Padayatty, SJ Katz, A Wang, YH Eck, P Kwon, O Lee, JH Chen, SL Corpe, C Dutta, A Dutta, SK Levine, M AF Padayatty, SJ Katz, A Wang, YH Eck, P Kwon, O Lee, JH Chen, SL Corpe, C Dutta, A Dutta, SK Levine, M TI Vitamin C as an antioxidant: Evaluation of its role in disease prevention SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Review DE ascorbic acid; oxidation; diet; low-density lipoproteins ID LOW-DENSITY-LIPOPROTEIN; OXIDATIVE DNA-DAMAGE; CORONARY-ARTERY DISEASE; GUINEA-PIG LIVER; RECOMMENDED DIETARY ALLOWANCE; ASCORBIC-ACID CONCENTRATIONS; ACUTE MYOCARDIAL-INFARCTION; PROTEIN CARBONYL FORMATION; SODIUM L-ASCORBATE; HUMAN-BLOOD PLASMA AB Vitamin C in humans must be ingested for survival. Vitamin C is an electron donor, and this property accounts for all its known functions. As an electron donor, vitamin C is a potent water-soluble antioxidant in humans. Antioxidant effects of vitamin C have been demonstrated in many experiments in vitro. Human diseases such as atherosclerosis and cancer might occur in part from oxidant damage to tissues. Oxidation of lipids, proteins and DNA results in specific oxidation products that can be measured in the laboratory. While these biomarkers of oxidation have been measured in humans, such assays have not yet been validated or standardized, and the relationship of oxidant markers to human disease conditions is not clear. Epidemiological studies show that diets high in fruits and vegetables are associated with lower risk of cardiovascular disease, stroke and cancer, and with increased longevity. Whether these protective effects are directly attributable to vitamin C is not known. Intervention studies with vitamin C have shown no change in markers of oxidation or clinical benefit. Dose concentration studies of vitamin C in healthy people showed a sigmoidal relationship between oral dose and plasma and tissue vitamin C concentrations. Hence, optimal dosing is critical to intervention studies using vitamin C. Ideally, future studies of antioxidant actions of vitamin C should target selected patient groups. These groups should be known to have increased oxidative damage as assessed by a reliable biomarker or should have high morbidity and mortality due to diseases thought to be caused or exacerbated by oxidant damage. C1 NIDDKD, Digest Dis Branch, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Sinai Hosp Baltimore, Div Gastroenterol, Baltimore, MD USA. RP Levine, M (reprint author), NIDDKD, Digest Dis Branch, Mol & Clin Nutr Sect, NIH, Bldg 10,Rm 4D52,MSC 1372, Bethesda, MD 20892 USA. RI Chen, Shenglin/B-4049-2010; Padayatty, Sebastian/A-8581-2012; OI Padayatty, Sebastian/0000-0001-8758-3170; Eck, Peter/0000-0003-2371-9774 NR 215 TC 550 Z9 578 U1 24 U2 136 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD FEB PY 2003 VL 22 IS 1 BP 18 EP 35 PG 18 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 643QZ UT WOS:000180873100003 PM 12569111 ER PT J AU McDermott, MM Greenland, P Liu, K Criqui, MH Guralnik, JM Celic, L Chan, C AF McDermott, MM Greenland, P Liu, K Criqui, MH Guralnik, JM Celic, L Chan, C TI Sex differences in peripheral arterial disease: Leg symptoms and physical functioning SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE disability; sex; intermittent claudication; peripheral arterial disease; physical activity ID LOWER-EXTREMITY FUNCTION; CHRONIC HEART-FAILURE; CARDIOVASCULAR HEALTH; SUBSEQUENT DISABILITY; OLDER ADULTS; CALTRAC ACCELEROMETER; TREADMILL WALKING; MUSCLE STRENGTH; 6-MINUTE WALK; WOMENS HEALTH AB OBJECTIVES: LTo compare lower extremity functioning and leg symptoms between women and men with peripheral arterial disease (PAD). DESIGN: Cross-sectional. SETTING: Three Chicago-area medical centers. PARTICIPANTS: One hundred eighty-seven women and 273 men with PAD identified consecutively in patients in the noninvasive vascular laboratories and a general medicine practice at the three medical centers. MEASUREMENTS: Walking speed, 6-minute walk, accelerometer-measured 7-day physical activity, and a summary performance score. The summary performance score combines data on walking velocity, time for five repeated chair rises, and standing balance to achieve a score on a 0 to 12 scale (12 = best). RESULTS: Women with PAD were older and had a lower prevalence of prior leg revascularization, a higher prevalence of spinal stenosis, and a lower prevalence of other cardiovascular disease than men with PAD. Mean ankle brachial index (ABI) values +/- standard deviation were similar in women and men with PAD (0.64 +/- 0.15 vs 0.66 +/- 0.14, P = .15). Women with PAD were significantly more likely than men with PAD to have exertional leg pain that sometimes begins at rest (27.8% vs 13.2%, P < .001). Women with PAD had slower walking speed (0.81 vs 0.92 m/s, P < .001), shorter 6-minute walk distance (1,047 vs 1,182 feet, P < .001), and a poorer summary performance score (8.9 vs 9.8, P < .001) than men with PAD, adjusting for age, race, height, comorbid disease, and leg symptoms. After adjusting for leg strength, sex differences in 6-minute walk performance and summary performance score were attenuated modestly (1,089 vs 1,177 feet for 6-minute walk, P = .022 and 9.2 vs 9.8 for summary performance score, P = .027). CONCLUSION: Women with PAD had a higher prevalence of leg pain on exertion and rest, poorer functioning, and greater walking impairment from leg symptoms than men with PAD. A higher prevalence of spinal stenosis in women may explain the observed sex differences in leg symptoms. Poorer leg strength in women may contribute to poorer lower extremity functioning in women with PAD than in men with PAD. C1 Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP McDermott, MM (reprint author), 675 N St Clair,Suite 15-200, Chicago, IL 60611 USA. FU NCRR NIH HHS [RR-00048]; NHLBI NIH HHS [R01-HL58099] NR 45 TC 57 Z9 58 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2003 VL 51 IS 2 BP 222 EP 228 DI 10.1046/j.1532-5415.2003.51061.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 639AL UT WOS:000180605400011 PM 12558719 ER PT J AU Miller, DL O'Grady, NP AF Miller, DL O'Grady, NP TI Guidelines for the prevention of intravascular catheter-related infections: Recommendations relevant to interventional radiology SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE catheters and catheterization; central venous access; infections ID CENTRAL VENOUS CATHETERS; INTENSIVE-CARE UNIT; CUFFED HEMODIALYSIS CATHETERS; PROSPECTIVE RANDOMIZED TRIAL; SILVER-IMPREGNATED CUFF; BLOOD-STREAM INFECTION; POVIDONE-IODINE; RISK-FACTORS; BACTEREMIA; MULTICENTER C1 Natl Naval Med Res Inst, Dept Radiol, Bethesda, MD 20889 USA. NIH, Dept Crit Care Med, Natl Naval Med Ctr, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Radiol & Nucl Med, Bethesda, MD 20814 USA. RP Miller, DL (reprint author), Natl Naval Med Res Inst, Dept Radiol, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 33 TC 10 Z9 11 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2003 VL 14 IS 2 BP 133 EP 136 DI 10.1097/01.RVI.0000058317.82956.1f PN 1 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 645UL UT WOS:000180997700002 PM 12582182 ER PT J AU He, Y Vassell, R Zaitseva, M Nguyen, N Yang, ZN Weng, YK Weiss, CD AF He, Y Vassell, R Zaitseva, M Nguyen, N Yang, ZN Weng, YK Weiss, CD TI Peptides trap the human immunodeficiency virus type 1 envelope glycoprotein fusion intermediate at two sites SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSMEMBRANE PROTEIN GP41; MEMBRANE-FUSION; HIV-1 GP41; LEUCINE ZIPPER; SIV GP41; INHIBITION; ECTODOMAIN; DOMAIN; ENTRY; CONFORMATION AB Human immunodeficiency virus type 1 (HIV-1) entry into target cells requires folding of two heptad-repeat regions (N-HR and C-HR) of gp41 into a trimer of N-HR and C-HR hairpins, which brings viral and target cell membranes together to facilitate membrane fusion. Peptides corresponding to the N-HR and C-HR of gp41 are potent inhibitors of HIV infection. Here we report new findings on the mechanism of inhibition of a N-HR peptide and compare these data with inhibition by a C-HR peptide. Using intact envelope glycoprotein (Env) under fusogenic conditions, we show that the N-HR peptide preferentially binds receptor-activated Env and that CD4 binding is sufficient for triggering conformational changes that allow the peptide to bind Env, results similar to those seen with the C-HR peptide. However, activation by both CD4 and chemokine receptors further enhances Env binding by both peptides. We also show that a nonconservative mutation in the N-HR of gp41 abolishes C-HR peptide but not N-HR peptide binding to gp41. These results indicate that there are two distinct sites in receptor-activated Env that are potential targets for drug or vaccine development. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMD, NIH, Bethesda, MD 20892 USA. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-466,NIH Bldg,29 Rm 532,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 28 TC 93 Z9 98 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2003 VL 77 IS 3 BP 1666 EP 1671 DI 10.1128/JVI.77.3.1666-1671.2003 PG 6 WC Virology SC Virology GA 637AD UT WOS:000180488700002 PM 12525600 ER PT J AU McCurdy, LH Graham, BS AF McCurdy, LH Graham, BS TI Role of plasma membrane lipid microdomains in respiratory syncytial virus filament formation SO JOURNAL OF VIROLOGY LA English DT Article ID LUNG-TRANSPLANT RECIPIENTS; RAFT MICRODOMAINS; ACTIN CYTOSKELETON; FUSION PROTEIN; GLYCOPROTEIN-G; ERM PROTEINS; RHO-GTPASES; INFECTION; ATTACHMENT; CELL AB The fusion protein (F) of respiratory syncytial virus (RSV) is the envelope glycoprotein responsible for the characteristic cytopathology of syncytium formation. RSV has been shown to bud from selective areas of the plasma membrane as pleomorphic virions, including both filamentous and round particles. With immunofluorescent microscopy, we demonstrated evidence of RSV filaments incorporating the fusion protein F and colocalizing with a lipid microdomain-specific fluorescent dye, 1,1-dihexadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate. Western blot analysis of Triton X-100 cold-extracted membrane fractions confirmed the presence of RSV proteins within the lipid microdomains. RSV proteins also colocalized with cellular proteins associated with lipid microdomains, caveolin-1, and CD44, as well as with RhoA, a small GTPase. ADP-ribosylation of RhoA by Clostridium botulinum exotoxin inactivated RhoA signaling and resulted in the absence of RSV-induced syncytia despite no significant change in viral titer. We demonstrated an overall decrease in both the number and length of the viral filaments and a shift in the localization of F to nonlipid microdomain regions of the membrane in the presence of C3 toxin. This suggests that the selective incorporation of RSV proteins into lipid microdomains during virus assembly may lead to critical interactions of F with cellular proteins, resulting in microvillus projections necessary for the formation of filamentous virus particles and syncytium formation. Thus, manipulation of membrane lipid microdomains may lead to alterations in the production of viral filaments and RSV pathogenesis and provide a new pharmacologic target for RSV therapy. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 2502,40 Convent Dr,MSC 3017, Bethesda, MD 20892 USA. FU NIAID NIH HHS [T32 AI007474, R01-AI-33933, T32 AI07474] NR 45 TC 58 Z9 60 U1 1 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 FEB PY 2003 VL 77 IS 3 BP 1747 EP 1756 DI 10.1128/JVI.77.3.1747-1756.2003 PG 10 WC Virology SC Virology GA 637AD UT WOS:000180488700010 PM 12525608 ER PT J AU Vorberg, I Groschup, MH Pfaff, E Priola, SA AF Vorberg, I Groschup, MH Pfaff, E Priola, SA TI Multiple amino acid residues within the rabbit prion protein inhibit formation of its abnormal isoform SO JOURNAL OF VIROLOGY LA English DT Article ID MOUSE NEUROBLASTOMA-CELLS; IN-VITRO CONVERSION; TRANSGENIC MICE; SPECIES BARRIER; SCRAPIE INFECTIVITY; SECONDARY STRUCTURE; RESISTANT FORMS; NMR STRUCTURE; HAMSTER PRP; TRANSMISSION AB Transmissible spongiform encephalopathies (TSEs) are neurological diseases that are associated with the conversion of the normal host-encoded prion protein (PrP-sen) to an abnormal protease-resistant form, PrP-res. Transmission of the TSE agent from one species to another is usually inefficient and accompanied by a prolonged incubation time. Species barriers to infection by the TSE agent are of particular importance given the apparent transmission of bovine spongiform encephalopathy to humans. Among the few animal species that appear to be resistant to infection by the TSE agent are rabbits. They survive challenge with the human kuru and Creutzfeldt-Jakob agents as well as with scrapie agent isolated from sheep or mice. Species barriers to the TSE agent are strongly influenced by the PrP amino acid sequence of both the donor and recipient animals. Here we show that rabbit PrP-sen does not form PrP-res in murine tissue culture cells persistently infected with the mouse-adapted scrapie agent. Unlike other TSE species barriers that have been studied, critical amino acid residues that inhibit PrP-res formation are located throughout the rabbit PrP sequence. Our results suggest that the resistance of rabbits to infection by the TSE agent is due to multiple rabbit PrP-specific amino acid residues that result in a PrP structure that is unable to refold to the abnormal isoform associated with disease. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. Fed Res Ctr Virus Dis Anim, Inst Novel & Emerging Infect Dis, D-17498 Insel Riems, Germany. Fed Res Ctr Virus Dis Anim, D-72076 Tubingen, Germany. RP Priola, SA (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NR 44 TC 75 Z9 79 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2003 VL 77 IS 3 BP 2003 EP 2009 DI 10.1128/JVI.77.3.2003-2009.2003 PG 7 WC Virology SC Virology GA 637AD UT WOS:000180488700036 PM 12525634 ER PT J AU Kim, R Trubetskoy, A Suzuki, T Jenkins, NA Copeland, NG Lenz, J AF Kim, R Trubetskoy, A Suzuki, T Jenkins, NA Copeland, NG Lenz, J TI Genome-based identification of cancer genes by proviral tagging in mouse retrovirus-induced T-cell lymphornas SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; MAMMARY-TUMOR VIRUS; INSERTIONAL MUTAGENESIS; TRANSGENIC MICE; NOTCH GENE; IN-VIVO; C-MYC; LYMPHOMAS; ACTIVATION; ONCOGENE AB The identification of tumor-inducing genes is a driving force for elucidating the molecular mechanisms underlying cancer. Many retroviruses induce tumors by insertion of viral DNA adjacent to cellular oncogenes, resulting in altered expression and/or structure of the encoded proteins. The availability of the mouse genome sequence now allows analysis of retroviral common integration sites in murine tumors to be used as a genetic screen for identification of large numbers of candidate cancer genes. By positioning the sequences of inverse PCR-amplified, virus-host junction fragments within the mouse genome, 19 target genes were identified in T-cell lymphomas induced by the retrovirus SL3-3. The candidate cancer genes included transcription factors (Fos, Gfi1, Lef1, Myb, Myc, Runx3, and Sox3), all three D cyclins, Ras signaling pathway components (Rras2/TC21 and Rasgrp1), and Cmkbr7/CCR7. The most frequent target was Rras2. Insertions as far as 57 kb away from the transcribed portion were associated with substantially increased transcription of Rras2, and no coding sequence mutations, including those typically involved in Ras activation, were detected. These studies demonstrate the power of genome-based analysis of retroviral insertion sites for cancer gene discovery, identify several new genes worth examining for a role in human cancer, and implicate the pathways in which those genes act in lymphomagenesis. They also provide strong genetic evidence that overexpression of unmutated Rras2 contributes to tumorigenesis, thus suggesting that it may also do so if it is inappropriately expressed in human tumors. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Lenz, J (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NCI NIH HHS [CA09060, CA44822, R01 CA044822, T32 CA009060] NR 43 TC 78 Z9 81 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 FEB PY 2003 VL 77 IS 3 BP 2056 EP 2062 DI 10.1128/JVI.77.3.2056-2062.2003 PG 7 WC Virology SC Virology GA 637AD UT WOS:000180488700042 PM 12525640 ER PT J AU Liu, XF Mayeda, A Tao, MF Zheng, ZM AF Liu, XF Mayeda, A Tao, MF Zheng, ZM TI Exonic splicing enhancer-dependent selection of the bovine papillornavirus type 1 nucleotide 3225 3 ' splice site can be rescued in a cell lacking splicing factor ASF/SF2 through activation of the phosphatidylinositol 3-kinase/Akt pathway SO JOURNAL OF VIROLOGY LA English DT Article ID PRE-MESSENGER-RNA; PROTEIN-KINASE-B; SR PROTEINS; ANTIGEN-RECEPTOR; SIGNAL-TRANSDUCTION; IN-VITRO; TRANSCRIPTION FACTOR; RS DOMAIN; PHOSPHORYLATION; BINDING AB Bovine papillomavirus type 1 (BPV-1) late pre-mRNAs are spliced in keratinocytes in a differentiation-specific manner: the late leader 5' splice site alternatively splices to a proximal 3' splice site (at nucleotide 3225) to express L2 or to a distal 3' splice site (at nucleotide 3605) to express L1. Two exonic splicing enhancers, each containing two ASF/SF2 (alternative splicing factor/splicing factor 2) binding sites, are located between the two 3' splice sites and have been identified as regulating alternative 3' splice site usage. The present report demonstrates for the first time that ASF/SF2 is required under physiological conditions for the expression of BPV-1 late RNAs and for selection of the proximal 3' splice site for BPV-1 RNA splicing in DT40-ASF cells, a genetically engineered chicken B-cell line that expresses only human ASF/SF2 controlled by a tetracycline-repressible promoter. Depletion of ASF/SF2 from the cells by tetracycline greatly decreased viral RNA expression and RNA splicing at the proximal 3' splice site while increasing use of the distal 3' splice site in the remaining viral RNAs. Activation of cells lacking ASF/SF2 through anti-immunoglobulin M-B-cell receptor cross-linking rescued viral RNA expression and splicing at the proximal 3' splice site and enhanced Akt phosphorylation and expression of the phosphorylated serine/arginine-rich (SR) proteins SRp30s (especially SC35) and SRp40. Treatment with wortmannin, a specific phosphatidylinositol 3-kinase/Akt kinase inhibitor, completely blocked the activation-induced activities. ASF/SF2 thus plays an important role in viral RNA expression and splicing at the proximal 3' splice site, but activation-rescued viral RNA expression and splicing in ASF/SF2-depleted cells is mediated through the phosphatidylinositol 3-kinase/Akt pathway and is associated with the enhanced expression of other SR proteins. C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Rm 10 S255,10 Ctr Dr,MSC-1868, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov NR 60 TC 30 Z9 30 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2003 VL 77 IS 3 BP 2105 EP 2115 DI 10.1128/JVI.77.3.2105-2115.2003 PG 11 WC Virology SC Virology GA 637AD UT WOS:000180488700047 PM 12525645 ER PT J AU Schmitz, JE Kuroda, MJ Santra, S Simon, MA Lifton, MA Lin, WY Khunkhun, R Piatak, M Lifson, JD Grosschupff, G Gelman, RS Racz, P Tenner-Racz, K Mansfield, KA Letvin, NL Montefiori, DC Reimann, KA AF Schmitz, JE Kuroda, MJ Santra, S Simon, MA Lifton, MA Lin, WY Khunkhun, R Piatak, M Lifson, JD Grosschupff, G Gelman, RS Racz, P Tenner-Racz, K Mansfield, KA Letvin, NL Montefiori, DC Reimann, KA TI Effect of humoral immune responses on controlling viremia during primary infection of rhesus monkeys with simian immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID B-CELL FUNCTION; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODY; CD8(+) LYMPHOCYTES; VIRAL REPLICATION; MACAQUES; COMPLEMENT; AIDS; PATHOGENESIS; PREVENTION AB Cellular immune responses mediated by CD8(+) lymphocytes exert efficient control of virus replication during primary simian immunodeficiency virus (SIV) infection. However, the role that antibodies may play in the early control of virus replication remains unclear. To evaluate how antibody responses may affect virus replication during primary SIVmac infection, we depleted rhesus monkeys of B cells with anti-CD20 antibody. In normal rhesus monkeys immunized with tetanus toxoid, anti-CD20 treatment and resulting depletion of B cells inhibited the generation of antitetanus antibodies, while tetanus-specific T-cell responses were preserved. During the first 4 weeks after inoculation with SIVmac251, development of SIV-specific neutralizing antibody was delayed, and titers were significantly lower in B-cell-depleted monkeys than control-antibody-treated monkeys. Despite the lower neutralizing antibody titers, the levels of plasma SIV RNA and the linear slope of the decline seen in B-cell-depleted monkeys did not differ from that observed in monkeys treated with control antibody. However, beginning at day 28 after SIV infection, the B-cell-depleted monkeys showed a significant inverse correlation between neutralizing antibody titers and plasma virus level. These results suggest that the rapid decline of peak viremia that typically occurs during the first 3 weeks of infection was not significantly affected by SIV-specific antibodies. However, the inverse correlation between neutralizing antibodies and plasma virus level during the postacute phases of infection suggests that humoral immune responses may contribute to the control of SIV replication. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Viral Pathogenesis, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Comparat Pathol, Southborough, MA 01772 USA. NCI, SAIC Frederick, AIDS Vaccine Program, Retroviral Pathogenesis Lab, Bethesda, MD 20892 USA. Bernhard Nocht Inst Trop Med, Hamburg, Germany. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Reimann, KA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Viral Pathogenesis, RE-113,330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [N01-CO-12400]; NCRR NIH HHS [K26 RR000168, P51 RR000168, R24 RR016001, RR00168, RR13150, RR16001]; NHLBI NIH HHS [R01 HL059747, HL59747]; NIAID NIH HHS [AI28691, P30 AI028691] NR 32 TC 95 Z9 98 U1 2 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 FEB PY 2003 VL 77 IS 3 BP 2165 EP 2173 DI 10.1128/JVI.77.3.2165-2173.2003 PG 9 WC Virology SC Virology GA 637AD UT WOS:000180488700053 PM 12525651 ER PT J AU Young, DF Andrejeva, L Livingstone, A Goodbourn, S Lamb, RA Collins, PL Elliott, RM Randall, RE AF Young, DF Andrejeva, L Livingstone, A Goodbourn, S Lamb, RA Collins, PL Elliott, RM Randall, RE TI Virus replication in engineered human cells that do not respond to interferons SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; GENE; PROTEIN; NS1; PATHOGENESIS; CHIMPANZEES; MECHANISMS AB The V protein of the paramyxovirus simian virus 5 blocks interferon (IFN) signaling by targeting STAT1 for proteasome-mediated degradation. Here we report on the isolation of human cell lines that express the V protein and can no longer respond to IFN. A variety of viruses, particularly slow-growing wild-type viruses and vaccine candidate viruses (which are attenuated due to mutations that affect virus replication, virus spread, or ability to circumvent the IFN response), form bigger plaques and grow to titers that are increased as much as 10- to 4,000-fold in these IFN-nonresponsive cells. We discuss the practical applications of using such cells in vaccine development and manufacture, virus diagnostics and isolation of newly emerging viruses, and studies on host cell tropism and pathogenesis. C1 Univ St Andrews, Sch Biol, St Andrews KY16 9TS, Fife, Scotland. Univ Glasgow, Inst Virol, Glasgow G11 5JR, Lanark, Scotland. Univ London St Georges Hosp, Sch Med, Dept Biochem & Immunol, London SW17 0RE, England. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. NIAID, Bethesda, MD 20892 USA. RP Randall, RE (reprint author), Univ St Andrews, Sch Biomed Sci, Biomol Sci Bldg,N Haugh St, St Andrews KY16 9TS, Fife, Scotland. FU NIAID NIH HHS [AI-23173, R01 AI023173] NR 23 TC 52 Z9 53 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 FEB PY 2003 VL 77 IS 3 BP 2174 EP 2181 DI 10.1128/JVI.77.3.2174-2181.2003 PG 8 WC Virology SC Virology GA 637AD UT WOS:000180488700054 PM 12525652 ER EF