FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Baldridge, MG Stahl, RL Gerstenberger, SL Tripoli, V Hutz, RJ AF Baldridge, MG Stahl, RL Gerstenberger, SL Tripoli, V Hutz, RJ TI Modulation of ovarian follicle maturation in long-Evans rats exposed to ammonium perchlorate (AP) in utero and lactationally. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53201 USA. Univ Wisconsin, NIEHS, Biomed Sci Ctr, Milwaukee, WI 53201 USA. Univ Nevada, Dept Environm Studies, Las Vegas, NV 89154 USA. NR 0 TC 0 Z9 0 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. PY 2003 VL 68 SU 1 MA 484 BP 311 EP 311 PG 1 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400538 ER PT J AU Horner, K Masciarelli, S Hinckley, M Nedachi, T Manganiello, V Conti, M AF Horner, K Masciarelli, S Hinckley, M Nedachi, T Manganiello, V Conti, M TI Phosphodiesterase 3A is essential for meiosis in the mouse oocyte. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Stanford Univ, Dept Gynecol & Obstet, Div Reprod Biol, Stanford, CA 94305 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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. PY 2003 VL 68 SU 1 MA 508 BP 321 EP 321 PG 1 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400562 ER PT J AU Berg, HA Westerlund, L Olsson, PE AF Berg, HA Westerlund, L Olsson, PE TI Differences in cortisol effects on vitellogenin and vitelline envelope protein production in the teleost, arctic char (Saluelinus alpinus). SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Umea Univ, Dept Biol Mol, Umea, Sweden. Natl Inst Environm Hlth Sci, Div Intramural Res, Cell Biol Sect, NIH, Res Triangle Pk, NC USA. Univ Orebro, Dept Nat Sci, Biol Sect, Orebro, Sweden. NR 0 TC 0 Z9 0 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. PY 2003 VL 68 SU 1 MA 574 BP 348 EP 349 PG 2 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400627 ER PT S AU Rohde, GK Pajevic, S Pierpaoli, C Basser, PJ AF Rohde, GK Pajevic, S Pierpaoli, C Basser, PJ BE Gee, JC Maintz, JBA Vannier, MW TI A comprehensive approach for multi-channel image registration SO BIOMEDICAL IMAGE REGISTRATION SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT 2nd International Workshop on Biomedical Image Registration CY JUN 23-24, 2003 CL Univ Penn, PHILADELPHIA, PA SP Siemens Med Solut, Siemens Corp Res, Natl Lib Med, Univ Penn, Vice Provost Res HO Univ Penn ID NONRIGID REGISTRATION; MUTUAL INFORMATION; MAGNETIC-RESONANCE; MR-IMAGES; BRAIN AB We describe a general framework for multi-channel image registration. A new similarity measure for registering two multi-channel. images, each with an arbitrary number of channels, is proposed. Results show that image registration performed based on different channels generates different results. In addition, we show that, when available, the inclusion of multi-channel data in the registration procedure helps produce more accurate results. C1 NICHD, STBB, LIMB, Bethesda, MD 20892 USA. NIH, MSCL, CIT, Bethesda, MD 20892 USA. Univ Maryland, Dept Math, College Pk, MD 20742 USA. RP NICHD, STBB, LIMB, Bethesda, MD 20892 USA. RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 NR 23 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-20343-5 J9 LECT NOTES COMPUT SC PY 2003 VL 2717 BP 214 EP 223 PG 10 WC Computer Science, Theory & Methods; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BY15G UT WOS:000187954800023 ER PT S AU Merritt, MM Sollers, JJ Evans, MK Zonderman, AB Thayer, JF AF Merritt, MM Sollers, JJ Evans, MK Zonderman, AB Thayer, JF BE Benghuzzi, H Tucci, M TI Relationships among spectral measures of baroreflex sensitivity and indices of cardiac vagal control SO BIOMEDICAL SCIENCES INSTRUMENTATION, VOL 39 SE BIOMEDICAL SCIENCES INSTRUMENTATION LA English DT Proceedings Paper CT 40th Annual Rocky Mountain Bioengineering Symposium/40th International ISA Biomedical Sciences Instrumentation Symposium CY APR 10-13, 2003 CL BILOXI, MS SP Instrumentat Syst & Automat Soc DE baroreflex sensitivity; vagal control; African-Americans; Fast-Fourier Transform (FFT); spectral analytic techniques; alpha index ID PRESSURE AB Traditionally baroreflex sensitivity (BRS) has been assessed with pharmacological approaches such as phenylephrine infusion. Recently, non-invasive approaches using spectral analytic techniques have been employed to combine heart rate and blood pressure variability parameters to estimate BRS (the alpha index). Some authors have argued that BRS assessed at different frequencies of cardiovascular variabilities provide identical information and they should be combined into a single index of BRS based on total variability. The present study examined the relationship between BRS assessed using low, high, and total heart rate and blood pressure variabilities, and indices of cardiac vagal control assessed by standard spectral measures. Participants were 105 older male and female African-Americans who were part of the Healthy Aging In Nationally Diverse Longitudinal Samples (HANDLS) Study. Heart rate and, blood pressure variabilities (HRV and BPV) were assessed using the Fast-Fourier Transform (FFT). The alpha index was computed as the square root of the ratio of low, high, or the mean of low and high frequency heart rate variability and the corresponding frequency ranges for systolic blood pressure variability. Correlations examining the relationships among BRS and various (e.g. log, normalized) indices of high frequency heart period variability (HF) were calculated for the total sample and by gender. Results indicated that the different BRS indices do not have the same relationship to all indices of HF. The results suggest that an aggregation of the power across bands is problematic at best, and indicates the need to examine the various frequency components separately. C1 NIA, Baltimore, MD 21224 USA. RP Merritt, MM (reprint author), NIA, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Zonderman, Alan B/0000-0002-6523-4778 NR 9 TC 3 Z9 3 U1 0 U2 2 PU INSTRUMENT SOC AMER PI RESEARCH TRIANGLE PARK PA 67 ALEXANDER DR, PO BOX 12277, RESEARCH TRIANGLE PARK, NC 27709 USA SN 0067-8856 J9 BIOMED SCI INSTRUM PY 2003 VL 39 BP 193 EP 198 PG 6 WC Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Instruments & Instrumentation SC Biochemistry & Molecular Biology; Computer Science; Engineering; Instruments & Instrumentation GA BW53U UT WOS:000182321800035 PM 12724893 ER PT S AU Dorsey, WC Tchounwou, PB AF Dorsey, WC Tchounwou, PB BE Benghuzzi, H Tucci, M TI CYP1A1, HSP70, P53, and c-fos expression in human liver carcinoma cells (HepG(2)) exposed to pentachlorophenol SO BIOMEDICAL SCIENCES INSTRUMENTATION, VOL 39 SE BIOMEDICAL SCIENCES INSTRUMENTATION LA English DT Proceedings Paper CT 40th Annual Rocky Mountain Bioengineering Symposium/40th International ISA Biomedical Sciences Instrumentation Symposium CY APR 10-13, 2003 CL BILOXI, MS SP Instrumentat Syst & Automat Soc DE pentachlorophenol; cytotoxicity; protein expression; HepG2 cells ID TRANSCRIPTION; RESPONSES; GENE AB Pentachlorophenol (PCP) is a widely used biocidal compound with several industrial, agricultural and domestic applications. Although it has been shown to induce systemic toxicity and carcinogenesis in several experimental studies, the literature is scarce regarding its toxic mechanisms of action. Recent investigations in our laboratory have shown that PCP induces cytotoxicity and transcriptionally activates stress genes in human liver carcinoma (HepG(2)) cells [1]. We hypothesized that PCP-induced expression of stress proteins may play a role in the molecular events leading to toxicity and tumorigenesis in liver cells. To test this hypothesis, we performed the MTT-assay for cell viability, and the Western Blot and densitometric analyses to assess the expression of cellular protein including CYP1A1, c-fos, HSP70, and p53. Data obtained from the MTT-assay indicated a strong dose-relationship with respect to PCP cytotoxicity. The LD50 Was computed to be 23.0+/-5.6 mug/mL. Western Blot and densitometric analyses also demonstrated a linear dose-response relationship with regard to CYP1A1 expression within the dose range of 0-50 mug/mL. However, a biphasic response was obtained with regard to HSP70, c-fos, and p53 expression, showing a peak induction at 25 mug/mL, and a drastic reduction in protein expression at 50 mug/mL, probably due to cell death at higher level of PCP exposure. At lower level of exposure, PCP was found to be mitogenic. C1 Jackson State Univ, Sch Sci & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Dorsey, WC (reprint author), Jackson State Univ, Sch Sci & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. FU NCRR NIH HHS [1GR12RR13459] NR 20 TC 18 Z9 18 U1 0 U2 0 PU INSTRUMENT SOC AMER PI RESEARCH TRIANGLE PARK PA 67 ALEXANDER DR, PO BOX 12277, RESEARCH TRIANGLE PARK, NC 27709 USA SN 0067-8856 J9 BIOMED SCI INSTRUM PY 2003 VL 39 BP 389 EP 396 PG 8 WC Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Instruments & Instrumentation SC Biochemistry & Molecular Biology; Computer Science; Engineering; Instruments & Instrumentation GA BW53U UT WOS:000182321800067 PM 12724925 ER PT J AU Zheng, G Freidlin, B Li, ZH Gastwirth, JL AF Zheng, G Freidlin, B Li, ZH Gastwirth, JL TI Choice of scores in trend tests for case-control studies of candidate-gene associations SO BIOMETRICAL JOURNAL LA English DT Article DE association; case-control; Cochran-Armitage trend test; optimal score ID ROBUST LINKAGE TESTS; SAMPLE-SIZE; CONTINGENCY-TABLES; AFFECTED SIBS; POWER; INDEPENDENCE; MARKERS AB When applying the Cochran-Armitage (CA) trend test for an association between a candidate allele and a disease in a case-control study, a set of scores must be assigned to the genotypes. SASIENI (1997, Biometrics 53, 1253-1261) suggested scores for the recessive, additive, and dominant models but did not examine their statistical properties. Using the criteria of minimizing the required sample size of the CA trend test to achieve prespecified type I and type II errors, we show that the scores given by SASIENI (1997) are optimal for the recessive and dominant models and locally optimal for the additive one. Moreover, the additive scores are shown to be locally optimal for the multiplicative model. The tests are applied to a real dataset. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Biostat Branch, Washington, DC 20052 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. NR 13 TC 57 Z9 58 U1 1 U2 3 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2003 VL 45 IS 3 BP 335 EP 348 DI 10.1002/bimj.200390016 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 675GV UT WOS:000182686400006 ER PT J AU Malley, JD Redner, RA Severini, TA Badner, JA Pajevic, S Bailey-Wilson, JE AF Malley, JD Redner, RA Severini, TA Badner, JA Pajevic, S Bailey-Wilson, JE TI Estimation of linkage and association from allele transmission data SO BIOMETRICAL JOURNAL LA English DT Article DE TDT; parameter estimation; association; linkage; integrated likelihood ID TRANSMISSION/DISEQUILIBRIUM TEST TDT; DISEQUILIBRIUM; PARAMETERS; PARENTS AB The TDT provides a hypothesis test for the presence of linkage or association (linkage disequilibrium). However, since the TDT is a single test statistic, it cannot be used to separate association and linkage. The importance of this difficulty, following a significant TDT result, has been recently emphasized by WHITTAKER, DENHAM AND MORRIS (2000), who alert the community to the possibility that a significant TDT may result from loose linkage and strong association, or from tight linkage and weak association. To attack this problem we start with the parametric model for family-based allele transmission data Of SHAM and CURTIS (1995) (or SHAM (1998)) and find that the parameters in the model are not always identifiable. So we introduce a reparameterization that resolves the identifiability issues and leads to a valid likelihood ratio (LR) test for linkage. Since the linkage and association parameters are both of interest, we next introduce and apply an integrated likelihood (IL) approach to provide separate point estimates and confidence intervals for these parameters. The estimates are shown to have generally small bias and mean square error, while the confidence intervals have good average length and coverage probabilities. We compare the power of the IL approach for testing linkage and, separately association, with the TDT and LR. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Tulsa, Dept Math & Comp Sci, Tulsa, OK 74104 USA. Northwestern Univ, Dept Stat, Evanston, IL 60208 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. NHGRI, NIH, Bethesda, MD 20892 USA. OI Bailey-Wilson, Joan/0000-0002-9153-2920 NR 20 TC 1 Z9 1 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2003 VL 45 IS 3 BP 349 EP 366 DI 10.1002/bimj.200390017 PG 18 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 675GV UT WOS:000182686400007 ER PT J AU Troendle, JF Yu, KF AF Troendle, JF Yu, KF TI Estimation of sample size for reference interval studies SO BIOMETRICAL JOURNAL LA English DT Article DE bootstrap; confidence interval; reference interval; sample size AB The currently used criterion for sample size calculation in a reference interval study is not well stated and leads to imprecise control of the ratio in question. We propose a generalization of the criterion used to determine sufficient sample size in reference interval studies. The generalization allows better estimation of the required sample size when the reference interval estimation will be using a power transformation or is nonparametric. Bootstrap methods are presented to estimate sample sizes required by the generalized criterion. Simulation of several distributions both symmetric and positively skewed is presented to compare the sample size estimators. The new method is illustrated on a data set of plasma glucose values from a 50-g oral glucose tolerance test. It is seen that the sample sizes calculated from the generalized criterion leads to more reliable control of the desired ratio. C1 NICHHD, Biometry & Math Stat Branch, DHHS, NIH, Bethesda, MD 20892 USA. RP Troendle, JF (reprint author), NICHHD, Biometry & Math Stat Branch, DHHS, NIH, Bld 6100,Room 7B05, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 2 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2003 VL 45 IS 5 BP 561 EP 572 DI 10.1002/bimj.200390033 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 707JW UT WOS:000184508400005 ER PT J AU Liu, A Schisterman, EF AF Liu, A Schisterman, EF TI Comparison of diagnostic accuracy of biomarkers with pooled assessments SO BIOMETRICAL JOURNAL LA English DT Article DE sensitivity; specificity; receiver operating characteristics curves; pooled analysis ID CHARACTERISTIC ROC CURVES; ESTIMATING PREVALENCE; MODELS; INFERENCE; MARKERS; DISEASE; TESTS AB New biomarkers are frequently being developed in laboratory settings for the early diagnosis of diseases. However, the assay can be so expensive to assess in some cases that the evaluation of a large number of assays becomes unfeasible. Under this setting pooling biospecimens becomes an appealing alternative. In this paper, we present the methodology to allow for general pooling strategies and different data structures, which include balanced and unbalanced pooling cases. An estimate of the area under the ROC curve of a single biomarker with its asymptotic mean and variance is provided. Furthermore, we develop a test statistic for comparing the areas under the ROC curves of two biomarkers. The methods are illustrated with data from a study evaluating biomarkers for coronary heart disease. C1 NICHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Schisterman, EF (reprint author), NICHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD 20852 USA. OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 24 TC 23 Z9 24 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2003 VL 45 IS 5 BP 631 EP 644 DI 10.1002/bimj.200390038 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 707JW UT WOS:000184508400010 ER PT J AU Freidlin, B Miao, W Gastwirth, JL AF Freidlin, B Miao, W Gastwirth, JL TI On the use of the Shapiro-Wilk test in two-stage adaptive inference for paired data from moderate to very heavy tailed distributions SO BIOMETRICAL JOURNAL LA English DT Article DE adaptive tests; paired data; power robustness; Shapiro-Wilk test ID T-TEST; ROBUST PROCEDURES; 2-SAMPLE TEST; NORMALITY; STATISTICS; EFFICIENCY; SAMPLES AB Paired data arises in a wide variety of applications where often the underlying distribution of the paired differences is unknown. When the differences are normally distributed, the t-test is optimum. On the other hand, if the differences are not normal, the t-test can have substantially less power than the appropriate optimum test, which depends on the unknown distribution. In textbooks, when the normality of the differences is questionable, typically the non-parametric Wilcoxon signed rank test is suggested. An adaptive procedure that uses the Shapiro-Wilk test of normality to decide whether to use the t-test or the Wilcoxon signed rank test has been employed in several studies. Faced with data from heavy tails, the U.S. Environmental Protection Agency (EPA) introduced another approach: it applies both the sign and t-tests to the paired differences, the alternative hypothesis is accepted if either test is significant. This paper investigates the statistical properties of a currently used adaptive test, the EPAs method and suggests an alternative technique. The new procedure is easy to use and generally has higher empirical power, especially when the differences are heavy-tailed, than currently used methods. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Macalester Coll, St Paul, MN 55105 USA. George Washington Univ, Washington, DC USA. RP Freidlin, B (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NR 35 TC 10 Z9 10 U1 1 U2 2 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2003 VL 45 IS 7 BP 887 EP 900 DI 10.1002/bimj.200390056 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 739PU UT WOS:000186356300008 ER PT J AU Colarusso, P Spring, KR AF Colarusso, P Spring, KR TI Imaging at low light levels with cooled and intensified charge-coupled device cameras SO BIOPHOTONICS, PT A SE METHODS IN ENZYMOLOGY LA English DT Article C1 Univ Calgary, Dept Physiol, Ctr Hlth Sci, Calgary, AB T2N 4N1, Canada. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Colarusso, P (reprint author), Univ Calgary, Dept Physiol, Ctr Hlth Sci, Calgary, AB T2N 4N1, Canada. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 360 BP 383 EP 394 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BW24N UT WOS:000181329600016 PM 12622160 ER PT J AU Eaton, WA AF Eaton, WA TI Linus Pauling and sickle cell disease SO BIOPHYSICAL CHEMISTRY LA English DT Article DE sickle cell disease; sickle hemoglobin; anemia ID HYDROXYUREA THERAPY; DEOXYHEMOGLOBIN-S; OXYGEN-BINDING; HEMOGLOBIN; GELATION; MECHANISM AB The 1949 paper by Linus Pauling et al. [Science 110 (1949) 543-548] describing the discovery of sickle cell anemia as the first molecular disease had a major impact on biology and medicine. Inspired by the scholarly works of John Edsall on the history of hemoglobin research, I present a brief retrospective analysis of Pauling's paper. This is followed by some personal recollections of Edsall and Pauling. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Eaton, WA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. NR 46 TC 14 Z9 15 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PY 2003 VL 100 IS 1-3 SI SI BP 109 EP 116 AR PII S0301-4622(02)00269-7 DI 10.1016/S0301-4622(02)00269-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 661GR UT WOS:000181883300013 PM 12646356 ER PT J AU Huang, CY Zhou, RX Yang, DCH Chock, PB AF Huang, CY Zhou, RX Yang, DCH Chock, PB TI Application of the continuous variation method to cooperative interactions: mechanism of Fe(II)-ferrozine chelation and conditions leading to anomalous binding ratios SO BIOPHYSICAL CHEMISTRY LA English DT Article DE continuous variation; job plot; anomalous stoichiometry; differentiation of cooperative systems; iron-ferrozine interaction ID FERROZINE; REAGENT; IRON AB The method of continuous variation, often known as the Job plot, has long been used for determining the stoichiometry of two interacting components. The correct binding ratio, n, is generally obtained when the total concentration of the reactants, C-o, is much greater than the dissociation constants involved. For non-cooperative binding systems, the stoichiometry varies between one and n as C-o increases; whereas for positive cooperative systems, values larger than n may be observed at low C-o. In this report, we present examples to illustrate how the changing apparent stoichiometries as a function of C-o can provide clues for differentiating various binding mechanisms. To test these concepts, we examined the chelation of Fe(II) with ferrozine in the range of C-o = 7 to 210 muM with Fe(II) expressed in molar concentration or in terms of its binding equivalents (three in this case). The results were analyzed according to several models and found to be most consistent with the mechanism of one-step complex formation or infinite cooperativity with a K-d of 8 muM. @ 2002 Elsevier Science B.V. All rights reserved. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Huang, CY (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2154,50 South Dr,MSC-8012, Bethesda, MD 20892 USA. RI Yang, David/A-7294-2009 NR 7 TC 31 Z9 32 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PY 2003 VL 100 IS 1-3 SI SI BP 143 EP 149 AR PII S0301-4622(02)00275-2 DI 10.1016/S0301-4622(02)00275-2 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 661GR UT WOS:000181883300017 PM 12646360 ER PT J AU Stan, G Thirumalai, D Lorimer, GH Brooks, BR AF Stan, G Thirumalai, D Lorimer, GH Brooks, BR TI Annealing function of GroEL: structural and bioinformatic analysis SO BIOPHYSICAL CHEMISTRY LA English DT Article DE GroEL; Escherichia coli; annealing; chaperonin function ID BACTERIAL CHAPERONIN GROEL; CRYSTAL-STRUCTURE; PROTEIN STRUCTURES; POLYPEPTIDE; MECHANISM; ATP; 2.8-ANGSTROM; SEQUENCES; ALLOSTERY; PATHWAYS AB The Escherichia coli chaperonin system, GroEL-GroES, facilitates folding of substrate proteins (SPs) that are otherwise destined to aggregate. The iterative annealing mechanism suggests that the allostery-driven GroEL transitions leading to changes in the microenvironment of the SP constitutes the annealing action of chaperonins. To describe the molecular basis for the changes in the nature of SP-GroEL interactions we use the crystal structures of GroEL (T state), GroEL-ATP (R state) and the GroEL-GroES-(ADP)(7) (R" state) complex to determine the residue-specific changes in the accessible surface area and the number of tertiary contacts as a result of the T --> R --> R" transitions. We find large changes in the accessible area in many residues in the apical domain, but relatively smaller changes are associated with residues in the equatorial domain. In the course of the T --> R transition the microenvironment of the SP changes which suggests that GroEL is an annealing machine even without GroES. This is reflected in the exposure of Glu386 which loses six contacts in the T --> R transition. We also evaluate the conservation of residues that participate in the various chaperonin functions. Multiple sequence alignments and chemical sequence entropy calculations reveal that, to a large extent, only the chemical identities and not the residues themselves important for the nominal functions (peptide binding, nucleotide binding, GroES and substrate protein release) are strongly conserved. Using chemical sequence entropy, which is computed by classifying aminoacids into four types (hydrophobic, polar, positively charged and negatively charged) we make several new predictions that are relevant for peptide binding and annealing function of GroEL. We identify a number of conserved peptide binding sites in the apical domain which coincide with those found in the 1.7 Angstrom crystal structure of 'mini-chaperone' complexed with the N-terminal tag. Correlated mutations in the HSP60 family, that might control allostery in GroEL, are also strongly conserved. Most importantly, we find that charged solvent-exposed residues in the T state (Lys 226, Glu 252 and Asp 253) are strongly conserved. This leads to the prediction that mutating these residues, that control the annealing function of the SP, can decrease the efficacy of the chaperonin function. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Chem & Biochem, Ctr Biomol Struct & Org, College Pk, MD 20742 USA. RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA. NR 35 TC 32 Z9 32 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PY 2003 VL 100 IS 1-3 SI SI BP 453 EP 467 AR PII S0301-4622(02)00298-3 DI 10.1016/S0301-4622(02)00298-3 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 661GR UT WOS:000181883300040 PM 12646383 ER PT J AU Grunewald, K Medalia, O Gross, A Steven, AC Baumeister, W AF Grunewald, K Medalia, O Gross, A Steven, AC Baumeister, W TI Prospects of electron cryotomography to visualize macromolecular complexes inside cellular compartments: implications of crowding SO BIOPHYSICAL CHEMISTRY LA English DT Article DE electron tomography; macromolecular crowding; eukaryote/prokaryote distinction; vitrification ID GREEN FLUORESCENT PROTEIN; NONLINEAR ANISOTROPIC DIFFUSION; TRANSLATIONAL DIFFUSION; PHYSICAL-PROPERTIES; ESCHERICHIA-COLI; EXCLUDED-VOLUME; LIVING CELLS; MICROSCOPY; TOMOGRAPHY; CYTOPLASM AB Electron cryotomography has unique potential for three-dimensional visualization of macromolecular complexes at work in their natural environment. This approach is based on reconstructing three-dimensional volumes from tilt series of electron micrographs of cells preserved in their native states by vitrification. Resolutions of 5-8 nm have already been achieved and the prospects for further improvement are good. Since many intracellular activities are conducted by complexes in the megadalton range with dimensions of 20-50 nm, current resolutions should suffice to identify many of them in tomograms. However, residual noise and the dense packing of cellular constituents hamper interpretation. Recently, tomographic data have been collected on vitrified eukaryotic cells (Medalia et al., Science (2002) in press). Their cytoplasm was found to be markedly less crowded than in the prokaryotes previously studied, in accord with differences in crowding between prokaryotic and eukaryotic cells documented by other (indirect) biophysical methods. The implications of this observation are twofold. First, complexes should be more easily identifiable in tomograms of eukaryotic cytoplasm. This applies both to recognizing known complexes and characterizing novel complexes. An example of the latter-a 5-fold symmetric particle is-given. Second, electron cryotomography offers an incisive probe to examine crowding in different cellular compartments. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Max Planck Inst Biochem, Dept Biol Struct, D-82152 Martinsried, Germany. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Baumeister, W (reprint author), Max Planck Inst Biochem, Dept Biol Struct, Klopferspitz 18A, D-82152 Martinsried, Germany. NR 91 TC 69 Z9 71 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PY 2003 VL 100 IS 1-3 SI SI BP 577 EP 591 AR PII S0301-4622(02)00307-1 DI 10.1016/S0301-4622(02)00307-1 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 661GR UT WOS:000181883300049 PM 12646392 ER PT J AU Felsenfeld, G AF Felsenfeld, G TI Quantitative approaches to problems of eukaryotic gene expression SO BIOPHYSICAL CHEMISTRY LA English DT Article DE gene expression; eukaryotic; nucleus; chromatin ID BETA-GLOBIN GENE; DNA-BINDING DOMAIN; 5' END; PROTEIN; NUCLEOSOME; CHROMATIN; GATA-1; REGION; SITE; INSULATORS AB During the past several years there has been intense interest in the mechanisms by which gene expression is regulated within the eukaryotic nucleus. We have made use of an avian P-globin locus to study various aspects of this problem, some of which are amenable to quantitative analysis. In the course of this work we have identified the transcription factor GATA-1, which is an essential regulatory factor for virtually all erythroid-specific genes, and studied the structure of its complex with its specific DNA binding site. The way in which GATA-1 forms tight interactions with DNA led to an understanding of how other zinc finger proteins of this class bind to DNA. We have extended such studies to examine interactions with DNA packaged as chromatin, and to studies of chromatin structure and function at higher levels of organization. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 24 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PY 2003 VL 100 IS 1-3 SI SI BP 607 EP 613 AR PII S0301-4622(02)00309-5 DI 10.1016/S0301-4622(02)00309-5 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 661GR UT WOS:000181883300051 PM 12646394 ER PT J AU Gorokhov, A Negishi, M Johnson, EF Pedersen, LC Perera, L Darden, TA Pedersen, LG AF Gorokhov, A Negishi, M Johnson, EF Pedersen, LC Perera, L Darden, TA Pedersen, LG TI Explicit water near the catalytic I helix Thr in the predicted solution structure of CYP2A4 SO BIOPHYSICAL JOURNAL LA English DT Article ID PARTICLE MESH EWALD; BURIED ACTIVE-SITE; CYTOCHROME P450CAM; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; FUNCTIONAL VERSATILITY; SUBSTRATE-SPECIFICITY; PRODUCTS EXIT; AMINO-ACID; BINDING AB The solution structure of mouse cytochrome P450 2A4 (CYP2A4), a monooxygenase of deoxysteroids, was obtained using homology modeling and molecular dynamics. The solvent-equilibrated CYP2A4 preserves the essential features of CYP450s. A comparison of the models CYP2A4 and CYP2A4 with testosterone bound CYP2A4/T illustrates the changes induced by the binding of the substrate. Experimental evidence links four amino acid residues to the catalytic activity, substrate specificity, and regioselectivity of this enzyme. Three of the four amino acids are found within contact distance of the testosterone substrate, and therefore may control the binding of the substrate through direct interaction. Remarkably, a water complex previously observed in x-ray crystal structure forms near the bulge in the central I helix that contains a conserved Thr. The properties of the I helix are computed in the context of the presence or absence of ligand. C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. Scripps Res Inst, La Jolla, CA 92037 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Pedersen, LG (reprint author), Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL-06350, P01 HL006350]; NIGMS NIH HHS [R01 GM031001] NR 39 TC 12 Z9 13 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 JAN PY 2003 VL 84 IS 1 BP 57 EP 68 PG 12 WC Biophysics SC Biophysics GA 682AJ UT WOS:000183067300006 PM 12524265 ER PT J AU Wagner, MA Andemariam, B Desai, SA AF Wagner, MA Andemariam, B Desai, SA TI A two-compartment model of osmotic lysis in Plasmodium falciparum-infected erythrocytes SO BIOPHYSICAL JOURNAL LA English DT Article ID RED-BLOOD-CELLS; PERMEATION PATHWAYS; MALARIA; MEMBRANE; PERMEABILITY; TRANSPORT; PARASITE; CHANNEL; SOLUTES AB We recently identified a voltage-dependent anion channel on the surface of human red blood cells (RBCs) infected with the malaria parasite, Plasmodium, falciparum. This channel, the plasmodial erythrocyte surface anion channel (PESAC), likely accounts for the increased permeability of infected RBCs to various small solutes, as assessed quantitatively with radioisotope flux and patch-clamp studies. Whereas this increased permeability has also been studied by following osmotic lysis of infected cells in permeant solutes, these experiments have been limited to qualitative comparisons of lysis rates. To pen-nit more quantitative examination of lysis rates, we have developed a mathematical model for osmotic fragility of infected cells based on diffusional uptake via PESAC and the two-compartment geometry of infected RBCs. This model, combined with! a simple light scattering assay designed to track osmotic lysis precisely, produced permeability coefficients that match both! previous isotope flux and patch-clamp estimates. Our model and light scattering assay also revealed Michaelian kinetics for inhibition of PESAC by furosemide, suggesting a 1:1 stoichiometry for their interaction. C1 NIAID, Mol Physiol Unit, Lab Malaria & Vector Biol, NIH, Bethesda, MD 20892 USA. NIH, HHMI NIH Res Scholars Program, Bethesda, MD 20892 USA. RP Desai, SA (reprint author), NIAID, Mol Physiol Unit, Lab Malaria & Vector Biol, NIH, Bldg 4,Rm 126, Bethesda, MD 20892 USA. RI Desai, Sanjay/B-7110-2009; Andemariam, Biree/B-6210-2015 OI Andemariam, Biree/0000-0002-2540-6037 FU NIAID NIH HHS [Z01 AI000882-05] NR 31 TC 48 Z9 50 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 JAN PY 2003 VL 84 IS 1 BP 116 EP 123 PG 8 WC Biophysics SC Biophysics GA 682AJ UT WOS:000183067300010 PM 12524269 ER PT J AU Hansen, PL Cohen, JA Podgornik, R Parsegian, VA AF Hansen, PL Cohen, JA Podgornik, R Parsegian, VA TI Osmotic properties of poly(ethylene glycols): Quantitative features of brush and bulk scaling laws SO BIOPHYSICAL JOURNAL LA English DT Article ID ELECTRON-SPIN-RESONANCE; PHASE-BEHAVIOR; PRESSURE DATA; POLYMER; PHOSPHOLIPIDS; BILAYERS; SCATTERING; MEMBRANES; SURFACES; FORCES AB From glycosylated cell surfaces to sterically stabilized liposomes, polymers attached to membranes attract biological and therapeutic interest. Can the scaling laws of polymer "brushes" describe the physical properties, of these coats? We delineate conditions where the Alexander-de Gennes theory of polymer brushes successfully fits the intermembrane distance versus applied osmotic stress data of Kenworthy et al. for poly(ethylene glycol)-grafted multilamellar liposomes. We establish that the polymer density and size in the brush must be high enough that, in a bulk solution of equivalent monomer density, the polymer osmotic pressure is independent of polymer molecular weight (the des Cloizeaux semidilute regime of bulk polymer solutions). The condition that attached polymers behave as semidilute bulk solutions offers a rigorous criterion for brush scaling-law behavior. There is a deep connection between the behaviors of semidilute polymer solutions in bulk and; polymers grafted to a surface at a density such that neighbors pack to form a uniform brush. In this regime, two-parameter unconstrained fits of the Alexander-de Gennes brush scaling laws to the Kenworthy et at. data yield effective monomer lengths of 3.3-3.6 Angstrom, which agree with structural predictions. The fitted distances between grafting sites are larger than expected from, the nominal mole fraction of poly(ethylene glycol)-lipids; the chains apparently saturate the surface. Osmotic stress measurements can be used to estimate the actual densities of membrane-grafted polymers. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ So Denmark, MEMPHYS, Ctr Biomembrane Phys, DK-5230 Odense M, Denmark. Univ Pacific, Dept Physiol, San Francisco, CA 94115 USA. Univ Ljubljana, Fac Math & Phys, Dept Phys, SI-1000 Ljubljana, Slovenia. RP Cohen, JA (reprint author), 2155 Webster St, San Francisco, CA 94115 USA. EM jcohen@uop.edu RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 26 TC 75 Z9 75 U1 3 U2 18 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 JAN PY 2003 VL 84 IS 1 BP 350 EP 355 PG 6 WC Biophysics SC Biophysics GA 682AJ UT WOS:000183067300029 PM 12524288 ER PT B AU Schneider, ME Rzadzinska, A Davies, C Kachar, B AF Schneider, ME Rzadzinska, A Davies, C Kachar, B BE Gummer, AW TI Formation and remodeling of hair bundles promoted by continuous actin polymerization at the tips of stereocilia: Mechanical considerations SO BIOPHYSICS OF THE COCHLEA: FROM MOLECULES TO MODELS LA English DT Proceedings Paper CT Conference on Biophysics of the Cochlea - Molecules to Models CY JUL 27-AUG 07, 2002 CL TITISEE, GERMANY ID CELLS; FILAMENTS; ADAPTATION; ISOFORMS; COCHLEA AB Mechanosensory transduction in the inner ear depends on the deflection of stereocilia, which are specialized microvilli that form a bundle on the surface of the hair cell. Previously, mature stereocilia were thought to be extremely stable because they are supported by a rigid semi-crystalline array of cross-linked parallel actin filaments of uniform polarity. Structural stability is deemed important for mechano-reception that is sensitive to displacements at the nanometer scale [1]. Recently, we showed that these actin filament bundles are continuously being remodeled by addition of actin monomers at the tips of the stereocilia and that the entire stereocilium is renewed every 48 hours [2]. Recognition of this dynamic aspect of stereocilia is essential to understanding the development and maintenance of normal sensory function. Such a dynamic renewal mechanism could also help understand the molecular basis of several genetic, environmental and age-related inner-car disorders that involve malformation or disruption of stereocilia. We discuss here the micromechanical consequences of this newly discovered stereocilia plasticity. C1 Natl Inst Deafness & Other Commun Disorders, Natl Inst Hlth, Sect Struct Cell Biol, Bethesda, MD 20892 USA. RP Schneider, ME (reprint author), Natl Inst Deafness & Other Commun Disorders, Natl Inst Hlth, Sect Struct Cell Biol, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-238-304-2 PY 2003 BP 28 EP 36 DI 10.1142/9789812704931_0003 PG 9 WC Acoustics; Biophysics; Cell Biology; Otorhinolaryngology SC Acoustics; Biophysics; Cell Biology; Otorhinolaryngology GA BCM39 UT WOS:000229998300003 ER PT B AU Dong, XX Ospeck, M Iwasa, KH AF Dong, XX Ospeck, M Iwasa, KH BE Gummer, AW TI Fast nonlinear currents in outer hair cells from the basal turn of the cochlea SO BIOPHYSICS OF THE COCHLEA: FROM MOLECULES TO MODELS LA English DT Proceedings Paper CT Conference on Biophysics of the Cochlea - Molecules to Models CY JUL 27-AUG 07, 2002 CL TITISEE, GERMANY ID BASILAR-MEMBRANE; GUINEA-PIG; MODEL AB Outer hair cells are mechanoreceptor cells in the mammalian ear that generate force in their cell bodies based on piezoelectricity. These cells are regarded as the key feedback element in the cochlear amplifier that gives the ear the exquisite sensitivity. Since the somatic motility in outer hair cells is driven by the receptor potential, the attenuation of the receptor potential by the membrane capacitance reduces the effectiveness of the somatic motility. This problem is known as the "RC time constant" problem. We report here that outer hair cells from the basal turn of the cochlea have fast outward-rectifying currents that can reduce the attenuation of the receptor potential. Further studies on detailed kinetic proper-ties of these currents could resolve the "RC time constant" problem, possibly establishing the significance of the somatic motility in the cochlear amplifier. C1 NIDCD, Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Dong, XX (reprint author), NIDCD, Biophys Sect, NIH, 50 South Dr, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-238-304-2 PY 2003 BP 161 EP 168 DI 10.1142/9789812704931_0020 PG 8 WC Acoustics; Biophysics; Cell Biology; Otorhinolaryngology SC Acoustics; Biophysics; Cell Biology; Otorhinolaryngology GA BCM39 UT WOS:000229998300020 ER PT B AU Cai, H Chadwick, RS AF Cai, H Chadwick, RS BE Gummer, AW TI Computation of modes and motion analysis in a transverse section of the cochlea SO BIOPHYSICS OF THE COCHLEA: FROM MOLECULES TO MODELS LA English DT Proceedings Paper CT Conference on Biophysics of the Cochlea - Molecules to Models CY JUL 27-AUG 07, 2002 CL TITISEE, GERMANY ID BASILAR-MEMBRANE; ORGAN; CORTI AB We use finite-element modeling to simulate passive transverse modes in the apical region of a guinea-pig cochlea. We prescribe the geometry of a transverse crosssection and the acoustic stimulus frequency, and then solve a fluid-solid interaction eigenvalue problem for the axial wavenumber, the modal fluid pressure, and the modal solid displacement fields. Our model includes transverse and axial motion of a viscous, incompressible fluid, as well as axial elastic coupling via a basilar membrane (BM) modeled as an orthotropic clamped plate. The tectorial membrane (TM) and organ of Corti (OC) are modeled as viscoelastic solids that are elastically coupled through the outer hair cell stereocilia. The OC contains inhomogeneities representing discrete cellular structures. For acoustic stimuli less than 1 kHz our results show a monophasic vibration of the BM. For an upward deflection of the BM, there is a synchronous clockwise rotation of three rows of outer hair cell stereocilia induced by a shearing motion between the recticular lamina (RL) and TM. We use our computed results to construct moving images of the OC and TM, and to validate our algorithm for motion analysis of successive video images of a transverse section of the cochlea. C1 Natl Inst Deafness & Other Commun Disorders, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA. RP Cai, H (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-238-304-2 PY 2003 BP 400 EP 408 DI 10.1142/9789812704931_0054 PG 9 WC Acoustics; Biophysics; Cell Biology; Otorhinolaryngology SC Acoustics; Biophysics; Cell Biology; Otorhinolaryngology GA BCM39 UT WOS:000229998300054 ER PT J AU Speare, JO Rush, TS AF Speare, JO Rush, TS TI IR spectra of cytochrome c denatured with deuterated guanidine hydrochloride show increase in beta sheet SO BIOPOLYMERS LA English DT Article DE IR spectroscopy; secondary structure; cytochrome c; protein denaturation ID TRANSFORM INFRARED-SPECTROSCOPY; RESOLVED CIRCULAR-DICHROISM; PROTEIN SECONDARY STRUCTURE; HEART FERRICYTOCHROME-C; HUMAN PRION PROTEIN; AQUEOUS-SOLUTIONS; FOLDING REACTIONS; RIBONUCLEASE-A; PROTON NMR; STATE AB Attenuated total reflectance Fourier transform IR (ATR-FTIR) spectra are obtained for horse heart ferricytochrome c in solutions of 0-7M guanidine hydrochloride and deuterated guanidine hydrochloride. Substitutions of deuterium for hydrogen in both the denaturant and protein provide resolvable amide I spectra over a wide range of denaturant concentrations. Deuteration enhances the ability to measure the true protein IR spectrum in the amide I region in which the secondary structure can be deduced, because spectra in D2O are less prone to spectral distortion upon background denaturant subtraction than spectra in H2O. Other investigators studying equilibrium unfolded cytochrome c were limited to guanidine concentrations below 3.0M because of detector saturation. Detector saturation is avoided with the use of ATR-FTIR spectroscopy, allowing one to obtain protein spectra at high denaturant concentrations. Second derivative spectra of samples show reductions in alpha helix and increases in beta sheet at high denaturant concentrations, contrary to expectations of finding primarily a random coil secondary structure. Using this new technique, the protein was estimated to consist of 51% beta sheet and only 15% random coil in the presence of 6.6M deuterated guanidine hydrochloride. (C) 2003 Wiley Periodicals, Inc. C1 Univ Montana, Dept Chem, Missoula, MT 59812 USA. RP Speare, JO (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NR 60 TC 24 Z9 24 U1 0 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 72 IS 3 BP 193 EP 204 DI 10.1002/bip.10337 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 676AU UT WOS:000182730400006 PM 12722115 ER PT J AU Bryant, SD Jinsmaa, Y Salvadori, S Okada, Y Lazarus, LH AF Bryant, SD Jinsmaa, Y Salvadori, S Okada, Y Lazarus, LH TI Dmt and opioid peptides: A potent alliance SO BIOPOLYMERS LA English DT Review DE Dmt; opioid peptides; Dmt-Tic pharmacophore; delta-opioid antagonists; delta-opioid agonists; mu-opioid agonists; opioid receptors; low energy conformations; x-ray diffraction; opioidmimetics; bioactivity; analgesia; molecular modeling ID RECEPTOR-BINDING ACTIVITY; DELTA-OPIATE RECEPTOR; TIC PHARMACOPHORE; HIGHLY POTENT; AMINO-ACIDS; PYRAZINONE RING; AMPHIBIAN SKIN; PHARMACOLOGICAL CHARACTERIZATION; DIKETOPIPERAZINE FORMATION; DIPEPTIDE ANTAGONISTS AB The introduction of the Dmt (2',6'-dimethyl-L-tyrosine)-Tic pharmacophore into the design of opioid ligands produced an extraordinary family of potent delta-opioid receptor antagonists and heralded a new phase in opioid research. First reviewed extensively in 1998, the incorporation of Dmt into a diverse group of opioid molecules stimulated the opioid field leading to the development of unique analogues with remarkable properties. This overview will document the crucial role played by this residue in the proliferation of opioid peptides with high receptor affinity (K-i equal to or less than I nM) and potent bioactivity. The discussion will include the metamorphosis between delta-opioid receptor antagonists to delta-agonists based solely on subtle structural changes at the C-terminal region of the Dmt-Tic pharmacophore as well as their behavior in vivo. Dmt may be considered promiscuous due to the acquisition of potent mu-agonism by dermorphin and endomorphin derivatives as well as by a unique class of opioidmimetics containing two Dmt residues separated by alkyl or pyrazinone linkers. Structural studies on the Dmt-Tic compounds were enhanced tremendously by x-ray diffraction data for three potent and biologically diverse Dmt-Tic opioidmimetics that led to the development of pharmacophores for both delta-opioid receptor agonists and antagonists. Molecular modeling studies of other unique Dmt opioid analogues illuminated structural differences between delta- and mu-receptor ligand interactions. The future of these compounds as therapeutic applications for various medical syndromes including the control of cancer-associated pain is only a matter of time and perseverance. (C) 2003 Wiley Periodicals, Inc. C1 NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, High Technol Res Ctr, Nishi Ku, Kobe, Hyogo 6512180, Japan. RP Bryant, SD (reprint author), NIEHS, LCBRA, MDC3-04,POB 12233, Res Triangle Pk, NC 27709 USA. OI SALVADORI, Severo/0000-0002-8224-2358 NR 122 TC 71 Z9 73 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 2 BP 86 EP 102 DI 10.1002/bip.10399 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 686VA UT WOS:000183340600002 PM 12767112 ER PT J AU Sundaran, R Walker, CM Lemonnier, FA Jacobson, S Rawale, SV Kaumaya, PTP AF Sundaran, R Walker, CM Lemonnier, FA Jacobson, S Rawale, SV Kaumaya, PTP TI Induction of protective CTL responses in HLA-A*0201 transgenic mice against HTLV-1 recombinant vaccinia virus using a multivalent CTL epitope peptide construct SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA. Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. NIH, Viral Immunol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA LY3 BP 277 EP 277 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800004 ER PT J AU Lee, K Gao, Y Phan, J Wu, L Liang, J Zhang, ZY Waugh, D Burke, TR AF Lee, K Gao, Y Phan, J Wu, L Liang, J Zhang, ZY Waugh, D Burke, TR TI Tripeptide inhibitors of Yersinia protein-tyrosine phosphatase as potential leads for therapeutic development against plague SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. NCI, Macromol Crystallog Lab, CCR, NIH, Frederick, MD 21702 USA. Albert Einstein Coll Med, Dept Mol Pharm, Bronx, NY 10461 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA LY8 BP 278 EP 278 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800009 ER PT J AU Burke, TR Shi, ZD Wei, CQ Wang, X Lee, K Liu, H Zhang, M Vasselli, J Linehan, WM Yang, D AF Burke, TR Shi, ZD Wei, CQ Wang, X Lee, K Liu, H Zhang, M Vasselli, J Linehan, WM Yang, D TI Macrocyclization in the design of tetra-peptide mimetics that display potent inhibition of GRB2 SH2 domain binding in whole cell systems SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. NCI, Urol Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA O52 BP 296 EP 296 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800093 ER PT J AU Roller, PP Li, P Zhang, M Long, YQ Peach, ML Nicklaus, M Liu, H Yang, D AF Roller, PP Li, P Zhang, M Long, YQ Peach, ML Nicklaus, M Liu, H Yang, D TI Peptidomimetic design of cyclic Grb2-SH2 domain antagonists not relying on pTyr or its mimics SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA O51 BP 296 EP 296 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800092 ER PT J AU Lee, K Gao, Y Phan, J Wu, L Liang, J Zhang, ZY Waugh, D Burke, TR AF Lee, K Gao, Y Phan, J Wu, L Liang, J Zhang, ZY Waugh, D Burke, TR TI Tripeptide inhibitors of yersinia protein-tyrosine phosphatase as potential leads for therapeutic development against plague SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. NCI, Macromol Crystallog Lab, CCR, NIH, Frederick, MD 21702 USA. Albert Einstein Coll Med, Dept Mol Pharm, Bronx, NY 10461 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P039 BP 313 EP 313 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800164 ER PT J AU Sundaram, R Walker, CM Lemonnier, FA Jacobson, S Rawale, SV Kaumaya, PTP AF Sundaram, R Walker, CM Lemonnier, FA Jacobson, S Rawale, SV Kaumaya, PTP TI Induction of protective CTL responses in HLA-A*0201 transgenic mice against HTLV-1-recombinant vaccinia virus using a multivalent CTL epitope peptide construct SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA. Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. NIH, Viral Immunol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P044 BP 314 EP 315 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800169 ER PT J AU Teruya, K Mazur, S Appella, E AF Teruya, K Mazur, S Appella, E TI Multiple condensations of peptide thio-esters prepared by the "satety-catch" resin approach: Synthesis of p53(303-393). SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P181 BP 344 EP 344 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800304 ER PT J AU Lazarus, LH Jinsmaa, Y Bryant, SD Salvadori, S Sasaki, Y Ambo, A Tsuda, Y Okada, Y AF Lazarus, LH Jinsmaa, Y Bryant, SD Salvadori, S Sasaki, Y Ambo, A Tsuda, Y Okada, Y TI Minimum opioid molecule (MOM): DMT and C-terminally extended analogs elicit mu-opioid receptor selective agonism and analgesia SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NIEHS, LCBRA, Peptide Neurochem, Res Triangle Pk, NC 27709 USA. Univ Ferrara, Dept Pharm Sci, I-44100 Ferrara, Italy. Tohoku Univ, Dept Biochem, Sendai, Miyagi 9818558, Japan. Kobe Gakuin Univ, Fac Pharm Sci, Kobe, Hyogo 6512180, Japan. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P258 BP 359 EP 360 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800381 ER PT J AU Miyazaki, A Tsuda, Y Tachibana, Y Yokoi, T Bryant, SD Lazarus, LH Keri, G Okada, Y AF Miyazaki, A Tsuda, Y Tachibana, Y Yokoi, T Bryant, SD Lazarus, LH Keri, G Okada, Y TI The synthesis of somatostatin analogs containing pyrazinone ring and examination of their bioactivities SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MA ID ANTITUMOR-ACTIVITY C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, High Technol Res Ctr, Nishi Ku, Kobe, Hyogo 6512180, Japan. NIEHS, Res Triangle Pk, NC 27709 USA. Semmelweis Univ, Dept Med Chem, H-1085 Budapest, Hungary. NR 3 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P292 BP 367 EP 367 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800415 ER PT J AU Jinsmaa, Y Okada, Y Tsuda, Y Sasaki, TY Ambo, A Bryant, SD Lazarus, LH AF Jinsmaa, Y Okada, Y Tsuda, Y Sasaki, TY Ambo, A Bryant, SD Lazarus, LH TI Potent antinociceptive activity of novel opioid compound, bis-Dmt(KO)pyrazinone SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NIEHS, Res Triangle Pk, NC 27709 USA. Tohoku Pharmaceut Univ, Aoba Ku, Sendai, Miyagi 9818558, Japan. Kobe Gakuin Univ, Nishi Ku, Kobe, Hyogo 6512180, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P309 BP 371 EP 371 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800432 ER PT J AU Krajewski, K Long, YQ Marchand, C Pommier, Y Roller, P AF Krajewski, K Long, YQ Marchand, C Pommier, Y Roller, P TI Synthesis and biological activity of dimeric HIV-1 integrase inhibitory peptides SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RI Marchand, Christophe/D-8559-2016 NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P331 BP 375 EP 375 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800453 ER PT J AU Li, P Peach, ML Zhang, M Liu, H Yang, D Nicklaus, M Roller, PP AF Li, P Peach, ML Zhang, M Liu, H Yang, D Nicklaus, M Roller, PP TI Potent GR132-SH2 domain antagonists discovered by extensive sar studies SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 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 PY 2003 VL 71 IS 3 MA P370 BP 383 EP 383 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800492 ER PT J AU Burke, TR Shi, ZD Wei, CQ Wang, X Lee, K Liu, H Zhang, M Vasselli, J Linehan, WM Yang, D AF Burke, TR Shi, ZD Wei, CQ Wang, X Lee, K Liu, H Zhang, M Vasselli, J Linehan, WM Yang, D TI Macrocyclization in the design of tetra-peptide mimetics that display potent inhibition of GR132 SH2 domain binding in whole cell systems SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. NCI, Urol Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P373 BP 384 EP 384 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800495 ER PT J AU Roller, PP Li, P Zhang, M Long, YQ Peach, ML Nicklaus, M Liu, H Yang, D AF Roller, PP Li, P Zhang, M Long, YQ Peach, ML Nicklaus, M Liu, H Yang, D TI Peptidomimetic design of cyclic Grb2-SH2 domain antagonists not relying on pTyr or its mimics. SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P371 BP 384 EP 384 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800493 ER PT J AU Bryant, SD Salvadori, S Guerrini, R Balboni, G Lazarus, LH AF Bryant, SD Salvadori, S Guerrini, R Balboni, G Lazarus, LH TI Molecular modeling of opioidmimetics containing the Dmt-Tic-Bid pharmacophores and docking with the delta-opioid receptor. SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Univ Cagliari, Cagliari, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P389 BP 387 EP 387 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800511 ER PT J AU Vives, E Richard, JP Melikov, K Chernomordik, L Lebleu, B AF Vives, E Richard, JP Melikov, K Chernomordik, L Lebleu, B TI Tat peptide-mediated cellular vectorization of nucleic acids SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Univ Montpellier 2, CNRS, UMR 5124, F-34093 Montpellier, France. NICHD, NIH, Bethesda, MD 20892 USA. RI Melikov, Kamran/A-6604-2009 NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P497 BP 409 EP 410 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800619 ER PT J AU Yamaguchi, H Houtman, JCD Samelson, LE Appella, E AF Yamaguchi, H Houtman, JCD Samelson, LE Appella, E TI Synthesis and application of large phosphopeptides from the linker for activation of T cells (LAT) protein SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P503 BP 411 EP 411 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800625 ER PT J AU Baker, SG Ko, CW Graubard, BI AF Baker, SG Ko, CW Graubard, BI TI A sensitivity analysis for nonrandomly missing categorical data arising from a National Health Disability Survey SO BIOSTATISTICS LA English DT Article DE complex sample surveys; depression; ignorable missing-data mechanism; missing at random; nonignorable missing-data mechanism; selection model ID QUALITY-OF-LIFE; NON-IGNORABLE NONRESPONSE; NONIGNORABLE NONRESPONSE; DATA SUBJECT; BINARY DATA; PARAMETER-ESTIMATION; LOGISTIC-REGRESSION; OUTCOME SUBJECT; DATA MECHANISM; MODELS AB Using data from 145 007 adults in the Disability Supplement to the National Health Interview Survey, we investigated the effect of balance difficulties on frequent depression after controlling for age, gender, race, and other baseline health status information. There were two major complications: (i) 80% of subjects were missing data on depression and the missing-data mechanism was likely related to depression, and (ii) the data arose from a complex sample survey. To adjust for (i) we investigated three classes of models: missingness in depression, missingness in depression and balance, and missingness in depression with an auxiliary variable. To adjust for (ii) we developed the first linearization variance formula for nonignorable missing-data models. Our sensitivity analysis was based on fitting a range of ignorable missing-data models along with nonignorable missing-data models that added one or two parameters. All nonignorable missing-data models that we considered fit the data substantially better than their ignorable missing-data counterparts. Under an ignorable missing-data mechanism, the odds ratio for the association between balance and depression was 2.0 with a 95% CI of (1.8, 2.2). Under 29 of the 30 selected nonignorable missing-data models, the odds ratios ranged from 2.7 with 95% CI of (2.3, 3.1) to 4.2 with 95% CI of (3.9, 4.6). Under one nonignorable missing-data model, the odds ratio was 7.4 with 95% CI of (6.3, 8.6). This is the first analysis to find a strong association between balance difficulties and frequent depression. C1 NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Clin Trials Epidemiol & Biostat Sect, Bethesda, MD USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, EPN 3131,6130 Execut Blvd MSC 7354, Bethesda, MD 20892 USA. NR 49 TC 16 Z9 16 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2003 VL 4 IS 1 BP 41 EP 56 DI 10.1093/biostatistics/4.1.41 PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 678YT UT WOS:000182894800004 PM 12925329 ER PT J AU Smith, RD Brown, B Ikonomi, P Schechter, AN AF Smith, RD Brown, B Ikonomi, P Schechter, AN TI Exogenous reference RNA for normalization of real-time quantitative PCR SO BIOTECHNIQUES LA English DT Article ID POLYMERASE CHAIN-REACTION; INTERNAL STANDARDS; MESSENGER-RNA; RT-PCR; DNA; AMPLIFICATION; HYBRIDIZATION; INHIBITORS; CELLS AB We have utilized an in vitro transcribed 3' mRNA fragment of the plant gene ribulose bisphosphate carboxylase (RuBisCO) as an exogenous standard for normalization of quantitative PCR data. Both K562 cells and primary erythroid CD34(+) progenitor cells were treated with sodium butyrate and changes in gamma-globin mRNA levels were assayed using a previously published TaqMan(R) probe and primer set, while RuBisCO levels were assayed by a SYBR(R) Green detection assay. The data presented show that a correction to measured gamma-globin induction was necessary with both cell types. The correction for the CD34(+) progenitor cells was a striking 95% increase, while that for the K562 cells was 44%. The use of an exogenous reference such as in vitro transcribed mRNA for the RuBisCO plant gene provides a robust and sample-independent method for the normalization of quantitative PCR data in bacterial and animal cells. C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Smith, RD (reprint author), NIDDK, Biol Chem Lab, NIH, Bldg 10,Room 9N318,10 Ctr Dr,MSC 1822, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 16 TC 47 Z9 48 U1 1 U2 8 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2003 VL 34 IS 1 BP 88 EP 91 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 634QF UT WOS:000180351300014 PM 12545545 ER PT J AU Jacobs, JM Bailey, BW Burritt, JB Morrison, SG Morrison, RP Dratz, EA Jesaitis, AJ Teintze, M AF Jacobs, JM Bailey, BW Burritt, JB Morrison, SG Morrison, RP Dratz, EA Jesaitis, AJ Teintze, M TI QSYP peptide sequence is selected from phage display libraries by bovine IgG contaminants in monoclonal antibody preparations SO BIOTECHNIQUES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; FILAMENTOUS PHAGE; MEMBRANE-PROTEIN; PURIFICATION; GLYCOPROTEIN; RHODOPSIN; EPITOPES; SURFACE; CULTURE; BINDING AB A consensus peptide sequence, QSYP, appears as an artifact during the mapping of monoclonal antibodies (MAbs) using a random peptide phage display library. Phage bearing this QSYP sequence were independently selected by four different laboratories screening separate MAb preparations with the same phage library. In each case, the QSYP sequence was selected in addition to a consensus sequence specific to the MAb. Phage that displayed the QSYP sequence were not bound by the MAb of interest, but rather bound to bovine IgG derived from the FBS present in the hybridoma growth media. The implications of this finding for the interpretation of phage library screening results and possible methods for the removal of bovine IgG from MAb preparations are discussed. C1 Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. NIH, Rockville, MD USA. RP Teintze, M (reprint author), Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. RI Bailey, Brian/B-1732-2009 FU NIAID NIH HHS [AI43187] NR 20 TC 8 Z9 8 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2003 VL 34 IS 1 BP 132 EP + PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 634QF UT WOS:000180351300019 PM 12545550 ER PT J AU Bleckwenn, NA Bentley, WE Shiloach, J AF Bleckwenn, NA Bentley, WE Shiloach, J TI Exploring vaccinia virus as a tool for large-scale recombinant protein expression SO BIOTECHNOLOGY PROGRESS LA English DT Article ID GREEN FLUORESCENT PROTEIN; INSECT CELLS; ESCHERICHIA-COLI; GENE-EXPRESSION; RNA-POLYMERASE; REAL-TIME; FUSION; SYSTEM; PURIFICATION; GENERATION AB A recombinant vaccinia virus was engineered to express enhanced green fluorescent protein (EGPP) under control of the T7 promoter using the VOTE expression system in HeLa cells. Infection of HeLa cells with this virus and induction with IPTG demonstrated the utility of this construct for easily measuring protein expression. This construct was used to evaluate several production parameters, specifically, multiplicity of infection (MOI), volume during infections and serum concentration during the infection phase. In static culture, increasing multiplicity of infection was found to increase expression of EGFP up to a plateau around MOI of 1.0. Expression eras also shown to increase with decreasing volume during the infection phase. Serum concentration during the infection phase was only marginally significant from 0 to 7.5%. Cytodex microcarriers were found to have the best characteristics for HeLa cell growth. These cells were grown and infected microcarier spinner flask culture, and tie maximum expression was 2.2 mug EGEP/(million cells at the dine of infection), demonstrating the ability of this system to successfully express recombinant proteins at larger scale. C1 NIDDK, Biotechnol Unit, LCDB, NIH, Bethesda, MD 20892 USA. Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA. Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Unit, LCDB, NIH, Bethesda, MD 20892 USA. NR 32 TC 11 Z9 13 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JAN-FEB PY 2003 VL 19 IS 1 BP 130 EP 136 DI 10.1021/bp0255762 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 645JU UT WOS:000180973100018 PM 12573015 ER PT J AU Brittenham, GM Badman, DG AF Brittenham, GM Badman, DG TI Noninvasive measurement of iron: report of an NIDDK workshop SO BLOOD LA English DT Article ID SICKLE-CELL DISEASE; FREE-RADICAL OXIDATIONS; MAGNETIC-RESONANCE; HEPATIC IRON; THALASSEMIA MAJOR; CHELATION-THERAPY; HYDROGEN-PEROXIDE; MRI EVALUATION; BRAIN IRON; OVERLOAD AB An international workshop on the noninvasive measurement of iron was conducted by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) on April 17, 2001, to assess the current state of the science and to identify areas needing further investigation. The workshop concluded that a clear clinical need is evident for quantitative, noninvasive, safe, accurate, and readily available means of measuring body storage iron to improve the diagnosis and management of patients with iron overload from such disorders as hereditary hemochromatosis, thalassemia major, sickle cell disease, aplastic anemia, and myelodysplasia, among others. Magnetic resonance imaging (MRI) potentially provides the best available technique for examining the 3-dimensional distribution of excess iron in the body, but further research is needed to develop means of making measurements quantitative. Bio-magnetic susceptometry provides the only noninvasive method to measure tissue iron stores that has been calibrated, validated, and used in clinical studies, but the complexity, cost, and technical demands of the liquid-helium-cooled superconducting instruments required at present have restricted clinical access to the method. The workshop identified basic and clinical research opportunities for deepening our understanding of the physical properties of iron and iron toxicity, for further investigation of MRI as a method for quantitative determinations of tissue iron, especially in liver, heart and brain, and for development of improved methods and more widely available instrumentation for biomagnetic susceptometry. C1 NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Badman, DG (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, 2 Democracy Plaza,Room 621 MSC 5458,6707 Democrac, Bethesda, MD 20892 USA. NR 41 TC 148 Z9 160 U1 1 U2 4 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 JAN 1 PY 2003 VL 101 IS 1 BP 15 EP 19 DI 10.1182/blood-2002-06-1723 PG 5 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500003 PM 12393526 ER PT J AU Alving, BM AF Alving, BM TI How I treat heparin-induced thrombocytopenia and thrombosis SO BLOOD LA English DT Article ID ECARIN CLOTTING TIME; OPEN-HEART-SURGERY; RECOMBINANT HIRUDIN; CARDIOPULMONARY BYPASS; UNFRACTIONATED HEPARIN; ANTICOAGULANT-THERAPY; ARGATROBAN; LEPIRUDIN; ANTIBODIES; PHARMACOKINETICS C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Alving, BM (reprint author), NHLBI, NIH, Room 5A47,Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA. NR 43 TC 51 Z9 54 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 JAN 1 PY 2003 VL 101 IS 1 BP 31 EP 37 DI 10.1182/blood-2002-04-1089 PG 7 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500005 PM 12393689 ER PT J AU Huhn, RD Fogarty, PF Nakamura, R Read, EJ Leitman, SF Rick, ME Kimball, J Greene, A Hansmann, K Gratwohl, A Young, N Barrett, AJ Dunbar, CE AF Huhn, RD Fogarty, PF Nakamura, R Read, EJ Leitman, SF Rick, ME Kimball, J Greene, A Hansmann, K Gratwohl, A Young, N Barrett, AJ Dunbar, CE TI High-dose cyclophosphamide with autologous lymphocyte-depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia SO BLOOD LA English DT Article ID PLATELET AUTOANTIBODIES; HEMOLYTIC-ANEMIA; EVANS-SYNDROME; TRANSPLANTATION; PURPURA; DISEASE; MORTALITY; THERAPY; PATIENT; ADULTS AB Patients with refractory chronic autoimmune thrombocytopenia (AITP) have a significant risk of morbidity and mortality related to hemorrhage. High-dose (HD) cytotoxic therapy may produce remissions but entails risks related to myelo-suppression. Hematopoietic stem cell support with lymphocyte-depleted grafts may accelerate hematologic recovery and concomitantly reduce repopulation by autoreactive immunocytes. Fourteen patients with chronic AITP, in whom multiple prior therapies including corticosterolds, splenectomy, intravenous immunoglobulin, and various cytotoxic or immunomodulatory regimens had failed, were treated with HD cyclophosphamide (50 mg/kg/d) and autologous granulocyte colony-stimulating factor (6-CSF)-mobilized leukocytes depleted of lymphocytes by immunomagnetic CD34(+) selection. There were no significant adverse events related to G-CSF, intravenous device insertion, or leukapheresis. Treatment-related complications included transient hemorrhagic cystitis (11 patient), vaginal bleeding (2 patients), gastrointestinal bleeding (11 patient), epistaxis (11 patient), and anti biotic-responsive febrile neutropenia (all patients). The mean time to absolute neutrophil count (ANC) more than 500/mm(3) was 9 +/- 0.6 days. Eight patients experienced antibiotic-responsive gram-positive bacteremia. A median of 2 platelet transfusions was required for stem cell mobilization, intravenous catheter insertion, and apheresis and a median of 9 platelet transfusions was required during hematopoietic recovery. Six patients obtained durable complete responses (platelet counts > 100 000/mm(3) without other therapy) with maximum follow-up of 42 months. Two additional patients obtained durable partial responses (platelet counts significantly increased over baseline with reduced medication requirements and cessation of bleeding complications). This therapeutic approach is feasible for patients with severe chronic AITP, a substantial proportion of whom may obtain durable remissions. Larger controlled trials are recommended. (C) 2003 by The American Society of Hematology. C1 Univ Basel, Kantonsspital, Dept Internal Med, CH-4031 Basel, Switzerland. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Huhn, RD (reprint author), Coriell Inst Med Res, 403 Haddon Ave, Camden, NJ 08103 USA. EM rhuhn@cimr.umdnj.edu NR 41 TC 57 Z9 61 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 JAN 1 PY 2003 VL 101 IS 1 BP 71 EP 77 DI 10.1182/blood-2001-12-0171 PG 7 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500011 PM 12393623 ER PT J AU Cristillo, AD Macri, MJ Bierer, BE AF Cristillo, AD Macri, MJ Bierer, BE TI Differential chemokine expression profiles in human peripheral blood T lymphocytes: dependence on T-cell coreceptor and calcineurin signaling SO BLOOD LA English DT Article ID CYCLOSPORINE-A; CHEMOTACTIC RESPONSIVENESS; TYROSINE PHOSPHORYLATION; PROTEIN PHOSPHATASE; RECEPTOR EXPRESSION; MOLECULAR-CLONING; IMMUNE-RESPONSES; IL-2 PRODUCTION; C ACTIVATION; TRANSCRIPTION AB The chemokine superfamily consists of small (8-10 kDa) molecules that function to attract, selectively, different subsets of leukocytes. Binding of chemokines to their appropriate G-protein-coupled receptors is necessary for primary immune responses and for homing of leukocytes; to lymphoid tissues. Here, we have characterized the signaling pathways in primary T lymphocytes that regulate chemokine gene induction using an RNase protection assay. Dependence on stimulation through the coreceptor CD28 and sensitivity to the calcineurin inhibitors cyclosporine and tacrolimus were studied using purified human peripheral blood lymphocytes. Lymphotactin (Ltn), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta were all rapidly induced and sensitive to cyclosporine treatment. At later time points, the expression of MIP-1alpha at and MIP-1beta, but not of Ltn, was restored despite the inhibition of calcineurin activity. By contrast, the induction of interleukin-8 was delayed and was found to be cyclosporine insensitive. Calcineurin activity of IP-10 mRNA induction was contingent on the specific T-cell stimulation conditions, suggesting that IP-10 expression is modulated by calcineurin-dependent and -independent signaling pathways. Differential chemokine expression profiles result from the engagement of T-cell coreceptors and the requirement for, and the dependence on, calcineurin phosphatase activity. C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. RP Bierer, BE (reprint author), Dana Farber Canc Inst, Dana 810,44 Binney St, Boston, MA 02115 USA. NR 68 TC 15 Z9 17 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 JAN 1 PY 2003 VL 101 IS 1 BP 216 EP 225 DI 10.1182/blood-2002-03-0697 PG 10 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500033 PM 12393716 ER PT J AU Aliberti, J Schulz, O Pennington, DJ Tsujimura, H Sousa, CRE Ozato, K Sher, A AF Aliberti, J Schulz, O Pennington, DJ Tsujimura, H Sousa, CRE Ozato, K Sher, A TI Essential role for ICSBP in the in vivo development of murine CD8 alpha(+) dendritic cells SO BLOOD LA English DT Article ID SEQUENCE-BINDING-PROTEIN; IN-VIVO; TRANSCRIPTION FACTOR; MYELOID PROGENITOR; MESSENGER-RNA; BACTERIAL-DNA; FLT3 LIGAND; LYMPH-NODES; IFN-GAMMA; MICE AB Interferon (IFN) consensus sequence-binding protein (ICSBP) is an important transcription factor regulating proinflammatory cytokine production and the development of mononuclear phagocytes in vitro. Here we analyzed the role of ICSBP in the in vivo differentiation of 3 major subsets of murine dendritic cells (DCs). We found that ICSBP is predominantly expressed by the CD8alpha(+) subset, and more important, that ICSBP-/- mice have a profound and selective deficiency in CD8alpha(+) IDEC205(+) DCs in lymphold tissues. Studies using wild-type/ICSBP-/- chimeras revealed that this defect in CD8alpha(+) DC development is intrinsic to bone marrow-derived progenitors and not dependent on ICSBP expression in the nonhemopoietic compartment. Because DC precursor frequencies are unaltered in the bone marrow of ICSBP-/- mice, ICSBP appears to function by regulating CD8alpha(+) DC differentiation downstream from the generation of common DC progenitors. Although CD8alpha(-) DCs are present in normal numbers in ICSBP-/- animals, up-regulation of CD40, CD80, and major histocompatibility complex (MHC) class II expression was found to be impaired in this subset after in vivo microbial stimulation. Together these results demonstrate that ICSBP is critically required for the in vivo differentiation of CD8alpha(+) DCs and may also influence the functional maturation of the CD8alpha(-) subsets. (C) 2003 by The American Society of Hematology. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Canc Res United Kingdom, London Res Inst, Immunobiol & Lymphocyte Mol Biol Labs, London, England. RP Aliberti, J (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 50 S Dr, 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 37 TC 188 Z9 189 U1 1 U2 4 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 JAN 1 PY 2003 VL 101 IS 1 BP 305 EP 310 DI 10.1182/blood-2002-04-1088 PG 6 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500046 PM 12393690 ER PT J AU Wandersee, NJ Birkenmeier, CS Bodine, DM Mohandas, N Barker, JE AF Wandersee, NJ Birkenmeier, CS Bodine, DM Mohandas, N Barker, JE TI Mutations in the murine erythroid alpha-spectrin gene alter spectrin mRNA and protein levels and spectrin incorporation into the red blood cell membrane skeleton SO BLOOD LA English DT Article ID INHERITED HEMOLYTIC-ANEMIAS; BETA-SPECTRIN; HEREDITARY ELLIPTOCYTOSIS; JAUNDICED MICE; ACTIN; CDNA; ANKYRIN; MOUSE; SPHEROCYTOSIS; THROMBOSIS AB Tetramers of alpha- and beta-spectrin heterodimers, linked by intermediary proteins to transmembrane proteins, stabilize the red blood cell cytoskeleton. Deficiencies of either alpha- or beta-spectrin can result in severe hereditary spherocytosis (HS) or hereditary elliptocytosis (HE) in mice and humans. Four mouse mutations, sph, sph(Dem), sph(2BC), and sph(J), affect the erythroid a-spectrin gene, Spna1, on chromosome 1 and cause severe HS and HE. Here we describe the molecular alterations in alpha-spectrin and their consequences in sph(2BC)/sph(2BC) and sph(J)/sph(J) erythrocytes. A splicing mutation, sph(2BC) initiates the skipping of exon 41 and premature protein termination before the site required for dimerization of alpha-spectrin with beta-spectrin. A nonsense mutation in exon 52, sph(J) eliminates the COOH-terminal 13 amino acids. Both defects result in instability of the red cell membrane and loss of membrane surface area in sph(2BC)/sph(2BC), barely perceptible levels of messenger RNA and consequent decreased synthesis of alpha-spectrin protein are primarily responsible for the resultant hemolysis. By contrast, sph(J)/sph(J) mice synthesize the truncated alpha-spectrin in which the 13-terminal amino acids are deleted at higher levels than normal, but they cannot retain this mutant protein in the cytoskeleton. The sph(J) deletion is near the 4.1/actin-binding region at the junctional complex providing new evidence that this 13-amino acid segment at the COOH-terminus of alpha-spectrin is crucial to the stability of the junctional complex. (C) 2003 by The American Society of Hematology. C1 Jackson Lab, Bar Harbor, ME 04609 USA. NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. New York Blood Ctr, New York, NY 10021 USA. RP Barker, JE (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. FU NCI NIH HHS [CA34196]; NHLBI NIH HHS [R01 HL29305]; NIDDK NIH HHS [F32 DK09482, R01 DK26263] NR 50 TC 18 Z9 20 U1 0 U2 4 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 JAN 1 PY 2003 VL 101 IS 1 BP 325 EP 330 DI 10.1182/blood-2002-01-0113 PG 6 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500049 PM 12393645 ER PT J AU Yipp, BG Baruch, DI Brady, C Murray, AG Looareesuwan, S Kubes, P Ho, M AF Yipp, BG Baruch, DI Brady, C Murray, AG Looareesuwan, S Kubes, P Ho, M TI Recombinant PfEMP1 peptide inhibits and reverses cytoadherence of clinical Plasmodium falciparum isolates in vivo SO BLOOD LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; MICROVASCULAR ENDOTHELIAL-CELLS; INFECTED ERYTHROCYTES; ANTIGENIC VARIATION; CEREBRAL MALARIA; VARIANT ANTIGEN; FLOW CONDITIONS; NECROSIS-FACTOR; E-SELECTIN; VAR GENES AB The parasite ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and host endothelial receptors represent potential targets for antiadhesive therapy for cytoadherence. In the present study, the major host receptor CD36 was targeted in vitro and in vivo with a recombinant peptide, PpMC-179, corresponding to the minimal CD36-binding domain from the cysteine-rich interdomain region 1 (CIDR1) within the Mcvar1 PfEMP1. The in vitro inhibitory effect of PpMC-179 on human dermal microvascular endothelial cells (HDMECs) expressing multiple relevant adhesion molecules was investigated using a parallel-plate flow chamber. Pretreatment of endothelial monolayers with PpMC-179 (2 muM) inhibited the adhesion of infected erythrocytes (IRBCs) from all clinical isolates tested by 84.4% on resting and 62.8% on tumor necrosis factor alpha (TNF-alpha)-stimulated monolayers. Adhesion to stimulated cells was further inhibited (90.4%) when PpMC-179 was administered with an inhibitory anti-intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody 84H10 (5 mug/mL). To determine the in vivo effectiveness of PpMC-179, we used a human/severe combined immunodeficiency (SCID) mouse chimeric model that allowed direct visualization of cytoadherence on intact human microvasculature. In unstimulated skin grafts, PpMC-179 inhibited adhesion by 86.3% and by 84.6% in TNF-alpha-stimulated skin grafts. More importantly, PpMC-179 administration resulted in the detachment of already adherent IRBCs by 80.7% and 83.3% on resting and stimulated skin grafts, respectively. The antiadhesive effect of PpMC-179 was rapid and sustained in vivo for at least 30 minutes. Our data indicate that targeting cytoadhesion in vivo is feasible and may offer a rapid antimalarial therapy. (C) 2003 by The American Society of Hematology. C1 Univ Calgary, Dept Microbiol & Infect Dis, Immunol Res Grp, Calgary, AB T2N 4N1, Canada. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Malaria Vaccine Dev Unit, NIH, Bethesda, MD 20892 USA. Univ Alberta, Dept Med, Edmonton, AB T6G 2M7, Canada. Mahidol Univ, Fac Trop Med, Bangkok, Thailand. RP Ho, M (reprint author), Univ Calgary, Dept Microbiol & Infect Dis, Immunol Res Grp, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. RI Murray, Allan/F-3204-2011 NR 36 TC 27 Z9 28 U1 0 U2 3 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 JAN 1 PY 2003 VL 101 IS 1 BP 331 EP 337 DI 10.1182/blood-2002-06-1725 PG 7 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500050 PM 12393525 ER PT J AU Kelly, PF Donahue, RE Vandergriff, JA Takatoku, M Bonifacino, AC Agricola, BA Metzger, ME Dunbar, CE Nienhuis, AW Vanin, EF AF Kelly, PF Donahue, RE Vandergriff, JA Takatoku, M Bonifacino, AC Agricola, BA Metzger, ME Dunbar, CE Nienhuis, AW Vanin, EF TI Prolonged multilineage clonal hematopoiesis in a rhesus recipient of CD34 positive cells marked with a RD114 pseudotyped oncoretroviral vector SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE gene transfer; hematopoiesis; RD114; rhesus; oncoretroviral; inverse PCR ID MEDIATED GENE-TRANSFER; CHRONIC GRANULOMATOUS-DISEASE; COLONY-STIMULATING FACTOR; FIBRONECTIN FRAGMENT CH-296; GREEN FLUORESCENT PROTEIN; SCID-REPOPULATING CELLS; BONE-MARROW-CELLS; STEM-CELLS; PERIPHERAL-BLOOD; CORD BLOOD AB The ability to efficiently transfer a gene into repopulating hematopoietic stem cells would create many therapeutic opportunities. We have evaluated the ability of particles bearing an alternative envelope protein, that of the feline endogenous vir-us (RD114), to transduce stem cells in a nonhuman primate autologous transplantation model using rhesus macaques. We have previously shown this pseudotyped vector to be superior to the amphotropic vector at transducing cells in umbilical cord blood capable of establishing hematopoiesis in immunodeficient mice. Gene transfer efficiency as reflected by the number of genetically modified cells in hematopoietic tissues varied among the five monkeys studied from low levels (< 1%) in three animals to much higher levels in two (20-60%). An animal that exhibited extremely high levels for several weeks was found by vector genome insertion site analysis to have reconstitution predominantly with a single clone of cells. This variability among animals is in keeping with computer simulations of reconstitution with limiting numbers of stem cells genetically modified at about 10% efficiency. Our studies provide insights into the biology of hematopoietic reconstitution and suggest approaches for increasing stem cell targeted gene transfer efficiency. (C) 2003 Elsevier Science (USA). All rights reserved. C1 St Jude Childrens Res Hosp, Dept Hematol Oncol, Div Expt Hematol, Memphis, TN 38105 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Nienhuis, AW (reprint author), St Jude Childrens Res Hosp, Dept Hematol Oncol, Div Expt Hematol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM arthur.nienhuis@stjude.org FU NCI NIH HHS [P30 CA 21765]; NHLBI NIH HHS [P01 HL 53749] NR 45 TC 19 Z9 19 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JAN-FEB PY 2003 VL 30 IS 1 BP 132 EP 143 DI 10.1016/S1079-9796(03)00005-6 PG 12 WC Hematology SC Hematology GA 666MZ UT WOS:000182182200015 PM 12667996 ER PT J AU Haque, KA Pfeiffer, RM Beerman, MB Struewing, JP Chanock, SJ Bergen, AW AF Haque, KA Pfeiffer, RM Beerman, MB Struewing, JP Chanock, SJ Bergen, AW TI Performance of high-throughput DNA quantification methods SO BMC BIOTECHNOLOGY LA English DT Article ID NIST MIXED STAIN; TIME PCR ASSAY; GENOME AMPLIFICATION; QUANTITATION; MULTIPLEX; SAMPLES; TOOL AB Background: The accuracy and precision of estimates of DNA concentration are critical factors for efficient use of DNA samples in high-throughput genotype and sequence analyses. We evaluated the performance of spectrophotometric (OD) DNA quantification, and compared it to two fluorometric quantification methods, the PicoGreen(R) assay (PG), and a novel real-time quantitative genomic PCR assay (QG) specific to a region at the human BRCA1 locus. Twenty-Two lymphoblastoid cell line DNA samples with an initial concentration of similar to350 ng/uL were diluted to 20 ng/uL. DNA concentration was estimated by OD and further diluted to 5 ng/uL. The concentrations of multiple aliquots of the final dilution were measured by the OD, QG and PG methods. The effects of manual and robotic laboratory sample handling procedures on the estimates of DNA concentration were assessed using variance components analyses. Results: The OD method was the DNA quantification method most concordant with the reference sample among the three methods evaluated. A large fraction of the total variance for all three methods (36.0-95.7%) was explained by sample-to-sample variation, whereas the amount of variance attributable to sample handling was small (0.8-17.5%). Residual error (3.2-59.4%), corresponding to un-modelled factors, contributed a greater extent to the total variation than the sample handling procedures. Conclusion: The application of a specific DNA quantification method to a particular molecular genetic laboratory protocol must take into account the accuracy and precision of the specific method, as well as the requirements of the experimental workflow with respect to sample volumes and throughput. While OD was the most concordant and precise DNA quantification method in this study, the information provided by the quantitative PCR assay regarding the suitability of DNA samples for PCR may be an essential factor for some protocols, despite the decreased concordance and precision of this method. C1 NCI, Core Genotyping Facil, SAIC Frederick Inc, NIH, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20879 USA. RP Haque, KA (reprint author), NCI, Core Genotyping Facil, SAIC Frederick Inc, NIH, Bethesda, MD 20892 USA. EM haquek@mail.nih.gov; pfeiffer@mail.nih.gov; beerman@mail.nih.gov; struewij@mail.nih.gov; chanocks@mail.nih.gov; bergena@mail.nih.gov RI Struewing, Jeffery/C-3221-2008; Pfeiffer, Ruth /F-4748-2011; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 20 TC 49 Z9 50 U1 2 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PY 2003 VL 3 AR 20 DI 10.1186/1472-6750-3-20 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 763WX UT WOS:000188124400020 PM 14583097 ER PT J AU Shiao, YH AF Shiao, YH TI A new reverse transcription-polymerase chain reaction method for accurate quantification SO BMC BIOTECHNOLOGY LA English DT Article ID TIME QUANTITATIVE PCR; GENE-EXPRESSION; KINETICS AB Background: Reverse transcription-polymerase chain reaction (RT-PCR) is a very sensitive technique to measure and to compare mRNA levels among samples. However, it is extremely difficult to maintain linearity across the entire procedure, especially at the step of PCR amplification. Specific genes have been used as baseline controls to be co-amplified with target genes to normalize the amplification efficiency, but development or selection of reliable controls itself has created a new challenge. Results: Here, we describe a new quantitative RT-PCR to compare two mRNA samples directly without the requirement of synthetic control DNAs for reference. First, chimeric RT primers carrying gene-specific and universal PCR priming sequences with or without a linker for size distinction were utilized to generate cDNAs. The size-different cDNAs were then combined in a single reaction for PCR amplification using the same primer set. The two amplified products were resolved and detected with gel electrophoresis and fluorescence imaging. Relative abundance of the two products was obtained after a baseline correction. Conclusion: This methodology is simple and accurate as indicated by equal amplification efficiency throughout PCR cycling. It is also easily implemented for many existing protocols. In addition, parameters affecting RT linearity are characterized in this report. C1 NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA. RP Shiao, YH (reprint author), NCI, Comparat Carcinogenesis Lab, NIH, Bldg 538,Room 205, Frederick, MD 21702 USA. EM shiao@mail.ncifcrf.gov NR 11 TC 6 Z9 7 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PY 2003 VL 3 AR 22 DI 10.1186/1472-6750-3-22 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 763WX UT WOS:000188124400022 PM 14664723 ER PT J AU Yu, HW Pandit, B Klett, E Lee, MH Lu, KM Helou, K Ikeda, I Egashira, N Sato, M Klein, R Batta, A Salen, G Patel, SB AF Yu, Hongwei Pandit, Bhaswati Klett, Eric Lee, Mi-Hye Lu, Kangmo Helou, Khalil Ikeda, Ikuo Egashira, Nami Sato, Masao Klein, Richard Batta, Ashok Salen, Gerald Patel, Shailendra B. TI The rat STSL locus: characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats SO BMC CARDIOVASCULAR DISORDERS LA English DT Article AB Background: Elevated plant sterol accumulation has been reported in the spontaneously hypertensive rat (SHR), the stroke-prone spontaneously hypertensive rat (SHRSP) and the Wistar-Kyoto (WKY) rat. Additionally, a blood pressure quantitative trait locus (QTL) has been mapped to rat chromosome 6 in a New Zealand genetically hypertensive rat strain (GH rat). ABCG5 and ABCG8 (encoding sterolin-1 and sterolin-2 respectively) have been shown to be responsible for causing sitosterolemia in humans. These genes are organized in a head-to-head configuration at the STSL locus on human chromosome 2p21. Methods: To investigate whether mutations in Abcg5 or Abcg8 exist in SHR, SHRSP, WKY and GH rats, we initiated a systematic search for the genetic variation in coding and non-coding region of Abcg5 and Abcg8 genes in these strains. We isolated the rat cDNAs for these genes and characterized the genomic structure and tissue expression patterns, using standard molecular biology techniques and FISH for chromosomal assignments. Results: Both rat Abcg5 and Abcg8 genes map to chromosome band 6q12. These genes span similar to 40 kb and contain 13 exons and 12 introns each, in a pattern identical to that of the STSL loci in mouse and man. Both Abcg5 and Abcg8 were expressed only in liver and intestine. Analyses of DNA from SHR, SHRSP, GH, WKY, Wistar, Wistar King A (WKA) and Brown Norway (BN) rat strains revealed a homozygous G to T substitution at nucleotide 1754, resulting in the coding change Gly583Cys in sterolin-1 only in rats that are both sitosterolemic and hypertensive (SHR, SHRSP and WKY). Conclusions: The rat STSL locus maps to chromosome 6q12. A non-synonymous mutation in Abcg5, Gly583Cys, results in sitosterolemia in rat strains that are also hypertensive (WKY, SHR and SHRSP). Those rat strains that are hypertensive, but not sitosterolemic (e. g. GH rat) do not have mutations in Abcg5 or Abcg8. This mutation allows for expression and apparent apical targeting of Abcg5 protein in the intestine. These rat strains may therefore allow us to study the pathophysiological mechanisms involved in the human disease of sitosterolemia. C1 [Yu, Hongwei; Pandit, Bhaswati; Klett, Eric; Lee, Mi-Hye; Lu, Kangmo; Klein, Richard; Patel, Shailendra B.] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. [Helou, Khalil] Inst NIH, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Helou, Khalil] Gothenburg Univ, Inst Selected Clin Sci, Dept Oncol, SE-41345 Gothenburg, Sweden. [Ikeda, Ikuo; Egashira, Nami; Sato, Masao] Kyushu Univ, Grad Sch Kyushu, Fac Agr, Dept Biosci & Biotechnol,Lab Nutr Chem, Fukuoka 8128581, Japan. [Batta, Ashok; Salen, Gerald] Dept Vet Affairs Med Ctr, Res Serv, E Orange, NJ USA. [Batta, Ashok; Salen, Gerald] Dept Vet Affairs Med Ctr, Med Serv, E Orange, NJ USA. RP Patel, SB (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, STR 541,114 Doughty St, Charleston, SC 29403 USA. EM yuh@musc.edu; pandit@musc.edu; klettel@musc.edu; leemih@musc.edu; luk@musc.edu; khalil.helou@oncology.gu.se; Iikeda@agr.kyushu-u.ac.jp; Iikeda@agr.kyushu-u.ac.jp; Iikeda@agr.kyushu-u.ac.jp; kleinrl@musc.edu; salenge@umdnj.edu; salenge@undnj.edu; patelsb@musc.edu FU NHLBI [U01 HL6657] FX We thank Dr. Jean Harris, University of Otago, New Zealand, for providing us with the DNA samples from GH and BN rats for this study, Drs. Howard Jacobs and Marijo Bilusic, Medical College of Wisconsin, Milwaukee, WI for plasma samples from GH rats (funded by the NHLBI Programs for Genomic Applications, U01 HL6657) and John Oatis IIIrd for providing technical assistance and animal husbandry. We also gratefully acknowledge the assistance of Dr. Thomas Ried in performing the FISH analyses. NR 49 TC 26 Z9 28 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2261 J9 BMC CARDIOVASC DISOR JI BMC Cardiovasc. Disord. PY 2003 VL 3 AR 4 DI 10.1186/1471-2261-3-4 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V22NI UT WOS:000208281500004 PM 12783625 ER PT J AU Jordan, IK Wolf, YI Koonin, EV AF Jordan, IK Wolf, YI Koonin, EV TI No simple dependence between protein evolution rate and the number of protein-protein interactions: only the most prolific interactors tend to evolve slowly SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID PATHOGEN HELICOBACTER-PYLORI; GENOME SEQUENCE; DATABASE; NETWORKS AB Background: It has been suggested that rates of protein evolution are influenced, to a great extent, by the proportion of amino acid residues that are directly involved in protein function. In agreement with this hypothesis, recent work has shown a negative correlation between evolutionary rates and the number of protein-protein interactions. However, the extent to which the number of protein-protein interactions influences evolutionary rates remains unclear. Here, we address this question at several different levels of evolutionary relatedness. Results: Manually curated data on the number of protein-protein interactions among Saccharomyces cerevisiae proteins was examined for possible correlation with evolutionary rates between S. cerevisiae and Schizosaccharomyces pombe orthologs. Only a very weak negative correlation between the number of interactions and evolutionary rate of a protein was observed. Furthermore, no relationship was found between a more general measure of the evolutionary conservation of S. cerevisiae proteins, based on the taxonomic distribution of their homologs, and the number of protein-protein interactions. However, when the proteins from yeast were assorted into discrete bins according to the number of interactions, it turned out that 6.5% of the proteins with the greatest number of interactions evolved, on average, significantly slower than the rest of the proteins. Comparisons were also performed using protein-protein interaction data obtained with high-throughput analysis of Helicobacter pylori proteins. No convincing relationship between the number of protein-protein interactions and evolutionary rates was detected, either for comparisons of orthologs from two completely sequenced H. pylori strains or for comparisons of H. pylori and Campylobacter jejuni orthologs, even when the proteins were classified into bins by the number of interactions. Conclusion: The currently available comparative-genomic data do not support the hypothesis that the evolutionary rates of the majority of proteins substantially depend on the number of protein-protein interactions they are involved in. However, a small fraction of yeast proteins with the largest number of interactions ( the hubs of the interaction network) tend to evolve slower than the bulk of the proteins. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM jordan@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov NR 22 TC 123 Z9 124 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PY 2003 VL 3 AR 1 DI 10.1186/1471-2148-3-1 PG 8 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 763VX UT WOS:000188122100001 PM 12515583 ER PT J AU Mirkin, BG Fenner, TI Galperin, MY Koonin, EV AF Mirkin, BG Fenner, TI Galperin, MY Koonin, EV TI Algorithms for computing parsimonious evolutionary scenarios for genome evolution, the last universal common ancestor and dominance of horizontal gene transfer in the evolution of prokaryotes SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID TRANSFER-RNA SYNTHETASES; PHYLOGENETIC CLASSIFICATION; BACTERIAL EVOLUTION; CHIMERIC ORIGIN; REVERSE GYRASE; TREES; PROTEIN; ARCHAEA; LIFE; DNA AB Background: Comparative analysis of sequenced genomes reveals numerous instances of apparent horizontal gene transfer (HGT), at least in prokaryotes, and indicates that lineage-specific gene loss might have been even more common in evolution. This complicates the notion of a species tree, which needs to be re-interpreted as a prevailing evolutionary trend, rather than the full depiction of evolution, and makes reconstruction of ancestral genomes a non-trivial task. Results: We addressed the problem of constructing parsimonious scenarios for individual sets of orthologous genes given a species tree. The orthologous sets were taken from the database of Clusters of Orthologous Groups of proteins (COGs). We show that the phyletic patterns ( patterns of presence-absence in completely sequenced genomes) of almost 90% of the COGs are inconsistent with the hypothetical species tree. Algorithms were developed to reconcile the phyletic patterns with the species tree by postulating gene loss, COG emergence and HGT (the latter two classes of events were collectively treated as gene gains). We prove that each of these algorithms produces a parsimonious evolutionary scenario, which can be represented as mapping of loss and gain events on the species tree. The distribution of the evolutionary events among the tree nodes substantially depends on the underlying assumptions of the reconciliation algorithm, e. g. whether or not independent gene gains (gain after loss after gain) are permitted. Biological considerations suggest that, on average, gene loss might be a more likely event than gene gain. Therefore different gain penalties were used and the resulting series of reconstructed gene sets for the last universal common ancestor (LUCA) of the extant life forms were analysed. The number of genes in the reconstructed LUCA gene sets grows as the gain penalty increases. However, qualitative examination of the LUCA versions reconstructed with different gain penalties indicates that, even with a gain penalty of 1 (equal weights assigned to a gain and a loss), the set of 572 genes assigned to LUCA might be nearly sufficient to sustain a functioning organism. Under this gain penalty value, the numbers of horizontal gene transfer and gene loss events are nearly identical. This result holds true for two alternative topologies of the species tree and even under random shuffling of the tree. Therefore, the results seem to be compatible with approximately equal likelihoods of HGT and gene loss in the evolution of prokaryotes. Conclusions: The notion that gene loss and HGT are major aspects of prokaryotic evolution was supported by quantitative analysis of the mapping of the phyletic patterns of COGs onto a hypothetical species tree. Algorithms were developed for constructing parsimonious evolutionary scenarios, which include gene loss and gain events, for orthologous gene sets, given a species tree. This analysis shows, contrary to expectations, that the number of predicted HGT events that occurred during the evolution of prokaryotes might be approximately the same as the number of gene losses. The approach to the reconstruction of evolutionary scenarios employed here is conservative with regard to the detection of HGT because only patterns of gene presence-absence in sequenced genomes are taken into account. In reality, horizontal transfer might have contributed to the evolution of many other genes also, which makes it a dominant force in prokaryotic evolution. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ London Birkbeck Coll, Sch Informat Syst & Comp Sci, London WC1E 7HX, England. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM mirkin@dcs.bbk.ac.uk; trevor@dcs.bbk.ac.uk; galperin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 84 TC 213 Z9 220 U1 1 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PY 2003 VL 3 AR 2 DI 10.1186/1471-2148-3-2 PG 34 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 763VX UT WOS:000188122100002 PM 12515582 ER PT J AU Mulkidjanian, AY Cherepanov, DA Galperin, MY AF Mulkidjanian, AY Cherepanov, DA Galperin, MY TI Survival of the fittest before the beginning of life: selection of the first oligonucleotide-like polymers by UV light SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID RNA WORLD; ULTRAVIOLET; CATALYSIS; EVOLUTION; ORIGIN; MONTMORILLONITE; EFFICIENCY; OLIGOMERS; RADIATION; HISTORY AB Background: A key event in the origin of life on this planet has been formation of self-replicating RNA-type molecules, which were complex enough to undergo a Darwinian-type evolution ( origin of the "RNA world"). However, so far there has been no explanation of how the first RNA-like biopolymers could originate and survive on the primordial Earth. Results: As condensation of sugar phosphates and nitrogenous bases is thermodynamically unfavorable, these compounds, if ever formed, should have undergone rapid hydrolysis. Thus, formation of oligonucleotide-like structures could have happened only if and when these structures had some selective advantage over simpler compounds. It is well known that nitrogenous bases are powerful quenchers of UV quanta and effectively protect the pentose-phosphate backbones of RNA and DNA from UV cleavage. To check if such a protection could play a role in abiogenic evolution on the primordial Earth ( in the absence of the UV-protecting ozone layer), we simulated, by using Monte Carlo approach, the formation of the first oligonucleotides under continuous UV illumination. The simulations confirmed that UV irradiation could have worked as a selective factor leading to a relative enrichment of the system in longer sugar-phosphate polymers carrying nitrogenous bases as UV-protectors. Partial funneling of the UV energy into the condensation reactions could provide a further boost for the oligomerization. Conclusion: These results suggest that accumulation of the first polynucleotides could be explained by their abiogenic selection as the most UV-resistant biopolymers. C1 Univ Osnabruck, Dept Biol & Chem, Div Biophys, D-49069 Osnabruck, Germany. Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119899, Russia. Russian Acad Sci, Inst Electrochem, Moscow 117071, Russia. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Dept Biol & Chem, Div Biophys, D-49069 Osnabruck, Germany. EM mulkidjanian@biologie.uni-osnabrueck.de; cherepanov@biologie.uni-osnabrueck.de; galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013; Mulkidjanian, Armen/J-8086-2013 OI Galperin, Michael/0000-0002-2265-5572; Mulkidjanian, Armen/0000-0001-5844-3064 FU Intramural NIH HHS [Z99 LM999999] NR 32 TC 24 Z9 24 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PY 2003 VL 3 AR 12 DI 10.1186/1471-2148-3-12 PG 7 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 763VX UT WOS:000188122100012 PM 12773209 ER PT J AU Elvevag, B Maylor, EA Gilbert, AL AF Elvevag, Brita Maylor, Elizabeth A. Gilbert, Abigail L. TI Habitual prospective memory in schizophrenia SO BMC PSYCHIATRY LA English DT Article AB Background: Prospective memory (PM), the act of remembering that something has to be done in the future without any explicit prompting to recall, provides a useful framework with which to examine problems in internal-source monitoring. This is because it requires distinguishing between two internally-generated processes, namely the intention to perform an action versus actual performance of the action. In habitual tasks, such as taking medicine every few hours, the same PM task is performed regularly and thus it is essential that the individual is able to distinguish thoughts (i.e., thinking about taking the medicine) from actions (i.e., actually taking the medicine). Methods: We assessed habitual PM in patients with schizophrenia by employing a laboratory analogue of a habitual PM task in which, concurrently with maneuvering a ball around an obstacle course (ongoing activity), participants were to turn over a counter once during each trial (PM task). After each trial, participants were asked whether they had remembered to turn the counter over. Results: Patients with schizophrenia made a disproportionate number of errors compared to controls of reporting that a PM response had been made (i.e., the counter turned over) after an omission error (i.e., the counter was not turned over). There was no group difference in terms of reporting that an omission error occurred (i.e., forgetting to turn over the counter) when in fact a PM response had been made. Conclusion: Patients with schizophrenia displayed a specific deficit distinguishing between two internally-generated sources, attributable to either poor source monitoring or temporal discrimination. C1 [Elvevag, Brita; Gilbert, Abigail L.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Maylor, Elizabeth A.] Univ Warwick, Dept Psychol, Coventry CV4 7AL, W Midlands, England. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Rm 4S235,MSC 1379, Bethesda, MD 20892 USA. EM elvevaab@intra.nimh.nih.gov; E.A.Maylor@warwick.ac.uk; gilberta@mail.nih.gov NR 51 TC 29 Z9 31 U1 6 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PY 2003 VL 3 AR 9 DI 10.1186/1471-244X-3-9 PG 7 WC Psychiatry SC Psychiatry GA V22MT UT WOS:000208280000009 PM 12890293 ER PT J AU Muraro, PA Wandinger, KP Bielekova, B Gran, B Marques, A Utz, U McFarland, HF Jacobson, S Martin, R AF Muraro, PA Wandinger, KP Bielekova, B Gran, B Marques, A Utz, U McFarland, HF Jacobson, S Martin, R TI Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders SO BRAIN LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Academy-of-Neurology CY APR 13-20, 2002 CL DENVER, COLORADO SP Amer Acad Neurol DE autoimmunity; HAM/TSP; Lyme disease; multiple sclerosis; T cell receptors; immunotherapy ID MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS PATIENTS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; PERIPHERAL-BLOOD; HEALTHY-INDIVIDUALS; RECEPTOR REPERTOIRE; SINGLE-CELL; DISEASE; LYMPHOCYTES AB T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases. Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology. Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and chronic Lyme neuroborreliosis. We developed and applied a highly specific and sensitive technique to track single CD4(+) and CD8(+) T cell clones through the detection and quantification of T cell receptor (TCR) alpha or beta chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)-PCR. We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease. Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both. By integrating clonotype tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/TSP. T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders. C1 Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Ctr Neurosci, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD USA. RP Muraro, PA (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013; OI Gran, Bruno/0000-0001-6384-2342; Muraro, Paolo/0000-0002-3822-1218 FU Intramural NIH HHS [Z01 NS002817-18, Z01 NS002817-19, Z01 NS003040-01] NR 53 TC 53 Z9 54 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 2003 VL 126 BP 20 EP 31 DI 10.1093/brain/awg021 PN 1 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 625NF UT WOS:000179822000003 PM 12477694 ER PT B AU Rapoport, SI AF Rapoport, SI BE Finch, CE Robine, JM Christen, Y TI How did longevity promote brain expansion during primate evolution? SO BRAIN AND LONGEVITY SE RESEARCH AND PERSPECTIVES IN LONGEVITY LA English DT Proceedings Paper CT Symposium on Brain and Longevity CY OCT 08, 2001 CL PARIS, FRANCE SP Fdn IPSEN ID HUMAN CEREBRAL-CORTEX; FREE-RADICAL THEORY; FUNCTIONAL-ANATOMY; METABOLIC-RATE; VISUAL-CORTEX; ATTENTION; MAMMALS; GROWTH; CONSTRAINTS; CHIMPANZEES AB Evidence indicates that cognitive ability, brain size and life span co-evolved during primate evolution. It is not difficult to conceive how prolongation of the initial phases of the life span - gestation, infancy and adolescence and young adulthood - contributed to this co-evolution. Prolonged gestation would have provided larger brains at birth, whereas prolonged infancy, adolescence and young adulthood would have extended brain neuroplasticity to allow experience and learning to modify brain structure in individuals (genotypes) faced with new cognitive and social stresses, making them more competitive and reproductively successful. Natural selection in primates also involved genetically related kinships. Through cooperation within kinships, older genotypes who were most cognitively and socially competitive because of their larger brains could contribute to the success of their kin, indirectly extending their own genes in the general population. In some cases, a new longer-lived, more cognitively-capable, larger-brained primate species appeared. C1 NIA, Neurosci Lab, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Neurosci Lab, Bldg 10,Room 6C 103 Natl,Rockville Pike, Bethesda, MD 20892 USA. RI Robine, Jean-Marie/F-5439-2011 OI Robine, Jean-Marie/0000-0002-4111-6195 NR 82 TC 0 Z9 0 U1 0 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-43958-7 J9 RES PERSPECT LONGEV PY 2003 BP 99 EP 110 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BW17J UT WOS:000181072900005 ER PT S AU McCarron, RM Shohami, E Panikashvili, D Chen, Y Golech, S Strasser, A Mechoulam, R Spatz, M AF McCarron, RM Shohami, E Panikashvili, D Chen, Y Golech, S Strasser, A Mechoulam, R Spatz, M BE Kuroiwa, T Baethmann, A Czernicki, Z Hoff, JT Ito, U Katayama, Y Mararou, A Mendelow, AD Reulen, HJ TI Antioxidant properties of the vasoactive endocannabinoid, 2-arachidonoyl glycerol (2-AG) SO BRAIN EDEMA XII SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 12th International Symposium on Brain Edema CY NOV 10-13, 2002 CL HAKONE, JAPAN DE brain endothelium; endothelin-1; 2-arachidonoyl glycerol; H2O2; ischemia; reperfusion; cerebral blood flow ID CLOSED-HEAD INJURY; ENDOTHELIAL-CELLS; BRAIN; MODEL; MICE AB Reactive oxygen species (ROS) were shown to play a role in altering blood-brain barrier (BBB) permeability and formation of brain edema induced by trauma and/or ischemia. 2-arachidonoyl glycerol (2-AG), a novel, potent vasodilatory and cytoprotective endocannabinoid has been implicated to act as an antioxidative agent. This study examines: 1) the possible 2-AG modulation of BBB injury and edema formation induced by closed head injury (CHI); and 2) comparable effects between 2-AG and 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TPL), a known antioxidant nitroxide on endothelial Ca2+ and cytoskeletal responses to H2O2 (ROS). 2-AG treatment reduced the CHI-induced increase in BBB permeability and brain edema. The endothelial H2O2-stimulated Ca2+ mobilization and cytoskeleton (vimentin) rearrangement was modified by either 2-AG or TPL. These findings provide evidence of 2-AG antioxidant activity and are consistent with the involvement of ROS in the pathomechanism of CHI-induced BBB injury and brain edema. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Spatz, M (reprint author), NINDS, Stroke Branch, NIH, 36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 18 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 3-211-00919-1 J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 2003 VL 86 BP 271 EP 275 PG 5 WC Clinical Neurology; Neuroimaging SC Neurosciences & Neurology GA BY46F UT WOS:000189318700059 PM 14753451 ER PT J AU Lipkowitz, S AF Lipkowitz, S TI The role of the ubiquitination-proteasome pathway in breast cancer - Ubiquitin mediated degradation of growth factor receptors in the pathogenesis and treatment of cancer SO BREAST CANCER RESEARCH LA English DT Review DE EGFR; growth factor receptor; protein degradation; ubiquitin ID TUMOR NECROSIS FACTOR; C-CBL; TRASTUZUMAB HERCEPTIN; MONOCLONAL-ANTIBODY; HORMONE RECEPTOR; TYROSINE KINASES; ADAPTER PROTEIN; PLASMA-MEMBRANE; ERBB RECEPTORS; FMS MUTATIONS AB Aberrant activity of growth factor receptors has been implicated in the pathogenesis of a wide variety of malignancies. The negative regulation of signaling by growth factor receptors is mediated in large part by the ubiquitination, internalization, and degradation of the activated receptor. Over the past few years, considerable insight into the mechanisms that control receptor downregulation has been gained. There are also data suggesting that mutations that lead to inhibition of downregulation of growth factor receptors could play a role in the pathogenesis of cancer. Therapies directed at enhancing the degradation of growth factor receptors offer a promising approach to the treatment of malignancies. C1 NCI, Ctr Canc Res, Natl Naval Med Ctr, Genet Branch, Bethesda, MD 20889 USA. RP Lipkowitz, S (reprint author), NCI, Ctr Canc Res, Natl Naval Med Ctr, Genet Branch, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. NR 67 TC 30 Z9 30 U1 2 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2003 VL 5 IS 1 BP 8 EP 15 DI 10.1186/bcr541 PG 8 WC Oncology SC Oncology GA 629JN UT WOS:000180046700005 PM 12559039 ER PT J AU Gruvberger, SK Ringner, M Eden, P Borg, A Ferno, M Peterson, C Meltzer, PS AF Gruvberger, SK Ringner, M Eden, P Borg, A Ferno, M Peterson, C Meltzer, PS TI Expression profiling to predict outcome in breast cancer: the influence of sample selection SO BREAST CANCER RESEARCH LA English DT Review DE breast cancer; estrogen receptor; gene expression; microarray; prognosis ID MOLECULAR CLASSIFICATION; PATTERNS AB Gene expression profiling of tumors using DNA microarrays is a promising method for predicting prognosis and treatment response in cancer patients. It was recently reported that expression profiles of sporadic breast cancers could be used to predict disease recurrence better than currently available clinical and histopathological prognostic factors. Having observed an overlap in those data between the genes that predict outcome and those that predict estrogen receptor-alpha status, we examined their predictive power in an independent data set. We conclude that it may be important to define prognostic expression profiles separately for estrogen receptor-alpha-positive and estrogen receptor-alpha-negative tumors. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Lund Hosp, Jubileum Inst, Dept Oncol, S-22185 Lund, Sweden. Lund Univ, Dept Theoret Phys, Complex Syst Div, S-22362 Lund, Sweden. RP Meltzer, PS (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RI Ringner, Markus/G-3641-2011 OI Ringner, Markus/0000-0001-5469-8940 NR 11 TC 36 Z9 37 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2003 VL 5 IS 1 BP 23 EP 26 DI 10.1186/bcr548 PG 4 WC Oncology SC Oncology GA 629JN UT WOS:000180046700007 PM 12559041 ER PT J AU Miyoshi, K Hennighausen, L AF Miyoshi, K Hennighausen, L TI beta-catenin: a transforming actor on many stages SO BREAST CANCER RESEARCH LA English DT Review DE beta-catenin; cell specification; mammary gland; transdifferentiation ID HAIR FOLLICLE MORPHOGENESIS; PROTEIN-KINASE CK2; MAMMARY-GLAND; CYCLIN D1; TRANSCRIPTIONAL ACTIVATION; COLON-CARCINOMA; FEMALE MICE; STEM-CELLS; TUMORIGENESIS; EXPRESSION AB Mutations and deletions that result in the stabilization of beta-catenin are frequently found in a number of tumors, including those of the colon, the liver and the ovary, but are less frequently found in breast cancer. To investigate and understand the molecular nature of cell-specific beta-catenin signaling, experimental mouse genetics has been employed extensively. Gain-of-function and loss-of-function mutations have provided evidence that beta-catenin plays essential roles in development and tumorigenesis. Specifically, the Wnt/beta-catenin signaling pathway controls cell fate decisions throughout development, and a unique role in differentiated epithelia has emerged. Not only beta-catenin, but also the activation of other components of this pathway in differentiated mammary epithelium and prostate epithelium of transgenic mice can induce neoplasias and transdifferentiation to squamous metaplasias. This suggests that the Wnt/beta-catenin pathway is dominant over existing differentiation programs and can impose an epidermal fate or neoplasias onto a variety of cell types. Although there is evidence for a contextual specificity of the Wnt signaling, the experimental systems and designs used in different studies probably influence the cellular responses. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Univ Tokushima, Sch Dent, Dept Biochem, Tokushima, Japan. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. NR 41 TC 32 Z9 35 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2003 VL 5 IS 2 BP 63 EP 68 DI 10.1186/bcr566 PG 6 WC Oncology SC Oncology GA 688LR UT WOS:000183436900007 PM 12631383 ER PT J AU Ambrosone, CB Moysich, KB Furberg, H Freudenheim, JL Bowman, ED Ahmed, S Graham, S Vena, JE Shields, PG AF Ambrosone, CB Moysich, KB Furberg, H Freudenheim, JL Bowman, ED Ahmed, S Graham, S Vena, JE Shields, PG TI CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors SO BREAST CANCER RESEARCH LA English DT Review DE breast neoplasms; cytochrome P450c17 alpha; epidemiology; genetic polymorphism ID AGE 40 YEARS; PROMOTER POLYMORPHISM; AUSTRALIAN WOMEN; NO ASSOCIATION; SUSCEPTIBILITY; ESTROGEN; GENOTYPE AB Background: Findings from previous studies regarding the association between the CYP17 genotype and breast cancer are inconsistent. We investigated the role of the MspAI genetic polymorphism in the 5' region of CYP17 on risk of breast cancer and as a modifier of reproductive risk factors. Methods: Questionnaire and genotyping data were obtained from a population-based, case - control study of premenopausal ( n = 182) and postmenopausal ( n = 214) European-American Caucasian women in western New York. Cases and controls were frequency matched by age and by county of residence. Odds ratios and 95% confidence intervals were used to estimate relative risks. Results: The CYP17 genotype was not associated with breast cancer risk; however, controls with the A2/A2 genotype ( associated with higher estrogens) had earlier menarche and earlier first full-term pregnancy. Premenopausal women with A1/A1 genotypes, but not with A2 alleles, were at significantly decreased risk with late age at menarche ( odds ratio = 0.37, 95% confidence interval = 0.14 - 0.99), and at increased risk with late age at first full-term pregnancy ( odds ratio = 4.30, 95% confidence interval = 1.46 - 12.67) and with use of oral contraceptives ( odds ratio = 3.24, 95% confidence interval = 1.08 - 9.73). Associations were weaker among postmenopausal women. Conclusion: These results suggest that the effects of factors that may alter breast cancer risk through a hormonal mechanism may be less important among premenopausal women with putative higher lifetime exposures to circulating estrogens related to the CYP17 A2 allele. C1 Roswell Pk Canc Inst, Dept Epidemiol, Rochester, NY 14623 USA. Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY USA. Univ Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Georgetown Univ, Div Canc Genet & Epidemiol, Lombardi Canc Ctr, Med Ctr, Washington, DC USA. RP Ambrosone, CB (reprint author), Roswell Pk Canc Inst, Dept Epidemiol, Elm & Carlton St, Rochester, NY 14623 USA. RI Shields, Peter/I-1644-2012 NR 27 TC 40 Z9 40 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2003 VL 5 IS 2 BP R45 EP R51 DI 10.1186/bcr570 PG 7 WC Oncology SC Oncology GA 688LR UT WOS:000183436900005 PM 12631398 ER PT J AU Anderson, WF Chu, KC AF Anderson, WF Chu, KC TI Comparison of preinvasive and invasive breast carcinomas in the surveillance, epidemiology, and end results program. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2003 VL 82 SU 1 MA 618 BP S147 EP S148 PG 2 WC Oncology SC Oncology GA 747AN UT WOS:000186783100466 ER PT J AU Chu, KC Anderson, WF AF Chu, KC Anderson, WF TI Temporal patterns in infiltrating ductal and lobular carcinoma rates and their relationships to combined hormone replacement therapies. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 82 SU 1 MA 617 BP S147 EP S147 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100465 ER PT J AU Hance, KW Anderson, WF Devesa, SS Levine, PH AF Hance, KW Anderson, WF Devesa, SS Levine, PH TI Trends in inflammatory breast carcinoma incidence and survival: The surveillance, epidemiology, and end results program at the National Cancer Institute. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 NCI, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC 20052 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 82 SU 1 MA 619 BP S148 EP S148 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100467 ER PT J AU Huh, JI Calvo, A Stafford, J Cheung, M Kumar, R Gadisetti, C Green, JE AF Huh, JI Calvo, A Stafford, J Cheung, M Kumar, R Gadisetti, C Green, JE TI Inhibitory effect of tumor progression and gene expression profiling using GW654652, KDR/Flk-1 tyrosine kinase inhibitor. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 NCI, NIH, Bethesda, MD 20892 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 82 SU 1 MA 555 BP S135 EP S135 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100430 ER PT J AU Low, J Croarkin, E Parks, R Zia, F Steinberg, S Berman, A Mannan, N Swain, S AF Low, J Croarkin, E Parks, R Zia, F Steinberg, S Berman, A Mannan, N Swain, S TI Assessment of neurotoxicity in patients receiving BMS-247550 for metastatic breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 82 SU 1 MA 358 BP S85 EP S86 PG 2 WC Oncology SC Oncology GA 747AN UT WOS:000186783100269 ER PT J AU Mohsin, SK Elledge, RM Arun, B Miller, A Wu, K Johnson, K Lamph, WW Brown, PH AF Mohsin, SK Elledge, RM Arun, B Miller, A Wu, K Johnson, K Lamph, WW Brown, PH TI Breast cancer prevention using RXR-selective retinoid (Targreting (R)) in high risk women - initial report of a phase II randomized clinical trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NCI, Bethesda, MD 20892 USA. Ligand Pharmaceut Inc, San Diego, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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. PY 2003 VL 82 SU 1 MA 1027 BP S176 EP S176 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100559 ER PT J AU Paik, S Shak, S Tang, G Kim, C Baker, J Cronin, M Baehner, R Walker, M Watson, D Park, T Bryant, J Wolmark, N AF Paik, S Shak, S Tang, G Kim, C Baker, J Cronin, M Baehner, R Walker, M Watson, D Park, T Bryant, J Wolmark, N TI Multi-gene RT-PCR assay for predicting recurrence in node negative breast cancer patients - NSABP studies B-20 and B-14 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Genomic Hlth Inc, Redwood City, CA USA. NSABP, Pittsburgh, PA USA. NR 0 TC 15 Z9 16 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. PY 2003 VL 82 SU 1 MA 16 BP S10 EP S11 PG 2 WC Oncology SC Oncology GA 747AN UT WOS:000186783100029 ER PT J AU Ramaswamy, B Rhoades, CA Kendra, K Hauger, M Allen, J Jhaveri, S Chen, H Cagnoni, P Eckhardt, GS Elias, A Shapiro, CL AF Ramaswamy, B Rhoades, CA Kendra, K Hauger, M Allen, J Jhaveri, S Chen, H Cagnoni, P Eckhardt, GS Elias, A Shapiro, CL TI CTEP-sponsored phase II trial of bevacizumab (Avastin (TM)) in combination with docetaxel (Taxotere (R)) in metastatic breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Univ Colorado, Denver, CO 80202 USA. RI Ramaswamy, Bhuvaneswari/E-3919-2011 NR 0 TC 5 Z9 5 U1 0 U2 0 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. PY 2003 VL 82 SU 1 MA 224 BP S50 EP S50 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100154 ER PT J AU Seo, HS Kim, HT Kong, G Desprez, PY Lamph, WW Johnson, KA Brown, PH AF Seo, HS Kim, HT Kong, G Desprez, PY Lamph, WW Johnson, KA Brown, PH TI Rexinoid-regulated biomarkers: Up-regulation of Id-1 correlates with rexinoid-induced growth suppression of normal and malignant breast cells. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Baylor Coll Med, Houston, TX 77030 USA. Calif Pacific Med Ctr, Geraldine Brush Canc Res Inst, San Francisco, CA 94115 USA. Ligand Pharmaceut Inc, San Diego, CA USA. NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 82 SU 1 MA 473 BP S115 EP S116 PG 2 WC Oncology SC Oncology GA 747AN UT WOS:000186783100366 ER PT J AU Haiman, CA Hankinson, SE De Vivo, I Guillemette, C Ishibe, N Hunter, DJ Byrne, C AF Haiman, CA Hankinson, SE De Vivo, I Guillemette, C Ishibe, N Hunter, DJ Byrne, C TI Polymorphisms in steroid hormone pathway genes and mammographic density SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; cancer susceptibility; mammographic density; molecular epidemiology; polymorphism ID BREAST-CANCER RISK; TETRANUCLEOTIDE REPEAT POLYMORPHISM; GROWTH-FACTOR-I; CYTOCHROME-P450IA1 GENE; QUANTITATIVE-ANALYSIS; POSTMENOPAUSAL WOMEN; LUNG-CANCER; ASSOCIATION; REGION; REPLACEMENT AB Mammographic density has been linked with exposure to endogenous and exogenous steroid hormones, and increased breast cancer risk. Variation in breast density may be due, in part, to polymorphisms in steroid hormone biosynthesis, metabolism and signaling genes. We conducted cross-sectional analyses within the Nurses' Health Study (n = 538), to investigate variation in mammographic breast density, by 10 polymorphisms in eight candidate genes (CYP17, CYP19, CYP1A1, CYP1B1, COMT, UGT1A1, AR, and AIB1). Breast density was assessed using a computer-assisted technique. We evaluated whether associations between variant alleles of these genes and breast density differed by menopause and postmenopausal hormone (PMH) use. Polymorphisms in CYP17, CYP19, CYP1B1, COMT, CYP1A1, or AR were not associated consistently with breast density among premenopausal or postmenopausal women. Premenopausal women with the 7/7 UGT1A1 genotype had lower breast density (difference compared to the 6/6 genotype of: 16.5% density; p = 0 04). In contrast, postmenopausal women with the 7/7 UGT1A1 genotype had greater breast density compared to those with the 6/6 genotype (+6.2% density; p = 0 05); this association was strongest among current PMH users (+13.0% density; p = 0 03). In analyses limited to postmenopausal women, breast density was also greater among women carrying short AIB1 alleles (less than or equal to26 glutamine repeats; +4.1% density; p = 0 04). Most of the variants in the candidate breast cancer genes evaluated in this study are not strong predictors of breast density. However, our findings of differences in associations for UGT1A1 and AIB1 genotypes with breast density by menopausal status needs additional corroboration. C1 Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Laval, Fac Pharm, CHUL, Oncol & Mol Endocrinol Res Ctr,CHUQ, Quebec City, PQ, Canada. Natl Canc Inst, Genet Epidemiol Branch, Rockville, MD USA. USC, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA. RP Byrne, C (reprint author), Harvard Univ, Sch Med, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. RI Guillemette, Chantal/J-6463-2012; Byrne, Celia/K-2964-2015; OI Byrne, Celia/0000-0001-8289-4252; Guillemette, Chantal/0000-0002-1113-1212 FU NCEH CDC HHS [EH00002]; NCI NIH HHS [CA49449, CA65725, CA75016, CA80111, CA87969] NR 35 TC 69 Z9 72 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 JAN PY 2003 VL 77 IS 1 BP 27 EP 36 DI 10.1023/A:1021112121782 PG 10 WC Oncology SC Oncology GA 617BX UT WOS:000179341300004 PM 12602902 ER PT J AU Holzer, RG MacDougall, C Cortright, G Atwood, K Green, JE Jorcyk, CL AF Holzer, RG MacDougall, C Cortright, G Atwood, K Green, JE Jorcyk, CL TI Development and characterization of a progressive series of mammary adenocarcinoma cell lines derived from the C3(1)/SV40 Large T-antigen transgenic mouse model SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE adenocarcinoma; C3(1)/Tag; cell lines; mammary; mouse; tumor progression ID HUMAN-BREAST-CANCER; ESTROGEN-RECEPTOR-ALPHA; LARGE-TUMOR-ANTIGEN; MICE; EXPRESSION; PROTEIN; GROWTH; BETA; PROSTATE; IODIDE AB We have developed four new mammary adenocarcinoma cell lines from the C3(1)/SV40 Large T-antigen (Tag) transgenic mouse model: M28(N2) and M27(H4) (weakly tumorigenic), M6 (carcinoma), and M6(C) (metastatic). The C3( 1) promoter directs Tag expression to the mammary epithelium and 100% of female C3(1)/Tag transgenic mice develop mammary adenocarcinoma in a predictable and progressive manner. The cell lines we developed from this model are demonstrated to be of epithelial origin and display growth rates, both in vitro and following subcutaneous inoculation into nude mice, that are consistent with their representative stage of tumor progression. The more tumorigenic cell lines, M6 and M6C, both express the sodium/iodide symporter, a mammary carcinoma cell marker with potential therapeutic and diagnostic applications. All of the cell lines express estrogen receptor (ER) alpha and ER beta mRNA, and Western blot analysis demonstrates that the ER alpha protein is down-regulated in the M6 and M6C cell lines. M28N2 cells also express progesterone receptor (PgR), which is very unusual in a mouse mammary carcinoma cell line. In addition, all of the cell lines display growth inhibition when plated in media supplemented with charcoal-stripped fetal calf serum (CS FBS). When CS FBS is supplemented with beta estradiol or the progestin MPA, no significant difference in growth rates is observed relative to growth in CS FBS. The development and characterization of a progressive series of new mammary carcinoma cell lines will aid in the study of mammary carcinoma progression both in vitro and in vivo. C1 Boise State Univ, Dept Biol, Boise, ID 83725 USA. Natl Canc Inst, Lab Cell Regulat & Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD USA. RP Jorcyk, CL (reprint author), Boise State Univ, Dept Biol, Sci Nursing Bldg,Room 227,1910 Univ Dr, Boise, ID 83725 USA. NR 39 TC 20 Z9 20 U1 0 U2 5 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 JAN PY 2003 VL 77 IS 1 BP 65 EP 76 DI 10.1023/A:1021175931177 PG 12 WC Oncology SC Oncology GA 617BX UT WOS:000179341300007 PM 12602905 ER PT J AU Syrjakoski, K Hyytinen, ER Kuukasjarvi, T Auvinen, A Kallioniemi, OP Kainu, T Koivisto, PA AF Syrjakoski, K Hyytinen, ER Kuukasjarvi, T Auvinen, A Kallioniemi, OP Kainu, T Koivisto, PA TI Androgen receptor gene alterations in Finnish male breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE androgen receptor; CAG repeat; male breast cancer; mutation; polymorphism ID CAG REPEAT LENGTH; FAMILY HISTORY; MUTATIONS; BRCA2; POLYMORPHISM; HYPOSPADIAS; POPULATION; AGE AB Mutations in the androgen receptor (AR) gene have been suggested to predispose to male breast cancer (MBC). Studies on MBC patients have not been based on the mutation screening of the entire coding region of the AR and the number of subjects has been small. Therefore, some AR gene alterations may have remained undetected. In the present study, we have comprehensively screened the entire coding region of the AR gene for mutations and also studied the role of AR CAG and GGC repeat lengths as risk factors for MBC in a cohort of 32 Finnish MBC patients. To estimate the possible involvement of the prostate cancer predisposing AR Arg726Leu germ-line mutation in MBC, this mutation was tested in 117 MBC patients. No germ-line mutations were found and the CAG and GGC repeat lengths were similar among MBC cases as among Scandinavian population. Our data indicate that the AR gene does not substantially contribute to MBC predisposition. C1 Tampere Univ Hosp, Dept Clin Genet, FIN-33521 Tampere, Finland. Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Pathol, FIN-33521 Tampere, Finland. Univ Tampere, Tampere Sch Publ Hlth, FIN-33101 Tampere, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Koivisto, PA (reprint author), Tampere Univ Hosp, Dept Clin Genet, POB 2000, FIN-33521 Tampere, Finland. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Auvinen, Anssi/0000-0003-1125-4818 NR 27 TC 27 Z9 28 U1 0 U2 0 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 JAN PY 2003 VL 77 IS 2 BP 167 EP 170 DI 10.1023/A:1021369508561 PG 4 WC Oncology SC Oncology GA 622FW UT WOS:000179637000008 PM 12602915 ER PT J AU Bleesing, JJH Janik, JE Fleisher, TA AF Bleesing, JJH Janik, JE Fleisher, TA TI Common expression of an unusual CD45 isoform on T cells from patients with large granular lymphocyte leukaemia and autoimmune lymphoproliferative syndrome SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE T-LGL leukaemia; autoimmune lympho-proliferative syndrome; CD45 isoforms; glycosylation; apoptosis ID APOPTOSIS; LEUKEMIA; MEMORY; B220 AB Patients with T-cell large granular lymphocyte (T-LGL) leukaemia and autoimmune lymphoproliferative syndrome (ALPS) share many features, including autoimmunity and an expansion of (cytotoxic) T cells, which in ALPS patients express an unusual (B220) isoform of CD45, corresponding to an altered O-glycosylation profile. Here we showed that T-LGL leukaemia cells also expressed this B220 isoform. We hypothesize that B220(+) T cells constitute proliferating T cells that have become competent to undergo apoptosis, but that constitutive (ALPS) or functional (T-LGL) defects prevent this process. Altered O-glycosylation of the extracellular domains of CD45 may have consequences for this tyrosine phosphatase as a regulator of cell proliferation and survival. C1 NCI, Serv Immunol, Dept Lab Med, Ctr Clin,NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bleesing, JJH (reprint author), Arkansas Childrens Hosp, Res Inst, 1120 Marshall St, Little Rock, AR 72202 USA. NR 12 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2003 VL 120 IS 1 BP 93 EP 96 DI 10.1046/j.1365-2141.2003.04034.x PG 4 WC Hematology SC Hematology GA 627RJ UT WOS:000179948000015 PM 12492582 ER PT J AU Cushman, M Costantino, JP Bovill, EG Wickerham, DL Buckley, L Roberts, JD Krag, DN AF Cushman, M Costantino, JP Bovill, EG Wickerham, DL Buckley, L Roberts, JD Krag, DN TI Effect of tamoxifen on venous thrombosis risk factors in women without cancer: the Breast Cancer Prevention Trial SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE tamoxifen; venous thromboembolism; blood coagulation; risk factor; breast cancer ID HORMONE-REPLACEMENT THERAPY; ACTIVATED PROTEIN-C; HEALTHY POSTMENOPAUSAL WOMEN; DEEP-VEIN THROMBOSIS; FACTOR-V-LEIDEN; ORAL-CONTRACEPTIVES; ACQUIRED-RESISTANCE; ANTITHROMBIN-III; S DEFICIENCY; COAGULATION AB Tamoxifen reduces breast cancer incidence among healthy women, but is associated with an increased risk of venous thrombosis. We studied the 6 month effects of tamoxifen on venous thrombosis risk factors in women without cancer. One hundred and eleven women at one centre who were participants in a multicentre breast cancer prevention trial were randomized, in double-blind fashion, to receive 20 mg/d of tamoxifen or placebo. The activated protein C (APC) ratio and concentrations of antithrombin, protein C antigen, and total protein S were measured at baseline and 6 months of treatment. None of the factors changed over 6 months in placebo-treated women. Among tamoxifen-treated women, antithrombin and protein S, but not protein C or APC ratio were reduced. Sequential antithrombin concentrations with tamoxifen were 114% and 104% (P = 0.001 compared with placebo). Sequential protein S concentrations with tamoxifen were 18.42 and 17.30 mug/ml (P = 0.02 compared with placebo). Reductions in antithrombin and protein S were greater in postmenopausal women, but did not differ by other risk factors for venous thrombosis, such as body mass index. Reductions of antithrombin and protein S, but not protein C or APC resistance, might relate to the increased risk of venous thrombosis associated with tamoxifen treatment. C1 Univ Vermont, Dept Med, Colchester, VT 05446 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. Allegheny Gen Hosp, Dept Surg Oncol, NSABP, Pittsburgh, PA 15212 USA. Virginia Commonwealth Univ, Dept Med, Richmond, VA 23284 USA. Virginia Commonwealth Univ, Dept Med & Pediat, Richmond, VA 23284 USA. Univ Vermont, Dept Surg, Burlington, VT 05405 USA. RP Cushman, M (reprint author), Univ Vermont, Dept Med, 208 S Pk Dr,Suite 2, Colchester, VT 05446 USA. FU NCI NIH HHS [U10-CA-699974, U10-CA-7377]; NHLBI NIH HHS [HL03618] NR 55 TC 42 Z9 45 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2003 VL 120 IS 1 BP 109 EP 116 DI 10.1046/j.1365-2141.2003.03976.x PG 8 WC Hematology SC Hematology GA 627RJ UT WOS:000179948000018 PM 12492585 ER PT J AU Tsilou, ET Thompson, D Lindblad, AS Reed, GF Rubin, B Gahl, W Thoene, J Del Monte, M Schneider, JA Granet, DB Kaiser-Kupfer, MI AF Tsilou, ET Thompson, D Lindblad, AS Reed, GF Rubin, B Gahl, W Thoene, J Del Monte, M Schneider, JA Granet, DB Kaiser-Kupfer, MI TI A multicentre randomised double masked clinical trial of a new formulation of topical cysteamine for the treatment of corneal cystine crystals in cystinosis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NEPHROPATHIC CYSTINOSIS; THERAPY; CHILDREN AB Aim: To evaluate the safety and efficacy of a new topical cysteamine formulation, stable at room temperature, for the treatment of corneal cystine crystals in cystinosis. Methods: 20 study subjects were enrolled in the safety study and 16 in the efficacy study. Both studies were randomised and double blind. The primary outcome for the safety study was the occurrence of predefined serious adverse reactions over 6 months and for the efficacy study the reduction of corneal cystine crystal score (CCCS) by 1.00 or more units on photographs graded by a reading centre using a standardised protocol. Results: No study subject developed any serious adverse reactions. In the efficacy study, 47% of eyes receiving the standard formulation experienced a reduction in the CCCS of greater than or equal to1.00 after 1 year, while 7% of eyes on the new formulation experienced such a decrease (p=0.04). Conclusion: Although no serious adverse reactions were observed with either formulation, the new formulation was not as effective as the standard formulation. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Hayward Genet Ctr, New Orleans, LA 70118 USA. Univ Michigan, Sch Med, Dept Pediat Ophthalmol, Ann Arbor, MI USA. Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Dept Ophthalmol, La Jolla, CA 92093 USA. RP Tsilou, ET (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 10 Ctr Dr,MSC-1860,Bldg 10,Room 10N226, Bethesda, MD 20892 USA. FU NCRR NIH HHS [M01 RR000827, M01 RR00827]; NEI NIH HHS [N01-EY-6-2112] NR 15 TC 16 Z9 18 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JAN PY 2003 VL 87 IS 1 BP 28 EP 31 DI 10.1136/bjo.87.1.28 PG 4 WC Ophthalmology SC Ophthalmology GA 631RN UT WOS:000180180700009 PM 12488257 ER PT J AU Blair, RJR AF Blair, RJR TI Neurobiological basis of psychopathy SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID ANTISOCIAL-BEHAVIOR; FACIAL EXPRESSIONS; PREFRONTAL CORTEX; VIOLENT OFFENDERS; DYSFUNCTION; DEFICITS; SADNESS; DAMAGE C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Program, 15K North Dr, Bethesda, MD 20892 USA. NR 22 TC 187 Z9 191 U1 8 U2 35 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JAN PY 2003 VL 182 BP 5 EP 7 DI 10.1192/bjp.182.1.5 PG 3 WC Psychiatry SC Psychiatry GA 634CX UT WOS:000180323400003 PM 12509310 ER PT J AU Li, KCP AF Li, KCP TI Angiogenesis imaging in the post-genomic era SO BRITISH JOURNAL OF RADIOLOGY LA English DT Editorial Material C1 NIH, Radiol & Imaging Sci Clin Ctr, Bethesda, MD 20892 USA. RP Li, KCP (reprint author), NIH, Radiol & Imaging Sci Clin Ctr, Bldg 10,1C660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PY 2003 VL 76 SI SI1 BP S1 EP S2 DI 10.1259/bjr/34932557 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 871TN UT WOS:000225156600001 PM 15456708 ER PT J AU Chesebro, B AF Chesebro, B TI Introduction to the transmissible spongiform encephalopathies or prion diseases SO BRITISH MEDICAL BULLETIN LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; GERSTMANN-STRAUSSLER SYNDROME; PROTEASE-RESISTANT PRP; CENTRAL-NERVOUS-SYSTEM; SINGLE AMINO-ACID; TRANSGENIC MICE; SCRAPIE INFECTIVITY; MINK ENCEPHALOPATHY; INCUBATION-TIME; VIRUS-LIKE AB Sheep scrapie has been known for at least 200 years and was described as a transmissible disease over 100 years ago. Since then, three groups of transmissible spongiform encephalopathies or TSE diseases have been identified in humans including familial, infectious and sporadic types. The discovery of the prion protein (PrP) in the 1980s greatly accelerated knowledge of the biology and pathogenesis of TSE diseases as this protein was found to play a critical role in disease susceptibility and the TSE species-barrier and may also be a component of the infectious agent itself. Nevertheless, the nature of the TSE agents remains an enigma. Proof of the protein-only hypothesis may require generation of biologically active transmissible agent in a cell-free environment where a virus cannot replicate. Conversely, proof of a viral aetiology will require identification and isolation of a candidate virus. Further understanding of the structure of the disease-associated protease-resistant PrP should help elucidate the mechanism of PrP conversion from the normal to the abnormal form. Such information should open up new approaches to both diagnosis and therapy. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 100 TC 105 Z9 108 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-1420 EI 1471-8391 J9 BRIT MED BULL JI Br. Med. Bull. PY 2003 VL 66 BP 1 EP 20 DI 10.1093/bmb/66.1.1 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 724KN UT WOS:000185486900001 PM 14522845 ER PT J AU Caughey, B AF Caughey, B TI Prion protein conversions: insight into mechanisms, TSE transmission barriers and strains SO BRITISH MEDICAL BULLETIN LA English DT Article ID CHRONIC WASTING DISEASE; INTERMOLECULAR DISULFIDE BONDS; CELL-FREE FORMATION; CONGO RED; RESISTANT STATE; SPONGIFORM ENCEPHALOPATHIES; NEUROBLASTOMA-CELLS; PRP ACCUMULATION; SPECIES BARRIERS; CULTURED-CELLS AB Conversion of PrPC to aberrant forms such as PrPSc appears to be critical in the transmission and pathogenesis of transmissible spongiform encephalopathies (TSEs) or prion diseases. In vitro studies have shown that TSE-associated, protease-resistant forms of PrP can cause PrPC to convert to forms that are similarly protease-resistant under a wide variety of conditions. These observations have provided evidence that pathological forms of PrP have at least limited capacity to propagate themselves, which is necessary for them to be infectious. PrP conversion reactions have proven to be highly specific and appear to account, at least in part, for TSE species barriers and the propagation of strains. Such in vitro conversion systems have yielded insights into the molecular mechanisms of TSE disease and are being exploited as screens for anti-TSE drugs and as bases for diagnostic tests. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 64 TC 47 Z9 48 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-1420 EI 1471-8391 J9 BRIT MED BULL JI Br. Med. Bull. PY 2003 VL 66 BP 109 EP 120 DI 10.1093/bmb/66.1.109 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 724KN UT WOS:000185486900009 PM 14522853 ER PT J AU Hariri, AR Weinberger, DR AF Hariri, AR Weinberger, DR TI Imaging genomics SO BRITISH MEDICAL BULLETIN LA English DT Article ID SEROTONIN TRANSPORTER GENE; ANXIETY-RELATED TRAITS; E TYPE-4 ALLELE; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; WORKING-MEMORY; PERSONALITY-TRAITS; BRAIN ACTIVATION; ASSOCIATION; POLYMORPHISM AB The recent completion of a working draft of the human genome sequence promises to provide unprecedented opportunities to explore the genetic basis of individual differences in complex behaviours and vulnerability to neuropsychiatric illness. Functional neuroimaging, because of its unique ability to assay information processing at the level of brain within individuals, provides a powerful approach to such functional genomics. Recent fMRI studies have established important physiological links between functional genetic polymorphisms and robust differences in information processing within distinct brain regions and circuits that have been linked to the manifestation of various disease states such as Alzheimer's disease, schizophrenia and anxiety disorders. Importantly, all of these biological relationships have been revealed in relatively small samples of healthy volunteers and in the absence of observable differences at the level of behaviour, underscoring the power of a direct assay of brain physiology like fMRI in exploring the functional impact of genetic variation. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, 10 Ctr Dr,Room 4S235, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 43 TC 210 Z9 219 U1 2 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-1420 EI 1471-8391 J9 BRIT MED BULL JI Br. Med. Bull. PY 2003 VL 65 BP 259 EP 270 DI 10.1093/bmb/65.1.259 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 664UN UT WOS:000182080300019 PM 12697630 ER PT J AU Robbins, JB Schneerson, R Gotschlich, EC Mohammed, I Nasidi, A Chippaux, JP Bernardino, L Maiga, MA AF Robbins, JB Schneerson, R Gotschlich, EC Mohammed, I Nasidi, A Chippaux, JP Bernardino, L Maiga, MA TI Meningococcal meningitis in sub-Saharan Africa: the case for mass and routine vaccination with available polysaccharide vaccines SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article DE meningitis; meningoccal/epidemiology/prevention and control; meningococcal vaccines/pharmacology; endemic diseases/prevention and control; mass immunization; immunization programs; Africa South of the Sahara ID GROUP-A; NEISSERIA-MENINGITIDIS; WEST-AFRICA; GROUP-C; COST-EFFECTIVENESS; EPIDEMIC; DISEASE; CHILDREN; IMMUNIZATION; INFANTS AB Endemic and epidemic group A meningococcal meningitis remains a major cause of morbidity and mortality in sub-Saharan Africa, despite the availability of the safe and inexpensive group A meningococcal polysaccharide vaccine, which is protective at all ages when administered as directed. Despite optimal therapy, meningococcal meningitis has a 10% fatality rate and at least 15% central nervous system damage. WHO's policy of epidemic containment prevents, at best, about 50% of cases and ignores endemic meningitis, which is estimated at 50,000 cases per year. The effectiveness of group A, C, W135, and Y capsular polysaccharides is the basis for recommending universal vaccination with group A meningococcal polysaccharide twice in infancy, followed by the four-valent vaccine in children aged two and six years. This could eliminate epidemic and endemic disease, prepare for the use of conjugates when they become available, and probably could have prevented the recent epidemics of groups A and W135 meningitis in Burkina Faso. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, New York, NY 10021 USA. Natl Programme Immunizat, Abuja, Nigeria. Fed Minist Hlth, Special Projects, Abuja, Nigeria. Inst Rech Dev, Anciennement Orstom, Dakar, Senegal. Hosp Pediat Luanda, Luanda, Angola. W Africian Hlth Org, Bobo Dioulasso, Burkina Faso. RP Robbins, JB (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 47 TC 27 Z9 29 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2003 VL 81 IS 10 BP 745 EP 750 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 741AF UT WOS:000186435100009 PM 14758435 ER PT J AU Young, MF AF Young, MF TI Bone matrix proteins: More than markers SO CALCIFIED TISSUE INTERNATIONAL LA English DT Editorial Material ID HEPARAN-SULFATE PROTEOGLYCANS; EXTRACELLULAR-MATRIX; OSTEOBLAST PHENOTYPE; I COLLAGEN; EXPRESSION; LOCALIZATION; GROWTH C1 Natl Inst Craniofacial & Skeletal Dis Branch, Mol Biol Bones & Teeth Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Young, MF (reprint author), Natl Inst Craniofacial & Skeletal Dis Branch, Mol Biol Bones & Teeth Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. NR 26 TC 10 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JAN PY 2003 VL 72 IS 1 BP 2 EP 4 DI 10.1007/s00223-002-1017-6 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 638BJ UT WOS:000180548900001 PM 12710463 ER PT J AU McGlynn, KA Devesa, SS Sigurdson, AJ Brown, LM Tsao, L Tarone, RE AF McGlynn, KA Devesa, SS Sigurdson, AJ Brown, LM Tsao, L Tarone, RE TI Trends in the incidence of testicular germ cell tumors in the United States SO CANCER LA English DT Article DE testicular germ cell tumor; seminoma; nonseminoma; SEER program; incidence; epidemiology ID BIRTH COHORT; TESTIS CANCER; TIME TRENDS; RISK; DENMARK; RATES; CRYPTORCHIDISM; AUSTRALIA; INCREASE; VICTORIA AB BACKGROUND. Recent reports have suggested that the increasing rates of testicular germ cell tumors in some populations have begun to plateau. This study was conducted to examine whether rates among white men in the United States have begun to stabilize and whether rates among black men in the United States have remained low. METHODS. Testicular germ cell tumor incidence data from in the Surveillance, Epidemiology, and End Results Program were analyzed for the years 1973-1998. Trends were examined separately for seminoma and nonseminoma. Using age-period-cohort analyses with 5-year age intervals and 5-year calendar-period intervals, changes in the slope of the trends in birth-cohort and calendar-period effects were examined. RESULTS. Among white men, rates of seminoma continued to increase, but the rate of increase steadily declined throughout the 26-year time span. Nonseminoma rates among whites increased more slowly during the first three time intervals, then plateaued in the final interval. Rates of both seminoma and nonseminoma in black men fluctuated throughout the first three time intervals. In the final interval, the rates of seminoma increased almost 100%, whereas the rates of nonseminoma increased more modestly. Age-period-cohort modeling of the incidence data in white men found that, whereas the dominant effect was that of birth cohort, there also was a period effect. CONCLUSIONS. Among white men in the United States, the incidence of testicular germ cell tumors varied by histology, with a continuing increase in risk only for seminoma. Among black men in the United States, the surprising increases seen between 1988 and 1998 were likely to be a calendar-period effect. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7060, Bethesda, MD 20892 USA. NR 34 TC 186 Z9 192 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2003 VL 97 IS 1 BP 63 EP 70 DI 10.1002/cncr.11054 PG 8 WC Oncology SC Oncology GA 634BE UT WOS:000180319500008 PM 12491506 ER PT J AU Shavers, VL Harlan, LC Stevens, JL AF Shavers, VL Harlan, LC Stevens, JL TI Racial/ethnic variation in clinical presentation, treatment, and survival among breast cancer patients under age 35 SO CANCER LA English DT Article DE breast cancer; young women; race; ethnicity; treatment; clinical characteristics; survival; health disparities ID RADIATION-THERAPY; YOUNG-WOMEN; OLDER WOMEN; BLACK-WOMEN; IN-SITU; CARCINOMA; PROGNOSIS; FATALISM; MASTECTOMY; WHITE AB BACKGROUND. The age specific breast cancer incidence rate for African-American women under age 35 is more than twice the rate for white women of similar age, and the mortality rate is more than three times higher. To determine factors that may explain racial/ethnic variation in outcomes among young women diagnosed with breast cancer, the authors examined the clinical presentation, treatment, and survival of African-American, Hispanic, and white women under age 35 years. METHODS. Surveillance, Epidemiology, and End Results (SEER) Program data for 1990-1998 and SEER Patterns of Care data for 1990, 1991, and 1995 were used for this analysis. Multivariate logistic regression analyses were performed to examine factors associated with the receipt of selected breast cancer treatments. Kaplan-Meier survival analyses and Cox proportional hazards regression analyses were used to examine 5-year overall survival and disease-specific survival. RESULTS. The authors found racial/ethnic variation in clinical presentation, treatment, and survival. Both African-American and Hispanic women presented with higher disease stage and a higher prevalence of adverse prognostic indicators compared to white women. African-American and Hispanic women received cancer-directed surgery and radiation less frequently after undergoing breast-conserving surgery. Racial/ethnic differences in clinical presentation and treatment were associated with poorer overall survival in unadjusted analyses. African-American and Hispanic women also had poorer overall survival after controlling for clinical and demographic characteristics and type of treatment. CONCLUSIONS. Future research studies should further examine the factors that influence racial/ethnic differences in incidence, clinical presentation, and treatment differentials among young women diagnosed with breast cancer. A better understanding of these factors will facilitate the development of strategies to help eliminate this health disparity. C1 NCI, Appl Res Program, Hlth Serv & Econ Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Informat Management Syst, Silver Spring, MD USA. RP Shavers, VL (reprint author), NCI, Appl Res Program, Hlth Serv & Econ Branch, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC-7344,EPN Room 4005, Bethesda, MD 20892 USA. NR 39 TC 187 Z9 189 U1 0 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2003 VL 97 IS 1 BP 134 EP 147 DI 10.1002/cncr.11051 PG 14 WC Oncology SC Oncology GA 634BE UT WOS:000180319500017 PM 12491515 ER PT J AU Montaner, S Sodhi, A Molinolo, A Bugge, TH Sawai, ET He, YS Li, Y Ray, PE Gutkind, JS AF Montaner, S Sodhi, A Molinolo, A Bugge, TH Sawai, ET He, YS Li, Y Ray, PE Gutkind, JS TI Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes SO CANCER CELL LA English DT Article ID PROTEIN-COUPLED RECEPTOR; FLICE-INHIBITORY PROTEIN; A AVIAN-LEUKOSIS; NF-KAPPA-B; RETROVIRAL VECTORS; TRANSGENIC MICE; CELL-DEATH; HERPESVIRUS; VIRUS; EXPRESSION AB The Kaposi's sarcoma herpesvirus (KSHV) has been identified as the etiologic agent of Kaposi's sarcoma (KS), but initial events leading to KS development remain unclear. Characterization of the KSHV genome reveals the presence of numerous potential oncogenes. To address their contribution to the initiation of the endothelial cell-derived KS tumor, we developed a novel transgenic mouse that enabled endothelial cell-specific infection in vivo using virus expressing candidate KSHV oncogenes. Here we show that transduction of one gene, vGPCR, was sufficient to induce angioproliferative tumors that strikingly resembled human KS. Endothelial cells expressing vGPCR were further able to promote tumor formation by cells expressing KSHV latent genes, suggestive of a cooperative role among viral genes in the promotion of Kaposi's sarcomagenesis. C1 Univ Calif Davis, Dept Med Pathol, Davis, CA 95616 USA. Univ Calif Davis, Compartat Pathol Grad Grp, Davis, CA 95616 USA. Childrens Natl Med Ctr, Res Ctr Mol Physiol, Washington, DC 20010 USA. George Washington Univ, Washington, DC 20010 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Natl Inst Dent & Craniofacial Res, Cell Growth Regulat Sect, Oral & Pharyngeal Canc Branch,NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch,NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Cell Growth Regulat Sect, Oral & Pharyngeal Canc Branch,NIH, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; OI Li, Yi/0000-0002-9976-518X FU NHLBI NIH HHS [2R0-1 HL 55605]; NIAID NIH HHS [R0-1 AI46145-01A2]; NIDDK NIH HHS [2R0-1 DK 49414] NR 57 TC 233 Z9 246 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2003 VL 3 IS 1 BP 23 EP 36 DI 10.1016/S1535610802002374 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 639LQ UT WOS:000180630600006 PM 12559173 ER PT J AU Hu, N Li, WJ Su, H Wang, CY Goldstein, AM Albert, PS Emmert-Buck, MR Kong, LH Roth, MJ Dawsey, SM He, LJ Cao, SF Ding, T Giffen, C Taylor, PR AF Hu, N Li, WJ Su, H Wang, CY Goldstein, AM Albert, PS Emmert-Buck, MR Kong, LH Roth, MJ Dawsey, SM He, LJ Cao, SF Ding, T Giffen, C Taylor, PR TI Common genetic variants of TP53 and BRCA2 in esophageal cancer patients and healthy individuals from low and high risk areas of northern China SO CANCER DETECTION AND PREVENTION LA English DT Article DE esophageal cancers; TP53; BRCA2; polymorphisms; cancer risk; China ID SQUAMOUS-CELL CARCINOMA; P53 CODON-72 POLYMORPHISM; LUNG-CANCER; BREAST-CANCER; ALLELIC LOSS; SUSCEPTIBILITY; POPULATION; IDENTIFICATION; ASSOCIATION; MUTATION AB TP53 and BRCA2 are frequently mutated in cancer and polymorphisms of these genes may modify cancer risk. We used SSCP and DNA sequencing to assess and compare frequencies of R72P (TP53) and 5UTR203G>A, N372H, and K1132K (BRCA2) polymorphisms in healthy Chinese subjects at varying risk for esophageal squamous cell carcinoma (ESCC) and in ESCC patients. Suggestive overall differences in the distributions of genotypes by risk groups were seen for all genotypes except K1132K. Differences in R72P and N372H were most likely a reflection of lack of Hardy-Weinberg equilibrium (HWE), however, the difference in 203G>A was due to low prevalence of GG in ESCC patients (0.22 versus 0.36 in high risk group (P = 0.047), and 0.22 versus 0.40 in low risk group (P = 0.010)), consistent with a disease association. These data suggest that the 203G>A polymorphism in BRCA2 may be associated with risk of ESCC. Published by Elsevier Science Ltd. on behalf of International Society for Preventive Oncology. C1 NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Shanxi Canc Hosp, Taiyuan 030013, Shanxi, Peoples R China. Natl Vaccine & Serum Inst, Beijing 100024, Peoples R China. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Yangcheng Canc Hosp, Shanxi 048100, Peoples R China. Informat Management Serv Inc, Silver Spring, MD 20904 USA. RP Taylor, PR (reprint author), NCI, Canc Prevent Studies Branch, Ctr Canc Res, 6116 Execut Blvd,Room 705, Bethesda, MD 20892 USA. NR 30 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2003 VL 27 IS 2 BP 132 EP 138 DI 10.1016/S0361-090X(03)00031-X PG 7 WC Oncology SC Oncology GA 668HF UT WOS:000182283700008 PM 12670525 ER PT J AU Molteni, M Rossetti, C Scrofani, S Bonara, P Scorza, R Kohn, LD AF Molteni, M Rossetti, C Scrofani, S Bonara, P Scorza, R Kohn, LD TI Regulatory CD8(+) T cells control thyrotropin receptor- specific CD4(+) clones in healthy subjects SO CANCER DETECTION AND PREVENTION LA English DT Article DE CD8(+) T lymphocytes; CD4(+) T lymphocytes; TSHR; suppression; anergy ID IN-VITRO; AUTOIMMUNE ENCEPHALOMYELITIS; GRAVES-DISEASE; SUPPRESSION; TOLERANCE; INHIBIT AB One of the mechanisms ensuring immunological unresponsiveness or tolerance depends on the action of CD8(+) lymphocytes. In this paper, we report that, in healthy subjects, a subset of CD8(+)CD28(-) T cells suppresses the specific response to TSH receptor (TSHR) of CD4(+) clones. Suppression was highly specific, required cell-cell interaction, and was not mediated by cytotoxicity. Co-incubation of CD8(+) and CD4(+) clones, followed by the removal of the CD8(+) cells from the cultures before testing CD4(+) responsiveness to TSHR, demonstrated that CD4(+) cells were anergic since they showed low response to the antigen and a significant impairment of IL-2 production. In CD8-mediated anergy induction, the T-cell receptor (TCR) on both CD4(+) and CD8(+) cells seems to play a role. Our results indicate that one of the mechanisms ensuring peripheral tolerance involve CD8(+)CD28(-) cells. A disregulation in the control of autoreactive clones by this subset might be important for the onset of autoimmune thyroid diseases. (C) 2003 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Milan, Osped Maggiore, IRCCS, Dept Internal Med, I-20122 Milan, Italy. Univ Insubria, Dept Struct & Funct Biol, I-21100 Varese, Italy. NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD USA. Ohio Univ, Coll Med, Edison Biotechnol Inst, Athens, OH 45701 USA. RP Molteni, M (reprint author), Univ Milan, Osped Maggiore, IRCCS, Dept Internal Med, Via F Sforza 35, I-20122 Milan, Italy. OI ROSSETTI, CARLO/0000-0002-6806-2975; Molteni, Monica/0000-0002-5990-3971 NR 27 TC 10 Z9 12 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2003 VL 27 IS 3 BP 167 EP 174 DI 10.1016/S0361-090X(03)00023-0 PG 8 WC Oncology SC Oncology GA 691GJ UT WOS:000183597400001 PM 12787722 ER PT J AU Benichou, J Byrne, C Capece, LA Carroll, LE Hurt-Mullen, K Pee, DY Salane, M Schairer, C Gail, MH AF Benichou, J Byrne, C Capece, LA Carroll, LE Hurt-Mullen, K Pee, DY Salane, M Schairer, C Gail, MH TI Secular stability and reliability of measurements of the percentage of dense tissue on mammograms SO CANCER DETECTION AND PREVENTION LA English DT Article DE breast cancer risk projection; breast cancer risk factor; measurement error; assessing mammographic density ID BREAST-CANCER RISK; DENSITIES; VALIDATION; LATERALITY; PATTERNS; COHORT AB Elevated mammographic density is associated with increased risk of breast cancer. We conducted a reliability study on mammographic density assessments to determine their potential usefulness for projecting individual breast cancer risk. We used baseline screening mammograms from 7251 women in the Breast Cancer Detection Demonstration Project (BCDDP). Repeated measurements from the same images were used to assess measurement variability by an experienced evaluator. Intraclass correlations of assessments over time usually exceeded 0.9, indicating usefulness for prospective applications. Data also indicated it may be reasonable to include cases identified in the first year of screening together with other cases in developing a risk model. Older ages and increased weight were associated with decreased mammographic density. The density of the right breast slightly exceeded that of the left. Among women who developed breast cancer, the baseline mammographic density of the ipsilateral (diseased) breast was 0.53 (95% confidence interval (CI) 0.20-0.86) percentage units higher than in the contralateral breast. (C) 2003 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Rouen, Sch Med, Dept Biostat, F-76031 Rouen, France. Rouen Univ Hosp, F-76031 Rouen, France. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Informat Management Serv Inc, Rockville, MD 20852 USA. Westat Corp, Rockville, MD 20892 USA. MSW Consulting, Bloomfield Hills, MI 48304 USA. RP Gail, MH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Byrne, Celia/K-2964-2015 OI Byrne, Celia/0000-0001-8289-4252 NR 22 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2003 VL 27 IS 4 BP 266 EP 274 DI 10.1016/S0361-090X(03)0092-8 PG 9 WC Oncology SC Oncology GA 713HA UT WOS:000184850400005 PM 12893074 ER PT J AU Rutten, LJF Iannotti, RJ AF Rutten, LJF Iannotti, RJ TI Health beliefs, salience of breast cancer family history, and involvement with breast cancer issues: adherence to annual mammography screening recommendations SO CANCER DETECTION AND PREVENTION LA English DT Article DE patient adherence; screening adherence; reminder systems; health belief model ID OLDER WOMEN; BARRIERS; BEHAVIORS; MODEL; PREDICTORS; GUIDELINES; RISK AB Involvement in breast cancer (BC) issues, and the degree to which family history of BC influences perceived risk (salience of family history), have been proposed as additions to the Health Belief Model as applied to mammography adherence. Barriers and benefits of mammography, perceived susceptibility, severity, cues to action, salience of family history, and issue involvement with respect to BC were examined in adherent (n = 97) and non-adherent (n = 213) women. Adherent women with positive family histories reported greater benefits of mammography, greater response to cues to action, and higher salience of family history than women with negative family histories. Non-adherent women with positive family histories reported fewer benefits of mammography and greater issue involvement, and perceived BC as less severe than those with negative family histories. Benefits (OR = 1.51), susceptibility (OR = 1.41), issue involvement (OR = 1.59), severity (OR = 0.66), and cues to action (OR = 0.75) were significantly associated with adherence. Results have implications for evidence-based interventions. Published by Elsevier Ltd. on behalf of International Society for Preventive Oncology. C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, US Dept HHS, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, US Dept HHS, Bethesda, MD 20892 USA. NICHHD, Div Epidemiol Stat & Prevent Res, US Dept HHS, Bethesda, MD 20892 USA. RP Rutten, LJF (reprint author), NCI, Canc Prevent Fellowship Program, Div Canc Prevent, US Dept HHS, 6130 Execut Blvd,Rm 4051A MSC 7365, Bethesda, MD 20892 USA. NR 46 TC 21 Z9 23 U1 3 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2003 VL 27 IS 5 BP 353 EP 359 DI 10.1016/S0361-090X(03)00133-8 PG 7 WC Oncology SC Oncology GA 741FB UT WOS:000186447100006 ER PT J AU Zeinoun, Z Teugels, E Vermeij, J Neyns, B Birrer, M De Greve, J AF Zeinoun, Z Teugels, E Vermeij, J Neyns, B Birrer, M De Greve, J TI Restoration of an impaired TGF-beta1 autocrine growth-inhibitory circuit results in growth inhibition of ovarian epithelial cancer cells and complete inhibition of their tumorigenicity SO CANCER DETECTION AND PREVENTION LA English DT Article DE TGF-beta1; recombinant adenovirus; ovarian cancer; autocrine growth inhibition ID FACTOR-BETA; TGF-BETA; RECOMBINANT ADENOVIRUSES; SIGNAL-TRANSDUCTION; CARCINOMA; EXPRESSION; VECTOR; GENE; FACTOR-BETA-1; APOPTOSIS AB The disruption of the transforming growth factor betal (TGF-beta1) autocrine growth-suppressive circuit is a major and possibly early event mediating the malignant transformation of normal epithelia. TGF-beta1 is secreted as a latent homodimer-peptide that, upon activation, binds a receptor complex. This in turn activates a signal transduction cascade that results in proliferation inhibition of epithelial cells. The growth-inhibitory pathway can be interrupted at several levels: insufficient secretion and activation of TGF-beta1 ligand, mutational inactivation of the receptors or signal transduction intermediates or at the level of the nuclear effector molecules. We have investigated the effect of restoring the growth-inhibitory autocrine circuit in epithelial cancer cells that have retained sensitivity to growth inhibition by TGF-beta1 but which produce and secrete insufficient amounts of endogenous peptide. These cancer cells were transduced with a recombinant adenovirus containing a TGF-beta1 cDNA driven by a CMV promoter and coding for a constitutively bioactive TGF-beta1 peptide. Restituting the TGF-beta1 autocrine growth-suppressive circuit in these cancer cells had a potent growth-inhibitory effect in vitro. Moreover, in vitro transduced cells lost their tumorigenicity in nude mice. As disruption of TGF-beta's autocrine growth circuit is thought to be an early event in the malignant transformation of several epithelial cancers, early correction of this defect might in the future lead to cancer preventive strategies. (C) 2003 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 Free Univ Brussels, Akad Ziekenhuis, Ctr Oncol, Lab Med & Mol Oncol, B-1090 Brussels, Belgium. NCI, Med Branch, Dept Cell & Canc Biol, NIH, Rockville, MD 20850 USA. RP De Greve, J (reprint author), Free Univ Brussels, Akad Ziekenhuis, Ctr Oncol, Lab Med & Mol Oncol, Laarbeeklaan 101, B-1090 Brussels, Belgium. RI De Greve, Jacques/J-4939-2012 OI De Greve, Jacques/0000-0002-2389-0742 NR 30 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2003 VL 27 IS 5 BP 380 EP 388 DI 10.1016/S0361-090X(03)00123-5 PG 9 WC Oncology SC Oncology GA 741FB UT WOS:000186447100009 PM 14585325 ER PT J AU De Roos, AJ Rothman, N Inskip, PD Linet, MS Shapiro, WR Selker, RG Fine, HA Black, PM Pittman, GS Bell, DA AF De Roos, AJ Rothman, N Inskip, PD Linet, MS Shapiro, WR Selker, RG Fine, HA Black, PM Pittman, GS Bell, DA TI Genetic polymorphisms in GSTM1,-P1,-T1, and CYP2E1 and the risk of adult brain tumors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; OCCUPATIONAL EXPOSURE; EXPRESSION; CANCER; GSTT1; SUSCEPTIBILITY; ASTROCYTOMA; MORTALITY; DELETION; CLONING AB GST and CYP2E1 genes are involved in metabolism of several compounds (e.g., solvents) that may play a role in brain cancer etiology. We evaluated associations between polymorphisms in these genes and adult brain tumor incidence. Cases were 782 patients with brain tumors diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples that had been collected from 1277 subjects (80% of all subjects; 604 controls; 422 gliomas, 17.2 meningiomas, and 79 acoustic neuromas), and genotyping was successfully conducted for GSTM1 null, GSTT1 null, GSTP 1105V, GSTP A114V, CYP2E1 RsaI, and CYP2E1 Ins96. The GSTP1 105 Val/Val genotype was associated with increased glioma incidence [odds ratio (OR), 1.8; 95% confidence limits (CLs), 1.2, 2.7], with the estimated effect following a trend of increasing magnitude by number of variant alleles (Ile/ Ile: OR, 1.0; Ile/Val: OR, 1.3; Val/Val: OR, 2.1). The CYP2E1 RsaI variant was weakly associated with glioma (OR, 1.4; 95% CL, 0.9, 2.4) and acoustic neuroma (OR, 2.3; 95% CL, 1.0, 5.3), with some indication of stronger associations among younger subjects. Estimated effects of the gene variants differed by glioma subtype. There was evidence of supermultiplicativity of the joint effect of GSTP1 I105V and CYP2E1 RsaI variants on both glioma and acoustic neuroma, even following adjustment of estimates toward a common prior distribution using hierarchical regression models. Previously reported associations between the GSTT1 null genotype and overall glioma incidence were not replicated, but an association with meningioma was observed (OR, 1.5; 95% CL, 1.0, 2.3). These findings may provide clues to both genetic and environmental determinants of brain tumors. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. St Josephs Hosp, Phoenix, AZ USA. Western Penn Hosp, Pittsburgh, PA 15224 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP De Roos, AJ (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA. NR 38 TC 62 Z9 66 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 JAN PY 2003 VL 12 IS 1 BP 14 EP 22 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 637WM UT WOS:000180536800004 PM 12540498 ER PT J AU Augustsson, K Michaud, DS Rimm, EB Leitzmann, MF Stampfer, MJ Willett, WC Giovannucci, E AF Augustsson, K Michaud, DS Rimm, EB Leitzmann, MF Stampfer, MJ Willett, WC Giovannucci, E TI A prospective study of intake of fish and marine fatty acids and prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; CELL-GROWTH; RISK; DIET; REPRODUCIBILITY; CONSUMPTION; VALIDITY; INDIANS; RATS AB Experimental studies suggest that marine fatty acids have an antitumor effect on prostate tumor cells. The aim of this study was to investigate whether high consumption of fish and marine fatty acids reduces the risk of prostate cancer in humans. We followed 47,882 men participating in the Health Professionals Follow-up Study. Dietary intake was assessed in 1986, 1990, and 1994, using a validated food frequency questionnaire. During 12 years of follow-up, 2,482 cases of prostate cancer were diagnosed, of which 617 were diagnosed as advanced prostate cancer including 278 metastatic prostate cancers. Eating fish more than three times per week was associated with a reduced risk of prostate cancer, and the strongest association was for metastatic cancer (multivariate relative risk, 0.56; 95% confidence interval, 0.37-0.86, compared with infrequent consumption, i.e., less than twice per month). Intake of marine fatty acids from food showed a similar but weaker association. Each additional daily intake of 0.5 g of marine fatty acid from food was associated with a 24% decreased risk of metastatic cancer. We found that men with high consumption of fish had a lower risk of prostate cancer, especially for metastatic cancer. Marine fatty acids may account for part of the effect, but other factors in fish may also play a role. C1 Karolinska Inst, Dept Med Epidemiol, SE-17177 Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. RP Augustsson, K (reprint author), Karolinska Inst, Dept Med Epidemiol, SE-17177 Stockholm, Sweden. RI Michaud, Dominique/I-5231-2014 FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL35464] NR 19 TC 154 Z9 161 U1 0 U2 7 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 JAN PY 2003 VL 12 IS 1 BP 64 EP 67 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 637WM UT WOS:000180536800012 PM 12540506 ER PT J AU Gottesman, MM Vieira, W Alexander, NS Garfield, S Arora, M Oppenheim, A Kimchi-Sarfaty, C AF Gottesman, MM Vieira, W Alexander, NS Garfield, S Arora, M Oppenheim, A Kimchi-Sarfaty, C TI SV40 in vitro packaging vectors - an effective gene delivery system in intact mice SO CANCER GENE THERAPY LA English DT Meeting Abstract CT 11th International Conference on Gene Therapy of Cancer CY DEC 12-14, 2002 CL SAN DIEGO, CALIFORNIA C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Hadassah Univ Hosp, IL-91010 Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN PY 2003 VL 10 SU 1 MA 65 BP S24 EP S24 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 642VT UT WOS:000180826700063 ER PT J AU Kimchi-Sarfaty, C Garfield, S Alexander, NS Arora, M Oppenheim, A Gottesman, MM AF Kimchi-Sarfaty, C Garfield, S Alexander, NS Arora, M Oppenheim, A Gottesman, MM TI Gene transfer using an SV40 in vitro packaging system SO CANCER GENE THERAPY LA English DT Meeting Abstract CT 11th International Conference on Gene Therapy of Cancer CY DEC 12-14, 2002 CL SAN DIEGO, CALIFORNIA C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Univ Hosp, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN PY 2003 VL 10 SU 1 MA 64 BP S23 EP S23 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 642VT UT WOS:000180826700062 ER PT J AU Liang, SB Hou, JWS Peace, DJ Fowler, DH Medin, JA AF Liang, SB Hou, JWS Peace, DJ Fowler, DH Medin, JA TI Vaccination with retrovirally-transduced dendritic cells introduces cellular and humoral immune responses along with specific protection against prostate antigen-expressing tumors SO CANCER GENE THERAPY LA English DT Meeting Abstract CT 11th International Conference on Gene Therapy of Cancer CY DEC 12-14, 2002 CL SAN DIEGO, CALIFORNIA C1 Ontario Canc Inst, Div Expt Therapeut, Toronto, ON M4X 1K9, Canada. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. Univ Illinois, Dept Med, Hematol Oncol Sect, Chicago, IL USA. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN PY 2003 VL 10 SU 1 MA 92 BP S34 EP S35 PG 2 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 642VT UT WOS:000180826700088 ER PT J AU Berger, A Baker, K Bolle, J Pereira, D AF Berger, A Baker, K Bolle, J Pereira, D TI Establishing a palliative care program in a research center: Evolution of a model SO CANCER INVESTIGATION LA English DT Article C1 NIH, Bethesda, MD 20892 USA. RP Berger, A (reprint author), NIH, Bldg 10,Rm 2N236,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 2 BP 313 EP 320 DI 10.1081/CNV-120019989 PG 8 WC Oncology SC Oncology GA 674YL UT WOS:000182665200015 PM 12743995 ER PT J AU Morse, MA Nair, SK Mosca, PJ Hobeika, AC Clay, TM Deng, YP Boczkowski, D Proia, A Neidzwiecki, D Clavien, PA Hurwitz, HI Schlom, J Gilboa, E Lyerly, HK AF Morse, MA Nair, SK Mosca, PJ Hobeika, AC Clay, TM Deng, YP Boczkowski, D Proia, A Neidzwiecki, D Clavien, PA Hurwitz, HI Schlom, J Gilboa, E Lyerly, HK TI Immunotherapy with autologous, human dendritic cells transfected with carcinoembryonic antigen mRNA SO CANCER INVESTIGATION LA English DT Article DE dendritic cells; immunotherapy; CEA; hepatic metastases ID ACTIVE SPECIFIC IMMUNOTHERAPY; IN-VITRO; TUMOR-CELLS; VACCINATION; PEPTIDE; CANCER; INDUCTION; IMMUNITY; METASTASES; CARCINOMA AB Immunizations with dendritic cells (DC) transfected with RNA encoding tumor antigens induce potent tumor antigen-specific immune responses in vitro and in murine models. We performed a phase I study of patients with advanced carcinoembryonic antigen (CEA)-expressing malignancies followed by a phase II study of patients with resected hepatic metastases of colon cancer to assess safety and feasibility of administering autologous DC loaded with CEA mRNA. The immunizations were well tolerated. Of the 24 evaluable patients in the dose-escalation phase, there was I complete response (by tumor marker), 2 minor responses, 3 with stable disease, and 18 with progressive disease. In the phase II study, 9 of 13 patients have relapsed at a median of 122 days. Evidence of an immunologic response was demonstrated in biopsies of DC injection sites and peripheral blood of selected patients. We conclude that it is feasible and safe to administer mRNA-loaded DC to patients with advanced malignancies. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat, Durham, NC 27710 USA. Eastern Virginia Med Sch, Dept Internal Med, Yorktown, VA USA. Natl Inst Hlth, Bethesda, MD USA. RP Morse, MA (reprint author), Duke Univ, Med Ctr, Dept Med, Box 3233, Durham, NC 27710 USA. RI Lyerly, Herbert/B-6528-2014 OI Lyerly, Herbert/0000-0002-0063-4770 FU NCI NIH HHS [P01-CA78673-01, R01-CA75472-01]; NCRR NIH HHS [M01RR00030] NR 22 TC 101 Z9 108 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 3 BP 341 EP 349 DI 10.1081/CNV-120018224 PG 9 WC Oncology SC Oncology GA 705WF UT WOS:000184418400002 PM 12901279 ER PT J AU Luo, J Isaacs, WB Trent, JM Duggan, DJ AF Luo, J Isaacs, WB Trent, JM Duggan, DJ TI Looking beyond morphology: Cancer gene expression profiling using DNA microarrays SO CANCER INVESTIGATION LA English DT Article DE gene expression profiling; microarray; prostate; diagnosis; cancer classification; outcome prediction ID B-CELL LYMPHOMA; BENIGN PROSTATIC HYPERPLASIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; METHYLACYL-COA RACEMASE; MOLECULAR CLASSIFICATION; CDNA MICROARRAYS; BREAST-CANCER; OLIGONUCLEOTIDE ARRAYS; PREDICT SURVIVAL; CLASS DISCOVERY AB Although molecular testing has been increasingly used in clinical practice, the precise diagnosis and prognosis of most human cancers still heavily rely on descriptive histopathological data. Identification of robust molecular markers associated with distinctive morphological parameters will assist in diagnostic and prognostic assessment. On the other hand, the diversity of morphologically identical/similar cancers can be manifested at multiple levels, most importantly at the level of clinical outcome. In the past several years, DNA microarray technology has been widely used in the context of cancer research, resulting in a deluge of new information that can be used to identify molecular alterations common to all tumors as well as signatory profiles unique to a subcategory of cancers. These new findings will very likely transform the clinical management of cancer patients in the near term. This article reviews recent advances in cancer gene expression-profiling results derived from the application of DNA microarray technology, with an emphasis on studies performed on human prostate cancer specimens. We discuss broad issues relevant to cancer expression profiling and attempt to illustrate the rapid pace of novel discoveries using prostate cancer as examples wherever appropriate. C1 Johns Hopkins Univ, James Buchanan Brady Urol Inst, Baltimore, MD 21218 USA. Translat Genom Res Inst, Phoenix, AZ USA. NHGRI, Bethesda, MD 20892 USA. RP Duggan, DJ (reprint author), Johns Hopkins Univ, James Buchanan Brady Urol Inst, Baltimore, MD 21218 USA. EM dduggan@tgen.org NR 89 TC 32 Z9 34 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 6 BP 937 EP 949 DI 10.1081/CNV-120025096 PG 13 WC Oncology SC Oncology GA 762RJ UT WOS:000187995700013 PM 14735697 ER PT J AU Risinger, JI Maxwell, GL Chandramouli, GVR Jazaeri, A Aprelikova, O Patterson, T Berchuck, A Barrett, JC AF Risinger, JI Maxwell, GL Chandramouli, GVR Jazaeri, A Aprelikova, O Patterson, T Berchuck, A Barrett, JC TI Microarray analysis reveals distinct gene expression profiles among different histologic types of endometrial cancer SO CANCER RESEARCH LA English DT Article ID FOLATE BINDING-PROTEIN; MICROSATELLITE INSTABILITY; CARCINOMA; MUTATIONS; SUPPRESSOR; OVEREXPRESSION; RECEPTOR; CATENIN; CELLS; PTEN AB Previous studies of oncogene and tumor suppressor gene alterations have suggested that differences exist in the molecular pathogenesis of the various histological types of endometrial cancer. To elucidate further the molecular events involved in endometrial carcinogenesis, we examined global expression patterns of 16 nonendometrioid cancers (13 serous papillary and 3 clear cell), 19 endometrioid cancers, and 7 age-matched normal endometria using cDNA microarrays. Unsupervised analysis of gene expression identified 191 genes that exhibited >2-fold differences (P < 0.001) between the histological groups. Many genes were similarly dysregulated in both nonendometrioid and endometrioid cancers relative to normal endometria. Gene expression differences in only 24 transcripts could distinguish serous from endometrioid cancers, the two most common subgroups. These data provide the basis for investigation of previously unrecognized novel pathways involved in the development of endometrial cancers. C1 NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Washington, DC 20013 USA. Duke Univ, Dept Obstet & Gynecol, Div Gynecol Oncol, Durham, NC 27710 USA. RP Barrett, JC (reprint author), NCI, Lab Biosyst & Canc, NIH, 900 Rockville Pike,Bldg 37,Room 5032,Mail Stop Co, Bethesda, MD 20892 USA. RI Jazaeri, Amir/A-2400-2008; Jazaeri, Amir/I-3458-2015 OI Jazaeri, Amir/0000-0003-4335-4151 NR 42 TC 130 Z9 136 U1 0 U2 4 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 JAN 1 PY 2003 VL 63 IS 1 BP 6 EP 11 PG 6 WC Oncology SC Oncology GA 633NZ UT WOS:000180290500002 PM 12517768 ER PT J AU Frias, S Van Hummelen, P Meistrich, ML Lowe, XR Hagemeister, FB Shelby, MD Bishop, JB Wyrobek, AJ AF Frias, S Van Hummelen, P Meistrich, ML Lowe, XR Hagemeister, FB Shelby, MD Bishop, JB Wyrobek, AJ TI NOVP chemotherapy for Hodgkin's disease transiently induces sperm aneuploidies associated with the major clinical aneuploidy syndromes involving chromosomes X, Y, 18, and 21 SO CANCER RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; TESTICULAR CANCER-PATIENTS; MAMMALIAN GERM-CELLS; LONG-TERM SURVIVORS; MULTICOLOR FISH; COMBINATION CHEMOTHERAPY; ADOLESCENT CANCER; GENETIC-DISEASE; HEALTHY-MEN; ABNORMALITIES AB The objective of this research was to determine whether Novantrone, Oncovin, Velban, and Prednisone (NOW) combination chemotherapy for Hodgkin's disease increases the frequencies of the specific types of aneuploid sperm that might elevate the risk of fathering a child with one of the major clinical aneuploidy syndromes, i.e., Down (disomy 21 sperm), Edward (disomy 18 sperm), Turner (nullisomy sex sperm), XYY (disomy Y sperm), triple X (disomy X sperm), or Klinefelter (XY sperm). A four-chromosome multicolor sperm fluorescence in-situ hybridization assay that simultaneously evaluates chromosomes 18, 21, X, and Y was applied to semen provided by four healthy men and to repeated samples of eight Hodgkin's disease patients before treatment, 35-50 days after treatment to examine the effects of treatment on male meiotic cells, and 1-2 years after treatment to measure the persistence of damage. There were chromosome-specific variations in baseline frequencies and significant inductions of all of the detectable types of sperm aneuploidies: XY sperm (14-fold increase), disomy 18 (7-fold), nullisomy sex (3-fold), disomy 21 (3-fold), and disomy X and Y (similar to2-fold each). Disomy 21 was about twice as frequent as disomy 18, and neither showed a preferential segregation with a sex chromosome. Extrapolating across the genome, similar to18% of sperm carried a numerical abnormality after NOW treatment of meiotic cells. Induced effects did not persist to 1-2 years after treatment, suggesting that persistent spermatogonial stem cells were not sensitive to NOW. These findings establish the hypothesis that conception shortly after certain chemotherapies can transiently increase the risks of fathering aneuploid pregnancies that terminate during development or result in the birth of children with major human aneuploidy syndromes. C1 Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program L448, Livermore, CA 94550 USA. Univ Nacl Autonoma Mexico, Inst Nacl Pediat Secretaria, Lab Citogenet, Mexico City 04510, DF, Mexico. Univ Nacl Autonoma Mexico, Fac Ciencias, Mexico City 04510, DF, Mexico. Univ Texas, MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Wyrobek, AJ (reprint author), Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program L448, 7000 East Ave, Livermore, CA 94550 USA. FU NCI NIH HHS [CA-78973] NR 56 TC 37 Z9 41 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 JAN 1 PY 2003 VL 63 IS 1 BP 44 EP 51 PG 8 WC Oncology SC Oncology GA 633NZ UT WOS:000180290500010 PM 12517776 ER PT J AU Kobayashi, T Yamaguchi, M Kim, S Morikawa, J Ogawa, S Ueno, S Suh, E Dougherty, E Shmulevich, I Shiku, H Zhang, W AF Kobayashi, T Yamaguchi, M Kim, S Morikawa, J Ogawa, S Ueno, S Suh, E Dougherty, E Shmulevich, I Shiku, H Zhang, W TI Microarray reveals differences in both tumors and vascular specific gene expression in de novo CD5(+) and CD5(-) diffuse large B-Cell lymphomas SO CANCER RESEARCH LA English DT Article ID DISTINCT; CD36 AB Malignant lymphoma is a heterogeneous disease with different clinical features. Among diffuse large B-cell lymphomas (DLBCLs), a unique subtype has been identified recently based on cell surface marker CD5 and clinicopathological features. These de novo CD5+ DLBCLs account for similar to10% of all of the DLBCLs and have poorer prognosis. To additionally ally understand this subtype of DLBCLs at the molecular level and to find genes that are differentially expressed in de novo CD5+ DLBCLs, CD(5-)DLBCLs, and mantle cell lymphomas, which also have poor prognosis, we performed gene expression profiling using cDNA microarray technology. Data from a total of 9 samples of CD5- DLBCLs, 11 samples of de novo CD5+ DLBCLs, and 10 samples of mantle cell lymphomas were acquired. A series of genes were identified that distinguish these three types of lymphomas. Among DLBCL cases, integrin beta1 and/or CD36 adhesion molecules were overexpressed in most cases of CD5+ DLBCL. An immunohistochemical confirmation study revealed that integrin beta1 was expressed on lymphoma cells, which may account for the high extranodal involvement and poor prognosis of CD5+ DLBCLs. In contrast, CD36 was overexpressed on vascular endothelia in CD5+ DLBCLs, although there was no difference in vascularity detected by von Wilbrand factor antibody between CD5+ and CD5- DLBCLs. Those results suggest that CD5+ and CD5- DLBCLs have different gene expression signatures in both tumor cells and their vascular systems. C1 Mie Univ, Sch Med, Dept Internal Med 2, Tsu, Mie 5148507, Japan. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Canc Genom Core Lab, Houston, TX 77030 USA. Texas A&M Univ, Dept Elect Engn, College Stn, TX 77840 USA. NIH, Ctr Informat Technol, Div Computat Biol, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. RP Kobayashi, T (reprint author), Mie Univ, Sch Med, Dept Internal Med 2, 2-174,Edobashi, Tsu, Mie 5148507, Japan. NR 23 TC 50 Z9 51 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 JAN 1 PY 2003 VL 63 IS 1 BP 60 EP 66 PG 7 WC Oncology SC Oncology GA 633NZ UT WOS:000180290500012 PM 12517778 ER PT J AU Seki, N Hayakawa, Y Brooks, AD Wine, J Wiltrout, RH Yagita, H Tanner, JE Smyth, MJ Sayers, TJ AF Seki, N Hayakawa, Y Brooks, AD Wine, J Wiltrout, RH Yagita, H Tanner, JE Smyth, MJ Sayers, TJ TI Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis is an important endogenous mechanism for resistance to liver metastases in murine renal cancer SO CANCER RESEARCH LA English DT Article ID NATURAL-KILLER-CELLS; FLICE-INHIBITORY PROTEIN; IN-VIVO; SIGNALING PATHWAYS; PIT CELLS; FAS; EXPRESSION; PERFORIN; DEATH; NK AB Recent reports have suggested that the death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may partially limit the formation of hepatic metastases of a variety of mouse tumors, and the major source of TRAIL in the liver was shown to be local natural killer cells. We isolated a clone (R331) of the murine renal cancer cell line Renca that was strikingly more sensitive to both Fas and TRAIL death receptor-mediated apoptosis in vitro. R331 grew in tissue culture in vitro at a rate similar to that of the parental Renca cell line but formed larger and more numerous colonies than parental Renca in soft agar. After s.c. implantation, R331 tumors progressed more rapidly than parental Renca tumors. However, R331 formed far fewer lung and liver metastases in wild-type (WT) BALB/c mice. Administration of antibodies that neutralized TRAIL dramatically increased the number of R331 liver metastases. Furthermore, numbers of R331 liver metastases were much greater in TRAIL(-/-) than in WT BALB/c mice. In contrast, no difference was seen in numbers of lung metastases when comparing TRAIL(-/-) and WT mice, suggesting that the antitumor effects of TRAIL in vivo were compartment specific. Transfection of cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein into R331 increased the numbers of liver metastases in BALB/c mice by up to 10-fold, indicating that local TRAIL in the liver was directly mediating tumor cell apoptosis. These organ-specific differences in the endogenous levels of death ligands may apply different selective pressures on the development of liver or lung metastases. Consequently, the efficacy of TRAIL therapy may vary depending on the location of the tumor metastases. C1 NCI, Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. Peter MacCallum Canc Inst, Melbourne, Vic 3002, Australia. Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 1138421, Japan. RP Sayers, TJ (reprint author), NCI, Sci Applicat Int Corp, Intramural Res Support Program, Bldg 560,Room 31-93, Frederick, MD 21702 USA. RI Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU PHS HHS [N01-C0-12400] NR 31 TC 74 Z9 76 U1 1 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 JAN 1 PY 2003 VL 63 IS 1 BP 207 EP 213 PG 7 WC Oncology SC Oncology GA 633NZ UT WOS:000180290500033 PM 12517799 ER PT J AU Wall, NR O'Connor, DS Plescia, J Pommier, Y Altieri, DC AF Wall, NR O'Connor, DS Plescia, J Pommier, Y Altieri, DC TI Suppression of survivin phosphorylation on Thr(34) by flavopiridol enhances tumor cell apoptosis SO CANCER RESEARCH LA English DT Article ID DEPENDENT KINASE INHIBITOR; CANCER CELLS; LUNG-CANCER; IN-VIVO; PROTEIN; GROWTH; BCL-2; CYCLE; DEGRADATION; EXPRESSION AB Survivin is a member of the inhibitor of apoptosis gene family that is expressed in most human cancers and may facilitate evasion from apoptosis and aberrant mitotic progression. Here, exposure of breast carcinoma MCF-7 or cervical carcinoma HeLa cells to anticancer agents, including Adriamycin, Taxol or UVB resulted in a 4-5-fold increased survivin expression. Changes in survivin levels after anticancer treatment did not involve modulation of survivin mRNA expression and were independent of de novo gene transcription. Conversely, inhibition of survivin phosphorylation on Thr(34) by the cyclin-dependent kinase inhibitor flavopiridol resulted in loss of survivin expression, and nonphosphorylatable survivin Thr(34) -->Ala exhibited accelerated clearance as compared with wild-type survivin. Sequential ablation of survivin phosphorylation on Thr34 enhanced tumor cell apoptosis induced by anticancer agents independently of p53 and suppressed tumor growth without toxicity in a breast cancer xenograft model in vivo. These data suggest that Thr34 phosphorylation critically regulates survivin levels in tumor cells and that sequential ablation of p34(cdc2) kinase activity may remove the survivin viability checkpoint and enhance apoptosis in tumor cells. C1 Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA 01605 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Altieri, DC (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, LRB 428,364 Plantat St, Worcester, MA 01605 USA. RI Wall, Nathan/H-7368-2015 OI Wall, Nathan/0000-0002-3235-4386 FU NCI NIH HHS [CA90917, 1 F32 CA097802, CA78810]; NHLBI NIH HHS [HL54131] NR 48 TC 217 Z9 237 U1 0 U2 8 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 JAN 1 PY 2003 VL 63 IS 1 BP 230 EP 235 PG 6 WC Oncology SC Oncology GA 633NZ UT WOS:000180290500036 PM 12517802 ER PT J AU Tam, AS Devereux, TR Patel, AC Foley, JF Maronpot, RR Massey, TE AF Tam, AS Devereux, TR Patel, AC Foley, JF Maronpot, RR Massey, TE TI Perturbations of the Ink4a/Arf gene locus in aflatoxin B-1-induced mouse lung tumors SO CARCINOGENESIS LA English DT Article ID DE-NOVO METHYLATION; CPG ISLAND METHYLATION; CELL-CYCLE ARREST; DNA METHYLATION; SUPPRESSOR GENE; DIFFERENTIAL EXPRESSION; ABERRANT METHYLATION; TRANSCRIPTION FACTOR; P15(INK4B) GENES; CHROMOSOME 9P21 AB Lung tumors from AC3F1 mice treated with aflatoxin B-1 (AFB(1)), were examined for loss of alleles, point mutations and hypermethylation of CpG sites within the promoters of the two genes in the Ink4a/Arf gene locus. Loss of microsatellite alleles in the Ink4a/Arf region occurred in 22 of 74 (30%) AFB(1)-induced lung tumors. Fifty-one of 61 (83%) tumors had at least partial methylation of CpG sites within the p16(Ink4a) promoter-exon 1alpha region. At least partial methylation of CpG sites was observed in 43 of 49 (88%) tumors analyzed for p19(Arf) promoter hypermethylation, with methylation of identified transcription factor binding sites or consensus sequences occurring in 21 tumors (DMPl/ Ets in two tumors, CTCF in four tumors, E2F in three tumors, Sp1 in 16 tumors). Two tumors contained point mutations in the p19(Arf) promoter. Nuclear staining for p19(Arf) was decreased by 80-100% in 41 of 71(58 %) tumors. The concordance between p19(Arf) molecular perturbations and altered protein expression was 63%. However, upon comparing p19(Arf) promoter perturbations (i.e. methylation of functional transcription factor binding sites and point mutations) and altered p19(Arf) expression, the concordance was 86%, suggesting a mechanism for changes in protein expression in some tumors. There was an absence of a mutually exclusive relationship between disruption of p53 and p19(Arf), since the concordance was 62%. Similarly, no evidence was found of inverse relationships between perturbation of p16(Ink4a) and p19(Arf) (43% concordance) or p16(Ink4a) and p53 (37% concordance), suggesting that inactivation of these genes occurs independently and provides evidence that, although these genes may participate in cooperative cellular pathways, they also have functions in independent pathways that are important in mouse lung tumorigenesis. C1 Queens Univ, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NCI, Bethesda, MD 20892 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Massey, TE (reprint author), Queens Univ, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada. NR 84 TC 13 Z9 14 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2003 VL 24 IS 1 BP 121 EP 132 DI 10.1093/carcin/24.1.121 PG 12 WC Oncology SC Oncology GA 644AP UT WOS:000180896000016 PM 12538357 ER PT J AU Shibata, A Parsonnet, J Longacre, TA Garcia, MI Puligandla, B Davis, RE Vogelman, JH Orentreich, N Habel, LA AF Shibata, A Parsonnet, J Longacre, TA Garcia, MI Puligandla, B Davis, RE Vogelman, JH Orentreich, N Habel, LA TI Cag A status of Helicobacter pylori infection and p53 gene mutations in gastric adenocarcinoma SO CARCINOGENESIS LA English DT Letter C1 Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Kaiser Permanente Med Care Program, Dept Pathol, Oakland, CA 94611 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. Orentreich Fdn Advancement Sci Inc, Cold Spring On Hudson, NY 10516 USA. RP Shibata, A (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2003 VL 24 IS 1 BP 147 EP 147 DI 10.1093/carcin/24.1.147 PG 1 WC Oncology SC Oncology GA 644AP UT WOS:000180896000020 ER PT J AU Liu, XK Katchman, A Whitfield, BH Wan, G Janowski, EM Woosley, RL Ebert, SN AF Liu, XK Katchman, A Whitfield, BH Wan, G Janowski, EM Woosley, RL Ebert, SN TI In vivo androgen treatment shortens the QT interval and increases the densities of inward and delayed rectifier potassium currents in orchiectomized male rabbits SO CARDIOVASCULAR RESEARCH LA English DT Article DE ECG; gender; gene expression; hormones; K-channel; repolarization ID TORSADES-DE-POINTES; USE-DEPENDENT BLOCK; VENTRICULAR MYOCYTES; K+ CURRENT; I-KR; CARDIAC-ARRHYTHMIA; GONADAL-STEROIDS; SEX-DIFFERENCES; FEMALE GENDER; RISK FACTOR AB Objectives: Women have longer rate-corrected QT intervals (QTc) and are at higher risk for developing life-threatening torsades de pointes ventricular arrhythmias than men, especially after taking medications that block cardiac human ether-a-go-go-related gene (HERG)-encoded K+ channels. The purpose of the present study was to determine if the male sex steroid hormone, dihydrotestosterone, (DHT), influences QT intervals in orchiectomized (Orch) male rabbits. Methods: ECG and whole-cell patch-clamp analyses were employed to evaluate cardiac repolarization and K+ currents in hearts isolated from orchiectomized (Orch) male New Zealand White rabbits receiving subcutaneous sustained release pellets for either dihydrotestosterone (DHT) or placebo. The efficacy of the treatment paradigm was monitored by measuring plasma DHT concentrations before and after the treatment period (10-14 days). Results: The results show that rate- and drug-induced QT-lengthening is attenuated in hearts from DHT-treated rabbits relative to placebo-treated controls. No significant changes in QRS were observed in response to DHT, thereby indicating that DHT influences QT primarily through an effect on ventricular repolarization. In addition, hearts from DHT-treated rabbits displayed significantly less QT lengthening in response to quinidine challenge compared to placebo controls. Current densities for two important cardiac repolarizing K+ currents, I-KI and I-Kr were found to be significantly increased in ventricular myocardium of DHT-treated rabbits. Further, the half-maximal voltage of activation (V-1/2) for I-Kr was significantly shifted to more negative potentials in myocytes from DHT vs. placebo hearts (21.2 +/- 1.2 vs. 30.2 +/- 1.4 mV, respectively, n = 12, P < 0.001). Corresponding changes in rabbit ether-a-go-go-related gene (RERG) mRNA were not found when examined by Northern blot hybridization. Conclusions: These results suggest that the presence of male sex steroid hormones in male rabbits helps to suppress rate- and drug-induced delays in cardiac repolarization. DHT action produces increased current densities for I-KI and I-Kr and a left-shift in the V-1/2 for I-Kr that could account, at least in part, for the observed QTc differences between males and females. Since little change was seen in ventricular RERG gene expression, DHT action in the heart may influence I, via post-transcriptional and/or post-translational mechanisms. (C) 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved. C1 Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Univ Arizona, Dept Med, Tucson, AZ USA. NIH, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MI USA. RP Ebert, SN (reprint author), Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. FU NHLBI NIH HHS [HL58743] NR 41 TC 81 Z9 90 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JAN PY 2003 VL 57 IS 1 BP 28 EP 36 AR PII S0008-6363(02)00673-9 DI 10.1016/S0008-6363(02)00673-9 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 637KH UT WOS:000180509900005 PM 12504811 ER PT S AU Jerebko, AK Malley, JD Franaszek, M Summers, RM AF Jerebko, AK Malley, JD Franaszek, M Summers, RM BE Lemke, HU Inamura, K Doi, K Vannier, MW Farman, AG Reiber, JHC TI Computer-aided polyp detection in CT colonography using an ensemble of support vector machines SO CARS 2003: COMPUTER ASSISTED RADIOLOGY AND SURGERY, PROCEEDINGS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 17th International Congress and Exhibition of Computer Assisted Radiology and Surgery CY JUN 25-28, 2003 CL LONDON, ENGLAND SP Amer Acad Oral & Maxillofacial Radiol, BAR, BIR, CRS, CURAC, DGBMT, DRG, EFSUMB, ESCR, ESEM, EuroPACS, Gesell Informatik, GMDS, IADMFR, IERAC, IEEE, Japanese Coll Radiol, Japan Radiol Soc, JSOMR, NVvR, Osterreich Rontgen Gesell, OWGTM, PMSR, Royal Coll Radiologists, Soc Francaise Radiol Med, SGR SSR, SICTCA, SIRM, SPIE, SRS, TUB, WABT DE computer-aided diagnosis; virtual colonoscopy; colon polyp; support vector machine; validation AB In this paper, we propose a new classification scheme for computer-aided detection (CAD) of colonic polyps in CT colonography (CTC). The scheme involves an ensemble of support vector machines (SVMs) for classification, a smoothed leave-one-out (SLOO) cross-validation method for obtaining error estimates, and the use of a bootstrap aggregation method for training and model selection. Our use of an ensemble of SVM classifiers with bagging (bootstrap aggregation), built on different feature subsets, is intended to improve classification performance when compared to single SVMs and to reduce the number of false positive detections. The bagging technique has the effect of a virtual increase in the training set size and, as a consequence, also helps to reduce the bias of error estimates when combined with a leave-one-out cross-validation approach. The bootstrap-based model selection technique is used for tuning the SVM parameters. (C) 2003 Published by Elsevier Science B.V. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Jerebko, AK (reprint author), Siemens Med Solut USA Inc, 51 Valley Stream Pkwy, Malvern, PA 19355 USA. NR 7 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51387-6 J9 INT CONGR SER PY 2003 VL 1256 BP 1019 EP 1024 DI 10.1016/S0531-5131(03)00314-5 PG 6 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BX53F UT WOS:000185617600157 ER PT B AU Tuan, RS AF Tuan, RS BE Hendrich, C Noth, U Eulert, J TI Skeletal tissue engineering in cartilage replacement: Future perspectives and the new age of regenerative medicine SO CARTILAGE SURGERY AND FUTURE PERSPECTIVES LA English DT Proceedings Paper CT Symposium on Cartilage Surgery and Future Perspectives CY NOV, 2002 CL WURZBURG, GERMANY ID MESENCHYMAL STEM-CELLS; HUMAN TRABECULAR BONE; IN-VITRO; MARROW; ADULT; DIFFERENTIATION; EXPANSION; MUSCLE C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-01054-8 PY 2003 BP 185 EP 197 PG 13 WC Materials Science, Biomaterials; Orthopedics; Surgery; Transplantation SC Materials Science; Orthopedics; Surgery; Transplantation GA BW88T UT WOS:000183489400021 ER PT S AU Long, LR Antani, SK Thoma, GR AF Long, LR Antani, SK Thoma, GR BE Krol, M Mitra, S Lee, DJ TI A prototype content-based image retrieval system for spine x-rays SO CBMS 2003: 16TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 16th IEEE Symposium on Computer-Based Medical Systems CY JUN 26-27, 2003 CL NEW YORK, NY SP IEEE Comp Soc Tech Comm Computat Med, Mt Sinai Sch Med Dept Anesthesiol, Texas Tech Univ Coll Engn AB At the Lister Hill National Center for Biomedical Communications, an R&D division of the National Library of Medicine, we are engaged in an effort in content-based image retrieval (CBIR) for biomedical image databases. Toward the goal of developing a functional and significant CBIR capability, we have created a prototype system for image indexing and retrieval which operates on a collection of spine x-rays and associated health survey data. In this paper, we present our prototype system functionality, performance results, ongoing research, and outstanding technical issues. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Long, LR (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 15 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1901-6 J9 COMP MED SY PY 2003 BP 156 EP 162 PG 7 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA BX13J UT WOS:000184365600024 ER PT B AU Risinger, JI Maxwell, GL Dainty, LA Chandramouli, GVR Berchuck, A Barrett, JC AF Risinger, JI Maxwell, GL Dainty, LA Chandramouli, GVR Berchuck, A Barrett, JC BE Kuramoto, H Nishida, M TI Molecular genetic profiles of serous and endometrioid endometrial cancers, genes downregulated in endometrial cancers, and the role of epigenetics SO CELL AND MOLECULAR BIOLOGY OF ENDOMETRIAL CARCINOMA LA English DT Proceedings Paper CT 15th International Symposium of the Japan-Human-Cell-Society (JHCS) CY AUG 30-31, 2002 CL KITASATO UNIV, KITASATO INST, TOKYO, JAPAN SP Japan Human Cell Soc HO KITASATO UNIV, KITASATO INST DE endometrial cancer; epigenetics; hypermethylation; expression array ID MICROSATELLITE INSTABILITY PHENOTYPE; HMLH1 PROMOTER HYPERMETHYLATION; MISMATCH REPAIR GENES; ESTROGEN-RECEPTOR; CARCINOMA; METHYLATION; EXPRESSION; MUTATIONS; DISEASES; TUMORS AB Endometrial cancers, like most other malignancies, develop, in part, as the result of oncogene activation and tumor suppressor and DNA repair gene inactivations. Available molecular data suggest that endometrial cancers of endometrioid and nonendometrioid histology develop by distinct etiologies. Endometrioid lesions are typified by PTEN, CTNNB1, and KRAS2 mutations, DNA mismatch repair deficiency, as evidenced by microsatellite instability, and are usually near diploid. Nonendometrioid histologies are characterized by mutation of TP53, overexpression of Her-2/neu, and are usually nondiploid, suggesting widespread chromosomal instability. Although these changes are observed in many endometrial cancers, they do not occur universally, suggesting that there are unrecognized pathways involved in the development of endometrial cancer. We examined the prevalence of these prototypical defects in a panel of 87 cancers. Interestingly, more than half the cancers did not contain mutations of PTEN, KRAS2, and TP53, or have microsatellite instability. Based, in part, on this observation, we believe that epigenetic mechanisms likely play a major role in the development of some endometrial cancers. Multiple epigenetic mechanisms are likely involved, including loss of imprinting, chromatin remodeling, and promoter hypermethylation. Our group has recently evaluated the role of promoter methylation in endometrial carcinogenesis and has found that methylation of specific promoters varies between endometrioid and nonendometrioid histologic types. We have also performed in vitro manipulation of endometrial carcinoma cells with agents that demethylate promoters prior to microarray analysis to identify genes that are upor downregulated. In addition, we have analyzed a panel of endometrial cancers using expression microarrays to identify downregulated genes in both endometrioid and nonendometrioid endometrial cancers. Following a cross-referencing of both array databases, genes common to both the global expression of primary endometrial cancers and in vitro experiments can be identified. These genes may be downregulated via epigenetic mechanisms and our laboratory is currently working to validate this hypothesis. C1 NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. RP Risinger, JI (reprint author), NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-00613-3 PY 2003 BP 245 EP 251 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Research & Experimental Medicine GA BX20C UT WOS:000184581700017 ER PT J AU Hamel, E AF Hamel, E TI Evaluation of antimitotic agents by quantitative comparisons of their effects on the polymerization of purified tubulin SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE antimitotic drugs; combretastatin A-4; docetaxel; GDP; glutamate; GTP; microtubules; paclitaxel; tubulin polymerization ID MICROTUBULE-ASSOCIATED PROTEINS; DIFFERENTIAL CYTOTOXICITY DATA; INDUCED SELF-ASSOCIATION; MARINE NATURAL PRODUCT; CALF BRAIN TUBULIN; BETA-TUBULIN; 2,4-DICHLOROBENZYL THIOCYANATE; EXCHANGEABLE NUCLEOTIDE; STABILIZING AGENTS; ASSEMBLED INVITRO AB Most antimitotic compounds have highly specific interactions with tubulin, the major protein component of microtubules. It is, therefore, often desirable to characterize interactions of these agents with tubulin. In particular, quantitative comparisons between new and old ("standard") agents, between different classes of agent, and between structural analogs (e.g., for a structure-activity relationship study) are important. Because antimitotic drugs have a variety of effects on tubulin and bind at multiple distinct sites on the protein, the tubulin assembly reaction is probably the only universally applicable reaction that can be analyzed. In my laboratory, we use the assembly of purified tubulin induced by higher concentrations of monosodium glutamate as our basic assay system. This report presents a detailed description of our current routine assay, including the effects of a variety of reaction components on the reaction. In addition, the variety of effects that reaction components can have on the quantitative results obtained with drugs, using the colchicine site drug combretastatin A-4 as a model compound, is described. C1 NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. RP Hamel, E (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. NR 76 TC 182 Z9 183 U1 2 U2 13 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2003 VL 38 IS 1 BP 1 EP 21 DI 10.1385/CBB:38:1:1 PG 21 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 663WJ UT WOS:000182029300001 PM 12663938 ER PT J AU Smolenicka, Z Pani, F Hwang, KJ Gruschus, JM Ferretti, JA AF Smolenicka, Z Pani, F Hwang, KJ Gruschus, JM Ferretti, JA TI Sequence of a conserved region of a new sea urchin homeobox gene from the NK family SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE homeobox; homeodomain; sea urchin; Paracentrotus lividus; NK family; development ID TRANSCRIPTION FACTOR; HOMEODOMAIN PROTEINS; HEART DEVELOPMENT; VENTRAL DOMAINS; EXPRESSION; DROSOPHILA; DNA; BINDING; SYSTEM; NKX3.1 AB The partial sequence of a novel homeobox-containing gene from Paracentrotus lividus is described. Both cDNA and genomic DNA were screened using probes from the vnd/NK-2 homeobox gene found in Drosophila melanogaster. The new DNA sequence found in P. lividus encodes a protein fragment that is closely related to the NK family of homeodomain transcriptional regulators originally discovered in the fruit fly. This study thus represents the first finding of a homeobox gene from the NK family in sea urchin. The DNA that was sequenced includes the most highly conserved region of the NK genes and contains the 180 base pair homeobox (i.e. the DNA segment that encodes the homeodomain), the NK-2 box that encodes the NK-2-specific domain (NK-2 SD), and the acidic box that encodes an acidic domain, but which is found only in a limited subset of the NK genes. In this deduced sequence, the 60 amino acid residue homeodomain contains tyrosine in position 54 and leucine in position 7, which implies that the protein will bind to an unusual sequence of DNA that contains 5'-CAAGTG-3' as its core. The presence of tyrosine in position 54 identifies the gene as a member of the NK-2 class of homeobox genes. Positions 37 and 56 of the homeodomain contain isoleucine and leucine, respectively, which is the first finding in the NK family of homeodomains of these particular amino acid residues in those positions. The presence of the NK-2 box is consistent with identification of the gene as a member of the NK-2 class, and suggests an important role for the C-terminal portion of the protein in transcriptional activation. The sequence homology of the NK-2 box and the spacing between it and the homeobox further suggest that this gene is a member of the NKx-2.2 subclass, whose genes typically are expressed in brain and play a role in axonal guidance, and whose full lengths often are of the order of 900 bases. Homologous NK genes have been found in such diverse invertebrate and vertebrate species, such as Amphioxus sp., Xenopus sp., Caenorhabditis elegans, zebra fish, chicken, hamster, mouse and humans. The finding of this new gene together with sequence comparisons suggests possible evolutionary relationships between sea urchins and vertebrates in the developmental pathways of their body plans. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Int Marine Ctr, Local Sa Mardini Torregrande OR, I-09072 Sardinia, Italy. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Smolenicka, Z (reprint author), Int Marine Ctr, Local Sa Mardini Torregrande OR, I-09072 Sardinia, Italy. EM z.smolenicky@imc-it.org NR 31 TC 1 Z9 2 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2003 VL 27 IS 2 BP 81 EP 87 DI 10.1016/S1065-6995(02)00351-7 PG 7 WC Cell Biology SC Cell Biology GA 658AW UT WOS:000181700300001 PM 12662965 ER PT J AU Chatterjee, B Meyer, RA Loredo, GA Coleman, CM Tuan, R Lo, CW AF Chatterjee, B Meyer, RA Loredo, GA Coleman, CM Tuan, R Lo, CW TI BMP regulation of the mouse connexin43 promoter in osteoblastic cells and embryos SO CELL COMMUNICATION AND ADHESION LA English DT Article DE BMP; connexin43; GDF5; osteoblast; promoter; SMAD; transcription ID BONE MORPHOGENETIC PROTEIN-2; GAP JUNCTIONAL COMMUNICATION; TGF-BETA-SUPERFAMILY; MULTIPOTENTIAL MESENCHYMAL CELLS; CHICK LIMB DEVELOPMENT; GENE-EXPRESSION; CHONDROGENIC DIFFERENTIATION; SKELETAL DEVELOPMENT; SIGNALING PATHWAYS; N-CADHERIN AB We examined BMP regulation of the gap junction gene Gjal (Cx43alpha1) using a series of lacZ reporter constructs containing up to 6.7 kbs of mouse Cx43alpha1 promoter sequence. Using transient transfection assays, we showed that BMP2, BMP4, and GDF5, but not BMP6 or BMP7, can modulate Cx43alpha1 promoter activity in the osteosarcoma cell line ROS17/2.8. Positive regulatory elements were found at the proximal and distal ends of the 6.7 kb promoter fragment, while negative regulatory elements were found in the intervening region. Comparison of Cx43alpha1 promoter sequences from the human vs. mouse showed five regions with significant sequence conservation, two of which contained Smad binding elements in conjunction with a BMP response element. Analysis of a transgenic mouse line containing a Cx43alpha1 promoter driven lacZ reporter construct revealed lacZ expression in the developing joints, an expression pattern similar to that previously reported for Gdf5 . LacZ expression was also observed in axial regions of the skeletal anlage, which in situ hybridization analysis confirmed as sites of Gdf5 transcript expression. When the Cx43alpha1 promoter driven lacZ transgene was bred into the brachypodism mouse Gdf5 bpJ ( bp ) harboring a Gdf5 loss of function mutation, lacZ expression was extinguished. This was observed in homozygous and heterozygous bp animals, suggesting that Cx43alpha1 promoter regulation by GDF5 is subject to haploinsufficiency. Overall, these observations are consistent with recent studies by others indicating a role for Cx43alpha1 in osteogenesis and osteoblastic function during mouse development. C1 NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. Sacramento VA Med Ctr, Mather, CA USA. NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA. RP Lo, CW (reprint author), NHLBI, Dev Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 61 TC 21 Z9 21 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5385 J9 CELL COMMUN ADHES JI Cell Commun. Adhes. PD JAN-FEB PY 2003 VL 10 IS 1 BP 37 EP 50 DI 10.1080/15419060390220422 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 701QR UT WOS:000184179300004 PM 12881039 ER PT J AU Yang, W Rogozin, IB Koonin, EV AF Yang, Wei Rogozin, Igor B. Koonin, Eugene V. TI Yeast POL5 Is an Evolutionarily Conserved Regulator of rDNA Transcription Unrelated to Any Known DNA Polymerases SO CELL CYCLE LA English DT Article DE DNA polymerase; Transcription regulation; MYB-binding proteins; Conserved sequence motifs; Multiple alignment; Protein secondary structure prediction AB We show that yeast protein Yel055cp, which has been identified as the fifth essential DNA polymerase in Saccharomyces cerevisiae (POL5), is a member of a family of predicted rDNA transcription regulators (typified by human MYB-binding protein MYBBP1A), which are represented by a single ortholog in all animals, fungi and plants with sequenced genomes. These proteins are confidently predicted to have an entirely a-helical structure and are unrelated to the B class DNA polymerases, as claimed for yeast POL5, or any other known polymerases. C1 [Yang, Wei; Rogozin, Igor B.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. [Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 17 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 2 BP 120 EP 122 DI 10.4161/cc.2.2.329 PG 3 WC Cell Biology SC Cell Biology GA V43OL UT WOS:000209690600017 PM 12695662 ER PT J AU Aravind, L Iyer, LM Koonin, EV AF Aravind, L. Iyer, L. M. Koonin, E. V. TI Scores of RINGs but No PHDs in Ubiquitin Signaling SO CELL CYCLE LA English DT Article DE Ubiquitin ligase; RING finger; PHD finger; Multiple sequence alignment; Structural signatures AB Recently, it has been reported that PHD fingers of MEKK1 kinase and a family of viral and cellular membrane proteins have E3 ubiquitin ligase activity. Here we describe unique sequence and structural signatures that distinguish PHD fingers from RING fingers, which function primarily as E3 ubiquitin ligases, and demonstrate that the Zn-binding modules of the above proteins are distinct versions of the RING domain rather than PHD fingers. Thus, currently available data reveal extreme versatility of RINGs and their derivatives that function as E3 ubiquitin ligases but provide no evidence of this activity among PHD fingers whose principal function appears to involve specific protein-protein and possibly protein-DNA interactions in chromatin. C1 [Aravind, L.; Iyer, L. M.; Koonin, E. V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 26 TC 68 Z9 71 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 2 BP 123 EP 126 DI 10.4161/cc.2.2.335 PG 4 WC Cell Biology SC Cell Biology GA V43OL UT WOS:000209690600018 PM 12695663 ER PT J AU Stein, WD Robey, R Cardarelli, C Gottesman, MM Bates, SE AF Stein, Wilfred D. Robey, Robert Cardarelli, Carol Gottesman, Michael M. Bates, Susan E. TI Low and High Concentrations of the Topo II Inhibitor Daunorubicin in NIH3T3 Cells Reversible G(2)/M Versus Irreversible G(1) and S Arrest SO CELL CYCLE LA English DT Article DE Daunorubicin; Cell cycle; Checkpoints; Multidrug resistance AB Daunorubicin (DNR) blocks the cell cycle by interfering with synthesis and repair of DNA. In both drug-sensitive 3T3 cells and drug-resistant 3T3 cells (NIH-MDR-6185, created by transfection with a human MDR1 cDNA), low concentrations of DNR (up to 80 ng/ml in sensitive cells, 1600 ng/ml in resistant cells) initially slowed S-phase progression for 2 to 3 hours, but the treated cells then continued in progression at a steady rate, close to that of untreated cells, and accumulated in G(2)/M. The 2 to 3 h lag period represents the time taken for fully establishing the G(2)/M block. The time required to bring about cessation of proliferation is the sum of this lag period and the time taken to travel through the cell cycle. This low concentration effect is cytostatic, and fully reversible on washing out the daunorubicin. At higher drug concentrations (above 160 ng/ml in sensitive cells, 3200 ng/ml in resistant cells) the cells became blocked in both G(1) and S, and did not reach G(2)/M. The high concentration effect was cytotoxic and irreversible, and was followed by cell death. Only cells that were in S phase were subject to this block in S, since cells that had accumulated in G(2)/M by using a low concentration (60 ng/ml DNR for 20 h) were not blocked in S, and did not die, when subsequently treated with high drug concentrations (320 ng/ml, 30 h). The low concentration effect occurred at the same maximal rate (4 %/h) in sensitive or resistant cells, but the external drug concentration required to produce half the maximal rate was, appropriately, twenty-fold higher in the resistant cells (20 ng/ml and 400 ng/ml, respectively). C1 [Stein, Wilfred D.] Hebrew Univ Jerusalem, Inst Life Sci, Biol Chem, IL-91904 Jerusalem, Israel. [Robey, Robert; Bates, Susan E.] NCI, Med Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cardarelli, Carol; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1A09,37 Convent Dr,MSC 4254, Bethesda, MD 20892 USA. NR 21 TC 7 Z9 7 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 2 BP 134 EP 142 DI 10.4161/cc.2.2.294 PG 9 WC Cell Biology SC Cell Biology GA V43OL UT WOS:000209690600020 PM 12695665 ER PT J AU Bulavin, DV Demidenko, ZN Phillips, C Moody, SA Fornace, AJ AF Bulavin, Dmitry V. Demidenko, Zoya N. Phillips, Crissy Moody, Sally A. Fornace, Albert J., Jr. TI Phosphorylation of Xenopus Cdc25C at Ser285 Interferes with Ability to Activate a DNA Damage Replication Checkpoint in Pre-Midblastula Embryos SO CELL CYCLE LA English DT Article DE Cdc25C; Chk1; DNA damage; Checkpoints; Phosphorylation; Xenopus; pre-MBT embryo AB We have recently demonstrated that negative regulation of human Cdc25 protein phosphatases by phosphorylation at their 14-3-3 site can be antagonized through phosphorylation at an adjacent site in the -2 position. 1 Based on structural homology for different Cdc25 phosphatases, a similar regulatory pathway also could be conserved in Xenopus embryos, where cell cycle checkpoints are not operational prior to the Midblastula Transition (MBT). Here, we demonstrate that before MBT, XeCdc25C is phosphorylated on Ser285, an analogous site to Ser214 in human Cdc25C or Ser307 in Cdc25B.(1) Phosphorylation of Ser285 prevents subsequent inhibitory phosphorylation of XeCdc25C on Ser287, thus maintaining XeCdc25C in an active form. Mutation of Ser285 to alanine allows the reconstitution of a DNA damage replication checkpoint. This effect is completely dependent on Ser287 phosphorylation as additional mutation of Ser287 to alanine fully reversed the cell cycle inhibitory effect of Ser285A XeCdc25C. We propose that phosphorylation of XeCdc25C Ser285 may account for the lack of a DNA replication checkpoint in cleaving Xenopus embryos prior to the MBT. C1 [Bulavin, Dmitry V.; Phillips, Crissy; Fornace, Albert J., Jr.] NCI, Gene Response Sect, NIH, Bethesda, MD 20892 USA. [Demidenko, Zoya N.; Moody, Sally A.] George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Washington, DC 20037 USA. RP Bulavin, DV (reprint author), NCI, Gene Response Sect, NIH, Bethesda, MD 20892 USA. EM bulavin@nih.gov NR 17 TC 19 Z9 19 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 3 BP 263 EP 266 DI 10.4161/cc.2.3.396 PG 4 WC Cell Biology SC Cell Biology GA V43OO UT WOS:000209690900026 PM 12775939 ER PT J AU Aravind, L Iyer, LM AF Aravind, L. Iyer, Lakshminarayan M. TI Provenance of SET-Domain Histone Methyltransferases Through Duplication of a Simple Structural Unit SO CELL CYCLE LA English DT Article DE SET domain; Methyltransferase; Chromatin structure; Enzyme evolution; Histones AB SET domains are protein lysine methyltransferases that methylate diverse proteins, such as, histones, Rubisco and cytochrome C. In particular, they play an important role in the dynamics of the eukaryotic chromatin and are present in several chromatin-associated proteins. Recently, structures of several SET domains have been solved, and they contain a conserved fold that is unrelated to previously characterized methyltransferases, which possess either Rossmann fold or SPOUT domains. Phylogenetic and phyletic-profile analysis of the SET domain suggests that it was an evolutionary "invention" of the eukaryotic lineage, with secondary lateral transfers to bacteria. We show that the conserved N- and C-terminal regions, which comprise the core barrel-like module of the SET domain, are symmetric repeats of a simple 3-stranded unit. Furthermore, the two symmetrically arranged repeats contribute to the binding sites for the two substrates of the SET domain. This suggests the SET domain arose from an ancestral dimer of this 3-stranded unit, with each unit probably functioning as generic-ligand binding structure. The divergence between the two repeat units appears to have arisen as a result of their interactions with the central module of the SET domain, which was inserted between the two repeats. One of the repeats appears to have acquired adaptations, which helped it to specialize in AdoMet binding, whereas the second repeat contributed to histone-interaction, and in orienting a crucial active site residue. The central module of the SET domain supplies a critical asparagine to the active site, and its structural features suggest that it may have also arisen from a further duplication of one of the repeats comprising the core barrel. However, it appears to have structurally diverged from the two canonical repeats due to the lack of an obligate dimerization partner. The spatial position of the two repeats in the ancestral dimer appears to have favored the formation of the structural knot typical of the SET domain. A comparable knot is seen in the SPOUT-domain methyltransferases, and this represents a case of convergent evolution of an active-site-associated configuration in two otherwise unrelated classes of methylases. Thus, the SET domain provides a model for the innovation of a complex enzymatic fold through the duplications of a structurally simple non-enzymatic unit. C1 [Aravind, L.; Iyer, Lakshminarayan M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov NR 58 TC 28 Z9 29 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 4 BP 369 EP 376 DI 10.4161/cc.2.4.419 PG 8 WC Cell Biology SC Cell Biology GA V43OS UT WOS:000209691300025 PM 12851491 ER PT J AU Gorospe, M AF Gorospe, Myriam TI HuR in the Mammalian Genotoxic Response Post-Transcriptional Multitasking SO CELL CYCLE LA English DT Article DE post-transcriptional gene expression; DNA damage; HuR; ultraviolet light; p53; translation; ELAV C1 [Gorospe, Myriam] NIA, Lab Cellular & Mol Biol, Intramural Res Program, NIH, 5600 Nathan Shock Dr,Box 12, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, Lab Cellular & Mol Biol, Intramural Res Program, NIH, 5600 Nathan Shock Dr,Box 12, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov NR 24 TC 84 Z9 86 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 5 BP 412 EP 414 DI 10.4161/cc.2.5.491 PG 3 WC Cell Biology SC Cell Biology GA V43OT UT WOS:000209691400005 PM 12963828 ER PT J AU Fernandez-Capetillo, O Celeste, A Nussenzweig, A AF Fernandez-Capetillo, Oscar Celeste, Arkady Nussenzweig, Andre TI Focusing on Foci H2AX and the Recruitment of DNA-Damage Response Factors SO CELL CYCLE LA English DT Article DE H2AX; irradiation; foci; DNA repair; chromatin C1 [Fernandez-Capetillo, Oscar; Celeste, Arkady; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B04, Bethesda, MD 20892 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B04, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov NR 23 TC 138 Z9 150 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 5 BP 426 EP 427 DI 10.4161/cc.2.5.509 PG 2 WC Cell Biology SC Cell Biology GA V43OT UT WOS:000209691400010 PM 12963833 ER PT J AU Trepel, J Birrer, MJ AF Trepel, Jane Birrer, Michael J. TI A Link Between Histone Deacetylase Inhibitors and NF-kappa B Signaling SO CELL CYCLE LA English DT Editorial Material DE Histone Deacetylase; Nf-kappa B; p21 C1 [Trepel, Jane] NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Birrer, Michael J.] NCI, Cell & Canc Biol Dept, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Birrer, MJ (reprint author), NCI, Cell & Canc Biol Dept, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM Birrerm@bprb.nci.nih.gov NR 15 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 5 BP 452 EP 453 DI 10.4161/cc.2.5.466 PG 2 WC Cell Biology SC Cell Biology GA V43OT UT WOS:000209691400018 PM 12963841 ER PT J AU Goloudina, A Yamaguchi, H Chervyakova, DB Appella, E Fornace, AJ Bulavin, DV AF Goloudina, Anastasia Yamaguchi, Hiroshi Chervyakova, Daria B. Appella, Ettore Fornace, Albert J., Jr. Bulavin, Dmitry V. TI Regulation of Human Cdc25A Stability by Serine 75 Phosphorylation Is Not Sufficient to Activate a S-phase Checkpoint SO CELL CYCLE LA English DT Article DE Cdc25A; p38MAPK; S-phase; checkpoint; stress; phosphorylation; protein stability AB Degradation of Cdc25A phosphatase is an ubiquitous feature of stress. There are some discrepancies in the reported roles for different phosphorylation sites in the regulation of Cdc25A stability. Using a panel of doxycycline-inducible phosphorylation mutants we show that the stability of human Cdc25A protein is dependent upon phosphorylation at S75. In non-stressed conditions and in non-mitotic cells, Cdc25A is unstable and its stability is regulated in a Chk1-dependent manner. During mitosis, Cdc25A becomes stable and does not undergo degradation after DNA damage. We further show that Chk1 kinase regulates Cdc25A stability after UV irradiation. Similar to Chk1 kinase, p38 MAPK controls Cdc25A protein level after osmotic stress. Using phospho-specific antibodies, we find that both kinases can phosphorylate S75 and S123 in vitro. Inactivation of either Chk1 after UV-irradiation or p38 MAPK after osmotic stress prevents activation of a S phase checkpoint and S75 and S123 phosphorylation. However, introduction of stable Cdc25A (S75A or S75/123A) proteins is not sufficient to overcome this checkpoint. We propose that regulation of human Cdc25A stability by its phosphorylation at S75 may contribute to S phase checkpoint activation only in cooperation with other regulatory mechanisms. C1 [Goloudina, Anastasia; Chervyakova, Daria B.; Fornace, Albert J., Jr.; Bulavin, Dmitry V.] NCI, Gene Response Sect, NIH, Bethesda, MD 20892 USA. [Yamaguchi, Hiroshi; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Goloudina, Anastasia] Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. RP Bulavin, DV (reprint author), NCI, Gene Response Sect, NIH, Bethesda, MD 20892 USA. EM bulavin@nih.gov RI Chervyakova, Darya/K-7148-2013 OI Chervyakova, Darya/0000-0002-4984-6176 NR 20 TC 69 Z9 71 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 5 BP 473 EP 478 DI 10.4161/cc.2.5.482 PG 6 WC Cell Biology SC Cell Biology GA V43OT UT WOS:000209691400024 PM 12963847 ER PT J AU Ostap, EM Maupin, P Doberstein, SK Baines, IC Korn, ED Pollard, TD AF Ostap, EM Maupin, P Doberstein, SK Baines, IC Korn, ED Pollard, TD TI Dynamic localization of myosin-I to endocytic structures in Acanthamoeba SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE motility; cytoskeleton; actin; macropinocytosis; phagocytosis; heterophagy ID RECEPTOR-MEDIATED ENDOCYTOSIS; SUCKER-LIKE STRUCTURES; HEAVY-CHAIN ISOFORM; DICTYOSTELIUM-DISCOIDEUM; MONOCLONAL-ANTIBODIES; UNCONVENTIONAL MYOSIN; ELECTRON-MICROSCOPY; NAEGLERIA-FOWLERI; ACTIN-FILAMENTS; ARP2/3 COMPLEX AB We used fluorescence microscopy of live Acanthamoeba to follow the time course of the concentration of myosin-I next to the plasma membrane at sites of macropinocytosis and phagocytosis. We marked myosin-I with a fluorescently labeled monoclonal antibody (Cy3-M1.7) introduced into the cytoplasm by syringe loading. M1.7 binds myosin-IA and -IC without affecting their activities, but does not bind myosin-IB. Cy3-M1.7 concentrates at two different macropinocytic structures: large circular membrane ruffles that fuse to create macropinosomes, and smaller endocytic structures that occur at the end of stalk-like pseudopodia. These dynamic structures enclose macropinosomes every 30-60 s. Cy3-MI.7 accumulates rapidly as these endocytic structures form and dissipate rapidly after they internalize. Double labeling fixed cells with Cy3-MI.7 and polyclonal antibodies specific for myosin-IA, -IB, or -IC revealed that all three myosin-I isoforms associate with macropinocytic structures, but individual structures vary in their myosin-I isoform composition. Myosin-I and actin also concentrate transiently at sites where amoebae ingest yeast or the pseudopodia of neighboring cells (heterophagy) by the process of phagocytosis. Within 3 min of yeast attachment to the amoeba, myosin-I concentrates around the phagocytic cup, yeast are internalized, and myosin-I de-localizes. Despite known differences in the regulation of macropinocytosis and phagocytosis, the morphology, protein composition, and dynamics of phagocytosis and macropinocytosis are similar, indicating that they share common structural properties and contractile mechanisms. C1 Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Penn Muscle Inst, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol & Anat, Baltimore, MD USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. RP Univ Penn, Sch Med, Dept Physiol, B400 Richards Bldg,3700 Hamilton Walk, Philadelphia, PA 19104 USA. EM ostap@mail.med.upenn.edu RI Korn, Edward/F-9929-2012; OI Aljarah, Ali/0000-0003-0535-090X FU NIGMS NIH HHS [GM-26132, GM-57247] NR 65 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD JAN PY 2003 VL 54 IS 1 BP 29 EP 40 DI 10.1002/cm.10081 PG 12 WC Cell Biology SC Cell Biology GA 629XF UT WOS:000180077000003 PM 12451593 ER PT J AU Perfetti, R Farilla, L Harlan, DH Hirshberg, B AF Perfetti, R Farilla, L Harlan, DH Hirshberg, B TI GLP-1 inhibits pancreatic islet cell apoptosis SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 6th International Congress of the Cell-Transplant-Society CY MAR 02-05, 2003 CL ATLANTA, GEORGIA SP Cell Transplant Soc C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 2 BP 168 EP 169 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CM UT WOS:000182958800062 ER PT J AU Knazek, RA AF Knazek, RA TI Islet cell resource center consortium SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 6th International Congress of the Cell-Transplant-Society CY MAR 02-05, 2003 CL ATLANTA, GEORGIA SP Cell Transplant Soc C1 NIH, Natl Ctr Res Resources, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 2 BP 175 EP 175 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CM UT WOS:000182958800076 ER PT J AU Zaman, V Li, Z Middaugh, L Ramamoorthy, S Rohrer, B Nelson, ME Tomac, AC Hoffer, BJ Gerhardt, GA Granholm, AC AF Zaman, V Li, Z Middaugh, L Ramamoorthy, S Rohrer, B Nelson, ME Tomac, AC Hoffer, BJ Gerhardt, GA Granholm, AC TI The noradrenergic system of aged GDNF heterozygous mice SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT Joint Meeting of the 8th International-Society-for-Neural-Transplantation-and-Repair/9th Annual Conference of the American-Soc-for-Neural-and-Transplantation-and-Repair CY JUN 13-16, 2002 CL KEYSTONE, COLORADO SP Int Soc Neural Transplantat & Repair, Amer Soc Neural Transplantat & Repair DE locus coeruleus; noradrenergic system; glial cell line-derived neurotrophic factor (GDNF); aging; neurotrophic factors ID MIDBRAIN DOPAMINERGIC-NEURONS; NEUROTROPHIC FACTOR GDNF; LOCUS-CERULEUS NEURONS; TGF-BETA SUPERFAMILY; RAT-BRAIN; KINDLING EPILEPSY; LOCOMOTOR TASKS; LACKING GDNF; IMPAIRED ACQUISITION; PARKINSONS-DISEASE AB Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for noradrenergic (NE) neurons of the pontine nucleus locus coeruleus (LC). Decreased function of the LC-NE neurons has been found during normal aging and in neurodegenerative disorders. We have previously shown that GDNF participates in the differentiation of LC-NE neurons during development. However, the continued role of GDNF for LC-NE neurons during maturation and aging has not been addressed. We examined alterations in aged mice that were heterozygous for the GDNF gene (Gdnf(+/-)). Wild-type (Gdnf(+/+)) and Gdnf(+/-) mice (18 months old) were tested for locomotor activity and brain tissues were collected for measuring norepinephrine levels and uptake, as well as for morphological analysis. Spontaneous locomotion was reduced in Gdnf(+/-) mice in comparison with Gdnf(+/+) mice. The reduced locomotor activity of Gdnf(+/-) mice was accompanied by reductions in NE transporter activity in the cerebellum and brain stem as well as decreased norepinephrine tissue levels in the LC. Tyrosine hydroxylase (TH) immunostaining demonstrated morphological alterations of LC-NE cell bodies and abnormal TH-positive fibers in the hippocampus, cerebellum, and frontal cortex of Gdnf(+/-) mice. These findings suggest that the LC-NE system of Gdnf(+/-) mice is impaired and suggest that GDNF plays an important role in continued maintenance of this neuronal system throughout life. C1 Med Univ S Carolina, Dept Physiol & Neurosci, Ctr Aging, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. NIDA, IRP, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat & Neurobiol, Albert B Chandler Med Ctr, Lexington, KY 40536 USA. RP Granholm, AC (reprint author), Med Univ S Carolina, Dept Physiol & Neurosci, Ctr Aging, 173 Ashley Ave, Charleston, SC 29425 USA. FU NEI NIH HHS [EY13520]; NIA NIH HHS [R01 AG015239, AG06434, AG15239]; NIMH NIH HHS [MH 62612, MH01245] NR 70 TC 14 Z9 14 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 3 BP 291 EP 303 PG 13 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CN UT WOS:000182958900010 PM 12797383 ER PT J AU Wahl, SM McCartney-Francis, N Chan, J Dionne, R Ta, L Orenstein, JM AF Wahl, SM McCartney-Francis, N Chan, J Dionne, R Ta, L Orenstein, JM TI Nitric oxide in experimental joint inflammation - Benefit or detriment? SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 2nd Scientific Meeting on Joint and Muscle Dysfunction of the Temporomandibular Joint CY MAY 06-08, 2002 CL BETHESDA, MARYLAND SP Temporomandibular Joint Assoc DE nitric oxide; inflammation; arthritis; tumor necrosis factor; temporomandibular joint disorder ID WALL-INDUCED ARTHRITIS; TUMOR-NECROSIS-FACTOR; TEMPOROMANDIBULAR-JOINT; SYNOVIAL-FLUID; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; SYNTHASE; SUPPRESSION; DISORDERS; INHIBITOR AB The host response to infection or injury initiates a cascade of events involving recruitment of leukocytes and the release of multiple inflammatory mediators. One of these mediators, nitric oxide (NO), not only represents an important microbicidal agent in host defense, but also functions as a biological signaling and effector molecule in inflammation and immunity. However, overproduction of NO can be autotoxic and contribute to tissue damage and has been implicated in pathogenesis of tumors, and infectious, autoimmune and chronic degenerative diseases. NO is generated via constitutive and inducible nitric oxide synthases (iNOS) which catalyze the oxidation of a guanidino nitrogen associated with L-arginine. Whereas endothelial NOS (eNOS) and neuronal NOS (nNOS) are constitutively expressed, iNOS is transcriptionally induced by bacterial constituents and inflammatory mediators, including TNFalpha and IL-1. In an experimental model of bacterial component-induced joint inflammation and tissue degradation, functionally distinct roles of the constitutive NOS and iNOS were demonstrated. Following systemic delivery of an arthritogenic dose of streptococcal cell walls (SCW), these bacterial peptidoglycan-polysaccharide complexes disseminate and target the peripheral joints, liver and spleen of the treated animals. Following deposition of the SCW in the peripheral joints, an initial innate inflammatory response to the bacterial components progresses into an adaptive immune response with the recruitment and activation of mononuclear phagocytes and T lymphocytes. With the release of cytokines and inflammatory mediators, there is an upregulation of gene expression for iNOS, but not the constitutive nNOS or eNOS. Nonetheless, the constitutive NOS isoforms, regulated by calcium fluxes and interaction with calmodulin, may also enhance NO production. Increased release of NO was detected not only in the synovium, but also in the circulation, and plasma levels of nitrate plus nitrite, the stable products of NO reactions, correlated with disease progression. Following inhibition of NO production with nonspecific NOS inhibitors, such as N-G-monomethyl-L-arginine, which target all three isoforms, there is a striking therapeutic benefit with reduced signs and symptoms of erosive arthritis. In contrast, selective targeting of iNOS with N-iminoethyl-L-lysine resulted in exacerbation of the synovial inflammation and degradation of joint structures. Based on these data, it appears that the constitutive isoforms of NOS contribute to the pathophysiology of the arthropathy, and that induced NOS and NO may function, in part, in a protective pathway. Moreover, the suppression of NO following treatment with TNFalpha antagonists results in reduced inflammation and the associated synovial pathology. Collectively, these data implicate discrete roles for the NOS isoforms in the emergence of local tissue pathology and underscore the need to define the specific pathways that are being targeted for interventional strategies. Copyright (C) 2003 S. Karger AG, Basel. C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC USA. RP Wahl, SM (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 36 TC 46 Z9 49 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2003 VL 174 IS 1-2 BP 26 EP 33 DI 10.1159/000070572 PG 8 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 691ZJ UT WOS:000183635600004 PM 12784039 ER PT B AU Read, EJ AF Read, EJ BE Sibinga, CTS DeLeij, LFM TI The new regulatory environment for cellular therapy products: Challenges for academic-based manufacturing facilities SO CELLULAR ENGINEERING AND CELLULAR THERAPIES SE DEVELOPMENTS IN HEMATOLOGY AND IMMUNOLOGY LA English DT Proceedings Paper CT 27th International Symposium on Blood Transfusion CY 2002 CL Groningen, NETHERLANDS SP Sanquin Div Blood Bank, WHO, Int Soc Blood Transfus, Sanquin Blood Supply Fdn C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Read, EJ (reprint author), NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-1713-8 J9 DEV HEMATOL PY 2003 VL 38 BP 45 EP 54 PG 10 WC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology SC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology GA BAJ86 UT WOS:000222604800006 ER PT B AU Solomon, SR Barrett, AJ AF Solomon, SR Barrett, AJ BE Sibinga, CTS DeLeij, LFM TI Reconstituting T cell immunity following hematopoietic stem cell transplantation SO CELLULAR ENGINEERING AND CELLULAR THERAPIES SE DEVELOPMENTS IN HEMATOLOGY AND IMMUNOLOGY LA English DT Proceedings Paper CT 27th International Symposium on Blood Transfusion CY 2002 CL Groningen, NETHERLANDS SP Sanquin Div Blood Bank, WHO, Int Soc Blood Transfus, Sanquin Blood Supply Fdn ID BONE-MARROW-TRANSPLANTATION; UNMANIPULATED GRAFTS; LYMPHOCYTE SUBSETS; THYMIC FUNCTION; IN-VIVO; REPERTOIRE; BLOOD; RECIPIENTS; EXPANSION; INTERLEUKIN-7 C1 NHLBI, Hematol Branch, Stem Cell Allotransplantat Sect, NIH, Bethesda, MD 20892 USA. RP Solomon, SR (reprint author), NHLBI, Hematol Branch, Stem Cell Allotransplantat Sect, NIH, Bethesda, MD 20892 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-1713-8 J9 DEV HEMATOL PY 2003 VL 38 BP 161 EP 169 PG 9 WC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology SC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology GA BAJ86 UT WOS:000222604800017 ER PT J AU Cho-Chung, YS AF Cho-Chung, YS TI Antisense protein kinase a RI alpha-induced tumor reversion: Portrait of a microarray SO CELLULAR & MOLECULAR BIOLOGY LETTERS LA English DT Article; Proceedings Paper CT 3rd International Conference on Inhibitors of Protein Kinases/Workshop on Phosphoral-Transfer Mechanisms CY JUN 22-28, 2003 CL WARSAW, POLAND SP Int Union Biochem & Mol Biol, Int Ctr Genet Engn & Biotechnol, Novartis Pharma AG, D Western Therapeut Inst, Lilly Res Labs, Discovery Chem Res, Polish Acad Sci, Comm Biochem & Biophys, ProQinase GmbH, Symbios Sp z o o, Schering AG Berlin, Struct Biol Div C1 NCI, NIH, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CELLULAR & MOLECULAR BIOLOGY LETTERS PI WROCLAW PA UNIV WROCLAW, INST BIOCHEM, DEPT GENETIC BIOCHEMISTRY, PRZBYSZEWSKIEGO 63/77, 51-148 WROCLAW, POLAND SN 1425-8153 J9 CELL MOL BIOL LETT JI Cell. Mol. Biol. Lett. PY 2003 VL 8 IS 2A BP 510 EP 511 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 701KH UT WOS:000184166400003 ER PT J AU Xia, QS Chou, MW Kadlubar, FF Chan, PC Fu, PP AF Xia, QS Chou, MW Kadlubar, FF Chan, PC Fu, PP TI Human liver microsomal metabolism and DNA adduct formation of the tumorigenic pyrrolizidine alkaloid, riddelliine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID FLAVIN-CONTAINING MONOOXYGENASE; PROTEIN CROSS-LINKS; MAMMALIAN-CELLS; N-OXIDATION; GUINEA-PIG; RAT-LIVER; IN-VITRO; SENECIONINE; BIOACTIVATION; TOXICITY AB Riddelliine, a widespread naturally occurring genotoxic pyrrolizidine alkaloid, induced liver tumors in rats and mice in an NTP 2-year carcinogenicity bioassay. We have determined that riddelline induces liver tumors in rats through a genotoxic mechanism involving the formation of (+/-)-6,7-dlhydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), which reacts with DNA to form a set of eight DNA adducts. To determine the relevance to humans of the results obtained in experimental animals, the metabolism of riddelline was conducted using human liver microsomes. As with rat liver microsomes, DHP and riddelline N-oxide were major metabolites in incubations conducted with human liver microsomes. The levels of DHP and riddelliine N-oxide were 0.20-0.62 and 0.03-0.15 nmol/min/mg protein, respectively, which are comparable to those obtained from rat liver microsomal metabolism. When metabolism was conducted in the presence of calf thymus DNA, the same set of eight DHP-derived DNA adducts was formed. Both the metabolism pattern and DNA adduct profile were very similar to those obtained from rat liver microsomes. When metabolism was conducted in the presence of the P450 3A4 enzyme inhibitor triacetyleandomycin, the formation of DHP and riddelline N-oxide was reduced 84 and 92%, respectively. For DHP formation, the K-m values were determined to be 0.37 +/- 0.05 and 0.66 +/- 0.08 mM from female rats and female humans; the V-max values from female rat and human liver microsomal metabolism were 0.48 +/- 0.03 and 1.70 +/- 0.09 nmol/min/mg protein, respectively. These results strongly indicate the mechanistic data on liver tumor induction obtained for riddelliine in laboratory rodents is highly relevant to humans. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 43 TC 47 Z9 48 U1 0 U2 12 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 JAN PY 2003 VL 16 IS 1 BP 66 EP 73 DI 10.1021/tx025605i PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 638PC UT WOS:000180578600009 PM 12693032 ER PT J AU Blumenthal, R Clague, MJ Durell, SR Epand, RM AF Blumenthal, R Clague, MJ Durell, SR Epand, RM TI Membrane fusion SO CHEMICAL REVIEWS LA English DT Review ID INFLUENZA-VIRUS HEMAGGLUTININ; HOMOTYPIC VACUOLE FUSION; VIRAL ENVELOPE PROTEIN; INDUCED CELL-FUSION; MEDIATED FUSION; SNARE COMPLEX; CONFORMATIONAL CHANGE; ELECTRON-MICROSCOPY; ENDOSOME FUSION; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE C1 Canc Res Ctr, Natl Canc Inst, NIH, Ft Detrick, MD 21702 USA. Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. McMaster Univ, Dept Biochem, Hamilton, ON L8N 3Z5, Canada. RP Blumenthal, R (reprint author), Canc Res Ctr, Natl Canc Inst, NIH, POB B,Bldg 469,Rm 216A,Miller Dr, Ft Detrick, MD 21702 USA. OI Clague, Michael/0000-0003-3355-9479 NR 204 TC 192 Z9 195 U1 3 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 J9 CHEM REV JI Chem. Rev. PD JAN PY 2003 VL 103 IS 1 BP 53 EP 69 DI 10.1021/cr000036+ PG 17 WC Chemistry, Multidisciplinary SC Chemistry GA 634BF UT WOS:000180319600003 PM 12517181 ER PT J AU Hurley, JH AF Hurley, JH TI Membrane proteins: Adapting to life at the interface SO CHEMISTRY & BIOLOGY LA English DT Editorial Material ID PHOSPHATIDYLINOSITOL PHOSPHATE KINASE; CRYSTAL-STRUCTURE AB A recent publication by Cravatt and colleagues which describes the structure of an integral membrane protein (FAAH) highlights that the structural differences between membrane proteins and soluble proteins are not as disparate as is sometimes believed. C1 NIDDKD, Mol Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 10 TC 6 Z9 6 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JAN PY 2003 VL 10 IS 1 BP 2 EP 3 DI 10.1016/S1074-5521(03)00006-1 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 680AP UT WOS:000182954400002 PM 12573692 ER PT J AU Abraham, AT Lin, JJ Newton, DL Rybak, S Hecht, SM AF Abraham, AT Lin, JJ Newton, DL Rybak, S Hecht, SM TI RNA cleavage and inhibition of protein synthesis by bleomycin SO CHEMISTRY & BIOLOGY LA English DT Article ID TUMOR-CELL-LINES; CYTOTOXIC RIBONUCLEASE; P-30 PROTEIN; STRAND SCISSION; DRUG SCREEN; IN-VITRO; ANGIOGENIN; MECHANISM; DNA; INACTIVATION AB Bleomycin is a clinically used antitumor antibiotic long thought to function therapeutically at the level of DNA cleavage. Recently, it has become clear that bleomycin can also cleave selected members of all major classes of RNA. Using the computer program COMPARE to search the database established by the Anticancer Drug Screening Program of the National Cancer Institute, a possible mechanism-based correlation was found between onconase, an antitumor ribonuclease currently being evaluated in phase III clinical trials, and the chemotherapeutic agent bleomycin. Following these observations, experimentation revealed that bleomycin caused tRNA cleavage and DNA-independent protein synthesis inhibition in rabbit reticulocyte lysate and when microinjected into Xenopus oocytes. The correlation of protein synthesis inhibition to the previously reported site-specific RNA cleavage caused by bleomycin supports the thesis that RNA cleavage may constitute an important element of the mechanism of action of bleomycin. C1 Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22901 USA. NCI, Lab Biochem Physiol, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Hecht, SM (reprint author), Univ Virginia, Dept Chem, Mccormick Rd, Charlottesville, VA 22901 USA. FU NCI NIH HHS [CA76297, N01-CO-56000] NR 51 TC 40 Z9 43 U1 4 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JAN PY 2003 VL 10 IS 1 BP 45 EP 52 DI 10.1016/S1074-5521(02)00306-X PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 680AP UT WOS:000182954400007 PM 12573697 ER PT J AU Towbin, KE AF Towbin, KE TI Strategies for phan-nacologic treatment of high functioning autism and Asperger syndrome SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; SEROTONIN REUPTAKE INHIBITORS; POSITRON-EMISSION-TOMOGRAPHY; DOUBLE-BLIND; MENTAL-RETARDATION; OPEN-LABEL; SELF-INJURY; OPEN TRIAL; CHILDREN; ADULTS AB There are valuable strategies that can be applied when providing medication to individuals with Asperger syndrome (AS) and high functioning autism (HFA). The treatment of complex, polymorphous disorders like HFA/AS always brings particular challenges to pharmacotherapy. The specific characteristics presented by HFA/AS introduce unique complications and place unusual demands on a clinician's skill and experience. Setting realistic expectations, working closely with parents and schools, and optimizing home and school programs are beneficial. Targeting symptom clusters, tracking them carefully, and placing them into a priority system that is based on the risks and impairment are necessary For HFA/AS it is particularly useful to coordinate behavioral and pharmacologic objectives. C1 NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Psychiat, Washington, DC 20010 USA. George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Behav Sci, Washington, DC 20010 USA. George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. RP Towbin, KE (reprint author), NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, Bldg 10,Room 3 S 228A,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 86 TC 30 Z9 30 U1 2 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2003 VL 12 IS 1 BP 23 EP + AR PII S1056-4993(02)0049-4 DI 10.1016/S1056-4993(02)00049-4 PG 24 WC Psychiatry SC Psychiatry GA 629CQ UT WOS:000180033200005 PM 12512397 ER PT J AU Modi, WS Serdyukova, NA Vorobieva, NV Graphodatsky, AS AF Modi, WS Serdyukova, NA Vorobieva, NV Graphodatsky, AS TI Chromosomal localization of six repeated DNA sequences among species of Microtus (Rodentia) SO CHROMOSOME RESEARCH LA English DT Article DE fluorescence in-situ hybridization; heterochromatin; highly repeated DNA; Microtus; sex chromosome ID TANDEM SATELLITE ARRAY; VOLE MICROTUS; ARVICOLIDAE MAMMALIA; SEX-CHROMOSOMES; COMMON VOLE; HETEROCHROMATIN; EVOLUTION; CHROTORRHINUS; AMPLIFICATION; HETEROGENEITY AB C-banding and fluorescence in situ hybridization (FISH) document the distribution of constitutive heterochromatin and six highly repeated DNA families (MSAT2570, MSAT21, MSAT160, MS2, MS4 and STR47) in the chromosomes of nine species of Microtus (M. chrotorrhinus, M. rossiaemeridionalis, M. arvalis, M. ilaeus, M. transcaspicus, M. cabrerae, M. pennsylvanicus, M. miurus and M. ochrogaster). Autosomal heterochromatin is largely centromeric and contains different repeated families in different species. Similarly, large C-band positive blocks on the sex chromosomes of four species contain different repeated DNAs. This interspecific variation in the chromosomal distribution and copy number of the repeats suggests that a common ancestor to modern species contained most of the repetitive families, and that descendant species selectively amplified or deleted different repeats on different chromosomes. C1 NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. RP Modi, WS (reprint author), NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RI Graphodatsky, Alexander/B-4922-2010; Serdyukova, Natalia/N-6476-2015; Vorobieva, Nadezhda/N-6461-2015 OI Graphodatsky, Alexander/0000-0002-8282-1085; FU NCI NIH HHS [N01-CO-124000] NR 27 TC 18 Z9 19 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PY 2003 VL 11 IS 7 BP 705 EP 713 DI 10.1023/A:1025922813756 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 726VH UT WOS:000185621500007 PM 14606632 ER PT J AU Munoz, E Baler, R AF Munoz, E Baler, R TI The circadian E-box: When perfect is not good enough SO CHRONOBIOLOGY INTERNATIONAL LA English DT Review DE review; circadian transcription; E-box ID LOOP-HELIX PROTEINS; KINASE-I-EPSILON; DNA-BINDING; RESPONSE ELEMENT; GENE-EXPRESSION; C-MYC; SUPRACHIASMATIC NUCLEUS; TRANSCRIPTION FACTORS; REGULATORY ELEMENTS; DROSOPHILA-MELANOGASTER AB Life on earth has evolved on a photic carousel, spinning through alternating periods of light and darkness. This playful image belies the fact that only those organisms that learned how to benefit from the recurring features in their environment were allowed to ride on. This selection process has engendered many daily rhythms in our biosphere, most of which rely on the anticipatory power of an endogenously generated marker of phase: the biological clock. The basic mechanisms driving this remarkable device have been really tough to decode but are finally beginning to unravel as chronobiologists probe deeper and wider in and around the recently discovered gears of the clock. Like its chemical predecessors, biological circadian oscillators are characterized by interlaced positive and negative feedback loops, but with constants and variables carefully balanced to achieve an approximately 24h period. The loops at the heart of these biological oscillators are sustained by specific patterns of gene expression and precisely tuned posttranscriptional modifications. It follows that a molecular understanding of the biological clock hinges, in no small measure, on a better understanding of the cis-acting elements that bestow a given gene with its circadian properties. The present review summarizes what is known about these elements and what remains to be elucidated. C1 NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Baler, R (reprint author), NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. OI Munoz, Estela/0000-0002-6701-1535 NR 109 TC 32 Z9 32 U1 2 U2 6 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0742-0528 J9 CHRONOBIOL INT JI Chronobiol. Int. PY 2003 VL 20 IS 3 BP 371 EP 388 DI 10.1081/CBI-120022525 PG 18 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 698WU UT WOS:000184023000001 PM 12868535 ER PT J AU Navoa, JAD Laal, S Pirofski, LA McLean, GR Dai, ZD Robbins, JB Schneerson, R Casadevall, A Glatman-Freedman, A AF Navoa, JAD Laal, S Pirofski, LA McLean, GR Dai, ZD Robbins, JB Schneerson, R Casadevall, A Glatman-Freedman, A TI Specificity and diversity of antibodies to Mycobacterium tuberculosis arabinomannan SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; NONTUBERCULOUS MYCOBACTERIA; ORGAN DISTRIBUTION; ANTIGENS; LIPOARABINOMANNAN; POLYSACCHARIDE; RESPONSES; RECEPTOR; CHILDREN; BINDING AB Arabinomannan (AM) is a polysaccharide antigen of the mycobacterial capsule. However, it is uncertain whether AM constitutes an immunologically distinct fraction of Mycobacterium tuberculosis. In this study, we analyzed the repertoire and specificity of antibodies to AM by using AM-binding murine monoclonal antibodies (MAbs) and human serum samples. Murine MAbs were found to be diverse in their specificity to AM and cross-reactivity with other arabinose-containing mycobacterial polysaccharides, with MAb 9d8 binding exclusively to AM. Human antibodies to AM were detected in serum samples from patients with pulmonary tuberculosis (TB), as well as in those from healthy, purified protein derivative-negative controls, with significantly higher titers among patients. The binding of human antibodies to AM was inhibited by MAb 9d8 in three patients with TB but not in controls. MAb 5c11, which recognizes other mycobacterial arabinose-containing carbohydrates in addition to AM, inhibited the binding of serum samples from 75% of patients and 76% of controls. Analysis of human antibodies with murine MAbs to human Vu determinants demonstrated diversity among antibodies to AM with qualitative and quantitative differences compared with antibodies to lipoarabinomannan. In summary, our study suggests that antibodies to AM are diverse and heterogeneous with respect to antigen recognition and V-II determinant expression, with human serum samples containing different subsets of antibodies to AM with the specificities of AM-binding murine MAbs. One MAb and a subset of human antibodies bind AM specifically, suggesting that this polysaccharide is antigenically distinct and is expressed in human infection. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Pediat, Div Infect Dis, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. NYU, Sch Med, Dept Pathol, New York, NY USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Glatman-Freedman, A (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Pediat, Div Infect Dis, Golding Bldg,Room 702,1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NHLBI NIH HHS [HL059842, R01 HL059842]; NIAID NIH HHS [R01 AI033774, AI001691, AI033142, AI033774, AI035370, AI044374, AI045459, AI053192, K08 AI001691, R01 AI033142, R01 AI035370, R01 AI044374, R01 AI045459, R03 AI053192, R37 AI033142] NR 37 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JAN PY 2003 VL 10 IS 1 BP 88 EP 94 DI 10.1128/CDLI.10.1.88-94.2003 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 636PL UT WOS:000180465000015 PM 12522045 ER PT J AU Brewer, MA Johnson, K Follen, M Gershenson, D Bast, R AF Brewer, MA Johnson, K Follen, M Gershenson, D Bast, R TI Prevention of ovarian cancer: Intraepithelial neoplasia SO CLINICAL CANCER RESEARCH LA English DT Review ID GROWTH-FACTOR-RECEPTOR; PROPHYLACTIC OOPHORECTOMY SPECIMENS; SURFACE EPITHELIAL-CELLS; IN-VIVO; FLUORESCENCE SPECTROSCOPY; DIFFUSE-REFLECTANCE; ORAL-CONTRACEPTIVES; MUTATION CARRIERS; CARCINOMA CELLS; RETINOIC ACID AB To reduce the incidence and mortality associated with invasive cancers, the Intraepithelial Neoplasia (IEN) Task Force recommends that carcinogenesis be viewed as a disease that requires treatment. This publication outlines the current knowledge of IEN of the ovary and reviews chemoprevention possibilities for ovarian cancer. Ovarian cancer has the highest mortality of all of the gynecological cancers and is the fourth leading cause of death from cancer in women. The IEN Task Force has defined precancer as a noninvasive lesion that has genetic abnormalities, loss of cellular control functions, and some phenotypic characteristics of invasive cancer with a substantial likelihood of developing invasive cancer. The IEN Task Force recommends targeting moderate to severe dysplasia for new IEN treatment agents in clinical trials. Ovarian cancer does not have a clear preinvasive lesion yet merits considerable study for new prevention strategies because of the high mortality associated with ovarian cancer. There is a great unmet clinical need for treatments that can prevent ovarian cancer by providing nonsurgical options that treat the entire epithelial layer. New prevention strategies hold significant promise to reduce the mortality from ovarian cancer. C1 Univ Arizona, Arizona Canc Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Tucson, AZ 85724 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Translat Res, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Obstet Gynecol & Reprod Sci, Houston, TX 77030 USA. RP Brewer, MA (reprint author), Univ Arizona, Arizona Canc Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, 1515 N Campbell Ave,Salmon Bldg,Room 1968, Tucson, AZ 85724 USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 107 TC 50 Z9 54 U1 0 U2 2 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 JAN PY 2003 VL 9 IS 1 BP 20 EP 30 PG 11 WC Oncology SC Oncology GA 635ZT UT WOS:000180430600003 PM 12538447 ER PT J AU Jones, MB Michener, CM Blanchette, JO Kuznetsov, VA Raffeld, M Serrero, G Emmert-Buck, MR Petricoin, EF Krizman, DB Liotta, LA Kohn, EC AF Jones, MB Michener, CM Blanchette, JO Kuznetsov, VA Raffeld, M Serrero, G Emmert-Buck, MR Petricoin, EF Krizman, DB Liotta, LA Kohn, EC TI The granulin-epithelin precursor/PC-cell-derived growth factor is a growth factor for epithelial ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GRANULIN/EPITHELIN PRECURSOR; GENE-EXPRESSION; FACTOR PCDGF; FACTOR-BETA; IN-VITRO; CARCINOMA; TUMORS; CDNA; SEQUENCE; LINE AB Purpose: The role of growth factors in ovarian cancer development and progression is complex and multifactorial. We hypothesized that new growth factors may be identified through the molecular analysis of ovarian tumors as they exist in their native environment. Experimental Design: RNA extracted from microdissected serous low malignant potential (LMP) and invasive ovarian tumors was used to construct cDNA libraries. A total of 7300 transcripts were randomly chosen for sequencing, and those transcripts were statistically evaluated. Reverse transcription-PCR and immunohistochemistry were used to validate the findings in tumor tissue samples. Ovarian cancer cell lines were used to test gene effects on monolayer growth, proliferative capacity, and density-independent growth. Results: Analysis of the pooled library transcripts revealed 26 genes differentially expressed between LMP and invasive ovarian cancers. The granulin-epithelin precursor [GEP/PC-cell derived growth factor (PCDGF)] was expressed only in the invasive ovarian cancer libraries (P < 0.028) and was absent in the LMP libraries (0 of 2872 clones). All of the invasive tumor epithelia, 20% of the LMP tumor epithelia, and all of the stroma from both subsets expressed GEP by reverse transcription-PCR. Immunohistochemical staining for GEP was diffuse and cytosolic in invasive ovarian cancer tumor cells compared with occasional, punctate, and apical staining in LMP tumor epithelia. Antisense transfection of GEP into ovarian cancer cell lines resulted in down-regulation of GEP production, reduction in cell growth (P < 0.002), decrease in the S-phase fraction (P < 0.04), and loss of density-independent growth potential (P < 0.01). Conclusion: cDNA library preparation from microdissected tumor epithelium provided a selective advantage for the identification of growth factors for epithelial ovarian cancer. Differential granulin expression in tumor samples and the antiproliferative effects of its antisense down-regulation suggest that GEP may be a new autocrine growth factor and molecular target for epithelial ovarian cancer. C1 NCI, Mol Signaling Sect, Pathol Lab, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Kohn, EC (reprint author), NCI, Mol Signaling Sect, Pathol Lab, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 39 TC 55 Z9 60 U1 0 U2 1 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 JAN PY 2003 VL 9 IS 1 BP 44 EP 51 PG 8 WC Oncology SC Oncology GA 635ZT UT WOS:000180430600006 PM 12538450 ER PT J AU Haas, NB Smith, M Lewis, N Littman, L Yeslow, G Joshi, ID Murgo, A Bradley, J Gordon, R Wang, H Rogatko, A Hudes, GR AF Haas, NB Smith, M Lewis, N Littman, L Yeslow, G Joshi, ID Murgo, A Bradley, J Gordon, R Wang, H Rogatko, A Hudes, GR TI Weekly bryostatin-1 in metastatic renal cell carcinoma: A phase II study SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; GROWTH-FACTOR RECEPTOR; FACTOR-ALPHA; CANCER; INTERLEUKIN-6; SURVIVAL; MALIGNANCY; EXPRESSION; PROGNOSIS; TRIAL AB Purpose: We conducted a Phase II trial of bryostatin-1, an inhibitor of protein kinase C, in advanced renal cell carcinoma to measure toxicity, response rate, time to progression, and induction of cytokines. Experimental Design: A total of 32 patients (26 male and 6 female) received bryostatin-1 at 35-40 mug/m(2) i.v. over 1 h on days 1, 8, and 15 of each 4-week cycle. Plasma interleukin-6, tumor necrosis factor-alpha, and C-reactive protein levels were assayed pretreatment, 1 and 23 h after completion of bryostatin-1 infusion at weeks 1 and 5. Results: Cycles (102) of bryostatin-1 were given (median 2, range 1-8). The most common grade 1 or 2 toxicities were myalgias (46.8%), fatigue (59.3%), and dyspnea (18.8%). Grade 3-4 toxicity included myalgias (40.6%), ataxia (9.3%), and dyspnea (15.6%). Four (12%) patients experienced cardiac events while on study (cardiac arrhythmias and congestive heart failure occurred in 2 patients, an 2 patients had fatal cardiac arrests). Of 32 patients evaluable for response, 2 (6.3%) had partial responses lasting 9 with 6 months. A total of 15 patients (46.8%) had stable disease, and 6 (18.8%) patients had stable disease for 6 months. Plasma interleukin-6 increased greater than or equal to2-fold over baseline measurements in 5 of 17 patients (29.4%) but did not correlate with response or toxicity. Conclusions: Although weekly bryostatin-1 at 35-40 mug/m(2) produced a low proportion of objective responses, prolonged (>6 months) stable disease or partial remission in 25% of patients suggests that this agent, or other inhibitors of protein kinase C, may have a role in the treatment of renal cell carcinoma, perhaps in combination with other agents. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Pinnacle Canc Ctr, Harrisburg, PA USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Haas, NB (reprint author), Dept Med Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. RI Rogatko, Andre/A-8099-2008; OI Smith, Mitchell/0000-0003-1428-8765 NR 29 TC 24 Z9 25 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 JAN PY 2003 VL 9 IS 1 BP 109 EP 114 PG 6 WC Oncology SC Oncology GA 635ZT UT WOS:000180430600014 PM 12538458 ER PT J AU Yang, XW Groshen, S Formenti, SC Davidson, NE Press, MF AF Yang, XW Groshen, S Formenti, SC Davidson, NE Press, MF TI P7 antigen expression in human breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY; CARCINOMAS; CELLS AB Purpose: Evaluate p7 expression in human breast cancer and determine whether chemotherapy and radiation therapy effect a change in p7 expression. Experimental Design: Using a p7-specific monoclonal antibody with immunohistochemistry and Western immunoblot analyses to assess p7 expression in archival, frozen breast cancer specimens both before and after therapy. Results: A novel 7 kDa protein (p7), originally identified in multidrug-resistant ovarian and breast cancer cell lines, was found to be expressed in 21 of 64 (32%) primary, unselected human breast cancer specimens by immunohistochemistry with the use of a p7-specific monoclonal antibody, 1D7. P7 was observed in malignant cells but not in other types of cells in the breast tissue. Western blot analysis confirmed the 7 kDa polypeptide in p7-positive breast carcinomas identified by inummohistochemistry. P7 expression was significantly associated with breast cancers having distant metastasis and/or local recurrence (P = 0.027, Fisher's exact test). In addition, p7 expression was significantly increased in post-treatment breast cancer biopsy specimens compared with pretreatment breast cancer biopsy specimens in patients with locally advanced breast cancer after 5-fluorouracil chemotherapy and radiation therapy [2 of 15 (13%) pretreatment breast cancers compared with 8 of 15 (53%) post-treatment breast cancers; P = 0.016, McNemar's test]. Conclusions: These findings demonstrate that expression of p7 is associated with malignant tumor cells in primary breast cancers, especially those showing recurrent or metastatic disease. Its specific association with the malignant phenotype suggests it may have potential for novel target-based therapies. The markedly increased expression in patients with locally advanced disease after neoadjuvant therapy suggests a role for p7 in treatment outcome. C1 Univ So Calif, Norris Canc Ctr, Dept Pathol, Sch Med, Los Angeles, CA 90033 USA. Univ So Calif, Norris Canc Ctr, Dept Prevent Med, Sch Med, Los Angeles, CA 90033 USA. Univ So Calif, Norris Canc Ctr, Dept Radiat Oncol, Sch Med, Los Angeles, CA 90033 USA. Johns Hopkins Univ, Ctr Oncol, Dept Oncol, Baltimore, MD 21231 USA. NCI, Canc Therapeut Branch, Bethesda, MD 20889 USA. RP Press, MF (reprint author), Univ So Calif, Norris Canc Ctr, Dept Pathol, Sch Med, 1441 Eastlake Ave,NOR 5410, Los Angeles, CA 90033 USA. FU NCI NIH HHS [5P50-CA1409] NR 12 TC 7 Z9 7 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 JAN PY 2003 VL 9 IS 1 BP 201 EP 206 PG 6 WC Oncology SC Oncology GA 635ZT UT WOS:000180430600026 PM 12538470 ER PT J AU Karp, JE Ross, DD Yang, WD Tidwell, ML Wei, YT Greer, J Mann, DL Nakanishi, T Wright, JJ Colevas, AD AF Karp, JE Ross, DD Yang, WD Tidwell, ML Wei, YT Greer, J Mann, DL Nakanishi, T Wright, JJ Colevas, AD TI Timed sequential therapy of acute leukemia with flavopiridol: In vitro model for a phase I clinical trial SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; DEPENDENT KINASE INHIBITOR; BREAST-CARCINOMA CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; HIGH-DOSE CYTARABINE; COUNCIL AML11 TRIAL; RNA-POLYMERASE-II; CONTINUOUS-INFUSION AB Purpose: The survival of adults with acute leukemias remains unsatisfactory and requires new treatment approaches. Flavopiridol modulates cell cycle progression, inhibits transcription, and induces apoptosis. We designed an in vitro model of timed sequential therapy for acute leukemia to determine whether flavopiridol can: (a) trigger apoptosis in fresh acute leukemia; and (b) recruit surviving leukemic cells to a proliferative state, thereby priming such cells for the S-phase-related cytotoxicity of 1-beta-D-arabino-furanosylcytosine (ara-C). Experimental Design: Bone marrow cells from 20 adults with relapsed and refractory acute leukemias were enriched for blasts by Ficoll Hypaque sedimentation. Blasts were cultured on day 0 in flavopiridol 250 nm for 24 h, removed from flavopiridol for 24 h, and then cultured in ara-C 1 mum for an additional 72 h (F(250)A(1)). Apoptosis and cell cycle phase distribution were estimated from cells stained with propidium iodide. Cell survival was determined after the 72 h ara-C exposure by double cytofluorescence assay with fluorescein diacetate and propidium iodide. Results: Flavopiridol induced a 4.3-fold increase in apoptosis in human leukemia samples within the first 24 h of culture. Subsequent removal of flavopiridol led to a 1.7-fold increase in the proportion of cells in S phase by day 2. Mean survival in F(250)A(1) cultures after 72 h exposure to ara-C was 35.6% compared with flavopiridol alone (F(250)A(0), 56.1%; P = 0.0003) and ara-C alone (F(0)A(1), 65.2%; P < 0.00001). Conclusions: Flavopiridol induces apoptosis in marrow blasts from patients with refractory acute leukemias. Furthermore, flavopiridol pretreatment increases the proapoptotic and cytotoxic effects of ara-C. The advantage of sequential FP(250)A(1) over either agent alone is seen for both acute myelogenous leukemia and acute lymphoblastic leukemia. These findings support a clinical trial of timed sequential therapy where flavopiridol is given for cytoreduction and subsequent priming of remaining leukemic cells for enhanced cycle-dependent drug cytotoxicity. C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Baltimore Vet Adm Med Ctr, Baltimore, MD USA. NCI, Invest Drug Branch, Clin Trials Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Karp, JE (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Bunting Blaustein Canc Res Bldg,1650 Orleans St,R, Baltimore, MD 21231 USA. RI Nakanishi, Takeo/C-3891-2015 OI Nakanishi, Takeo/0000-0002-6561-7138 FU NCI NIH HHS [U01 CA69854, R01 CA77545, R24 CA82888] NR 57 TC 44 Z9 44 U1 0 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 JAN PY 2003 VL 9 IS 1 BP 307 EP 315 PG 9 WC Oncology SC Oncology GA 635ZT UT WOS:000180430600039 PM 12538483 ER PT J AU Nelson, KK Ranganathan, AC Mansouri, J Rodriguez, AM Providence, KM Rutter, JL Pumiglia, K Bennett, JA Melendez, JA AF Nelson, KK Ranganathan, AC Mansouri, J Rodriguez, AM Providence, KM Rutter, JL Pumiglia, K Bennett, JA Melendez, JA TI Elevated Sod2 activity augments matrix metalloproteinase expression: Evidence for the involvement of endogenous hydrogen peroxide in regulating metastasis SO CLINICAL CANCER RESEARCH LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; HT-1080 FIBROSARCOMA CELLS; GASTRIC-CANCER; MESSENGER-RNA; TUMOR-CELLS; INHIBITION; ACTIVATION; INVASION; CATALASE; OVEREXPRESSION AB Purpose: Elevated manganese superoxide dismutase (Sod2) levels have been reported to be associated with an increased frequency of tumor invasion and metastasis in certain cancers, and the aim of this study is to examine the molecular mechanisms by which this occurs. Experimental Design: Sod2 and catalase overexpressing HT-1080 fibrosarcoma cell lines were used to evaluate the H2O2-dependent regulation of matrix metalloproteinase (MMP)-1 promoter activity, mitogen-activated protein (MAP) kinase signaling, DNA-binding activity, and MMP mRNA levels. The invasive and metastatic potential of Sod2 overexpressing cells was characterized using subrenal capsular implantation or tail vein injection of tumor cells into nude mice, respectively. Results: Our data reveal that Sod2 overexpression increases the DNA-binding activity of transcription factors critical for MMP expression but also enhances MMP-1 promoter activity via the Ras//MAP/extracellular signal-regulated kinase (MEK) signaling cascade. A single nucleotide polymorphism that creates an Ets site at position - 1607 bp confers Sod2-dependent MMP-1 promoter activity. Sod2 overexpression also increases the mRNA levels of MMPs-2, -3, -7, -10, -9, -11 and enhances the metastatic potential of fibrosarcoma cells when implanted in immunodeficient mice. The Sod2-dependent increases in AP-1 and SP-1 DNA-binding activity, MMP-1 promoter activity, general MMP expression, and collagen degradation can be reversed by the hydrogen peroxide-detoxifying enzyme, catalase. Conclusion: MMPs play a critical role in the process of stromal invasion and metastasis, and these findings suggest that the association between increased Sod2 and poor prognosis in certain cancers may be attributed to elevated MMP production. C1 Wake Forest Univ, Sch Med, Dept Radiat Oncol, Sect Radiat Biol, Winston Salem, NC 27157 USA. Albany Med Coll, Ctr Immunol & Microbial Dis, Albany, NY 12208 USA. Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA. New York State Dept Hlth, Wadsworth Ctr, Div Genet Disorders, Albany, NY 12201 USA. NCI, DCEG, LPG, NIH, Bethesda, MD 20892 USA. RP Melendez, JA (reprint author), Wake Forest Univ, Sch Med, Dept Radiat Oncol, Sect Radiat Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA. OI Rutter, Joni/0000-0002-6502-2361; Pumiglia, Kevin/0000-0003-4655-0334 FU NCI NIH HHS [R01 CA081419] NR 36 TC 88 Z9 93 U1 1 U2 4 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 JAN PY 2003 VL 9 IS 1 BP 424 EP 432 PG 9 WC Oncology SC Oncology GA 635ZT UT WOS:000180430600052 PM 12538496 ER PT J AU Schepers, RJF Oyler, JM Joseph, RE Cone, EJ Moolchan, ET Huestis, MA AF Schepers, RJF Oyler, JM Joseph, RE Cone, EJ Moolchan, ET Huestis, MA TI Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers SO CLINICAL CHEMISTRY LA English DT Article ID SALIVA; DRUGS; ABUSE; METABOLITES; MECHANISMS; EXCRETION; SWEAT AB Background: Methamphetamine (METH) and amphetamine (AMP) concentrations in 200 plasma and 590 oral fluid specimens were used to evaluate METH pharmacokinetics and pharmacodynamics after oral administration of sustained-release METH. Methods: Eight participants received four oral 10-mg S-(+)-METH hydrochloride sustained-release tablets within 7 days. Three weeks later, five participants received four oral 20-mg doses. Blood samples were collected for up to 24 h and oral fluid for up to 72 h after drug administration. Results: After the first oral dose, initial plasma METH detection was within 0.25-2 h; c(max) was 14.5-33.8 mug/L (10 mg) and 26.2-44.3 mug/L (20 mg) within 2-12 h. In oral fluid, METH was detected as early as 0.08-2 h; c(max) was 24.7-312.2 mug/L (10 mg) and 75.3-321.7 mug/L (20 mg) and occurred at 2-12 h. The median oral fluid-plasma METH concentration ratio was 2.0 across 24 h and was highly variable. Neutral cotton swab collection yielded significantly higher METH and AMP concentrations than citric acid candy-stimulated expectoration. Mean (SD) areas under the curve for AMP were 21%+/-25% and 24%+/-11% of those observed for METH in plasma and oral fluid, respectively. After a single low or high dose, plasma METH was >2.5 mug/L for up to 24 h in 9 of 12 individuals (mean, 7.3+/-5.5 mug/L at 24 h); in oral fluid the detection window was at least 24 h (mean, 18.8+/-18.0 mug/L at 24 h). The plasma and oral fluid 24-h METH detection rates were 54% and 60%, respectively. After four administrations, METH was measurable for 36-72 h (mean, 58.3+/-14.5 h). Conclusions: Perceived advantages of oral fluid for verifying METH exposure compared with urine include simpler specimen collection and reduced potential for adulteration, but urine offers higher analyte concentrations and a greater window of detection. (C) 2003 American Association for Clinical Chemistry. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Amgen Inc, Clin Affairs, Thousand Oaks, CA 91320 USA. ConeChem Res, Severna Pk, MD 21146 USA. RP Schepers, RJF (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 33 TC 127 Z9 141 U1 2 U2 16 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2003 VL 49 IS 1 BP 121 EP 132 DI 10.1373/49.1.121 PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 631YK UT WOS:000180195700016 PM 12507968 ER PT J AU Hellerud, C Burlina, A Gabelli, C Ellis, JR Nyholm, PG Lindstedt, S AF Hellerud, C Burlina, A Gabelli, C Ellis, JR Nyholm, PG Lindstedt, S TI Glycerol metabolism and the determination of triglycerides - Clinical, biochemical and molecular findings in six subjects SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE congenital adrenal hypoplasia; glycerol; glycerol-kinase deficiency; missense mutation; splice-site mutation; triglycerides ID CONGENITAL ADRENAL HYPOPLASIA; KINASE-DEFICIENCY; DEHYDROGENASE GENE; FRUCTOSE-1,6-DIPHOSPHATASE DEFICIENCY; PRENATAL-DIAGNOSIS; MUSCULAR-DYSTROPHY; JAPANESE PATIENTS; ESCHERICHIA-COLI; MUTATIONS; COMPLEX AB Recent recommendations in the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATPIII) are expected to increase the number of triglyceride (TG) determinations and consequently the risk of misinterpretation of "non-blanked" results with co-determination of free glycerol. Glycerol-kinase deficiency (GKD) is one cause of falsely elevated TG results. The natural history of isolated GKD with symptom-free cases and cases with e.g. severe episodes of hypoglycemia and/or ketoacidosis challenges the laboratories to identify cases of GKD and family members at risk. "Blanked" methods reporting both glycerol and TG concentration are therefore desirable. Molecular studies of the glycerol kinase (GK) and DAX1 genes were performed on four cases of "persistent hypertriglyceridemia" found in an Italian population and on two pediatric cases with high serum glycerol concentration. Two new missense mutations were found (C358Y, T96I). Molecular modeling on GK from E. coli, indicate that these mutations are located in parts of the enzyme important for enzyme formation or activity. One splice-site mutation, (IVS9A-1G>A), was found in two brothers. Splice-junction analysis indicates that destroys the splice site and results in a mixture of mRNA. Deletion of the GK and DAX1 genes was found in one child with symptoms of adrenal failure. A female with glycerolemia and glyceroluria had normal GK activity but possibly slightly decreased ability to oxidize glycerol. C1 Gothenburg Univ, Sahlgrens Univ Hosp, Dept Clin Chem, S-41345 Gothenburg, Sweden. Univ Padua, Dept Pediat, Padua, Italy. Univ Padua, Dept Internal Med, I-35100 Padua, Italy. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. Gothenburg Univ, Inst Med Biochem, Gothenburg, Sweden. RP Hellerud, C (reprint author), Gothenburg Univ, Sahlgrens Univ Hosp, Dept Clin Chem, S-41345 Gothenburg, Sweden. NR 50 TC 12 Z9 13 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PY 2003 VL 41 IS 1 BP 46 EP 55 DI 10.1515/CCLM.2003.009 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 639ND UT WOS:000180635000009 PM 12636049 ER PT J AU Salerno, M Ouatas, T Palmieri, D Steeg, PS AF Salerno, M Ouatas, T Palmieri, D Steeg, PS TI Inhibition of signal transduction by the nm23 metastasis suppressor: Possible mechanisms SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE breast; metastasis; Nm23; suppressor ID NUCLEOSIDE-DIPHOSPHATE KINASE; SQUAMOUS-CELL CARCINOMA; HUMAN BREAST-CARCINOMA; HUMAN HEPATOCARCINOMA CELLS; GTP-BINDING PROTEINS; NERVE GROWTH-FACTOR; TUMOR-METASTASIS; IN-VITRO; PHOSPHOTRANSFERASE ACTIVITY; DROSOPHILA DEVELOPMENT AB The first metastasis suppressor gene identified was nm23. Transfection of nm23 into metastatic cell lines resulted in the inhibition of metastasis, but not primary tumor size in vivo. 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. Candidate biochemical mechanisms are identified and discussed herein. C1 NCI, Womens Canc Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Salerno, M (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 91 TC 25 Z9 42 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2003 VL 20 IS 1 BP 3 EP 10 DI 10.1023/A:1022578000022 PG 8 WC Oncology SC Oncology GA 648BA UT WOS:000181128900002 PM 12650601 ER PT J AU Ajmani, RS Fleg, JL Demehin, AA Wright, JG O'Connor, F Heim, JM Tarien, E Rifkind, JM AF Ajmani, RS Fleg, JL Demehin, AA Wright, JG O'Connor, F Heim, JM Tarien, E Rifkind, JM TI Oxidative stress and hemorheological changes induced by acute treadmill exercise SO CLINICAL HEMORHEOLOGY AND MICROCIRCULATION LA English DT Article DE exercise; hemorheology; oxidative stress ID ERYTHROCYTE-MEMBRANE; LIPID-PEROXIDATION; BLOOD RHEOLOGY; IN-VIVO; DAMAGE; RATS; HYPERTENSION; MUSCLE; FLOW; ANTIOXIDANTS AB The present investigation was designed to evaluate the acute effect of aerobic exercise on oxidative stress and the flow properties of the blood. Fourteen clinically healthy subjects (7 men and 7 women aged 56+/-19 yr) underwent maximal treadmill exercise with blood samples drawn prior to and immediately after exercise. Post-exercise significant increases were observed in plasma lipid hydroperoxides from 6.5+/-2.0 muM to 7.9+/-1.9 muM (p<0.0001) and the relative concentration of plasma fluorescent products associated with red cell peroxidation from 138+/-28 RF to 220+/-92 RF (p<0.005). After exercise there was a rise in the hematocrit from 41.4+/-3.7% to 44.4+/-4.1% (p<0.0001), increases in whole blood viscosity at shear rates of 22.5/sec to 450/sec (p<0.0005), an increase in plasma viscosity from 1.27+/-0.12 cP to 1.36+/-0.11 cP (p<0.01), an increase in red cell rigidity from 2.44+/-0.48 cP to 2.62+/-0.42 cP (p<0.001) and a decrease in erythrocyte sedimentation rate from 26.9+/-18.6 mm/h to 22.5+/-15.9 mm/h (p<0.01). The findings suggest that acute aerobic exercise induces oxidative damage to red blood cells and adversely affects rheological properties of the peripheral blood. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 53 TC 34 Z9 36 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1386-0291 J9 CLIN HEMORHEOL MICRO JI Clin. Hemorheol. Microcirc. PY 2003 VL 28 IS 1 BP 29 EP 40 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 657GT UT WOS:000181658600004 PM 12632010 ER PT J AU Kuroiwa, T Schlimgen, R Illei, GG Boumpas, DT AF Kuroiwa, T Schlimgen, R Illei, GG Boumpas, DT TI Monocyte response to Th1 stimulation and effector function toward human mesangial cells are not impaired in patients with lupus nephritis SO CLINICAL IMMUNOLOGY LA English DT Article DE systemic lupus erythematosus; monocytes; mesangial cells; Th1; interferon-gamma ID CD40 LIGAND; T-CELLS; INFLAMMATORY RESPONSES; DISEASE-ACTIVITY; ERYTHEMATOSUS; AUTOIMMUNITY; EXPRESSION; INDUCTION; CYTOKINES; IL-12 AB Monocytes/macrophages activated by Th1 stimulation such as interferon-gamma (IFN-gamma) and CD40 ligand (CD40L) infiltrate the kidney and play a critical role in the progression of lupus nephritis (LN). We examined the monocyte response to Th1 stimulation and their effector function toward activating renal resident cells in patients with LN. Following stimulation with IFN-gamma granulocyte macrophage-colony stimulating factor (GM-CSF)/recombinant CD40L the production of tumor necrosis factor-alpha and IL-12 p70 by PBMC was significantly higher in LN patients. In coculture experiments employing activated monocytes and human mesangial cells, there was a trend toward higher monocyte chemoattractant protein-1 production by lupus monocytes compared to normal controls. Basal expression of CD40, ICAM-1, and STAT-1 was significantly higher in monocytes from LN patients, suggesting ongoing activation. Monocyte response to IFN-gamma, as accessed by intercellular adhesion molecule-1 upregulation and phosphorylation of STAT-1, was comparable between the two groups. Thus, in contrast to earlier reports, Th1-dependent monocyte activation is not impaired. In this disease activated monocytes appear to be fully capable of inducing renal injury. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Gunma Univ, Sch Med, Dept Internal Med 3, Maebashi, Gumma 3718500, Japan. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Crete, Iraklion, Greece. RP Kuroiwa, T (reprint author), Gunma Univ, Sch Med, Dept Internal Med 3, 3-35-15 Showa Machi, Maebashi, Gumma 3718500, Japan. NR 27 TC 19 Z9 23 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JAN PY 2003 VL 106 IS 1 BP 65 EP 72 DI 10.1016/S1521-6616(02)00022-0 PG 8 WC Immunology SC Immunology GA 651FB UT WOS:000181308900011 PM 12584053 ER PT J AU Schambra, HM Sawaki, L Cohen, LG AF Schambra, HM Sawaki, L Cohen, LG TI Modulation of excitability of human motor cortex (M1) by 1 Hz transcranial magnetic stimulation of the contralateral M1 SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial magnetic stimulation; physiology; motor system; excitability ID INTERHEMISPHERIC INHIBITION; TRANSCALLOSAL INHIBITION; CORPUS-CALLOSUM; REDUCTION; SYSTEM; AREAS AB Ojective: Previous studies demonstrated that single-pulse transcranial magnetic stimulation (TMS) of one motor cortex (M1) exerts a brief inhibitory effect on the contralateral MI. The purpose of this study was to test the hypothesis that 30 min of 1 Hz TMS of M I will result in a lasting increase in excitability in the contralateral MI. Methods: Healthy volunteers were tested on 2 separate days, before (baseline) and after one of two interventions: (a) stimulation of M1 with 1 Hz TMS for 30 min at 115% of resting motor threshold, and (b) sham stimulation. Recruitment curves to TMS, pinch force, and simple reaction time were assessed in the hand contralateral to the unstimulated motor cortex. Results: The main finding of this study was that 30 min of I Hz significantly increased recruitment curves in the contralateral motor cortex in the real stimulation condition relative to sham (P < 0.005, factorial analysis of variance (ANOVA)). This change outlasted the stimulation period for at least 15 min and occurred in the absence of changes in pinch force or reaction time. Conclusions: These results raise the potential for inducing lasting modulation of excitability in M1 by 1 Hz TMS of the other M1, a phenomenon possibly reflecting modulation of interhemispheric interactions. Significance: It is conceivable that I Hz TMS applied to MI may be used to modulate excitability in the opposite motor cortex for therapeutic purposes. Published by Elsevier Science Ireland Ltd. C1 NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bldg 10,Rm 5N226,10 Ctr Dr,MSC1428, Bethesda, MD 20892 USA. NR 23 TC 102 Z9 103 U1 0 U2 2 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 JAN PY 2003 VL 114 IS 1 BP 130 EP 133 AR PII S1388-2457(02)00342-5 DI 10.1016/S1388-2457(02)00342-5 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 636BN UT WOS:000180434800017 PM 12495773 ER PT J AU ten Tije, AJ Verweij, J Loos, WJ Sparreboom, A AF ten Tije, AJ Verweij, J Loos, WJ Sparreboom, A TI Pharmacological effects of formulation vehicles - Implications for cancer chemotherapy SO CLINICAL PHARMACOKINETICS LA English DT Review ID METASTATIC BREAST-CANCER; CELL LUNG-CANCER; MULTIDRUG-RESISTANCE PHENOTYPE; CREMOPHOR EL MICELLES; ADVANCED SOLID TUMORS; PHASE-I TRIAL; P-GLYCOPROTEIN; CYCLOSPORINE-A; FATTY-ACIDS; ORAL BIOAVAILABILITY AB The non-ionic surfactants Cremophor(R) EL (CrEL; polyoxyethyleneglycerol triricinoleate 35) and polysorbate 80 (Tween(R) 80; polyoxyethylene-sorbitan-20-monooleate) are widely used as drug formulation vehicles, including for the taxane anticancer agents paclitaxel and docetaxel. A wealth of recent experimental data has indicated that both solubilisers are biologically and pharmacologically active compounds, and their use as drug formulation vehicles has been implicated in clinically important adverse effects, including acute hypersensitivity reactions and peripheral neuropathy. CrEL and Tween(R) 80 have also been demonstrated to influence the disposition of solubilised drugs that are administered intravenously. The overall resulting effect is a highly increased systemic drug exposure and a simultaneously decreased clearance, leading to alteration in the pharmacodynamic characteristics of the solubilised drug. Kinetic experiments revealed that this effect is primarily caused by reduced cellular uptake of the drug from large spherical micellar-like structures with a highly hydrophobic interior, which act as the principal carrier of circulating drug. Within the central blood compartment, this results in a profound alteration of drug accumulation in erythrocytes, thereby reducing the free drug fraction available for cellular partitioning and influencing drug distribution as well as elimination routes. The existence of CrEL and Tween(R) 80 in blood as large polar micelles has also raised additional complexities in the case of combination chemotherapy regimens with taxanes, such that the disposition of several coadministered drugs, including anthracyclines and epipodophyllotoxins, is significantly altered. In contrast to the enhancing effects of Tween(R) 80, addition of CrEL to the formulation of oral drug preparations seems to result in significantly diminished drug uptake and reduced circulating concentrations. The drawbacks presented by the presence of CrEL or Tween(R) 80 in drug formulations have instigated extensive research to develop alternative delivery forms. Currently, several strategies are in progress to develop Tween(R) 80- and CrEL-free formulations of docetaxel and paclitaxel, which are based on pharmaceutical (e.g. albumin nanoparticles, emulsions and liposomes), chemical (e.g. polyglutamates, analogues and prodrugs), or biological (e.g. oral drug administration) strategies. These continued investigations should eventually lead to more rational and selective chemotherapeutic treatment. C1 NCI, Med Oncol Clin Res Unit, Ctr Canc Res, Bethesda, MD 20892 USA. Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Erasmus MC, NL-3008 AE Rotterdam, Netherlands. RP Sparreboom, A (reprint author), NCI, Med Oncol Clin Res Unit, Ctr Canc Res, Bldg 10,9000 Rockville Pike,Room 5A01,MSC1910, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008 NR 203 TC 286 Z9 297 U1 5 U2 61 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2003 VL 42 IS 7 BP 665 EP 685 DI 10.2165/00003088-200342070-00005 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 708WM UT WOS:000184593100005 PM 12844327 ER PT J AU Donaldson, MS AF Donaldson, MS TI Applying the institute of medicine's report, Crossing the Quality Chasm, to QOL assessment in clinical practice SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 3rd Conference on Quality of Life - Translating the Science of Quality-of-Life Assessment into Clinical Practice CY OCT 02-04, 2003 CL MAYO CLINIC, SCOTTSDALE, ARIZONA HO MAYO CLINIC C1 NCI, NIH, Rockville, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 2 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. PY 2003 VL 25 SU D MA 35 BP D49 EP D50 DI 10.1016/S0149-2918(03)80279-5 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742LN UT WOS:000186519000037 ER PT J AU Guyatt, G Ferrans, C Halyard, M Revicki, DA Symonds, T Varricchio, C Alonso, J AF Guyatt, G Ferrans, C Halyard, M Revicki, DA Symonds, T Varricchio, C Alonso, J CA Clinical Significance Consensus Me TI What is the value added to the clinician of health-related quality-of-life information from clinical research and using QOL measures in clinical practice? SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 3rd Conference on Quality of Life - Translating the Science of Quality-of-Life Assessment into Clinical Practice CY OCT 02-04, 2003 CL MAYO CLINIC, SCOTTSDALE, ARIZONA HO MAYO CLINIC C1 McMaster Univ, Hlth Sci Ctr, Hamilton, ON, Canada. Univ Illinois, Chicago, IL USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. MEDTAP Int Inc, Bethesda, MD USA. Pfizer Ltd, Sandwich, Kent, England. NCI, NIH, Bethesda, MD 20892 USA. IMIM IMAS, Inst Municipal Invest Med, Mexico City, DF, Mexico. Natl Autonomous Univ Mexico, Mexico City 04510, DF, Mexico. RI Alonso, Jordi/A-5514-2010 OI Alonso, Jordi/0000-0001-8627-9636 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 25 SU D MA 1 BP D6 EP D7 DI 10.1016/S0149-2918(03)80245-X PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742LN UT WOS:000186519000003 ER PT J AU Snyder, CF Gotay, CC Lipscomb, J AF Snyder, CF Gotay, CC Lipscomb, J TI The Cancer Outcomes Measurement Working Group: A panel discussion of findings related to translating quality-of-life assessment into clinical practice SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 3rd Conference on Quality of Life - Translating the Science of Quality-of-Life Assessment into Clinical Practice CY OCT 02-04, 2003 CL MAYO CLINIC, SCOTTSDALE, ARIZONA HO MAYO CLINIC C1 NCI, Bethesda, MD 20892 USA. Univ Hawaii, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 25 SU D MA 17 BP D25 EP D26 DI 10.1016/S0149-2918(03)80261-8 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742LN UT WOS:000186519000019 ER PT J AU Stegon, NR Johnson-Taylor, WL Cleary, SD Young, HA AF Stegon, NR Johnson-Taylor, WL Cleary, SD Young, HA TI Relationship of body mass index, race, age, education, and income to self-reported health-related quality of life in middle-aged women SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 3rd Conference on Quality of Life - Translating the Science of Quality-of-Life Assessment into Clinical Practice CY OCT 02-04, 2003 CL MAYO CLINIC, SCOTTSDALE, ARIZONA HO MAYO CLINIC C1 George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 2003 VL 25 SU D MA 34 BP D48 EP D49 DI 10.1016/S0149-2918(03)80278-3 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742LN UT WOS:000186519000036 ER PT J AU Smith-Arica, JR Thomson, AJ Ansell, R Chiorini, J Davidson, B McWhir, J AF Smith-Arica, JR Thomson, AJ Ansell, R Chiorini, J Davidson, B McWhir, J TI Infection efficiency of human and mouse embryonic stem cells using adenoviral and adeno-associated viral vectors SO CLONING AND STEM CELLS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; VIRUS TYPE-2; GENE-TRANSFER; HUMAN BLASTOCYSTS; TRANSDUCTION; RECEPTOR; DIFFERENTIATION; EXPRESSION; BINDING; LINES AB Human and mouse embryonic stem (ES) cells have the capacity to differentiate into derivatives of all three germ layers, suggesting novel therapies for degenerative, metabolic, and traumatic disorders. ES-based regenerative medicine will be further advanced by the development of reliable methods for transgene introduction and expression. Here, we show infection of human and mouse embryonic stem (ES) cells with two of the most popular vectors in gene transfer, adenovirus type 5 (Ad5) and adeno-associated virus (AAV; serotypes 2, 4, and 5). All vectors express the nuclear-localized marker gene beta-galactosidase expressed from the Rous Sarcoma Virus long terminal repeat (RSV-LTR). Both Ad5 and AAV2 infected human and mouse ES cells and gave rise to beta-galactosidase expression. AAV4 and 5 did not yield detectable levels of beta-galactosidase expression. Quantitative PCR analysis of virally infected human and mouse ES cells revealed that only Ad5 and AAV2 are capable of transducing both cell-types. No viral DNA was detected in cells infected with either AAV4 or AAV5. Infection and subsequent differentiation of mouse and human ES cells with Ad5 showed that beta-galactosidase-expressing cells were restricted to cells in the interior of the embryoid body mass. No beta-galactosidase expression was observed in AAV-infected cells following differentiation. There was no difference in morphology or differentiation patterns between infected and noninfected differentiating mouse and human ES cells. Differentiation of hES cells prior to infection led to transduction of neuronally differentiated cells with good efficiency using all vectors. These data show that Ad5- and AAV2-based vectors are capable of infecting both human and mouse ES cells, in both their undifferentiated and differentiated states, whereas AAV4 and AAV5 can infect human and mouse ES cells only following differentiation. C1 Roslin Inst, Dept Gene Express & Dev, Roslin EH29 5PS, Midlothian, Scotland. Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD USA. Univ Iowa, Coll Med, Dept Internal Med, Program Gene Therapy, Iowa City, IA 52242 USA. RP McWhir, J (reprint author), Roslin Inst, Dept Gene Express & Dev, Roslin EH29 5PS, Midlothian, Scotland. NR 32 TC 68 Z9 69 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1536-2302 J9 CLONING STEM CELLS JI Cloning Stem Cells PY 2003 VL 5 IS 1 BP 51 EP 62 DI 10.1089/153623003321512166 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Genetics & Heredity SC Cell Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 755BV UT WOS:000187384600007 PM 12713701 ER PT J AU Carpenter, MK Rosler, E Rao, MS AF Carpenter, MK Rosler, E Rao, MS TI Characterization and differentiation of human embryonic stem cells SO CLONING AND STEM CELLS LA English DT Review ID KERATAN SULFATE PROTEOGLYCAN; TRANSCRIPTION FACTOR; MONOCLONAL-ANTIBODIES; HEMATOPOIETIC STEM; MOLECULAR-CLONING; NEURAL PRECURSORS; HUMAN BLASTOCYSTS; MAMMALIAN EMBRYO; CARCINOMA-CELLS; TISSUE-CULTURE AB Cell replacement therapies have been limited by the availability of sufficient quantities of cells for transplantation. Human ES (hES) cell lines have recently been generated by several laboratories. When maintained for over 1 year in vitro, they remain karyotypically and phenotypically stable and may therefore provide an excellent source material for cell therapies. Currently, data is available for 26 hES cell lines. Although limited characterization has been performed on most of these lines, there are remarkable similarities in expression of markers. hES cell lines derived in different laboratories show similar expression profiles of surface markers, including SSEA-4, Tra-1-60, and Tra-1-81. In addition, markers associated with pluripotent cells such as OCT-4 are expressed at in all cell lines tested. These cells express high levels of telomerase and appear to have indefinite growth potential. The generation of the large quantities of cells necessary for cell replacement therapies will require a cell population which is stable over long term culture. We have characterized the properties of multiple hES cell lines that have been maintained in culture for extended periods. Quantitative analyses demonstrate that all of the cell lines examined show consistent marker expression and retain a normal karyotype after long-term culture. hES cells have been differentiated into the derivatives of all three germ layers. Specifically this includes cardiomyocytes, neural cells, hepatocyte-like cells, endothelial cells and hematopoietic progenitor cells. These data demonstrating the karyotypic and phenotypic stability of hES cells and their extensive differentiative capacity indicate that they may be an appropriate source of cells for multiple regenerative medicine applications. C1 Geron Corp, Menlo Pk, CA 94025 USA. NIA, Baltimore, MD 21224 USA. RP Carpenter, MK (reprint author), Geron Corp, 230 Constitut Dr, Menlo Pk, CA 94025 USA. NR 49 TC 188 Z9 199 U1 2 U2 20 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1536-2302 J9 CLONING STEM CELLS JI Cloning Stem Cells PY 2003 VL 5 IS 1 BP 79 EP 88 DI 10.1089/153623003321512193 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Genetics & Heredity SC Cell Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 755BV UT WOS:000187384600010 PM 12713704 ER PT J AU Collins, FS AF Collins, FS TI Genome research: The next generation SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 67th Cold Spring Harbor Symposium on Quantitative Biology CY 2003 CL Cold Spring Harbor, NY SP Natl Human Genome Res Inst, Natl Inst Hlth, Natl Canc Inst, US DOE, Amgen Inc, Aventis Pharma AG, Bristol-Myers Squibb Co, Eli Lilly & Co, GlaxoSmithKline, Novartis Pharma AG, Pfizer Inc, Appl Biosyst, AstraZeneca, Bio Ventures Inc, Cogene BioTech Ventures Lt, Diagnost Products Corp, Forest Lab Inc, Johnson & Johnson Pharmaceuit Res & Dev L L C, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Lab, New England BioLabs Inc, OSI Pharmaceut Inc, Pall Corp, Schering-Plough Res Inst, Wyeth Genet Inst C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 3 U1 2 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2003 VL 68 BP 49 EP 54 DI 10.1101/sqb.2003.68.49 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 841YT UT WOS:000222969300007 PM 15338602 ER PT J AU Margulies, EH Green, ED AF Margulies, EH Green, ED CA NISC Comparative Sequencing Progr TI Detecting highly conserved regions of the human genome by multispecies sequence comparisons SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 67th Cold Spring Harbor Symposium on Quantitative Biology CY 2003 CL Cold Spring Harbor, NY SP Natl Human Genome Res Inst, Natl Inst Hlth, Natl Canc Inst, US DOE, Amgen Inc, Aventis Pharma AG, Bristol-Myers Squibb Co, Eli Lilly & Co, GlaxoSmithKline, Novartis Pharma AG, Pfizer Inc, Appl Biosyst, AstraZeneca, Bio Ventures Inc, Cogene BioTech Ventures Lt, Diagnost Products Corp, Forest Lab Inc, Johnson & Johnson Pharmaceuit Res & Dev L L C, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Lab, New England BioLabs Inc, OSI Pharmaceut Inc, Pall Corp, Schering-Plough Res Inst, Wyeth Genet Inst ID REGULATORY ELEMENTS; NONCODING SEQUENCES; MOUSE GENOME; GENE; PREDICTION; CFTR; DNA; ALIGNMENTS; NUCLEOTIDE; STRATEGIES C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NISC, NIH, Bethesda, MD 20892 USA. RP NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 42 TC 12 Z9 14 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2003 VL 68 BP 255 EP 263 DI 10.1101/sqb.2003.68.255 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 841YT UT WOS:000222969300030 PM 15338625 ER PT J AU Rogozin, IB Babenko, VN Fedorova, ND Jackson, JD Jacobs, AR Krylov, DM Makarova, KS Mazumder, R Mekhedov, SL Mirkin, BG Nikolskaya, AN Rao, BS Smirnov, S Sorokin, AV Sverdlov, AV Vasudevan, S Wolf, YI Yin, JJ Natale, DA Koonin, EV AF Rogozin, IB Babenko, VN Fedorova, ND Jackson, JD Jacobs, AR Krylov, DM Makarova, KS Mazumder, R Mekhedov, SL Mirkin, BG Nikolskaya, AN Rao, BS Smirnov, S Sorokin, AV Sverdlov, AV Vasudevan, S Wolf, YI Yin, JJ Natale, DA Koonin, EV TI Evolution of eukaryotic gene repertoire and gene structuret: Discovering the unexpected dynamics of genome evolution SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 67th Cold Spring Harbor Symposium on Quantitative Biology CY 2003 CL Cold Spring Harbor, NY SP Natl Human Genome Res Inst, Natl Inst Hlth, Natl Canc Inst, US DOE, Amgen Inc, Aventis Pharma AG, Bristol-Myers Squibb Co, Eli Lilly & Co, GlaxoSmithKline, Novartis Pharma AG, Pfizer Inc, Appl Biosyst, AstraZeneca, Bio Ventures Inc, Cogene BioTech Ventures Lt, Diagnost Products Corp, Forest Lab Inc, Johnson & Johnson Pharmaceuit Res & Dev L L C, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Lab, New England BioLabs Inc, OSI Pharmaceut Inc, Pall Corp, Schering-Plough Res Inst, Wyeth Genet Inst ID INTRONS-LATE THEORY; SPLICEOSOMAL INTRONS; ISOMERASE GENE; COG DATABASE; CLASSIFICATION; POSITIONS; PROKARYOTES; DIVERGENCE; PROTEINS; ORIGIN C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. Univ London Birkbeck Coll, Sch Informat Syst & Comp Sci, London WC1E 7HX, England. RP Rogozin, IB (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. RI Babenko, Vladimir/K-5609-2014; Abrams, Natalie/F-4845-2011 OI Abrams, Natalie/0000-0001-9698-2819 NR 46 TC 2 Z9 2 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2003 VL 68 BP 293 EP 301 DI 10.1101/sqb.2003.68.293 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 841YT UT WOS:000222969300034 PM 15338629 ER PT J AU Merikangas, KR AF Merikangas, KR TI Implications of Genomics for public health: The role of genetic epidemiology SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 67th Cold Spring Harbor Symposium on Quantitative Biology CY 2003 CL Cold Spring Harbor, NY SP Natl Human Genome Res Inst, Natl Inst Hlth, Natl Canc Inst, US DOE, Amgen Inc, Aventis Pharma AG, Bristol-Myers Squibb Co, Eli Lilly & Co, GlaxoSmithKline, Novartis Pharma AG, Pfizer Inc, Appl Biosyst, AstraZeneca, Bio Ventures Inc, Cogene BioTech Ventures Lt, Diagnost Products Corp, Forest Lab Inc, Johnson & Johnson Pharmaceuit Res & Dev L L C, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Lab, New England BioLabs Inc, OSI Pharmaceut Inc, Pall Corp, Schering-Plough Res Inst, Wyeth Genet Inst ID COMPLEX HUMAN-DISEASES; SAMPLE-SIZE CALCULATIONS; ENVIRONMENT INTERACTIONS; ALZHEIMER-DISEASE; EMERGING IMPORTANCE; RISK-FACTORS; POPULATION; CANCER; FUTURE; LIFE C1 NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Merikangas, KR (reprint author), NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 55 TC 3 Z9 3 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2003 VL 68 BP 359 EP 364 DI 10.1101/sqb.2003.68.359 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 841YT UT WOS:000222969300042 PM 15338637 ER PT J AU Drayna, D Kim, UK Coon, H Jorgenson, E Risch, N Leppert, M AF Drayna, D Kim, UK Coon, H Jorgenson, E Risch, N Leppert, M TI A model system for identifying genes underlying complex traits SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 67th Cold Spring Harbor Symposium on Quantitative Biology CY 2003 CL Cold Spring Harbor, NY SP Natl Human Genome Res Inst, Natl Inst Hlth, Natl Canc Inst, US DOE, Amgen Inc, Aventis Pharma AG, Bristol-Myers Squibb Co, Eli Lilly & Co, GlaxoSmithKline, Novartis Pharma AG, Pfizer Inc, Appl Biosyst, AstraZeneca, Bio Ventures Inc, Cogene BioTech Ventures Lt, Diagnost Products Corp, Forest Lab Inc, Johnson & Johnson Pharmaceuit Res & Dev L L C, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Lab, New England BioLabs Inc, OSI Pharmaceut Inc, Pall Corp, Schering-Plough Res Inst, Wyeth Genet Inst ID PHENYLTHIOCARBAMIDE TASTE SENSITIVITY; HUMAN GENOME; FAMILY; RECEPTORS; MAP C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. RP Drayna, D (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. FU NHGRI NIH HHS [T32 HG00044]; PHS HHS [Z01-000046-04] NR 17 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2003 VL 68 BP 365 EP 371 DI 10.1101/sqb.2003.68.365 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 841YT UT WOS:000222969300043 PM 15338638 ER PT J AU McCallion, AS Emison, ES Kashuk, CS Bush, RT Kenton, M Carrasquillo, MM Jones, KW Kennedy, GC Portnoy, ME Green, ED Chakravarti, A AF McCallion, AS Emison, ES Kashuk, CS Bush, RT Kenton, M Carrasquillo, MM Jones, KW Kennedy, GC Portnoy, ME Green, ED Chakravarti, A TI Genomic variation in multigenic traits: Hirschsprung disease SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 67th Cold Spring Harbor Symposium on Quantitative Biology CY 2003 CL Cold Spring Harbor, NY SP Natl Human Genome Res Inst, Natl Inst Hlth, Natl Canc Inst, US DOE, Amgen Inc, Aventis Pharma AG, Bristol-Myers Squibb Co, Eli Lilly & Co, GlaxoSmithKline, Novartis Pharma AG, Pfizer Inc, Appl Biosyst, AstraZeneca, Bio Ventures Inc, Cogene BioTech Ventures Lt, Diagnost Products Corp, Forest Lab Inc, Johnson & Johnson Pharmaceuit Res & Dev L L C, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Lab, New England BioLabs Inc, OSI Pharmaceut Inc, Pall Corp, Schering-Plough Res Inst, Wyeth Genet Inst ID AMYOTROPHIC-LATERAL-SCLEROSIS; GENE; RET; SEQUENCES; DNA; EXPRESSION; ALIGNMENT; MODEL; MOUSE; IDENTIFICATION C1 Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Affymetrix, Santa Clara, CA 95051 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP McCallion, AS (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. NR 34 TC 20 Z9 20 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2003 VL 68 BP 373 EP 381 DI 10.1101/sqb.2003.68.373 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 841YT UT WOS:000222969300044 PM 15338639 ER PT J AU Chiba-Falek, O Nussbaum, RL AF Chiba-Falek, O Nussbaum, RL TI Regulation of alpha-synuclein expression: Implications for Parkinson's disease SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 67th Cold Spring Harbor Symposium on Quantitative Biology CY 2003 CL Cold Spring Harbor, NY SP Natl Human Genome Res Inst, Natl Inst Hlth, Natl Canc Inst, US DOE, Amgen Inc, Aventis Pharma AG, Bristol-Myers Squibb Co, Eli Lilly & Co, GlaxoSmithKline, Novartis Pharma AG, Pfizer Inc, Appl Biosyst, AstraZeneca, Bio Ventures Inc, Cogene BioTech Ventures Lt, Diagnost Products Corp, Forest Lab Inc, Johnson & Johnson Pharmaceuit Res & Dev L L C, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Lab, New England BioLabs Inc, OSI Pharmaceut Inc, Pall Corp, Schering-Plough Res Inst, Wyeth Genet Inst ID EARLY-ONSET PARKINSONISM; UP-REGULATION; NACP/ALPHA-SYNUCLEIN; SUBSTANTIA-NIGRA; DOPAMINERGIC-NEURONS; ALZHEIMERS-DISEASE; SEQUENCE-ANALYSIS; ALLELIC VARIATION; LEWY BODY; IN-VITRO C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Chiba-Falek, O (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 56 TC 6 Z9 6 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2003 VL 68 BP 409 EP 415 DI 10.1101/sqb.2003.68.409 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 841YT UT WOS:000222969300048 PM 15338643 ER PT J AU Morrell, CH Brant, LJ Pearson, JD Verbeke, GN Fleg, JL AF Morrell, CH Brant, LJ Pearson, JD Verbeke, GN Fleg, JL TI Applying linear mixed-effects models to the problem of measurement error in epidemiologic studies SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE attenuation; logistic regression; measurement error bias; mixed-effects regression; regression dilution bias ID PERSON MEASUREMENT ERROR; CONFIDENCE-INTERVALS; BLOOD-PRESSURE; REGRESSION; VARIABILITY; DISEASE; CANCER AB Although studies of the relationship between risk factors measured at baseline and a binary outcome are common problems occurring in statistical analyses of epidemiologic studies, little has been written about what constitutes a good measure of the true baseline value of a risk factor. This paper considers different schemes of providing for baseline risk factor data and proposes and compares methods for correcting estimates of relative risks for bias due to measurement error. Repeated measurements taken at baseline appear to allow for a correction in the estimate of risk that is comparable to the correction based on repeated measurements over a number of visits close to baseline. The procedures proposed are regression calibration/imputation type methods that involve estimating the covariates with less error and using these estimates in the standard model for the risk factor analysis. Shrinkage estimates from a linear mixed-effects model for multiple measurements at baseline are proposed as a method for estimating the true level of a risk factor at baseline. A simulation study shows that these shrinkage estimates give estimates of the risk of the outcome which have a smaller mean square error and confidence interval coverage proportions much closer to the nominal level than would be obtained using the observed data. This new imputation method is compared to the measurement error correction method earlier proposed by Rosner et al. (Rosner, B., Spiegelman, D., Willett, W. C. (1992). Correction of logistic regression relative risk estimates and confidence intervals for random within-person measurement error. American Journal of Epidemiology 136:1400-1413). In addition, the standard errors from the new method are compared to a nonparametric bootstrap estimate of the standard errors as well as to the asymptotic standard errors obtained using a method proposed by Carroll and Stefanski. C1 Loyola Coll, Baltimore, MD 21210 USA. NIA, Gerontol Res Ctr, Baltimore, MD USA. Merck Res Labs, W Point, PA USA. Katholieke Univ Leuven, Biostat Ctr, Louvain, Belgium. NHLBI, DECA, Bethesda, MD USA. RI Verbeke, Geert/I-5587-2015 NR 24 TC 2 Z9 2 U1 1 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 2003 VL 32 IS 2 BP 437 EP 459 DI 10.1081/SAC-120017500 PG 23 WC Statistics & Probability SC Mathematics GA 685GV UT WOS:000183254800009 ER PT J AU MacEachren, AM Hardisty, F Dai, XP Pickle, L AF MacEachren, AM Hardisty, F Dai, XP Pickle, L TI Supporting visual analysis of federal geospatial statistics SO COMMUNICATIONS OF THE ACM LA English DT Article C1 Penn State Univ, GeoVISTA Ctr, University Pk, PA 16802 USA. NCI, Stat Res & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP MacEachren, AM (reprint author), Penn State Univ, GeoVISTA Ctr, University Pk, PA 16802 USA. RI MacEachren, Alan/E-9444-2011 OI MacEachren, Alan/0000-0002-0356-7323 NR 5 TC 4 Z9 4 U1 0 U2 0 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 1515 BROADWAY, NEW YORK, NY 10036 USA SN 0001-0782 J9 COMMUN ACM JI Commun. ACM PD JAN PY 2003 VL 46 IS 1 BP 59 EP 60 PG 2 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA 631JH UT WOS:000180164000021 ER PT J AU Mayer, GD Leach, A Kling, P Olsson, PE Hogstrand, C AF Mayer, GD Leach, A Kling, P Olsson, PE Hogstrand, C TI Activation of the rainbow trout metallothionein-A promoter by silver and zinc SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE metallothionein; MT; zinc; silver; MTF-1; RTG-2; CHSE-214 ID TRANSCRIPTION FACTOR; I GENE; EXPRESSION; INDUCTION; CELLS; INTERACTS; EXPOSURE; RTG-2 AB In fish, the synthesis of metallothionein (MT) is increased by a number of heavy metals. The rainbow trout MT-A gene promoter region contains six known metal responsive elements (MREs), that mediate promoter activation by metals. In the present study, two fish cell lines differing in their ability to produce MT, RTG-2 (produce MT protein) and CHSE-214 (produce no detectable NIT protein), were used to help elucidate the roles of Zn, Ag and MT in the activation of the MT promoter. The hypothesis tested was that Ag activates the MT-A promoter indirectly by displacing Zn from pre-existing Zn-MT and that this liberated Zn subsequently induces MT synthesis. Both cell lines were transfected with a luciferase reporter gene construct containing the rainbow trout MT-A promoter, exposed to various concentrations of Zn or Ag, and assayed for luciferase activity. CHSE-214 cells showed five times greater production of luciferase than RTG-2 cells when exposed to identical concentrations of Ag. Thus, Ag can likely induce MT transcription without displacing Zn from pre-existing Zn-MT. Furthermore, Ag activated the MT promoter at concentrations 100-fold lower than those required for Zn to initiate transcription, suggesting that zinc displaced from other sites by such low concentrations of Ag would not be sufficient to initiate MT transcription. This interpretation was further supported by radiotracer studies indicating that Ag did not cause a redistribution of Zn-65 within either of the two cell types. These combined results indicate that Ag may be a direct inducer of MT. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Univ Kentucky, TH Morgan Sch Biol Sci, Lexington, KY 40506 USA. Umea Univ, Dept Cell & Mol Biol, Unit Physiol, S-90187 Umea, Sweden. Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. Kings Coll London, Div Life Sci, London SE1 8WA, England. RP Mayer, GD (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. EM gmayer@rsmas.miami.edu RI Perez , Claudio Alejandro/F-8310-2010; Mayer, Gregory/K-4496-2012; Hogstrand, Christer/C-9041-2013; Mayer, Gregory/A-8459-2017 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Mayer, Gregory/0000-0002-2652-9856; Mayer, Gregory/0000-0002-2652-9856 NR 19 TC 25 Z9 25 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD JAN PY 2003 VL 134 IS 1 BP 181 EP 188 AR PII S1096-4959(02)00248-8 DI 10.1016/S1096-4959(02)00248-8 PG 8 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 637KG UT WOS:000180509800017 PM 12524046 ER PT J AU Silva, AC Kim, SG AF Silva, AC Kim, SG TI Perfusion-based functional magnetic resonance imaging SO CONCEPTS IN MAGNETIC RESONANCE PART A LA English DT Article DE arterial spin labeling; brain; cerebral blood flow; magnetic resonance imaging ID CEREBRAL BLOOD-FLOW; RECOVERY FAIR TECHNIQUE; HUMAN BRAIN ACTIVATION; SPIN-ECHO FMRI; RAT-BRAIN; ARTERIAL WATER; OXIDATIVE-METABOLISM; MULTISLICE PERFUSION; SENSORY STIMULATION; SIGNAL CHANGES AB The measurement of cerebral blood flow (CBF) is a very important way of assessing tissue viability, metabolism, and function. CBF can be measured noninvasively with magnetic resonance imaging (MRI) by using arterial water as a perfusion tracer. Because of the tight coupling between neural activity and CBF, functional MRI (fMRI) techniques are having a large impact in defining regions of the brain that are activated due to specific stimuli. Among the different fMRI techniques, CBF-based fMRI has the advantages of being specific to tissue signal change, a critical feature for quantitative measurements within and across subjects, and for high-resolution functional mapping. Unlike the conventional blood oxygenation level dependent (BOLD) technique, the CBF change is an excellent index of the magnitude of neural activity change. Thus, CBF-based fMRI is the tool of choice for longitudinal functional imaging studies. A review of the principles and theoretical backgrounds of both continuous and pulsed arterial spin labeling methods for measuring CBF is presented, and a general overview of their current applications in the field of functional brain mapping is provided. In particular, examples of the use of CBF-based fMRI to investigate the fundamental hemodynamic responses induced by neural activity and to determine the signal source of the most commonly used BOLD functional imaging are reviewed. (C) 2003 Wiley Periodicals, Inc. C1 NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15261 USA. RP Silva, AC (reprint author), NINDS, Lab Funct & Mol Imaging, 10 Ctr Dr,Bldg 10,Room B1D118, Bethesda, MD 20892 USA. RI Silva, Afonso/A-7129-2009 NR 58 TC 12 Z9 12 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-7347 J9 CONCEPTS MAGN RESO A JI Concepts Magn. Reson. Part A PD JAN PY 2003 VL 16A IS 1 BP 16 EP 27 DI 10.1002/cmr.a.10050 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 670MH UT WOS:000182412200003 ER PT J AU Silva, AC Merkle, H AF Silva, AC Merkle, H TI Hardware considerations for functional magnetic resonance imaging SO CONCEPTS IN MAGNETIC RESONANCE PART A LA English DT Article DE hardware; functional magnetic resonance imaging; blood oxygenation level dependence; cerebral blood flow and volume ID PERIPHERAL-NERVE STIMULATION; ACOUSTIC NOISE-REDUCTION; PHASED-ARRAY DETECTORS; HEAD GRADIENT COILS; HUMAN BRAIN; SENSORY STIMULATION; AUDITORY-CORTEX; FIELD-STRENGTH; BIRDCAGE COIL; TIME-COURSE AB Functional magnetic resonance imaging (fMRI) techniques based on changes in blood oxygenation or regional cerebral blood flow or volume have had great impact in mapping the regions of the brain that are activated by specific stimuli. The basic strategy of fMRI paradigms is to acquire data during two different brains states: one state usually comprises a resting condition, while in the other state the subject is performing a specific sensory or cognitive task. The signal difference between the activated and resting signals is on the order of only a few percent, and therefore the reliability and reproducibility with which it can be detected limit both the temporal and spatial resolution of fMRI experiments. The era of fMRI has significantly contributed to advancing the state of the art of MRI scanners. Every hardware component in modern MRI scanners, from the magnet itself to the gradient, shim, and RF coils to peripheral stimulus delivery equipment, has been (re)designed to perform to the limit of currently available technology and to improve the quality of MRI data, particularly fMRI data. The current state of the art of MRI scanners is described in light of their use in fMRI experiments. (C) 2003 Wiley Periodicals, Inc. C1 NINDS, NIH, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. NIH, MRI Res Facil, Bethesda, MD 20892 USA. RP Merkle, H (reprint author), NINDS, NIH, Lab Funct & Mol Imaging, 10 Ctr Dr,Bldg 10-B1D118, Bethesda, MD 20892 USA. EM merkleh@ninds.nih.gov RI Silva, Afonso/A-7129-2009 NR 65 TC 10 Z9 11 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-7347 J9 CONCEPTS MAGN RESO A JI Concepts Magn. Reson. Part A PD JAN PY 2003 VL 16A IS 1 BP 35 EP 49 DI 10.1002/cmr.a.10052 PG 15 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 670MH UT WOS:000182412200005 ER PT J AU Fisher, LW Fedarko, NS AF Fisher, LW Fedarko, NS TI Six genes expressed in bones and teeth encode the current members of the SIBLING family of proteins SO CONNECTIVE TISSUE RESEARCH LA English DT Article; Proceedings Paper CT 7th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-09, 2001 CL PONTE VEDRA, FLORIDA DE bone sialoprotein; complement; integrin-binding; osteopontin; SIBLING ID COMPLEMENT-MEDIATED ATTACK; AMINO-ACID-SEQUENCE; MATRIX GLA PROTEIN; CHROMOSOMAL LOCALIZATION; HUMAN OSTEOPONTIN; SIALOPROTEIN; CDNA; BINDING; CLONING; ORGANIZATION AB Bone sialoprotein (BSP), dentin matrix protein 1 (DMPI), dentin sialophosphoprotein (DSPP), enamelin (ENAM), matrix extracellular phosphoglycoprotein (MEPE), and osteopontin (OPN) are glycophosphoproteins expressed in bones and/or teeth. Direct comparison of their amino acid sequences do not suggest that they belong to a single genetic family, but a detailed analysis of their chromosomal location and gene structure does. Analysis of human brain mRNA by RT-PCR has led to the discovery of two additional exons thereby making it more convincing that MEPE is a member of the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family. We propose that the members of this SIBLING family are extended, flexible proteins in solution that can facilitate the formation of a number of different complexes. For example, OPN can bridge complement Factor H to either an RGD-dependent integrin or to CD44 forming a membrane-bound complex that actively suppresses the alternate complement pathway. Two possible mechanisms for inhibiting the lytic pathway of alternate complement are presented. C1 NIDCR, Mat Biochem Unit, Craniofacial & Skeletal Dis Branch, NIH,HHS, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Med, Div Geriatr, Baltimore, MD USA. RP Fisher, LW (reprint author), NIDCR, Mat Biochem Unit, Craniofacial & Skeletal Dis Branch, NIH,HHS, Room 228,Bldg 30, Bethesda, MD 20892 USA. EM LFISHER@dir.nidcr.nih.gov OI Fedarko, Neal/0000-0001-6055-6279 NR 25 TC 259 Z9 272 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 2003 VL 44 SU 1 BP 33 EP 40 DI 10.1080/03008200390152061 PG 8 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 660AD UT WOS:000181811000008 PM 12952171 ER PT J AU Goldberg, M Rapoport, O Septier, D Palmier, K Hall, R Embery, G Young, M Ameye, L AF Goldberg, M Rapoport, O Septier, D Palmier, K Hall, R Embery, G Young, M Ameye, L TI Proteoglycans in predentin: The last 15 micrometers before mineralization SO CONNECTIVE TISSUE RESEARCH LA English DT Article; Proceedings Paper CT 7th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-09, 2001 CL PONTE VEDRA, FLORIDA DE biglycan; decorin; dentin; fibromodulin; mineralization; proteoglycans ID RAT INCISOR; MATRIX METALLOPROTEINASES; DENTIN PROTEOGLYCANS; DECORIN; PROTEINS; BIGLYCAN; COLLAGEN; SULFATE; GROWTH; HYDROXYAPATITE AB Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix organization. In order to investigate the distribution and potential functions of decorin, biglycan (BGN), and fibromodulin (3 SLRPs, potentially related to dentinogenesis), we performed light and electron immunochemistry on teeth from rats, and on wildtype and biglycan knockout mice (BGN KO). Immunohistochemical data demonstrate that chondroitin sulfate/dermatan sulfate (CS/DS) and keratan sulfate (KS) distributions displayed reverse gradients in predentin. The decrease of CS/DS labeling from the proximal to the distal predentin contrasted with the sharp decorin increase observed in the distal predentin near the predentin/dentin transition, an effect possibly attributable to the deglycosylation action of stromelysin-1. In contrast, BGN concentration was apparently constant throughout the whole predentin. Additional immunolabelings showed, for the first time, the presence of fibromodulin in predentin. Compared with the wild-type mouse, the mean diameter of collagen fibrils in the BGN KO was smaller in the proximal predentin but larger in the central and distal predentin, the metadentin was broader, and the dentin mineralization appeared altered and heterogeneous. Altogether, our data suggest an important role for BGN in dentin formation and mineralization. C1 Univ Paris 05, Fac Chirurg Dent, F-92120 Montrouge, France. Univ Liverpool, Liverpool Dent Sch, Liverpool L69 3BX, Merseyside, England. NIH, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. RP Goldberg, M (reprint author), Univ Paris 05, Fac Chirurg Dent, 1 Rue Maurice Arnoux, F-92120 Montrouge, France. EM mgoldod@aol.com NR 31 TC 26 Z9 27 U1 2 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 2003 VL 44 SU 1 BP 184 EP 188 DI 10.1080/03008200390152304 PG 5 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 660AD UT WOS:000181811000032 PM 12952195 ER PT J AU Beertsen, W Holmbeck, K Niehof, A Bianco, P Chrysovergis, K Birkedal-Hansen, H Everts, V AF Beertsen, W Holmbeck, K Niehof, A Bianco, P Chrysovergis, K Birkedal-Hansen, H Everts, V TI Inhibition of molar eruption and root elongation in MT1-MMP-deficient mice SO CONNECTIVE TISSUE RESEARCH LA English DT Article; Proceedings Paper CT 7th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-09, 2001 CL PONTE VEDRA, FLORIDA DE eruption; MT1-MMP; periodontal ligament; root growth AB To study whether eruption of teeth and root growth require remodeling of collagen in the peridental tissues, we studied molar development in mice deficient in MT1-MMP, an enzyme essential for remodeling of soft tissue-hard tissue interfaces. The lower jaws of deficient mice and their wildtype littermates were subjected to stereologic analysis. It was shown that in deficient animals, eruption and root elongation were severely inhibited, signifying a role of the enzyme in these developmental processes. C1 Univ Amsterdam, Acad Ctr Dent Amsterdam, Dept Periodontol, Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Beertsen, W (reprint author), ACTA, Dept Periodontol, Louwesweg 1, NL-1066 EA Amsterdam, Netherlands. EM w.beertsen@acta.nl RI Beertsen, Wouter/B-5308-2013 OI Beertsen, Wouter/0000-0001-5698-5986 NR 5 TC 9 Z9 9 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 2003 VL 44 SU 1 BP 298 EP 299 DI 10.1080/03008200390181807 PG 2 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 660AD UT WOS:000181811000049 PM 12952212 ER PT J AU Hawk, ET Viner, JL Umar, A AF Hawk, ET Viner, JL Umar, A TI Non-steroidal anti-inflammatory and cyclooxygenase-2-selective inhibitors in clinical cancer prevention trials SO COX-2: A NEW TARGET FOR CANCER PREVENTION AND TREATMENT SE PROGRESS IN EXPERIMENTAL TUMOR RESEARCH LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; ABERRANT CRYPT FOCI; PROSTAGLANDIN E-2 LEVELS; UPPER GASTROINTESTINAL TOXICITY; RANDOMIZED CONTROLLED-TRIAL; RECEPTOR SUBTYPE EP1; COLON CARCINOGENESIS; SULINDAC THERAPY; INTESTINAL POLYPOSIS; ALPHA-DIFLUOROMETHYLORNITHINE C1 NCI, Gastrointestinal & Other Canc Res Grp, Div Canc Prevent, EPN, Bethesda, MD 20892 USA. RP Hawk, ET (reprint author), NCI, Gastrointestinal & Other Canc Res Grp, Div Canc Prevent, EPN, Suite 2141,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 130 TC 7 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0079-6263 J9 PROG EXP TUMOR RES JI Prog.Exp.Tumor Res. PY 2003 VL 37 BP 210 EP 242 PG 33 WC Oncology SC Oncology GA BX58M UT WOS:000185760800013 PM 12795057 ER PT J AU O'Grady, NP Gerberding, JL Weinstein, RA Masur, H AF O'Grady, NP Gerberding, JL Weinstein, RA Masur, H TI Patient safety and the science of prevention: The time for implementing the Guidelines for the Prevention of Intravascular Catheter-Related Infections is now SO CRITICAL CARE MEDICINE LA English DT Article ID CENTRAL VENOUS CATHETERS; TOTAL PARENTERAL NUTRITION; BLOOD-STREAM INFECTION; COMPLICATIONS C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Off Director, Atlanta, GA USA. Cook Cty Hosp, Chicago, IL 60612 USA. Rush Med Coll, Chicago, IL 60612 USA. RP O'Grady, NP (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr MSC 1662, Bethesda, MD 20892 USA. NR 12 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2003 VL 31 IS 1 BP 291 EP 292 DI 10.1097/01.CCM.0000046324.72815.5B PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 640XU UT WOS:000180714800046 PM 12545031 ER PT J AU Banks, SM Gerstenberger, E Eichacker, PQ Natanson, C AF Banks, SM Gerstenberger, E Eichacker, PQ Natanson, C TI Long-term cost effectiveness of drotrecogin alfa (activated): An unanswered question SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE activated protein C; sepsis; cost effectiveness ID SEVERE SEPSIS; EPIDEMIOLOGY C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Banks, SM (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 7 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2003 VL 31 IS 1 BP 308 EP 309 DI 10.1097/00003246-200301000-00050 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 640XU UT WOS:000180714800050 PM 12545035 ER PT J AU Eichacker, PQ Natanson, C AF Eichacker, PQ Natanson, C TI Recombinant human activated protein C in sepsis: Inconsistent trial results, an unclear mechanism of action, and safety concerns resulted in labeling restrictions and the need for phase IV trials SO CRITICAL CARE MEDICINE LA English DT Review C1 NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 7D43, Bethesda, MD 20892 USA. NR 8 TC 44 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2003 VL 31 IS 1 SU S BP S94 EP S96 DI 10.1097/01.CCM.0000042473.84847.EA PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 642VE UT WOS:000180825500013 PM 12544982 ER PT J AU Rigden, DJ Galperin, MY Jedrzejas, MJ AF Rigden, DJ Galperin, MY Jedrzejas, MJ TI Analysis of structure and function of putative surface-exposed proteins encoded in the Streptococcus pneumoniae genome: A bioinformatics-based approach to vaccine and drug design SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review ID RECOMBINANT ESCHERICHIA-COLI; CROSS-REACTIVE ANTIBODIES; CHOLINE-BINDING PROTEINS; ENZYME ACTIVE-SITES; CELL-WALL; STAPHYLOCOCCUS-AUREUS; CRYSTAL-STRUCTURE; VIRULENCE FACTOR; EVOLUTIONARY RELATIONSHIPS; PHOSPHOGLYCERATE MUTASE AB Streptococcus pneumoniae is the most common cause of fatal community-acquired pneumonia, middle ear infection, and meningitis. The prevention and treatment of this infection have become a top priority for the medical-scientific community. The present polysaccharide-based vaccine used to immunize susceptible hosts is only similar to60% effective and is ineffective in children younger than 2 years of age. The new conjugate vaccine, based on the engineered diphtheria toxin coupled to polysaccharide antigens, is approved only for use in children under 2 years of age to treat invasive disease. While penicillin is the drug of choice to treat infections secondary to S. pneumoniae, increasing numbers of bacterial strains are resistant to penicillin as well as to broad spectrum antibiotics such as vancomycin. Thus, there is a need to identify new strategies to prevent and treat diseases caused by to S. pneumoniae. In this article, we summarize the utilization of the recently available S. pneumoniae genomic information in order to identify and characterize novel proteins likely located on the surface of this Gram-positive pathogenic bacterium. Because only a limited number of surface proteins of S. pneumoniae have been characterized to date, this information provides new insights into the pathogenesis of this organism as well as highlights possible avenues for its treatment and/or prevention in the future. The review is divided into two sections. First, we briefly summarize current information about known surface-exposed proteins of S. pneumoniae. This is followed by the illustration of procedures for the identification of new putative surface-exposed proteins. These have signal peptides required for their extra-cytoplasmic transport and/or additional signature sequences. Some of these will be S. pneumoniae virulence factors. The signature sequences we have chosen are those leading to protein binding to choline present on the bacterial surface, attachment to peptidoglycan of the cell wall, or anchoring to lipids of the cytoplasmic membrane. All these signatures are indicative of binding of proteins to the surface of this organism. Secondly, we illustrate the application of bioinformatics and modeling tools to these selected proteins in order to provide information about their likely functions and preliminary three-dimensional structure models. The focal point of the analysis of these proteins, their sequences, and structures is the evaluation of their antigenic properties and possible roles in pathogenicity. The information obtained from the genome analysis will be instrumental in the development of a more effective, prophylactic and/or therapeutic agents to prevent and to treat infections due to S. pneumoniae. C1 Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Cenargen EMBRAPA, Natl Ctr Genet Resources & Biotechnol, BR-70770900 Brasilia, DF, Brazil. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Jedrzejas, MJ (reprint author), Childrens Hosp Oakland, Res Inst, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA. EM mjedrzejas@chori.org RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Rigden, Daniel/0000-0002-7565-8937 FU NIAID NIH HHS [AI44079] NR 141 TC 44 Z9 48 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1040-9238 EI 1549-7798 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PY 2003 VL 38 IS 2 BP 143 EP 168 DI 10.1080/713609215 PG 34 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677XZ UT WOS:000182835700003 PM 12749697 ER PT J AU Meek, ME Bucher, JR Cohen, SM Dellarco, V Hill, RN Lehman-McKeeman, LD Longfellow, DG Pastoor, T Seed, J Patton, DE AF Meek, ME Bucher, JR Cohen, SM Dellarco, V Hill, RN Lehman-McKeeman, LD Longfellow, DG Pastoor, T Seed, J Patton, DE TI A framework for human relevance analysis of information on carcinogenic modes of action SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE risk assessment; carcinogenic mode of action; human relevance of animal carcinogens; acrylonitrile; atrazine; chloroform; ethylene oxide; d-limonene; melamine; phenobarbital ID MAJOR RISK-FACTOR; REGENERATIVE CELL-PROLIFERATION; THYROID-HORMONE METABOLISM; N-NITROSODIMETHYLAMINE-DEMETHYLASE; CHLOROFORM-INDUCED NEPHROTOXICITY; HYALINE DROPLET NEPHROPATHY; RECEPTOR-MEDIATED RESPONSES; MICROSOMAL-ENZYME INDUCERS; TRIAZINE-DERIVED COMPOUNDS; ETHYLENE-OXIDE DOSIMETRY AB The human relevance framework (HRF) outlines a four-part process, beginning with data on the mode of action (MOA) in laboratory animals, for evaluating the human relevance of animal tumors. Drawing on U.S. EPA and IPCS proposals for animal MOA analysis, the HRF expands those analyses to include a systematic evaluation of comparability, or lack of comparability, between the postulated animal MOA and related information from human data sources. The HRF evolved through a series of case studies representing several different MOAs. HRF analyses produced divergent outcomes, some leading to complete risk assessment and others discontinuing the process, according to the data available from animal and human sources. Two case examples call for complete risk assessments. One is the default: When data are insufficient to confidently postulate a MCA for test animals, the animal tumor data are presumed to be relevant for risk assessment and a complete risk assessment is necessary. The other is the product of a data-based finding that the animal MOA is relevant to humans. For the specific MOA and endpoint combinations studied for this article, full risk assessments are necessary for potentially relevant MOAs involving cytotoxicity and cell proliferation in animals and humans (Case Study 6, chloroform) and formation of urinary-tract calculi (Case Study 7, melamine). In other circumstances, when data-based findings for the chemical and endpoint combination studied indicate that the tumor-related animal MOA is unlikely to have a human counterpart, there is little reason to continue the risk assessment for that combination. Similarly, when qualitative considerations identify MOAs specific to the test species or quantitative considerations indicate that the animal MOA is unlikely to occur in humans, such hazard findings are generally conclusive and further risk assessment is not necessary for the endpoint-MOA combination under study. Case examples include a tumor-related protein specific to test animals (Case Study 3, d-limonene), the tumor consequences of hormone suppression typical of laboratory animals but not humans (Case Study 4, atrazine), and chemical-related enhanced hormone clearance rates in animals relative to humans (Case Study 5, phenobarbital). The human relevance analysis is highly specific for the chemical-MOA-tissue-endpoint combination under analysis in any particular case: different tissues, different endpoints, or alternative MOAs for a given chemical may result in different human relevance findings. By providing a systematic approach to using MOA data, the HRF offers a new tool for the scientific community's overall effort to enhance the predictive power, reliability and transparency of cancer risk assessment. C1 ILSI Risk Sci Inst, Washington, DC 20005 USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. US EPA, Washington, DC 20460 USA. Bristol Myers Squibb Co, Princeton, NJ USA. NCI, NIH, Rockville, MD USA. Syngenta Crop Protect, Greensboro, NC USA. RP Patton, DE (reprint author), ILSI Risk Sci Inst, 1 Thomas Circle NW,Suite 900, Washington, DC 20005 USA. EM dpatton@ilsi.org NR 305 TC 235 Z9 243 U1 3 U2 15 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PY 2003 VL 33 IS 6 BP 591 EP 653 DI 10.1080/10408440390250136 PG 63 WC Toxicology SC Toxicology GA 758YJ UT WOS:000187703200002 PM 14727733 ER PT J AU Isenberg-Feig, H Justice, JP Keane-Myers, A AF Isenberg-Feig, H Justice, JP Keane-Myers, A TI Animal models of allergic asthma SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Article ID MAJOR BASIC-PROTEIN; INDUCED AIRWAY HYPERRESPONSIVENESS; HUMANIZED MONOCLONAL-ANTIBODY; MURINE MODEL; GUINEA-PIGS; BRONCHIAL HYPERREACTIVITY; HUMAN INTERLEUKIN-5; PRIMATE MODEL; MONKEY MODEL; T-CELLS AB We are fortunate to have many species of animals that can serve as adequate models for allergic disease in humans. This review is focused mostly on models of allergic airway disease, and some major categories of animals used for asthma research are discussed, including rodents and non-human primates. Furthermore-evidence that supports and criticizes the use of animal models of asthma is provided. There is no animal model that exactly reproduces the pathology of human asthma. However, these models are necessary for the development of novel therapies and an understanding of the detailed pathogenesis of the response of mammals to respirable allergens. C1 NIAID, Lab Allerg Dis, Eosinophil Biol Sect, NIH, Rockville, MD 20852 USA. RP Keane-Myers, A (reprint author), NIAID, Lab Allerg Dis, Eosinophil Biol Sect, NIH, Room 200E,Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 44 TC 16 Z9 17 U1 0 U2 0 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD JAN PY 2003 VL 3 IS 1 BP 70 EP 78 DI 10.1007/s11882-003-0015-8 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 694BP UT WOS:000183754200013 PM 12542998 ER PT J AU Khanna, C Vail, DM AF Khanna, Chand Vail, David M. TI Targeting the Lung: Preclinical and Comparative Evaluation of Anticancer Aerosols in Dogs with Naturally Occurring Cancers SO CURRENT CANCER DRUG TARGETS LA English DT Article AB Pet dogs with naturally occurring cancers offer a novel opportunity for the study of both cancer biology and therapy. The following review will provide the rationale for the use of these spontaneous cancer models in translational research, particularly in the development of anticancer aerosols. A summary of work involving pet dogs with primary and metastatic cancers to the lung and the investigation of therapeutic chemotherapy and cytokine immunotherapy aerosols will be presented. C1 [Khanna, Chand] NCI, Ctr Canc Res, Comparat Oncol Program, NIH, Bethesda, MD 20892 USA. [Vail, David M.] Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA. [Vail, David M.] Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA. RP Khanna, C (reprint author), NCI, Ctr Canc Res, Comparat Oncol Program, NIH, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov NR 71 TC 27 Z9 27 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PY 2003 VL 3 IS 4 BP 265 EP 273 DI 10.2174/1568009033481903 PG 9 WC Oncology SC Oncology GA V33YB UT WOS:000209053000004 PM 12871057 ER PT J AU Marcu, MG Neckers, LM AF Marcu, Monica G. Neckers, Leonard M. TI The C-Terminal Half of Heat Shock Protein 90 Represents a Second Site for Pharmacologic Intervention in Chaperone Function SO CURRENT CANCER DRUG TARGETS LA English DT Article AB The molecular chaperone heat shock protein 90 (Hsp90) is required for stability and function of multiple mutated, chimeric, and over-expressed signaling proteins that promote cancer cell growth and/or survival. It is also critical for the function of many normally expressed proteins, including protein kinases, steroid receptors and other transcription factors, and it may protect the cell from incapacitating or deleterious mutations. The recent identification of a nucleotide binding pocket within the first 220 amino acids of the protein, together with the discovery that at least two structurally distinct classes of antibiotic can replace nucleotide at this site and alter chaperone activity, has deservedly focused attention on Hsp90's amino terminus as an important regulator of function. However, data continue to accumulate pointing to the C-terminal half of the chaperone as an equally important regulator of activity, and small molecules that bind to this portion of Hsp90 have been identified. C1 [Marcu, Monica G.; Neckers, Leonard M.] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Rockville, MD 20850 USA. RP Neckers, LM (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM len@helix.nih.gov NR 48 TC 18 Z9 20 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PY 2003 VL 3 IS 5 BP 343 EP 347 DI 10.2174/1568009033481804 PG 5 WC Oncology SC Oncology GA V33YC UT WOS:000209053100006 PM 14535286 ER PT J AU Sausville, EA Tomaszewski, JE Ivy, P AF Sausville, Edward A. Tomaszewski, Joseph E. Ivy, Percy TI Clinical Development of 17-Allylamino, 17-Demethoxygeldanamycin SO CURRENT CANCER DRUG TARGETS LA English DT Article AB 17-allylamino, 17-demethoxygeldanamycin (17AAG; NSC 330507) is the first modulator of heat shock protein 90 (Hsp90) to enter clinical trials. Hsp90 serves a chaperone role to properly fold and deliver client proteins to appropriate intracellular locations. Interest in Hsp90 modulators for the experimental therapeutics of cancer has arisen based on pre-clinical evaluations suggesting that Hsp90 client proteins regulate signaling pathways critical to the molecular economy of many types of tumors, including oncogene signaling, cyclin-dependent kinase activation, steroid hormone receptors, and mediators of invasion and metastasis. Thus, Hsp90-directed agents could affect molecules upon which tumors depend for their proliferation and survival. Initial clinical studies have therefore sought to incorporate assessment of these endpoints into initial clinical evaluations. Three schedules of administration have been supported for initial evaluation in Phase I studies sponsored by the National Cancer Institute (NCI) or supported by NCI and sponsored by Cancer Research UK. In the daily times five schedule, a recommended Phase II dose (RPTD) of 40 mg/m(2) has been reached, while once weekly or three of four weekly schedules are defining RPTDs of 295 and 308 mg/m(2). Toxicity is tolerable and appears dominated by hepatic, gastrointestinal, and constitutional symptoms. Concentrations of drug at peak of similar to 1700-3000 nM are concordant with concentrations predictive of useful outcomes in pre-clinical model systems. Evidence of modulation of Hsp90 partner molecules has been obtained in both surrogate and some tumor compartments. These very early results encourage additional clinical evaluations of 17AAG and related molecules. C1 [Sausville, Edward A.; Tomaszewski, Joseph E.] NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Rockville, MD 20852 USA. [Ivy, Percy] NCI, Invest Drug Branch, Therapy Evaluat Program, Rockville, MD 20852 USA. RP Sausville, EA (reprint author), NCI, Div Canc Treatment & Diag, Dev Therapeut Program, 6130 Executive Blvd,Rm 8018, Rockville, MD 20852 USA. EM sausville@nih.gov NR 24 TC 199 Z9 205 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PY 2003 VL 3 IS 5 BP 377 EP 383 DI 10.2174/1568009033481831 PG 7 WC Oncology SC Oncology GA V33YC UT WOS:000209053100010 PM 14529389 ER PT J AU Ruff, MR Polianova, M Yang, QE Leoung, GS Ruscetti, FW Pert, CB AF Ruff, MR Polianova, M Yang, QE Leoung, GS Ruscetti, FW Pert, CB TI Update on D-Ala-Peptide T-Amide (DAPTA): A viral entry inhibitor that blocks CCR5 chemokine receptors SO CURRENT HIV RESEARCH LA English DT Review DE peptide T; entry inhibitor; immune reconstitution; antiviral; IFN gamma; chemokine; cytokine; reservoir ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ENVELOPE GLYCOPROTEIN GP120; NECROSIS-FACTOR-ALPHA; PLACEBO-CONTROLLED TRIAL; CENTRAL-NERVOUS-SYSTEM; TYPE-1 ISOLATE; HIV-INFECTION; CELL-DEATH; REPLICATION-COMPETENT AB Peptide T, named for its high threonine content (ASTTTNYT), was derived by a database search which assumed that a relevant receptor binding epitope within env (gp120) would have sequence homology to a known signaling peptide. Binding of radiolabeled gp120 to brain membranes was displaced by peptide T and three octapeptide analogs (including "DAPTA", Dalai-peptide T-amide, the protease- resistant analog now in Phase If clinical trials) with the same potency that these four octapeptides blocked infectivity of an early passage patient isolate. This 1986 report was controversial due to a number of laboratories' failure to find peptide T antiviral effects; we now know that peptide T is a potent HIV entry inhibitor selectively targeting CCR5 receptors with minimal effects on the X4 tropic lab adapted virus exclusively in use at that time. Early clinical trials, which demonstrated lack of toxicity and focused on neurological and neurocognitive benefits, are reviewed and data from a small ongoing Phase II trial --- the first to assess peptide T's antiviral effects --- are presented. Studies using infectivity, receptor binding, chemotaxis, and blockade of gp120-induced neurotoxicity in vitro and in vivo are reviewed, discussed and presented here. Peptide T and analogs of its core pentapeptide, present near the V2 stem of numerous gp120 isolates, are potent ligands for CCR5. Clinical data showing peptide T's immunomodulation of plasma cytokine levels and increases in the percentage of IFNgamma secreting CD8(+) T cells in patients with HIV disease are presented and suggests additional therapeutic mechanisms via regulation of specific immunity. C1 Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20057 USA. NCI, Lab Antiviral Drug Mech, Screening Technol Branch, FCRDC, Frederick, MD 21702 USA. St Francis Mem Hosp, HIVCare, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NCI, Ctr Canc Res, Leukocyte Biol Sect, FCRDC, Frederick, MD 21702 USA. RP Ruff, MR (reprint author), Georgetown Univ, Sch Med, Dept Physiol & Biophys, Box 571460, Washington, DC 20057 USA. NR 103 TC 26 Z9 27 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JAN PY 2003 VL 1 IS 1 BP 51 EP 67 DI 10.2174/1570162033352066 PG 17 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 761VC UT WOS:000187935300005 PM 15043212 ER PT J AU Acosta, MT Leon-Sarmiento, FE AF Acosta, MT Leon-Sarmiento, FE TI Repetitive transcranial magnetic stimulation (rTMS): new tool, new therapy and new hope for ADHD SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE ADHD; dopamine; methylphenidate; pharmacology; TMS ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER; CAUDATE-NUCLEUS; BASAL GANGLIA; HUMAN BRAIN; METHYLPHENIDATE; RESONANCE; BOYS; ASSOCIATION AB Attention-deficit hyperactivity disorder (ADHD) is the most common developmental disorder that is associated with environmental and genetic factors. Neurobiological evidence suggests that fronto-striatum-cerebellum circuit abnormalities, mainly in the right hemisphere, are responsible for most of the disturbed sensorimotor integration; dopamine seems to be the main neurochemical alteration underlying these morphological abnormalities. Different conventional treatments have been employed on ADHD; however, repetitive transcranial magnetic stimulation (rTMS), a new and useful option for the clinical/research investigation of several neuropsychiatric disorders involving dopamine circuits, has yet to be considered as a therapeutic tool and possible drug-free option for ADHD. Here the authors explore the available evidence that makes this tool a rational therapeutic possibility for patients with ADHD, calling attention to safety issues, while highlighting the potentials of such an approach and the new hope it may bring for patients, parents, researchers and clinicians. The authors advocate carefully conducted clinical trials to investigate efficacy, safety, cost-effectiveness and clinical utility of rTMS for AND patients - in comparison to both placebo and standard treatments. C1 Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. UIS, Dept Med Interna & Ciencias Basicas, Unidad Neurol Clin & Neurociencias Aplicadas, Bucaramanga, Colombia. UIS, Fac Salud, Bucaramanga, Colombia. RP Leon-Sarmiento, FE (reprint author), NINDS, Brain Stimulat Unit, NIH, 10 Ctr Dr,Bldg 10,Room 5N234, Bethesda, MD 20892 USA. NR 57 TC 11 Z9 14 U1 3 U2 11 PU LIBRAPHARM PI NEWBURY PA C/O DR. PETER L CLARKE, GEMINI HOUSE, 162 CRAVEN RD, NEWBURY RG14 5NR, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PY 2003 VL 19 IS 2 BP 125 EP 130 DI 10.1185/030079903125001541 PG 6 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 673UY UT WOS:000182599700008 PM 12740156 ER PT J AU McCright, B AF McCright, B TI Notch signaling in kidney development SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE Alagille's syndrome; glomerular vascularization; Jagged1; kidney development; Notch2 ID ALAGILLE-SYNDROME; ARTERIOHEPATIC DYSPLASIA; CELL FATE; MICE; GENE; DELTA; ENDOTHELIUM; EXPRESSION; REQUIRES; MUTATION AB Purpose of review Notch signaling is a highly conserved mechanism used by multicellular animals to specify cell fate decisions during the formation of complex structures such as the kidney. A number of studies have recently identified requirements for Notch signaling during kidney organogenesis and tissue repair. This review will summarize these studies and compare Notch signaling in the mammalian kidney with Notch signaling in other organ systems. Recent findings A targeted mutation in the mouse Notch2 receptor resulted in kidneys that are devoid of glomerular endothelial and mesangial cells. The mutant epithelial cells of the developing glomerulus have reduced amounts of vascular endothelial growth factor expression, which may be responsible for the lack of vascularization observed in these glomeruli. Notch2 is expressed in the epithelial cells of the developing glomerulus, and a potential ligand, Jagged1, is expressed in the endothelial cells of the glomerulus. Mice simultaneously heterozygous for mutations in both Notch2 and Jagged1 phenocopy the kidney defects seen in mice homozygous for the Notch2 mutation. These doubly heterozygous mice also display liver and heart developmental abnormalities reminiscent of Alagille's syndrome. Summary Notch signaling is required for kidney development, and the expression of Notch genes is increased in response to kidney damage. Further studies of Notch signaling will be important in order to understand kidney development and tissue repair. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP McCright, B (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN13, Bethesda, MD 20892 USA. NR 41 TC 45 Z9 52 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JAN PY 2003 VL 12 IS 1 BP 5 EP 10 DI 10.1097/01.mnh.0000049802.69874.c0 PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 635MP UT WOS:000180403500002 PM 12496659 ER PT J AU Langford, CA AF Langford, CA TI Lessons from the past and views to the future SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Editorial Material C1 NIAID, MHS, Immunol Dis Sect, Immunoregulat Lab,NIH, Bethesda, MD 20892 USA. RP Langford, CA (reprint author), NIAID, MHS, Immunol Dis Sect, Immunoregulat Lab,NIH, Bldg 10,Room 11B-13, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD JAN PY 2003 VL 15 IS 1 BP 1 EP 2 DI 10.1097/00002281-200301000-00001 PG 2 WC Rheumatology SC Rheumatology GA 629ND UT WOS:000180055000001 ER PT J AU Langford, CA Sneller, MC AF Langford, CA Sneller, MC TI Biologic therapies in the vasculitides SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review ID HEPATITIS-C VIRUS; MONOCLONAL-ANTIBODY THERAPY; INTERFERON-ALPHA TREATMENT; GIANT-CELL ARTERITIS; II MIXED CRYOGLOBULINEMIA; CHURG-STRAUSS-SYNDROME; POLYARTERITIS-NODOSA; B VIRUS; WEGENERS-GRANULOMATOSIS; LONG-TERM AB Monoclonal antibody and recombinant DNA technologies have led to the development of biologic therapies capable of directly targeting selected components of the immune response. With the steady expansion of knowledge regarding the mechanisms of vascular inflammation, the safety and efficacy of biologic agents in the vasculitic diseases are being increasingly investigated. By targeting specific effector mechanisms involved in the pathogenesis of vasculitis, these agents may provide a less toxic means of inducing remission and lessening relapse. However, the study of biologic therapies in the vasculitides must be approached with caution, as unanticipated effects on disease activity and disease-specific toxicities can occur. Studies to examine these agents must recognize the potential for active vasculitis to be organ- or life-threatening as well as the current existence of effective therapies. In the research setting, investigation of biologic agents in the treatment of vasculitic diseases may also provide important insights into pathogenesis of these syndromes. C1 NIAID, Immunol Dis Sect, Immunoregulat Lab, MHS,NIH, Bethesda, MD 20892 USA. RP Langford, CA (reprint author), NIAID, Immunol Dis Sect, Immunoregulat Lab, MHS,NIH, Bldg 10,Room 11B-13, Bethesda, MD 20892 USA. NR 66 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD JAN PY 2003 VL 15 IS 1 BP 3 EP 10 DI 10.1097/00002281-200301000-00002 PG 8 WC Rheumatology SC Rheumatology GA 629ND UT WOS:000180055000002 PM 12496503 ER PT J AU Hull, KM Shoham, N Chae, JJ Aksentijevich, I Kastner, DL AF Hull, KM Shoham, N Chae, JJ Aksentijevich, I Kastner, DL TI The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review ID FAMILIAL MEDITERRANEAN FEVER; PERIODIC SYNDROME; CROHNS-DISEASE; BLAU-SYNDROME; TNF RECEPTOR; MUTATIONS; PYRIN; GENE; PROTEIN; COLD AB The authors review the genes, and their respective proteins, responsible for eight autoinflammatory conditions. Familial Mediterranean fever is caused by mutations in pyrin, which is the prototype of a new family of proteins belonging to the death-domain superfamily. This new group of proteins, which regulate apoptosis, inflammation, and cytokine processing, share an approximately 90-amino-acid N-terminal sequence called the PYRIN domain. Mutations in another PYRIN domain protein, termed cryopyrin, are responsible for three clinically defined illnesses, Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and NOMID/CINCA. A related protein encoded by the gene CARD15/NOD2 is responsible for the Mendelian disorder, Blau syndrome, and also predisposes to Crohn disease. The gene responsible for PAPA syndrome has recently been identified as CD2BP1, and preliminary results from the authors' laboratory also implicate its protein product in these pathways. Lastly, the authors discuss the broadening genetic and clinical spectrum of TRAPS, an autoinflammatory syndrome resulting from mutations in the 55-kDa receptor for tumor necrosis factor. C1 NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA. NIAMSD, Genet & Genomics Branch, NIH, Bethesda, MD 20892 USA. RP Hull, KM (reprint author), NIAMS, NIH, Bldg 10,Room 9S205,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 142 Z9 147 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD JAN PY 2003 VL 15 IS 1 BP 61 EP 69 DI 10.1097/00002281-200301000-00011 PG 9 WC Rheumatology SC Rheumatology GA 629ND UT WOS:000180055000011 PM 12496512 ER PT J AU Piccirillo, CA Prud'homme, GJ AF Piccirillo, CA Prud'homme, GJ TI Immune modulation by plasmid DNA-mediated cytokine gene transfer SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID NONOBESE DIABETIC MICE; COLLAGEN-INDUCED ARTHRITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TRANSFORMING GROWTH FACTOR-BETA-1; INTERFERON-GAMMA RECEPTOR/IGG1; IN-VIVO ELECTROPORATION; SKELETAL-MUSCLE; AUTOIMMUNE-DISEASES; INTRAMUSCULAR INJECTION; TGF-BETA AB Autoimmune diseases frequently develop as a result of an abnormal activation of autoreactive T cells, excessive production of proinflammatory cytokines, particularly by CD4(+) Th1 cells, and subsequent tissue destruction. Cytokine-dependent immunotherapy can be applied to alter the balance between Th1 and Th2 cell activity, or proinflammatory versus immunosuppressive cytokine profiles. Cytotoxic T lymphocyte (CTL) and/or macrophage activity can also be suppressed. Gene transfer offers numerous advantages for the in vivo delivery of cytokines or their receptors for immunotherapeutic use. We have relied on the injection of naked plasmid DNA into skeletal muscle to deliver therapeutic genes. In particular, we have successfully used this approach to deliver neutralizing cytokine receptors such as interferon gamma (IFNgamma)-receptor-Ig fusion proteins or anti-inflammatory cytokines such as transforming growth factor beta-1 (TGF-beta1) and interleukin 4 (IL-4). Intramuscular gene therapy is effective in protecting against several experimental autoimmune diseases including insulin-dependent diabetes mellitus (IDDM), experimental allergic encephalomyelitis (EAE), and systemic lupus erythematosus (SLE). Another promising approach involves DNA vaccination by plasmid-based codelivery of genes encoding an autoantigen and either a cytokine or other immunomodulatory molecule. Plasmid vectors offer interesting advantages over viral vectors, since they are simple to produce, nonimmunogenic and non-pathogenic. They can be repeatedly administered with relatively prolonged periods of expression in vivo, ranging from weeks to months after each injection. Plasmid-based intramuscular gene transfer has great therapeutic potential in the areas of autoimmune and. inflammatory disorders. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. McGill Univ, Dept Pathol, Montreal, PQ H3A 2B4, Canada. RP Prud'homme, GJ (reprint author), St Michaels Hosp, Dept Lab Med & PathoBiol, 30 Bond St, Toronto, ON M5B 1W8, Canada. NR 118 TC 13 Z9 13 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 1 BP 83 EP 94 DI 10.2174/1381612033392404 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 633PB UT WOS:000180290700011 PM 12570678 ER PT J AU Moody, TW Chan, D Fahrenkrug, J Jensen, RT AF Moody, TW Chan, D Fahrenkrug, J Jensen, RT TI Neuropeptides as autocrine, growth factors in cancer cells SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE bombesin; neurotensin; somatostatin; vasoactive intestinal peptide; lung cancer ID VASOACTIVE-INTESTINAL-PEPTIDE; GASTRIN-RELEASING-PEPTIDE; FOCAL ADHESION KINASE; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; BOMBESIN-LIKE PEPTIDES; SWISS 3T3 CELLS; SIGNAL-TRANSDUCTION PATHWAY; ELEVATES CYTOSOLIC CALCIUM; HIGH-AFFINITY BINDING; IN-VITRO EVALUATION AB Neuropeptides can function as autocrine growth factors in cancer cells. High levels of bombesin (BB) and neurotensin (NT)-like immunoreactivity are present in small cell lung cancer (SCLC), a neuroendocrine tumor, Vasoactive intestinal peptide (VIP) stimulates and somatostatin (SST) inhibits the release of BB-like peptides from SCLC cells. BB-like peptides bind to BB2 receptors, which are present on the cell surface. BB-like peptides stimulate the mitogen activated protein kinase (MAPK) cascade leading to increased expression of nuclear oncogenes and growth factors in SCLC cells. Due to the high density of neuropeptide receptors present on the cell surface, SST analogs have been radiolabelcd to image neuroendocrine tumors. VIP receptors are present,in many epithelial cancers including breast, colon, non-small cell lung cancer (NSCLC), pancreatic and prostate cancers. Due to the high density of VIP receptors on lung cancer cells, radiolabeled VIP agonists may be,used to image these tumors. VIP receptor antagonists, such as VIP hybrid, inhibit the growth of cancer cell lines in vitro and in vivo. VIP hybrid and SR48692, a NT receptor antagonist, potentiate the cytotoxicity of chemotherapeutic drugs. These results suggest that neuropeptide receptor antagonists may be useful in the treatment of cancer. C1 NCI, Off Director, CCR, Bethesda, MD 20892 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Bispebjerg Hosp, Dept Clin Chem, DK-2400 Copenhagen, Denmark. NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA. RP NCI, Off Director, CCR, Bldg 31,Rm 3A34,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov NR 184 TC 90 Z9 98 U1 3 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 6 BP 495 EP 509 DI 10.2174/1381612033391621 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 634FU UT WOS:000180330000007 PM 12570813 ER PT J AU Patton, AM Kassis, J Doong, H Kohn, EC AF Patton, AM Kassis, J Doong, H Kohn, EC TI Calcium as a molecular target in angiogenesis SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE molecular therapeutics; endothelial cell; calcium influx; migration ID CYTOSOLIC-FREE CALCIUM; ENDOTHELIAL GROWTH-FACTOR; OPERATED CA2+ ENTRY; FLUID SHEAR-STRESS; PHASE-I TRIAL; SIGNAL-TRANSDUCTION; CELL MOTILITY; LYSOPHOSPHATIDIC ACID; CARBOXYAMIDO-TRIAZOLE; INOSITOL PHOSPHATES AB The plethora of cellular pathways and events involved in angiogenesis are a prime example of the widespread role of calcium ion flux in biological functions. Indeed, calcium is a main point of intersection for many distinct molecular signaling pathways that promote and modulate angiogenesis. Here, we illustrate some of the important aspects of calcium induction, function, downstream effects, and resulting cellular changes that ensue. We describe some of the main mechanisms of calcium regulation in cells as well as intracellular and cross-membrane flux, highlighting key players that are known to facilitate these events. We review some of the major signaling pathways that tie into angiogenesis, and also describe how cellular phenotypic changes that occur during angiogenesis require processes rich in calcium ion stimulation of gradient shifts. Lastly, we hypothesize on current thinking of the role of calcium as a whole in angiogenic cellular function and propose new insight into calcium as a universal effector molecule and a prime target for therapeutic intervention. C1 NIH, Mol Signaling Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), 10 Ctr Dr MSC1500, Bethesda, MD 20892 USA. NR 84 TC 46 Z9 46 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 7 BP 543 EP 551 DI 10.2174/1381612033391559 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 646JJ UT WOS:000181031600005 PM 12570802 ER PT J AU Rushing, PA AF Rushing, PA TI Central amylin signaling and the regulation of energy homeostasis SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE hormone; ingestion; obesity; satiety; peptide; food intake ID GENE-RELATED PEPTIDE; ISLET AMYLOID POLYPEPTIDE; CONDITIONED TASTE-AVERSION; AREA POSTREMA NUCLEUS; BLOOD-BRAIN-BARRIER; REDUCES FOOD-INTAKE; BODY-WEIGHT; NEUROPEPTIDE-Y; FEEDING-BEHAVIOR; RAT-BRAIN AB Amylin is a 37-amino acid peptide hormone that is co-secreted with insulin by pancreatic B cells in response to food intake. Exogenous amylin potently and dose-dependently reduces feeding in rats and mice, with both central and peripheral sites being effective. Although amylin has been characterized as a satiety signal that regulates short-term food intake (i.e., meal size), recent data indicate that amylin may. have long term effects on food intake and body weight. In fact, amylin shares many properties with the established adiposity signals, leptin and insulin. Like leptin and insulin, amylin is not synthesized within the brain, but is rapidly and efficiently transported across the blood-brain barrier (BBB) to a variety of discrete brain regions, including the hypothalamus, where populations of amylin binding sites are found. Further, amylin secretion and plasma levels are correlated with the degree of body adiposity, as is the case for leptin and insulin. In the following brief review, a summary of the findings from recent reports is presented supporting the hypothesis that amylin's role in the control of food intake is not limited to that of purely a satiety signal that brings individual bouts of ingestion to an end, but also serves as an adiposity signal acting within the brain to regulate long-term energy homeostasis. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. RP Rushing, PA (reprint author), NIDDKD, NIH, 6707 Democracy Blvd,Room 747, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK17844, DK54080] NR 105 TC 21 Z9 21 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 10 BP 819 EP 825 DI 10.2174/1381612033455387 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 656HL UT WOS:000181602500006 PM 12678881 ER PT J AU Tataranni, PA AF Tataranni, PA TI Treatment of obesity: Should we target the individual or society? SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID DOUBLY-LABELED WATER; AUTOSOMAL GENOMIC SCAN; BODY-WEIGHT REGULATION; II DIABETES-MELLITUS; ENERGY-EXPENDITURE; PIMA-INDIANS; AFFLUENT SOCIETIES; INSULIN-RESISTANCE; RECOMBINANT LEPTIN; ADIPOSE-TISSUE AB Obesity is a heritable disease that affects millions of people, is disproportionately prevalent in some ethnic groups, and has serious health consequences. Molecular mechanisms causing excessive adiposity are being discovered at an unprecedented rate in animal models. The same cannot be said for humans and, in fact, the etiology of obesity in the majority of people. remains unknown. Furthermore, we are far from fully understanding how an obesogenic environment increases the severity of the disease in people who are genetically susceptible to weight gain. Due to these uncertainties, it is perhaps not surprising that current antiobesity treatments are moderately effective at best. This manuscript provides a brief review of current and future strategies for the treatment of obesity and how they relate to our current knowledge of its pathophysiology. It is concluded that there are reasons to be moderately optimistic that effective pharmacological means to palliate obesity will eventually be identified. However, reversing the current pandemic will require a greater understanding not only of the molecular and physiological underpinnings, but also social and political causes of this disease. C1 NIDDK, Obes Diabet & Energy Metab Unit, Clin Diabet & Nutr Sect, NIH,DHHS, Phoenix, AZ USA. RP Tataranni, PA (reprint author), NIDDK, Obes Diabet & Energy Metab Unit, Clin Diabet & Nutr Sect, NIH,DHHS, 4212 N 16th St,Room 541-A, Phoenix, AZ USA. NR 108 TC 12 Z9 12 U1 3 U2 5 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 15 BP 1151 EP 1163 DI 10.2174/1381612033454946 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 677MR UT WOS:000182812600002 PM 12769743 ER PT J AU Tozser, J Oroszlan, S AF Tozser, J Oroszlan, S TI Proteolytic events of HIV-1 replication as targets for therapeutic intervention SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE HIV-1; life-cycle; proteolysis; viral protease; envelope protein; ubiquitin; proteasomal degradation ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-ANEMIA VIRUS; PROTEASE CLEAVAGE SITE; MURINE LEUKEMIA-VIRUS; TYPE-1 PROTEASE; VIRAL PROTEASE; REVERSE-TRANSCRIPTASE; IN-VITRO; RETROVIRAL PROTEINASES; ANTIRETROVIRAL THERAPY AB Acquired immunodeficiency syndrome (AIDS) is a worldwide epidemic caused by infection with HIV, a human retrovirus. Proteolysis occurs at many points of the retroviral life-cycle, and these events can be considered as targets for chemotherapy. The most well-known proteolytic action in the retroviral life-cycle is the processing of the Gag and Gag-Pro-Pol polyproteins with the virally encoded protease at the late phase of viral infection. Protease inhibitors, together with reverse transcriptase inhibitors, are important components of the drug combinations currently used to treat HIV patients. The current combination therapy substantially reduced morbidity and mortality in HIV-infected patients. However, these drugs do not allow viral eradication, therefore their long-term use is required, allowing the development of resistance in a large portion of patients. Furthermore, several adverse metabolic side effects have been observed associated with the therapy. Thus, new approaches are required to eradicate HIV infection, which may include targeting of the potential early-phase function of the viral protease, and other crucial proteolytic events of the viral replication, such as the ubiquitin-dependent proteolytic degradation of the unfolded viral proteins as well as the inhibition of envelope protein processing. C1 Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. RP Tozser, J (reprint author), Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, POB 6, H-4012 Debrecen, Hungary. EM tozser@indi.biochem.dote.hu RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 NR 104 TC 29 Z9 30 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 22 BP 1803 EP 1815 DI 10.2174/1381612033454478 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 708HZ UT WOS:000184562300005 PM 12871198 ER PT J AU Kojima, H Sitkovsky, MV Cascalho, M AF Kojima, H Sitkovsky, MV Cascalho, M TI HIF-1 alpha deficiency perturbs T and B cell functions SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE HIF-1 alpha; T-lymphocyte; B-lymphocyte; lymphocyte development ID INDUCIBLE FACTOR 1-ALPHA; UBIQUITIN-PROTEASOME PATHWAY; LYMPHOCYTE DEVELOPMENT; O-2 HOMEOSTASIS; HIF-ALPHA; DEGRADATION DOMAIN; HYPOXIC CONDITIONS; FACTOR-I; MICE; OXYGEN AB The immune system protects organisms from pathogens. The immune cells, in particular T- and B-lymphocytes, develop and acquire effector functions in specialized tissues called the lymphoid organs. The lymphoid organs exhibit lower oxygen tensions than the blood or the atmosphere. Furthermore, inflammatory and tumor environments where lymphocytes execute effector functions also have very low,oxygen tensions. These findings led to the hypothesis that lymphocytes may have evolved adaptive mechanisms to function under hypoxic conditions. Cellular responses to hypoxia are triggered by the hypoxia inducible factor-1alpha (HIF-1alpha). In this paper we review the development and function of T- and B-lymphocytes in the absence HIF-1alpha. Our studies suggest that HIF-1alpha deficiency depresses the function of cytotoxic T-lymphocytes and blocks B-cell development in the bone marrow. B1 lymphocytes of fetal origin, on the other hand, accumulate and may produce auto-antibodies and autoimmunity. C1 Mayo Clin, Dept Surg, Rochester, MN 55905 USA. Mayo Clin, Dept Immunol, Rochester, MN 55905 USA. Dokkyo Univ, Sch Med, Inst Med Sci, Div Immunol, Mibu, Tochigi 321093, Japan. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Cascalho, M (reprint author), Mayo Clin, Dept Surg, 200 1st St SW,Med Sci 2-113, Rochester, MN 55905 USA. NR 50 TC 16 Z9 18 U1 2 U2 2 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 23 BP 1827 EP 1832 DI 10.2174/1381612033454388 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 713HG UT WOS:000184851000002 PM 12871187 ER PT J AU Bergmann-Leitner, ES Duncan, EH Leitner, WW AF Bergmann-Leitner, ES Duncan, EH Leitner, WW TI Identification and targeting of tumor escape mechanisms: A new hope for cancer therapy? SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE tumor escape; radio-resistance; drug-resistance; immunotherapy ID DNA MISMATCH REPAIR; CARCINOMA CELL-LINES; CLASS-I ANTIGENS; ENDOTHELIAL GROWTH-FACTOR; REACTIVE T-CELLS; MHC CLASS-I; INDUCED APOPTOSIS; MULTIDRUG-RESISTANCE; OVARIAN-CANCER; FAS LIGAND AB Conventional cancer therapy is administered in the form of surgery, radiotherapy or chemotherapy. Immunotherapy is the latest asset to the panel of anti-cancer treatments. This approach appears favorable over the other more conventional methods for various reasons: (1) it is highly specific for cancer cells and, therefore, low toxicity should be expected; (2) it recognizes and eliminates cancer cells regardless of their phase in the cell cycle; (3) tumors that developed drug resistances would still be a suitable target for immunotherapy. (4) Immunotherapy offers the possibility of preventive immunization of high-risk patients. Due to the diverse mechanisms that result in the transformation of cells and subsequent tumor development, not all cancers respond similarly to treatment. Significant effort is currently invested in the characterization of the underlying regulatory network in individual cancers responsible for tumorigenesis. Understanding tumors better allows on one hand the identification of essential pathways that can be intercepted to kill the transformed cells more specifically. On the other hand, these insights also allow LIS to exclude therapeutic strategies with little chance of success when dealing with tumor escape mutants thus saving valuable time and resources. Any tumor therapy puts selective pressure on tumors thus favoring the outgrowth of therapy-resistant variants. This review summarizes current knowledge on tumor escape mechanisms and some of the efforts to overcome these mechanisms. C1 Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Bergmann-Leitner, ES (reprint author), Walter Reed Army Inst Res, Dept Immunol, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner, Wolfgang/0000-0003-3125-5922 NR 189 TC 11 Z9 11 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 25 BP 2009 EP 2023 DI 10.2174/1381612033454199 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 721CV UT WOS:000185300200002 PM 14529412 ER PT J AU Frankel, AE Koo, HM Leppla, SH Duesbery, NS Vande Woude, GF AF Frankel, AE Koo, HM Leppla, SH Duesbery, NS Vande Woude, GF TI Novel protein targeted therapy of metastatic melanoma SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID ANTHRAX LETHAL FACTOR; ALLOGENEIC-TUMOR VACCINE; NODE-NEGATIVE MELANOMA; PROTECTIVE ANTIGEN; MALIGNANT-MELANOMA; PROGNOSTIC FACTORS; INTERMEDIATE-THICKNESS; ADJUVANT IMMUNOTHERAPY; BACILLUS-ANTHRACIS; III MELANOMA AB Metastatic melanoma patients have a dismal prognosis with poor responsiveness to chemotherapy, radiation therapy and current immunotherapy regimens and a median survival of less than six months. Novel therapies directed at melanoma-selective molecular targets are urgently needed. Based on the frequent constitutive activation of the mitogenactivated protein kinase (MAPK) signaling pathway in malignant melanomas and the selective inhibition of MAPK signaling by anthrax lethal factor which proteolytically cleaves MAPK kinases, anthrax lethal toxin may be a useful agent for patients with metastatic melanoma. Anthrax lethal toxin consists of two proteins--protective antigen and lethal factor. These two proteins have been separately produced in good yields and in high purity. The three-dimensional structures of these proteins have been solved, and their molecular mechanisms of cell binding and action determined. Preclinical studies with anthrax lethal toxin show sensitivity of malignant melanoma cell lines in tissue culture and anti-tumor efficacy in melanoma xenograft models. Additional studies to define the maximal tolerated doses and dose-limiting toxicity of anthrax lethal toxin in rodent and primate models should pave the way for phase I studies testing the efficacy of the anthrax lethal toxin in patients with metastatic melanoma. C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA. Van Andel Res Inst, Grand Rapids, MI USA. Natl Inst Hlth, Bethesda, MD USA. RP Frankel, AE (reprint author), Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA. OI DUESBERY, NICK/0000-0002-4258-5655 NR 64 TC 14 Z9 15 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 25 BP 2060 EP 2066 DI 10.2174/1381612033454162 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 721CV UT WOS:000185300200006 PM 14552326 ER PT J AU Meng, LH Liao, ZY Pommier, Y AF Meng, LH Liao, ZY Pommier, Y TI Non-camptothecin DNA topoisomerase I inhibitors in cancer therapy SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE topoisomerase I; camptothecin; indolocarbazoles; indenoisoquinolines; benzimidazoles; minor groove binders; chemotherapy; DNA damage ID SYSTEM TUMOR XENOGRAFTS; COMPOUND 6-N-FORMYLAMINO-12,13-DIHYDRO-1,11-DIHYDROXY-13-(BETA-D-GLUCOPYRANOSYL); <2,3-A>PYRROLO <3,4-C>CARBAZOLE-5,7(6H)-DIONE NB-506; DIOL EPOXIDE ADDUCTS; MINOR-GROOVE; ANTITUMOR-ACTIVITY; CELL-LINES; INDOLOCARBAZOLE COMPOUND; ANTICANCER AGENTS; PHASE-I AB Human DNA topoisomerase I is the target of camptothecins, which have been recently introduced in the clinic for cancer chemotherapy. The discovery of novel non-camptothecin inhibitors is facilitated by the availability of biochemical and cellular assays for testing topoisomerase I activity. Among the non-camptothecin inhibitors, the indolocarbazoles (NB-506 and J-107088) are the most advanced in their development, and are in clinical trials. A number of indenoisoquinolines and minor groove binders (benzimidazoles) have been reported recently. Their antitumor activity is promising for further development. The potential binding site(s) of topoisomerase I inhibitors in the enzyme I-DNA complex is discussed. C1 NCI, Canc Res Ctr, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Canc Res Ctr, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NR 130 TC 94 Z9 100 U1 0 U2 13 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2003 VL 3 IS 3 BP 305 EP 320 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 653PN UT WOS:000181445700004 PM 12570765 ER PT J AU Lee, K Burke, TR AF Lee, K Burke, TR TI CD45 protein-tyrosine phosphatase inhibitor development SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID STRUCTURE-BASED DESIGN; SOLID-PHASE SYNTHESIS; SIGNAL-TRANSDUCTION; SUBSTRATE RECOGNITION; PHENYLARSINE OXIDE; T-CELLS; POTENT; MECHANISM; PEPTIDES; PTP1B AB The protein-tyrosine phosphatase (PTP) CD45 serves both positive and negative signaling elements by dephosphorylating regulatory pTyr residues on Src-family protein-tyrosine kinases. Although its physiological participation in immune function makes it an important point of intervention for treatment of a variety of inflammatory and immune disorders, comparatively little has been reported on development of CD45 inhibitors. Frequently, when inhibitory data against CD45 is reported, the data has been generated secondarily to other target PTPs. The focus of the current review is to summarize the types of structures that have been found to inhibit CD45, even in cases the compounds themselves were designed as antagonists of other PTPs. The review's organization begins with generic broad spectrum PTP inhibitors and progresses from peptide-based inhibitors and small molecule peptide mimetics to inhibitors that have resulted from screening hits. Although potent and moderately selective CD45 inhibitors have been reported, no single dominant theme has yet emerged in the design of these CD45 directed agents. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, POB B,Bldg 376 Boyles St, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 NR 73 TC 12 Z9 16 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2003 VL 3 IS 7 BP 797 EP 807 DI 10.2174/1568026033452267 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 653XP UT WOS:000181462600006 PM 12678845 ER PT S AU Gu, XX Jiao, X Hirano, T Hou, Y Hu, WG AF Gu, XX Jiao, X Hirano, T Hou, Y Hu, WG BE Yamanaka, N TI Mucosal vaccines for Moraxella catarrhalis SO CURRENT TOPICS ON TONSILS AND MUCOSAL BARRIERS OF UPPER AIRWAYS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 5th International Symposium on Tonsils and Mucosal Barriers of Upper Airways CY APR 09-11, 2003 CL Barriers Upper Airways, Wakayama, JAPAN HO Barriers Upper Airways DE Moraxella catarrhalis; mucosal vaccine; adjuvant; delivery systems; animal models ID BRANHAMELLA CATARRHALIS; PULMONARY CLEARANCE; IMMUNE-RESPONSES; IMMUNIZATION; ENHANCEMENT; MODEL AB Moraxella catarrhalis is an important human mucosal pathogen that causes otitis media in children and respiratory tract infections in adults. An optimal defense against mucosal pathogens would be mucosal vaccines. Since 1994, researchers have attempted to use different mucosal immunization regimes in mice such as oral, intra-Peyer's patches (IPP), intra-tracheal (IT), and intranasal (IN) administration either on killed cells or on outer membrane proteins. Among them, the only effective mucosal regimen turned out to be a combination of IPP and IT immunization. We investigated the mucosal immune response elicited by IN with a detoxified lipooligosaccharide-cross-reactive mutant of diphtheria toxin (dLOS-CRM) conjugate. IN immunization with dLOS-CRM induced specific mucosal and systemic immunity and provided effective bacterial clearance in mouse lungs. To further enhance the mucosal immune response, intra-nasal-associated lymphoid tissue (NALT) administration of vaccines, was developed. In addition, a nasopharyngeal clearance mouse model is being tested. Although many vaccine candidates have been investigated by systemic immunization, mucosal vaccines for M. catarrhalis have been limited by the lack of appropriate adjuvants, vaccine delivery systems, and animal models. Future expectations are discussed. (C) 2003 Elsevier B.V. All rights reserved. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. RP Gu, XX (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court,Room 2A31, Rockville, MD 20850 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51538-0 J9 INT CONGR SER PY 2003 VL 1257 BP 63 EP 67 DI 10.1016/S0531-5131(03)01399-2 PG 5 WC Immunology; Infectious Diseases; Otorhinolaryngology SC Immunology; Infectious Diseases; Otorhinolaryngology GA BY62K UT WOS:000189423800009 ER PT B AU Gonzalez, FJ Yu, A Granvil, CP Kupfer, A Idle, JR AF Gonzalez, FJ Yu, A Granvil, CP Kupfer, A Idle, JR BE Anzenbacher, P Hudecek, J TI The study of xenobiotic-metabolizing P450s using transgenic mice SO CYTOCHROMES P450, BIOCHEMISTRY, BIOPHYSICS AND DRUG METABOLISM LA English DT Proceedings Paper CT 13th International Conference on Cytochromes P450 CY JUN 29-JUL 03, 2003 CL PRAGUE, CZECH REPUBLIC ID HUMAN CYP2D6; DEBRISOQUINE; CYP1A2; MOUSE; GENE; PHARMACOKINETICS; SUSCEPTIBILITY; ACETAMINOPHEN; EXPRESSION C1 Natl Canc Inst, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), Natl Canc Inst, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-3141-1 PY 2003 BP 35 EP 40 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Genetics & Heredity; Pharmacology & Pharmacy GA BX99S UT WOS:000187165400006 ER PT J AU Modi, WS AF Modi, WS TI Morphological, chromosomal, and molecular evolution are uncoupled in pocket mice SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID PEROGNATHUS-AMPLUS; PATTERNS; AMERICAN; RODENTS; PHYLOGEOGRAPHY; LONGIMEMBRIS; CHAETODIPUS; GENE AB C-, and G-banded chromosomes are presented for Perognathus amplus and Perognathus longimembris from Arizona, USA and Chaetodipus nelsoni from Coahuila, Mexico. The two species of Perognathus reveal similar C-band patterns, and extensive autosomal and X chromosome G-band identity with only pericentric inversions distinguishing pairs 4 and 6 and a difference in the morphology of pair 20. Three pairs of autosomal secondary constrictions were found in P. amplus and only one in P. longimembris. Only 50% of the amplus/ longimembris G-banded karyotype could be aligned with that of C nelsoni indicating extensive chromosomal restructuring has taken place since these genera last shared a common ancestor. A review of the literature suggests variable rates of morphological, chromosomal and molecular evolution in these animals. Copyright (C) 2003 S. Karger AG, Basel C1 NCI, SAIC Frederick, Basic Res Program, Ft Detrick, MD 21702 USA. RP Modi, WS (reprint author), NCI, SAIC Frederick, Basic Res Program, Ft Detrick, MD 21702 USA. EM modi@ncifcrf.gov FU NCI NIH HHS [N01-CO-124000] NR 30 TC 2 Z9 3 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2003 VL 103 IS 1-2 BP 150 EP 154 DI 10.1159/000076303 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 807ZE UT WOS:000220538600026 PM 15004479 ER PT J AU Lieto, LD Cothran, EG AF Lieto, LD Cothran, EG TI The epitheliogenesis imperfecta locus maps to equine chromosome 8 in American Saddlebred horses SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; DINUCLEOTIDE REPEAT LOCI; MICROSATELLITE LOCI; LAMB3 GENE; MARKERS; GENOME; IDENTIFICATION; LAMININ-5; MUTATIONS; ASSIGNMENTS AB Epitheliogenesis imperfecta (EI) is a hereditary junctional mechanobullous disease that occurs in newborn American Saddlebred foals. The pathological signs of epitheliogenesis imperfecta closely match a similar disease in humans known as Herlitz junctional epidermolysis bullosa, which is caused by a mutation in one of the genes (LAMA3, LAMB3 and LAMC2) coding for the subunits of the laminin 5 protein (laminin 0, laminin 03 and laminin 72). The LAMA3 gene has been assigned to equine chromosome 8 and LAMB3 and LAMC2 have been mapped to equine chromosome 5. Linkage disequilibrium between microsatellite markers that mapped to equine chromosome 5 and equine chromosome 8 and the El disease locus was tested in American Saddlebred horses. The allele frequencies of microsatellite alleles at 11 loci were determined for both epitheliogenesis imperfecta affected and unaffected populations of American Saddlebred horses by genotyping and direct counting of alleles. These were used to determine fit to Hardy-Weinberg equilibrium for control and El populations using Chi square analysis. Two microsatellite loci located on equine chromosome 8q, ASB14 and AHT3, were not in Hardy-Weinberg equilibrium in affected American Saddlebred horses. In comparison, all of the microsatellite markers located on equine chromosome 5 were in Hardy-Weinberg equilibrium in affected American Saddlebred horses. This suggested that the El disease locus was located on equine chromosome 8q, where LAMA3 is also located. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ Kentucky, Dept Vet Sci, Lexington, KY 40506 USA. RP Lieto, LD (reprint author), NIAID, RCBS, LAD, NIH, Twinbrook 11 RM 205,12441 Parklawn Dr, Rockville, MD 20852 USA. EM llicto@niaid.nih.gov NR 29 TC 9 Z9 9 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2003 VL 102 IS 1-4 BP 207 EP 210 DI 10.1159/000075750 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 807ZD UT WOS:000220538500035 PM 14970704 ER PT J AU Menotti-Raymond, M David, VA Agarwala, R Schaffer, AA Stephens, R O'Brien, SJ Murphy, WJ AF Menotti-Raymond, M David, VA Agarwala, R Schaffer, AA Stephens, R O'Brien, SJ Murphy, WJ TI Radiation hybrid mapping of 304 novel microsatellites in the domestic cat genome SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID COMPREHENSIVE GENETIC-MAP; IMMUNODEFICIENCY VIRUS; MOUSE GENOME; FELIS-CATUS; MAMMALS; INTEGRATION; LESSONS; CANINE; LOCI AB Effective utilization of the domestic cat as an animal model for hereditary and infectious disease requires the development and implementation of high quality gene maps incorporating microsatellites and conserved coding gene markers. Previous feline linkage and radiation hybrid maps have lacked sufficient microsatellite coverage on all chromosomes to make effective use of full genome scans. Here we report the isolation and genomic mapping of 304 novel polymorphic repeat loci in the feline genome. The new loci were mapped in the domestic cat radiation hybrid panel using an automated fluorescent Taq-Man based assay. The addition of these 304 microsatellites brings the total number of microsatellites mapped in the feline genome to 580, and the total number of loci placed onto the RH map to 1,126. Microsatellites now span every autosome with an average spacing of roughly one polymorphic STR every five centimorgans, and full genome coverage of one marker every 2.7 megabases. These loci now provide a useful tool for undertaking full-genome scans to identify genes associated with phenotypes of interest, such as those relating to hereditary disease, coat color, patterning and morphology. These resources can also be extended to the remaining 36 species of the cat family for population genetic and evolutionary genomic analyses. Copyright (C) 2003 S. Karger AG, Basel C1 NCI, Lab Genom Divers, Dept Hlth & Human Serv, Frederick, MD 21702 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, CBB, Bethesda, MD 20894 USA. NCI, Adv Biomed Comp Ctr, Dept Hlth & Human Serv, Frederick, MD 21701 USA. NCI, SAIC Frederick Inc, Lab Genom Divers, Basic Res Program,Dept Hlth & Human Serv, Frederick, MD 21701 USA. RP Menotti-Raymond, M (reprint author), NCI, Lab Genom Divers, Dept Hlth & Human Serv, Bldg 560,Rm 21-48, Frederick, MD 21702 USA. EM raymond@ncifcrf.gov; murphywi@ncifcrf.gov RI Schaffer, Alejandro/F-2902-2012 NR 33 TC 42 Z9 42 U1 2 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2003 VL 102 IS 1-4 BP 272 EP 276 DI 10.1159/000075762 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 807ZD UT WOS:000220538500047 PM 14970716 ER PT J AU Greene, E Handa, V Kumari, D Usdin, K AF Greene, E Handa, V Kumari, D Usdin, K TI Transcription defects induced by repeat expansion: fragile X syndrome, FRAXE mental retardation, progressive myoclonus epilepsy type 1, and Friedreich ataxia SO CYTOGENETIC AND GENOME RESEARCH LA English DT Review ID CYSTATIN-B GENE; FMR1 MESSENGER-RNA; PREMATURE OVARIAN FAILURE; TRIPLET REPEATS; CGG-REPEAT; DNA METHYLATION; HISTONE H3; IN-VITRO; PROMOTER METHYLATION; HAIRPIN STRUCTURES AB Fragile X mental retardation syndrome, FRAXE mental retardation, Progressive myoclonus epilepsy Type 1, and Friedreich ataxia are members of a larger group of genetic disorders known as the Repeat Expansion Diseases. Unlike other members of this group, these four disorders all result from Basel. a primary defect in the initiation or elongation of transcription. In this review, we discuss current models for the relationship between the expanded repeat and the disease symptoms. Copyright (C) 2002 S. Karger AG. C1 NIDDKD, Sect Genom Struct & Funct, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDKD, Sect Genom Struct & Funct, Lab Mol & Cellular Biol, NIH, 8 Ctr Dr,MSC 08230, Bethesda, MD 20892 USA. NR 136 TC 9 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2003 VL 100 IS 1-4 BP 65 EP 76 DI 10.1159/000072839 PG 12 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 738EZ UT WOS:000186274900005 PM 14526165 ER PT J AU Ludes-Meyers, JH Bednarek, AK Popescu, NC Bedford, M Aldaz, CM AF Ludes-Meyers, JH Bednarek, AK Popescu, NC Bedford, M Aldaz, CM TI WWOX, the common chromosomal fragile site, FRA16D, cancer gene SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID CARCINOMA IN-SITU; TUMOR-SUPPRESSOR GENE; COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN BREAST-CANCER; ALLELIC LOSS; PROSTATE-CANCER; DELETED REGIONS; ARM 16Q; MULTIPLE-MYELOMA; HIGH-FREQUENCY AB Gross chromosomal rearrangements and aneuploidy are among the most common somatic genomic abnormalities that occur during cancer initiation and progression, in particular in human solid tumor carcinogenesis. The loss of large chromosomal regions as consequence of gross rearrangements (e.g. deletions.. monosomies, unbalanced translocations and mitotic recombination) have been traditionally associated with the existence of tumor suppressor genes within the areas affected by the loss of genetic material. The long arm of chromosome 16 was identified as being frequently associated with structural abnormalities in multiple neoplasias, that led us to focus attention on the detailed genetic dissection of this region resulting in the cloning of the putative tumor suppressor gene, WWOX (WW domain containing Oxidoreductase). Interestingly, the WWOX gene resides in the very same region as that of the common chromosomal fragile site 16D (FRA16D). The WWOX gene encodes a protein that contains two WW domains, involved in protein-protein interactions, and a short chain dehydrogenase (SDR) domain, possibly involved in sex-steroid metabolism. We have identified the WWOX WW domain ligand as the PPXY motif confirming the biochemical activity of this domain. WWOX normally resides in the Golgi and we will demonstrate that Golgi localization requires an intact SDR. Inactivation of the WWOX gene during tumorigenesis can occur by homozygous deletions and possibly mutation, however, aberrantly spliced forms of WWOX mRNA have been observed even when one allele is still intact. The aberrantly spliced mRNAs have deletions of the exons that encode the SDR and these WWOX protein isoforms display abnormal intracellular localization to the nucleus possibly functioning as dominant negative inhibitors of full length WWOX. Thus, generation of aberrant transcripts of WWOX may represent a novel mechanism to functionally inactivate WWOX without genomic alteration of the remaining allele. In this article we will review the cloning and identification of WWOX as the target of FRA16D. In addition, we will discuss the possible biochemical functions of WWOX and present evidence that ectopic WWOX expression inhibits tumor growth. Copyright (C) 2002 S. Karger AG, Basel. C1 Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78957 USA. Med Univ Lodz, IPh&B Dept Med Biochem, Lodz, Poland. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Aldaz, CM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Sci Pk Res Div,POB 389, Smithville, TX 78957 USA. RI Bedford, Mark/E-7856-2011; Bednarek, Andrzej/S-9664-2016 FU NCI NIH HHS [R01 CA102444-02, R01 CA102444, R01 CA102444-01, R01 CA102444-03, R01 CA102444-04, R01 CA102444-05, R01 CA102444-06A1, R01 CA102444-07] NR 56 TC 59 Z9 62 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2003 VL 100 IS 1-4 BP 101 EP 110 DI 10.1159/000072844 PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 738EZ UT WOS:000186274900010 PM 14526170 ER PT J AU Fleming, K Riser, DK Kumari, D Usdin, K AF Fleming, K Riser, DK Kumari, D Usdin, K TI Instability of the fragile X syndrome repeat in mice: the effect of age, diet and mutations in genes that affect DNA replication, recombination and repair proficiency SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID WERNER-SYNDROME HELICASE; TRANSGENIC MICE; HOMOLOGOUS RECOMBINATION; TRINUCLEOTIDE REPEATS; CHROMOSOME BREAKAGE; ESCHERICHIA-COLI; TRIPLET REPEATS; MISMATCH REPAIR; HUNTINGTONS-DISEASE; MYOTONIC-DYSTROPHY AB Repeat expansion diseases such as fragile X syndrome (FXS) result from increases in the size of a specific tandem repeat array. In addition to large expansions, small changes in repeat number and deletions are frequently seen in FXS pedigrees. No mouse model accurately recapitulates all aspects of this instability, particularly the occurrence of large expansions. This may be due to differences between mice and humans in cis and/or trans-acting factors that affect repeat stability. The identification of such factors may help reveal the expansion mechanism and allow the development of suitable animal models for these disorders. We have examined the effect of age, dietary folate, and mutations in the Werner's syndrome helicase (Wrn) and Trp53 genes on FXS repeat instability in mice. WRN facilitates replication of the FXS repeat and enhances Okazaki fragment processing, thereby reducing the incidence of processes that have been suggested to lead to expansion. p53 is a protein involved in DNA damage surveillance and repair. We find two types of repeat instability in these mice, small changes in repeat number that are seen at frequencies approaching 100%, and large deletions which occur at a frequency of about 10%. The frequency of these events was independent of WRN, p53, parental age, or folate levels. The large deletions occur at the same frequency in mice homozygous and heterozygous for the repeat suggesting that they are not the result of an interallelic recombination event. In addition, no evidence of large expansions was seen. Our data thus show that the absence of repeat expansions in mice is not due to a more efficient WRN protein or p53-mediated error correction mechanism, and suggest that these proteins, or the pathways in which they are active, may not be involved in expansion in humans either. Moreover, the fact that contractions occur in the absence of expansions suggests that these processes occur by different mechanisms. Copyright (C) 2002 S. KargerAG, Basel. C1 NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 202,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. NR 59 TC 5 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2003 VL 100 IS 1-4 BP 140 EP 146 DI 10.1159/000072848 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 738EZ UT WOS:000186274900014 PM 14526174 ER PT J AU Bleesing, JJH Fleisher, TA AF Bleesing, JJH Fleisher, TA TI Human B cells express a CD45 isoform that is siniflar to murine B220 and is downregulated with acquisition of the memory B-CeH marker CD27 SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE B cells; CD45 antigen; CD27 antigen; B220 antigen; flow cytometry ID T-CELLS; BIOSYNTHESIS; COMPARTMENT; ACTIVATION; RECEPTORS; DEFECTS; SUBSETS AB Background: Differences between human and murine B cells exist at all stages of B-cell development, including the stage of memory B-cell formation. B cells in mice are identified with the pan-B-cell-specific CD45 isoform, B220. In initial studies in humans, it appeared that B220 expression did not include all B cells. This study was performed to expand on those preliminary findings. Methods: Multiparameter flow cytometric detection of B220 expression on B cells was combined with a variety of B-cell markers. Results: In contrast to mice, B220 was not a pan-B-cell marker in humans but was downregulated in the majority of B cells that acquired the human memory B-cell marker, CD27, whereas a minor memory B-cell subset remained B220(+), suggesting differences in differentiation. Conclusions: The B220 isoform in humans is developmentally regulated in humans, tied to the acquisition of a memory phenotype, and as such can be used as a differentiation-specific CD45 isoform, akin to the use of CD45 isoforms to distinguish between naive and memory T-cell subsets. Patients with immunodeficiency disorders, associated with defective memory B-cell generation and absent or reduced CD27(+) B cells, showed a corresponding lack of B220 downregulation consistent with altered differentiation of B-cell subsets. Published 2002 Wiley-Liss, Inc. C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. RP Bleesing, JJH (reprint author), UAMS, Arkansas Childrens Hosp, Inst Res, 1120 Marshall St,Slot 512-13, Little Rock, AR 72202 USA. NR 23 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 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2003 VL 51B IS 1 BP 1 EP 8 DI 10.1002/cyto.b.10007 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 671EP UT WOS:000182452600001 PM 12500291 ER PT J AU Carvallo, C Childs, R AF Carvallo, C Childs, R TI Nonmyeloablative stem cell transplantation as immunotherapy for kidney cancer and other metastatic solid tumors SO CYTOTECHNOLOGY LA English DT Article DE allogeneic transplant; immunotherapy; graft-versus tumor; Nonmyeloablative stem cell transplant; Renal Cell Carcinoma ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; DONOR LYMPHOCYTE INFUSIONS; CHRONIC MYELOID-LEUKEMIA; HOST-DISEASE; HEMATOLOGIC MALIGNANCIES; ADOPTIVE IMMUNOTHERAPY; BREAST-CANCER AB Over the past few decades, great strides have been made to advance the field of allogeneic hematopoietic stem cell transplantation. The donor immune mediated graft-vs-tumor effect that follows the procedure is now widely accepted as the most effective form cancer immunotherapy available for patients with a variety of advanced hematological malignancies. Recognition that a transplanted immune system could cure patients with treatment refractory leukemia led to the development of 'low-intensity' conditioning regimens, which have improved the safety of the procedure and broadened the application of allogeneic immunotherapy to a growing list of neoplastic diseases. Here we discuss the investigational use of allogeneic transplantation as immunotherapy for patients with metastatic, treatment-refractory solid tumors. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 67 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-9069 J9 CYTOTECHNOLOGY JI Cytotechnology PY 2003 VL 41 IS 2-3 BP 197 EP 206 DI 10.1023/A:1024839225920 PG 10 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 703LD UT WOS:000184280100016 PM 19002956 ER PT J AU Read, EJ AF Read, EJ TI Going where the action is: cellular therapy for diabetes mellitus SO CYTOTHERAPY LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; GENE-THERAPY; ISLET TRANSPLANTATION; IN-VITRO; INSULIN; ALLOTRANSPLANTATION; DIFFERENTIATION; TISSUE; MARROW; LIVER C1 NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Read, EJ (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bldg 10,Rm 1C711, Bethesda, MD 20892 USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2003 VL 5 IS 3 BP 241 EP 242 DI 10.1080/14653240310001820 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 700VX UT WOS:000184132800009 PM 12850792 ER PT J AU Scheinberg, P AF Scheinberg, P TI Stem-cell transplantation for autoimmune diseases SO CYTOTHERAPY LA English DT Review ID BONE-MARROW-TRANSPLANTATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; NONOBESE DIABETIC MICE; HIGH-DOSE CHEMOTHERAPY; ZEALAND BLACK MICE; RHEUMATOID-ARTHRITIS; IMMUNOLOGICAL RECONSTITUTION; INTENSIVE CHEMOTHERAPY; PROLONGED REMISSION; ADOPTIVE TRANSFER AB The use of intensive immunosuppressive treatment coupled with BM stem-cell transplantation (SCT) to treat human autoimmune diseases (AID) follows anecdotal observations of responses of AID to allogeneic SCT and an extensive background of experience with SCT in animals with AID. hi the last decade, numerous clinical trials have been initiated to explore a potential benefit of (mainly autologous) SCT in advanced and debilitating cases of rheumatoid arthritis, scleroderma, systemic lupus e erythematosis and multiple sclerosis. In this review the etiology of AID and the experimental basis of SCT is presented, together with recent clinical results of SCT for AID. While much has been learned about the risks and benefits of SCT in AID, the underlying mechanisms regulating remission and relapse of AID after treatment remain largely unknown. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. OI Scheinberg, Phillip/0000-0002-9047-4538 NR 46 TC 3 Z9 4 U1 2 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2003 VL 5 IS 3 BP 243 EP 251 DI 10.1080/14653240310001505 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 700VX UT WOS:000184132800010 PM 12850793 ER PT J AU Hakkarainen, R Partonen, T Haukka, J Virtamo, J Albanes, D Lonnqvist, J AF Hakkarainen, R Partonen, T Haukka, J Virtamo, J Albanes, D Lonnqvist, J TI Association of dietary amino acids with low mood SO DEPRESSION AND ANXIETY LA English DT Article DE proteins; amino acids; depressive disorder; diet; mood; suicide ID SEASONAL AFFECTIVE-DISORDER; TRYPTOPHAN DEPLETION; DEPRESSION; SERINE; PLASMA; AUGMENTATION; INSTRUMENTS; METABOLISM; PSYCHOSIS; GLYCINE AB Diet may affect mood and cognitive functions. Tryptophan and serine augmentation strategies have been applied for patients with mood or psychotic disorders. We studied the association between dietary intake of amino acids and low mood. We studied 29,133 men aged 50-69 years for 5-8 years in a population-based trial in Finland. Intake of amino acids was calculated from a diet history questionnaire completed by 27,111 men at baseline. Self-reports of depressed mood were recorded thrice a year, data on hospital treatment due to depressive disorders were derived from the national Hospital Discharge Register, and suicides were identified from death certificates. Participants were smokers at study entry. Strengths of our study include detailed data on food consumption, a substantial number of study participants, a long prospective follow-up time, and versatile data on indices of low mood. We found no association between the dietary intake of amino acids and self-report of depressed mood or risk of suicide. However, dietary intake of lysine and serine was associated with risk of hospital treatment due to major depressive disorder but these associations disappeared after excluding from analysis those who bad reported depressed mood at study entry. There is no consistent association between dietary intake of amino acids and low mood. (C) 2003 Wiley-Liss, Inc. C1 Natl Publ Hlth Inst, Res Associate, Dept Mental Hlth & Alcohol Res, FIN-00300 Helsinki, Finland. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Hakkarainen, R (reprint author), Natl Publ Hlth Inst, Res Associate, Dept Mental Hlth & Alcohol Res, Mannerheimintie 166, FIN-00300 Helsinki, Finland. RI Partonen, Timo/G-1105-2012; Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Partonen, Timo/0000-0003-1951-2455; Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [CN-45035, N01-CN-45165] NR 27 TC 10 Z9 10 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2003 VL 18 IS 2 BP 89 EP 94 DI 10.1002/da.10120 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 726HJ UT WOS:000185592600006 PM 12964176 ER PT J AU Tsao, JCI Craske, MG AF Tsao, JCI Craske, MG TI Fear of loss of vigilance: Development and preliminary validation of a self-report instrument SO DEPRESSION AND ANXIETY LA English DT Article DE nocturnal panic; panic disorder; post-traumatic stress disorder; vigilance; sleep; traumatic events; hypnosis ID TRAIT-ANXIETY-INVENTORY; PANIC ATTACKS; PSYCHOMETRIC PROPERTIES; SENSITIVITY; SLEEP; POPULATION; DISORDER; AROUSAL AB We describe the development and initial validation of the Fear of Loss of Vigilance Questionnaire (FLOVQ). Recent investigations indicate that individuals with nocturnal panic (NP) demonstrate increased anxiety and panic in response to meditative relaxation and imagined hypnosis, compared to those with daytime panic (DP) only, suggesting that NP individuals fear situations that involve a loss of vigilance (e.g., relaxation, fatigue and altered states of consciousness). The FLOVQ was designed to assess this construct and was tested in five non-clinical samples and one clinical sample. The 14-item instrument demonstrated good internal consistency and test-retest reliability. Non-clinical respondents who experienced NP endorsed greater fear of loss of vigilance than non-panickers; those who only experienced DP did not differ from the other groups. By contrast, on measures of trait and state anxiety, and anxiety sensitivity, both panic groups scored higher than non-panickers, suggesting that these latter measures were related to broader factors pertaining to a general tendency to panic versus a specific factor associated with NP No group differences were found between NPs and DPs in either the non-clinical or the clinical sample, suggesting that fear of loss of vigilance may be a vulnerability factor for the development of NP and that the FLOVQ has more utility as a research rather than as a clinical instrument. (C) 2003 Wiley-Liss, Inc. C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. RP Tsao, JCI (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, Box 100165 HSC, Gainesville, FL 32610 USA. FU NIMH NIH HHS [MH 49713-01A2, R01 MH49713] NR 31 TC 6 Z9 6 U1 4 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2003 VL 18 IS 4 BP 177 EP 186 DI 10.1002/da.10074 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 760GD UT WOS:000187802500002 PM 14661187 ER PT J AU Tsao, JCI Craske, MG AF Tsao, JCI Craske, MG TI Reactivity to imagery and nocturnal panic attacks SO DEPRESSION AND ANXIETY LA English DT Article DE nocturnal panic; imagery; panic attacks; panic disorder; vigilance; sleep; trauma; traumatic events; psychophysiology ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOPHYSIOLOGICAL ASSESSMENT; EMOTIONAL IMAGERY; VETERANS; ANXIETY; SLEEP AB We assessed psychophysiological responses to imagery of traumatic events, panic attacks, and loss of vigilance (i.e., being hypnotized) in participants diagnosed with panic disorder. Participants were either currently experiencing nocturnal panic or daytime panics only. It was hypothesized that nocturnal panickers would exhibit heightened responsivity to imagery of their worst panic and worst trauma, as well as being hypnotized, compared to day panickers. Using established imagery procedures, heart rate, skin conductance, and frontalis electromyogram were recorded as participants imagined each scene. Nocturnal and day panickers differed in their responses to the hypnosis scene only. As predicted, nocturnal panickers endorsed more panic symptoms in response to imagery of being hypnotized. Contrary to expectation, nocturnal and daytime panickers showed no differences in physiologic reactivity or self-reported distress to worst trauma or worst panic imagery. The findings are discussed with respect to the role of fear of loss of vigilance for nocturnal panic. (C) 2003 Wile -Liss, Inc. C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. RP Tsao, JCI (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, Box 100165 HSC, Gainesville, FL 32610 USA. FU NIMH NIH HHS [MH49713-01A2, R01 MH49713] NR 26 TC 8 Z9 8 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2003 VL 18 IS 4 BP 205 EP 213 DI 10.1002/da.10091 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 760GD UT WOS:000187802500005 PM 14661190 ER PT J AU Shapira, NA Lessig, MC Goldsmith, TD Szabo, ST Lazoritz, M Gold, MS Stein, DJ AF Shapira, NA Lessig, MC Goldsmith, TD Szabo, ST Lazoritz, M Gold, MS Stein, DJ TI Problematic Internet use: Proposed classification and diagnostic criteria SO DEPRESSION AND ANXIETY LA English DT Article DE addiction; comorbidity; impulse-control disorder; pathological gambling; mania ID COMPULSIVE COMPUTER USE; BEHAVIORAL ADDICTIONS; DISORDER; FEATURES; PSYCHOLOGY; NETWORKS; IMPACT; SEX; MEN AB Since the mid-1990s, there have been frequent reports of individuals whose use of the computer and internet is problematic. Given the recent expansion and the expected increase in internet availability and usage in the coming years, it is important that healthcare professionals be informed about this behavior and its associated problems. Recently, psychological and psychiatric literature has described individuals that exhibit problematic internet use who often suffer from other psychiatric disorders. In the face of this comorbidity, it is essential to evaluate whether these individuals represent a distinct class of disorder, or a manifestation/coping mechanism related to other underlying diagnosis. In either event, problematic internet use negatively impacts social and emotional functioning. Based on the current limited empirical evidence, problematic internet use may best be classified as an impulse control disorder. It is therefore imperative that problematic internet use be appropriately identified among symptomatic individuals. For these reasons, we propose specific diagnostic criteria that will allow for consistent identification and assist in further study of this behavior. (C) 2003 Wiley-Liss, Inc. C1 Univ Florida, Dept Psychiat, EF & WL McKnight Brain Inst, Gainesville, FL 32610 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Stellenbosch, Dept Psychiat, Cape Town, South Africa. RP Shapira, NA (reprint author), Univ Florida, Dept Psychiat, EF & WL McKnight Brain Inst, Gainesville, FL 32610 USA. RI Stein, Dan/A-1752-2008 OI Stein, Dan/0000-0001-7218-7810 NR 64 TC 233 Z9 246 U1 12 U2 63 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2003 VL 17 IS 4 BP 207 EP 216 DI 10.1002/da.10094 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 698AF UT WOS:000183974900003 PM 12820176 ER PT J AU Brown, JL Fritsch, C Mueller, J Kassis, JA AF Brown, JL Fritsch, C Mueller, J Kassis, JA TI The Drosophila pho-like gene encodes a YY1-related DNA binding protein that is redundant with pleiohomeotic in homeotic gene silencing SO DEVELOPMENT LA English DT Article DE polycomb group genes; gene silencing; Drosophila ID POLYCOMB RESPONSE ELEMENT; LONG-RANGE REPRESSION; GAGA-FACTOR; BITHORAX COMPLEX; CHROMOSOMAL PROTEIN; MELANOGASTER; EXPRESSION; CHROMATIN; MAINTENANCE; TRITHORAX AB Polycomb group proteins (PcG) repress homeotic genes in cells where these genes must remain inactive during Drosophila and vertebrate development. This repression depends on cis-acting silencer sequences, called Polycomb group response elements (PREs). Pleiohomeotic (Pho), the only known sequence-specific DNA-binding PcG protein, binds to PREs but pho mutants show only mild phenotypes compared with other PcG mutants. We characterize pho-like, a gene encoding a protein with high similarity to Pho. Pho-like binds to Pho-binding sites in vitro and pho-like, pho double mutants show more severe misexpression of homeotic genes than do the single mutants. These results suggest that Pho and Pho-like act redundantly to repress homeotic genes. We examined the distribution of five PcG proteins on polytene chromosomes from pho-like, pho double mutants. Pc, Psc, Scm, E(z) and Ph remain bound to polytene chromosomes at most sites in the absence of Pho and Pho-like. At a few chromosomal locations, however, some of the PcG proteins are no longer present in the absence of Pho and Pho-like, suggesting that Pho-like and Pho may anchor PcG protein complexes to only a subset of PREs. Alternatively, Pho-like and Pho may not participate in the anchoring of PcG complexes, but may be necessary for transcriptional repression mediated through PREs. In contrast to Pho and Pho-like, removal of Trithorax-like/GAGA factor or Zeste, two other DNA-binding proteins implicated in PRE function, does not cause misexpression of homeotic genes or reporter genes in imaginal disks. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. European Mol Biol Lab, Gene Express Programme, D-69117 Heidelberg, Germany. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. RP Kassis, JA (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. OI Kassis, Judith/0000-0001-9268-3213 NR 59 TC 111 Z9 114 U1 1 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 JAN PY 2003 VL 130 IS 2 BP 285 EP 294 DI 10.1242/dev.00204 PG 10 WC Developmental Biology SC Developmental Biology GA 641FH UT WOS:000180733900005 PM 12466196 ER PT J AU Gutierrez, L Zurita, M Kennison, JA Vazquez, M AF Gutierrez, L Zurita, M Kennison, JA Vazquez, M TI The Drosophila trithorax group gene tonalli (tna) interacts genetically with the Brahma remodeling complex and encodes an SP-RING finger protein SO DEVELOPMENT LA English DT Article DE homeotic gene regulation; brahma; trithorax group; sumoylation; chromatin remodeling; SWI/SNF; taranis; tonalli; drosophila melanogaster ID DOSAGE-DEPENDENT MODIFIERS; SUMO E3 LIGASE; MEDIATOR COMPLEX; HOMEOTIC GENE; TRANSCRIPTIONAL ACTIVATION; SEGMENT IDENTITY; DISC DEVELOPMENT; NUCLEAR-BODIES; TARGET GENES; P53 ACTIVITY AB The trithorax group genes are required for positive regulation of homeotic gene function. The trithorax group gene brahma encodes a SW12/SNF2 family ATPase that is a catalytic subunit of the Brm chromatin-remodeling complex. We identified the tonalli (tna) gene in Drosophila by genetic interactions with brahma. tna mutations suppress Polycomb phenotypes and tna is required for the proper expressions of the Antennapedia, Ultrabithorax and Sex combs reduced homeotic genes. The tna gene encodes at least two proteins, a large isoform (TnaA) and a short isoform (TnaB). The TnaA protein has an SP-RING Zn finger, conserved in proteins from organisms ranging from yeast to human and thought to be involved in the sumoylation of protein substrates. Besides the SP-RING finger, the TnaA protein also has extended homology with other eukaryotic proteins, including human proteins. We show that tna mutations also interact with mutations in additional subunits of the Brm, complex, with mutations in subunits of the Mediator complex, and with mutations of the SW12/SNF2 family ATPase gene kismet. We propose that Tna is involved in postranslational modification of transcription complexes. C1 Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Fisiol Mol & Genet Desarrollo, Cuernavaca 62250, Morelos, Mexico. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Vazquez, M (reprint author), Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Fisiol Mol & Genet Desarrollo, Cuernavaca 62250, Morelos, Mexico. EM mvazquez@ibt.unam.mx NR 77 TC 34 Z9 34 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN PY 2003 VL 130 IS 2 BP 343 EP 354 DI 10.1242/dev.00222 PG 12 WC Developmental Biology SC Developmental Biology GA 641FH UT WOS:000180733900010 PM 12466201 ER PT J AU Kelley, MW AF Kelley, MW TI Cell adhesion molecules during inner ear and hair cell development, including Notch and its ligands SO DEVELOPMENT OF AUDITORY AND VESTIBULAR SYSTEMS 3: MOLECULAR DEVELOPMENT OF THE INNER EAR SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID 7-PASS TRANSMEMBRANE RECEPTOR; DEPENDENT NEURITE OUTGROWTH; CENTRAL-NERVOUS-SYSTEM; MIND-BOMB MUTANT; SYNDROME TYPE 1D; IMMUNOGLOBULIN SUPERFAMILY; POLYSIALIC ACID; USHER-SYNDROME; N-CAM; EXTRACELLULAR-MATRIX C1 Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, Rockville, MD 20850 USA. RP Kelley, MW (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, Rockville, MD 20850 USA. NR 186 TC 26 Z9 30 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 J9 CURR TOP DEV BIOL PY 2003 VL 57 BP 321 EP 356 DI 10.1016/S0070-2153(03)57011-9 PG 36 WC Developmental Biology SC Developmental Biology GA BY12R UT WOS:000187793300011 PM 14674486 ER PT J AU Suemizu, H Aiba, K Yoshikawa, T Sharov, AA Shimozawa, N Tamaoki, N Ko, MSH AF Suemizu, H Aiba, K Yoshikawa, T Sharov, AA Shimozawa, N Tamaoki, N Ko, MSH TI Expression profiling of placentomegaly associated with nuclear transplantation of mouse ES cells SO DEVELOPMENTAL BIOLOGY LA English DT Article DE placentomegaly; gene expression; expression profiling; nuclear transplantation; ES cell; NIA mouse 15k cDNA microarray ID EMBRYONIC STEM-CELLS; FETAL OVERGROWTH; CLONED MICE; DNA METHYLATION; SOMATIC-CELLS; CLONING; ADULT; GENOME; PLACENTA; CULTURE AB Transplantation of nuclei (NT) from engineered mouse ES cells is a potentially powerful and rapid route to create knockout mice, obviating the need for matings to obtain germ-line chimeras. However, such an application is currently impossible, because NT often results in abnormalities in embryo and placenta. Although the epigenetic instability of several imprinted genes in ES cells and ES-derived NT mice has been demonstrated, it is not clear yet what causes the abnormalities. To gain perspective on the extent and types of changes, we have done gene expression profiling for mouse placentas produced by NT of ES cells and compared them with the expression profiles of placentas produced by NT of one-cell embryos. Based on microarray studies with the NIA 15K mouse cDNA collection, we report five principal aberrant events: (1) inappropriate expression of imprinted genes; (2) altered expression of regulatory genes involved in global gene expression, such as DNA methyltransferase and histone acetyltransferase; (3) increased expression of oncogenes and growth promoting genes; (4) overexpression of genes involved in placental growth, such as Plac1; and (5) identification of many novel genes overexpressed in ES-derived NT mouse placentas, including Pitrm1, a new member of the metalloprotease family. The results indicate that placentomegaly in ES-derived NT mice is associated with large-scale dysregulation of normal gene expression patterns. The study also suggests the presence of two regulatory pathways that may lead to histologically discernable placentomegaly. The discovery of groups of genes with altered expression may provide potential targets for intervention to mimic natural regulation more faithfully in NT mice. (C) 2003 Elsevier Science (USA). C1 NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. Cent Inst Expt Anim, Miyamae Ku, Kawasaki, Kanagawa 2160001, Japan. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 42 TC 55 Z9 59 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 2003 VL 253 IS 1 BP 36 EP 53 DI 10.1006/dbio.2002.0870 PG 18 WC Developmental Biology SC Developmental Biology GA 629PG UT WOS:000180057600003 PM 12490196 ER PT J AU Lee, J Wu, YY Qi, YC Xue, HP Liu, Y Scheel, D German, M Qiu, MS Guillemot, F Rao, M AF Lee, J Wu, YY Qi, YC Xue, HP Liu, Y Scheel, D German, M Qiu, MS Guillemot, F Rao, M TI Neurogenin3 participates in gliogenesis in the developing vertebrate spinal cord SO DEVELOPMENTAL BIOLOGY LA English DT Article DE bHLH; homeodomain; Ngn3; Nkx2.2; development; differentiation; oligodendrocytes; astrocytes; glia; spinal cord ID CENTRAL-NERVOUS-SYSTEM; HOMEODOMAIN TRANSCRIPTION FACTOR; FIBRILLARY ACIDIC PROTEIN; VENTRAL NEURAL-TUBE; OLIGODENDROCYTE LINEAGE; PROGENITOR CELLS; SONIC HEDGEHOG; GLIAL FATE; BHLH PROTEINS; MICE LACKING AB To study the role of basic helix-loop-helix (bHLH) transcription factors in gliogenesis, we examined whether bHLH transcription factors were expressed in glial precursor cells and participated in regulating oligodendrocyte and astrocyte development. As assessed by reverse transcription-polymerase chain reaction (RT-PCR), Neurogenin3 (Ngn3) was transiently expressed in bipotential glial cells fated to become either oligodendrocytes or astrocytes. Mice lacking Ngn3 displayed a loss of Nkx2.2 expression, a transcription factor required for proper oligodendrogliogenesis. Furthermore, a reduction in the expression of myelin basic protein (MBP), proteolipid protein (PLP), and glial fibrillary acidic protein (GFAP), markers for mature oligodendrocytes and astrocytes, was observed in the Ngn3 null mice. Overexpression of Ngn3 was sufficient to drive expression from the PLP promoter in transient cotransfection assays. Overall, the data suggest that Ngn3 may regulate glial differentiation at a developmental stage prior to the segregation of the oligodendrocyte and astrocyte lineage. (C) 2003 Elsevier Science (USA). C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY 40241 USA. Univ Calif San Francisco, Hormone Res Inst, San Francisco, CA 94143 USA. Univ Strasbourg 1, IGBMC, F-67404 Illkirch Graffenstaden, CU De Strasbour, France. RP Rao, M (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Gradwohl, Gerard/H-8543-2014 OI Gradwohl, Gerard/0000-0002-6730-2615 NR 63 TC 48 Z9 49 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 2003 VL 253 IS 1 BP 84 EP 98 DI 10.1006/dbio.2002.0868 PG 15 WC Developmental Biology SC Developmental Biology GA 629PG UT WOS:000180057600006 PM 12490199 ER PT J AU Itoh, M Kim, CH Palardy, G Oda, T Jiang, YJ Maust, D Yeo, SY Lorick, K Wright, GJ Ariza-McNaughton, L Weissman, AM Lewis, J Chandrasekharappa, SC Chitnis, AB AF Itoh, M Kim, CH Palardy, G Oda, T Jiang, YJ Maust, D Yeo, SY Lorick, K Wright, GJ Ariza-McNaughton, L Weissman, AM Lewis, J Chandrasekharappa, SC Chitnis, AB TI Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by delta SO DEVELOPMENTAL CELL LA English DT Article ID AMINO-ACID PERMEASE; CELL FATE; PRIMARY NEUROGENESIS; LATERAL INHIBITION; XENOPUS EMBRYOS; ANKYRIN REPEAT; DANIO-RERIO; ZEBRAFISH; DROSOPHILA; HOMOLOG AB Lateral inhibition, mediated by Notch signaling, leads to the selection of cells that are permitted to become neurons within domains defined by proneural gene expression. Reduced lateral inhibition in zebrafish mib mutant embryos permits too many neural progenitors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a RING ubiquitin ligase. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalization. Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells. These observations support a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell. This facilitates intramembranous cleavage of the remaining Notch receptor, release of the Notch intracellular fragment, and activation of target genes in neighboring cells. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Canc Res UK, Vertebrate Dev Lab, London WC2A 3PX, England. NCI, Regulat Prot Funct Lab, NIH, Frederick, MD 21702 USA. RP Chitnis, AB (reprint author), NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RI Lewis, Julian/E-8733-2010; Jiang, Yun-Jin/E-3995-2010 OI Jiang, Yun-Jin/0000-0003-0499-7306 NR 59 TC 512 Z9 523 U1 5 U2 28 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2003 VL 4 IS 1 BP 67 EP 82 DI 10.1016/S1534-5807(02)00409-4 PG 16 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 643LD UT WOS:000180862000011 PM 12530964 ER PT J AU Hukriede, NA Tsang, TE Habas, R Khoo, PL Steiner, K Weeks, DL Tam, PPL Dawid, IB AF Hukriede, NA Tsang, TE Habas, R Khoo, PL Steiner, K Weeks, DL Tam, PPL Dawid, IB TI Conserved requirement of Lim1 function for cell movements during gastrulation SO DEVELOPMENTAL CELL LA English DT Article ID MOUSE EMBRYO; PARAXIAL PROTOCADHERIN; XENOPUS GASTRULATION; BODY PLAN; SPEMANNS ORGANIZER; TISSUE SEPARATION; PRIMITIVE STREAK; HEAD FORMATION; SMALL GTPASES; GENE XLIM-1 AB To investigate Lim1 function during gastrulation, we used transcript depletion through DEED antisense oligonucleotides in Xenopus and cell transplantation in mice. Xenopus embryos depleted of Lim1 lack anterior head structures and fail to form a proper axis as a result of a failure of gastrulation movements, even though mesodermal cell identities are specified. Similar disruption of cell movements in the mesoderm is also observed in Lim1(-/-) mice. Paraxial protocadherin (PAPC) expression is lost in the nascent mesoderm of Lim1(-/-) mouse embryos and in the organizer of Lim1-depleted Xenopus embryos; the latter can be rescued to a considerable extent by supplying PAPC exogenously. We conclude that a primary function of Lim1 in the early embryo is to enable proper cell movements during gastrulation. C1 NICHHD, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. Childrens Med Res Inst, Embryol Unit, Wentworthville, NSW 2145, Australia. Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. RP Dawid, IB (reprint author), NICHHD, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. RI Weeks, Daniel/F-6216-2010 NR 61 TC 76 Z9 81 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2003 VL 4 IS 1 BP 83 EP 94 DI 10.1016/S1534-5807(02)00398-2 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 643LD UT WOS:000180862000012 PM 12530965 ER PT J AU Nelson, KB AF Nelson, KB TI 'Defining hypoxic-ischemic birth events' SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Letter ID MATERNAL FEVER; HISTOLOGIC CHORIOAMNIONITIS; INFECTION; INFANTS; LABOR C1 NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. RP Nelson, KB (reprint author), NINDS, Neuroepidemiol Branch, Bldg 10,Room 5S221, Bethesda, MD 20892 USA. NR 10 TC 5 Z9 5 U1 0 U2 0 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 JAN PY 2003 VL 45 IS 1 BP 71 EP 71 DI 10.1017/S0012162203210136 PG 1 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 640TR UT WOS:000180704500012 PM 12549759 ER PT J AU Bastian, ML Sponberg, AC Sponberg, AC Suomi, SJ Higley, JD AF Bastian, ML Sponberg, AC Sponberg, AC Suomi, SJ Higley, JD TI Long-term effects of infant rearing condition on the acquisition of dominance rank in juvenile and adult rhesus macaques (Macaca mulatta) SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE rhesus monkey; rearing condition; aggression; dominance; weight gain ID NONHUMAN PRIMATE MODEL; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; EXCESSIVE ALCOHOL-CONSUMPTION; DIMINISHED SOCIAL COMPETENCE; EARLY EXPERIENCE; MONKEYS; STRESS AB We examined the effects of early rearing experience on the development of dominance status in 53 juvenile (age 3) and then in 38 adult (ages 5-8) rhesus macaques. Based-on previous research investigating the behavioral outcomes of nursery-rearing, we predicted that mother-reared outrank peer-only reared (PR) monkeys, which would in turn outrank surrogatel. peer-reared (SPR) subjects. Juvenile MR and PR subjects did not differ in ranks, but monkeys from both rearing backgrounds outranked SPR cage-mates at age 3. Independent of rearing condition, high-ranking juveniles gained the most weight between ages 1-3, suggesting that low status may be associated with decreases in early weight gain. Adult MR subjects outranked both PR and SPR subjects, with PR animals occupying intermediate ranks. These results indicate that impoverished early experiences, such as adult absence and limited social interaction, are useful predictors of future social success in rhesus macaques. Published 2003 Wiley Periodicals, Inc. C1 NICHHD, Lab Comparat Ethol, Anim Ctr, NIH, Poolesville, MD 20837 USA. RP Bastian, ML (reprint author), NIAAA, DICBR, Lab Clin Studies Primate Unit, Anim Ctr,NIH, Poolesville, MD 20837 USA. NR 40 TC 55 Z9 55 U1 4 U2 23 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD JAN PY 2003 VL 42 IS 1 BP 44 EP 51 DI 10.1002/dev.10091 PG 8 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 631MC UT WOS:000180170700005 PM 12471635 ER PT S AU Schwarz, MJ Offenbaecher, M Neumeister, A Ackenheil, M AF Schwarz, MJ Offenbaecher, M Neumeister, A Ackenheil, M BE Allegri, G Costa, CVL Ragazzi, E Steinhart, H Varesio, L TI Experimental evaluation of an altered tryptophan metabolism in fibromyalgia SO DEVELOPMENTS IN TRYPTOPHAN AND SEROTONIN METABOLISM SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 10th International Meeting of the International-Study-Group-for-Tryptophan-Research (ISTRY) CY JUN 25-29, 2002 CL Univ Padova, Padova, ITALY SP Int Study Grp Tryptophan, MIUR, Italian Chem Soc, Div Pharmaceut Chem, Padova City, Veneto Reg HO Univ Padova ID PITUITARY-ADRENOCORTICAL AXIS; INTERFERON-GAMMA; 5-HYDROXYINDOLEACETIC ACID; INTERLEUKIN-6 PRODUCTION; RHEUMATOID-ARTHRITIS; AFFECTIVE-DISORDERS; FIBROSITIS SYNDROME; GENERAL-POPULATION; NORMAL VOLUNTEERS; BRAIN TRYPTOPHAN AB Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesised underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and Interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism and IL-6 production. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia. C1 Univ Munich, Hosp Psychiat, D-80336 Munich, Germany. NIMH, Bethesda, MD 20892 USA. Univ Munich, Dept Phys Med & Rehabil, Munich, Germany. RP Schwarz, MJ (reprint author), Univ Munich, Hosp Psychiat, Nussbaumstr 7, D-80336 Munich, Germany. EM mschwarz@psy.med.uni-muenchen.de NR 51 TC 7 Z9 7 U1 3 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47755-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 527 BP 265 EP 275 PG 11 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Physiology SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Physiology GA BY58X UT WOS:000189415400030 PM 15206740 ER PT J AU Lindsay, RS Hanson, RL Wiedrich, C Knowler, WC Bennett, PH Baier, LJ AF Lindsay, RS Hanson, RL Wiedrich, C Knowler, WC Bennett, PH Baier, LJ TI The insulin gene variable number tandem repeat class I/III polymorphism is in linkage disequilibrium with birth weight but not type 2 diabetes in the pima population SO DIABETES LA English DT Article ID SUSCEPTIBILITY LOCUS IDDM2; 5' FLANKING REGION; ASSOCIATION; INDIANS; TRANSCRIPTION; EXPRESSION; OBESITY; MINISATELLITE; PREGNANCY; MAGNITUDE AB The insulin gene variable number tandem repeat (INS-VNTR) is proposed to exert pleiotropic genetic effects on birth weight and diabetes susceptibility. In our study, we examined the influence of a polymorphism in tight linkage disequilibrium with INS-VNTR (-23Hph1) on birth weight and type 2 diabetes in the Pima population. A parent-offspring "trio" design was used to assess parent-of-origin effects and population stratification. The presence of the -23Hph1 T-allele was associated with lower birth weight (n = 192; - 140 g per copy of the T-allele; P = 0.04), even after adjustment for effects of population stratification (P = 0.03). The effects of paternally transmitted T-alleles were greater than those of maternally transmitted alleles (paternally transmitted: -250 g, P = 0.05; maternally transmitted: -111 g, P = 0.43), but this difference was not statistically significant (P = 0.50). The -23Hph1 T-allele was associated with an increased prevalence of type 2 diabetes (P = 0.009), which family-based association analysis suggested was attributable to population structure (P = 0.04) without significant evidence of linkage disequilibrium between diabetes prevalence and genotype (P = 0.86). Thus allelic variation of the INS gene is associated with lower birth weight and increased prevalence of type 2 diabetes. Significant linkage disequilibrium was found between -23Hph1 and birth weight but not type 2 diabetes, an observation that supports a potential functional role of INS polymorphisms in the regulation of birth weight. C1 NIDDK, NIH, Phoenix, AZ 85014 USA. RP Hanson, RL (reprint author), NIDDK, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 34 TC 47 Z9 48 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2003 VL 52 IS 1 BP 187 EP 193 DI 10.2337/diabetes.52.1.187 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631FK UT WOS:000180157300026 PM 12502511 ER PT J AU Urbanek, M Du, YZ Silander, K Collins, FS Steppan, CM Strauss, JF Dunaif, A Spielman, RS Legro, RS AF Urbanek, M Du, YZ Silander, K Collins, FS Steppan, CM Strauss, JF Dunaif, A Spielman, RS Legro, RS TI Variation in resistin gene promoter not associated with polycystic ovary syndrome SO DIABETES LA English DT Article ID LINKAGE DISEQUILIBRIUM; DIABETES-MELLITUS; HUMAN GENOME; WOMEN; FOLLISTATIN; PREVALENCE; EXPRESSION; DISEASE; GLUCOSE; OBESITY AB Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and affects similar to4-7% of reproductive age women in the U.S. It is characterized by hyperandrogenemia and chronic anovulation and is associated with insulin resistance, obesity, and increased risk for type 2 diabetes. In a screen of candidate genes, a region on chromosome 19p13.3 was identified that shows significant evidence for both linkage and association with PCOS. A promising candidate gene for PCOS, resistin, maps to exactly this region. Resistin is a protein hormone thought to modulate glucose tolerance and insulin action. We tested for association between a single nucleotide polymorphism in the promoter region of the resistin gene and three phenotypes: PCOS, obesity, and insulin resistance. We did not find evidence for association with any of the phenotypes. It is therefore unlikely that variation in the resistin gene accounts for the strong association that we observe between chromosome 19p13.3 and PCOS. Instead, this association is most likely due to a gene or genetic element in this region that has not been identified. C1 Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Northwestern Univ, Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Obstet & Gynecol, Hershey, PA 17033 USA. RP Spielman, RS (reprint author), Univ Penn, Sch Med, Dept Genet, Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA. FU NICHD NIH HHS [HD0118, U54 HD34449]; NIDDK NIH HHS [DK40465, DK47481] NR 24 TC 52 Z9 58 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2003 VL 52 IS 1 BP 214 EP 217 DI 10.2337/diabetes.52.1.214 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631FK UT WOS:000180157300031 PM 12502516 ER PT J AU Volpato, S Ferrucci, L Blaum, C Ostir, G Cappola, A Fried, LP Fellin, R Guralnik, JM AF Volpato, S Ferrucci, L Blaum, C Ostir, G Cappola, A Fried, LP Fellin, R Guralnik, JM TI Progression of lower-extremity disability in older women with diabetes - The Women's Health and Aging Study SO DIABETES CARE LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; RISK-FACTORS; ASSOCIATION; MELLITUS; ADULTS; CLASSIFICATION; PERFORMANCE; DIAGNOSIS; PREDICTOR; AGE AB OBJECTIVE - Older patients with diabetes are more likely to have a higher prevalence of multiple risk factors for physical disability, as a result of diabetic complications. We evaluated the pace of decline in lower-extremity function and the risk for progression of disability in older women with diabetes. RESEARCH DESIGN AND METHODS - We conducted a 3-year longitudinal cohort study of a random sample of 729 physically impaired older women (age greater than or equal to65 years) living in the community (Baltimore, MD). Diabetes was ascertained by standard criteria. Self-reported functional status and objective performance measures were assessed at baseline and over six semiannual follow-up visits. RESULTS - The baseline prevalence of diabetes was 14.4%. After adjustment for age and compared with women without diabetes, those with diabetes had an RR of 1.8 (95% CI 1.3-2.5) for incident mobility disability and 1.6 (1.2-2.1)for incident activity of daily living disability. The increased incidence of new disability associated with diabetes was paralleled by a greater decline in objective measures of lower-extremity function. Adjustment for multiple risk factors for disability did not significantly attenuate the risk for disability associated with diabetes. CONCLUSIONS - in older patients, impaired lower-extremity function is a long-term diabetic complication. Comprehensive assessment of older diabetic patients should include a standardized evaluation of lower-extremity performance. C1 Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med 2, I-44100 Ferrara, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. INRCA, Dept Geriatr, Florence, Italy. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Texas, Med Branch, Sealy Ctr Aging, Galveston, TX 77550 USA. Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. RP Volpato, S (reprint author), Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med 2, Via Savonarola 9, I-44100 Ferrara, Italy. RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [N01-AG-1-2112] NR 30 TC 57 Z9 57 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2003 VL 26 IS 1 BP 70 EP 75 DI 10.2337/diacare.26.1.70 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UK UT WOS:000185504900010 PM 12502660 ER PT J AU Krakoff, J Lindsay, RS Looker, HC Nelson, RG Hanson, RL Knowler, WC AF Krakoff, J Lindsay, RS Looker, HC Nelson, RG Hanson, RL Knowler, WC TI Incidence of retinopathy and nephropathy in youth-onset compared with adult-onset type 2 diabetes SO DIABETES CARE LA English DT Article ID PIMA-INDIANS; URINE SAMPLES; CARDIOVASCULAR-DISEASE; CREATININE RATIOS; BLOOD-PRESSURE; PROTEINURIA; MELLITUS; CHILDREN; NIDDM; QUANTITATION AB OBJECTIVE - To examine the risk of retinopathy and nephropathy in participants in whom type 2 diabetes was diagnosed in youth (before 20 years of age) compared with those in whom type 2 diabetes was diagnosed at older ages. RESEARCH DESIGN AND METHODS - Subjects in whom youth-onset or adult-onset diabetes was diagnosed in the longitudinal study of health in the Pima Indians of Arizona were followed for microvascular complications. Diabetes was diagnosed in 178 subjects before 20 years of age (youth), in 1,359 subjects at 20-39 years of age (younger adults), and in 971 subjects at 40-59 years of age (older adults). Incidence rates of diabetic retinopathy diagnosed by direct ophthalmoscopy through dilated pupils and nephropathy (protein-to-creatinine ratio greater than or equal to0.5 g/g) were calculated by age at diagnosis. RESULTS - Over 25 years, nephropathy developed in 35 of the participants with youth-onset type 2 diabetes; this incidence rate was not significantly different from that in patients with adult-onset diabetes (P = 0.77). Incidence rates of retinopathy, however, were significantly lower for the youth-onset group (P = 0.007). Adjusted for sex, glycemia, and blood pressure risk of retinopathy was lower in patients with youth-onset diabetes than in those with adult-onset diabetes (hazard rate ratio [HRR] 0.42, 95% CI 0.24-0.74, P = 0.003), but risk of nephropathy was not different (HRR 1.2, 95% CI 0.77-1.3, P = 0.38). CONCLUSIONS - In Pima Indians, the risk of nephropathy as a function of duration of diabetes is similar in all age groups. By contrast, the risk of retinopathy is lower in patients with youth-onset type 2 diabetes. C1 NIDDKD, Diabet & Arthritis Epidemiol Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. RP Krakoff, J (reprint author), NIDDKD, Diabet & Arthritis Epidemiol Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 34 TC 57 Z9 59 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2003 VL 26 IS 1 BP 76 EP 81 DI 10.2337/diacare.26.1.76 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UK UT WOS:000185504900011 PM 12502661 ER PT J AU Boheler, KR AF Boheler, KR TI ES cell differentiation to the cardiac lineage SO DIFFERENTIATION OF EMBRYONIC STEM CELLS SE METHODS IN ENZYMOLOGY LA English DT Review ID EMBRYONIC STEM-CELLS; IN-VITRO; MOUSE EMBRYOS; CARDIOMYOCYTES; MODEL; CARCINOMA; MUSCLE; GENE C1 NIA, Mol Cardiol Unit, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Boheler, KR (reprint author), NIA, Mol Cardiol Unit, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 22 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 365 BP 228 EP 241 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24R UT WOS:000188419200016 PM 14696349 ER PT J AU Kim, JH Panchision, D Kittappa, R McKay, R AF Kim, JH Panchision, D Kittappa, R McKay, R TI Generating CNS neurons from embryonic, fetal, and adult stem cells SO DIFFERENTIATION OF EMBRYONIC STEM CELLS SE METHODS IN ENZYMOLOGY LA English DT Review ID ASTROCYTIC DIFFERENTIATION; PRECURSORS; GROWTH; FATE C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, JH (reprint author), NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Kim, Jong-Hoon/F-2504-2013; Kim, Jong-Hoon/H-1476-2015 NR 24 TC 21 Z9 22 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 365 BP 303 EP + PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24R UT WOS:000188419200022 PM 14696355 ER PT J AU Sviridov, D Hoeg, JM Eggerman, T Demosky, SJ Safonova, IG Brewer, HB AF Sviridov, D Hoeg, JM Eggerman, T Demosky, SJ Safonova, IG Brewer, HB TI Low-density lipoprotein receptor and apolipoprotein A-I and B expression in human enterocytes SO DIGESTION LA English DT Article DE lipoproteins; apolipoproteins; low-density lipoprotein receptor; enterocytes; hepatocytes ID ELEMENT-BINDING PROTEINS; EPITHELIAL-CELLS; SMALL-INTESTINE; MESSENGER-RNA; LDL RECEPTOR; CHOLESTEROL; DEGRADATION; LIVER; ACID AB Low-density lipoprotein receptor (LDL-R) was found to be expressed in human small intestine epithelial cells, enterocytes. The relative abundance of LDL-R mRNA and protein was compared with that of apolipoproteins A-1 (apoA-1) and B (apoB) in enterocytes and two other cell types: CaCo-2 and HepG2. The LDL-R mRNA content was comparable in three cell types. Human enterocytes expressed 5.2- to 14-fold more apoA-1 mRNA than the other cells. In contrast, HepG2 cells expressed 10-to 19-fold more apoB mRNA than CaCo-2 cells and human enterocytes. Immunoprecipitation of [S-35]methionine pulse-labeled intracellular proteins from these cell types demonstrated that human enterocytes synthesize more apoA-1 and apoB, while HepG2 cells synthesize a slightly higher amount of LDL-R. Copyright (C) 2003 S. Karger AG, Basel. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Inst Expt Cardiol, Cardiol Res Ctr, Moscow, Russia. RP Sviridov, D (reprint author), Baker Med Res Inst, POB 6492,St Kilda Rd Cent, Melbourne, Vic 3008, Australia. RI Sviridov, Dmitri/E-7943-2010 NR 17 TC 3 Z9 3 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 J9 DIGESTION JI Digestion PY 2003 VL 67 IS 1-2 BP 67 EP 70 DI 10.1197/000070395 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 683AP UT WOS:000183124800011 PM 12743443 ER PT B AU Suzman, R Theofilatou, M Scherer, P Bohiga, L de Cock, J AF Suzman, R Theofilatou, M Scherer, P Bohiga, L de Cock, J GP OECD OECD TI Summary of roundtable panel discussion SO DISEASE-BASED COMPARISON OF HEALTH SYSTEMS: WHAT IS BEST AND AT WHAT COST? LA English DT Proceedings Paper CT Workshop on Disease Based Comparison of Health Systems CY JUN 20-21, 2002 CL PARIS, FRANCE SP Natl Inst Aging U S, Natl Board Hlth & Welfare Japan C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ORGANIZATION ECONOMIC COOPERATION & DEVELOPMENT PI PARIS PA 2, RUE ANDRE PASCAL, CEDEX 16, 75775 PARIS, FRANCE BN 92-64-09981-6 PY 2003 BP 355 EP 359 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA BX11X UT WOS:000184328200020 ER PT J AU Mehta, AI Ross, S Lowenthal, MS Fusaro, V Fishman, DA Petricoin, EF Liotta, LA AF Mehta, AI Ross, S Lowenthal, MS Fusaro, V Fishman, DA Petricoin, EF Liotta, LA TI Biomarker amplification by serum carrier protein binding SO DISEASE MARKERS LA English DT Article ID MOLECULAR WEIGHT PROTEINS; PROSTATE-CANCER; PROTEOMIC PATTERNS; OVARIAN-CANCER; ALBUMIN; IDENTIFICATION; DISCOVERY; ELECTROPHORESIS; BIOINFORMATICS; MS AB Mass spectroscopic analysis of the low molecular mass (LMM) range of the serum/plasma proteome is a rapidly emerging frontier for biomarker discovery. This study examined the proportion of LMM biomarkers, which are bound to circulating carrier proteins. Mass spectroscopic analysis of human serum following molecular mass fractionation, demonstrated that the majority of LMM biomarkers exist bound to carrier proteins. Moreover, the pattern of LMM biomarkers bound specifically to albumin is distinct from those bound to non-albumin carriers. Prominent SELDI-TOF ionic species (m/z 6631.7043) identified to correlate with the presence of ovarian cancer were amplified by albumin capture. Several insights emerged: a) Accumulation of LMM biomarkers on circulating carrier proteins greatly amplifies the total serum/plasma concentration of the measurable biomarker, b) The total serum/plasma biomarker concentration is largely determined by the carrier protein clearance rate, not the unbound biomarker clearance rate itself, and c) Examination of the LMM species bound to a specific carrier protein may contain important diagnostic information. These findings shift the focus of biomarker detection to the carrier protein and its biomarker content. C1 Howard Hughes Med Inst, Bethesda, MD 20814 USA. US FDA, FDA NCI Clin Proteom Program, Off Director, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, FDA NCI Clin Proteom Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Natl Ovarian Canc Early Detect Program, Chicago, IL 60611 USA. RP Mehta, AI (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 2A33, Bethesda, MD 20892 USA. EM arpita.mehta@tufts.edu NR 34 TC 144 Z9 150 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 1 BP 1 EP 10 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 818TA UT WOS:000221266200001 PM 14757941 ER PT J AU Croft, BY AF Croft, BY TI Special Issue: Functional Imaging of Early Markers of Disease. Part 2 - Foreword SO DISEASE MARKERS LA English DT Editorial Material C1 Natl Canc Inst, Biomed Imaging Program, NIH, Rockville, MD 20852 USA. RP Croft, BY (reprint author), Natl Canc Inst, Biomed Imaging Program, NIH, Rockville, MD 20852 USA. RI Croft, Barbara/D-1248-2013 OI Croft, Barbara/0000-0003-2544-150X NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 2-3 BP 47 EP 47 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 820MK UT WOS:000221393200001 ER PT J AU Croft, BY AF Croft, BY TI The future of medical imaging in the detection of early markers of disease SO DISEASE MARKERS LA English DT Article ID IN-VIVO; CONTRAST AGENTS; OPTICAL SPECTROSCOPY; MR ELASTOGRAPHY; BREAST; ULTRASOUND; TOMOGRAPHY; PHANTOM; CANCER; GENE AB Imaging techniques are a combination of a contrast mechanism, exogenous or endogenous. and all instrument to exploit that contrast. This final chapter of these two special issues Of this journal points to possible ways to improve the ability of imaging systems to exploit markers of cancer in the early detection of that disease. The aim not only is to find cancer at an earlier, more treatable stage, but to determine whether the disease discovered is dangerous and to indicate the possibilities for successful treatment. These topics are explored for each imaging system, with in emphasis on directions for future improvements. C1 NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA. RP Croft, BY (reprint author), NCI, Canc Imaging Program, NIH, 6130 Execut Blvd,EPN 6064, Bethesda, MD 20892 USA. EM croftb@mail.nih.gov RI Croft, Barbara/D-1248-2013 OI Croft, Barbara/0000-0003-2544-150X NR 32 TC 0 Z9 0 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 2-3 BP 155 EP 165 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 820MK UT WOS:000221393200008 PM 15096711 ER PT J AU Veenstra, TD Srivastava, S AF Veenstra, TD Srivastava, S TI Proteomics in diagnostics SO DISEASE MARKERS LA English DT Editorial Material C1 SAIC Frederick Inc, NCI, Biomed Proteom Program, Lab Proteom & Analyt Technol, Ft Detrick, MD 21702 USA. NCI, Canc Biomarkers Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Veenstra, TD (reprint author), SAIC Frederick Inc, NCI, Biomed Proteom Program, Lab Proteom & Analyt Technol, POB B, Ft Detrick, MD 21702 USA. EM veenstra@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 4-5 BP 167 EP 168 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 837TY UT WOS:000222665000001 PM 15258331 ER PT J AU Van, QN Klose, JR Lucas, DA Prieto, DA Luke, B Collins, J Burt, SK Chmurny, GN Issaq, HJ Conrads, TP Veenstra, TD Keay, SK AF Van, QN Klose, JR Lucas, DA Prieto, DA Luke, B Collins, J Burt, SK Chmurny, GN Issaq, HJ Conrads, TP Veenstra, TD Keay, SK TI The use of urine proteomic and metabonomic patterns for the diagnosis of interstitial cystitis and bacterial cystitis SO DISEASE MARKERS LA English DT Article ID NMR-SPECTROSCOPY; EPIDEMIOLOGY; MARKERS AB The advent of systems biology approaches that have stemmed from the sequencing of the human genome has led to the search for new methods to diagnose diseases. While much effort has been focused on the identification of disease-specific biomarkers, recent efforts are underway toward the use of proteomic and metabonomic patterns to indicate disease. We have developed and contrasted the use of both proteomic and metabonomic patterns in urine for the detection of interstitial cystitis (IC). The methodology relies on advanced bioinformatics to scrutinize information contained within mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance (H-1-NMR) spectral patterns to distinguish IC-affected from non-affected individuals as well as those suffering from bacterial cystitis (BC). We have applied a novel pattern recognition tool that employs an unsupervised system (self-organizing-type cluster mapping) as a fitness test for a supervised system (a genetic algorithm). With this approach, a training set comprised of mass spectra and H-1-NMR spectra from urine derived from either unaffected individuals or patients with IC is employed so that the most fit combination of relative, normalized intensity features defined at precise m/z or chemical shift values plotted in n-space can reliably distinguish the cohorts used in training. Using this bioinformatic approach, we were able to discriminate spectral patterns associated with IC-affected, BC-affected, and unaffected patients with a success rate of approximately 84%. C1 SAIC Frederick Inc, NCI Frederick, Lab Proteom & Analyt Technol, Frederick, MD USA. SAIC Frederick Inc, NCI Frederick, Adv Biomed Comp Ctr, Frederick, MD USA. Univ Maryland, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21201 USA. VA Maryland Hlth Care Syst, Res Serv, Baltimore, MD 21201 USA. RP Keay, SK (reprint author), VA Med Ctr, Room 3B-184,10 N Greene St, Baltimore, MD 21201 USA. EM skeay@umaryland.edu FU NCI NIH HHS [N01-CO-12400]; NIDDK NIH HHS [R01 DK52596] NR 21 TC 31 Z9 32 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 4-5 BP 169 EP 183 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 837TY UT WOS:000222665000002 PM 15258332 ER PT J AU Grizzle, WE Adam, BL Bigbee, WL Conrads, TP Carroll, C Feng, ZD Izbicka, E Jendoubi, M Johnsey, D Kagan, J Leach, RJ McCarthy, DB Semmes, OJ Srivastava, S Srivastava, S Thompson, IM Thornquist, MD Verma, M Zhang, Z Zou, ZQ AF Grizzle, WE Adam, BL Bigbee, WL Conrads, TP Carroll, C Feng, ZD Izbicka, E Jendoubi, M Johnsey, D Kagan, J Leach, RJ McCarthy, DB Semmes, OJ Srivastava, S Srivastava, S Thompson, IM Thornquist, MD Verma, M Zhang, Z Zou, ZQ TI Serum protein expression profiling for cancer detection: Validation of a SELDI-based approach for prostate cancer SO DISEASE MARKERS LA English DT Article DE SELDI-TOF-MS; prostate adenocarcinoma; validation ID DIGITAL RECTAL EXAMINATION; PROTEOMIC PATTERNS; SURVIVAL RATES; SCREENING-TEST; ANTIGEN; CARCINOMA; MORTALITY; TRIAL; MEN AB Multiple studies have reported that analysis of serum and other bodily fluids using surface enhanced laser desorption/ionization time of flight mass spectroscopy (SELDI-TOF-MS) can identify a "fingerprint" or "signature" of spectral peaks that can separate patients with a specific disease from normal control patients. Ultimately, classification by SELDI-TOF-MS relies on spectral differences in position and amplitude of resolved peaks. Since the reproducibility of quantitation, resolution and mass accuracy of the SELDI-TOF-MS, or any high throughput mass spectrometric technique, has never been determined this method has come under some skepticism as to its clinical usefulness. This manuscript describes a detailed design of a three-phase study to validate the clinical usefulness of SELDI-TOF-MS in the identification of patients with prostatic adenocarcinoma (PCA). At the end of this validation study, the usefulness of the general SELDI-TOF-MS approach to identifying patients with PCA will be demonstrated and how it compares with PCA diagnosis by measuring prostate specific antigen. C1 Univ Alabama, Birmingham, AL 35233 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. SAIC Frederick, Frederick, MD USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. San Antonio Canc Inst, Inst Drug Dev, San Antonio, TX USA. Milagen Inc, Richmond, CA USA. NCI, Rockville, MD USA. Ciphergen Biosyst Inc, Fremont, CA USA. Uniformed Serv Univ Hlth Sci, Rockville, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Grizzle, WE (reprint author), Univ Alabama, Zeigler Res Bldg,Room 408,703 S 19th St, Birmingham, AL 35233 USA. FU NCI NIH HHS [P30 CA54174, U01 CA085067] NR 28 TC 41 Z9 46 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 4-5 BP 185 EP 195 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 837TY UT WOS:000222665000003 PM 15258333 ER PT J AU Johann, DJ McGuigan, MD Tomov, S Fusaro, VA Ross, S Conrads, TP Veenstra, TD Fishman, DA Whiteley, GR Petricoin, EF Liotta, LA AF Johann, DJ McGuigan, MD Tomov, S Fusaro, VA Ross, S Conrads, TP Veenstra, TD Fishman, DA Whiteley, GR Petricoin, EF Liotta, LA TI Novel approaches to visualization and data mining reveals diagnostic information in the low amplitude region of serum mass spectra from ovarian cancer patients SO DISEASE MARKERS LA English DT Article DE ovarian cancer; SELDI-TOF MS; data visualization; diagnosis ID PROTEOMIC PATTERNS; PROSTATE-CANCER AB The ability to identify patterns of diagnostic signatures in proteomic data generated by high throughput mass spectrometry (MS) based serum analysis has recently generated much excitement and interest from the scientific community. These data sets can be very large, with high-resolution MS instrumentation producing 1-2 million data points per sample. Approaches to analyze mass spectral data using unsupervised and supervised data mining operations would greatly benefit from tools that effectively allow for data reduction without losing important diagnostic information. In the past, investigators have proposed approaches where data reduction is performed by a priori "peak picking" and alignment/warping/smoothing components using rule-based signal-to-noise measurements. Unfortunately, while this type of system has been employed for gene microarray analysis, it is unclear whether it will be effective in the analysis of mass spectral data, which unlike microarray data, is comprised of continuous measurement operations. Moreover, it is unclear where true signal begins and noise ends. Therefore, we have developed an approach to MS data analysis using new types of data visualization and mining operations in which data reduction is accomplished by culling via the intensity of the peaks themselves instead of by location. Applying this new analysis method on a large study set of high resolution mass spectra from healthy and ovarian cancer patients, shows that all of the diagnostic information is contained within the very lowest amplitude regions of the mass spectra. This region can then be selected and studied to identify the exact location and amplitude of the diagnostic biomarkers. C1 NCI, FDA, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Div Informat Technol, Upton, NY 11973 USA. SAIC Frederick Inc, NCI, Lab Proteom & Analyt Technol, Frederick, MD USA. Northwestern Univ, Sch Med, Natl Ovarian Canc Early Detect Program, Chicago, IL 60611 USA. SAIC Frederick, Clin Proteom Reference Lab, NCI FDA Clin Proteom Program, Gaithersburg, MD USA. NCI, FDA Clin Proteom Program, Off Cell & Gene Therapy, Ctr Biol Evaluat & Res Food & Drug Adm, Bethesda, MD 20892 USA. RP Johann, DJ (reprint author), NCI, FDA, Clin Proteom Program, Pathol Lab,Ctr Canc Res, 8800 Rockville Pike,Bldg 29A,Room 2A21, Bethesda, MD 20892 USA. EM dj151o@nih.gov NR 14 TC 9 Z9 9 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 4-5 BP 197 EP 207 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 837TY UT WOS:000222665000004 PM 15258334 ER PT J AU Yu, LR Zhou, M Conrads, TP Veenstra, TD AF Yu, LR Zhou, M Conrads, TP Veenstra, TD TI Diagnostic proteomics: Serum proteomic patterns for the detection of early stage cancers SO DISEASE MARKERS LA English DT Article DE proteomic patterns; cancer detection; serum; mass spectrometry ID PROSTATE-CANCER; MASS-SPECTROMETRY; OVARIAN-CANCER; BENIGN; MEN AB The ability to interrogate thousands of proteins found in complex biological samples using proteomic technologies has brought the hope of discovering novel disease-specific biomarkers. While most proteomic technologies used to discover diagnostic biomarkers are quite sophisticated, "proteomic pattern analysis" has emerged as a simple, yet potentially revolutionary, method for the early diagnosis of diseases. Utilizing this technology, hundreds of clinical samples can be analyzed per day and several preliminary studies suggest proteomic pattern analysis has the potential to be a novel, highly sensitive diagnostic tool for the early detection of cancer. C1 NCI, SAIC Frederick Inc, Biomed Proteom Program, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, SAIC Frederick Inc, Biomed Proteom Program, Lab Proteom & Analyt Technol, POB B, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 26 TC 6 Z9 6 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 4-5 BP 209 EP 218 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 837TY UT WOS:000222665000005 PM 15258335 ER PT B AU Rehermann, B AF Rehermann, B BE Galle, PR Gerken, G Schmidt, WE Wiedenmann, B TI Cellular immune responses and recovery from hepatitis C SO DISEASE PROGRESSION AND CARCINOGENESIS IN THE GASTROINTESTINAL TRACT SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Gastroenterology Week 2002 CY OCT 06-11, 2002 CL FREIBURG, GERMANY SP Falk Fdn ID T-LYMPHOCYTE RESPONSE; VIRUS-INFECTION; HETEROLOGOUS VIRUSES; PROTECTIVE IMMUNITY; VIRAL CLEARANCE; MEMORY; CELLS; CHIMPANZEES; ANTIGENS; REPLICATION C1 NIDDK, DHHS, Liver Dis Sect, DDB,NIH, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, DHHS, Liver Dis Sect, DDB,NIH, Bldg 10,Room 9B-16, Bethesda, MD 20892 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8785-6 J9 FALK SYMP PY 2003 VL 132 BP 79 EP 85 PG 7 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BX89G UT WOS:000186757900006 ER PT J AU Heath, EI Canto, MI Wu, TT Piantadosi, S Hawk, E Unalp, A Gordon, G Forastiere, AA AF Heath, EI Canto, MI Wu, TT Piantadosi, S Hawk, E Unalp, A Gordon, G Forastiere, AA CA CBET Res Grp TI Chemoprevention for Barrett's Esophagus Trial. Design and outcome measures SO DISEASES OF THE ESOPHAGUS LA English DT Article DE Barrett's esophagus; chemoprevention; cyclo-oxygenase inhibitor; esophageal disease; prostaglandin ID FAMILIAL ADENOMATOUS POLYPOSIS; E-CADHERIN EXPRESSION; CYCLOOXYGENASE-2 EXPRESSION; CYCLIN-D; CANCER; RISK; ADENOCARCINOMA; CARCINOMA; P53; INHIBITOR AB Barrett's esophagus is a premalignant condition in which normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. It is a known risk factor for the development of esophageal adenocarcinoma. With the incidence of esophageal adenocarcinoma rising, it is reasonable to study Barrett's esophagus as a potential target for therapy that may prevent, delay and/or reverse ongoing tumorigenic processes. Epidemiologic and animal studies support the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the chemoprevention of several cancers, including esophageal cancer. Cyclo-oxygenase-2 (COX-2) inhibitors are a new class of NSAIDs that inhibit prostaglandin synthesis by selectively blocking the COX-2 enzyme. The COX-2 enzyme has been reported to be over-expressed in premalignant and malignant states, including in Barrett's esophagus and esophageal adenocarcinoma. The Chemoprevention for Barrett's Esophagus Trial (CBET) is a phase IIb, multicenter, randomized, double-masked, placebo-controlled study of the selective COX-2 inhibitor, celecoxib, in patients with Barrett's dysplasia. The sample size is 200 patients with high or low grade Barrett's dysplasia. Celecoxib is administered orally, 200 mg twice per day; the dosing schedule for placebo is the same. Randomization is stratified by dysplasia grade and by clinic. Endoscopy with biopsies is performed at specified time intervals according to the highest grade of dysplasia determined at randomization. The primary outcome measure is the change from baseline to I year in the proportion of biopsies exhibiting dysplasia. Secondary outcomes include change from baseline in the maximal grade, extent and surface area of dysplasia. Tertiary outcomes will include measurements of various relevant biomarkers. C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21231 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Canc Inst, Bethesda, MD USA. John Hopkins Ctr Clin Trials, Baltimore, MD USA. Ovat Pharmaceut, Lincolnshire, IL USA. RP Heath, EI (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. FU NCI NIH HHS [N01-CN-85185] NR 50 TC 28 Z9 29 U1 0 U2 0 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PY 2003 VL 16 IS 3 BP 177 EP 186 DI 10.1046/j.1442-2050.2003.00325.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 743ZY UT WOS:000186604500001 PM 14641306 ER PT S AU Kim, JW Le, DX Thoma, GR AF Kim, JW Le, DX Thoma, GR BE Kanungo, T Smith, EHB Hu, JY Kantor, PB TI Automated labeling of bibliographic data extracted from biomedical online journals SO DOCUMENT RECOGNITION AND RETRIEVAL X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval X CY JAN 22-24, 2003 CL SANTA CLARA, CA SP Soc Imaging Sci & Technol, SPIE DE HTML; online journals; labeling; fuzzy rule-based algorithm; statistics; WebMARS; NLM AB dA prototype system has been designed to automate the extraction of bibliographic data (e.g., article title, authors, abstract, affiliation and others) from online biomedical journals to populate the National Library of Medicine's MEDLINE(R) database. This paper describes a key module in this system: the labeling module that employs statistics and fuzzy rule-based algorithms to identify segmented zones in an article's HTML pages as specific bibliographic data. Results from experiments conducted with 1, 149 medical articles from forty-seven journal issues are presented. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. EM kimj@mail.nlm.nih.gov NR 9 TC 7 Z9 7 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4810-9 J9 PROC SPIE PY 2003 VL 5010 BP 47 EP 56 DI 10.1117/12.476047 PG 10 WC Computer Science, Artificial Intelligence; Optics; Imaging Science & Photographic Technology SC Computer Science; Optics; Imaging Science & Photographic Technology GA BW36L UT WOS:000181749800006 ER PT S AU Hauser, S Schlaifer, J Sabir, T Demner-Fushman, D Thoma, G AF Hauser, S Schlaifer, J Sabir, T Demner-Fushman, D Thoma, G BE Kanungo, T Smith, EHB Hu, JY Kantor, PB TI Correcting OCR text by association with historical datasets SO DOCUMENT RECOGNITION AND RETRIEVAL X SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval X CY JAN 22-24, 2003 CL SANTA CLARA, CA SP Soc Imaging Sci & Technol, SPIE DE OCR correction; partial string matching; performance improvement AB The Medical Article Records System (MARS) developed by the Lister Hill National Center for Biomedical Communications uses scanning, OCR and automated recognition and reformatting algorithms to generate electronic bibliographic citation data from paper biomedical journal articles. The multi-engine OCR server incorporated in MARS performs well in general, but fares less well with text printed in small or italic fonts. Affiliations are often printed in small italic fonts in the journals processed by MARS. Consequently, although the automatic processes generate much of the citation data correctly, the affiliation field frequently contains incorrect data, which must be manually corrected by verification operators. In contrast, author names are usually printed in large, normal fonts that are correctly converted to text by the OCR server. The National Library of Medicine's MEDLINE(R) database contains 11 million indexed citations for biomedical journal articles. This paper documents our effort to use the historical author, affiliation relationships from this large dataset to find potential correct affiliations for MARS articles based on the author and the affiliation in the OCR output. Preliminary tests using a table of about 400,000 author/affiliation pairs extracted from the corrected data from MARS indicated that about 44% of the author/affiliation pairs were repeats and that about 47% of newly converted author names would be found in this set. A text-matching algorithm was developed to determine the likelihood that an affiliation found in the table corresponding to the OCR text of the first author was the current, correct affiliation. This matching algorithm compares an affiliation found in the author/affiliation table (found with the OCR text of the first author) to the OCR output affiliation, and calculates a score indicating the similarity of the affiliation found in the table to the OCR affiliation. Using a ground truth set of 519 OCR author/OCR affiliation/correct affiliation triples, the matching algorithm is able to select a correct affiliation for the author 43% of the time with a false positive rate of 6%, a true negative rate of 44% and a false negative rate of 7%. MEDLINE citations with United States affiliations typically include the zip code. In addition to using author names as clues to correct affiliations, we are investigating the value of the OCR text of zip codes as clues to correct USA affiliations. Current work includes generation of an author/affiliation/zipcode table from the entire MEDLINE database and development of a daemon module to implement affiliation selection and matching for the MARS system using both author names and zip codes. Preliminary results from the initial version of the daemon module and the partially filled author/affiliation/zipcode table are encouraging. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Hauser, S (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4810-9 J9 P SOC PHOTO-OPT INS PY 2003 VL 5010 BP 84 EP 93 DI 10.1117/12.476046 PG 10 WC Computer Science, Artificial Intelligence; Optics; Imaging Science & Photographic Technology SC Computer Science; Optics; Imaging Science & Photographic Technology GA BW36L UT WOS:000181749800010 ER PT J AU Blaug, S Quinn, R Quong, J Jalickee, S Miller, SS AF Blaug, S Quinn, R Quong, J Jalickee, S Miller, SS TI Retinal pigment epithelial function: a role for CFTR? SO DOCUMENTA OPHTHALMOLOGICA LA English DT Article; Proceedings Paper CT Symposium on Basic and Clinical Aspects of Retinal Function CY FEB 14, 2002 CL ZURICH, SWITZERLAND DE retinal pigment epithelium; fluid transport; EOG; cystic fibrosis; potassium; Cl channels; ERG C-wave ID TRANSMEMBRANE CONDUCTANCE REGULATOR; ION-TRANSPORT MECHANISMS; SUBRETINAL SPACE VOLUME; CYSTIC-FIBROSIS; LIGHT PEAK; FAST OSCILLATION; FLUID TRANSPORT; CL TRANSPORT; FROG; HYPERPOLARIZATION AB In the vertebrate eye, the photoreceptor outer segments and the apical membrane of the retinal pigment epithelium (RPE) are separated by a small extracellular (subretinal) space whose volume and chemical composition varies in the light and dark. Light onset triggers relatively fast (ms) retinal responses and much slower voltage and resistance changes (s to min) at the apical and basolateral membranes of the RPE. Two of these slow RPE responses, the fast oscillation (FO) and the light peak, are measured clinically as part of the electrooculogram (EOG). Both EOG responses are mediated in part by apical and basolateral membranes proteins that form a pathway for the movement of salt and osmotically obliged fluid across the RPE, from retina to choroid. This transport pathway serves to control the volume and chemical composition of the subretinal and choroidal extracellular spaces. In human fetal RPE, we have identified one of these proteins, the cystic fibrosis transmembrane conductance regulator (CFTR) by RT-PCR, immunolocalization, and electrophysiological techniques. Evidence is presented to suggest that the FO component of the EOG is mediated directly or indirectly by CFTR. C1 Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Texas, Dept Zool, Austin, TX 78712 USA. Lawrence Livermore Natl Lab, Analyt & Nucl Chem Div, Livermore, CA 94550 USA. RP Miller, SS (reprint author), NEI, NIH, 31Ctr Dr,Bld 31,6A20, Bethesda, MD 20891 USA. NR 35 TC 31 Z9 31 U1 3 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0012-4486 J9 DOC OPHTHALMOL JI Doc. Ophthalmol. PD JAN PY 2003 VL 106 IS 1 BP 43 EP 50 DI 10.1023/A:1022514031645 PG 8 WC Ophthalmology SC Ophthalmology GA 694KU UT WOS:000183774400008 PM 12675485 ER PT J AU Song, MO Fort, DJ McLaughlin, DL Rogers, RL Thomas, JH Buzzard, BO Noll, AM Myers, NK AF Song, MO Fort, DJ McLaughlin, DL Rogers, RL Thomas, JH Buzzard, BO Noll, AM Myers, NK TI Evaluation of Xenopus tropicalis as an alternative test organism for Frog Embryo Teratogenesis Assay-Xenopus (FETAX) SO DRUG AND CHEMICAL TOXICOLOGY LA English DT Article DE xenopus tropicalis; FETAX; developmental toxicity; isoniazid; methotrexatel; 6-aminonicotinamide ID INDUCED DEVELOPMENTAL TOXICITY; POND WATER; VALIDATION; DECLINES; BIOTRANSFORMATION; DETOXIFICATION; MORTALITY; SEDIMENT; EXTRACTS; LAEVIS AB As a formal recommendation from an Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) workshop review of the Frog Embryo Teratogenesis Assay-Xenopus (FETAX) developmental toxicity model, the use of Xenopus tropicalis as an alternative test species for this model was evaluated. Three test substances with varying developmental toxicity potentials were evaluated using FETAX modified to accommodate the use of X. tropicalis. Two separate definitive concentration-response tests were performed with isoniazid, methotrexate, and 6-aminonicotinamide. Historical FETAX results with X. laevis were compared to the results from FETAX assays with X. tropicalis. Test with X. tropicalis indicated that each of the compounds possessed teratogenic potential with varying degrees of potency: 6-aminonicotinamide > methotrexate > isoniazid. Based on overt teratogenicity, but not embryo-lethality, results from these studies indicated that these two species responded similarly to the test compounds. Malformation syndromes induced in both species were similar in X. tropicalis and X. laevis. These results suggested that X. tropicalis should be further evaluated as an alternative test organism for the FETAX model. C1 Ft Environm Labs, Stillwater, OK 74074 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Oklahoma State Univ, Dept Zool, Stillwater, OK 74078 USA. RP Fort, DJ (reprint author), Ft Environm Labs, Stillwater, OK 74074 USA. NR 35 TC 19 Z9 21 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0148-0545 J9 DRUG CHEM TOXICOL JI Drug Chem. Toxicol. PY 2003 VL 26 IS 3 BP 177 EP 189 DI 10.1081/DCT-120022647 PG 13 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology SC Chemistry; Pharmacology & Pharmacy; Toxicology GA 709KV UT WOS:000184625100003 PM 12953658 ER PT J AU Pohl, LR AF Pohl, LR TI Role of anti-inflammatory and other factors in determining susceptibility to idiosyncratic drug-induced liver disease SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 NHLBI, Sect Mol & Cellular Toxicol, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 5 BP 3 EP 3 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300006 ER PT J AU Dean, M Shulenin, S Annilo, T Chen, ZQ AF Dean, M Shulenin, S Annilo, T Chen, ZQ TI ATP-binding cassette transporters and human disease SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21702 USA. RI Annilo, Tarmo/J-2900-2013 OI Annilo, Tarmo/0000-0002-9588-3058 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 13 BP 7 EP 7 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300014 ER PT J AU Selkirk, JK Waters, M Tennant, RW AF Selkirk, JK Waters, M Tennant, RW TI The NIEHS national toxicogenomics initiative SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 NIEHS, Natl Ctr Toxicogenom, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 28 BP 14 EP 14 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300029 ER PT J AU Gonzalez, FJ Yu, AM Akiyama, T Cheung, C AF Gonzalez, FJ Yu, AM Akiyama, T Cheung, C TI P450 and nuclear receptor humanized mice SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 8th European Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) CY APR 27-MAY 01, 2003 CL DIJON, FRANCE SP Int Soc Study Xenobiotics C1 NCI, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 1 MA 30 BP 15 EP 15 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 665NW UT WOS:000182128400030 ER PT J AU Griffth, L Tannenbaum, S Domansky, K Sivaraman, A AF Griffth, L Tannenbaum, S Domansky, K Sivaraman, A TI Tissue engineered liver for high information content assays SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 MIT, Biol Engn Div, Cambridge, MA 02139 USA. MIT, Biotechnol Proc Engn Ctr, Cambridge, MA 02139 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 33 BP 17 EP 17 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300033 ER PT J AU Idle, JR AF Idle, JR TI P450 humanized mice: Novel animal models for the study of drug and carcinogen metabolism, and the search for endogenous human P450 substrates and functions SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 NCI, Metab Lab, Bethesda, MD 20892 USA. Univ Bern, Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 37 BP 19 EP 19 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300037 ER PT J AU Yu, AM Cheung, C Akiyama, TE Granvil, CP Idle, JR Gonzalez, FJ AF Yu, AM Cheung, C Akiyama, TE Granvil, CP Idle, JR Gonzalez, FJ TI P450 humanized mice for the study of xenobiotics SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 62 BP 31 EP 31 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300060 ER PT J AU Bhatia, D Yu, AM O'Callaghan, JP Miller, DB Gonzalez, FJ Haining, RL AF Bhatia, D Yu, AM O'Callaghan, JP Miller, DB Gonzalez, FJ Haining, RL TI Does CYP2D6-humanization provide resistance to MPTP-induced toxicity in mice? SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 W Virginia Univ, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. NIOSH, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. RI O'Callaghan, James/O-2958-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 126 BP 63 EP 63 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300123 ER PT J AU Yu, AM Haining, RL Idle, JR Gonzalez, FJ AF Yu, AM Haining, RL Idle, JR Gonzalez, FJ TI Functional difference in biotransformation of drugs and endogenous subsrates by CYP2D6 allelic isoforms SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. W Virginia Univ, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. Univ Bern, Dept Clin Pharmacol, CH-3010 Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 127 BP 64 EP 64 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300124 ER PT J AU Crowell, JA Page, JG Reed, G Hurwitz, A Kapetanovic, IM AF Crowell, JA Page, JG Reed, G Hurwitz, A Kapetanovic, IM TI Effects of indole-3-carbinol on phase I enzymes in women and rats SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 8th European Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) CY APR 27-MAY 01, 2003 CL DIJON, FRANCE SP Int Soc Study Xenobiotics C1 NCI, Div Canc Prevent, NIH, DHHS, Bethesda, MD 20892 USA. So Res Inst, Birmingham, AL 35205 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 1 MA 156 BP 78 EP 78 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 665NW UT WOS:000182128400156 ER PT J AU DeLozier, TC Tsao, CC Coulter, SJ Zeldin, DC Goldstein, JA AF DeLozier, TC Tsao, CC Coulter, SJ Zeldin, DC Goldstein, JA TI CYP2C44, a new murine CYP2C that metabolizes arachidonic acid SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 NIEHS, Pharmacol & Chem Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 207 BP 104 EP 104 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300203 ER PT J AU Chen, YP Ferguson, SS Negishi, M Goldstein, JA AF Chen, YP Ferguson, SS Negishi, M Goldstein, JA TI Induction of human CYP2C9 is regulated by the pregnane X receptor (PXR) SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 231 BP 116 EP 116 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300225 ER PT J AU Wang, HB Faucette, S Graham, R Sueyoshi, T Negishi, M LeCluyse, E AF Wang, HB Faucette, S Graham, R Sueyoshi, T Negishi, M LeCluyse, E TI Phenytoin induction of CYP3A4 and 2B6 involves a PXR-independent signaling pathway SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 Univ N Carolina, Div Drug Delivery & Disposist, Sch Pharm, Chapel Hill, NC 27599 USA. NIEHS, LRDT, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 236 BP 118 EP 118 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300230 ER PT J AU Nichols, RC Williams, LM Roy, KM Ding, XX Wood, SG Bement, JL Sinclair, PR Gonzalez, FJ Sinclair, JF AF Nichols, RC Williams, LM Roy, KM Ding, XX Wood, SG Bement, JL Sinclair, PR Gonzalez, FJ Sinclair, JF TI Alcohols increase CYP2A5 expression in wild-type mice but not in CYP2E1(-/-) mice by a post-transcriptional mechanism SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 VA Med Ctr, White River Jct, VT 05009 USA. Dartmouth Coll Sch Med, Dept Pharmacol Toxicol, Hanover, NH 03756 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03756 USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. NCI, Dept Metab, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Microbiol Immunol, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Med, Lebanon, NH 03756 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 272 BP 136 EP 136 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300264 ER PT J AU Wolf, KK Wood, SG Bement, JL Sinclair, PR Wrighton, SA Jeffery, E Gonzalez, FJ Sinclair, JF AF Wolf, KK Wood, SG Bement, JL Sinclair, PR Wrighton, SA Jeffery, E Gonzalez, FJ Sinclair, JF TI Role of mouse CYP2E1 in the o-hydroxylation of p-nitrophenol: Comparison of activities in CYP2E1(-/-) and wild-type mice SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 VA Med Ctr, White River Jct, VT 05009 USA. Dartmouth Coll Sch Med, Dept Pharmacol Toxicol, Hanover, NH 03756 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03756 USA. Eli Lilly & Co, Lilly Res Labs, Dept Drug Disposit, Indianapolis, IN 46285 USA. Univ Illinois, Dept Food Sci Human Nutr, Urbana, IL 61801 USA. NCI, Dept Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 271 BP 136 EP 136 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300263 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI Role of gene knockout and transgenic mice in the study of xenobiotic metabolism SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 8th European ISSX Meeting CY APR 27-MAY 01, 2003 CL DIJON, FRANCE DE drug metabolism; xenobiotics; cytochromes P450; gene knockout mice; transgenic mice ID CYP1B1 DETERMINES SUSCEPTIBILITY; MICROSOMAL EPOXIDE HYDROLASE; ARYL-HYDROCARBON RECEPTOR; BENZENE-INDUCED TOXICITY; OXIDOREDUCTASE-1 DEFICIENCY; QUINONE OXIDOREDUCTASE-1; CYTOCHROME-P450 2E1; TARGETED DISRUPTION; BLOOD-PRESSURE; HUMAN CYP2D6 AB The role of P450s in xenobiotic metabolism, toxicity, and carcinogenicity has been studied for many years by using in vitro approaches and limited in vivo investigations. Genetic analysis to study the effects of xenobiotics in intact animals has only recently been carried out by use of gene knockout mice. Mice lacking expression of these enzymes have no or only modest phenotypes, indicating that their xenobiotic-metabolizing enzymes are not critical for mammalian development or physiological homeostasis. The null mice have been used to study the roll of xenobiotic-metabolizing enzymes in chemical toxicity and carcinogenicity. There are marked species differences in the expression and catalytic activities of P450s that metabolize xenobiotics, and this complicates the extrapolation of data obtained in rodents for use in drug development and human risk assessment. This is especially notable between mice and rats, commonly used experimental models, and humans. To begin to develop more predictive models, P450 humanized mice were produced and characterized by using genomic clones containing the complete coding and regulatory regions of genes, as transgenes. Humanized lines expressing CYP2D6 and CYP3A4 human P450 were characterized and found to accurately express human P450 proteins and catalytic activities at levels comparable to or higher than the corresponding activities found in human tissues. These novel mouse lines offer the opportunity to predict human drug and carcinogen metabolism and disposition and to search for endogenous substrates for human P450s. C1 NCI, Lab Metab, NIH, Bethesda, MD 20814 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106B1, Bethesda, MD 20814 USA. NR 51 TC 40 Z9 41 U1 2 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 IS 4 BP 319 EP 335 DI 10.1081/DMR-120026496 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 757ZV UT WOS:000187608800006 PM 14705864 ER PT J AU Launer, LJ AF Launer, LJ TI Nonsteroidal anti-inflammatory drug use and the risk for Alzheimer's disease - Dissecting the epidemiological evidence SO DRUGS LA English DT Article ID AMYLOID PRECURSOR PROTEIN; TRANSGENIC MICE; ANTIINFLAMMATORY DRUGS; CONTROLLED TRIAL; CONTROL BRAIN; BETA-PEPTIDE; DOUBLE-BLIND; DEMENTIA; IBUPROFEN; MICROGLIA AB Inflammation is hypothesised to contribute to the genesis of pathology causing or contributing to Alzheimer's disease (AD). As a part of the immune response in the brain, the prostaglandin pathway is-induced; this pathway is the target for NSAIDs, the most widely used anti-inflammatory medication. There are many epidemiological studies, which are reviewed here, suggesting NSAIDs reduce the risk for AD. The most recent of these studies suggest NSAID should be taken for at least 2 years. There are little data in humans about whether one type of NSAID is more effective than another. To date; randomised, double-blind, clinical trials in patients with AD have been negative. There is one prevention trial that will yield valuable information about the efficacy of NSAIDs in slowing down the progression of, or preventing, AD. At present, no recommendations can be made concerning the when, what, who and for how long a person should take an NSAID to reduce his or her risk for AD. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway 3C-309, Bethesda, MD 20892 USA. NR 58 TC 47 Z9 50 U1 1 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2003 VL 63 IS 8 BP 731 EP 739 DI 10.2165/00003495-200363080-00001 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 669UG UT WOS:000182368400001 PM 12662122 ER PT J AU Dionne, RA AF Dionne, RA TI Tramadol/paracetamol - A viewpoint SO DRUGS LA English DT Editorial Material C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD USA. RP Dionne, RA (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2003 VL 63 IS 11 BP 1087 EP 1088 DI 10.2165/00003495-200363110-00009 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 687ZF UT WOS:000183406600009 ER PT J AU Kannel, WB AF Kannel, WB TI Prevalence and implications of uncontrolled systolic hypertension SO DRUGS & AGING LA English DT Review ID CARDIOVASCULAR RISK FACTOR; CORONARY HEART-DISEASE; BLOOD-PRESSURE; PULSE PRESSURE; FRAMINGHAM; MANAGEMENT; POPULATION; PREVENTION; PLACEBO; CARE AB Risk of cardiovascular disease (CVD) increases incrementally with blood pressure, even within the high-normal range. In the general population, 27% of CVD in women and 37% in men is attributable to hypertension. A high percentage of these hypertension-related events occur in those with high-normal blood pressure and mild hypertension; about one-fourth of CVD events in elderly women and one-third in elderly men in the Framingham Study occured in persons who had blood pressures of 140-159mm Hg systolic and/or 90-95mm Hg diastolic. The average systolic blood pressure (SBP) at which coronary heart disease occurs is rather modest (141mm Hg), as is the pulse pressure (59-63mm Hg). Of the CVD events in elderly participants in the Framingham Study, 24% in men and 36% in women occurred in persons receiving treatment for hypertension. There is a growing recognition of the importance of the systolic component of blood pressure. About 65% of hypertension in the elderly is isolated systolic hypertension (ISH), and CVD risk increases with pulse pressure. Pulse pressure is not simply a marker for stiff diseased arteries; treatment of ISH in trials promptly reduces the CVD risk, indicating that the pulse pressure generated by the stiff artery is the culprit. Analysis of data from clinical trials indicates that greater reliance should be placed on systolic pressure in evaluating the CVD potential of hypertension. Hypertension, including ISH, seldom occurs in isolation from other risk factors and overt CVD. Risk varies widely depending on the burden of accompanying risk factors. This makes global risk assessment mandatory for evaluating risk and the urgency and nature of treatment required. Evidence incriminating systolic pressure as the dominant blood pressure determinant of CVD has not been translated into clinical practice. Most of the uncontrolled hypertension observed in the Framingham Study is concentrated in those with ISH. This also extends to African-Americans, people with diabetes mellitus and the elderly. When should SBP be considered controlled? Substantial evidence supports the value of treating ISH with SBP exceeding 160mm Hg. Trial data are not yet available to support recommendations to treat lesser elevations of ISH or pulse pressure per se, but since one-half of patients with mild ISH have two or more additional risk factors, most are candidates for treatment. In such patients, ISH should be considered controlled when their global CVD risk is reduced to below the average for their age. C1 Boston Univ, Sch Med, Framingham Study, NHLBI, Framingham, MA 01702 USA. RP Kannel, WB (reprint author), Boston Univ, Sch Med, Framingham Study, NHLBI, 73 Mt Wayte Ave, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-25195] NR 34 TC 28 Z9 29 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2003 VL 20 IS 4 BP 277 EP 286 DI 10.2165/00002512-200320040-00004 PG 10 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 665XJ UT WOS:000182146300004 PM 12641483 ER PT J AU Tudge, JRH Odero, DA Hogan, DM Etz, KE AF Tudge, JRH Odero, DA Hogan, DM Etz, KE TI Relations between the everyday activities of preschoolers and their teachers' perceptions of their competence in the first years of school SO EARLY CHILDHOOD RESEARCH QUARTERLY LA English DT Article DE ecological theory; preschoolers' activities; parents' beliefs; teachers' perceptions; longitudinal ID UNITED-STATES; EARLY INTERVENTION; HOME ENVIRONMENTS; LIFE-COURSE; FOLLOW-UP; CHILDREN; TRANSITION; KINDERGARTEN; PERSPECTIVE; PERFORMANCE AB This paper contributes to a growing literature that suggests that in order to understand the transition to school, one should employ an ecological approach. Such an approach involves simultaneous consideration of individual and contextual factors, studied over time. Much of the current literature on the transition focuses on the transition from the perspective of school, but we were interested in relations between what occurs prior to school and performance in school. We used Bronfenbrenner's Process-Person-Context-Time (PPCT) ecological model to focus primarily on the relations between school-relevant activities of preschool-aged children and teachers' subsequent perception of the children's competence once they had entered school. At Time I we observed 20 3-year-olds' engagement in everyday activities (Process) and their initiation of those activities (Person) over a 20-hour period covering the equivalent of an entire waking day. Children were drawn from two social classes (Context). The preschool observations were followed by 2 consecutive years of teacher reports of academic competence following entry into elementary school (Times 2 and 3). Middle-class preschoolers engaged in more school-relevant activities than did working-class children, and preschoolers who initiated and engaged in more conversations were subsequently perceived by their teachers as being more competent. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ N Carolina, Dept Human Dev & Family Studies, Greensboro, NC 27402 USA. Egerton Univ, Dept Home Econ, Egerton, Kenya. Univ Dublin Trinity Coll, Dept Psychol, Dublin 2, Ireland. Natl Inst Drug Abuse, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. RP Tudge, JRH (reprint author), Univ N Carolina, Dept Human Dev & Family Studies, POB 26170, Greensboro, NC 27402 USA. EM jrtudge@uncg.edu NR 88 TC 19 Z9 19 U1 6 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-2006 J9 EARLY CHILD RES Q JI Early Childhood Res. Q. PY 2003 VL 18 IS 1 BP 42 EP 64 DI 10.1016/S0885-2006(03)00005-X PG 23 WC Education & Educational Research; Psychology, Developmental SC Education & Educational Research; Psychology GA 672PP UT WOS:000182529800004 ER PT J AU Atha, DH Miller, K Sanow, AD Xu, JF Hess, JL Wu, OC Wang, W Srivastava, S Highsmith, WE AF Atha, DH Miller, K Sanow, AD Xu, JF Hess, JL Wu, OC Wang, W Srivastava, S Highsmith, WE TI High-throughput analysis of telomerase by capillary electrophoresis SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 16th International Symposium on Microscale Separation and Analysis CY JAN 17-22, 2003 CL SAN DIEGO, CALIFORNIA DE capillary electrophoresis; telomerase ID CANCER; CELLS; DNA AB The enzyme telomerase is expressed in (85-90)% of all human cancers, but not in normal, non-stem cell somatic tissues. Clinical assays for telomerase in easily obtained body fluids would have great utility as noninvasive, cost-effective methods for the early detection of cancer. The most commonly used method for the detection and quantification of telomerase enzyme activity is the polymerase chain reaction (PCR)-based assay known as the telomerase repeat amplification protocol or TRAP assay. Most of the TRAP assay systems use a slab-gel based electrophoresis system to size and quantify the PCR-amplified extension products. We are developing high-throughput capillary electrophoresis (CE) methods for the analysis of TRAP/PCR products. The TRAP assay was conducted on lysates of the human lung cancer cell line A-549 in reactions containing 5-100 cells. TRAP/PCR products were generated using a fluorescent 4,7,2'4'5'7',-hexachloro-6-carboxyfluorescein(HEX)-labeled TS primer and analyzed on the Applied Biosystems Model 310 CE system using POP4(TM) polymer. After analysis with GeneScan(TM) and Genotyper(TM) software, the total peak areas of the TRAP ladder extension products were computed using Microsoft Excel(TM). Results were compared with unlabeled TRAP/PCR products analyzed on the Bio-Rad BioFocus 3000 CE system using 6% high molecular weight polyvinylpyrrolidone (HMW PVP) polymer and SYBR(TM) Green I dye. Both CE systems were able to resolve the TRAP ladder products with high reproducibility and sensitivity (5-15 cells). With the appropriate robotic sample handling system, these CE methods would enable performing the telomerase TRAP assay with increased sensitivity, reproducibility and automation over slab-gel methods. C1 NIST, Div Biotechnol, Gaithersburg, MD 20899 USA. Natl Canc Inst, Div Canc Prevent, Rockville, MD USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP Atha, DH (reprint author), NIST, Div Biotechnol, Bld 227,Rm A243, Gaithersburg, MD 20899 USA. RI Highsmith, William/B-6175-2008 FU NCI NIH HHS [CN-0103-02, U01CA84988] NR 20 TC 19 Z9 19 U1 1 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JAN PY 2003 VL 24 IS 1-2 BP 109 EP 114 DI 10.1002/elps.200390001 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 639NZ UT WOS:000180637300015 PM 12652580 ER PT S AU Terracciano, A Merritt, M Zonderman, AB Evans, MK AF Terracciano, A Merritt, M Zonderman, AB Evans, MK BE Ekman, P Campos, JJ Davidson, RJ DeWaal, FBM TI Personality traits and sex differences in emotion recognition among African Americans and Caucasians SO EMOTIONS INSIDE OUT: 130 YEARS AFTER DARWIN'S THE EXPRESSION OF THE EMOTIONS IN MAN AND ANIMALS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Emotions Inside Out, 130 Years after Darwins the Expression of the Emotions in Man and Animals CY NOV 16-17, 2002 CL New York, NY SP New York Acad Sci, Mushett Family Fdn DE emotion recognition; personality traits; sex differences; cross-cultural; openness ID 5-FACTOR MODEL; ALEXITHYMIA C1 NIA, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. RP Terracciano, A (reprint author), NIA, Dept Hlth & Human Serv, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM TerraccianoA@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS [ZIA AG000183-22, Z99 AG999999, ZIA AG000183-23] NR 8 TC 18 Z9 19 U1 0 U2 12 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-464-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1000 BP 309 EP 312 DI 10.1196/annals.1280.032 PG 4 WC History & Philosophy Of Science; Multidisciplinary Sciences; Psychology; Psychology, Multidisciplinary SC History & Philosophy of Science; Science & Technology - Other Topics; Psychology GA BY70Q UT WOS:000189443500025 PM 14766644 ER PT J AU Akingbemi, BT Ge, RS Rosenfeld, CS Newton, LG Hardy, DO Catterall, JF Lubahn, DB Korach, KS Hardy, MP AF Akingbemi, BT Ge, RS Rosenfeld, CS Newton, LG Hardy, DO Catterall, JF Lubahn, DB Korach, KS Hardy, MP TI Estrogen receptor-alpha gene deficiency enhances androgen biosynthesis in the mouse Leydig cell SO ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; MALE REPRODUCTIVE-TRACT; CHAIN CLEAVAGE ENZYME; LUTEINIZING-HORMONE; WILD-TYPE; ER-ALPHA; PITUITARY GONADOTROPINS; TESTOSTERONE SECRETION; TISSUE DISTRIBUTION AB Leydig cells, which produce the primary male steroid hormone testosterone (T), express the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, and have the capacity to convert testosterone to the natural estrogen 17beta-estradiol. Thus, Leydig cells are subject to estrogen action. The development of transgenic mice that are homozygous for targeted deletion of genes encoding the ER subtypes provides an opportunity to examine the role of estrogen in Leydig cell function. In this study androgen biosynthesis was analyzed in Leydig cells from mice that were homozygous for targeted deletion of the ERalpha gene (alphaERKO). T production by alphaERKO Leydig cells was 2-fold higher than that in wild-type (WT) cells. Serum T levels were accordingly higher in alphaERKO compared with WT mice (5.1 +/- 1.1 vs. 2.2 +/- 0.4 ng/ml; P less than or equal to 0.01) as were serum LH levels (1.31 +/- 0.3 vs. 0.45 +/- 0.08 ng/ml; P less than or equal to 0.01). Mice that were treated with the pure antiestrogen ICI 182,780 at 100 mug/kg(.)d for 7 d, effectively abrogating ER-mediated activity, also had 2-fold elevations in the serum levels of LH (1.15 +/- 0.3 vs. 0.45 +/- 0.2 ng/ml) and T (4.3 +/- 1.1 vs. 2.2 +/- 0.2 ng/ml; P less than or equal to 0.01). Increased androgen biosynthesis by alphaERKO Leydig cells was associated with higher steroidogenic enzyme activity, especially of cytochrome P450(17alpha)-hydroxylase/17-20 lyase (P450(17alpha)) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD), as measured by conversion of radiolabeled steroid substrates to T or its precursors. The largest increases in enzymatic activity were observed for P450(17alpha) (423 +/- 45 pmol/min(.)10(6) cells in alphaERKO Leydig cells vs. 295 +/- 27 pmol/min.10(6) cells in WT cells; P < 0.01). Consistent with steroidogenic enzyme activity, the testis of aERKO mice expressed higher steady state mRNA levels for steroidogenic acute regulatory protein and two enzymes involved in androgen biosynthesis, P450(17)alpha and 17beta-HSD type III, as determined by semiquantitative RT-PCR. Compared with the controls, higher steady state mRNA levels for steroidogenic acute regulatory protein and P450(17alpha) were also measured in the testis of ICI 182,780-treated mice. In a second set of experiments estrogen administration reduced serum LH and T levels in WT controls, whereas alphaERKO mice were unaffected. Although exposure of WT and alphaERKO Leydig cells to estrogen in vitro did not affect androgen biosynthesis, incubation with ICI 182,780 reduced T production by WT, but not alphaERKO, Leydig cells. These observations indicate that abrogation of the ERalpha gene by targeted deletion or treatment with an antiestrogen increases Leydig cell steroidogenesis in association with elevations in the serum levels of LH, which presumably is the result of estrogen insensitivity at the level of the hypothalamus and/or pituitary gonadotropes. Furthermore, the decrease in T production by WT Leydig cells and not alphaERKO Leydig cells occasioned by incubation with ICI 182,780 suggests that of the ER subtypes, ERalpha has a regulatory role in Leydig cell steroidogenic function. C1 Populat Council, Ctr Biomed Res, New York, NY 10021 USA. Univ Missouri, Dept Anim Sci, Columbia, MO 65211 USA. Univ Missouri, Dept Vet Biomed Sci, Columbia, MO 65211 USA. Univ Missouri, Dept Biochem & Child Hlth, Columbia, MO 65211 USA. NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Hardy, MP (reprint author), Populat Council, Ctr Biomed Res, 1230 York Ave, New York, NY 10021 USA. OI Korach, Kenneth/0000-0002-7765-418X FU FIC NIH HHS [TWO-5350]; NICHD NIH HHS [U54-HD-13541, HD-32588]; NIEHS NIH HHS [ES-10233] NR 58 TC 93 Z9 99 U1 1 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2003 VL 144 IS 1 BP 84 EP 93 DI 10.1210/en.2002-220292 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631PL UT WOS:000180176100013 PM 12488333 ER PT J AU Ogawa, S Chan, J Gustafsson, JA Korach, KS Pfaff, DW AF Ogawa, S Chan, J Gustafsson, JA Korach, KS Pfaff, DW TI Estrogen increases locomotor activity in mice through estrogen receptor alpha: Specificity for the type of activity SO ENDOCRINOLOGY LA English DT Article ID BETA MESSENGER-RNA; CIRCADIAN-RHYTHMS; FEMALE RAT; GONADAL-HORMONES; SEX-DIFFERENCES; ESTRADIOL; BEHAVIORS; SYSTEM; FOREBRAIN; GENETICS AB Estrogens are known to increase running wheel activity of rodents primarily by acting on the medial preoptic area (mPOA). The mechanisms of this estrogenic regulation of running wheel activity are not completely understood. In particular, little is known about the separate roles of two types of estrogen receptors, ERalpha and ERbeta, both of which are expressed in mPOA neurons. In the present study the effects of continuous estrogen treatment on running wheel activity were examined in male and female mice specifically lacking either the ERalpha (alphaERKO) or the ERbeta (betaERKO) gene. Mice were gonadectomized and 1 wk later implanted with either a low dose (16 ng/d) or a high dose (160 ng/d) of estradiol benzoate (EB) or with a placebo control pellet. Home cage running wheel activity was recorded for 9 d starting 10 d after EB implants. The same mice were also tested for open field activity before and after EB implants. In both female and male alphaERKO mice, running wheel activity was not different from that in corresponding wild-type (alphaWT) mice in placebo control groups. In both females and males it was increased by EB only in alphaWT, not alphaERKO, mice. In betaERKO mice, on the other hand, both doses of EB equally increased running wheel activity in both sexes just as they did in betaWT mice. Absolute numbers of daily revolutions of EB-treated groups, however, were significantly lower in betaERKO females compared with alphaWT females. Before EB treatment, gonadectomized alphaERKO female were significantly less active than alphaWT mice in open field tests, whereas betaERKO females tended to be more active than alphaWT mice. In male mice there were no effect of ERalpha or ERbeta gene knockout on open field activity. Unlike its effect on running wheel activity, EB treatment induced only a small increase in open field activity in female, but not male, mice. These findings indicate that 1) in both sexes estrogenic regulation of running wheel activity is primarily mediated through the ERa, not the ERP; and 2) hormone/genotype effects are specific to the type of locomotor activity (i.e. home cage running wheel activity and open field activity) measured. C1 Rockefeller Univ, Neurobiol & Behav Lab, New York, NY 10021 USA. Karolinska Inst, Dept Med Nutr, S-14186 Huddinge, Sweden. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Ogawa, S (reprint author), Rockefeller Univ, Neurobiol & Behav Lab, 1230 York Ave,Box 275, New York, NY 10021 USA. OI Korach, Kenneth/0000-0002-7765-418X FU PHS HHS [62147] NR 30 TC 136 Z9 139 U1 0 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2003 VL 144 IS 1 BP 230 EP 239 DI 10.1210/en.2002-220519 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631PL UT WOS:000180176100029 PM 12488349 ER PT J AU Van Sande, J Massart, C Beauwens, R Schoutens, A Costagliola, S Dumont, JE Wolff, J AF Van Sande, J Massart, C Beauwens, R Schoutens, A Costagliola, S Dumont, JE Wolff, J TI Anion selectivity by the sodium iodide symporter SO ENDOCRINOLOGY LA English DT Article ID THYROID NA+/I SYMPORTER; TRANSPORT; CELLS; RE-188-PERRHENATE; PERCHLORATE; BALLOON; GLAND; CLO4; SCN AB The iodide transporter of the thyroid (NIS) has been cloned by the group of Carrasco. The NIS-mediated transport was studied by electrophysiological methods in NIS-expressing Xenopus oocytes. Using this method, the anion selectivity of NIS was different from that previously reported for thyroid cells, whereas perchlorate and perrhenate were found not transported. In this study we compared the properties of human NIS, stably transfected in COS-7 cells to those of the transport in a thyroid cell line, the FRTL5 cells, by measuring the transport directly. We measured the uptake of I-125(-), (ReO4-)-Re-186, and (TcO4-)-Tc-99m and studied the effect on it of known competing anions, i.e. ClO4-, SCN-, ClO3-, ReO4-, and Br-. We conclude that the properties of the NIS transporter account by themselves for the properties of the thyroid iodide transporter as described previously in thyroid slices. The order of affinity was: ClO4- > ReO4- > I- greater than or equal to SCN- > ClO3- > Br-. NIS is also inhibited by dysidenin (as in dog thyroid). C1 Free Univ Brussels, Sch Med, Inst Rech Interdisciplinaire Biol Humaine & Mol, B-1070 Brussels, Belgium. Erasme Univ Hosp, Dept Nucl Med, B-1070 Brussels, Belgium. NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Van Sande, J (reprint author), Free Univ Brussels, Sch Med, Inst Rech Interdisciplinaire Biol Humaine & Mol, 808 Route Lennik,Campus Erasme,Bldg C, B-1070 Brussels, Belgium. RI costagliola, sabine/D-4864-2012; OI Massart, Claude/0000-0002-2680-6788 NR 23 TC 104 Z9 106 U1 1 U2 6 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2003 VL 144 IS 1 BP 247 EP 252 DI 10.1210/en.2002-220744 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631PL UT WOS:000180176100031 PM 12488351 ER PT J AU Cawley, NX Rodriguez, YM Maldonado, A Loh, YP AF Cawley, NX Rodriguez, YM Maldonado, A Loh, YP TI Trafficking of mutant carboxypeptidase E to secretory granules in a beta-cell line derived from Cpe(fat)/Cpe(fat) mice SO ENDOCRINOLOGY LA English DT Article ID PATHWAY-SORTING RECEPTOR; ENZYME-ACTIVITY; CPE(FAT) MICE; E MUTATION; PROINSULIN; IDENTIFICATION; PROHORMONES; DEFICIENT; BINDING AB We have reinvestigated the stability and intracellular routing of mutant carboxypeptidase E in NIT3 cells, a pancreatic beta-cell line derived from the Cpe(fat)/Cpe(fat) mouse. Pulse-chase experiments demonstrated that this protein has a half-life of approximately 3 h in these cells and that up to 45% of the proCPE(202) can escape degradation by the proteosome. In double-label immunofluorescence microscopy, a portion of the mutant CPE did not colocalize with calnexin, an endoplasmic reticulum marker, but was found in prohormone convertase 2-containing secretory granules, demonstrating that it had escaped degradation and arrived at a post-Golgi compartment. The mutant CPE as well as prohormone convertase 2 were secreted into the medium in a stimulated manner by treatment with the physiological secretagogue, glucagon-like peptide-1, consistent with its presence in granules of the regulated secretory pathway. The presence of mutant carboxypeptidase E in granules supports a potential role for its involvement as a sorting/retention receptor in the trafficking of proinsulin to the regulated secretory pathway. C1 Natl Inst Child Hlth & Human Dev, Dev Neurobiol Lab, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), Bldg 49,Rm 5A38,49 Convent Dr,MSC 4490, Bethesda, MD 20892 USA. NR 23 TC 18 Z9 20 U1 2 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2003 VL 144 IS 1 BP 292 EP 298 DI 10.1210/en.2002-220588 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631PL UT WOS:000180176100037 PM 12488357 ER PT J AU Malling, HV Delongchamp, RR Valentine, CR AF Malling, HV Delongchamp, RR Valentine, CR TI Three origins of Phi X174 am39 revertants in transgenic cell culture SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE Phi X174; transgenic; embryonic cells; revertants; ENU; single burst assay ID ESCHERICHIA-COLI; PHIX174 AM3; IN-VITRO; DETECTING MUTATION; MICE; MUTAGENESIS; SINGLE; CS70; LINE; FREQUENCIES AB Transgenic systems for measuring mammalian mutagenesis often use recoverable viral vectors. We hypothesize that mutations in these transgenic systems can arise from three different origins of DNA damage and replication errors and that these three origins of mutations (in vivo, ex vivo, and in vitro) can be differentiated in the PhiX174 am3, cs70 single burst assay (SBA) on the basis of burst size (BS). In vivo mutations are fixed in the animal, ex vivo mutations are fixed in bacterial cells during recovery of the phage, and in vitro revertants arise during the first replications of nonmutant phages under selective conditions. PX-2 cells, derived from a homozygous embryo of a PhiX174 transgenic mouse, were treated with vehicle or N-ethyl-N-nitrosourea (ENU). An algorithm was developed to estimate the BS that resulted in the highest induced revertant frequency; the estimate was 56. In vivo revertants were defined as having BS >55, ex vivo revertants as having a BS of 13-56, and in vitro revertants as having a BS of <14. The frequencies of in vivo revertants at 0, 100, and 200 mg/kg ENU were 0.06, 0.36, and 4.10 x 10(-6) (dose response, P = 0.004); ex vivo revertants were 0.36, 0.46, and 0.41 x 10(-6) (P = 0.37), and in vitro revertants were 0.39, 0.46, and 0.41 x 10(-6) (P = 0.55), respectively. These results show that only in vivo revertants reflect mutagen treatment. They also provide a basis for identifying PhiX174 am3 revertants induced in vivo and may increase the sensitivity of the assay for in vivo mutation. Published 2003 Wiley-Liss, Inc.(dagger). C1 NIEHS, Mammalian Mutagenesis Grp, Lab Toxicol Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Malling, HV (reprint author), NIEHS, Mammalian Mutagenesis Grp, Lab Toxicol Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM mailing@niehs.nih.gov NR 23 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2003 VL 42 IS 4 BP 258 EP 273 DI 10.1002/em.10195 PG 16 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 760ZA UT WOS:000187864100005 PM 14673871 ER PT J AU Chang, PY Mirsalis, J Riccio, ES Bakke, JP Lee, PS Shimon, J Phillips, S Fairchild, D Hara, Y Crowell, JA AF Chang, PY Mirsalis, J Riccio, ES Bakke, JP Lee, PS Shimon, J Phillips, S Fairchild, D Hara, Y Crowell, JA TI Genotoxicity and toxicity of the potential cancer-preventive agent polyphenon E SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE polyphenon E; salmonella test; Tk; micronucleus; lacl/cll transgenic; mutation ID GREEN TEA CATECHINS; INDUCED ACUTE-PANCREATITIS; CELL-CYCLE DYSREGULATION; MOUSE LYMPHOMA-CELLS; EPIGALLOCATECHIN GALLATE; MUTAGENICITY TEST; ASSAY SYSTEM; RATS; MICE; CARCINOGENESIS AB The potential health benefits of green tea continue to attract public and scientific interests and are attributed in part to polyphenolic catechin constituents. Polyphenon E (Poly E) is a decaffeinated green tea catechin mixture containing about 50% epigallocatechin gallate and 30% other catechins. We evaluated the toxicity and genotoxicity of Poly E by using two in vitro assays: bacterial mutagenesis in a Salmonella typhimurium-E. coli assay and the L5178Y mouse lymphoma cell thymidine kinase (Tk) gene mutation assay. In addition, we used two in vivo genotoxicity assays: the mouse micronucleus assay and the Big Blue cll transgenic mouse mutation assay. Repeat-dose toxicity evaluations were performed in mice in parallel with the Big Blue transgenic mutation assays. No significant increases in the revertant colonies were found in increase in the mutant frequency (MF) at the A locus was observed in the mouse lymphoma test system. We observed toxicity in mice when Poly E was administered at doses of 2,000 mg/kg/day. Lower doses produced no significant increases in micronucleated erythrocytes in the bone marrow of Swiss-Webster mice and no significant increases in cll transgene MF in the liver, lung, or spleen compared with controls. These results indicate that Poly E, although toxic at high doses (2,000 mg/kg/day), poses minimal genotoxic concern. In addition, these studies highlight the importance of using both in vitro and in vivo systems in genetic toxicity screening of pharmaceuticals before they are administered to humans. (C) 2003 Wiley-Liss, Inc. C1 SRI Int, Biopharmaceut Dev Div, Menlo Pk, CA 94025 USA. Tokyo Food Techno Co Ltd, Shizuoka, Japan. NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD USA. RP Chang, PY (reprint author), SRI Int, Biopharmaceut Dev Div, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. FU NCI NIH HHS [N01 CN 75024] NR 48 TC 25 Z9 25 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2003 VL 41 IS 1 BP 43 EP 54 DI 10.1002/em.10129 PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 640QD UT WOS:000180698700006 PM 12552591 ER PT J AU Witt, KL Hughes, LA Burka, LT McFee, AF Mathews, JM Black, SL Bishop, JB AF Witt, KL Hughes, LA Burka, LT McFee, AF Mathews, JM Black, SL Bishop, JB TI Mouse bone marrow micronucleus test results do not predict the germ cell mutagenicity of N-hydroxymethylacrylamide in the mouse dominant lethal assay SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE N-methylolocrylamide; genotoxicity; micronuclei; heritable chromosome damage ID ACRYLAMIDE; CHEMICALS; MICE AB N-Hydroxymethylacrylamide (NHMA), a mouse carcinogen inactive in the Salmonella assay and mouse micronucleus (MN) assay, was tested for reproductive effects in a mouse continuous breeding study. In that study, increased embryonic deaths were observed after 13 weeks exposure of parental animals to NHMA via drinking water (highest dose, 360 ppm); the results indicated the possible induction of chromosome damage in germ cells of treated males. An additional mouse MN test was conducted using a 31-day treatment period to better match the dosing regimen used in the breeding study; the results were negative. Additional studies were conducted to explore the germ cell activity of NHMA. A male mouse dominant lethal study was conducted using a single intraperitoneal injection of 150 mg/kg NHMA; the results were negative. A follow-up study was conducted using fractionated dosing, 50 mg/kg/day for 5 days; again, no increase in dominant lethal mutations was observed. NHMA (180-720 ppm) was then administered to male mice in drinking water for 13 weeks, during which three sets of matings occurred. Two weeks after mating, females were killed and the uterine contents were analyzed. Large, dose-related increases in dominant lethal mutations were observed with increasing length of exposure. The magnitude of the increases stabilized after 8 weeks of treatment. However, the frequency of micronucleated peripheral blood erythrocytes was not elevated in mice treated for 13 weeks with NHMA in drinking water. Thus, NHMA appears to be unique in inducing genetic damage in germ cells but not somatic cells of male mice. Published 2003 Wiley-Liss, Inc.(dagger). C1 NIEHS, Expt Toxicol Program, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Informat Sci Div, Res Triangle Pk, NC USA. Oak Ridge Natl Lab, Oak Ridge, TN USA. Oak Ridge Inst Sci & Educ, Dept Genet, Oak Ridge, TN USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Bishop, JB (reprint author), NIEHS, Expt Toxicol Program, MD B3-05,POB 12233, Res Triangle Pk, NC 27709 USA. NR 15 TC 16 Z9 16 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2003 VL 41 IS 2 BP 111 EP 120 DI 10.1002/em.10139 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 653HJ UT WOS:000181428900005 PM 12605380 ER PT J AU Ward, EM Schulte, PA Bayard, S Blair, A Brandt-Rauf, P Butler, MA Dankovic, D Hubbs, AF Jones, C Karstadt, M Kedderis, GL Melnick, R Redlich, CA Rothman, N Savage, RE Sprinker, M Toraason, M Weston, A AF Ward, EM Schulte, PA Bayard, S Blair, A Brandt-Rauf, P Butler, MA Dankovic, D Hubbs, AF Jones, C Karstadt, M Kedderis, GL Melnick, R Redlich, CA Rothman, N Savage, RE Sprinker, M Toraason, M Weston, A CA Natl Occupational Res Agenda Team TI Priorities for development of research methods in occupational cancer SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE cancer research; National Occupational Research Agenda; occupational health; research priorities ID PETROLEUM MIDDLE DISTILLATES; NATIONAL-TOXICOLOGY-PROGRAM; PREDICT HUMAN CANCER; NESTED CASE-CONTROL; UNITED-STATES; EXPOSURE ASSESSMENT; BREAST-CANCER; LUNG-CANCER; CHILDHOOD-CANCER; VINYL-CHLORIDE AB Occupational cancer research methods was identified in 1996 as 1 of 21 priority research areas in the National Occupational Research Agenda (NORA). To implement NORA, teams of experts from various sectors were formed and given the charge to further define research needs and develop strategies to enhance or augment research in each priority area. This article is a product of that process. Focus on occupational cancer research methods is important both because occupational factors play a significant role in a number of cancers, resulting in significant morbidity and mortality, and also because occupational cohorts (because of higher exposure levels) often provide unique opportunities to evaluate health effects of environmental toxicants and understand the carcinogenic process in humans. Despite an explosion of new methods for cancer research in general, these have not been widely applied to occupational cancer research. In this article we identify needs and gaps in occupational cancer research methods in four broad areas: identification of occupational carcinogens, design of epidemiologic studies, risk assessment, and primary and secondary prevention. Progress in occupational cancer will require interdisciplinary research involving epidemiologists, industrial hygienists, toxicologists, and molecular biologists. C1 NIOSH, Cincinnati, OH 45226 USA. Occupat Safety & Hlth Adm, Washington, DC USA. NCI, Bethesda, MD 20892 USA. Columbia Univ, Sch Publ Hlth, New York, NY USA. US Mine Safety & Hlth Adm, Arlington, VA USA. US EPA, Washington, DC 20460 USA. Chem Ind Inst Toxicol, Ctr Hlth Res, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Yale Univ, Occupat Environm Med Program, New Haven, CT USA. Int Chem Workers Union Council, United Food & Commercial Workers, Akron, OH USA. RP Schulte, PA (reprint author), NIOSH, 4676 Columbia Pkwy, Cincinnati, OH 45226 USA. RI Zahm, Shelia/B-5025-2015 NR 126 TC 13 Z9 16 U1 1 U2 1 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 JAN PY 2003 VL 111 IS 1 BP 1 EP 12 DI 10.1289/ehp.5537 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 642MF UT WOS:000180807600020 PM 12524210 ER PT J AU Longnecker, MP Wolff, MS Gladen, BC Brock, JW Grandjean, P Jacobson, JL Korrick, SA Rogan, WJ Weisglas-Kuperus, N Hertz-Picciotto, I Ayotte, P Stewart, P Winneke, G Charles, MJ Jacobson, SW Dewailly, E Boersma, ER Altshul, LM Heinzow, B Pagano, JJ Jensen, AA AF Longnecker, MP Wolff, MS Gladen, BC Brock, JW Grandjean, P Jacobson, JL Korrick, SA Rogan, WJ Weisglas-Kuperus, N Hertz-Picciotto, I Ayotte, P Stewart, P Winneke, G Charles, MJ Jacobson, SW Dewailly, E Boersma, ER Altshul, LM Heinzow, B Pagano, JJ Jensen, AA TI Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE child development; environmental exposure; environmental pollutants; neurotoxins; polychlorinated biphenyls ID THYROID-HORMONE LEVELS; HUMAN BLOOD-PLASMA; HUMAN-MILK; DICHLORODIPHENYL DICHLOROETHENE; ENVIRONMENTAL EXPOSURE; FISH CONSUMPTION; ADIPOSE-TISSUE; PCB CONGENERS; SERUM; DDE AB Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that a) the distribution of PCB 153 exposure in most studies overlapped substantially, b) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and c) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Quebec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Univ So Denmark, Inst Publ Hlth, Odense, Denmark. Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Erasmus Univ, Div Neonatol, Dept Pediat, Rotterdam, Netherlands. Univ Rotterdam Hosp, Sophia Childrens Hosp, Rotterdam, Netherlands. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. CHUL, CHUQ, Res Ctr, Publ Hlth Res Unit, Beauport, PQ, Canada. Univ Laval, Dept Social & Prevent Med, Beaufort, PQ, Canada. SUNY Coll Oswego, Dept Psychol, Oswego, NY 13126 USA. Univ Dusseldorf, Med Inst Environm Hyg, D-4000 Dusseldorf, Germany. Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. Univ Groningen Hosp, Dept Obstet Pediat, Groningen, Netherlands. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. SUNY Coll Oswego, Environm Res Ctr, Oswego, NY 13126 USA. Inst Environm Toxicol, Kiel, Germany. DK Teknik Energy & Environm, Soborg, Denmark. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; Longnecker, Matthew/0000-0001-6073-5322; Grandjean, Philippe/0000-0003-4046-9658 NR 42 TC 187 Z9 189 U1 0 U2 15 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 JAN PY 2003 VL 111 IS 1 BP 65 EP 70 DI 10.1289/ehp.5463 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 642MF UT WOS:000180807600028 PM 12515680 ER PT J AU Goehl, TJ AF Goehl, TJ TI A new look for a dynamic journal SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Goehl, TJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2003 VL 111 IS 1 BP A15 EP A15 DI 10.1289/ehp.111-a15 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 642MF UT WOS:000180807600002 ER PT J AU Silverman, DT Hoover, RN Brown, LM Swanson, GM Schiffman, M Greenberg, RS Hayes, RB Lillemoe, KD Schoenberg, JB Schwartz, AG Liff, J Pottern, LM Fraumeni, JF AF Silverman, DT Hoover, RN Brown, LM Swanson, GM Schiffman, M Greenberg, RS Hayes, RB Lillemoe, KD Schoenberg, JB Schwartz, AG Liff, J Pottern, LM Fraumeni, JF TI Why do black Americans have a higher risk of pancreatic cancer than white Americans? SO EPIDEMIOLOGY LA English DT Article DE race; cigarette smoking; alcohol consumption; body mass index; diabetes mellitus; socioeconomic factors; pancreatic neoplasm ID ALCOHOL-CONSUMPTION; DIABETES-MELLITUS; CIGARETTE-SMOKING; UNITED-STATES; FRANCOPHONE-COMMUNITY; SOCIOECONOMIC-STATUS; NUTRITIONAL FACTORS; ATTRIBUTABLE RISK; EXOCRINE PANCREAS; DIRECT INTERVIEWS AB Background. For several decades, the incidence of pancreatic cancer has been 50% to 90% higher among blacks than among whites in the United States. The purpose of this study was to identify risk factors that may contribute to this racial disparity. Methods. We conducted a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey counties from August 1986 through April 1989. In-person interviews were exclusively with subjects (526 cases and 2153 population controls), rather than with next of kin. Results. The determinants of the higher incidence of pancreatic cancer among blacks than among whites differed by sex. Among men, established risk factors (ie, cigarette smoking, long-term diabetes mellitus, family history of pancreatic cancer) account for 46% of the disease in blacks and 37% in whites, potentially explaining all but 6% of the excess risk among blacks. Among women, however, other factors appear to contribute to the racial disparity, notably moderate/heavy alcohol consumption (>7 drinks per week) and elevated body mass index (above the first quartile). When these less accepted risk factors were combined with the established risk factors, 88% of the disease in black women and 47% in white women were explained, potentially accounting for all of the excess risk among blacks in our female study population. Conclusions. Among men, the established risk factors (mainly cigarette smoking and diabetes mellitus) explain almost the entire black/white disparity in incidence. Among women, however, other factors appear to contribute to the racial disparity, notably moderate/heavy alcohol consumption and elevated body mass index. In the absence of these factors, pan. creatic cancer incidence rates among blacks probably would not exceed those among whites of either sex. C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Barbara Ann Karmanos Canc Ctr, Detroit, MI USA. Emory Univ, Sch Publ Hlth, Div Epidemiol, Atlanta, GA 30322 USA. Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. New Jersey Dept Hlth & Senior Serv, Canc Epidemiol Serv, Trenton, NJ USA. RP Silverman, DT (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Room 8108, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-51089, N01-CN-05225, N01-CN-05227, N01-CN-31022, N01-CP-51090, N01-CP-51092] NR 84 TC 47 Z9 49 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2003 VL 14 IS 1 BP 45 EP 54 DI 10.1097/00001648-200301000-00013 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 631KE UT WOS:000180166300012 PM 12500045 ER PT S AU Dunn, BK Verma, M Umar, A AF Dunn, BK Verma, M Umar, A BE Verma, M Dunn, BK Umar, A TI Epigenetics in cancer prevention: Early detection and risk assessment - Introduction SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE acetylation; biomarker; cancer detection; epigenetics; methylation; microarray; prevention; risk assessment ID ESOPHAGEAL ADENOCARCINOMA; PROMOTER HYPERMETHYLATION; METHYLATION; DNA; ACETYLTRANSFERASES; TUMORIGENESIS; PROGRESSION; CHROMATIN; PATTERNS; DELETION C1 NCI, Basic Prevent Sci Res Grp, Div Canc Prevent, NIH, Rockville, MD 20852 USA. RP Dunn, BK (reprint author), NCI, Basic Prevent Sci Res Grp, Div Canc Prevent, NIH, Execut Pl N,Room 2056,6130 Execut Blvd, Rockville, MD 20852 USA. NR 27 TC 6 Z9 7 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 1 EP 4 PG 4 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800001 PM 12724207 ER PT S AU Dunn, BK AF Dunn, BK BE Verma, M Dunn, BK Umar, A TI Hypomethylation: One side of a larger picture SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE hypomethylation; 5-methylcytosine; cancer; repetitive sequences; hypermethylation; transposable elements ID MOUSE-LIVER TUMORS; C-MYC GENE; GENOMIC METHYLATION PATTERNS; HUMAN TRANSPOSABLE ELEMENT; DNA METHYLATION; CELL-LINES; RAT-LIVER; 5-METHYLCYTOSINE CONTENT; HUMAN CANCERS; CHROMOSOME INSTABILITY AB Hypomethylation signifies one end of a spectrum of DNA methylation states. In most cases hypomethylation refers to a relative state that represents a change from the "normal" methylatign level. Hypomethylation, when approached from a topographical perspective; has been used to describe either overall decreases in the methylation status of the entire genome (global hypomethylation) or more localized relative demethylation of specific subsets of the genome, such as the promoter regions of protooncogenes or normally highly methylated repetitive sequences. Global hypomethylation accompanied by gene-specific hypermethylation is observed in at least two important settings: cancer and aging. Global hypomethylation is generally reflective of decreased methylation in CpGs dispersed throughout repetitive sequences as Well as the bodies of genes. Hypomethylation of repetitive and parasitic DNA sequences correlates with a number of adverse outcomes. For example, decreased methylation of repetitive sequences in the satellite DNA of the pericentric region of chromosomes is associated with increased chromosomal rearrangements, a hallmark of cancer. Decreased methylation of proviral sequences can lead to reactivation and increased infectivity. However, hypomethylation in cancer can also affect the CpGs in the promoters of specific genes-namely, protooncogenes-leading to their overexpression and resulting in the functional outcome of increased cell proliferation. Thus, hypomethylation, in a variety of. settings in which it represents a deviation from "normal," appears to correlate with progression to cancer and offers potential mechanisms to explain the carcinogenic process. C1 NCI, Basic Prevent Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Dunn, BK (reprint author), NCI, Basic Prevent Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. NR 127 TC 104 Z9 107 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 28 EP 42 PG 15 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800004 PM 12724210 ER PT S AU Muegge, K Young, H Ruscetti, F Mikovits, J AF Muegge, K Young, H Ruscetti, F Mikovits, J BE Verma, M Dunn, BK Umar, A TI Epigenetic control during lymphoid development and immune responses - Aberrant regulation, viruses, and cancer SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE methylation; acetylation; lymphopoiesis; immune response; viruses ID EPSTEIN-BARR-VIRUS; INTERFERON-GAMMA GENE; T-CELL DIFFERENTIATION; DE-NOVO METHYLATION; DNA METHYLTRANSFERASE GENE; V(D)J RECOMBINATION; IFN-GAMMA; CHROMOSOMAL TRANSLOCATIONS; INTERLEUKIN-7 RECEPTOR; TRANSCRIPTION FACTOR AB Methylation of cytosines controls a number of biologic processes such as imprinting and X chromosomal inactivation. DNA hypermethylation is closely associated with transcriptional silencing, while DNA hypomethylation is associated with transcriptional activation. Hypoacetylation of histones leads to compact chromatin with reduced accessibility to the transcriptional machinery. Methyl-CpG binding proteins can recruit corepressors and histone deacetylases; thus, the interplay between these epigenetic mechanisms regulates gene activation. Methylation has been implicated as an important mechanism during immune development, controlling VDJ recombination, lineage-specific expression of cell surface antigens, and transcriptional regulation of cytokine genes during immune responses. Aberrations in epigenetic machinery, either by genetic mutations or by somatic changes such as viral infections, are associated with early alterations in chronic diseases such as immunodeficiency and cancer. C1 EpiGenX Pharmaceut Inc, Santa Barbara, CA 93111 USA. SAIC, Labs Mol Immunoregulat, Frederick, MD 21702 USA. NCI, Canc Res Ctr, Frederick, MD 21702 USA. RP Mikovits, J (reprint author), EpiGenX Pharmaceut Inc, 5385 Hollister Ave, Santa Barbara, CA 93111 USA. NR 111 TC 11 Z9 11 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 55 EP 70 PG 16 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800006 PM 12724212 ER PT S AU Lee, MP AF Lee, MP BE Verma, M Dunn, BK Umar, A TI Genotine-wide analysis of epigenetics in cancer SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE genomics; bioinformatics; cancer; epigenetics; genomic imprinting ID BECKWITH-WIEDEMANN-SYNDROME; FACTOR-II GENE; IMPRINTED ANTISENSE RNA; CPG-ISLAND METHYLATION; ANGELMAN SYNDROME; COLORECTAL-CANCER; FREQUENT LOSS; IDENTIFICATION; REGION; TUMOR AB Human cancers are caused by multiple mechanisms. Research in the last 30 years has firmly established the roles of a group of genes including oncogenes, tumor suppressor genes, and DNA repair genes in human cancers. The activation and inactivation of these cancer genes can be caused by genetic mutations or epigenetic alterations. The epigenetic changes in cancers include methylation of CpG islands, loss of imprinting, and chromatin modification. The completion of the genome sequences of many organisms including the human has transformed the traditional approach to molecular biology research into an era of functional genome research. Traditional research usually involves the study of one or a few genes (proteins) in a particular biological process in normal physiology or disease. Functional genome research takes advantage of newly available genome sequences and high-throughput genome technologies to study genes and/or proteins to inform the perspective of entire biological processes. I will focus on recent progress in the identification of imprinted genes and methylation of CpG islands through genome-wide analysis. C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. RP Lee, MP (reprint author), NCI, Lab Populat Genet, 41 Lib Dr,D702C, Bethesda, MD 20892 USA. NR 54 TC 15 Z9 19 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 101 EP 109 PG 9 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800009 PM 12724215 ER PT S AU Barker, PE AF Barker, PE BE Verma, M Dunn, BK Umar, A TI Cancer biomarker validation: Standards and process - Roles for the National Institute of Standards and Technology (NIST) SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE cancer biomarker; assay validation; early detection; genetic technology; SRM; DNA; SELDI; standards; analytical validation ID PATTERNS; GENE; DNA AB Rigorous validation of biomarkers for early detection of cancer differs at the National Institute of Standards and Technology (NIST) from similar processes common among research laboratories. As a newly discovered biomarker assay makes the transition from a research setting to the clinical diagnostic laboratory, it should progress through defined stages of assay confirmation. The first task of a validation laboratory is evaluation of research assay technology, performance, and specifications (analytical validation). However, the ultimate goal is initial validation of the test to identify early stage cancer (clinical validation). Upon technical and clinical confirmation, assays are moved systematically toward a standardized, reproducible, high-throughput format for clinical diagnostic implementation. With laboratory performance rigorously established, the clinical variables can subsequently be analyzed to define limitations, applications, and clinical utility. The role of NIST in technology evaluation for early cancer testing is described in the context of similar programs and prior experience at NIST. Here we conceptualize the validation steps of cancer test development and examine how NIST activities impact health care through institutional focus on measurement, technology, and standards development programs. C1 NIST, NCI, Biomarkers Validat Lab, DNA Technol Grp,Biotechnol Div, Gaithersburg, MD 20899 USA. RP Barker, PE (reprint author), NIST, NCI, Biomarkers Validat Lab, DNA Technol Grp,Biotechnol Div, Gaithersburg, MD 20899 USA. NR 21 TC 32 Z9 34 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 142 EP 150 PG 9 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800013 PM 12724219 ER PT S AU Li, SF Hursting, SD Davis, BJ McLachlan, JA Barrett, JC AF Li, SF Hursting, SD Davis, BJ McLachlan, JA Barrett, JC BE Verma, M Dunn, BK Umar, A TI Environmental exposure, DNA methylation, and gene regulation - Lessons from diethylstilbesterol-induced cancers SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE methylation; estrogen; diethylstilbesterol; perinatal exposure; carcinogenesis ID MOUSE UTERUS; NEOPLASTIC TRANSFORMATION; UTERINE ADENOCARCINOMA; BREAST-CANCER; C-FOS; EXPRESSION; ESTROGEN; METHYLTRANSFERASE; EMBRYO; MICE AB DNA methylation is an epigenetic mechanism that regulates chromosomal stability and gene expression. Abnormal DNA methylation patterns have been observed in many types of human tumors, including those of the breast, prostate, colon, thyroid, stomach, uterus, and cervix. We and others have shown that exposure to a wide variety of xenobiotics during critical periods of mammalian development can persistently alter the pattern of DNA methylation, resulting in potentially adverse biological effects such as aberrant gene expression. Thus, this epigenetic mechanism may underlie the observed increased risk in adulthood of several chronic diseases, including cancer, in response to xenobiotic exposures early in life. We present here the lessons learned from studies on the effects of perinatal diethylstilbesterol (DES) exposure on the methylation pattern of the promoters of several estrogen-responsive genes associated with the development of reproductive organs. Perinatal DES exposure, which induces epithelial tumors of the uterus in mice and is associated with several reproductive tract abnormalities and increased vaginal and cervical cancer risk in women, provides a clear example of how estrogenic xenobiotic exposure during a critical period of development can abnormally demethylate DNA sequences during organ development and possibly increase cancer risk later in life. In addition, nutritional factors and stress may also alter DNA methylation during early life and modulate the risk of cancer and other chronic diseases in adulthood. We suggest that DNA methylation status may be influenced by environmental exposures in early life, leading to increased risk of cancer in adulthood. C1 NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. Tulane Univ, Med Ctr, Tulane Xavier Ctr Bioenvironm res, New Orleans, LA 70112 USA. RP Barrett, JC (reprint author), NCI, Lab Biosyst & Canc, NIH, Bldg 37,Rm 5032,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 62 TC 129 Z9 138 U1 1 U2 8 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 161 EP 169 PG 9 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800015 PM 12724221 ER PT S AU Vernia, M AF Vernia, M BE Verma, M Dunn, BK Umar, A TI Viral genes and methylation SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE acetylation; acetyltransferase; cancer; early detection; epigenetics; long-terminal repeat; methylation; methyltransferase; prevention; risk assessment ID EPSTEIN-BARR-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; T-CELL LEUKEMIA; HTLV-I LTR; DNA METHYLATION; TRANSGENIC MICE; ABERRANT METHYLATION; KAPOSIS-SARCOMA; PROMOTER METHYLATION; CANCER EPIGENETICS AB Epigenetics represents a new frontier in cancer research. Methylation is the best studied of the epigenetic mechanisms that regulate gene expression. Regulation of gene expression by means of methylation has been reported for tumor suppressor genes, oncogenes, viral promoters, and age-related genes. In this review, the regulation of viral gene expression by methylation is discussed, with particular emphasis on: (1) the virus-specific factors that bind to promoter regions; (2) the implications of this knowledge for designing viral vectors that can be used to deliver genes for the purpose of gene therapy; and (3) the use of this knowledge for the early detection and prevention of cancer. Since methylation can be reversed by a variety of exogenous agents, great potential exists to develop interventions that target cancer-associated aberrant methylation in an effort to reverse or prevent carcinogenesis. C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Rockville, MD 20852 USA. RP Vernia, M (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Execut Plaza N,Room 3144,6130 Execut Blvd, Rockville, MD 20852 USA. NR 54 TC 0 Z9 0 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 170 EP 180 PG 11 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800016 ER PT S AU Moore, LE Huang, WY Chung, J Hayes, RB AF Moore, LE Huang, WY Chung, J Hayes, RB BE Verma, M Dunn, BK Umar, A TI Epidemiologic considerations to assess altered DNA methylation from environmental exposures in cancer SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE epidemiology; DNA methylation; epigenetics; environmental carcinogenesis ID CYSTATHIONINE BETA-SYNTHASE; CHROMATE-EXPOSED WORKERS; EXFOLIATED BLADDER CELLS; CPG ISLAND METHYLATION; TUMOR-SUPPRESSOR GENE; METHYLENETETRAHYDROFOLATE REDUCTASE; COLORECTAL-CANCER; IN-VITRO; SODIUM ARSENITE; PROSTATE-CANCER AB Epidemiologic studies in human populations have identified a broad spectrum of risk factors for cancer. Gene-damaging agents have been a primary focus of cancer epidemiology; however, all xenobiotics do not interact with DNA directly. Some exogenous agents induce epigenetic changes. In view of this, markers that measure changes to the epigenome must also be incorporated into molecular epidemiologic studies. We review the current understanding of the impact of exogenous agents including: micronutrients, chemotherapeutic agents, metals, and others, on DNA methylation. Two categories of genes are described: (1) genes that can alter susceptibility to aberrant DNA methylation and (2) genes that increase susceptibility to cancer when they are silenced through DNA methylation. Methods for incorporating markers of DNA methylation status into etiologic investigations of the impact of environmental exposures on disease (e.g., cancer) are discussed. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Moore, LE (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7034,MSC 7240, Bethesda, MD 20892 USA. NR 117 TC 28 Z9 29 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 181 EP 196 PG 16 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800017 PM 12724223 ER PT S AU Ross, SA AF Ross, SA BE Verma, M Dunn, BK Umar, A TI Diet and DNA methylation interactions in cancer prevention SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE epigenetics; DNA methylation; nutrition; diet; cancer prevention ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; MODERATE FOLATE-DEPLETION; ACID-DEFINED DIETS; RAT-LIVER; COMMON MUTATION; PROSTATE-CANCER; HYPOMETHYLATION; DEFICIENCY; METHYLTRANSFERASE; EXPRESSION AB Epigenetic events constitute an important mechanism by which gene function is selectively activated or inactivated. Since epigenetic events are susceptible to change they offer potential explanations of how environmental factors, including diet, may modify cancer risk and tumor behavior. Abnormal methylation patterns are a nearly universal finding in cancer, as changes in DNA methylation have been observed in many cancer tissues (e.g., colon, stomach, uterine cervix, prostate, thyroid, and breast). Site-specific alterations in DNA methylation have also been observed in cancer and may play a significant role in gene regulation and cancer development. This review presents intriguing evidence that part of the anticancer properties attributed to several bioactive food components, encompassing both essential nutrients and nonessential components, may relate to DNA methylation patterns. Four sites where dietary factors may be interrelated with DNA methylation are discussed. First, dietary factors may influence the supply of methyl groups available for the formation of S-adenosylmethionine (SAM). Second, dietary factors may. modify the utilization of methyl groups by processes including shifts in DNA methyltransferase (Dnmt) activity. A third plausible mechanism may relate to DNA demethylation activity. Finally, the DNA methylation patterns may influence the response to a bioactive food component. C1 NCI, Nutr Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Ross, SA (reprint author), NCI, Nutr Sci Res Grp, Div Canc Prevent, 6130 Execut Blvd,EPN 3157,MSC 7328, Bethesda, MD 20892 USA. NR 56 TC 104 Z9 112 U1 1 U2 17 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 197 EP 207 PG 11 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800018 PM 12724224 ER PT S AU Risinger, JI Maxwell, GL Berchuck, A Barrett, JC AF Risinger, JI Maxwell, GL Berchuck, A Barrett, JC BE Verma, M Dunn, BK Umar, A TI Promoter hypermethylation as an epigenetic component in type I and type II endometrial cancers SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE endometrial cancer; promoter hypermethylation; adenomatous polyposis coli; hMLH1 ID BETA-CATENIN MUTATIONS; MICROSATELLITE INSTABILITY; ESTROGEN-RECEPTOR; CPG HYPERMETHYLATION; UTERINE ENDOMETRIUM; ALPHA-CATENIN; E-CADHERIN; CARCINOMA; GENE; EXPRESSION AB Epigenetic mechanisms that result in aberrant gene expression are a prominent feature of many cancer types. One main epigenetic mechanism for gene silencing involves promoter hypermethylation. Type I and type 11 endometrial cancers exhibit differing clinical, histologic, and molecular genetic characteristics. We hypothesize that these differences also extend to epigenetic phenomena. Promoter methylation analysis of 11 genes in a panel of endometrial cancers supports this hypothesis. These initial data indicate that promoter hypermethylation events occur frequently in type I cancer and were not detected in type 11 cancers using this panel of loci. These data tend to support the hypothesis that type I and type 11 endometrial cancers will exhibit distinct patterns of gene silencing based on promoter hypermethylation events. C1 NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Duke Univ, Dept Obstet & Gynecol, Div Gynecol Oncol, Durham, NC 27710 USA. RP Barrett, JC (reprint author), NCI, Lab Biosyst & Canc, NIH, Bldg 37,Rm 5032,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 30 Z9 34 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 208 EP 212 PG 5 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800019 PM 12724225 ER PT S AU Kalebic, T AF Kalebic, T BE Verma, M Dunn, BK Umar, A TI Epigenetic changes: Potential therapeutic targets SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE methylation; acetylation; cancer; markers; clinical treatment ID HISTONE DEACETYLASE INHIBITORS; INDUCED DNA HYPERMETHYLATION; CPG-ISLAND METHYLATION; DRUG-RESISTANCE; HUMAN CANCERS; REPRESSES TRANSCRIPTION; CELL-DIFFERENTIATION; CHROMATIN STRUCTURE; GENE; 5-AZA-2'-DEOXYCYTIDINE AB Recent advances in human genome research have resulted in novel approaches for the identification of epigenetic modifications associated with cancer. Modulators of DNA methylation and chromatin structure have a dramatic effect on gene expression, cellular proliferation, differentiation, and apoptosis. Molecular pathways regulating epigenetic events that occur during tumorigenesis have been exploited as new targets for therapeutic intervention. Clinical studies exploring the effectiveness of therapeutic agents targeting DNA methylation and acetylation of histones have yielded promising results. Molecular profiles of epigenetic alterations in cancer cells could allow better stratification of patients who may show responsiveness to specific treatments. C1 NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Kalebic, T (reprint author), Nova Pharmaceut Corp, Novartis Oncol, 1 Hlth Plaza, E Hanover, NJ 07936 USA. NR 61 TC 27 Z9 30 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 278 EP 285 PG 8 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800026 PM 12724232 ER PT S AU Patel, A Groopman, JD Umar, A AF Patel, A Groopman, JD Umar, A BE Verma, M Dunn, BK Umar, A TI DNA methylation as a cancer-specific biomarker - From molecules to populations SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE DNA methylation; biomarkers; serum markers; early cancer detection ID CELL LUNG-CANCER; HYPERMETHYLATION-ASSOCIATED INACTIVATION; ABERRANT PROMOTER METHYLATION; ARBITRARILY PRIMED-PCR; TUMOR-SUPPRESSOR GENE; OVARIAN-CANCER; BREAST-CANCER; CPG ISLAND; COLORECTAL-CANCER; MULTIPLE GENES AB Cancer contributes to a large proportion of the mortality and morbidity in the United States and worldwide. Despite advances in diagnosis and treatment of various cancers, early detection and treatment of cancer remain a challenge. Diagnosis of cancer often occurs once the disease has progressed to a point where currently available intervention options provide limited success. Therefore, techniques that enable early detection followed by targeted interventions would influence stage at diagnosis and, in turn, mortality associated with cancer. Identification of molecular biomarkers, especially those that are associated with cancer initiation and progression, shows promise as an effective strategy in this regard. One potential early detection biomarker is DNA methylation of the promoter region of certain cancer-associated genes, which results in gene inactivation. Examination of serum for circulating tumor DNA with abnormal methylation patterns offers a possible method for early detection of several cancers and serves as a point for early intervention and prevention strategies. Additionally, it is imperative to consider how such a screening mechanism can be implemented in populations at risk, especially in resource-poor settings. Thus, the challenge is to validate DNA methylation as a cancer-specific biomarker, with the ultimate goal of designing a research plan that integrates the current knowledge base regarding cancer detection and diagnosis into specific prevention and intervention strategies that can be applied at a population level. C1 NCI, Ctr Canc Res, Lab Tumor Immunol & Biol, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. RP Patel, A (reprint author), NCI, Ctr Canc Res, Lab Tumor Immunol & Biol, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. NR 84 TC 29 Z9 33 U1 1 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 286 EP 297 PG 12 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800027 PM 12724233 ER PT S AU Verma, M Dunn, BK Ross, S Jain, P Wang, W Hayes, R Umar, A AF Verma, M Dunn, BK Ross, S Jain, P Wang, W Hayes, R Umar, A BE Verma, M Dunn, BK Umar, A TI Early detection and risk assessment - Proceedings and recommendations from the workshop on epigenetics in cancer prevention SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE acetylatlon; biomarker; cancer detection; epigenetics; methylation; microarray; prevention; risk assessment ID CPG-ISLAND HYPERMETHYLATION; DNA METHYLATION; PROMOTER HYPERMETHYLATION; HISTONE-DEACETYLASE; LUNG-CANCER; PROSTATE ADENOCARCINOMA; NICKEL CARCINOGENESIS; MOLECULAR-BIOLOGY; COLORECTAL-CANCER; GENE-EXPRESSION AB Recent advances in molecular biology that have provided a greater understanding of multistage carcinogenesis include the use of biomarkers of early detection and risk assessment. Prominent among such biomarkers are epigenetic changes. The field of epigenetics has seen a recent surge of interest among cancer researchers since alterations in DNA methylation have emerged as one of the most consistent molecular alterations in multiple neoplasms. Chromatin condensation, histone deacetylation, and promoter methylation are major steps in the epigenetic regulation of gene expression. Epigenetic changes may occur due to environmental factors, aging, and genomic imprinting. An important distinction between genetic and epigenetic alterations in cancer prevention is that the latter might be more easily reversed using therapeutic interventions. In the workshop the following areas of research were recognized for emphasis in future work: (1) basic epigenetic mechanisms in cancer need further investigation; (2) technology development in the area of epigenetics, such as high-throughput quantitative assays and increased sensitivity/specificity, is essential for the early detection and risk assessment of cancer; (3) the clinical application of epigenetic changes to cancer prevention and risk assessment needs further investigation. Further research will lead to the identification of new targets for cancer prevention. C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Rockville, MD 20852 USA. US FDA, Rockville, MD 20857 USA. NCI, Div Epidemiol, NIH, Rockville, MD 20852 USA. RP Verma, M (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Execut Plaza N,Room 3144,6130 Execut Blvd, Rockville, MD 20852 USA. NR 82 TC 23 Z9 26 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 298 EP 319 PG 22 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800028 PM 12724234 ER PT J AU Theodore, W AF Theodore, W TI The treatment gap in North America: Poverty, isolation, ethnicity SO EPILEPSIA LA English DT Meeting Abstract CT 25th International Epilepsy Congress CY OCT 12-16, 2003 CL LISBON, PORTUGAL SP Int League Against Epilepsy, Int Bureau Epilepsy C1 NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2003 VL 44 SU 8 BP 18 EP 18 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 758LV UT WOS:000187636400067 ER PT J AU Jacobs, MP AF Jacobs, MP TI The need for the development of specific Benchmarks SO EPILEPSIA LA English DT Meeting Abstract CT 25th International Epilepsy Congress CY OCT 12-16, 2003 CL LISBON, PORTUGAL SP Int League Against Epilepsy, Int Bureau Epilepsy C1 NINDS, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2003 VL 44 SU 8 BP 19 EP 19 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 758LV UT WOS:000187636400073 ER PT J AU Theodore, W Giovacchini, G Toczek, M Lang, L Fraser, C Herscovitch, P Eckelman, W Carson, R AF Theodore, W Giovacchini, G Toczek, M Lang, L Fraser, C Herscovitch, P Eckelman, W Carson, R TI Reduced 5-HT1A receptors in temporal lobe epilepsy: Partial volume corrected [18F]FCWAY PET SO EPILEPSIA LA English DT Meeting Abstract CT 25th International Epilepsy Congress CY OCT 12-16, 2003 CL LISBON, PORTUGAL SP Int League Against Epilepsy, Int Bureau Epilepsy C1 NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2003 VL 44 SU 8 BP 50 EP 51 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 758LV UT WOS:000187636400197 ER PT J AU Smorenburg, CH ten Tije, AJ Verweij, J Bontenbal, M Mross, K van Zomeren, DM Seynaeve, C Sparreboom, A AF Smorenburg, CH ten Tije, AJ Verweij, J Bontenbal, M Mross, K van Zomeren, DM Seynaeve, C Sparreboom, A TI Altered clearance of unbound paclitaxel in elderly patients with metastatic breast cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE paclitaxel; elderly patients; breast cancer; pharmacokinetics; pharmacology ID CREMOPHOR EL; HUMAN PLASMA; PHASE-II; DRUG-METABOLISM; AGE; OLDER; PHARMACOKINETICS; PHARMACOLOGY; INFUSIONS; TOXICITY AB The pharmacokinetic behaviour of anticancer drugs may be altered with aging due to (for example) differences in body composition and decreased hepatic and renal function. To address this issue for paclitaxel, we studied the pharmacokinetics of the drug in eight elderly women (greater than or equal to 70 years) with metastatic breast cancer (median age (range), 77 years (70-84 years)) and a control group of 15 patients aged < 70 years (median age (range), 54 years (22-69 years)). Paclitaxel was administered as a 1-h intravenous (i.v.) infusion at a dose of 80 (elderly) or 100 mg/m(2) (< 70 years), and serial blood samples were obtained at baseline, and up to 24 h after the end of infusion. Paclitaxel concentration-time profiles were fitted to a linear three-compartment model without any demonstration of saturable behaviour. The clearance of unbound paclitaxel was 124+/-35.0 (elderly) versus 247+/-55.4 l/h/m(2) (< 70 years) (P=0.002), and was inversely related to the patient's age (R-2 = 0.857; P < 0.00001). Total plasma clearance of the formulation vehicle Cremophor EL (CrEL) was 150+/-60.7 (elderly) versus 115+/-39.2 ml/h/m(2) (<70 years) (P=0.04). These data indicate an approximately 50% change in total body clearance of unbound paclitaxel and a concomitant significant increase in systemic exposure with age, most likely as a,result of altered CrEL disposition. The clinical relevance of these observations with respect to toxicity profiles and antitumour efficacy requires further evaluation. (C) 2002 Published by Elsevier Science Ltd. C1 Dr Daniel Den Hoed Canc Ctr, Erasmus MC, Dr Daniel Denhoed Canc Ctr, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands. Univ Freiburg, Dept Med Oncol & Clin Pharmacol, D-79106 Freiburg, Germany. RP Sparreboom, A (reprint author), NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008 NR 35 TC 47 Z9 49 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2003 VL 39 IS 2 BP 196 EP 202 AR PII S0959-8049(02)00611-1 DI 10.1016/S0959-8049(02)00611-1 PG 7 WC Oncology SC Oncology GA 659QR UT WOS:000181789200020 PM 12509952 ER PT J AU Christov, KT Shilkaitis, AL Kim, ES Steele, VE Lubet, RA AF Christov, KT Shilkaitis, AL Kim, ES Steele, VE Lubet, RA TI Chemopreventive agents induce a senescence-like phenotype in rat mammary tumours SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE senescence; mammary tumors; telomerase activity; chemoprevention ID TELOMERASE ACTIVITY; BREAST-CANCER; EPITHELIAL-CELLS; IN-SITU; GLAND; IMMORTALIZATION; CARCINOGENESIS; PROLIFERATION; INHIBITORS; VOROZOLE AB Terminal replicative senescence (TRS) is a physiological process associated with terminal differentiation, shortening of the telomere, and lack of proliferative activity. Immortalised and tumour cells have lost their differentiation potential and the ability to develop a senescence phenotype. Recently, others and we [11] have observed that some antitumour agents and radiation induce a senescence-like phenotype (SLP) in human immortalized and tumour cell lines. The main purpose of this study was to identify senescence-like cells (SLC) in mammary tumours of rats and assess whether chemopreventive agents that have been used for the prevention and/or treatment of breast cancer can induce a SLP in tumour cells. Sprague-Dawley rats with N-methyl-N-nitrosourea (MNU)-induced mammary tumours were randomised and treated with tamoxifen, vorozole, 4-(hydroxyphenyl)retinamide (4-HPR), or 9-cis-retinoic acid (9cRA). The SLC in mammary tumours were identified and characterised by: (a) SA-beta-Gal staining method, which has been considered specific for human cells in TRS (b) staining for lipofuscin, which, although not specific, accumulates in the cytoplasm of cells in senescence; (c) lack of 5-Bromodeoxyuridine (BrdU) labelling after continuous (7 days) infusion of BrdU via osmotic pumps; (d) 90degrees side light scatter (90LS) as evaluated by flow cytometry; and (e) decreased telomerase activity. We found that in control tumours, SA-P-Gal-positive cells were rare (below 1.0%) among the tumour cells, stroma fibroblast, myoepithelial and endothelial cells. SA-P-Gal-positive cells increased significantly in the tumours treated with chemopreventive agents and this was associated with a lack of proliferative activity, increased cell granularity, lipofuscin accumulation, and decreased telomerase activity. Thus, in this study we provide for the first time evidence that cells in replicative senescence are present in mammary tumours of rats and that chemopreventive agents can suppress tumor growth by a novel cellular mechanism, inducing a SLP in the tumor cells. (C) 2002 Published by Elsevier Science Ltd. C1 Univ Illinois, Dept Surg Oncol, Chicago, IL 60612 USA. NCI, Div Canc Prevent, Rockville, MD 20852 USA. RP Christov, KT (reprint author), Univ Illinois, Dept Surg Oncol, 840 S Wood St, Chicago, IL 60612 USA. EM christov@uic.edu FU NCI NIH HHS [CN-55179, CN-65123] NR 34 TC 24 Z9 24 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2003 VL 39 IS 2 BP 230 EP 239 AR PII S0959-8049(02)00497-5 DI 10.1016/S0959-8049(02)00497-5 PG 10 WC Oncology SC Oncology GA 659QR UT WOS:000181789200024 PM 12509956 ER PT J AU Minneci, P Deans, K Natanson, C Eichacker, PQ AF Minneci, P Deans, K Natanson, C Eichacker, PQ TI Increasing the efficacy of anti-inflammatory agents used in the treatment of sepsis SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Review ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PLACEBO-CONTROLLED TRIAL; CONTROLLED MULTICENTER TRIAL; HIGH-DOSE METHYLPREDNISOLONE; HUMAN SEPTIC SHOCK; DOUBLE-BLIND; FACTOR-ALPHA; MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI AB Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of septic shock. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Despite promising preclinical results, several different mediator-specific anti-inflammatory agents failed to demonstrate significant benefit in patients. There was, however, a significant difference in mortality between preclinical and clinical trials. The median control mortality in preclinical trials, performed almost uniformly in highly lethal sepsis models, was 88%. In clinical trials however, the median control mortality rate was much lower, at 41%. A recent meta-regression analysis of these preclinical and clinical trials in combination with prospective confirmatory studies demonstrated that risk of death as assessed by control group mortality rate significantly altered the treatment effect of these agents in both humans and animals. While anti-inflammatory agents were very beneficial in groups with high control mortality rates, they were ineffective or harmful in groups with low control mortality rates. Thus, variation in the risk of death due to sepsis provides a basis for the marked difference in the efficacy of these anti-inflammatory agents in preclinical and clinical trials over the last decade. In contrast to mediator-specific anti-inflammatory agents, glucocorticoids and activated protein C have recently demonstrated significant beneficial effects in individual clinical trials. However, glucocorticoids were studied only in patients with vasopressor-dependent septic shock, which is associated with a high control mortality rate (i.e. 61%) similar to the level at which mediator-specific agents would have been expected to be markedly beneficial. Furthermore, consistent with earlier findings for mediator-specific anti-inflammatory agents, analysis of the activated protein C study also demonstrated a relationship between risk of death and effect of treatment. Developing better methods to define high-risk septic populations for treatment with anti-inflammatory agents will increase the efficacy of this therapeutic approach and minimize its potential for harm. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Minneci, P (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 83 TC 16 Z9 18 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JAN PY 2003 VL 22 IS 1 BP 1 EP 9 DI 10.1007/s10096-002-0857-3 PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 655ET UT WOS:000181538900001 PM 12582737 ER PT J AU Porta, M Vioque, J Ayude, D Alguacil, J Jariod, M Ruiz, L Murillo, JA AF Porta, M Vioque, J Ayude, D Alguacil, J Jariod, M Ruiz, L Murillo, JA TI Coffee drinking: The rationale for treating it as a potential effect modifier of carcinogenic exposures SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE caffeine; cell cycle; coffee/etiology; coffee/genetics; coffee/metabolism; coffee/physiology; DNA repair; epidemiology; epidemiology/methods; molecular; mutation/genetics; neoplasms/genetics ID POLYCYCLIC AROMATIC AGENTS; K-RAS MUTATIONS; BLADDER-CANCER; PANCREATIC-CANCER; RISK-FACTORS; LIFE-STYLE; DNA-DAMAGE; BLACK TEA; CAFFEINE; CONSUMPTION AB Clinical and epidemiological studies on cancer etiology seldom treat coffee drinking as a potential effect modifier. Yet caffeine exerts significant effects upon a large variety of physiologic, cellular and molecular systems. Caffeine, 'the world's most popular drug', is also a fundamental research tool, widely used in clinical studies on drug metabolism, and in experimental studies on cell cycle checkpoints, DNA repair, and apoptosis, among many other. Caffeine can profoundly alter cell cycle checkpoint function and several mechanisms of DNA repair, as well as carcinogen metabolism. The impact of caffeine on cell cycle checkpoint function occurs in spite of it being nonmutagenic in traditional mutagenesis assays. A complex body of biologic evidence suggests that caffeine-containing beverages can both enhance and antagonise potentially carcinogenic exposures. However, most pathways leading to the ultimate effects in human beings remain unknown. It is unclear whether any of the hundreds of compounds contained in coffee and tea exert a direct and significant carcinogenic effect per se in any human tissue at usual conditions of use. Reasons exist to consider that coffee may sometimes be an indirect, positive confounder. The study of interactions between caffeine-containing beverages and environmental agents in well defined groups of healthy and diseased people could yield new insights into checkpoint signal transduction and other mechanisms of carcinogenesis. Information on the use of caffeine-containing beverages should more often be integrated in studies on the role of gene environment interactions in the pathogenesis of cancer. C1 Univ Autonoma Barcelona, Inst Municipal Invest Med, E-08003 Barcelona, Spain. Univ Miguel Hernandez, Dept Publ Hlth, Alacant, Spain. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Porta, M (reprint author), Univ Autonoma Barcelona, Inst Municipal Invest Med, Carrer Dr Aiguader 80, E-08003 Barcelona, Spain. RI Porta, Miquel/B-5787-2008; vioque, jesus/A-1066-2008; OI Porta, Miquel/0000-0003-1684-7428; Vioque, Jesus/0000-0002-2284-148X NR 94 TC 33 Z9 36 U1 1 U2 13 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PY 2003 VL 18 IS 4 BP 289 EP 298 DI 10.1023/A:1023700216945 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 673MD UT WOS:000182584000003 PM 12803368 ER PT J AU Chatterjee, N Hartge, P AF Chatterjee, N Hartge, P TI Apportioning causes, targeting populations and predicting risks: Population attributable fractions SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material C1 NCI, Biostat Branch, DHHS, NIH, Bethesda, MD 20892 USA. NCI, Off Director, Epidemiol & Biostat Program, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Bethesda, MD 20892 USA. RP Chatterjee, N (reprint author), 6120 Execut Blvd,EPS 8038, Rockville, MD 20852 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PY 2003 VL 18 IS 10 BP 933 EP 935 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 724XY UT WOS:000185514600002 PM 14598922 ER PT J AU Eddington, ND Cox, DS Khurana, M Salama, NN Stables, JP Harrison, SJ Negussie, A Taylor, RS Tran, UQ Moore, JA Barrow, JC Scott, KR AF Eddington, ND Cox, DS Khurana, M Salama, NN Stables, JP Harrison, SJ Negussie, A Taylor, RS Tran, UQ Moore, JA Barrow, JC Scott, KR TI Synthesis and anticonvulsant activity of enaminones Part 7. Synthesis and anticonvulsant evaluation of ethyl 4-[(substituted phenyl)amino]-6-methyl-2-oxocyclohex-3-ene-1-carboxylates and their corresponding 5-methylcyclohex-2-enone derivatives SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE enaminones; maximal electroshock seizure test; anticonvulsant activity; structure-activity relationship; LC/MS analysis ID ANTIEPILEPTIC DRUG DEVELOPMENT; CATION-PI INTERACTIONS; HIPPOCAMPAL SEIZURES; TOXICITY; BINDING; PROFILE; ESTERS; TISSUE; CELLS; RATS AB Further investigation of the potential anticonvulsant activity of the enaminones was attempted to discern the possible role of metabolites as the active/co-active entities of the esters of the enaminones. A series of 5-methyl-2-cyclohexene enaminones, the hypothesised metabolites corresponding to a sequence of active and inactive esters were synthesised and evaluated for anticonvulsant activity. With two exceptions, ethyl 4-[(4-cyanophenyl)amino]-6-methyl-2-oxocyclohex-3-ene-1-carboxylate (1k), and 3-[N-(4-cyanophenyl)amino]-5-methyl-2-cyclohexenone (3g), and ethyl 4-(phenylamino)-6-methyl-2-cyclohexenone (1n), and 3N-(phenylamino)-5-methyl-2-cyclohexenone (3j), anticonvulsant screening data were parallel, with the ester and their putative decarboxylated analogue displaying similar activity. The most active analogue evaluated in this series, ethyl 4-[(4-chloropheny-1)amino]-6-methyl-2-oxocyclohex-3-ene-1-carboxylate (le), which displayed an ED(50) of 16.7 mg kg(-1) and a TD(50) of 110.7 mg kg(-1) (protective index, PI = TD(50)/ED(50) = 6.6) in the maximal electroshock seizure (MES) test in mice and an ED50 of 3.0 mg kg(-1) and a TD(50) > 250 mg kg(-1) (PI > 83.3) in rats in the same evaluation, making this compound the most potent enaminone emanating from our laboratories. Pharmacokinetic evaluation of compound le in rats using LC/MS analysis unequivocally provides evidence that this compound is converted into the decarboxylated analogue 3a in the brain and the urine. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. Howard Univ, Sch Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA. Howard Univ, Coll Engn Architecture & Comp Sci, Dept Chem Engn, Washington, DC 20059 USA. NINDS, Epilepsy Branch, Div Convulsive Dev & Neuromuscular Disorders, Bethesda, MD 20892 USA. RP Scott, KR (reprint author), Howard Univ, Coll Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA. EM kscott@fac.howard.edu FU NIGMS NIH HHS [1 R21 GM63494-01] NR 43 TC 43 Z9 46 U1 1 U2 3 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 JAN PY 2003 VL 38 IS 1 BP 49 EP 64 AR PII S0223-5234(02)00006-5 DI 10.1016/S0223-5234(02)00006-5 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 658LT UT WOS:000181723000006 PM 12593916 ER PT J AU Frattali, C Duffy, JR Litvan, I Patsalides, AD Grafman, J AF Frattali, C Duffy, JR Litvan, I Patsalides, AD Grafman, J TI Yes/no reversals as neurobehavioral sequela: a disorder of language, praxis, or inhibitory control? SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE inhibitory control; language; neurocognitive disorders; praxis; yes/no reversals ID CORTICOBASAL DEGENERATION; APRAXIA AB This study identifies a linguistic phenomenon suggestive of damage to fronto-subcortical circuitry. Our objective was to determine the occurrence and neuroradiological/neurobehavioral correlates of yes/no reversals in corticobasal degeneration (CBD), and document occurrence of reversals in other neurological conditions. In a prospective study, we evaluated 34 CBD patients using a neuropsychologic battery and magnetic resonance imaging. Patients were subdivided into two groups: those with (n = 11) and without (n = 23) yes/no reversals. In a retrospective study conducted during the period of 1991-2001, we identified 33 patients for whom yes/no reversals occurred to compare correlates with prospective study findings. In the prospective study, 11 patients (32.3%) had yes/no reversals. Significant between-group differences were found in scores of lexical fluency (P = 0.02) and prehension (P = 0.03). Prehension scores correlated with facial praxis (P < 0.0001) and upper limb praxis scores (P < 0.0001) in the yes/no reversal group only. In the retrospective study, nine CBD patients and 24 non-CBD patients had yes/no reversals, with damage to fronto-subcortical areas present in all patients. Results suggest an association with deficits in mental flexibility and inhibitory control. High within-group correlations of lexical fluency and prehension with praxis scores suggest a relationship of yes/no reversals with multiple factors. C1 NIH, Speech Language Pathol Sect, Dept Rehabil Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Mayo Clin, Dept Neurol, Div Speech Pathol, Rochester, MN USA. Univ Louisville, Sch Med, Dept Neurol, Movement Disorder Program, Louisville, KY 40292 USA. NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Frattali, C (reprint author), NIH, Speech Language Pathol Sect, Dept Rehabil Med, Warren G Magnuson Clin Ctr, Bldg 10,Rm 6S 235,MSC 1604, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 10 TC 9 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD JAN PY 2003 VL 10 IS 1 BP 103 EP 106 DI 10.1046/j.1468-1331.2003.00545.x PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 635JA UT WOS:000180394700020 PM 12535005 ER PT J AU Freedman, NMT Sundaram, SK Kurdziel, K Carrasquillo, JA Whatley, M Carson, JM Sellers, D Libutti, SK Yang, JC Bacharach, SL AF Freedman, NMT Sundaram, SK Kurdziel, K Carrasquillo, JA Whatley, M Carson, JM Sellers, D Libutti, SK Yang, JC Bacharach, SL TI Comparison of SUV and Patlak slope for monitoring of cancer therapy using serial PET scans SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE PET; FDG; SUV; Patlak ID STANDARDIZED UPTAKE VALUES; POSITRON-EMISSION-TOMOGRAPHY; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; F-18 FLUORODEOXYGLUCOSE; BODY-WEIGHT; GRAPHICAL EVALUATION; FDG PET; TUMORS; REPRODUCIBILITY AB The standardized uptake value (SUV) and the slope ofthe Patlak plot (K) have both been proposed as indices to monitor the progress of disease during cancer therapy. Although a good correlation has been reported between SUV and K, they are not equivalent, and may not be equally affected by metabolic changes occurring during disease progression. or therapy. We wished to compare changes in tumor SUV with changes in K during serial positron emission tomography (PET) scans for monitoring therapy. Thirteen patients enrolled in a protocol to treat renal cell carcinoma metastases were studied. Serial dynamic fluorodeoxyglucose (FDG) PET scans and computed tomography (CT) and magnetic resonance (MR) scans were performed once prior to treatment, once at 36 2 days after the start of treatment, and (in 7/13 subjects, 16/27 lesions) a third time at 92 9 days after the start of treatment. This resulted in a total of 33 scans, and 70 tumor Patlak and SUV values (one value for each lesion at each time point). SUV and K were measured over one to four predefined tumors/patient at each time point. The input function was obtained from regions of interest over the heart, combined, if necessary, with late blood samples. Over all tumors and scans, SUV and K correlated well (r=0.97, P<0.0001). However, change in SUV with treatment over all tumor scan pairs was much less well correlated with the corresponding change in K (r=0.73, P<0.0001). The absolute difference in % change was outside the 95% confidence limits expected from previous variability studies in 6 of 43 pairs of tumor scans, and greater than 50% in 2 of 43 tumor scan pairs. In four of the six cases, the two indices predicted opposing therapeutic outcomes. Similar results were obtained for SUV normalized by body weight or body surface area and for SUVs using mean or maximum count. Changes in CT and MR-tumor cross-product dimensions correlated poorly with each other (r=0.47, P=NS), and so could not be used to determine the "correct" PET index. Absolute values of SUV and K correlated well over the patient population. However, when monitoring individual patient therapy serially, large differences in the % changes in the two indices were occasionally found, sometimes sufficient to produce opposing conclusions regarding the progression of disease. C1 NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. RP Bacharach, SL (reprint author), NIH, Bldg 10,Room 1C401, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; Sundaram, Senthil/B-3905-2013; OI Sundaram, Senthil/0000-0002-0382-0536; Carrasquillo, Jorge/0000-0002-8513-5734 NR 23 TC 54 Z9 55 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JAN PY 2003 VL 30 IS 1 BP 46 EP 53 DI 10.1007/s00259-002-0981-4 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 640MC UT WOS:000180691800008 PM 12483409 ER PT J AU Djalilian, AR Cantrill, HC Samuelson, TW AF Djalilian, AR Cantrill, HC Samuelson, TW TI Intraocular hemorrhage after systemic thrombolytic therapy in a patient with exudative macular degeneration SO EUROPEAN JOURNAL OF OPHTHALMOLOGY LA English DT Article DE intraocular; hemorrhage thrombolytic; complication; macular degeneration ID MYOCARDIAL-INFARCTION AB PURPOSE. To report a hemorrhagic complication from thrombolytic therapy in a patient with exudative macular degeneration CASE REPORT. A 75 year old patient with exudative macular degeneration developed pain and loss of vision in the left eye shortly after receiving tissue plasminogen activator (t-PA) for a myocardial infarction. Examination revealed the patient to be in angle closure. A CT scan revealed the etiology of the angle closure to be a dense vitreous hemorrhage pushing the iris-lens diaphragm forward. Intraocular pressure was treated successfully, but the final visual acuity was only light perception CONCLUSIONS. Thrombolytic therapy can lead to devastating intraocular hemorrhages. The presence of exudative macular degeneration may potentially increase the risk of developing such complications. C1 Reg Hosp, Dept Ophthalmol, St Paul, MN USA. RP Djalilian, AR (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1120-6721 J9 EUR J OPHTHALMOL JI Eur. J. Ophthalmol. PD JAN-FEB PY 2003 VL 13 IS 1 BP 96 EP 98 PG 3 WC Ophthalmology SC Ophthalmology GA 650KH UT WOS:000181262200017 PM 12635684 ER PT J AU Terracciano, A McCrae, RR Costa, PT AF Terracciano, A McCrae, RR Costa, PT TI Factorial and construct validity of the Italian Positive and Negative Affect Schedule (PANAS) SO EUROPEAN JOURNAL OF PSYCHOLOGICAL ASSESSMENT LA English DT Article DE positive/negative affect; CFA; estimation method; tripartite model of anxiety and depression; crosscultural ID CONFIRMATORY FACTOR-ANALYSIS; CROSS-CULTURAL CONVERGENCE; FACTOR-ANALYTIC VALIDATION; NEO PERSONALITY-INVENTORY; 5-FACTOR MODEL; MULTIVARIATE SKEWNESS; EMOTIONAL EXPERIENCE; TRIPARTITE MODEL; AGE; SAMPLE AB This study, provides evidence that an Italian version of the Positive and Negative Affect Schedule (PANAS) is a reliable and valid self-report measure. In an Italian sample (N = 600), the PANAS showed solid psychometric properties, and several American findings with the PANAS were replicated. The replicability of the PANAS factor structure was confirmed by high congruence coefficients between the American and Italian varimax solutions. Alternative models were tested with Confirmatory Factor Analysis; as in previous studies, the two-factor model achieved the best fit, but absolute fit indices varied with the estimation methods used. The independence/bipolarity issue was also explored. Positive and negative affect scales remain substantially independent after accounting for measurement error and acquiescence. Some predictions from the tripartite model of anxiety and depression were confirmed, and external correlates of the PANAS replicated those found in other language and cultures. These analyses offer strong support for the construct validity of the Italian PANAS. C1 NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. RP Terracciano, A (reprint author), NIA, Lab Personal & Cognit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI terracciano, antonio/B-1884-2008; OI Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS [Z99 AG999999, ZIA AG000180-25, ZIA AG000180-26] NR 70 TC 112 Z9 114 U1 4 U2 19 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 1015-5759 J9 EUR J PSYCHOL ASSESS JI Eur. J. Psychol. Assess. PY 2003 VL 19 IS 2 BP 131 EP 141 DI 10.1027//1015-5759.19.2.131 PG 11 WC Psychology, Applied SC Psychology GA 674KB UT WOS:000182635000006 PM 20467578 ER PT J AU Puente, D Malats, N Cecchini, L Tardon, A Garcia-Closas, R Serra, C Carrato, A Sala, M Boixeda, R Dosemeci, M Real, FX Kogevinas, A AF Puente, D Malats, N Cecchini, L Tardon, A Garcia-Closas, R Serra, C Carrato, A Sala, M Boixeda, R Dosemeci, M Real, FX Kogevinas, A TI Gender-related differences in clinical and pathological characteristics and therapy of bladder cancer SO EUROPEAN UROLOGY LA English DT Article DE bladder cancer; sex ratio; women; treatment; stage; pathological characteristics ID TRANSITIONAL-CELL-CARCINOMA; BACILLUS-CALMETTE-GUERIN; PROGNOSTIC FACTORS; NATURAL-HISTORY; RISK; EPIDEMIOLOGY; TUMORS; STAGE; ORGANIZATION; DIAGNOSIS AB Objective: To confirm the very high male:female ratios previously observed among Spanish bladder cancer patients and to assess gender differences in tumoral characteristics, diagnostic procedures, and treatment in a large series of consecutive bladder cancer patients. Patients and Methods: All newly diagnosed bladder cancer patients (n = 615) in 17 Spanish hospitals, between 1997-2000, were included. Information was collected both through personal interviews to patients and from medical records using a structured form. Results: Seventy-six percent of tumours were superficial. The male:female ratio was 6.7 and it was similar for superficial and infiltrating tumours. Women were older than men at the diagnosis of bladder cancer (68.2 +/- 9.4 years versus 65.7 +/- 9.7 years, p = 0.01). Ten percent of superficial tumours in women, versus 3% in men, were classified as "other histological types" (p = 0.008). TIGIII tumours were more frequent among men (17% versus 7%,p = 0.047). On the other hand, women were more likely to present with 0a-stage tumours (48.6% versus 35.5%, p = 0.04), multiple tumours (50% versus 29%, trend test: 0.005), multi-centric tumours (54% versus 38%, p = 0.019), and larger infiltrating masses (5.2 cm versus 3.8 cm, p = 0.03) than men. Among Oa-stage tumours, only 23% of women compared to 54% of men received transurethral resection (TUR) alone (p = 0.002). Women were almost five-fold more likely to receive additional therapies to TUR (p = 0.004) after adjusting for age, geographical area, stage, tumoral size, nuclear grade, and multiplicity. Conclusion: The study confirms the very high male:female ratio of bladder cancer in Spain. We found substantial differences in the pathological characteristics of tumours from men and women. There was a tendency for women to receive more frequently non-standard, more aggressive, therapy than men. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Pompeu Fabra, Inst Municipal Invest Medica, E-08003 Barcelona, Spain. Hosp Badalona Germans Trias & Pujol, Badalona, Spain. Univ Oviedo, Asturias, Spain. Univ Hosp, Tenerife, Spain. Consorci Hosp Parc Tauli, Sabadell, Spain. Hosp Gen Elche, Alicante, Spain. NCI, Bethesda, MD 20892 USA. RP Malats, N (reprint author), Univ Pompeu Fabra, Inst Municipal Invest Medica, Carrer Aiguader 80, E-08003 Barcelona, Spain. EM nuria@imim.es RI sala, maria/A-2593-2011; Serra, C/E-6879-2014; Martinez, Esther/H-2562-2013; Fernandez , Irene/E-5705-2016; OI Serra, C/0000-0001-8337-8356; Sala Serra, Maria/0000-0002-5516-5967 NR 38 TC 32 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JAN PY 2003 VL 43 IS 1 BP 53 EP 62 AR PII S0302-2838(02)00496-7 DI 10.1016/S0302-2838(02)00496-7 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 643TF UT WOS:000180876000011 PM 12507544 ER PT J AU Kondrashov, AS AF Kondrashov, AS TI Accumulation of Dobzhansky-Muller incompatibilities within a spatially structured population SO EVOLUTION LA English DT Article DE allele; allopatry; incompatibility; parapatry; speciation ID PARAPATRIC SPECIATION; SELECTION; GENETICS; EVOLUTION AB A simple, deterministic analysis predicts that accumulation of Dobzhansky-Muller incompatibilities by a spatially structured population strongly depends on the number of negative interactions of an allele. If an allele can be incompatible with alleles at only one locus, incompatibilities accumulate linearly with time. In contrast, if an allele can participate in multiple pairwise incompatibilities with alleles at different loci, the expected number of incompatibilities eventually increases quadratically. C1 Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Kondrashov, AS (reprint author), Natl Ctr Biotechnol Informat, NIH, 45 Ctr Dr, Bethesda, MD 20892 USA. NR 17 TC 38 Z9 39 U1 1 U2 12 PU SOC STUDY EVOLUTION PI LAWRENCE PA 810 E 10TH STREET, LAWRENCE, KS 66044 USA SN 0014-3820 J9 EVOLUTION JI Evolution PD JAN PY 2003 VL 57 IS 1 BP 151 EP 153 PG 3 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 648NC UT WOS:000181156600013 PM 12643575 ER PT J AU Sohn, YH Jung, HY Kaelin-Lang, A Hallett, M AF Sohn, YH Jung, HY Kaelin-Lang, A Hallett, M TI Excitability of the ipsilateral motor cortex during phasic voluntary hand movement SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE transcranial magnetic stimulation; motor cortex; voluntary movements; corpus callosum ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN CORTICOSPINAL EXCITABILITY; CORPUS-CALLOSUM CONNECTIONS; FINGER MOVEMENTS; INTERHEMISPHERIC INHIBITION; ELECTRICAL-STIMULATION; HEMISPHERIC-ASYMMETRY; INTRACORTICAL FACILITATION; TRANSCALLOSAL INHIBITION; DIFFERENT COMPLEXITIES AB We investigated the influence of self-paced, phasic voluntary hand movement on the excitability of the ipsilateral motor cortex. Single- and paired-pulse transcranial magnetic stimulation (TMS) was applied to the right motor cortex triggered by EMG onset of self-paced movements of individual right hand fingers at intervals ranging from 13 to 2,000 ins. Motor evoked potentials (MEPs) were evaluated in several left arm muscles. Significant suppression of MEP amplitudes was observed when TMS was applied between 35 and 70 ms after EMG onset. This inhibition was diffuse, affecting "adjacent" muscles (those near the homologous muscle in the same extremity) as well as homologous muscles, but more inhibition was observed in adjacent and distal muscles than homologous and proximal muscles. Significant inhibition of ipsilateral motor cortex was produced by index finger movements (both the extensor indicis proprius and the first dorsal interosseus), but not by little finger movement (the abductor digiti minimi). Paired-pulse TMS (at 2- and 10-ms interstimulus intervals) showed a significant increase in intracortical facilitation (ICF) selectively in the homologous muscle when triggered by self-paced movement of the opposite hand, but no change was observed in intracortical inhibition. When stimulation was triggered by self-paced movements, the silent period of the homologous muscle was significantly shortened, but the F-wave and compound muscle action potential were unchanged. Our findings demonstrate that voluntary hand movement exerts an inhibitory influence on a diffuse area of the ipsilateral motor cortex. This inhibitory influence is both time and movement dependent. The inhibitory influence is nonselective, while the facilitatory influence (enhancing ICF) appears to act selectively on the homologous muscles. These effects are most likely mediated by a transcallosal pathway. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Yonsei Univ, Coll Med, Dept Neurol, Seoul, South Korea. Yonsei Univ, Coll Med, Brain Res Inst, Seoul, South Korea. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10-5N226,10 Ctr Dr, Bethesda, MD 20892 USA. NR 54 TC 86 Z9 87 U1 1 U2 8 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 JAN PY 2003 VL 148 IS 2 BP 176 EP 185 DI 10.1007/s00221-002-1292-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 641GD UT WOS:000180736100005 PM 12520405 ER PT J AU Mattison, JA Lane, MA Roth, GS Ingram, DK AF Mattison, JA Lane, MA Roth, GS Ingram, DK TI Calorie restriction in rhesus monkeys SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on the Neurobiology and Neuroendocrinology of Aging CY JUL 21-26, 2002 CL BREGENZ, AUSTRIA SP SO Illinois Univ, Sch Med, Orentreich Fdn Advancement Sci, Paul F Glenn Sponsorship Fund, Amer Federat Aging Res, Junifur Fdn, Servier, Rech Interne Alliances Strateg, Land Vorarlbert & Landeshauptstadt Bregenz DE aging; nutritional modulation; glucoregulation; biomarkers; lifespan ID DEHYDROEPIANDROSTERONE-SULFATE CONCENTRATIONS; TERM DIETARY RESTRICTION; FOOD RESTRICTION; BODY-SIZE; MACACA-MULATTA; CARDIOVASCULAR-DISEASE; PLASMA-CONCENTRATIONS; SQUIRREL-MONKEYS; PINEAL-GLAND; AGING MALE AB Calorie restriction (CR) extends lifespan and reduces the incidence and age of onset of age-related disease in several animal models. To determine if this nutritional intervention has similar actions in a long-lived primate species, the National Institute on Aging (NIA) initiated a study in 1987 to investigate the effects of a 30% CR in male and female rhesus macaques (Macaca mulatta) of a broad age range. We have observed physiological effects of CR that parallel rodent studies and may be predictive of an increased lifespan. Specifically, results from the NIA study have demonstrated that CR decreases body weight and fat mass, improves glucoregulatory function, decreases blood pressure and blood lipids, and decreases body temperature. Juvenile males exhibited delayed skeletal and sexual maturation. Adult bone mass was not affected by CR in females nor were several reproductive hormones or menstrual cycling. CR attenuated the age-associated decline in both dehydroepiandrosterone (DHEA) and melatonin in males. Although 81% of the monkeys in the study are still alive, preliminary evidence suggests that CR will have beneficial effects on morbidity and mortality. We are now preparing a battery of measures to provide a thorough and relevant analysis of the effectiveness of CR at delaying the onset of age-related disease and maintaining function later into life. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Mattison, JA (reprint author), NIA, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X NR 79 TC 173 Z9 178 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JAN-FEB PY 2003 VL 38 IS 1-2 BP 35 EP 46 AR PII S0531-5565(02)00146-8 DI 10.1016/S0531-5565(02)00146-8 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 648ML UT WOS:000181155100006 PM 12543259 ER PT J AU Risitano, AM Holada, K Chen, GB Simak, J Vostal, JG Young, NS Maciejewski, JP AF Risitano, AM Holada, K Chen, GB Simak, J Vostal, JG Young, NS Maciejewski, JP TI CD34(+) cells from paroxysmal nocturnal hemoglobinuria (PNH) patients are deficient in surface expression of cellular prion protein (PrPc) SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID PERIPHERAL-BLOOD LEUKOCYTES; SOMATIC MUTATIONS; FLOW-CYTOMETRY; SCRAPIE; HEMATOPOIESIS; ACTIVATION; DISEASES; FAILURE; BIOLOGY; GENE AB Objective. Cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI)-anchored protein (GPI-AP) constitutively expressed by neurons but also in hematopoietic cells. In trasmissible spongiform encephalopathies, the protease-resistant form of prion (PrPsc) converts the host PrPc into the pathologic form. We have investigated PrPc expression in hematopoietic cells from paroxysmal nocturnal hemoglobinuria (PNH). In this disease, due to somatic mutations in PIG-A gene, biosynthesis of the (GPI)-anchor is impaired and affected cells lack membrane expression of all GPI-AP. Methods. Normal and PNH hematopoietic progenitors and paired wild-type (WT) and PIG-A mutant cell lines were used for analysis of intracellular and surface PrPc expression using flow cytometry and Western blot. Results. By flow cytometry, PrPc was constitutively present on normal CD34(+) cells, including more immature CD38(dim) cells, as well as hernatopoietic cell lines. Similar results were obtained in purified CD34(-). Phospholipase C treatment confirmed that PrPc, was expressed on the membrane via the GPI-anchor. In PNH patients, GPI-AP-deficient CD34(-) cells lacked PrPc membrane expression. PIG-A-mutated cell lines (Jurkat, K562, C-EBV, A(EBV)), in contrast to their normal counterparts, did not express surface PrPc. However, we detected intracellular PrPc at approximately equivalent levels in both normal and PIG-A-mutated cells using intracellular flow, cytometry and Western blotting. Conclusion. Cells and cell lines with PNH phenotype together with their normal counterparts may be a suitable system to explore the function of membrane PrPc in the hernatopoietic system. Conversely, PrPc is a good model to elucidate the fate of GPI-AP in PIG-A-deficient cells. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Maciejewski, JP (reprint author), Taussig Canc Ctr, Expt Hematol & Hematopoiesis Sect, R40,9500 Euclid Ave, Cleveland, OH 44195 USA. RI Simak, Jan/C-1153-2011 NR 30 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JAN PY 2003 VL 31 IS 1 BP 65 EP 72 AR PII S0301-472(02)01011-1 DI 10.1016/S0301-472X(02)01011-1 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 639CT UT WOS:000180610600007 PM 12543108 ER PT J AU Wulff, M Plech, A Eybert, L Randler, R Schotte, F Anfinrud, P AF Wulff, M Plech, A Eybert, L Randler, R Schotte, F Anfinrud, P TI The realization of sub-nanosecond pump and probe experiments at the ESRF SO FARADAY DISCUSSIONS LA English DT Article ID X-RAY-DIFFRACTION; LAUE DATA; RECOMBINATION; RESOLUTION; MYOGLOBIN; SPECTRUM; LIQUIDS; IODINE AB We present beamline ID09B that is designed for pump and probe experiments to 50 ps time-resolution. The beamline has been refurbished with a narrow-bandwidth undulator for Laue diffraction and diffraction from liquids. The new undulator has 235 poles, a 17 mm magnetic period and is operated at 6.5 mm gap. It produces a spectral flux of 2.0 x 10(8) photon/0.1% bw/pulse (10 mA) at the fundamental at 15.5 keV and an integral flux of 1.1 x 10(10) photon pulse 1 in a 2.5% bandwidth. The optics has been renewed with a high-precision toroidal mirror and a cryogenic monochromator. The X-ray chopper used for single pulse selection is also described together with the femtosecond laser. Finally the diffraction from excited iodine molecules in CCl4 is investigated on the nanosecond time-scale. It turns out that the high-angle scattering is insensitive to the thermal chock from the laser; these oscillations are therefore readily used for structure determination. Conversely, the low-angle scattering probes the hydrodynamics of the liquid over longer length scales and the oscillations are believed to originate from thermal stress and expansion of the solvent. C1 European Synchrotron Radiat Facil, F-38043 Grenoble, France. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Wulff, M (reprint author), European Synchrotron Radiat Facil, 6 Rue Jules Horowitz,BP 220, F-38043 Grenoble, France. RI Plech, Anton/E-4895-2010; OI Plech, Anton/0000-0002-6290-9303 NR 16 TC 37 Z9 37 U1 2 U2 10 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1364-5498 J9 FARADAY DISCUSS JI Faraday Discuss. PY 2003 VL 122 BP 13 EP 26 DI 10.1039/b202740m PG 14 WC Chemistry, Physical SC Chemistry GA 607AE UT WOS:000178767600002 ER PT J AU Cho, H Kozasa, T Bondjers, C Betsholtz, C Kehrl, JH AF Cho, H Kozasa, T Bondjers, C Betsholtz, C Kehrl, JH TI Pericyte-specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation SO FASEB JOURNAL LA English DT Article DE RGS; G-protein signal transduction; blood vessel physiology ID PROTEIN-COUPLED RECEPTOR; SMOOTH-MUSCLE CELLS; KINASE ACTIVATION; DEFICIENT MICE; REGULATOR; GENES; ALPHA; SPHINGOSINE-1-PHOSPHATE; G-ALPHA(11); RESPONSES AB RGS proteins finely tune heterotrimeric G-protein signaling. Implying the need for such fine-tuning in the developing vascular system, in situ hybridization revealed a striking and extensive expression pattern of Rgs5 in the arterial walls of E12.5-E17.5 mouse embryos. The distribution and location of the Rgs5-positive cells typified that of pericytes and strikingly overlapped the known expression pattern of platelet-derived growth factor receptor (PDGFR)-beta. Both E14.5 PDGFR-beta- and platelet-derived growth factor (PDGF)-B-deficient mice exhibited markedly reduced levels of Rgs5 in their vascular plexa and small arteries. This likely reflects the loss of pericytes in the mutant mice. RGS5 acts as a potent GTPase activating protein for Gialpha and Gqalpha and it attenuated angiotensin II-, endothelin-1-, sphingosine-1-phosphate-, and PDGF-induced ERK-2 phosphorylation. Together these results indicate that RGS5 exerts control over PDGFR-beta and GPCR-mediated signaling pathways active during fetal vascular maturation. C1 NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Pharmacol, Chicago, IL USA. Univ Gothenburg, Dept Med Biochem, Gothenburg, Sweden. RP Kehrl, JH (reprint author), NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bldg 10,Rm 11B-13,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 27 TC 104 Z9 111 U1 0 U2 3 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 JAN PY 2003 VL 17 IS 1 BP 440 EP + DI 10.1096/fj.02-0340fje PG 17 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 653TT UT WOS:000181453700020 PM 12514120 ER PT J AU Frattarelli, JL Leondires, MP McKeeby, JL Miller, BT Segars, JH AF Frattarelli, JL Leondires, MP McKeeby, JL Miller, BT Segars, JH TI Blastocyst transfer, decreases multiple pregnancy rates in in vitro fertilization cycles: a randomized controlled trial SO FERTILITY AND STERILITY LA English DT Editorial Material ID EMBRYO-TRANSFER; CULTURE; IMPLANTATION; GESTATION; IVF C1 Tripler Army Med Ctr, Dept Obstet & Gynecol, Honolulu, HI 96859 USA. Uniformed Serv Univ Hlth Sci, Natl Naval Med Ctr, Walter Reed Army Med Ctr, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Combined Fed Program Reprod Endocrinol, Bethesda, MD 20814 USA. NIH, Bethesda, MD 20892 USA. Reprod Med Associates New Jersey, Morristown, NJ USA. RP Frattarelli, JL (reprint author), Tripler Army Med Ctr, Dept Obstet & Gynecol, 1 Jarrett White Rd, Honolulu, HI 96859 USA. NR 16 TC 50 Z9 51 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2003 VL 79 IS 1 BP 228 EP 230 AR PII S0015-0282(02)04558-2 DI 10.1016/S0015-0282(02)04558-2 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 634XX UT WOS:000180368700046 PM 12524098 ER PT S AU Kullman, L Winterhalter, M Bezrukov, SM AF Kullman, L Winterhalter, M Bezrukov, SM BE Bezrukov, SM Frauenfelder, H Moss, F TI Static and dynamic disorder in protein folding: Experiments with single Maltoporin channels SO FLUCTUATIONS AND NOISE IN BIOLOGICAL, BIOPHYSICAL, AND BIOMEDICAL SYSTEMS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 1st International Symposium on Fluctuations and Noise CY JUN 01-04, 2003 CL SANTA FE, NM SP SPIE, Natl Semicond Corp, Fred Seitz Mat Res Lab, Natl High Magnet Field Lab, Natl Sci Fdn, Telecommun Task Force DE single molecules; enzymatic reactions; ionic conductance; channel reconstitution; lipid bilayers ID COLI OUTER-MEMBRANE; ESCHERICHIA-COLI; SUGAR TRANSLOCATION; LAMB CHANNEL; MALTODEXTRINS; TRANSPORT; NOISE; KINETICS; RECEPTOR; LEVEL AB The reversible binding of sugar to a single maltoporin channel allows us to study time and ensemble variations in the channel functional properties and interpret them using the language of static and dynamic disorder in protein folding. The channel is a trimer that is characterized by two primary parameters: the rate of sugar binding and the ion conductance. Time-resolved binding of maltohexaose molecules shows that whereas dynamic disorder - the fluctuations in binding rate or in ionic conductance of a single trimer channel with time - is relatively small, static disorder - the heterogeneity of reaction rates or conductances among different trimers - is highly pronounced. This heterogeneity suggests variations in maltoporin folding. The disorder in conductance shows no measurable correlation with the disorder in binding strength; variations in protein folding that are responsible for variations in ionic conductance do not seem to affect sugar binding. We find 'cooperativity' in static disorder: conductances of monomers in the same trimer are closely similar compared to the range, of possible conductances seen over an ensemble of trimers. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Kullman, L (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4970-9 J9 P SOC PHOTO-OPT INS PY 2003 VL 5110 BP 50 EP 56 DI 10.1117/12.500833 PG 7 WC Biology; Neurosciences; Physiology SC Life Sciences & Biomedicine - Other Topics; Neurosciences & Neurology; Physiology GA BX06A UT WOS:000184147100007 ER PT S AU Nestorovich, EM Danelon, C Winterhalter, M Bezrukov, SM AF Nestorovich, EM Danelon, C Winterhalter, M Bezrukov, SM BE Bezrukov, SM Frauenfelder, H Moss, F TI Noise analysis of antibiotic permeation through bacterial channels SO FLUCTUATIONS AND NOISE IN BIOLOGICAL, BIOPHYSICAL, AND BIOMEDICAL SYSTEMS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 1st International Symposium on Fluctuations and Noise CY JUN 01-04, 2003 CL SANTA FE, NM SP SPIE, Natl Semicond Corp, Fred Seitz Mat Res Lab, Natl High Magnet Field Lab, Natl Sci Fdn, Telecommun Task Force DE single molecules; antibiotic transport; channel reconstitution; lipid bilayers ID ESCHERICHIA-COLI; SINGLE-CHANNEL; FLUCTUATIONS; MALTOPORIN; TRANSPORT; KINETICS; PORINS AB Statistical analysis of high-resolution current recordings from a single ion channel reconstituted into a planar lipid membrane allows us to study transport of antibiotics at the molecular detail. Working with the general bacterial porin, OmpF, we demonstrate that addition of zwitterionic beta-lactam antibiotics to the membrane-bathing solution introduces transient interruptions in the small-ion current through the channel. Time-resolved measurements reveal that one antibiotic molecule blocks one of the monomers in the OmpF trimer for characteristic times from microseconds to hundreds of microseconds. Spectral noise analysis enables us to perform measurements over a wide range of changing parameters. In all cases studied, the residence time of an antibiotic molecule in the channel exceeds the estimated time for free diffusion by orders of magnitude. This demonstrates that, in analogy to substrate-specific channels that evolved to bind specific metabolite molecules, antibiotics have 'evolved' to be channel-specific. The charge distribution of an efficient antibiotic complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a zone of attraction inside the channel and compensates the penetrating molecule's entropy loss and desolvation energy. This facilitates antibiotic translocation through the narrowest part of the channel and accounts for higher antibiotic permeability rates. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Nestorovich, EM (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4970-9 J9 P SOC PHOTO-OPT INS PY 2003 VL 5110 BP 57 EP 62 DI 10.1117/12.500928 PG 6 WC Biology; Neurosciences; Physiology SC Life Sciences & Biomedicine - Other Topics; Neurosciences & Neurology; Physiology GA BX06A UT WOS:000184147100008 ER PT S AU Iwasa, KH Dong, XX AF Iwasa, KH Dong, XX BE Bezrukov, SM Frauenfelder, H Moss, F TI Motor noise in outer hair cells SO FLUCTUATIONS AND NOISE IN BIOLOGICAL, BIOPHYSICAL, AND BIOMEDICAL SYSTEMS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 1st International Symposium on Fluctuations and Noise CY JUN 01-04, 2003 CL SANTA FE, NM SP SPIE, Natl Semicond Corp, Fred Seitz Mat Res Lab, Natl High Magnet Field Lab, Natl Sci Fdn, Telecommun Task Force DE charge fluctuation; membrane capacitance; current noise spectrum ID MECHANICAL RESPONSES; COCHLEAR AMPLIFIER; MEMBRANE; CAPACITANCE; MOTILITY; CURRENTS; CHARGE AB Outer hair cells in the mammalian ear has a membrane based motor which directly converts electrical energy into mechanical energy. Such a motor is associated with the function of these cells in providing feedback to vibration in the inner ear. To obtain insights into the motor mechanism, we examined kinetics of charge transfer across the membrane in two different modes. One is to monitor charge transfer induced by changes in the membrane potential as an excess membrane capacitance. The other is to measure spontaneous flip-flops of charges across the membrane under voltage clamp condition as current noise. The noise spectrum of current was inverse Lorentzian and the capacitance was Lorentzian as theoretically expected. The characteristic frequency of the capacitance was about 10 kHz and that for current noise was about 30 kHz. This result is inconsistent with the prediction. The difference can be explained by a reciprocal effect of being a piezoelectric motor in that mechanical motion which is subjected to friction affects the frequency response. C1 Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4970-9 J9 P SOC PHOTO-OPT INS PY 2003 VL 5110 BP 151 EP 160 DI 10.1117/12.497616 PG 10 WC Biology; Neurosciences; Physiology SC Life Sciences & Biomedicine - Other Topics; Neurosciences & Neurology; Physiology GA BX06A UT WOS:000184147100018 ER PT J AU Bradbury, CM Gius, D AF Bradbury, CM Gius, D TI Thioredoxin reductase as a potential molecular target in the HeLa cellular oxidative stress response SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 515 BP S166 EP S166 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900538 ER PT J AU Cha, MK Kim, WC Kim, IH AF Cha, MK Kim, WC Kim, IH TI Escherichia coli thiol peroxidase (p20) as a heat-shock inducible protein acts as an antioxidant against a cellular oxidative damage caused by heat shock SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NHLBI, Biochem Lab, NIH, Bethesda, MD USA. Paichai Univ, Dept Biochem, Taejon, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 199 BP S67 EP S67 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900219 ER PT J AU Chen, YR Chen, CL Zweier, JL Mason, RP AF Chen, YR Chen, CL Zweier, JL Mason, RP TI Evaluation of cytochrome C as a potential biomarker of mitochondrial oxidative stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Ohio State Univ, DHLRI, Columbus, OH 43210 USA. NIEHS, LPC, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 316 BP S102 EP S102 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900338 ER PT J AU Chen, YR Chen, CL Zweier, JL Mason, RP AF Chen, YR Chen, CL Zweier, JL Mason, RP TI Formation of protein tyrosine orthosemiquinone radical (TOQ(center dot)) and nitrotyrosine from mitochondrial cytochrome c-derived tyrosyl radical (CCY center dot) SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Ohio State Univ, DHLRI, Columbus, OH 43210 USA. NIEHS, LPC, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 21 BP S18 EP S18 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900039 ER PT J AU Chung, NY Lee, BC Lee, YK Stadtman, ER Bang, WG AF Chung, NY Lee, BC Lee, YK Stadtman, ER Bang, WG TI Cloning and characterization of antioxidant enzyme methionine sulfoxide-S-reductase from Caenorhabditis elegans SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Korea Univ, Coll Life & Environm Sci, Seoul, South Korea. NHLBI, Biochem Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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. PY 2003 VL 35 SU 1 MA 317 BP S102 EP S102 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900339 ER PT J AU Crawford, JH Gladwin, MT Kim-Shapiro, DB Patel, RP AF Crawford, JH Gladwin, MT Kim-Shapiro, DB Patel, RP TI Metabolism of nitrite to a vasodilator by deoxyhemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 2003 VL 35 SU 1 MA 249 BP S82 EP S82 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900269 ER PT J AU Huang, Z Wong, AL Partovi, KS Schechter, AN Gladwin, MT AF Huang, Z Wong, AL Partovi, KS Schechter, AN Gladwin, MT TI A novel allosterically regulated nitrite reductase/oxidase function of hemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NIDDK, LCB, NIH, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA 90089 USA. NIH, CCMD, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 2003 VL 35 SU 1 MA 293 BP S95 EP S95 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900314 ER PT J AU Hunter, C Blood, A Job, L Gladwin, M Power, G AF Hunter, C Blood, A Job, L Gladwin, M Power, G TI Effect of inhaled L-arginine on pulmonary hypertension in lambs induced by hypoxia or arginine deficiency SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Loma Linda Sch Med, Ctr Perinatal Biol, Loma Linda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 254 BP S83 EP S83 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900274 ER PT J AU Keszler, A Mason, RP Hogg, N AF Keszler, A Mason, RP Hogg, N TI Immunologic and EPR/spin-trapping detection of hemoglobin radical derived from nitrite-mediated oxidation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. NIH, Lab Pharmacol & Chem, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 326 BP S105 EP S105 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900348 ER PT J AU Lardinois, O de Montellano, PO AF Lardinois, O de Montellano, PO TI Autoreduction of the ferryl derivative of myoglobin: Specificity for tyrosine residues as 'sinks' for oxidizing equivalents generated at the heme iron SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Free Rad Metabolite Sect, Res Triangle Pk, NC USA. Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 27 BP S20 EP S20 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900045 ER PT J AU Matsumoto, K Thirumaran, A Chandrika, B Devasahayam, N Cook, J Mitchell, J Subramanian, S Krishna, M AF Matsumoto, K Thirumaran, A Chandrika, B Devasahayam, N Cook, J Mitchell, J Subramanian, S Krishna, M TI In vivo electron paramagnetic resonance oxymetry: Comparison of continuous wave and pulsed techniques SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 462 BP S147 EP S148 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900485 ER PT J AU Nagababu, E Fabry, M Suzuka, S Nagel, R Rifkind, J AF Nagababu, E Fabry, M Suzuka, S Nagel, R Rifkind, J TI Heme degradation in sickle cell, thalassemia and hemoglobin-C transgenic mice: An in vivo measurement of oxidative stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NIA, Mol Dynam Sect, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 31 BP S20 EP S21 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900049 ER PT J AU Qian, S Kadiiska, M Mason, R AF Qian, S Kadiiska, M Mason, R TI Identification of radical adducts from in vitro/in vivo interaction of hydroxyl radical with DMSO: Dual spin-trapping, LC/ESR, and MS study SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 34 BP S21 EP S21 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900052 ER PT J AU Ramirez, DC Mejiba, SEG Corbett, JT Mason, RP AF Ramirez, DC Mejiba, SEG Corbett, JT Mason, RP TI The reaction between Cu,Zn-superoxide dismutase and hydrogen peroxide explored by immuno-spin trapping SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 2003 VL 35 SU 1 MA 466 BP S148 EP S148 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900489 ER PT J AU Rhee, SG AF Rhee, SG TI Intracellular messenger function of hydrogen peroxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA P11 BP S7 EP S7 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900012 ER PT J AU Rifkind, J Nagababu, E Ramasamy, S Abernethy, D AF Rifkind, J Nagababu, E Ramasamy, S Abernethy, D TI Bioactive red cell nitric oxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NIA, Mol Dynam Sect, Bethesda, MD 20892 USA. NIA, Clin Invest Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 274 BP S88 EP S88 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900294 ER PT J AU Sato, K Kadiiska, MB Corbett, J Arimoto, T Tashiro, Y Chibana, S Suga, M Mason, RP AF Sato, K Kadiiska, MB Corbett, J Arimoto, T Tashiro, Y Chibana, S Suga, M Mason, RP TI In vivo direct evidence of free radical formation and its mechanism in pneumonia model induced by Pseudomonas aeruginosa SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Kumamoto Univ, Sch Med, Kumamoto 860, Japan. NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 163 BP S57 EP S57 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900183 ER PT J AU Towner, R Qian, S Kadiiska, M Mason, R AF Towner, R Qian, S Kadiiska, M Mason, R TI In vivo identification of aflatoxin-induced radicals in bile SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 59 BP S29 EP S29 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900079 ER PT J AU VanRollins, M Sprecher, HW Salem, N Buettner, GR AF VanRollins, M Sprecher, HW Salem, N Buettner, GR TI Arachidonate epoxides occur in human plasma at concentrations that dilate coronary resistance vessels SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Univ Iowa, Iowa City, IA 52242 USA. Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. NIAAA, Lab Membrane Biochem Biophys, NIH, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 357 BP S112 EP S113 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900379 ER PT J AU Wang, XD Tanos-Santos, J Reiter, C Hogg, N Gladwin, M AF Wang, XD Tanos-Santos, J Reiter, C Hogg, N Gladwin, M TI Nitrite, rather than S-nitroso-thiol, is the circulating plasma storage form of nitric oxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Biophys Res Inst, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 279 BP S90 EP S90 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900299 ER PT J AU Xu, X Cho, M Spencer, N Patel, N Huang, Z Shields, H King, S Gladwin, M Hogg, N Kim-Shapiro, D AF Xu, X Cho, M Spencer, N Patel, N Huang, Z Shields, H King, S Gladwin, M Hogg, N Kim-Shapiro, D TI Nitric oxide does not transfer between heme and B-93 thiol of human hemoglobin during cycles of oxygenation and deoxygenation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 303 BP S97 EP S97 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900324 ER PT J AU Zhong, Z Connor, HD Lind, H Mason, RP Lemasters, JJ AF Zhong, Z Connor, HD Lind, H Mason, RP Lemasters, JJ TI Ischemic preconditioning (IP) attenuates injury of small-for-size rat liver grafts by decreasing free radical production SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Univ N Carolina, Chapel Hill, NC 27515 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 436 BP S136 EP S136 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900459 ER PT J AU Zhong, Z Connor, HD Lind, H Mason, RP Lemasters, JJ AF Zhong, Z Connor, HD Lind, H Mason, RP Lemasters, JJ TI C-sinenesis polyphenols prevent increases of reactive oxygen and nitrogen species in small-for-size liver grafts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Univ N Carolina, Chapel Hill, NC 27515 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2003 VL 35 SU 1 MA 136 BP S49 EP S49 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900156 ER PT J AU Pagliaro, P Mancardi, D Rastaldo, R Penna, C Gattullo, D Miranda, KM Feelisch, M Wink, DA Kass, DA Paolocci, N AF Pagliaro, P Mancardi, D Rastaldo, R Penna, C Gattullo, D Miranda, KM Feelisch, M Wink, DA Kass, DA Paolocci, N TI Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ischemia/reperfusion; preconditioning; myocardial necrosis; nitroxyl; Angeli's salt; nitric oxide; diethylamine/NO complex; N-acetyl-L-cysteine; free radicals ID NITRIC-OXIDE SYNTHASE; K-ATP CHANNELS; DIAZOXIDE-INDUCED CARDIOPROTECTION; GENERATING FREE-RADICALS; GENE-RELATED PEPTIDE; RAT ISOLATED HEARTS; PROTEIN-KINASE-C; NO-CENTER-DOT; CONSCIOUS RABBITS; SUPEROXIDE-DISMUTASE AB Nitric oxide (NO) donors mimic the early phase of ischemic preconditioning (IPC). The effects of nitroxyl (HNO/NO-), the one-electron reduction product of NO, on ischemia/reperfusion (I/R) injury are unknown. Here we investigated whether HNO/NO-, produced by decomposition of Angeli's salt (AS; Na2N2O3), has a cardioprotective effect in isolated perfused rat hearts. Effects were examined after intracoronary perfusion (19 min) of either AS (1 muM), the NO donor diethylamine/NO (DEA/NO, 0.5 muM), vehicle (100 nM NaOH) or buffer, followed by global ischemia (30 min) and reperfusion (30 min or 120 min in a subset of hearts). IPC was induced by three cycles of 3 min ischemia followed by 10 min reperfusion prior to I/R. The extent of I/R injury under each intervention was assessed by changes in myocardial contractility as well as lactate dehydrogenase (LDH) release and infarct size. Postischemic contractility, as indexed by developed pressure and dP/dt(max), was similarly improved with IPC and pre-exposure to AS, as opposed to control or DEA/NO-treated hearts. Infarct size and LDH release were also significantly reduced in IPC and AS groups, whereas DEA/NO was less effective in limiting necrosis. Co-infusion in the triggering phase of AS and the nitroxyl scavenger, N-acetyl-L-cysteine (4 mM) completely reversed the beneficial effects of AS, both at 30 and 120 min reperfusion. Our data show that HNO/NO- affords myocardial protection to a degree similar to IPC and greater than NO, suggesting that reactive nitrogen oxide species are not only necessary but also sufficient to trigger myocardial protection against reperfusion through species-dependent, pro-oxidative, and/or nitrosative stress-related mechanisms. (C) 2002 Elsevier Science Inc. C1 NCI, NIH, Radiat Biol Branch, Bethesda, MD 20892 USA. Louisiana State Univ, Ctr Hlth Sci, Dept Mol & Cellular Physiol, Shreveport, LA 71105 USA. Johns Hopkins Med Inst, Div Cardiol, Dept Med, Baltimore, MD 21205 USA. Univ Turin, Dipartimento Sci Clin & Biol, Orbassano, Italy. RP Pagliaro, P (reprint author), Univ Turin, Osped S Luigi, Dipartimento Sci Clin & Biol, Regione Gonzole 10, I-10043 Orbassano, TO, Italy. RI Miranda, Katrina/B-7823-2009; Pagliaro, Pasquale/E-5239-2010; Feelisch, Martin/C-3042-2008; OI Feelisch, Martin/0000-0003-2320-1158; MANCARDI, Daniele/0000-0003-3809-6047 NR 64 TC 143 Z9 144 U1 1 U2 7 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 JAN 1 PY 2003 VL 34 IS 1 BP 33 EP 43 AR PII S0891-5849(02)01179-6 DI 10.1016/S0891-5849(02)01179-6 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 628XW UT WOS:000180022200004 PM 12498977 ER PT J AU Mitchell, JB Xavier, S DeLuca, AM Sowers, AL Cook, JA Krishna, MC Hahn, SM Russo, A AF Mitchell, JB Xavier, S DeLuca, AM Sowers, AL Cook, JA Krishna, MC Hahn, SM Russo, A TI A low molecular weight antioxidant decreases weight and lowers tumor incidence SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE antioxidant; aging; obesity; oxidative stress; carcinogenesis; nitroxide; uncoupling protein; free radicals ID SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; SKELETAL-MUSCLE; UNCOUPLING PROTEIN-3; CALORIC RESTRICTION; NITROXIDE TEMPOL; METABOLIC-RATE; FREE-RADICALS; LIFE-SPAN; DAMAGE AB Stable free radical nitroxides are potent antioxidants possessing superoxide dismutase- and catalase-mimetic activity that protect cells and animals against a variety of oxidative insults. Tempol, as a representative nitroxide, was evaluated for its influence on weight maintenance and spontaneous tumor incidence in C3H mice. Tempol administered in either the drinking water or food did not show any untoward effects and prevented animals from becoming obese. Tempol-treated animals' leptin levels were reduced. Long-term treatment with Tempol significantly decreased tumorigenesis when compared to controls (10 vs. 40%, respectively). Selected tissues from Tempol-treated animals exhibited elevated levels of mitochrondrial uncoupling protein-2 (UCP-2) and HSP70. The present data suggest that nitroxides upregulate UCP-2, obviate weight gain, and decrease age-related spontaneous tumor incidence. As a class, nitroxides may provide overall health benefits by contributing to decreased obesity and tumor incidence. (C) 2002 Elsevier Science Inc. C1 NCI, Canc Res Ctr, Radiat Biol Branch, Bethesda, MD 20892 USA. Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Mitchell, JB (reprint author), NCI, Canc Res Ctr, Radiat Biol Branch, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. NR 56 TC 71 Z9 78 U1 1 U2 3 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 JAN 1 PY 2003 VL 34 IS 1 BP 93 EP 102 AR PII S0891-5849(02)01193-0 DI 10.1016/S0891-5849(02)01193-0 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 628XW UT WOS:000180022200011 PM 12498984 ER PT J AU Yang, BK Vivas, EX Reiter, CD Gladwin, MT AF Yang, BK Vivas, EX Reiter, CD Gladwin, MT TI Methodologies for the sensitive and specific measurement of S-nitrosothiols, iron-nitrosyls, and nitrite in biological samples SO FREE RADICAL RESEARCH LA English DT Review ID REGIONAL BLOOD-FLOW; BIOCHEMICAL-CHARACTERIZATION; RELAXING FACTOR; OXYGEN-BINDING; HUMAN PLASMA; OXIDE; NITROSOHEMOGLOBIN; HEMOGLOBIN; NITROSOALBUMIN; NITROSATION C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 25 TC 163 Z9 164 U1 3 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2003 VL 37 IS 1 BP 1 EP 10 DI 10.1080/1071576021000033112 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615RH UT WOS:000179260100001 PM 12653211 ER PT J AU Missirlis, F Phillips, JP Jackle, H Rouault, T AF Missirlis, F Phillips, JP Jackle, H Rouault, T TI Genetic studies in Drosophila emphasize the functional importance of subcellular compartment boundaries for oxidative stress metabolism SO FREE RADICAL RESEARCH LA English DT Meeting Abstract CT Meeting on Free Radicals and Oxidative Stress CY 2003 CL LOANNINA, GREECE SP Soc Free Radical Res C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Univ Guelph, Guelph, ON N1G 2W1, Canada. Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany. EM missirlf@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2003 VL 37 SU 1 BP 73 EP 73 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 706NA UT WOS:000184458700115 ER PT J AU Vaananen, AJ Moed, M Tuominen, RK Helkamaa, TH Wiksten, M Liesi, P Chiueh, CC Rauhala, P AF Vaananen, AJ Moed, M Tuominen, RK Helkamaa, TH Wiksten, M Liesi, P Chiueh, CC Rauhala, P TI Angeli's salt induces neurotoxicity in dopaminergic neurons in vivo and in vitro SO FREE RADICAL RESEARCH LA English DT Article DE Angeli's salt; dopamine; free radicals; lipid peroxidation; neurotoxicity; nitroxyl anion ID NITRIC-OXIDE SYNTHASE; NO-CENTER-DOT; LIPID-PEROXIDATION; NITROXYL ANION; SUPEROXIDE-DISMUTASE; S-NITROSOGLUTATHIONE; BIOLOGICAL-SYSTEMS; RADICAL FORMATION; GENERATION; HNO AB In this study, we investigated the hypothesis that the pro-oxidative properties of Angeli's salt (AS), a nitroxyl anion (HNO/NO-) releasing compound, cause neurotoxicity in dopaminergic neurons. The pro-oxidative properties were demonstrated in vitro by measuring hydroxylation products of salicylate and peroxidation of lipids under various redox conditions. AS (0-1000 muM) released high amounts of hydroxylating species in a concentration dependent manner. AS also increased lipid peroxidation in brain homogenates at concentrations below 100 muM, while inhibiting it at 1000 muM concentration. The AS induced pro-oxidative effects were completely suppressed by copper (II), which converts nitroxyl anion to nitric oxide, as well as by a potent nitroxyl anion scavenger glutathione. Neurotoxicity towards dopaminergic neurons was tested in rat nigrostriatal dopaminergic system in vivo and by using primary mesencephalic dopaminergic neuronal cultures in vitro . Intranigral infusion of AS (0-400 nmol) caused neurotoxicity reflected as a dose dependent decrease of striatal dopamine seven days after treatment. The effect of the 100 nmol dose was more pronounced when measured 50 days after the infusion. Neurotoxicity was also confirmed as a decrease of tyrosine hydroxylase positive neurons in the substantia nigra. Neither sulphononoate, a close structural analog of AS, nor sodiumnitrite caused changes in striatal dopamine, thus reflecting lack of neurotoxicity. In primary dopaminergic neuronal cultures AS reduced [H-3] dopamine uptake with concentrations over 200 muM confirming neurotoxicity. In line with the quite low efficacy to increase lipid peroxidation in vitro , infusion of AS into substantia nigra did not cause increased formation of fluorescent products of lipid peroxidation. These results support the hypothesis that AS derived species oxidize critical thiol groups, rather than membrane lipids, potentially leading to protein oxidation/dysfunction and demonstrated neurotoxicity. These findings may have pathophysiological relevance in case of excess formation of nitroxyl anion. C1 Univ Helsinki, Inst Biomed Pharmacol, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Pharm, FIN-00014 Helsinki, Finland. Univ Helsinki, Inst Biomed Anat, Biomedicum Helsinki, Brain Lab, FIN-00014 Helsinki, Finland. NIMH, Unit Neurodegenerat & Neuroprotect, Clin Sci Lab, NIH,Clin Ctr, Bethesda, MD 20892 USA. RP Rauhala, P (reprint author), Univ Helsinki, Inst Biomed Pharmacol, POB 63,Haartmainkatu 8, FIN-00014 Helsinki, Finland. OI Rauhala, Pekka/0000-0003-2036-3522 NR 30 TC 23 Z9 23 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2003 VL 37 IS 4 BP 381 EP 389 DI 10.1080/1071576031000061011 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 643AD UT WOS:000180839000004 PM 12747732 ER PT J AU Ali-Ahmad, D Bonville, CA Rosenberg, HF Domachowske, JB AF Ali-Ahmad, D Bonville, CA Rosenberg, HF Domachowske, JB TI Replication of respiratory syncytial virus is inhibited in target cells generating nitric oxide in situ SO FRONTIERS IN BIOSCIENCE LA English DT Article DE respiratory syncytial virus; nitric oxide; antiviral host defense ID EPITHELIAL-CELLS; ANTIMICROBIAL ACTIVITY; IMMUNE-RESPONSE; GENE-EXPRESSION; INFECTION; SYNTHASE; ASTHMA AB Nitric oxide (NO) is generated by recruited inflammatory cells and by pulmonary epithelial cells in response to respiratory virus infection, although the relative antiviral efficacy of NO from each of these sources had not been clarified. To compare the direct, antiviral potency of NO from an exogenous source with that generated by target epithelial cells in situ, we transduced HEp-2 epithelial cells with the retroviral construct, pMFGS-NOS and cloned transductant lines that generated NO constitutively. We found that NO-producing HEp-2 cells could be infected with RSV, but the titer correlated inversely with NO production, an effect that was reversed by the NOS inhibitor, N-G-methyl-L-arginine (N(G)MMA). Our results demonstrate that NO has significant direct antiviral activity against RSV, and interestingly, that the inhibitory effect is more potent in the presence of continuous, endogenous NO production than in response to NO from an exogenous source. C1 SUNY Upstate Med Univ, Div Infect Dis, Dept Pediat, Syracuse, NY 13210 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), SUNY Upstate Med Univ, Div Infect Dis, Dept Pediat, 750 E Adams St, Syracuse, NY 13210 USA. NR 34 TC 13 Z9 14 U1 1 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN PY 2003 VL 8 BP A48 EP A53 DI 10.2741/986 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 633DQ UT WOS:000180266400007 PM 12456366 ER PT J AU Hu, WS Rhodes, T Dang, Q Pathak, V AF Hu, WS Rhodes, T Dang, Q Pathak, V TI Retroviral recombination: Review of genetic analyses SO FRONTIERS IN BIOSCIENCE LA English DT Review DE retroviral recombination; dynamic copy-choice; high negative interference; double infection; heteryozygotic virion; minus-strand DNA synthesis; DNA strand displacement-assimilation; recombination rate; template switching; review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; ZIDOVUDINE-RESISTANT HIV-1; HIGH NEGATIVE INTERFERENCE; INJECTING DRUG-USERS; STRAND DNA TRANSFER; FULL-LENGTH GENOME; FORMER SOVIET-UNION; REVERSE-TRANSCRIPTASE; SUBTYPE-G AB Retroviruses package two copies of genomic RNA into one virion. One of the essential steps of replication is reverse transcription, in which the virally encoded enzyme reverse transcriptase (RT) uses the packaged RNA as a template to synthesize viral DNA. Because two copies of RNA are present in one virion, it is possible for RT to switch from one copy of the viral RNA to the other copy during DNA synthesis, thereby generating a recombinant containing some genetic information from each of the RNAs. Recombination occurs at high frequencies during retroviral replication. This frequent recombination has a significant impact on the current human immunodeficiency virus type 1 (HIV-1) epidemic as well as the development of retrovirus-based systems for gene therapy. In this review, the rates, mechanisms, and properties of retroviral recombination are summarized from recent genetic studies. Implications of these studies are also discussed. C1 NCI Frederick, HIV Drug Resistance Program, FCRDC, Frederick, MD 21702 USA. W Virginia Univ, Sch Med, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. RP Hu, WS (reprint author), NCI Frederick, HIV Drug Resistance Program, FCRDC, Room 336,Bldg 535, Frederick, MD 21702 USA. NR 131 TC 28 Z9 30 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN PY 2003 VL 8 BP D143 EP D155 DI 10.2741/940 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 633DQ UT WOS:000180266400023 PM 12456341 ER PT J AU Muriaux, D Rein, A AF Muriaux, D Rein, A TI Encapsidation and transduction of cellular genes by retroviruses SO FRONTIERS IN BIOSCIENCE LA English DT Article DE RNA packaging; virus evolution; readthrough transcription; reverse transcription; review ID DIFFERENT TRANSFER-RNAS; PRIMER BINDING-SITE; LEUKEMIA-VIRUS; REVERSE TRANSCRIPTION; MESSENGER-RNA; GENOMIC RNA; C-ERBB; SARCOMA-VIRUS; SEQUENCES; ONCOGENE AB Retroviruses normally package their genomic RNA with high fidelity. However, the fidelity is apparently imperfect, since some cellular mRNA is present in standard retrovirus particles. Further, transcripts originating in the 5' LTR of the integrated provirus sometimes extend beyond the 3' end of the provirus, resulting in the production of chimeric RNAs containing both viral and cellular sequences. These RNAs can be exported to the cytoplasm and packaged into assembling virus particles. When such particles infect a new host cell, reverse transcriptase may copy the cellular sequences, as well as viral sequences, into DNA. In turn, recombinational events during reverse transcription can result in the incorporation of cellular sequences into retroviral genomes. If the cellular sequences encode proteins involved in the control of cell growth, then the high or inappropriate expression of these sequences as part of the retroviral genome may cause the malignant transformation of the infected cell. Viruses of this type, that transduce cellular transforming genes, are known as acute transforming viruses. They can only arise in animals infected with replication-competent retroviruses, and in general cannot produce progeny viruses without replication-competent "helper" viruses. Since they are produced by a complex, multi-step pathway, acute transforming viruses are only generated at very low frequencies. C1 NCI Frederick, Hiv Drug REsistance Program, Frederick, MD 21702 USA. RP Rein, A (reprint author), NCI Frederick, Hiv Drug REsistance Program, POB B, Frederick, MD 21702 USA. NR 41 TC 14 Z9 14 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN PY 2003 VL 8 BP D135 EP D142 DI 10.2741/950 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 633DQ UT WOS:000180266400022 PM 12456352 ER PT J AU Svarovskaia, ES Cheslock, SR Zhang, WH Hu, WS Pathak, VK AF Svarovskaia, ES Cheslock, SR Zhang, WH Hu, WS Pathak, VK TI Retroviral mutation rates and reverse transcriptase fidelity SO FRONTIERS IN BIOSCIENCE LA English DT Review DE retrovirus; mutation rate; genetic variation; fidelity; reverse transcriptase; RNase H primer grip; template-primer structure; dNTP-binding site; misinsertions; mismatch extension; RNA polymerase II; transcription fidelity; review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; DEPENDENT DNA-SYNTHESIS; SPLEEN NECROSIS VIRUS; RNA-POLYMERASE-II; MISPAIR EXTENSION FREQUENCIES; HIGH NEGATIVE INTERFERENCE; AMINO-ACID SUBSTITUTIONS; SINGLE REPLICATION CYCLE; INFECTIOUS-ANEMIA VIRUS AB Genetic variation in retroviral populations provides a mechanism for retroviruses to escape host immune responses and develop resistance to all known antiretroviral drugs. Retroviruses, like all RNA viruses, exhibit a high mutation rate. Polymerization errors during DNA synthesis by reverse transcriptase, which lacks a proofreading activity, is a major mechanism for generating genetic variation within retroviral populations. In this review, we summarize our current understanding of the processes that contribute to the generation of mutations in retroviruses. An overview of in vivo and in vitro studies of retroviral mutation rates determined by various fidelity assays is provided. Extensive mutational analyses of RTs are beginning to elucidate the relationship between structural determinants of RTs and fidelity of DNA synthesis. Recently, it was observed that the Y586F mutation in MLV RT results in a dramatic increase in the mutation rate in the vicinity of adenine-thymie tracts (AAAA, TTTT, and AATT), which are associated with bends in DNA. These results indicate that the template-primer duplex is a component of the polymerase active site and its structure can influence nucleotide selectivity and the mutation rate. Additionally, the results also suggest that the Y586 residue and the RNase H primer grip are structural determinants of RT that have evolved to attenuate the effects of unusual conformations of the template-primer duplex, such as bends in DNA, on fidelity of DNA synthesis. C1 NCI, HIV Drug Resistance Program, CCR, Frederick, MD 21702 USA. W Virginia Univ, Dept Microbiol & Immunol, Morgantown, WV 26506 USA. RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, CCR, Bldg 535,Rm 334, Frederick, MD 21702 USA. NR 144 TC 49 Z9 49 U1 2 U2 16 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN PY 2003 VL 8 BP D117 EP D134 DI 10.2741/957 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 633DQ UT WOS:000180266400021 PM 12456349 ER PT J AU Schnaper, HW Kopp, JB AF Schnaper, HW Kopp, JB TI Renal fibrosis SO FRONTIERS IN BIOSCIENCE LA English DT Review DE fibrosis; glomerulosclerosis; kidney; interstitial fibrosis; progressive kidney disease; review ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; TISSUE GROWTH-FACTOR; HUMAN MESANGIAL CELLS; PROLYL 4-HYDROXYLASE INHIBITOR; GLYCATION END-PRODUCTS; PLASMINOGEN-ACTIVATOR INHIBITOR-1; UNILATERAL URETERAL OBSTRUCTION; DEPENDENT DIABETES-MELLITUS; COLLAGEN GENE-TRANSCRIPTION; TUBULAR EPITHELIAL-CELLS AB Renal fibrosis causes significant morbidity and mortality as the primary acquired lesion leading to the need for dialysis or kidney transplantation. Fibrosis can occur in either the filtering or reabsorptive component of the nephron, the functional unit of the kidney. Experimental models have identified a number of factors that contribute to renal scarring, particularly derangements of physiology involved in the autoregulation of glomerular filtration. This in turn leads to replacement of normal structures with accumulated extracellular matrix (ECM). A spectrum of changes in the physiology of individual cells leads to the production of numerous peptide and non-peptide fibrogens that stimulate alterations in the balance between ECM synthesis and degradation to favor scarring. Other proteins and small molecules may have anti-fibrotic effects. Manipulation of these opposing systems holds the promise of effective treatments for chronic progressive kidney disease. C1 NIDDKD, Kidney Dis Sect, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Div Pediat Nephrol, Chicago, IL 60611 USA. RP Schnaper, HW (reprint author), Pediat W-140,303 E Chicago Ave, Chicago, IL 60611 USA. FU NIDDK NIH HHS [DK49362] NR 194 TC 15 Z9 19 U1 0 U2 4 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN PY 2003 VL 8 BP E68 EP E86 DI 10.2741/925 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 633DQ UT WOS:000180266400054 PM 12456333 ER PT B AU Kruth, HS Huang, W Ishii, I Zhang, WY Zhao, B AF Kruth, HS Huang, W Ishii, I Zhang, WY Zhao, B BE Lewis, BS Halon, DA Flugelman, MY Gensini, GF TI Macrophage foam cell formation without LDL modification SO FRONTIERS IN CORONARY ARTERY DISEASE LA English DT Proceedings Paper CT 5th International Congress on Coronary Artery Disease CY OCT 19-22, 2003 CL FLORENCE, ITALY ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; HUMAN ATHEROSCLEROTIC LESIONS; MOUSE PERITONEAL-MACROPHAGES; TISSUE FACTOR EXPRESSION; CULTURED-CELLS; CHOLESTEROL; RECEPTOR; METABOLISM AB Low-density lipoprotein (LDL) is believed to be the main source of cholesterol that accumulates in monocyte-derived macrophages within atherosclerotic plaques converting these macrophages into enlarged foam cells. Previously, only modified but not native LDL has been shown to produce macrophage cholesterol accumulation. We have found that activation of human monocyte-derived macrophages with phorbol 12-myristate 13-acetate (PMA) stimulates native LDL uptake and degradation, and acyl-CoA:cholesterol acyltransferase (ACAT)-mediated esterification of LDL-derived cholesterol, resulting in massive macrophage cholesterol accumulation. The mechanism of LDL uptake by these macrophages is PMA-stimulated endocytosis of LDL taken up as part of the bulk-phase fluid (i.e., fluid-phase endocytosis). This novel mechanism of macrophage cholesterol accumulation shows that modification of LDL is not necessary for foam cell formation to occur. In addition, the findings direct attention to macrophage fluid-phase endocytosis as a relevant pathway, to target for modulating macrophage cholesterol accumulation in atherosclerosis. C1 NHLBI, Sect Expt Atherosclerosis, DHHS, NIH, Bethesda, MD 20892 USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, DHHS, NIH, Bethesda, MD 20892 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-3161-6 PY 2003 BP 1 EP 8 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA BY09J UT WOS:000187617500001 ER PT B AU Pacher, P Liaudet, L Mabley, JG Szabo, C AF Pacher, P Liaudet, L Mabley, JG Szabo, C BE Lewis, BS Halon, DA Flugelman, MY Gensini, GF TI A novel ultrapotent poly (ADP-ribose) polymerase inhibitor improves cardiac and endothelial dysfunction in rat model of chronic heart failure SO FRONTIERS IN CORONARY ARTERY DISEASE LA English DT Proceedings Paper CT 5th International Congress on Coronary Artery Disease CY OCT 19-22, 2003 CL FLORENCE, ITALY ID EFFICIENCY; ACTIVATION AB Overactivation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) contributes to the development of cell dysfunction and tissue injury in various pathophysiological conditions associated with oxidative and nitrosative stress, including myocardial reperfusion injury, heart transplantation, diabetic cardiomyopathy and chronic heart failure. We investigated the effects of a novel ultrapotent PARP inhibitor, INO1001, on cardiac and endothelial dysfunction in rat model of chronic heart failure (CHF) induced by permanent ligation of the left anterior descending coronary artery. CHF was accompanied by depressed left ventricular performance and impaired vascular relaxation of aortic rings. PARP inhibition significantly improved both cardiac dysfunction and vascular relaxation. Thus, PARP inhibition may represent a novel approach for the experimental therapy of CHF. C1 NAAA, NIH, Rockville, MD USA. RP Pacher, P (reprint author), NAAA, NIH, Rockville, MD USA. RI Mabley, Jon/D-2296-2010; Liaudet, Lucas/E-1322-2017 OI Liaudet, Lucas/0000-0003-2670-4930 NR 10 TC 0 Z9 0 U1 0 U2 4 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-3161-6 PY 2003 BP 35 EP 39 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA BY09J UT WOS:000187617500009 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States SO GASTROENTEROLOGY LA English DT Article ID FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; INSULIN-RESISTANCE; LEPTIN CONCENTRATIONS; METABOLIC SYNDROME; NATURAL-HISTORY; OBESITY; INJURY; ABNORMALITIES; SENSITIVITY AB Background & Aims: In the absence of other causes, overweight and obesity increase the risk of liver disease. We examined whether central adiposity and metabolic markers explain the association of body mass index (BMI as kg/m(2)) with abnormal serum alanine aminotransferase (ALT) activity in a national, population-based study. Methods: Adult participants (5724) in the third U.S. National Health and Nutrition Examination Survey (1988-1994) underwent anthropometric measures and phlebotomy after an overnight fast. Participants with excessive alcohol consumption, hepatitis B, hepatitis C, iron overload, or known diabetes were excluded. Results: Elevated ALT levels were found in 2.8% of the population. In univariate analysis, factors associated with elevated ALT levels (P < 0.05) included younger age, male sex, Mexican-American ethnicity, and higher BMI, waist-to-hip circumference ratio (WHR), and fasting serum leptin, triglyceride, insulin, and glucose concentrations. The proportion of elevated ALT activity due to overweight and obesity (BMI greater than or equal to25 kg/m(2)) was 65%. In multivariate logistic regression analysis, control for WHR, demographic factors, and glucose concentration diminished but did not eliminate the association of higher BMI with elevated ALT activity. After adding leptin and insulin concentrations, abnormal ALT activity was most strongly associated with higher WHR (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.12-:1.56) and leptin (OR, 1.12; 95% CI, 1.01-1.24) and insulin (OR, 1.27; 95% CI, 1.01-1.60) concentrations, whereas BMI was not independently related. Conclusions: In this large, national, population-based study, central adiposity, hyperleptinemia, and hyperinsulinemia were the major determinants of the association of overweight with elevated serum ALT activity. C1 Social & Sci Syst Inc, Silver Spring, MD 20910 USA. NIDDKD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NIDDK NIH HHS [N01 DK 12478] NR 48 TC 336 Z9 349 U1 3 U2 10 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 JAN PY 2003 VL 124 IS 1 BP 71 EP 79 DI 10.1053/gast.2003.50004 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 631GP UT WOS:000180160000011 PM 12512031 ER PT J AU Ghany, MG Kleiner, DE Alter, H Doo, E Khokar, F Pomrat, K Herion, D Park, Y Liang, TJ Hoofnagle, JH AF Ghany, MG Kleiner, DE Alter, H Doo, E Khokar, F Pomrat, K Herion, D Park, Y Liang, TJ Hoofnagle, JH TI Progression of fibrosis in chronic hepatitis C SO GASTROENTEROLOGY LA English DT Article ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; PLACEBO-CONTROLLED TRIAL; PEGINTERFERON ALPHA-2A; CLINICAL OUTCOMES; INITIAL TREATMENT; RANDOMIZED TRIAL; LIVER FIBROSIS; DOUBLE-BLIND; VIRUS; INFECTION AB Background & Aims: Fibrosis is the hallmark of hepatic cirrhosis, worsening of which is probably the best surrogate marker for progression of chronic liver disease. We evaluated a large cohort of patients with chronic hepatitis C (CHC) using liver histology to assess the rate and predictors of progression of fibrosis. Methods: The cohort consisted of 123 patients with CHC who underwent 2 liver biopsies 4-212 months (mean, 44 months) apart without intervening treatment. Liver histology was graded using the histology activity index (score, 0-18) and fibrosis staged using a scoring system of 0 (no fibrosis) to 6 (cirrhosis). Results: Among 123 patients, 48 (39%) showed progression in fibrosis scores, 46 (37%) showed no change, and 29 (24%) showed improvement. Of those with worsening fibrosis, 75% had a 1-point increase and 25% a 2-point or greater increase in scores, and 39% showed progression to cirrhosis. The overall rate of progression was 0.12 fibrosis units per year, a rate that predicts progression to cirrhosis in 50 years if progression was linear. The rate of fibrosis progression was variable, and it was higher among older patients, those with higher serum alanine and aspartate aminotransferase levels, and those with the most extensive periportal necrosis on initial liver biopsy. Conclusions: The best predictors of fibrosis progression in CHC are the extent of serum aminotransferase elevations and the degree of hepatocellular necrosis and inflammation on liver biopsy. These findings support the recommendation that patients with normal aminotransferase levels and mild liver histology can safely defer treatment. C1 NIDDKD, Liver Dis Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), NIDDKD, Liver Dis Sect, Digest Dis Branch, NIH, Bldg 10,Room 9B-06,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. OI Kleiner, David/0000-0003-3442-4453 NR 29 TC 247 Z9 258 U1 1 U2 3 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 JAN PY 2003 VL 124 IS 1 BP 97 EP 104 DI 10.1053/gast.2003.50018 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 631GP UT WOS:000180160000014 PM 12512034 ER PT J AU Haskell, RE Hughes, SM Chiorini, JA Alisky, JM Davidson, BL AF Haskell, RE Hughes, SM Chiorini, JA Alisky, JM Davidson, BL TI Viral-mediated delivery of the late-infantile neuronal ceroid lipofuscinosis gene, TPP-I to the mouse central nervous system SO GENE THERAPY LA English DT Article DE Batten disease; CLN2; gene therapy; CNS; lysosomal storage disease ID TRIPEPTIDYL-PEPTIDASE-I; MUCOPOLYSACCHARIDOSIS TYPE-VII; RECOMBINANT ADENOVIRUS VECTORS; ENZYME-REPLACEMENT THERAPY; LYSOSOMAL STORAGE DISEASE; ATP SYNTHASE; SUBUNIT C; VIRUS VECTORS; CLN2 PROTEIN; TRANSDUCTION AB Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is caused by mutations in tripeptidyl peptidase I (TPP-I), a pepstatin-insensitive lysosomal protease, resulting in neurodegeneration, acute seizures, visual and motor dysfunction. In vitro studies suggest that TPP-I is secreted from cells and subsequently taken up by neighboring cells, similar to other lysosomal enzymes. As such, TPP-I is an attractive candidate for enzyme replacement or gene therapy. In the present studies, we examined the feasibility of gene transfer into mouse brain using recombinant adenovirus (Ad), feline immunodeficiency virus (FIV) and adeno-associated virus (AAV) vectors expressing TPP-I, after single injections into the striatum or cerebellum. A dual TPP-I- and beta-galactosidase-expressing adenovirus vector (AdTTP-I/nlsbetagal) was used to distinguish transduced (beta-galactosidase positive) cells from cells that endocytosed secreted TTP-I. Ten days after striatal injection of AdTTP-I/nlsbetagal, beta-galactosidasepositive cells were concentrated around the injection site, corpus callosum, ependyma and choroid plexus. In cerebellar injections, beta-galactosidase expression was confined to the region of injection and in isolated neurons of the brainstem. Immunohistochemistry for TPP-I expression showed that TPP-I extended beyond areas of beta-galactosidase activity. Immunohistochemistry for TTP-I after F1VTTP-I and AA V5TTP-I injections demonstrated TPP-I in neurons of the striatum, hippocampus and Purkinje cells. For all three vectors, TPP-I activity in brain homogenates was 3-7-fold higher than endogenous levels in the injected hemispheres. Our results indicate the feasibility of vector-mediated gene transfer of TPP-I to the CNS as a potential therapy for LINCL. C1 Univ Iowa, Coll Med, Program Gene Therapy, Dept Internal Med, Iowa City, IA 52252 USA. Univ Iowa, Coll Med, Program Gene Therapy, Dept Neurol, Iowa City, IA 52252 USA. Univ Iowa, Coll Med, Program Gene Therapy, Dept Biophys, Iowa City, IA 52252 USA. Univ Iowa, Coll Med, Program Gene Therapy, Dept Physiol, Iowa City, IA 52252 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Davidson, BL (reprint author), Univ Iowa, Coll Med, Program Gene Therapy, Dept Internal Med, 200 EMRB, Iowa City, IA 52252 USA. FU NIDDK NIH HHS [DK 54759] NR 32 TC 41 Z9 46 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JAN PY 2003 VL 10 IS 1 BP 34 EP 42 DI 10.1038/sj.gt.3301843 PG 9 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 637DM UT WOS:000180496400004 PM 12525835 ER PT J AU Kugoh, H Shigenami, K Funaki, K Barrett, JC Oshimura, M AF Kugoh, H Shigenami, K Funaki, K Barrett, JC Oshimura, M TI Human chromosome 5 carries a putative telomerase repressor gene SO GENES CHROMOSOMES & CANCER LA English DT Article ID CARCINOMA CELL-LINE; CATALYTIC SUBUNIT; NEOPLASTIC TRANSFORMATION; HUMAN FIBROBLASTS; IMMORTAL CELLS; MOUSE CELLS; HTERT GENE; LIFE-SPAN; SENESCENCE; HUMAN-CHROMOSOME-3 AB Telomerase, the ribonucleoprotein enzyme that maintains the telomere, is active in human germ and stem cells and in a majority of tumor tissues and immortalized cell lines. In contrast, telomerase activity is not detected in most somatic cells, suggesting that normal human cells contain a regulatory factor(s) to repress this activity. To identify which human chromosomes carry a gene or genes that function as telomerase repressors, we investigated telomerase activity in hybrids of the B16-F10 cell line, which contain individual human chromosomes transferred previously by microcell fusion and therefore represent a hybrid panel for the entire genome except for the Y chromosome. Microcell hybrids with an introduced normal human chromosome 5 showed inhibition of telomerase activity, but clones at a late passage exhibited reactivation of telomerase activity. Reactivation of telomerase activity was accompanied by deletion and/or rearrangement of the transferred human chromosome 5. The introduction of other human chromosomes did not significantly affect the telomerase activity of B16-F10 cells. The effect of suppression of telomerase activity in microcell hybrids containing chromosome 5 was accompanied by a reduction in the level of mTERT mRNA, which encodes a component of the telomerase complex. The putative telomerase repressor gene was mapped to human chromosome bands 5p11-p13 by a combination of functional analysis using transfer of subchromosomal transferable fragments of chromosome 5 into B16-F10 cells and deletion mapping of revertant clones with reactivated telomerase activity. Thus, these results suggest that loss of a gene(s) on this chromosome was responsible for telomerase reactivation, indicating that human chromosome 5 contains a gene or genes that can regulate the expression of mTERT in B16-F10 cells. (C) 2003 Wiley-Liss, Inc. C1 Tottori Univ, Dept Mol & Cell Genet, Sch Life Sci, Fac Med, Tottori 6838503, Japan. Shimane Univ, Dept Sci Educ, Fac Educ, Shimane, Japan. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Oshimura, M (reprint author), Tottori Univ, Dept Mol & Cell Genet, Sch Life Sci, Fac Med, 86 Nishimachi, Tottori 6838503, Japan. NR 46 TC 16 Z9 17 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JAN PY 2003 VL 36 IS 1 BP 37 EP 47 DI 10.1002/gcc.10135 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 619QM UT WOS:000179487700005 PM 12461748 ER PT J AU Almasy, L Cupples, LA Daw, EW Levy, D Thomas, D Rice, JP Santangelo, S MacCluer, JW AF Almasy, L Cupples, LA Daw, EW Levy, D Thomas, D Rice, JP Santangelo, S MacCluer, JW TI Genetic analysis workshop 13: Introduction to workshop summaries SO GENETIC EPIDEMIOLOGY LA English DT Editorial Material C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Harvard Univ, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA USA. RP Almasy, L (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. OI Cupples, L. Adrienne/0000-0003-0273-7965 FU NIGMS NIH HHS [GM31575] NR 5 TC 5 Z9 5 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2003 VL 25 SU 1 BP S1 EP S4 DI 10.1002/gepi.10278 PG 4 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 751GP UT WOS:000187044700001 PM 14635163 ER PT J AU Diego, VP Atwood, L Mathias, RA Almasy, L AF Diego, VP Atwood, L Mathias, RA Almasy, L TI Consistency of genetic analyses in longitudinal data: Observations from the GAW13 Framingham Heart Study data SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 13th Genetic Analysis Workshop CY NOV 11-14, 2002 CL NEW ORLEANS, LOUISIANA DE heritability; linkage; genotype x age interaction; relative risk ID ENVIRONMENTAL-INFLUENCES; BLOOD-PRESSURE; QUEBEC FAMILY; LIFE; AGE; STABILITY; TWINS AB This paper examines the consistency of genetic analyses across time, both in the context of replicating results from one data collection point to the next, and from the perspective of modeling longitudinal processes. This summary originates from the examination of findings from nine papers from Genetic Analysis Workshop (GAW) 13 that reported on analyses of longitudinal data of a variety of traits from the Framingham Heart Study. These analyses include both assessments of consistency of aggregate genetic effects, in the form of estimation of heritability and relative risk of disease, as well as localization of quantitative trait loci (QTLs) by genome-wide linkage screens. Consistency varied widely by trait, possibly reflecting differences in measurement error, secular trends, or underlying biological features such as genotype x age interaction. Quantitatively, comparing magnitudes of estimates across age or time, heritability estimates showed greater consistency than LOD scores. However, qualitatively, the same regions of interest were often identified in genome scans from different time points or different ages. Estimates of sibling recurrence risk, on the other hand, showed little consistency. Heritabilities were greater when participants were matched by age than when they were matched by date of examination. Multivariate approaches, either in use of multiple traits or in use of multiple measures of the same trait, appeared to provide stronger genetic signals both for relative risk and for linkage. Finally, modeling of longitudinal processes provided evidence for genotype x age interactions that may partially explain variation in results of genetic analyses across time or age. (C) 2003 Wiley-Liss, Inc. C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. SUNY Binghamton, Dept Anthropol, Binghamton, NY USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. NHGRI, Genometr Sect, NIH, Baltimore, MD USA. RP Almasy, L (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. OI Diego, Vincent/0000-0002-0007-2085 FU NIGMS NIH HHS [GM31575]; NIMH NIH HHS [MH59490] NR 20 TC 2 Z9 2 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2003 VL 25 SU 1 BP S29 EP S35 DI 10.1002/gepi.10281 PG 7 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 751GP UT WOS:000187044700004 PM 14635166 ER PT J AU Goldin, LR Camp, NJ Keen, KJ Martin, LJ Moslehi, R Ghosh, S North, KE Wyszynski, DF Blacker, D AF Goldin, LR Camp, NJ Keen, KJ Martin, LJ Moslehi, R Ghosh, S North, KE Wyszynski, DF Blacker, D TI Analysis of metabolic syndrome phenotypes in Framingham Heart Study families from Genetic Analysis Workshop 13 SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 13th Genetic Analysis Workshop CY NOV 11-14, 2002 CL NEW ORLEANS, LA DE metabolic syndrome; longitudinal measures; linkage methods; susceptibility genes ID QUANTITATIVE-TRAIT LOCI; MULTILOCUS LINKAGE ANALYSIS; BODY-MASS INDEX; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; BLOOD-PRESSURE; OBESITY; HYPERTENSION; RISK AB Twelve teams of investigators constituted a group which analyzed phenotypes related to metabolic syndrome, making use of the available longitudinal measurements from the family component of the Framingham Heart Study or the simulated data, as distributed by Genetic Analysis Workshop 13 (GAW13). Body mass index, obesity, lipid abnormalities, glucose, or combinations of these traits were analyzed by this group. A wide variety of approaches were taken to construct phenotypes from the longitudinal measurements, including considering single or multiple cross-sectional time points, single ages, minimum values, maximum values, means, other lifetime values, ever/never dichotomy, or age at onset of some threshold value. Approaches also differed in the family structures utilized (sib pairs to full extended pedigrees), the genetic data considered (two-point or multipoint), and the statistics calculated (model-free and parametric), and led to a diverse set of analyses being performed. Inferences were made about heritability, and attempts were made to map underlying genes. Over 40 genome-wide linkage analyses were conducted. Despite the broad range of approaches, several regions of the genome were repeatedly identified across multiple analyses. Published 2003 Wiley-Liss, Inc dagger. C1 NCI, DCEG, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Univ Utah, Sch Med, Dept Med Informat, Div Genet Epidemiol, Salt Lake City, UT USA. Case Western Reserve Univ, Dept Epidemiol, Cleveland, OH 44106 USA. Cincinnati Childrens Hosp Med Ctr, Ctr Biostat & Epidemiol, Cincinnati, OH USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Indian Stat Inst, Appl Stat Unit, Kolkata 700035, W Bengal, India. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Goldin, LR (reprint author), NCI, DCEG, Genet Epidemiol Branch, 6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. EM goldinl@mail.nih.gov RI Keen, Kevin/D-5628-2013; Martin, Lisa/E-2425-2016 OI Keen, Kevin/0000-0001-5695-0505; Martin, Lisa/0000-0001-8702-9946 NR 56 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2003 VL 25 SU 1 BP S78 EP S89 DI 10.1002/gepi.10288 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 751GP UT WOS:000187044700011 PM 14635173 ER PT J AU Hauser, ER Hsu, FC Daley, D Olson, JM Rampersaud, E Lin, JP Paterson, AD Poisson, LM Chase, GA Dahmen, G Ziegler, A AF Hauser, ER Hsu, FC Daley, D Olson, JM Rampersaud, E Lin, JP Paterson, AD Poisson, LM Chase, GA Dahmen, G Ziegler, A TI Effects of covariates: A summary of Group 5 contributions SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 13th Genetic Analysis Workshop CY NOV 11-14, 2002 CL NEW ORLEANS, LOUISIANA DE linkage; association; covariates; statistical methods; simulations; framingham heart study ID LINKAGE ANALYSIS; GENOME SCAN; GENES AB This report summarizes the contributions of Genetic Analysis Workshop 13 (GAW13) related to the use of covariates in genetic analysis. Seven papers are summarized, five of which analyzed the Framingham Heart Study Data, and two the simulated data. Five papers examined the role of covariates in linkage analysis, using a variety of statistical approaches including affected sibling pair analysis, conditional logistic regression, and variance components methods. One paper examined the impact of covariates on family-based association analysis. In each of these papers, the detection of genetic effects could be influenced by the incorporation of covariates. The final paper examined the role of transmission ratio distortion in the analysis of complex traits and the role of covariates in the variability in transmission ratio distortion. While each paper takes a different approach to the genetic analysis of complex traits, a common thread running through each is that the inclusion of covariates can have a substantial impact on the results of the analysis. Care must be taken to understand how the covariates are being used in each analysis, what assumptions are being made, and how these assumptions might affect the results and their interpretation. Finally, the results of Group 5 studies show that inclusion of covariates can increase the power to detect genes for complex traits, and has the potential to advance an understanding of the role of genes in these complex traits. (C) 2003 Wiley-Liss, Inc. C1 Duke Univ, Med Ctr, Ctr Human Genet, Dept Med,Sect Med Genet, Durham, NC 27710 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Biostat Sect, Winston Salem, NC 27103 USA. Case Western Reserve Univ, Rammelkamp Ctr Educ & Res, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. NHLBI, DECA, Off Biostat Res, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Hlth Evaluat Sci, Hershey, PA 17033 USA. Univ Lubeck, Univ Hosp Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany. RP Hauser, ER (reprint author), Duke Univ, Med Ctr, Ctr Human Genet, Dept Med,Sect Med Genet, Box 3445, Durham, NC 27710 USA. RI Paterson, Andrew/A-4088-2011; OI Paterson, Andrew/0000-0002-9169-118X; Hauser, Elizabeth/0000-0003-0367-9189; Ziegler, Andreas/0000-0002-8386-5397 FU NIMH NIH HHS [MH59258] NR 16 TC 8 Z9 8 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2003 VL 25 SU 1 BP S43 EP S49 DI 10.1002/gepi.10283 PG 7 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 751GP UT WOS:000187044700006 PM 14635168 ER PT J AU Saccone, NL Goode, EL Bergen, AW AF Saccone, NL Goode, EL Bergen, AW TI Genetic Analysis Workshop 13: Summary of analyses of alcohol and cigarette use phenotypes in the Framingham Heart Study SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 13th Genetic Analysis Workshop CY NOV 11-14, 2002 CL NEW ORLEANS, LOUISIANA DE linkage; familial correlation; genome screen; longitudinal data; addiction; consumption; nicotine; tobacco ID LINKAGE ANALYSIS; DEPENDENCE; CHROMOSOME-4; SAMPLE; MODELS; TRAIT; SCAN AB Data from the Framingham Heart Study were provided for Genetic Analysis Workshop 13. This paper summarizes six contributed papers that focused on the analysis of the longitudinal alcohol and/or cigarette use phenotypes available in these data, with the goal of detecting genes influencing these traits. For several of these contributions, the primary phenotype was maximum daily substance use reported over the longitudinal data. Others focused on a cross section by taking the daily use reported at a fixed time interval for all individuals, and others considered dichotomous phenotypes defined by thresholds of use. A variety of covariates were considered, including age (or year of birth) and sex. Most studies included unexposed individuals (those reporting no alcohol/cigarette use at all available assessments) in the linkage analyses, though one study compared results when defining the phenotype for unexposed individuals to be zero vs. defining the phenotype for unexposed individuals to be unknown. Linkage findings varied across studies. However, there was some concordance of evidence on chromosome 9 for alcohol traits, and of weaker evidence on chromosome 20 for cigarette traits. Analytical issues arose which may be crucial for genetic studies of substance use and dependence, including the choice of how to handle unexposed or substance-naive individuals, use of dichotomous vs. quantitative traits, and consideration of transformations and covariates. (C) 2003 Wiley-Liss, Inc. C1 Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. NCI, Ctr Adv Technol, Core Genotyping Facil, DHHS,NIH, Gaithersburg, MD USA. RP Saccone, NL (reprint author), Washington Univ, Sch Med, Dept Genet, Div Human Genet, Box 8232,4566 Scott Ave, St Louis, MO 63110 USA. OI Bergen, Andrew/0000-0002-1237-7644 FU NCRR NIH HHS [RR03655]; NIDA NIH HHS [DA15129] NR 22 TC 2 Z9 3 U1 3 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2003 VL 25 SU 1 BP S90 EP S97 DI 10.1002/gepi.10289 PG 8 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 751GP UT WOS:000187044700012 PM 14635174 ER PT J AU Pfeiffer, RM Hildesheim, A Gail, MH Pee, D Chen, CJ Goldstein, AM Diehl, SR AF Pfeiffer, RM Hildesheim, A Gail, MH Pee, D Chen, CJ Goldstein, AM Diehl, SR TI Robustness of inference on measured covariates to misspecification of genetic random effects in family studies SO GENETIC EPIDEMIOLOGY LA English DT Article DE ascertainment; conditional logistic regression; correlated binary data; misspecified model; nested random effects model ID LINEAR MIXED MODELS; NASOPHARYNGEAL CARCINOMA; LOGISTIC-MODELS AB Family studies to identify disease-related genes frequently collect only families with multiple cases. It is often desirable to determine if risk factors that are known to influence disease risk in the general population also play a role in the study families. If so, these factors should be incorporated into the genetic analysis to control for confounding. Pfeiffer et al. [2001 Biometrika 88: 933-948] proposed a variance components or random effects model to account for common familial effects and for different genetic correlations among family members. After adjusting for ascertainment, they found maximum likelihood estimates of the measured exposure effects. Although it is appealing that this model accounts for genetic correlations as well as for the ascertainment of families, in order to perform an analysis one needs to specify the distribution of random genetic effects. The current work investigates the robustness of the proposed model with respect to various misspecifications of genetic random effects in simulations. When the true underlying genetic mechanism is polygenic with a small dominant component, or Mendelian with low allele frequency and penetrance, the effects of misspecification on the estimation of fixed effects in the model are negligible. The model is applied to data from a family study on nasopharyngeal carcinoma in Taiwan. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD USA. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. Univ Med & Dent New Jersey, New Jersey Dent Sch, Ctr Pharmacogenom & Complex Dis Res, Newark, NJ 07103 USA. RP Pfeiffer, RM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8030, Bethesda, MD 20892 USA. RI Chen, Chien-Jen/C-6976-2008; Pfeiffer, Ruth /F-4748-2011 NR 18 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2003 VL 24 IS 1 BP 14 EP 23 DI 10.1002/gepi.10191 PG 10 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 632EJ UT WOS:000180210500002 PM 12508252 ER PT J AU Park, CJ Song, SG Lee, PR Shou, WY Deshaies, RJ Lee, KS AF Park, CJ Song, SG Lee, PR Shou, WY Deshaies, RJ Lee, KS TI Loss of CDC5 function in Saccharomyces cerevisiae leads to defects in Swe1p regulation and Bfa1p/Bub2p-independent cytokinesis SO GENETICS LA English DT Article ID CELL-CYCLE PROGRESSION; MAMMALIAN POLO KINASE; XENOPUS EGG EXTRACTS; BUDDING-YEAST; SCHIZOSACCHAROMYCES-POMBE; CONTRACTILE RING; FISSION YEAST; MITOTIC EXIT; SEPTIN; PROTEIN AB In many organisms, polo kinases appear to play multiple roles during M-phase progression. To provide new insights into the function of budding yeast polo kinase Cdc5p, we generated novel temperature-sensitive cdc5 mutants by mutagenizing the C-terminal domain. Here we show that, at a sernipermissive temperature, the cdc5-3 mutant exhibited a synergistic bud elongation and growth defect with loss of HSL1, a component important for normal G(2)/M transition. Loss of SWE1, which phosphorylates and inactivates the budding yeast Cdk1 homolog Cdc28p, suppressed the cdc5-3 hsl1Delta defect, suggesting that Cdc5p functions at a point upstream of Swe1p. In addition, the cdc5-4 and cdc5-7mutants exhibited chained cell morphologies with shared cytoplasms between the connected cell bodies, indicating a cytokinetic defect. Close examination of these mutants revealed delayed septin assembly at the incipient bud site and loosely organized septin rings at the mother-bud neck. Components in the mitotic exit network (MEN) play important roles in normal cytokinesis. However, loss of BFA1 or BUB2 negative regulators of the MEN, failed to remedy the cytokinetic defect of these mutants, indicating that Cdc5p promotes cytokinesis independently of Bfa1p and Bub2p. Thus, Cdc5p contributes to the activation of the Swelp-dependent Cdc28p/Clb pathway, normal septin function, and cytokinesis. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. RP NCI, Lab Metab, NIH, 9000 Rockville Pike,Bldg 37,Rm 3D25, Bethesda, MD 20892 USA. EM kyunglee@pop.nci.nih.gov RI Deshaies, Raymond/B-8354-2014 OI Deshaies, Raymond/0000-0002-3671-9354 NR 51 TC 31 Z9 31 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD JAN PY 2003 VL 163 IS 1 BP 21 EP 33 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 646MW UT WOS:000181039700003 PM 12586693 ER PT J AU Sundararajan, A Lee, BS Garfinkel, DJ AF Sundararajan, A Lee, BS Garfinkel, DJ TI The Rad27 (Fen-1) nuclease inhibits Ty1 mobility in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; SHORT-SEQUENCE RECOMBINATION; EUKARYOTIC DNA-REPLICATION; YEAST RETROTRANSPOSON TY1; VIRUS-LIKE PARTICLES; FLAP ENDONUCLEASE-1; MUTATION AVOIDANCE; HOMOLOGOUS RECOMBINATION; FUNCTIONAL-ANALYSIS; MULTIMERIC ARRAYS AB Although most Tyl elements in Saccharomyces cerevisiae are competent for retrotransposition, host defense genes can inhibit different steps of the Tyl life cycle. Here, we demonstrate that Rad27, a structure-specific nuclease that plays an important role in DNA replication and genome stability, inhibits Tyl at a post-translational level. We have examined the effects of various rad27 mutations on Tyl element retrotransposition and cDNA recombination, termed Tyl mobility. The point mutations rad27-G67S, rad27-G240D, and rad27-E158D that cause defects in certain enzymatic activities in vitro result in variable increases in Tyl mobility, ranging from 4- to 22-fold. The C-terminal frameshift mutation rad27-324 confers the maximum increase in Tyl mobility (198-fold), unincorporated cDNA, and insertion at preferred target sites. The null mutation differs from the other rad27alleles by increasing the frequency of multimeric Tyl insertions and cDNA recombination with a genomic element. The rad27 mutants do not markedly alter the levels of Tyl RNA or the TyAl-gag protein. However, there is an increase in the stability of unincorporated Tyl cDNA in rad27-324 and the null mutant. Our results suggest that Rad27 inhibits Tyl mobility by destabilizing unincorporated Tyl cDNA and preventing the formation of Tyl multimers. C1 NCI, Gen Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Garfinkel, DJ (reprint author), NCI, Gen Regulat & Chromosome Biol Lab, POB B, Frederick, MD 21702 USA. NR 67 TC 24 Z9 24 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2003 VL 163 IS 1 BP 55 EP 67 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 646MW UT WOS:000181039700006 PM 12586696 ER PT J AU Oh, SW Kingsley, T Shin, H Zheng, ZY Chen, HW Chen, X Wang, H Ruan, PZ Moody, M Hou, SX AF Oh, SW Kingsley, T Shin, H Zheng, ZY Chen, HW Chen, X Wang, H Ruan, PZ Moody, M Hou, SX TI A P-element insertion screen identified mutations in 455 novel essential genes in Drosophila SO GENETICS LA English DT Article ID MATERNAL EFFECT PHENOTYPES; ZYGOTIC LETHAL MUTATIONS; GENOME SEQUENCE; MELANOGASTER; LOCI; MUTAGENESIS; CHROMOSOME; POLARITY; PROJECT; PATTERN AB With the completion of the nucleotide sequences of several complex eukaryotic genomes, tens of thousands of genes have been predicted. However, this information has to be correlated with the functions of those genes to enhance our understanding of biology and to improve human health care. The Drosophila transposon P-element-induced mutations are very useful for directly connecting gene products to their biological function. We designed an efficient transposon P-element-mediated gene disruption procedure and performed genetic screening for single P-element insertion mutations, enabling us to recover 2500 lethal mutations. Among these, 2355 are second chromosome mutations. Sequences flanking >2300 insertions that identify 850 different genes or ESTs (783 genes on the second chromosome and 67 genes on the third chromosome) have been determined. Among these, 455 correspond to genes for which no lethal mutation has yet been reported. The Drosophila genome is thought to contain similar to3600 vital genes; 1400 are localized on the second chromosome. Our mutation collection represents similar to56% of the second chromosome vital genes and similar to24% of the total vital Drosophila genes. C1 NCI, Immunobiol Lab, NIH, Frederick, MD 21702 USA. RP NCI, Immunobiol Lab, NIH, Frederick, MD 21702 USA. EM shou@maii.ncifcrf.gov RI Chen, Hua-Wei/A-8018-2011 NR 25 TC 70 Z9 70 U1 0 U2 1 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD JAN PY 2003 VL 163 IS 1 BP 195 EP 201 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 646MW UT WOS:000181039700017 PM 12586707 ER PT J AU Steingrimsson, E Arnheiter, H Hallsson, JH Lamoreux, ML Copeland, NG Jenkins, NA AF Steingrimsson, E Arnheiter, H Hallsson, JH Lamoreux, ML Copeland, NG Jenkins, NA TI Interallelic complementation at the mouse Mitf locus SO GENETICS LA English DT Article ID TRANSCRIPTION FACTOR FAMILY; MICROPHTHALMIA LOCUS; GENE; MUTATIONS; EXPRESSION; REGULATOR; DEAFNESS; PROTEIN; ISOFORM AB Mutations at the mouse microphthalmia locus (Mitf) affect the development of different cell types, including melanocytes, retinal pigment epithelial cells of the eye, and osteoclasts. The MITF protein is a member of the MYC supergene family of basic-helix-loop-helix-leucine-zipper (bHLHZip) transcription factors and is known to regulate the expression of cell-specific target genes by binding DNA as homodimer or as heterodimer with related proteins. The many mutations isolated at the locus have different effects on the phenotype and can be arranged in an allelic series in which the phenotypes range from near normal to white microphthalmic animals with osteopetrosis. Previous investigations have shown that certain combinations of Mitf alleles complement each other, resulting in a phenotype more normal than that of each homozygote alone. Here we analyze this interallelic complementation in detail and show that it is limited to one particular allele, Mitf(Mi-white) (Mitf(Mi-wh)), a mutation affecting the DNA-binding domain. Both loss- and gain-of-function mutations are complemented, as are other Mitf mutations affecting the DNA-binding domain. Furthermore, this behavior is not restricted to particular cell types: Both eye development and coat color phenotypes are complemented. Our analysis suggests that Mitf(Mi-wh)-associated interallefic complementation is due to the unique biochemical nature of this mutation. C1 Univ Iceland, Fac Med, Dept Biochem & Mol Biol, IS-101 Reykjavik, Iceland. Natl Inst Neruol Disorders & Stroke, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. NCI FCRF, Mouse Canc Genet Program, NCI, Ft Detrick, MD 21702 USA. RP Steingrimsson, E (reprint author), Univ Iceland, Fac Med, Dept Biochem & Mol Biol, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland. NR 28 TC 20 Z9 22 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 JAN PY 2003 VL 163 IS 1 BP 267 EP 276 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 646MW UT WOS:000181039700024 PM 12586714 ER PT J AU Liberfarb, RM Levy, HP Rose, PS Wilkin, DJ Davis, J Balog, JZ Griffith, AJ Szymko-Bennett, YM Johnston, JJ Francomano, CA AF Liberfarb, RM Levy, HP Rose, PS Wilkin, DJ Davis, J Balog, JZ Griffith, AJ Szymko-Bennett, YM Johnston, JJ Francomano, CA TI The Stickler syndrome: Genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1 SO GENETICS IN MEDICINE LA English DT Article DE Stickler syndrome; genotype/phenotype correlation; prevalence of clinical features ID PROGRESSIVE ARTHRO-OPHTHALMOPATHY; PREMATURE TERMINATION CODONS; MITRAL-VALVE PROLAPSE; PROCOLLAGEN GENE; SYNDROME ARTHROOPHTHALMOPATHY; IMPEDANCE AUDIOMETRY; STOP CODON; LINKAGE; COL11A1; MANIFESTATIONS AB Purpose: To evaluate a cohort of clinically diagnosed Stickler patients in which the causative COL2A1 mutation has been identified, determine the prevalence of clinical features in this group as a whole and as a function of age, and look for genotype/phenotype correlations. Methods: Review of medical records, clinical evaluations, and mutational analyses of clinically diagnosed Stickler patients. Results: Patients with seven defined COL2A1 mutations had similar phenotypes, though both inter- and intrafamilial variability were apparent and extensive. The prevalence of certain clinical features was a function of age. Conclusion: Although the molecular determination of a COL2A1 mutation can predict the occurrence of Stickler syndrome, the variability observed in the families described here makes it difficult to predict the severity of the phenotype on the basis of genotype. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Microarray Core Facil, Los Angeles, CA 90048 USA. Mayo Clin & Mayo Grad Sch Med, Dept Orthoped Surg, Rochester, MN 55901 USA. Johns Hopkins Univ, Sch Med, Dept Internal Med, Baltimore, MD USA. RP Liberfarb, RM (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. FU NIDCD NIH HHS [Z01 DC000060-01] NR 55 TC 29 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JAN-FEB PY 2003 VL 5 IS 1 BP 21 EP 27 DI 10.1097/01.GIM.0000048704.65405.D8 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 740EV UT WOS:000186390700004 PM 12544472 ER PT J AU McQuillan, GM Porter, KS Agelli, M Kington, R AF McQuillan, GM Porter, KS Agelli, M Kington, R TI Consent for genetic research in a general population: The NHANES experience SO GENETICS IN MEDICINE LA English DT Article DE informed consent; genetic research; survey; representative sample; household population ID INFORMED CONSENT; DISEASE PREVENTION; CANCER; FAMILIES; SAMPLES AB Purpose: To determine the sociodemographic factors associated with consent for storage of DNA for future genetic research. Methods: Analysis of the characteristics of consenting individuals participating in the National Health and Nutrition Examination Survey, a nationally representative survey of the US household population. Results: In 1999, 84% (95% confidence interval 82.4-85.6) of eligible participants consented to have their blood samples included in a national repository for genetic research. In 2000, 85.3% (95% confidence interval 84.0-86.6) consented. Females and black participants in both years were least likely to consent (1999, 82.2% and 73.2%; 2000, 83.6% and 81.3%, respectively). An assessment by logistic regression demonstrated that in both years only non-Hispanic black race/ethnicity was a significant independent predictor for not consenting to future genetic research. Conclusion: Although non-Hispanic black individuals have overall response rates similar to those of the other racial/ethnic groups, they are less likely to agree to have a blood sample saved for future genetic research. In balance, however, these findings demonstrate wide acceptance among survey participants for allowing storage of specimens for future genetic research across many demographic variables. C1 NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. RP McQuillan, GM (reprint author), 6525 Belcrest Rd,Room 1000, Hyattsville, MD 20782 USA. NR 20 TC 97 Z9 98 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JAN-FEB PY 2003 VL 5 IS 1 BP 35 EP 42 DI 10.1097/01.GIM.0000048372.64172.15 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 740EV UT WOS:000186390700006 PM 12544474 ER PT J AU Haga, SB Boughman, JA AF Haga, SB Boughman, JA TI The genetics workforce and workload SO GENETICS IN MEDICINE LA English DT Letter C1 NIH, Off Biotechnol Act, Bethesda, MD 20892 USA. Amer Soc Human Genet, Bethesda, MD USA. RP Haga, SB (reprint author), NIH, Off Biotechnol Act, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JAN-FEB PY 2003 VL 5 IS 1 BP 55 EP 57 DI 10.1097/00125817-200301000-00009 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 740EV UT WOS:000186390700009 PM 12544477 ER PT J AU Anantharaman, V Aravind, L AF Anantharaman, V Aravind, L TI New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system SO GENOME BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; MULTIPLE SEQUENCE ALIGNMENT; DNA-BINDING PROTEINS; RANGE PLASMID RK2; ESCHERICHIA-COLI; CAENORHABDITIS-ELEGANS; COMPARATIVE GENOMICS; FUNCTIONAL-ANALYSIS; NUTRITIONAL STRESS; EVOLUTION AB Background: Several prokaryotic plasmids maintain themselves in their hosts by means of diverse post-segregational cell killing systems. Recent findings suggest that chromosomally encoded copies of toxins and antitoxins of post-segregational cell killing systems - such as the RelE system - might function as regulatory switches under stress conditions. The RelE toxin cleaves ribosome-associated transcripts, whereas another post-segregational cell killing toxin, ParE, functions as a gyrase inhibitor. Results: Using sequence profile analysis we were able unify the RelE- and ParE-type toxins with several families of small, uncharacterized proteins from diverse bacteria and archaea into a single superfamily. Gene neighborhood analysis showed that the majority of these proteins were encoded by genes in characteristic neighborhoods, in which genes encoding toxins always co-occurred with genes encoding transcription factors that are also antitoxins. The transcription factors accompanying the RelE/ParE superfamily may belong to unrelated or distantly related superfamilies, however. We used this conserved neighborhood template to transitively search genomes and identify novel post-segregational cell killing-related systems. One of these novel systems, observed in several prokaryotes, contained a predicted toxin with a PilT-N terminal ( PIN) domain, which is also found in proteins of the eukaryotic nonsense-mediated RNA decay system. These searches also identified novel transcription factors ( antitoxins) in post-segregational cell killing systems. Furthermore, the toxin Doc defines a potential metalloenzyme superfamily, with novel representatives in bacteria, archaea and eukaryotes, that probably acts on nucleic acids. Conclusions: The tightly maintained gene neighborhoods of post-segregational cell killing-related systems appear to have evolved by in situ displacement of genes for toxins or antitoxins by functionally equivalent but evolutionarily unrelated genes. We predict that the novel postsegregational cell killing-related systems containing a PilT-N terminal domain toxin and the eukaryotic nonsense-mediated RNA decay system are likely to function via a common mechanism, in which the PilT-N terminal domain cleaves ribosome-associated transcripts. The core of the eukaryotic nonsense-mediated RNA decay system has probably evolved from a post-segregational cell killing-related system. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 59 TC 148 Z9 149 U1 2 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 12 AR R81 DI 10.1186/gb-2003-4-12-r81 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 748ZR UT WOS:000186894600011 PM 14659018 ER PT J AU Anantharaman, V Aravind, L AF Anantharaman, V Aravind, L TI Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes SO GENOME BIOLOGY LA English DT Article ID CELL-WALL HYDROLASE; LECITHIN-RETINOL ACYLTRANSFERASE; PROTEIN-STRUCTURE PREDICTION; ALA DIPEPTIDASE VANX; BACILLUS-SUBTILIS; VANCOMYCIN RESISTANCE; GLUTATHIONYLSPERMIDINE SYNTHETASE/AMIDASE; BACTERIAL PEPTIDOGLYCAN; LISTERIA-MONOCYTOGENES; CRITHIDIA-FASCICULATA AB Background: Peptidoglycan is hydrolyzed by a diverse set of enzymes during bacterial growth, development and cell division. The NlpC/P60 proteins define a family of cell-wall peptidases that are widely represented in various bacterial lineages. Currently characterized members are known to hydrolyze D-gamma-glutamyl-meso-diaminopimelate or N-acetylmuramate-L-alanine linkages. Results: Detailed analysis of the NlpC/P60 peptidases showed that these proteins define a large superfamily encompassing several diverse groups of proteins. In addition to the well characterized P60-like proteins, this superfamily includes the AcmB/LytN and YaeF/YiiX families of bacterial proteins, the amidase domain of bacterial and kinetoplastid glutathionylspermidine synthases (GSPSs), and several proteins from eukaryotes, phages, poxviruses, positive-strand RNA viruses, and certain archaea. The eukaryotic members include lecithin retinol acyltransferase (LRAT), nematode developmental regulator Egl-26, and candidate tumor suppressor H-rev107. These eukaryotic proteins, along with the bacterial YaeF/poxviral G6R family, show a circular permutation of the catalytic domain. We identified three conserved residues, namely a cysteine, a histidine and a polar residue, that are involved in the catalytic activities of this superfamily. Evolutionary analysis of this superfamily shows that it comprises four major families, with diverse domain architectures in each of them. Conclusions: Several related, but distinct, catalytic activities, such as murein degradation, acyl transfer and amide hydrolysis, have emerged in the NlpC/P60 superfamily. The three conserved catalytic residues of this superfamily are shown to be equivalent to the catalytic triad of the papain-like thiol peptidases. The predicted structural features indicate that the NlpC/P60 enzymes contain a fold similar to the papain-like peptidases, transglutaminases and arylamine acetyltransferases. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 76 TC 196 Z9 201 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 2 AR R11 DI 10.1186/gb-2003-4-2-r11 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 675KH UT WOS:000182693100007 PM 12620121 ER PT J AU Aravind, L Iyer, LM Anantharaman, V AF Aravind, L Iyer, LM Anantharaman, V TI The two faces of Alba: the evolutionary connection between proteins participating in chromatin structure and RNA metabolism SO GENOME BIOLOGY LA English DT Article ID HUMAN RIBONUCLEASE-P; DNA-BINDING PROTEIN; CRYSTAL-STRUCTURE; METHANOPYRUS-KANDLERI; ARCHAEAL; DOMAIN; COMPLEX; SUBUNIT; IDENTIFICATION; PURIFICATION AB Background: There is considerable heterogeneity in the phyletic patterns of major chromosomal DNA-binding proteins in archaea. Alba is a well-characterized chromosomal protein from the crenarchaeal genus Sulfolobus. While Alba has been detected in most archaea and some eukaryotic taxa, its exact functions in these taxa are not clear. Here we use comparative genomics and sequence profile analysis to predict potential alternative functions of the Alba proteins. Results: Using sequence-profile searches, we were able to unify the Alba proteins with RNase P/MRP subunit Rpp20/Pop7, human RNase P subunit Rpp25, and the ciliate Mdp2 protein, which is implicated in macronuclear development. The Alba superfamily contains two eukaryote-specific families and one archaeal family. We present different lines of evidence to show that both eukaryotic families perform functions related to RNA metabolism. Several members of one of the eukaryotic families, typified by Mdp2, are combined in the same polypeptide with RNA-binding RGG repeats. We also investigated the relationships of the unified Alba superfamily within the ancient RNA-binding IF3-C fold, and show that it is most closely related to other RNA-binding members of this fold, such as the YhbY and IF3-C superfamilies. Based on phyletic patterns and the principle of phylogenetic bracketing, we predict that at least some of the archaeal members may also possess a role in RNA metabolism. Conclusions: The Alba superfamily proteins appear to have originated as RNA-binding proteins which formed various ribonucleoprotein complexes, probably including RNase P. It was recruited as a chromosomal protein possibly only within the crenarchaeal lineage. The evolutionary connections reported here suggest how a diversity of functions based on a common biochemical basis emerged in proteins of the Alba superfamily. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 50 TC 81 Z9 82 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 10 AR R64 DI 10.1186/gb-2003-4-10-r64 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 727TH UT WOS:000185675600009 PM 14519199 ER PT J AU Bussey, KJ Kane, D Sunshine, M Narasimhan, S Nishizuka, S Reinhold, WC Zeeberg, B Ajay Weinstein, JN AF Bussey, KJ Kane, D Sunshine, M Narasimhan, S Nishizuka, S Reinhold, WC Zeeberg, B Ajay Weinstein, JN TI MatchMiner: a tool for batch navigation among gene and gene product identifiers SO GENOME BIOLOGY LA English DT Article ID MOLECULAR PHARMACOLOGY; CANCER; DATABASE AB MatchMiner is a freely available program package for batch navigation among gene and gene product identifier types commonly encountered in microarray studies and other forms of 'omic' research. The user inputs a list of gene identifiers and then uses the Merge function to find the overlap with a second list of identifiers of either the same or a different type or uses the LookUp function to find corresponding identifiers. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. SRA Int Inc, Fairfax, VA 22033 USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bldg 37, Bethesda, MD 20892 USA. EM weinstein@dtpax2.ncifcrf.gov NR 10 TC 90 Z9 96 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 4 AR R27 DI 10.1186/gb-2003-4-4-r27 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 675LK UT WOS:000182696200009 PM 12702208 ER PT J AU Dennis, G Sherman, BT Hosack, DA Yang, J Gao, W Lane, HC Lempicki, RA AF Dennis, G Sherman, BT Hosack, DA Yang, J Gao, W Lane, HC Lempicki, RA TI DAVID: Database for annotation, visualization, and integrated discovery SO GENOME BIOLOGY LA English DT Article ID PROTEIN INFORMATION; RESOURCE AB The distributed nature of biological knowledge poses a major challenge to the interpretation of genome-scale datasets, including those derived from microarray and proteomic studies. This report describes DAVID, a web-accessible program that integrates functional genomic annotations with intuitive graphical summaries. Lists of gene or protein identifiers are rapidly annotated and summarized according to shared categorical data for Gene Ontology, protein domain, and biochemical pathway membership. DAVID assists in the interpretation of genome-scale datasets by facilitating the transition from data collection to biological meaning. C1 NCI, Sci Applicat Int Corp, Clin Serv Program, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP NCI, Sci Applicat Int Corp, Clin Serv Program, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA. EM rlempicki@niaid.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 13 TC 635 Z9 645 U1 4 U2 55 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 9 AR R60 DI 10.1186/gb-2003-4-9-r60 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 716UR UT WOS:000185048100013 ER PT J AU Hosack, DA Dennis, G Sherman, BT Lane, HC Lempicki, RA AF Hosack, DA Dennis, G Sherman, BT Lane, HC Lempicki, RA TI Identifying biological themes within lists of genes with EASE SO GENOME BIOLOGY LA English DT Article ID MICROARRAY DATA; EXPRESSION; DATABASE; TOOL; RESOURCES; ONTOLOGY; PROTEINS; PATHWAYS; PROFILE; GENMAPP AB EASE is a customizable software application for rapid biological interpretation of gene lists that result from the analysis of microarray, proteomics, SAGE and other high-throughput genomic data. The biological themes returned by EASE recapitulate manually determined themes in previously published gene lists and are robust to varying methods of normalization, intensity calculation and statistical selection of genes. EASE is a powerful tool for rapidly converting the results of functional genomics studies from 'genes' to 'themes'. C1 SAIC Frederick Inc, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA. NIAID, Clin & Mol Retrovirol Sect, NIH, Bethesda, MD 20892 USA. RP Lempicki, RA (reprint author), SAIC Frederick Inc, Lab Immunopathogenesis & Bioinformat, POB B, Frederick, MD 21702 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 30 TC 995 Z9 1015 U1 2 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 10 AR R70 DI 10.1186/gb-2003-4-10-r70 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 727TH UT WOS:000185675600015 PM 14519205 ER PT J AU Koonin, EV Rogozin, IB AF Koonin, EV Rogozin, IB TI Getting positive about selection SO GENOME BIOLOGY LA English DT Article C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 8 AR 331 DI 10.1186/gb-2003-4-8-331 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 707XZ UT WOS:000184536400005 PM 12914654 ER PT J AU Koonin, EV Makarova, KS Rogozin, IB Davidovic, L Letellier, MC Pellegrini, L AF Koonin, EV Makarova, KS Rogozin, IB Davidovic, L Letellier, MC Pellegrini, L TI The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers SO GENOME BIOLOGY LA English DT Article ID BAYESIAN-INFERENCE; DROSOPHILA RHOMBOID-1; PROVIDENCIA-STUARTII; PROTEIN; EVOLUTION; SEQUENCE; MECHANISM; PHYLOGENY; GENOMES; ORIGIN AB Background: The rhomboid family of polytopic membrane proteins shows a level of evolutionary conservation unique among membrane proteins. They are present in nearly all the sequenced genomes of archaea, bacteria and eukaryotes, with the exception of several species with small genomes. On the basis of experimental studies with the developmental regulator rhomboid from Drosophila and the AarA protein from the bacterium Providencia stuartii, the rhomboids are thought to be intramembrane serine proteases whose signaling function is conserved in eukaryotes and prokaryotes. Results: Phylogenetic tree analysis carried out using several independent methods for tree constructions and the corresponding statistical tests suggests that, despite its broad distribution in all three superkingdoms, the rhomboid family was not present in the last universal common ancestor of extant life forms. Instead, we propose that rhomboids evolved in bacteria and have been acquired by archaea and eukaryotes through several independent horizontal gene transfers. In eukaryotes, two distinct, ancient acquisitions apparently gave rise to the two major subfamilies, typified by rhomboid and PARL (presenilins-associated rhomboid-like protein), respectively. Subsequent evolution of the rhomboid family in eukaryotes proceeded by multiple duplications and functional diversification through the addition of extra transmembrane helices and other domains in different orientations relative to the conserved core that harbors the protease activity. Conclusions: Although the near-universal presence of the rhomboid family in bacteria, archaea and eukaryotes appears to suggest that this protein is part of the heritage of the last universal common ancestor, phylogenetic tree analysis indicates a likely bacterial origin with subsequent dissemination by horizontal gene transfer. This emphasizes the importance of explicit phylogenetic analysis for the reconstruction of ancestral life forms. A hypothetical scenario for the origin of intracellular membrane proteases from membrane transporters is proposed. C1 Univ Laval, Ctr Rech, Quebec City, PQ G1J 2G3, Canada. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pellegrini, L (reprint author), Univ Laval, Ctr Rech, Chemin Canardiere, Quebec City, PQ G1J 2G3, Canada. NR 48 TC 118 Z9 123 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 3 AR R19 DI 10.1186/gb-2003-4-3-r19 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 675KU UT WOS:000182694200008 PM 12620104 ER PT J AU Lee, JK Bussey, KJ Gwadry, FG Reinhold, W Riddick, G Pelletier, SL Nishizuka, S Szakacs, G Annereau, JP Shankavaram, U Lababidi, S Smith, LH Gottesman, MM Weinstein, JN AF Lee, JK Bussey, KJ Gwadry, FG Reinhold, W Riddick, G Pelletier, SL Nishizuka, S Szakacs, G Annereau, JP Shankavaram, U Lababidi, S Smith, LH Gottesman, MM Weinstein, JN TI Comparing cDNA and oligonucleotide array data: concordance of gene expression across platforms for the NCI-60 cancer cells SO GENOME BIOLOGY LA English DT Article ID ANTICANCER DRUG SCREEN; HUMAN BREAST-CARCINOMA; MOLECULAR PHARMACOLOGY; LINES; IDENTIFICATION; PATTERNS; INHIBITORS; MELANOMA; RECEPTOR; PATHWAY AB Microarray gene-expression profiles are generally validated one gene at a time by real-time RT-PCR. We describe here a different approach based on simultaneous mutual validation of large numbers of genes using two different expression-profiling platforms. The result described here for the NCI-60 cancer cell lines is a consensus set of genes that give similar profiles on spotted cDNA arrays and Affymetrix oligonucleotide chips. Global concordance is parameterized by a 'correlation of correlations' coefficient. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, JK (reprint author), Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Charlottesville, VA 22908 USA. RI Szakacs, Gergely/A-2580-2009 OI Szakacs, Gergely/0000-0002-9311-7827 NR 27 TC 79 Z9 84 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 12 AR R82 DI 10.1186/gb-2003-4-12-r82 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 748ZR UT WOS:000186894600012 PM 14659019 ER PT J AU Makarova, KS Koonin, EV AF Makarova, KS Koonin, EV TI Comparative genomics of archaea: how much have we learned in six years, and what's next? SO GENOME BIOLOGY LA English DT Editorial Material ID HORIZONTAL GENE-TRANSFER; TRANSFER-RNA SYNTHETASE; DNA-REPLICATION PROTEINS; STRUCTURAL GENOMICS; BACTERIAL HYPERTHERMOPHILES; PYROCOCCUS-FURIOSUS; PHYLOGENETIC CLASSIFICATION; THERMOPLASMA-ACIDOPHILUM; METHANOCOCCUS-JANNASCHII; THERMOPHILIC ARCHAEA AB Archaea comprise one of the three distinct domains of life (with bacteria and eukaryotes). With 16 complete archaeal genomes sequenced to date, comparative genomics has revealed a conserved core of 313 genes that are represented in all sequenced archaeal genomes, plus a variable 'shell' that is prone to lineage-specific gene loss and horizontal gene exchange. The majority of archaeal genes have not been experimentally characterized, but novel functional pathways have been predicted. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 142 TC 66 Z9 71 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 8 AR 115 DI 10.1186/gb-2003-4-8-115 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 707XZ UT WOS:000184536400002 PM 12914651 ER PT J AU Muegge, K AF Muegge, K TI Modifications of histone cores and tails in V(D)J recombination SO GENOME BIOLOGY LA English DT Review ID ACCESSIBILITY AB The organization of chromatin and modifications to the tails of histone proteins are thought to be important in regulating the rearrangement of V, D and J gene segments, which encode immunoglobulins and T-cell receptors. A recent study shows that methylated lysine 79 in the core region of histone H3 also plays a role by providing a euchromatic 'mark' that may regulate access of the V( D) J recombinase. C1 NCI, Mol Immunoregulat Lab, SAIC Basic Sci Program, Frederick, MD 21701 USA. RP Muegge, K (reprint author), NCI, Mol Immunoregulat Lab, SAIC Basic Sci Program, Frederick, MD 21701 USA. FU PHS HHS [N01-C0-12400] NR 17 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 4 AR 211 DI 10.1186/gb-2003-4-4-211 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 675LK UT WOS:000182696200004 PM 12702201 ER PT J AU Omelchenko, MV Makarova, KS Wolf, YI Rogozin, IB Koonin, EV AF Omelchenko, MV Makarova, KS Wolf, YI Rogozin, IB Koonin, EV TI Evolution of mosaic operons by horizontal gene transfer and gene displacement in situ SO GENOME BIOLOGY LA English DT Article ID SELFISH OPERONS; COMPLETE GENOMES; PROTEINS; SEQUENCE; PROKARYOTES; BACTERIAL; CLASSIFICATION; ORGANIZATION; EUKARYOTES; ALIGNMENT AB Background: Shuffling and disruption of operons and horizontal gene transfer are major contributions to the new, dynamic view of prokaryotic evolution. Under the 'selfish operon' hypothesis, operons are viewed as mobile genetic entities that are constantly disseminated via horizontal gene transfer, although their retention could be favored by the advantage of coregulation of functionally linked genes. Here we apply comparative genomics and phylogenetic analysis to examine horizontal transfer of entire operons versus displacement of individual genes within operons by horizontally acquired orthologs and independent assembly of the same or similar operons from genes with different phylogenetic affinities. Results: Since a substantial number of operons have been identified experimentally in only a few model bacteria, evolutionarily conserved gene strings were analyzed as surrogates of operons. The phylogenetic affinities within these predicted operons were assessed first by sequence similarity analysis and then by phylogenetic analysis, including statistical tests of tree topology. Numerous cases of apparent horizontal transfer of entire operons were detected. However, it was shown that apparent horizontal transfer of individual genes or arrays of genes within operons is not uncommon either and results in xenologous gene displacement in situ, that is, displacement of an ancestral gene by a horizontally transferred ortholog from a taxonomically distant organism without change of the local gene organization. On rarer occasions, operons might have evolved via independent assembly, in part from horizontally acquired genes. Conclusions: The discovery of in situ gene displacement shows that combination of rampant horizontal gene transfer with selection for preservation of operon structure provides for events in prokaryotic evolution that, a priori, seem improbable. These findings also emphasize that not all aspects of operon evolution are selfish, with operon integrity maintained by purifying selection at the organism level. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 34 TC 83 Z9 86 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 9 AR R55 DI 10.1186/gb-2003-4-9-r55 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 716UR UT WOS:000185048100008 PM 12952534 ER PT J AU Szak, ST Pickeral, OK Landsman, D Boeke, JD AF Szak, ST Pickeral, OK Landsman, D Boeke, JD TI Identifying related L1 retrotransposons by analyzing 3 ' transduced sequences SO GENOME BIOLOGY LA English DT Article ID HUMAN TRANSPOSABLE ELEMENT; REVERSE TRANSCRIPTION; IN-VIVO; LINE-1 RETROTRANSPOSITION; MOBILE ELEMENTS; HUMAN-GENOME; INSERTION; PROTEIN; RNA; TRANSPOSITION AB Background: A large fraction of the human genome is attributable to LI retrotransposon sequences. Not only do LIs themselves make up a significant portion of the genome, but LI-encoded proteins are thought to be responsible for the transposition of other repetitive elements and processed pseudogenes. In addition, LIs can mobilize non-LI, 3'-flanking DNA in a process called 3' transduction. Using computational methods, we collected DNA sequences from the human genome for which we have high confidence of their mobilization through LI-mediated 3' transduction. Results: The precursors of LIs with transduced sequence can often be identified, allowing us to reconstruct LI element families in which a single parent LI element begot many progeny LIs. Of the LIs exhibiting a sequence structure consistent with 3' transduction (LI with transduction-derived sequence, LI-TD), the vast majority were located in duplicated regions of the genome and thus did not necessarily represent unique insertion events. Of the remaining LI-TDs, some lack a clear polyadenylation signal, but the alignment between the parent-progeny sequences nevertheless ends in an A-rich tract of DNA. Conclusions: Sequence data suggest that during the integration into the genome of RNA representing an LI-TD, reverse transcription may be primed internally at A-rich sequences that lie downstream of the LI 3' untranslated region. The occurrence of LI-mediated transduction in the human genome may be less frequent than previously thought, and an accurate estimate is confounded by the frequent occurrence of segmental genomic duplications. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Boeke, JD (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, 725 N Wolfe St, Baltimore, MD 21205 USA. EM jboeke@jhmi.edu RI Landsman, David/C-5923-2009 FU NCI NIH HHS [P01 CA016519, CA16519] NR 54 TC 14 Z9 14 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 5 AR R30 DI 10.1186/gb-2003-4-5-r30 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 675MG UT WOS:000182698600006 PM 12734010 ER PT J AU Zeeberg, BR Feng, WM Wang, G Wang, MD Fojo, AT Sunshine, M Narasimhan, S Kane, DW Reinhold, WC Lababidi, S Bussey, KJ Riss, J Barrett, JC Weinstein, JN AF Zeeberg, BR Feng, WM Wang, G Wang, MD Fojo, AT Sunshine, M Narasimhan, S Kane, DW Reinhold, WC Lababidi, S Bussey, KJ Riss, J Barrett, JC Weinstein, JN TI GoMiner: a resource for biological interpretation of genomic and proteomic data SO GENOME BIOLOGY LA English DT Article ID EXPRESSION AB We have developed GoMiner, a program package that organizes lists of 'interesting' genes ( for example, under- and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. GoMiner provides quantitative and statistical output files and two useful visualizations. The first is a tree-like structure analogous to that in the AmiGO browser and the second is a compact, dynamically interactive 'directed acyclic graph'. Genes displayed in GoMiner are linked to major public bioinformatics resources. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Georgia Inst Technol, Wallace H Coulter Biomed Engn Dept, Atlanta, GA 30332 USA. Emory Univ, Atlanta, GA 30332 USA. Georgia Inst Technol, Dept Comp Sci, Atlanta, GA 30332 USA. Georgia Inst Technol, Dept Chem, Atlanta, GA 30332 USA. SRA Int, Fairfax, VA 22033 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NR 11 TC 816 Z9 842 U1 4 U2 24 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 4 AR R28 DI 10.1186/gb-2003-4-4-r28 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 675LK UT WOS:000182696200010 PM 12702209 ER PT J AU Frazer, KA Elnitski, L Church, DM Dubchak, I Hardison, RC AF Frazer, KA Elnitski, L Church, DM Dubchak, I Hardison, RC TI Cross-species sequence comparisons: A review of methods and available resources SO GENOME RESEARCH LA English DT Review ID GENOMIC DNA; CONSERVED SEQUENCES; MOUSE GENOME; GENE; REGIONS; ALIGNMENTS; PREDICTION; PROGRAMS AB With the availability of whole-genome sequences for an increasing number of species, we are now faced with the challenge of decoding the information contained within these DNA sequences. Comparative analysis of DNA sequences from multiple species at varying evolutionary distances is a powerful approach for identifying coding and functional noncoding sequences, as well as sequences that are unique for a given organism. In this review, we outline the strategy for choosing DNA sequences from different species for comparative analyses and describe the methods used and the resources publicly available for these studies. C1 Perlegan Sci, Mountain View, CA 94043 USA. Penn State Univ, Dept Comp Sci & Engn, University Pk, PA 16802 USA. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Genome Sci Dept, Berkeley, CA 94720 USA. RP Frazer, KA (reprint author), Perlegan Sci, Mountain View, CA 94043 USA. EM kelly_frazer@perlegen.com RI Hardison, Ross/G-1142-2010 OI Hardison, Ross/0000-0003-4084-7516 FU NHGRI NIH HHS [HG02325, F32 HG002325, HG02238, R01 HG002238]; NIDDK NIH HHS [DK27635]; NIGMS NIH HHS [GM-5748202] NR 36 TC 151 Z9 156 U1 3 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2003 VL 13 IS 1 BP 1 EP 12 DI 10.1101/gr.222003 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 638BZ UT WOS:000180550800001 PM 12529301 ER PT J AU Thomas, JW Schueler, MG Summers, TJ Blakesley, RW McDowell, JC Thomas, PJ Idol, JR Maduro, VVB Lee-Lin, SQ Touchman, JW Bouffard, GG Beckstrom-Sternberg, SM Green, ED AF Thomas, JW Schueler, MG Summers, TJ Blakesley, RW McDowell, JC Thomas, PJ Idol, JR Maduro, VVB Lee-Lin, SQ Touchman, JW Bouffard, GG Beckstrom-Sternberg, SM Green, ED CA NISC Comparative Sequencing Progra TI Pericentromeric duplications in the laboratory mouse SO GENOME RESEARCH LA English DT Article ID HUMAN-GENOME; DNA-SEQUENCES; CHROMOSOME 10; EVOLUTION; REGIONS; MAP; HUMAN-CHROMOSOME-19; GENES AB Duplications have long been postulated to be an important mechanism by which genomes evolve. Interspecies genomic comparisons are one method by which the origin and molecular mechanism of duplications can be inferred. By comparative mapping in human, mouse, and rat, we previously found evidence for a recent chromosome-fission event that occurred in the mouse lineage. Cytogenetic mapping revealed that the genomic segments flanking the fission site appeared to be duplicated, with copies residing near the centromere of multiple mouse chromosomes. Here we report the mapping and sequencing of the regions of mouse chromosomes 5 and 6 involved in this chromosome-fission event as well as the results of comparative sequence analysis with the orthologous human and rat genomic regions. Our data indicate that the duplications associated with mouse chromosomes 5 and 6 are recent and that the resulting duplicated segments share significant sequence similarity with a series of regions near the centromeres of the mouse chromosomes previously identified by cytogenetic mapping. We also identified pericentromeric duplicated segments shared between mouse chromosomes 5 and 1. Finally, novel mouse satellite sequences as well as putative chimeric transcripts were found to be associated with the duplicated segments. Together, these findings demonstrate that pericentromeric duplications are not restricted to primates and may be a common mechanism for genome evolution in mammals. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. RP Green, ED (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM egreen@nhgri.nih.gov NR 43 TC 28 Z9 31 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2003 VL 13 IS 1 BP 55 EP 63 DI 10.1101/gr.791403 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 638BZ UT WOS:000180550800006 PM 12529306 ER PT J AU Park, YG Clifford, R Buetow, KH Hunter, KW AF Park, YG Clifford, R Buetow, KH Hunter, KW TI Multiple cross and inbred strain haplotype mapping of complex-trait candidate genes SO GENOME RESEARCH LA English DT Article ID MICE; LOCI AB Identifying complex-trait candidate genes after initial low-resolution mapping has proven to be a difficult and labor-intensive undertaking, usually requiring years to develop and analyze congenic strains. As a result, to date, few complex-trait genes have been discovered. Recently it was suggested that SNP haplotype analysis in inbred strains might be useful for mapping of complex traits. In this study, we have combined medium-resolution haplotype mapping with multiple experimental cross-mapping experiments to reduce the number of potential candidate genes in a complex-trait candidate interval. Coincident mapping of a modifier gene in multiple experimental crosses using different inbred strains is consistent with the common inheritance of a modifier allele. A haplotype map was developed in four inbred strains of mice used in our complex-trait mapping crosses across the proximal 10 cM of proximal Chromosome 19 to identify haplotype blocks that segregate appropriately. Only similar to23 out of >400 genes met this criteria. This strategy coupled with tissue and expression arrays, as well as our recently described common pathway analysis to reduce the number of high-priority candidates, may provide a rapid, efficient method to identify and prioritize complex-trait candidate genes without requiring construction of congenic mouse strains. C1 NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hunter, KW (reprint author), NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 14 TC 56 Z9 58 U1 0 U2 1 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 JAN PY 2003 VL 13 IS 1 BP 118 EP 121 DI 10.1101/gr.786403 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 638BZ UT WOS:000180550800014 PM 12529314 ER PT S AU Hinnebusch, BJ AF Hinnebusch, BJ BE Skurnik, M Bengoechea, JA Granfors, K TI Transmission factors: Yersinia pestis genes required to infect the flea vector of plague SO GENUS YERSINIA: ENTERING THE FUNCTIONAL GENOMIC ERA SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 8th International Symposium on Yersinia CY SEP 04-08, 2002 CL TURKU, FINLAND SP Univ Turku, Turku Microbiol Soc ID PHOSPHOLIPASE-D; MURINE TOXIN; EXPRESSION; VIRULENCE; INCLUDES; MIDGUT; LOCUS C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. NR 22 TC 21 Z9 21 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47759-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 529 BP 55 EP 62 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA BW75U UT WOS:000183072900011 PM 12756729 ER PT J AU Serlin, D AF Serlin, D TI Crippling masculinity - Queerness and disability in US military culture, 1800-1945 SO GLQ-A JOURNAL OF LESBIAN AND GAY STUDIES LA English DT Article C1 Bard Early Coll, New York, NY USA. NIH, Bethesda, MD USA. RP Serlin, D (reprint author), Bard Early Coll, New York, NY USA. NR 89 TC 8 Z9 8 U1 0 U2 2 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1064-2684 J9 GLQ-J LESBIAN GAY ST JI GLQ-J. Lesbian Gay Stud. PY 2003 VL 9 IS 1-2 BP 149 EP 179 DI 10.1215/10642684-9-1-2-149 PG 31 WC Humanities, Multidisciplinary; Social Sciences, Interdisciplinary SC Arts & Humanities - Other Topics; Social Sciences - Other Topics GA 661LM UT WOS:000181892100007 ER PT S AU Lipsky, RH Goldman, D AF Lipsky, RH Goldman, D BE Moghaddam, B Wolf, M TI Genomics and variation of ionotropic glutamate receptors SO GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Glutamate and Disorders of Cognition and Motivation CY APR 13-15, 2003 CL NEW HAVEN, CONNECTICUT SP Acad Sci, Natl Inst Ment Mental, Eli Lilly & Co DE ionotropic glutamate receptor genes; missense variant; genomics; polymorphism ID SINGLE-NUCLEOTIDE POLYMORPHISMS; MEDIAL PREFRONTAL CORTEX; NMDA RECEPTOR; SCHIZOPHRENIA; MICE; GENE; EXPRESSION; RESPONSES; DOPAMINE; COCAINE AB Sequencing of the human, mouse, and rat genomes has enabled a comprehensive informatics approach to gene families. This approach is informative for identification of new members of gene families, for cross-species sequence conservation related to functional conservation, for within-species diversity related to functional variation, and for historical effects of selection. This genome informatics approach also focuses our attention on genes whose genomic locations coincide with linkages to phenotypes. We are identifying ionotropic glutamate receptor (IGR) sequence variation by resequencing technologies, including denaturing high-performance liquid chromoatography (dHPLC), for screening and direct sequencing, and by information mining of public (e.g., dbSNP and ENSEMBL) and private (i.e., Celera Discovery System) sequence databases. Each of the 16 known IGRs is represented in these databases, their positions on a canonical physical map (for example, the Celera map) are established, and comparison to mouse and rat sequences has been performed, revealing substantial conservation of these genes, which are located on different chromosomes but found within syntenic groups of genes. A collection of 38 missense variants were identified by the informatics and resequencing approaches in several of these receptor genes, including GRIN2B, GRIN3B, GRIA2, GRIA3, and GRIK1. This represents only a fraction of the sequence variation across these genes, but, in fact, these may constitute a large fraction of the common polymorphisms at these genes, and these polymorphisms are a starting point for understanding the role of these receptors in neurogenetic variation. Genetically influenced human neurobehavioral phenotypes that are likely to be linked to IGR genetic variants include addictions, anxiety/dysphoria disorders, post-brain injury behavioral disorders, schizophrenia, epilepsy, pain perception, learning, and cognition. Thus, the effects of glutamate receptor variation may be protean, and the task of relating variation to behavior difficult. However, functional variants of (1) catechol-O-methyltransferase, (2) serotonin transporter, and (3) brain-derived neurotrophic factor have recently been linked both to behavioral differences and to intermediate phenotypes, suggesting a pathway by which functional variation at IRS can be tied to an etiologically complex phenotype. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RP Lipsky, RH (reprint author), NIAAA, Neurogenet Lab, NIH, 12420 Parklawn Dr,Suite 451,MSC 8110, Rockville, MD 20852 USA. EM rlipsky@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 NR 33 TC 20 Z9 22 U1 1 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-476-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1003 BP 22 EP 35 DI 10.1196/annals.1300.003 PG 14 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BY31Q UT WOS:000188893500003 PM 14684433 ER PT S AU Krystal, JH Petrakis, IL Krupitsky, E Schutze, C Trevisan, L D'Souza, DC AF Krystal, JH Petrakis, IL Krupitsky, E Schutze, C Trevisan, L D'Souza, DC BE Moghaddam, B Wolf, M TI NMDA receptor antagonism and the ethanol intoxication signal - From alcoholism risk to pharmacotherapy SO GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Glutamate and Disorders of Cognition and Motivation CY APR 13-15, 2003 CL NEW HAVEN, CONNECTICUT SP Acad Sci, Natl Inst Ment Mental, Eli Lilly & Co DE ethanol; alcoholism; alcohol dependence; phenotype; alcoholism vulnerability; pharmacotherapy; glutamate; N-methyl-D-aspartate receptor; ketamine ID GLUTAMATERGIC NEUROTRANSMISSION; ACAMPROSATE; MEN; KETAMINE; DEXTROMETHORPHAN; DEPENDENCE; NALTREXONE; CHALLENGE AB This paper reviews clinical evidence suggesting that antagonism of the N-methyl-D-aspartate subtype of glutamate receptors by ethanol may convey an important component of the ethanol intoxication signal, that is, subjective and objective responses associated with the consumption of a large amount of ethanol. It will then review recent evidence that two phenotypes associated with increased risk for heavy alcohol consumption, recovering ethanol-dependent patients, and healthy individuals with a family history of alcohol dependence, exhibit reduced sensitivity to the dysphoric consequences of administration of the NMDA receptor antagonist, ketamine. Each of these groups displays reduced sensitivity to a potentially important response that might normally trigger the cessation of ethanol consumption. These data raise the possibility that alterations in NMDA receptor function that reduce the response to the NMDA antagonist component of ethanol may increase the risk for heavy drinking. This hypothesis is consistent with growing evidence that NMDA receptor antagonists may play a role in the treatment of alcoholism by suppressing alcohol withdrawal, reducing the development or expression of alcohol tolerance, or preventing or reversing the sensitiziation to ethanol effects. C1 VA Connecticut Healthcare Syst, Alcohol Res Ctr, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. Connecticut Mental Hlth Ctr, NIAAA, Ctr Translat Neurosci Alcholism, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA. St Petersburg State Univ, Dept Pharmacol, St Petersburg, Russia. Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. RP Krystal, JH (reprint author), VA Connecticut Healthcare Syst, Alcohol Res Ctr, 950 Campbell Ave,116-A, West Haven, CT 06516 USA. EM john.krystal@yale.edu FU NIAAA NIH HHS [P50 AA99-005, K02 AA 00261-01, R01 AA11321-01A1] NR 35 TC 80 Z9 80 U1 3 U2 9 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-476-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1003 BP 176 EP 184 DI 10.1196/annals.1300.010 PG 9 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BY31Q UT WOS:000188893500015 PM 14684445 ER PT S AU Lovinger, DM Partridge, JG Tang, KC AF Lovinger, DM Partridge, JG Tang, KC BE Moghaddam, B Wolf, M TI Plastic control of striatal glutamatergic transmission by ensemble actions of several neurotransmitters and targets for drugs of abuse SO GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Glutamate and Disorders of Cognition and Motivation CY APR 13-15, 2003 CL NEW HAVEN, CONNECTICUT SP Acad Sci, Natl Inst Ment Mental, Eli Lilly & Co DE acetylcholine; addiction; basal ganglia; dopamine; habit formation; long-term depression; long-term potentiation; learning and memory; synaptic plasticity ID LONG-TERM DEPRESSION; SPINY STRIATONIGRAL NEURONS; BASAL GANGLIA; CORTICOSTRIATAL SYNAPSES; SYNAPTIC-TRANSMISSION; DORSAL STRIATUM; RAT NEOSTRIATUM; PROJECTION NEURONS; RECEPTOR PROTEINS; NUCLEUS-ACCUMBENS AB Long-lasting alterations in the efficacy of glutamatergic synapses, such as long-term potentiation (LTP) and long-term depression (LTD), are prominent models for mechanisms of information storage in the brain. It has been suggested that exposure to drugs of abuse produces synaptic plasticity at glutamatergic synapses that shares many features with LTP and LTD, and that these synaptic changes may play roles in addiction. We have examined the involvement of particular neurotransmitters in synaptic plasticity at glutamatergic synapses within the striatum, a-brain region with prominent roles in initiation and sequencing of actions, as well as habit formation. Our studies indicate that multiple neurotransmitters interact to produce striatal synaptic plasticity, and that the relative strength and patterning of the afferent inputs that release the various neurotransmitters determines whether UP or LTD is activated. Drugs of abuse interact with glutamatergic synaptic plasticity in multiple ways, including alterations in dopamine release and more direct effects on glutamate release and glutamate receptors. We hypothesize that these effects contribute to addiction by facilitating the formation of new, drug-centered habits, and by disruption of more adaptive behaviors. C1 NIAAA, Lab Integrat Neurosci, Div Intramural Clin & Basic Res, NIH, Rockville, MD 20852 USA. NIAAA, Lab Mol Physiol, Div Intramural Clin & Basic Res, NIH, Rockville, MD 20852 USA. Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA. Univ Calif San Francisco, Dept Neurol, Emeryville, CA 94608 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Div Intramural Clin & Basic Res, NIH, Rockville, MD 20852 USA. EM lovindav@mail.nih.gov NR 70 TC 58 Z9 60 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-476-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1003 BP 226 EP 240 DI 10.1196/annals.1300.014 PG 15 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BY31Q UT WOS:000188893500019 PM 14684449 ER PT S AU Zarate, CA Du, J Quiroz, J Gray, NA Denicoff, KD Singh, J Charney, DS Manji, HK AF Zarate, CA Du, J Quiroz, J Gray, NA Denicoff, KD Singh, J Charney, DS Manji, HK BE Moghaddam, B Wolf, M TI Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders - Role of the glutamatergic system SO GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Glutamate and Disorders of Cognition and Motivation CY APR 13-15, 2003 CL NEW HAVEN, CONNECTICUT SP Acad Sci, Natl Inst Ment Mental, Eli Lilly & Co DE antidepressant; bipolar disorder; depression; glutamate; memantine; mood stabilizer; NMDA/AMPA/kainate; riluzole ID METHYL-D-ASPARTATE; EXCITATORY AMINO-ACIDS; MAJOR DEPRESSIVE DISORDER; NMDA RECEPTOR COMPLEX; TREATMENT-RESISTANT DEPRESSION; ANTERIOR CINGULATE CORTEX; HUMAN FRONTAL-CORTEX; BIPOLAR DISORDER; CORTICAL-NEURONS; VALPROIC ACID AB There is increasing evidence from a variety of sources that mood disorders are associated with regional reductions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamatergic system-which is known to play a major role in neuronal plasticity and cellular resilience-may be involved in the pathophysiology and treatment of mood disorders. Preclinical studies have shown that the glutamatergic system represents targets (often indirect) for the actions of antidepressants and mood stabilizers. There are a number of glutamatergic "plasticity enhancing" strategies that may be of considerable utility in the treatment of mood disorders. Among the most immediate ones are NMDA antagonists, inhibitors of glutamate-release agents, and AMPA potentiators; this research progress holds much promise for the development of novel therapeutics for the treatment of severe, refractory mood disorders. C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Unit 3, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Unit 3, 9000 Rockville Pike,Bldg 10,Room 3S20, Bethesda, MD 20892 USA. EM zaratec@intra.nimh.nih.gov NR 127 TC 117 Z9 121 U1 1 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-476-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1003 BP 273 EP 291 DI 10.1196/annals.1300.017 PG 19 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BY31Q UT WOS:000188893500022 PM 14684452 ER PT S AU Du, J Gray, NA Falke, C Yuan, PX Szabo, S Manji, HK AF Du, J Gray, NA Falke, C Yuan, PX Szabo, S Manji, HK BE Moghaddam, B Wolf, M TI Structurally dissimilar antimanic agents modulate synaptic plasticity by regulating AMPA glutamate receptor subunit GluR1 synaptic expression SO GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Glutamate and Disorders of Cognition and Motivation CY APR 13-15, 2003 CL NEW HAVEN, CONNECTICUT SP Acad Sci, Natl Inst Ment Mental, Eli Lilly & Co DE lithium; valproate; GluR1; mood disorders AB A growing body of data from clinical and preclinical studies suggests that the glutamatergic system may represent a novel therapeutic target for severe recurrent mood disorders. Since synapse-specific glutamate receptor expression/localization is known to play critical roles in synaptic plasticity, we investigated the effects of mood stabilizers on AMPA receptor expression. Rats were treated chronically with lithium or valproate, hippocampal synaptosomes were isolated, and GluR1 levels were determined. Additionally, hippocampal neurons were prepared from E18 rat embryos and treated with lithium or valproate. Surface expression of GluR1 was determined using a biotinylation assay, and double-immunostaining with anti-GluR1 and anti-synaptotagmin antibodies was used to determine synaptic GluR1 levels. The AMPA receptor subunit GluR1 expression in hippocampal synaptosomes was significantly reduced by both chronic lithium and valproate. Overall, these studies show that AMPA receptor subunit GluR1 is a common target for two structurally highly dissimilar, but highly efficacious, mood stabilizers, lithium and valproate. These studies suggest that regulation of glutamatergically mediated synaptic plasticity may play a role in the treatment of mood disorders, and raise the possibility that agents more directly affecting synaptic GluR1 may represent novel therapies for this devastating illness. C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. EM Manjih@intra.nimh.nih.gov NR 3 TC 35 Z9 36 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-476-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1003 BP 378 EP 380 DI 10.1196/annals.1300.031 PG 3 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BY31Q UT WOS:000188893500036 PM 14684466 ER PT S AU Gray, NA Du, J Falke, CS Yuan, PX Manji, HK AF Gray, NA Du, J Falke, CS Yuan, PX Manji, HK BE Moghaddam, B Wolf, M TI Lithium regulates total and synaptic expression of the AMPA glutamate receptor GluR2 in vitro and in vivo SO GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Glutamate and Disorders of Cognition and Motivation CY APR 13-15, 2003 CL NEW HAVEN, CONNECTICUT SP Acad Sci, Natl Inst Ment Mental, Eli Lilly & Co DE lithium; GluR2; bipoloar disorder; expression; localization C1 US Dept HHS, NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), US Dept HHS, NIMH, Mol Pathophysiol Lab, NIH, MSC 4405,Bldg 49,Room B1EE16, Bethesda, MD 20892 USA. EM manjih@intra.nimh.nih.gov NR 1 TC 16 Z9 16 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-476-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1003 BP 402 EP 404 DI 10.1196/annals.1300.036 PG 3 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BY31Q UT WOS:000188893500042 PM 14684472 ER PT S AU Law, AJ Weickert, CS Webster, MJ Herman, MM Kleinman, JE Harrison, PJ AF Law, AJ Weickert, CS Webster, MJ Herman, MM Kleinman, JE Harrison, PJ BE Moghaddam, B Wolf, M TI Changes in NMDA receptor subunit mRNAs and cyclophilin mRNA during development of the human hippocampus SO GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Glutamate and Disorders of Cognition and Motivation CY APR 13-15, 2003 CL NEW HAVEN, CONNECTICUT SP Acad Sci, Natl Inst Ment Mental, Eli Lilly & Co DE glutamate receptor; cyclophilin; neonate; hippocampus; in situ hybridization; ontogeny ID RAT-BRAIN; EXPRESSION C1 Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England. NIMH, Clin Brain Disorders, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Stanley Lab Brain Res, Bethesda, MD 20814 USA. RP Law, AJ (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Neurosci Bldg, Oxford OX3 7JX, England. EM amanda.law@psych.ox.ac.uk RI Shannon Weickert, Cynthia/G-3171-2011; OI Law, Amanda/0000-0002-2574-1564 NR 3 TC 11 Z9 11 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-476-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1003 BP 426 EP 430 DI 10.1196/annals.1300.043 PG 5 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BY31Q UT WOS:000188893500049 PM 14684479 ER PT J AU Ten Hagen, KG Fritz, TA Tabak, LA AF Ten Hagen, KG Fritz, TA Tabak, LA TI All in the family: the UDP-GalNAc : polypeptide N-acetylgalactosaminyltransferases SO GLYCOBIOLOGY LA English DT Review DE O-glycosylation/O-linked oligosaccharides; UDP GalNAc : polypeptide N-acetylgalactosaminyltransferases; UDP GalNAc ID ACETYL-D-GALACTOSAMINE; ALPHA-D-GALACTOSAMINE; O-GLYCOSYLATION SITES; MUCIN MOTIF PEPTIDES; AMINO-ACID-SEQUENCE; CONSECUTIVE THREONINE RESIDUES; HAMSTER OVARY CELLS; TANDEM REPEAT UNIT; IN-VIVO; IGA NEPHROPATHY AB Mucin-type linkages (GalNAcalpha1-O-Ser/Thr) are initiated by a family of glycosyltransferases known as the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyl-transferases (ppGaNTases, EC 2.4.1.41). These enzymes transfer GalNAc from the sugar donor UDP-GalNAc to serine and threonine residues, forming an alpha anomeric linkage. Despite the seeming simplicity of ppGaNTase catalytic function, it is estimated on the basis of in silico analysis that there are 24 unique ppGaNTase human genes. ppGaNTase isoforms display tissue-specific expression in adult mammals as well as unique spatial and temporal patterns of expression during murine development. In vitro assays suggest that a subset of the ppGaNTases have overlapping substrate specificities, but at least two ppGaNTases (ppGaNTase-T7 and -T9 [now designated -T10]) appear to require the prior addition of GalNAc to a synthetic peptide before they can catalyze sugar transfer to this substrate. Site-specific O-glycosylation by several ppGaNTases is influenced by the position and structure of previously added O-glycans. Collectively, these observations argue in favor of a hierarchical addition of core GalNAc residues to the apomucin. Various forms of O-glycan pathobiology may be reexamined in light of the existence of an extensive ppGaNTase family of enzymes. Recent work has demonstrated that at least one ppGaNTase isoform is required for normal development in Drosophila melanogaster. Structural insights will no doubt lead to the development of isoform-specific inhibitors. Such tools will prove valuable to furthering our understanding of the functional roles played by O-glycans. C1 NIDDKD, Biol Chem Sect, NIH, Bethesda, MD 20892 USA. RP Tabak, LA (reprint author), NIDDKD, Biol Chem Sect, NIH, Bethesda, MD 20892 USA. NR 163 TC 202 Z9 205 U1 1 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD JAN PY 2003 VL 13 IS 1 BP 1R EP 16R DI 10.1093/glycob/cwg007 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653UC UT WOS:000181454600002 PM 12634319 ER PT J AU Viard, M Parolini, I Rawat, SS Fecchi, K Sargiacomo, M Puri, A Blumenthal, R AF Viard, M Parolini, I Rawat, SS Fecchi, K Sargiacomo, M Puri, A Blumenthal, R TI The role of glycosphingolipids in HIV signaling, entry and pathogenesis SO GLYCOCONJUGATE JOURNAL LA English DT Article DE HIV infection; glycosphingolipids; PPMP; membrane fusion; membrane rafts; transcytosis; CD4; chemokine receptors; signal transduction; HIV pathogenesis; cytoskeleton ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-TYROSINE KINASE; CELL-SURFACE GLYCOSPHINGOLIPIDS; CHEMOKINE RECEPTOR 5; CD4(+) T-CELLS; SRC HOMOLOGY 2; LIPID RAFTS; ENVELOPE GLYCOPROTEIN; GANGLIOSIDE GM3; MEMBRANE MICRODOMAINS AB Although HIV uses CD4 and coreceptors (CCR5 and CXCR4) for productive infection of T cells, glycosphingolipids (GSL) may play ancillary roles in lymphoid and non-lymphoid cells. Interactions of the HIV Envelope Glycoprotein (Env) with GSL may help HIV in various steps of its pathogenesis. Physical-chemical aspects of the interactions between HIV Env and GSL leading to CD4-dependent entry into lymphocytes, the role of GSL in HIV transcytosis, and CD4-independent entry into non-lymphoid cells are reviewed. An overview of signaling properties of HIV receptors is provided with some speculation on how GSL may play a role in these events by virtue of being in membrane rafts. Finally, we summarize how interactions between HIV and coreceptors leading to signaling and/or fusion can be analyzed by the use of various tyrosine kinase and cytoskeletal inhibitors. Published in 2004. C1 NCI Frederick, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Frederick, MD 21701 USA. Ist Super Sanita, I-00161 Rome, Italy. RP Blumenthal, R (reprint author), NCI Frederick, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Frederick, MD 21701 USA. EM blumen@helix.nih.gov RI parolini, Isabella/J-9955-2016 NR 89 TC 1 Z9 1 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PY 2003 VL 20 IS 3 BP 213 EP 222 DI 10.1023/B:GLYC.0000024253.48791.d9 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 812WI UT WOS:000220869200009 ER PT J AU Spechler, S Nieman, LK Premkumar, A Stratton, P AF Spechler, S Nieman, LK Premkumar, A Stratton, P TI The Keeper((R)), a menstrual collection device, as a potential cause of endometriosis and adenomyosis SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION LA English DT Article DE Keeper((R)); menstrual collection device; endometriosis; adenomyosis ID RISK AB Barrier contraceptive devices like the cervical cap and diaphragm and menstrual collecting devices may block menstrual flow, increase retrograde menstruation, and thus theoretically increase the likelihood of developing endometriosis or adenomyosis. We describe the case of a woman with a prior tubal ligation who after 4 years of regular use of the Keeper((R)), a menstrual collecting device, developed adenomyosis and endometriosis. Copyright (C) 2003 S. Karger AG, Basel. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), Gynecol Consult Serv, 10 Ctr Dr,MSC 1583,Bldg 10,Room 9D42, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 2 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-7346 J9 GYNECOL OBSTET INVES JI Gynecol.Obstet.Invest. PY 2003 VL 56 IS 1 BP 35 EP 37 DI 10.1159/000072329 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 719JN UT WOS:000185200000008 PM 12867766 ER PT J AU Menczer, J Chetrit, A Barda, G Lubin, F Fishler, Y Altaras, M Levavi, H Struewing, JP Sadetzki, S Modan, B AF Menczer, J Chetrit, A Barda, G Lubin, F Fishler, Y Altaras, M Levavi, H Struewing, JP Sadetzki, S Modan, B TI Frequency of BRCA mutations in primary peritoneal carcinoma in Israeli Jewish women SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian carcinoma; primary peritoneal carcinoma; BRCA1,2 mutations ID PAPILLARY SEROUS CARCINOMA; FAMILIAL-OVARIAN-CANCER; X-CHROMOSOME INACTIVATION; UNIFOCAL ORIGIN; PROPHYLACTIC OOPHORECTOMY; MOLECULAR EVIDENCE; ASHKENAZI; BREAST AB Objective. The aim of the present study was to compare demographic and clinical characteristics of primary peritoneal carcinoma (PPC) to ovarian carcinoma (OvC) with regard to BRCA mutation frequencies. Methods. Incident cases of histologically confirmed cancer of the ovary or peritoneum diagnosed in Israeli Jewish women between March 1, 1994, and June 30, 1999, were identified within the framework of an ongoing nationwide epidemiological study of these neoplasms in Israel. The present study comprises 609 (81.5%, of 747) Jewish women with epithelial stage III-IV OvC and 68 (77.3% of 88) Jewish women with PPC who were genetically tested for the BRCA mutations. Data from each patient were collected by the aid of a prestructured questionnaire and medical records. Blood samples or tumor tissue was tested for the 185deLAG and 5382insC mutations in BRCA1 and the 6174delT mutations in BRCA2. Results. A carrier rate of 28% of any BRCA 1/2 mutation was observed among the PPC group and of 30% among the invasive stage III-IV OvC. No differences were found between PPC and OvC neither in the overall distribution of BRCA1/2 mutation carrier rates nor according to type of mutation, age, ethnic origin, and histologic subtype. Among women with a positive family history, a higher rate of mutation carriers was observed in the PPC group compared to the OvC group (72.7 vs 43.8%, respectively, P = 0.07). Conclusions. The similar frequency distribution of BRCA1/2 mutations in PPC and OvC observed in the present study indicates that these mutations may predispose to PPC as well and that this neoplasm is part of the hereditary breast-ovarian cancer syndrome. (C) 2002 Elsevier Scicrice (USA). C1 E Wolfson Med Ctr, Dept Gynecol & Obstet, Gynecol Oncol Unit, Holon, Israel. Chaim Sheba Med Ctr, Inst Epidemiol & Hlth Policy Res, Canc Epidemiol Unit, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Ctr Hlth Policy, IL-52621 Tel Hashomer, Israel. Sapir Med Ctr, Dept Obstet & Gynecol, Gynecol Oncol Unit, Kefar Sava, Israel. Rabin Med Ctr, Dept Obstet & Gynecol, Gynecol Oncol Unit, Petah Tiqwa, Israel. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Menczer, J (reprint author), E Wolfson Med Ctr, Dept Gynecol & Obstet, Gynecol Oncol Unit, Holon, Israel. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 25 TC 18 Z9 20 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP 58 EP 61 DI 10.1006/gyno.2002.6853 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 629QQ UT WOS:000180060700011 PM 12504628 ER PT J AU Balkwill, F Schlom, J Berek, J Epenetos, A Bookman, M Freedman, R Wilbanks, G AF Balkwill, F Schlom, J Berek, J Epenetos, A Bookman, M Freedman, R Wilbanks, G TI Discussion: Immunological therapeutics in ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN C1 Imperial Canc Res Fund, Translat Oncol Lab, John Vane Sci Ctr, London, England. London Queen Marys Med Sch, London, England. NCI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ S Florida, Tampa, FL 33620 USA. RP Balkwill, F (reprint author), Imperial Canc Res Fund, Translat Oncol Lab, John Vane Sci Ctr, London, England. NR 0 TC 3 Z9 3 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S110 EP S113 DI 10.1002/gyno.2002.6696 PN 2 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000025 ER PT J AU Hodge, JW Tsang, KY Poole, DJ Schlom, J AF Hodge, JW Tsang, KY Poole, DJ Schlom, J TI General keynote: Vaccine strategies for the therapy of ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN ID HUMAN CARCINOEMBRYONIC ANTIGEN; COLONY-STIMULATING FACTOR; T-CELL RESPONSES; RECOMBINANT ANTICANCER VACCINES; VECTOR-DRIVEN HYPEREXPRESSION; COSTIMULATORY MOLECULE B7; PULSED DENDRITIC CELLS; REGIONAL LYMPH-NODES; ANTITUMOR IMMUNITY; PRESENTING CELLS C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Hodge, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 91 TC 8 Z9 10 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S97 EP S104 DI 10.1006/gyno.2002.6694 PN 2 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000023 PM 12586096 ER PT J AU Jones, MB Spooner, M Kohn, EC AF Jones, MB Spooner, M Kohn, EC TI The granulin-epithelin precursor: a putative new growth factor for ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN ID FACTOR-BETA; CELL-LINE; GRANULIN/EPITHELIN PRECURSOR; FACTOR PCDGF; CARCINOMA; CDNA; GENE; EXPRESSION; RECEPTOR; IDENTIFICATION C1 Mayo Clin, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. RP Jones, MB (reprint author), Mayo Clin, Rochester, MN USA. NR 31 TC 29 Z9 31 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S136 EP S139 DI 10.1006/gyno.2002.6704 PN 2 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000032 PM 12586105 ER PT J AU Karlan, BY Boyd, J Strong, L Fountain, J Beller, U AF Karlan, BY Boyd, J Strong, L Fountain, J Beller, U TI Discussion: Hereditary ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Ctr, Boston, MA USA. NCI, Bethesda, MD 20892 USA. Shaare Zedek Med Ctr, Jerusalem, Israel. RP Karlan, BY (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 3 Z9 3 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S11 EP S13 DI 10.1006/gyno.2002.6675 PN 2 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000004 ER PT J AU Kohn, EC Fidler, IJ Fishman, D Jaffe, R Liotta, LA Van Trappen, P Mills, GB Trope, C AF Kohn, EC Fidler, IJ Fishman, D Jaffe, R Liotta, LA Van Trappen, P Mills, GB Trope, C TI Discussion: Metastasis and angiogenesis in epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN ID ENDOTHELIAL GROWTH-FACTOR; LYMPH-NODE METASTASIS; TUMOR ANGIOGENESIS; FACTOR EXPRESSION; BREAST CANCERS; FACTOR-C; CELLS; VEGF; CARCINOMA; PROMOTES C1 NCI, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Northwestern Univ, Evanston, IL 60208 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. St Bartholomews Hosp, London, England. Norwegian Radium Hosp, Oslo, Norway. RP Kohn, EC (reprint author), NCI, Bethesda, MD 20892 USA. NR 39 TC 1 Z9 2 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S37 EP S42 DI 10.1006/gyno.2002.6681 PN 2 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000010 ER PT J AU Kramer, BS AF Kramer, BS TI General keynote: Cancer screening: Translation of principles into practice SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN ID LUNG-CANCER; PROSTATE-CANCER C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Off Dis Prevent, Bethesda, MD USA. RP Kramer, BS (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 15 TC 3 Z9 3 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S71 EP S74 DI 10.1006/gyno.2002.6688 PN 2 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000017 PM 12586090 ER PT J AU Liotta, LA Petricoin, EF Ardekani, AM Hitt, BA Levine, PJ Fusaro, VA Steinberg, SM Mills, GB Simone, C Fishman, DA Kohn, EC AF Liotta, LA Petricoin, EF Ardekani, AM Hitt, BA Levine, PJ Fusaro, VA Steinberg, SM Mills, GB Simone, C Fishman, DA Kohn, EC TI General keynote: Proteomic patterns in sera serve as biomarkers of ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN C1 US FDA, NCI, Clin Proteom Program, Rockville, MD 20857 USA. NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Northwestern Univ, Sch Med, Evanston, IL 60208 USA. RP Liotta, LA (reprint author), US FDA, NCI, Clin Proteom Program, Rockville, MD 20857 USA. NR 7 TC 20 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S25 EP S28 DI 10.1006/gyno.2002.6679 PN 2 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000008 PM 12586081 ER PT J AU Mills, GB Fang, XJ Lu, YL Hasegawa, Y Eder, A Tanyi, J Tabassam, FH Mao, ML Wang, HW Cheng, KW Nakayama, Y Kuo, WL Erickson, J Gershenson, D Kohn, EC Jaffe, R Bast, RC Gray, J AF Mills, GB Fang, XJ Lu, YL Hasegawa, Y Eder, A Tanyi, J Tabassam, FH Mao, ML Wang, HW Cheng, KW Nakayama, Y Kuo, WL Erickson, J Gershenson, D Kohn, EC Jaffe, R Bast, RC Gray, J TI Specific keynote: Molecular therapeutics in ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN ID GROWTH-FACTOR RECEPTOR; CANDIDATE TUMOR-SUPPRESSOR; CHRONIC MYELOID-LEUKEMIA; LYSOPHOSPHATIDIC ACID; GERMLINE MUTATIONS; TYROSINE KINASE; IN-VITRO; CLINICAL-TRIALS; COWDEN-DISEASE; GENE C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. AGY Biotechnol, San Francisco, CA USA. RP Mills, GB (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 61 TC 12 Z9 15 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S88 EP S92 DI 10.1006/gyno.2002.6692 PN 2 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000021 PM 12586094 ER PT J AU Trimble, E Berry, D Gore, M Kavanagh, J Cohen, C Pecorelli, S Creasman, W Mason, P Heinz, P AF Trimble, E Berry, D Gore, M Kavanagh, J Cohen, C Pecorelli, S Creasman, W Mason, P Heinz, P TI Discussion: Crrent issues in the design of ovarian cancer treatment trials SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN C1 NCI, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Royal Marsden Hosp, London SW3 6JJ, England. European Inst Oncol, Florence, Italy. Med Univ S Carolina, Charleston, SC 29425 USA. St Marys Hosp, London, England. Univ Utrecht, NL-3508 TC Utrecht, Netherlands. RP Kavanagh, J (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S122 EP S123 DI 10.1006/gyno.2002.6699 PN 2 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000028 ER PT J AU Kreps, GL AF Kreps, GL TI The impact of communication on cancer risk, incidence, morbidity, mortality, and quality of life SO HEALTH COMMUNICATION LA English DT Article ID INTERVENTION RESEARCH; RANDOMIZED TRIAL; VEGETABLE INTAKE; BREAST-CANCER; BAD-NEWS; CARE; PHYSICIANS; PATIENT; WOMEN; MAMMOGRAPHY AB Health communication has great potential to help reduce cancer risks, incidence, Morbidity, and mortality while enhancing quality of life across the continuum of cancer care (prevention, detection, diagnosis, treatment, survivorship, and end-of-life care). Effective health communication can encourage cancer prevention, inform cancer detection and diagnosis, guide cancer treatment, support successful cancer survivorship, and promote the best end-of-life care. This article examines the influences of, health communication in confronting cancer and promoting important health outcomes. Implications of this analysis are drawn for directing informed cancer communication research and practice. C1 NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Commun & Informat Res Branch,NIH, Bethesda, MD 20892 USA. RP Kreps, GL (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Commun & Informat Res Branch,NIH, Bethesda, MD 20892 USA. NR 56 TC 19 Z9 21 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1041-0236 J9 HEALTH COMMUN JI Health Commun. PY 2003 VL 15 IS 2 BP 161 EP 169 DI 10.1207/S15327027HC1502_4 PG 9 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 667JL UT WOS:000182228400004 PM 12742767 ER PT J AU Szymko-Bennett, YM Kurima, K Olsen, B Seegmiller, R Griffith, AJ AF Szymko-Bennett, YM Kurima, K Olsen, B Seegmiller, R Griffith, AJ TI Auditory function associated with Col11a1 haploinsufficiency in chondrodysplasia (cho) mice SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT Midwinter Research Meeting of the Association-for-Research-in-Otolaryngology CY FEB 04-08, 2001 CL ST PETERSBURG, FLORIDA SP Assoc Res Otolaryngol DE genetic; hearing; deafness; Stickler; Marshall; collagen ID STICKLER-SYNDROME; HEARING-LOSS; MARSHALL-SYNDROME; INBRED STRAINS; GENE; COLLAGEN; MUTATIONS; DEFECT; LOCUS AB Heterozygosity for mutations in the fibrillar collagen gene COLIIAl causes sensorineural hearing loss in patients with Stickler syndrome or Marshall syndrome. Chondrodysplasia (cho) is a functional null allele of ColIIal that causes lethal chondrodysplasia in cholcho newborn mice, and osteoarthritis in chol+ heterozygotes. To determine if Col11al haploinsufficiency causes hearing loss in chol+ mice, auditory brainstem response (ABR) thresholds were measured at 2, 4, 6 8 and 10 months of age. There was no difference in ABR thresholds for click and tone burst stimuli between chol+ and +/+ mice at all ages. In contrast to the conclusion of a previous report, our results indicate that Col11al haploinsufficiency does not cause significant hearing loss on the C5713L/6 strain background. We conclude that Stickler syndrome and Marshall syndrome mutations in COL11Al cause hearing loss via dominant negative effects upon wild-type fibrillar collagen polypeptides in the extracellular matrices of the cochlea. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Natl Inst Deafness & Other Commun Disorders, Hearing Sect, NIH, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Sect Gene Structure & Funct, NIH, Rockville, MD 20850 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Brigham Young Univ, Dept Zool, Provo, UT 84602 USA. RP Griffith, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Hearing Sect, NIH, 5 Res Court, Rockville, MD 20850 USA. FU NIDCD NIH HHS [Z01 DC 000060-01] NR 23 TC 14 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JAN PY 2003 VL 175 IS 1-2 BP 178 EP 182 AR PII S0378-5955(02)00736-0 DI 10.1016/S0378-5955(02)00736-0 PG 5 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 638JF UT WOS:000180567300017 PM 12527136 ER PT B AU Kruth, HS Huang, W Ishii, I Zhang, WY Zhao, B AF Kruth, HS Huang, W Ishii, I Zhang, WY Zhao, B BE Kimchi, A TI How macrophages get fat SO HEART DISEASE: PATHOGENESIS, DIAGNOSIS AND TREATMENT LA English DT Proceedings Paper CT 3rd World Congress on Heart Disease CY JUL 12-15, 2003 CL Washington, DC SP Int Acad Cardiol ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; HUMAN ATHEROSCLEROTIC LESIONS; MOUSE PERITONEAL-MACROPHAGES; TISSUE FACTOR EXPRESSION; FOAM CELL-FORMATION; CULTURED-CELLS; CHOLESTEROL; RECEPTOR; METABOLISM AB Low-density lipoprotein (LDL) is believed to be the main source of cholesterol that accumulates in monocyte-derived macrophages within atherosclerotic plaques converting these macrophages into enlarged foam cells. Previously, only modified but not native LDL has been shown to produce macrophage cholesterol accumulation. We have found that activation of human monocyte-derived macrophages with phorbol 12-myristate 13-acetate (PMA) stimulates native LDL uptake and degradation, and acyl-CoA: cholesterol acyltransferase (ACAT)-mediated esterification of LDL-derived cholesterol, resulting in massive macrophage cholesterol accumulation. The mechanism of LDL uptake by these macrophages is PMA-stimulated endocytosis of LDL taken up as part of the bulk-phase fluid (i.e., fluid-phase endocytosis). This novel mechanism of macrophage cholesterol accumulation shows that modification of LDL is not necessary for foam cell formation to occur. In addition, the findings direct attention to macrophage fluid-phase endocytosis as a relevant pathway to target for modulating macrophage cholesterol accumulation in atherosclerosis. C1 NHLBI, Sect Expt Atherosclerosis, DHHS, NIH, Bethesda, MD 20892 USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, DHHS, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 26 TC 0 Z9 0 U1 0 U2 1 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-004-7 PY 2003 BP 169 EP 176 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BBE82 UT WOS:000225160700026 ER PT B AU Goldstein, D AF Goldstein, D BE Kimchi, A TI Sympathoadrenal imbalance before neurocardiogenic syncope SO HEART DISEASE: PATHOGENESIS, DIAGNOSIS AND TREATMENT LA English DT Proceedings Paper CT 3rd World Congress on Heart Disease CY JUL 12-15, 2003 CL Washington, DC SP Int Acad Cardiol ID NEURALLY-MEDIATED SYNCOPE; VASOVAGAL SYNCOPE AB Neurocardiogenic syncope is the most common cause of acute loss of consciousness. Of 12 patients with tilt-induced syncope who had blood sampled before loss of consciousness, all 12 had markedly increased plasma epinephrine levels (mean 11 times baseline, p<0.001). Simultaneously obtained norepinephrine levels were unchanged or increased less than did epinephrine levels ("sympathoadrenal imbalance"). The proportionate decrease in forearm vascular resistance correlated with that of the increase in the the epinephrine: norepinephrine ratio (r=0.75, p<0.001). Adrenomedullary stimulation and relative sympathoinhibition precedes and may contribute to precipitation of neurocardiogenic syncope. C1 NIH, Clin Neurocardiol Sect, Natl Inst Neruol Disorders & Stroke, Bethesda, MD 20892 USA. RP Goldstein, D (reprint author), NIH, Clin Neurocardiol Sect, Natl Inst Neruol Disorders & Stroke, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-004-7 PY 2003 BP 405 EP 408 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BBE82 UT WOS:000225160700060 ER PT J AU Linders, JTM Mirsadeghi, S Flippen-Anderson, JL George, C Jacobson, AE Rice, KC AF Linders, JTM Mirsadeghi, S Flippen-Anderson, JL George, C Jacobson, AE Rice, KC TI Probes for narcotic receptor mediated phenomena - Synthesis of rac-(3R,6aS,11aR)-1,3,4,5,6,11a-hexahydro-2-methyl-2H-3,6a-methanobenzof uro[2,3-c]azocin-8-ol, an epoxy isomer of 5-phenylmorphan SO HELVETICA CHIMICA ACTA LA English DT Article ID ANTAGONISTS; PARKINSONISM AB The synthesis of a series of epoxy 5-phenylmorphans is being explored in order to determine the conformational requirements of the phenolic ring in a phenylmorphan Molecule that may be needed both for binding to a specific opioid receptor and for exhibiting opioid agonist or antagonist activity. Of the twelve possible ortho- and para-bridged isomers (a-f) (Fig. 1). we now report the synthesis of the para-d isomer, rac-(3R,6aS,11aR)-2-methyl-1,3,4,5,6,11 a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocin-8-ol (3). Compound 3 was synthesized via construction of the 5-phenylazabicyclo[3.3.1]non-3-ene skeleton (Scheme 1) and subsequent closure of the epoxy bridge (Scheme 2). As determined by an X-ray diffraction study, the epoxy bridge, restricting the phenyl-ring rotation, fixed the dihedral angle between the least-squares planes through the phenyl ring and atoms N(2), C(3), C(11a), and C(6a) of the piperidine ring (Fig. 2) at 43.0degrees, and the torsion angle C(12)-C(6a)-C(6b)-C(10a) at -95.0degrees. C1 NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, NIH, Bldg 8,Room B1-23, Bethesda, MD 20892 USA. EM kr21f@nih.gov NR 27 TC 15 Z9 15 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0018-019X J9 HELV CHIM ACTA JI Helv. Chim. Acta PY 2003 VL 86 IS 2 BP 484 EP 493 DI 10.1002/hlca.200390048 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 655UP UT WOS:000181571300023 ER PT S AU Schmidt, M Glimm, H Wissler, M Hoffmann, G Olsson, K Sellers, S Carbonaro, D Tisdale, JF Leurs, C Hanenberg, H Dunbar, CE Kiem, HP Karlsson, S Kohn, DB Williams, D von Kalle, C AF Schmidt, M Glimm, H Wissler, M Hoffmann, G Olsson, K Sellers, S Carbonaro, D Tisdale, JF Leurs, C Hanenberg, H Dunbar, CE Kiem, HP Karlsson, S Kohn, DB Williams, D von Kalle, C BE Orlic, D Brummendorf, TH Fibbe, W Sharkis, S Kanz, L TI Efficient characterization of retro-, lenti-, and foamyvector-transduced cell populations by high-accuracy insertion site sequencing SO HEMATOPOIETIC STEM CELLS 2002: GENETICS AND FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Symposium on Hematopoietic Stem Cells CY SEP 19-21, 2002 CL UNIV TUBINGEN, TUBINGEN, GERMANY SP Amgen Europe, Kirin Japan HO UNIV TUBINGEN DE investigative techniques; insertion sequence elements; stem cells; gene therapy; proviruses ID SEVERE COMBINED IMMUNODEFICIENCY; HEMATOPOIETIC STEM-CELLS; LIGATION MEDIATED PCR; UMBILICAL-CORD BLOOD; VIVO GENE DELIVERY; PROGENITOR CELLS; FLANKING DNA; VECTOR; THERAPY; ENGRAFTMENT AB The identification of unknown genomic flanking DNA sequences can be used for the molecular monitoring of retro-, lenti- and foamyviral integration, transgenes in early embryogenesis, insertional mutagenesis, cell fate, and stem cell plasticity. Most existing methods reflect shortcomings in sensitivity and or specificity, thus limiting genomic sequencing of unknown flanking DNA to clonal preparations. The application of linear amplification-mediated PCR (LAM-PCR), a recently developed direct sequencing technique for flanking DNA, should circumvent current limitations in different research fields. This technique combines preamplification of target DNA with a unique succession of enzymatic reactions on solid-phase. Using LAM-PCR, we show the previously unfeasible in vivo retro-, lenti- and foamyvirus integration site analysis in primate peripheral blood hematopoietic cells and human xenograft hematopoiesis. In light of two severe adverse events that occurred in a clinical SCID-X1 gene therapy trial, in vivo monitoring of the reinfused transduced cell pool by integration site analysis will be an important component of each gene transfer and therapy study aimed at clinical use. C1 Univ Freiburg, Inst Mol Med & Cell Res, D-79106 Freiburg, Germany. Univ Freiburg, Dept Internal Med 1, D-79106 Freiburg, Germany. Lund Univ, Dept Mol Med & Gene Therapy, S-22184 Lund, Sweden. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Div Pediat Hematol & Oncol, Childrens Hlth Ctr, D-40225 Dusseldorf, Germany. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Childrens Hosp Los Angeles, Div Immunol Res, BMT, Los Angeles, CA 90029 USA. Univ So Calif, Dept Pediat, Keck Sch Med, Los Angeles, CA 90029 USA. Univ So Calif, Dept Microbiol, Keck Sch Med, Los Angeles, CA 90029 USA. Childrens Hosp Res Fdn, Div Expt Hematol, Cincinnati, OH 45229 USA. RP von Kalle, C (reprint author), Univ Freiburg, Inst Mol Med & Cell Res, Hugstetter Str 55, D-79106 Freiburg, Germany. RI Kohn, Donald/N-5085-2016 OI Kohn, Donald/0000-0003-1840-6087 NR 37 TC 16 Z9 17 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-466-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 996 BP 112 EP 121 PG 10 WC Cell Biology; Hematology; Multidisciplinary Sciences SC Cell Biology; Hematology; Science & Technology - Other Topics GA BW93G UT WOS:000183697800014 PM 12799289 ER PT S AU Orlic, D AF Orlic, D BE Orlic, D Brummendorf, TH Fibbe, W Sharkis, S Kanz, L TI Adult bone marrow stem cells regenerate myocardium in ischemic heart disease SO HEMATOPOIETIC STEM CELLS 2002: GENETICS AND FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Symposium on Hematopoietic Stem Cells CY SEP 19-21, 2002 CL UNIV TUBINGEN, TUBINGEN, GERMANY SP Amgen Europe, Kirin Japan HO UNIV TUBINGEN DE stem cells; myocardium; infarction; cytokines; plasticity ID INFARCTED MYOCARDIUM; IN-VIVO; TRANSPLANTATION; NEOVASCULARIZATION; PURIFICATION; PROGENITORS; EXPRESSION; HUMANS; REPAIR; FUSION AB Recent studies have demonstrated the existence of several populations of primitive cells in mouse and human bone marrow that have the capacity, both in vitro and in vivo, to give rise to cells of all three germ layers. Mesenchymal/stromal stem cells and hematopoietic stem cells are the leading candidates for this activity that some believe may recapitulate the potential of embryonic stem cells. Very little is known about the molecular controls for this adult stem cell activity commonly referred to as transdifferentiation or plasticity. Regeneration of a large number of cell types and tissues has been investigated with one of the most extensively studied being the myocardium. These studies involved ligation of the left coronary artery in adult mice and the direct injection or mobilization of bone marrow stem cells. Using this protocol we, and others, have observed the generation of new cardiomyocytes and endothelial cells in the zone of ischemic myocardium. This approach has progressed to clinical trials at several academic institutions. Although the preliminary findings from these trials do not permit unequivocal conclusions, they do suggest that safety and feasibility are not significant problems that would argue against extending these trials in a large, randomized, double-blinded study. When considerations such as these are addressed, cell therapy may become a new modality in the treatment of heart patients. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Orlic, D (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. NR 32 TC 77 Z9 96 U1 0 U2 8 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-466-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 996 BP 152 EP 157 PG 6 WC Cell Biology; Hematology; Multidisciplinary Sciences SC Cell Biology; Hematology; Science & Technology - Other Topics GA BW93G UT WOS:000183697800018 PM 12799293 ER PT J AU Qiao, M Murata, K Davis, AR Jeong, SH Liang, TJ AF Qiao, M Murata, K Davis, AR Jeong, SH Liang, TJ TI Hepatitis C virus-like particles combined with novel adjuvant systems enhance virus-specific immune responses SO HEPATOLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSE; STRUCTURAL PROTEINS; VIRAL CLEARANCE; CELL RESPONSE; INSECT CELLS; INFECTION; VACCINE; PROTECTION; MICE; IMMUNIZATION AB We have previously described the generation of hepatitis C virus-like particles (HCV-LPs) in insect cells and shown that immunization with HCV-LPs elicited both humoral and cellular immune responses in mice. To further characterize the HCV-LPs as a vaccine candidate, we evaluated the effects of adjuvant AS01B (monophosphoryl lipid A [MPL] and QS21), CpG 10105, and the combination of the 2 adjuvants on the immunogenicity of HCV-LPs in AAD mice (transgenic for HLA-A2.1). All HCV-LP-immunized mice (with or without adjuvant) developed high titers of anti-HCV E1/E2 antibodies after 4 injections intramuscularly. However, antibody titers in mice immunized with HCV-LP plus AS01B, plus CpG 10 105, or plus the combination of AS01B and CpG 10 105 were 4, 3, and 10 times higher, respectively, than that of HCV-LP alone. Isotype analysis of the induced anti-envelope antibodies showed that HCV-LP alone induced a predominant immunoglobulin (Ig) G1 response. In contrast, when the 2 adjuvants AS01B and CpG 10105 were combined, the response became predominantly IgG2a whereas HCV-LP plus AS01B or CpG 10105 gave a mixed IgG1 and IgG2a response, indicating that AS01B and CpG 10105 promote a more T-helper type 1 (Th1) response and that combining the 2 adjuvants results in an additive or synergistic interaction. These observations were further confirmed by the results of CD4(+) enzyme-linked immunospot assay for interferon (IFN)-gamma and interleukin (IL)-4 and intracellular cytokine staining of IFN-gamma producing CD8(+) cells. In conclusion, HCV-LP is a promising vaccine candidate against HCV infection and the adjuvants used arc potent immune enhancers for this approach. C1 NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDKD, Liver Dis Sect, NIH, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. RI Jeong, Sook-Hyang/D-5726-2012; Jeong, Sook-Hyang/J-5642-2012 NR 41 TC 34 Z9 37 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2003 VL 37 IS 1 BP 52 EP 59 DI 10.1053/jhep.2003.50000 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 630FU UT WOS:000180097500010 PM 12500188 ER PT J AU Zhu, XX Yu, QS Greig, NH Flippen-Anderson, JL Brossi, A AF Zhu, XX Yu, QS Greig, NH Flippen-Anderson, JL Brossi, A TI A simple one-pot synthesis of benzoxazine-2,4-diones and benzothiazine-2,4-diones SO HETEROCYCLES LA English DT Article ID HYDROXY-ACIDS; DERIVATIVES; EFFICIENT AB A simple and efficient procedure has been developed for a one-pot synthesis of substituted benzoxazine-2,4-diones and benzothiazine-2,4-diones directly from salicylic acid (or thiosalicylic acid) and amines. C1 Natl Inst Aging Intramural Program, Drug Design & Dev Sect, Lab Neurosci, Gerontol Res Ctr 4E02,NIH, Baltimore, MD 21224 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Greig, NH (reprint author), Toyama Womens Coll, 444 Gankaiji, Toyama, Japan. EM greign@vax.grc.nia.nih.gov NR 13 TC 8 Z9 8 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD JAN 1 PY 2003 VL 59 IS 1 BP 115 EP 128 PG 14 WC Chemistry, Organic SC Chemistry GA 634GJ UT WOS:000180331400016 ER PT J AU Stocca, G Lovinger, DM AF Stocca, G Lovinger, DM TI Phorbol ester uncouples adenosine inhibition of presynaptic Ca2+transients at hippocampal synapses SO HIPPOCAMPUS LA English DT Article DE Ca2+channel; PKC; A1 receptor; synaptic transmission; CA1 subfield ID PROTEIN-KINASE-C; SYNAPTIC TRANSMISSION; RAT HIPPOCAMPUS; NEUROTRANSMITTER RELEASE; TRANSMITTER RELEASE; PYRAMIDAL NEURONS; CALCIUM CHANNELS; CA2+ CHANNELS; MODULATION; RECEPTORS AB Synaptic transmission involves Ca2+ influx at presynaptic terminals. Adenosine receptors inhibit transmission, and this effect can be abolished by activation of PKC with phorbol esters. Whether protein kinase C (PKC) acts via alterations in Ca2+ entry at the presynaptic terminal is unknown. In the present study, we recorded the presynaptic Ca2+ transients (preCaDelta) in hippocampal stratum radiatum, using fluorescence photometry. The calcium dye Fura-2 AM was used to load the Schaffer collateral/commissural tract and its terminals. Tetrodotoxin (TTX)-sensitive Na+ channels and Cd2+-sensitive, high-voltage activated Ca2+ channels (HVACCs) were required to elicit the preCaDelta. Application of the phorbol ester phorbol-12,11 3-dibutyrate (PDBu) abolished the adenosine inhibition of both preCaA and the field excitatory postsynaptic potentials (fEPSPs). PDBu consistently potentiated fEPSPs, and also increased preCaDelta in a large majority of the slices examined. Regardless of whether potentiation was observed, PDBu always prevented adenosine inhibition of preCaDelta. In contrast, the inactive phorbol ester, 4alpha-phorbol, did not alter adenosine inhibition of preCaDelta, indicating that PKC activation is necessary for the occurrence of the observed effects. Our findings suggest that PKC activation abolishes adenosine's inhibitory effect on synaptic activity involving presynaptic Ca2+ entry. (C) 2003 Wiley-Liss, Inc. C1 Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. RP Stocca, G (reprint author), NIAAA, Pk 5 Bldg,12420 Parklawn Dr, Rockville, MD 20852 USA. FU NINDS NIH HHS [NS30470] NR 31 TC 3 Z9 3 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 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2003 VL 13 IS 3 BP 355 EP 360 DI 10.1002/hipo.10088 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 669PR UT WOS:000182360100006 PM 12722976 ER PT J AU Hsia, SCV Tomita, A Obata, K Paul, B Buchholz, D Shi, YB AF Hsia, SCV Tomita, A Obata, K Paul, B Buchholz, D Shi, YB TI Role of chromatin disruption and histone acetylation in thyroid hormone receptor action: Implications in the regulation of HIV-1 LTR SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE thyroid hormone receptor; HIV; AIDS; chromatin; histone acetylation ID IMMUNODEFICIENCY SYNDROME AIDS; LONG TERMINAL REPEAT; NUCLEAR RECEPTOR; TRANSCRIPTIONAL REPRESSION; N-COR; MOLECULAR MECHANISMS; COREPRESSOR COMPLEX; RESPONSE ELEMENT; GENE-REGULATION; CELLULAR-LEVEL AB Thyroid hormone (TH) affects a wide variety of biological processes, from development to physiological function of different cells and organs. Alterations in plasma TH concentrations lead to developmental abnormalities and pathological consequences. Earlier studies have observed that plasma TH levels vary in AIDS patients such that low levels of TH correlate with survival rate. Furthermore, studies on the regulation of the human immunodeficiency virus type 1 (HIV-1) have shown that TH receptor (TR) is capable of binding to two regions within the long terminal repeat (LTR), which controls the transcription of HIV-1 genome. The frog oocyte is an in vivo system that allows microinjected DNA to be chromatinized in a process mimicking the process that occurs in somatic cells. Studies in the frog oocyte have provided in vivo evidence on the role of chromatin remodeling in transcriptional regulation by TR and have shown that TR utilizes similar mechanisms in the regulation of the HIV-1 LTR. That is, TR binds to LTR in chromatin in vivo and represses the LTR in the absence of TH by recruiting corepressor complexes containing histone deacetylases, and upon TH binding, TR causes chromatin remodeling and LTR activation. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 18 T,Rm 10, Bethesda, MD 20892 USA. RI Obata, Keiko/E-2019-2012 NR 77 TC 8 Z9 9 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JAN PY 2003 VL 18 IS 1 BP 323 EP 331 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 634LH UT WOS:000180340500032 PM 12507309 ER PT J AU Vottero, A Kimchi-Sarfaty, C Kratzsch, J Miller, G Lafferty, A Chrousos, GP Hochberg, Z AF Vottero, A Kimchi-Sarfaty, C Kratzsch, J Miller, G Lafferty, A Chrousos, GP Hochberg, Z TI Relative abundance of growth hormone receptor isoforms in Rhesus monkey tissues and human transformed lymphocytes SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the Endocrine-Society CY JUN 21-24, 2000 CL TORONTO, CANADA SP Endocrine Soc DE growth hormone receptor isoforms; R. monkey tissues; human lymphocytes ID GH-BINDING-PROTEIN; PERIPHERAL-BLOOD LYMPHOCYTES; MESSENGER-RNA; GENE-EXPRESSION; 2 ISOFORMS; SERUM; INSULIN; DOMAIN; OBESITY; LIVER AB The growth hormone receptor (GHR) is expressed as one active, full-sequence isoform and one truncated, inactive one that lacks the intracellular signaling domain. The aim of this study was to investigate the variation in the tissue expression of the full and truncated mRNA and protein. Epstein-Barr virus-transformed human B lymphocyte lines were established from 9 normal individuals with a height standard deviation score (SDS) of -0.1 +/- 1.1 (mean +/- SD). Tissues were also collected from 3 Rhesus monkeys, whose GHR has 94.1% homology with the human molecule. mRNA quantitation was determined by Real Time Quantitative PCR. Growth hormone receptor expression in transformed lymphocytes was also studied by fluorescence-activated cell sorter analysis. Both isoforms were expressed in transformed lymphocytes, but individual variation in the relative mRNA expression was small (truncated isoform percentage of total receptor mRNA: 17.1 +/- 4.4, mean +/- SD). There was no correlation between donors' height SDS and the expression of either isoform or the ratio between them. Protein expression by FACS analysis showed wider variation among the subjects; however, the relative ratio was similar in all the subjects. In monkey tissues, the truncated receptor showed a tissue-specific distribution. In conclusion, the expression of both isoforms in transformed lymphocytes from normal subjects shows small differences at the RNA or protein levels, and does not correlate with height SDS. Growth hormone splice isoforms show tissue specificity, suggesting local regulation of splicing. Tissues with relatively high expression of the truncated isoform are likely to be more resistant to the effects of GH due to the dominant negative effect of this isoform. in addition, the differential tissue expression might influence the levels of growth hormone binding protein in the immediate milieu of each tissue. C1 NICHD, PREB, NIH, Bethesda, MD USA. NCI, LCB, NIH, Bethesda, MD USA. Univ Leipzig, Inst Clin Chem, Leipzig, Germany. VRP, ORS, OD, NIH, Bethesda, MD USA. Monash Univ, Dept Pediat, Melbourne, Vic 3004, Australia. Rambam Med Ctr, Dept Pediat, Haifa, Israel. RP Vottero, A (reprint author), Univ Parma, Dept Pediat, I-43100 Parma, Italy. EM vottero@nemo.unipr.it NR 28 TC 3 Z9 3 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JAN PY 2003 VL 35 IS 1 BP 1 EP 6 DI 10.1055/s-2003-38383 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 663JD UT WOS:000182001700001 PM 12669263 ER PT J AU Vottero, A Kimchi-Sarfaty, C Kratzsch, J Chrousos, GP Hochberg, Z AF Vottero, A Kimchi-Sarfaty, C Kratzsch, J Chrousos, GP Hochberg, Z TI Transcriptional and translational regulation of the splicing lsoforms of the growth hormone receptor by glucocorticoids SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE splicing regulation; growth hormone receptor; cDNA and protein expression ID GH-BINDING-PROTEIN; HEPATOMA-CELL LINE; MESSENGER-RNA; DEXAMETHASONE; EXPRESSION; RAT; ISOFORM; HEPATOCYTES; SUPPRESSION; DOMAIN AB Glucocorticoids exert multiple effects on the growth hormone IGF-I axis. The GH receptor is expressed as an active, full-sequence molecule and a truncated, inactive one that lacks the intracellular signaling domain. We used the HuH7 human hepatoma cell line to investigate the effect of glucocorticoids on growth hormone receptor mRNA and protein expression. cDNA quantification was performed by Real Time Quantitative PCR. Growth hormone receptor expression at the protein level was studied by fluorescence-activated cell sorter analysis using specific polyclonal antibodies raised against the two isoform unique C-terminal sequences. Cells were treated with pharmacologic doses of dexamethasone (Dex 10(-7) - 10(-5) M) to assess its acute (1 hour or overnight) and chronic effects (7 days). Dex induced a dose-dependent increase of both the full (427%) and truncated (180%) mRNAs. At the protein level, Dex upregulated the full sequence more (183%) than the truncated (126%) protein. For a better understanding of this regulation system, cells were incubated with Dex 10(-6) M for 24 h in the absence or presence of a transcriptional inhibitor, actinomycin D, or a translational inhibitor, cycloheximide. Actinomycin D had no effect on Dex-induced upregulation, while cycloheximide blocked the truncated mRNA but not the full sequence mRNA upregulation, suggesting that this effect of glucocorticoids is a post-transcriptional event. After 7 days of chronic treatment, Dex induced a dose-dependent downregulation of the active receptor without any changes in the expression of the truncated isoform either at the mRNA or protein levels. We conclude that short-term glucocorticoid treatment results in an enhancement of the growth hormone receptor expression, while long-term treatment has a suppressive effect, through both transcriptional and translational mechanisms ultimately influencing both isoforms of the receptor. C1 NICHD, PREB, NIH, Bethesda, MD USA. NCI, LCB, NIH, Bethesda, MD USA. Univ Leipzig, Inst Clin Chem, Leipzig, Germany. Rambam Med Ctr, Dept Pediat, Haifa, Israel. RP Vottero, A (reprint author), Univ Parma, Dept Pediat, I-43100 Parma, Italy. EM vottero@nemo.unipr.it NR 28 TC 13 Z9 13 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JAN PY 2003 VL 35 IS 1 BP 7 EP 12 DI 10.1055/s-2003-38384 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 663JD UT WOS:000182001700002 PM 12669264 ER PT S AU Schmidt, PJ Rubinow, DR AF Schmidt, PJ Rubinow, DR BE Genazzani, AR TI The perimenopause and depressive illness SO HORMONE REPLACEMENT THERAPY AND THE BRAIN: THE CURRENT STATUS OF RESEARCH AND PRACTICE SE CONTROVERSIAL ISSUES IN CLIMACTERIC MEDICINE SERIES LA English DT Proceedings Paper CT Workshop on Hormone Replacement Therapy in Climacteric and Aging Brain CY MAR 15-MAY 18, 2003 CL PISA, ITALY ID DEHYDROEPIANDROSTERONE-SULFATE; POSTMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; MENOPAUSAL WOMEN; MAJOR DEPRESSION; HORMONE LEVELS; DOUBLE-BLIND; PSYCHOLOGIC DISTRESS; AFFECTIVE-DISORDERS; NATURAL MENOPAUSE C1 NIMH, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Bldg 10,Room 3N238,10 Ctr Dr,MDC 1276, Bethesda, MD 20892 USA. NR 72 TC 0 Z9 0 U1 1 U2 1 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND SN 1474-3930 BN 1-84214-168-6 J9 CONTRO ISSU CLIM MED PY 2003 BP 141 EP 149 PG 9 WC Endocrinology & Metabolism; Neurosciences; Obstetrics & Gynecology; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Obstetrics & Gynecology; Psychiatry GA BX91W UT WOS:000186825500017 ER PT S AU Gold, PW AF Gold, PW BE Genazzani, AR TI Depression, aging and the metabolic syndrome SO HORMONE REPLACEMENT THERAPY AND THE BRAIN: THE CURRENT STATUS OF RESEARCH AND PRACTICE SE CONTROVERSIAL ISSUES IN CLIMACTERIC MEDICINE SERIES LA English DT Proceedings Paper CT Workshop on Hormone Replacement Therapy in Climacteric and Aging Brain CY MAR 15-MAY 18, 2003 CL PISA, ITALY ID CORTICOTROPIN-RELEASING HORMONE; CORONARY-HEART-DISEASE; ATYPICAL DEPRESSION; BIOCHEMICAL MANIFESTATIONS; MAJOR DEPRESSION; UNITED-STATES; STRESS; DISORDERS; RISK; NEUROBIOLOGY C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Gold, PW (reprint author), NIMH, Clin Neuroendocrinol Branch, Bldg 10,Room 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND SN 1474-3930 BN 1-84214-168-6 J9 CONTRO ISSU CLIM MED PY 2003 BP 195 EP 203 PG 9 WC Endocrinology & Metabolism; Neurosciences; Obstetrics & Gynecology; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Obstetrics & Gynecology; Psychiatry GA BX91W UT WOS:000186825500024 ER PT J AU Harman, SM Blackman, MR AF Harman, SM Blackman, MR TI The effects of growth hormone and sex steroid on lean body mass, fat mass, muscle strength, cardiovascular endurance and adverse events in healthy elderly women and men SO HORMONE RESEARCH LA English DT Article; Proceedings Paper CT 6th KIGS/KIMS Expert Meeting on Growth Hormone and Growth Disorders CY NOV 08-09, 2002 CL FLORENCE, ITALY SP KIGS, KIMS DE growth hormone; testosterone; oestrogen; sex hormones; elderly population; lean body mass; fat mass; adverse events ID GH REPLACEMENT; IGF-I; ADULTS; TESTOSTERONE; SAFETY AB Decreases in growth hormone (GH) and insulin-like growth factor I occur with age, in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men. These age-related hormonal changes may contribute to reductions in lean body mass, muscle strength and cardiac endurance, which can be partially reversed in elderly people with GH treatment, and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women, respectively. These treatments are, however, thought to have potentially serious adverse effects. We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition, muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people. The results of the study showed that although there were beneficial effects with GH and sex steroid treatment, a high percentage of adverse effects occurred after 26 weeks of treatment, demonstrating a need for more research on the safety of hormonal therapy in the elderly population. Copyright (C) 2003 S. Karger AG, Basel. C1 NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Internal Med, Div Endocrinol, Baltimore, MD USA. RP Harman, SM (reprint author), Kronos Longev Res Inst, 2222 E Highland,Suite 220, Phoenix, AZ 85016 USA. NR 16 TC 33 Z9 35 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2003 VL 60 SU 1 BP 121 EP 124 DI 10.1159/000071236 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724ZN UT WOS:000185518300019 PM 12955028 ER PT J AU Charmandari, E Kino, T Souvatzoglou, E Chrousos, GP AF Charmandari, E Kino, T Souvatzoglou, E Chrousos, GP TI Pediatric stress: Hormonal mediators and human development SO HORMONE RESEARCH LA English DT Review DE stress system; neuroendocrinology of stress; stress-related disorders ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING HORMONE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; SEXUALLY ABUSED GIRLS; GROWTH-HORMONE; CUSHINGS-SYNDROME; GENE-EXPRESSION; NEUROPEPTIDE-Y; MATERNAL-CARE AB Stress activates the central and peripheral components of the stress system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis and the arousal/sympathetic system. The principal effectors of the stress system are corticotropin-releasing hormone (CRH), arginine vasopressin, the proopiomelanocortin-derived peptides alpha-melanocyte-stimulating hormone and beta-endorphin, the glucocorticoids, and the catecholamines norepinephrine and epinephrine. Appropriate responsiveness of the stress system to stressors is a crucial prerequisite for a sense of well-being, adequate performance of tasks and positive social interactions. By contrast, inappropriate responsiveness of the stress system may impair growth and development, and may account for a number of endocrine, metabolic, autoimmune and psychiatric disorders. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors and the timing of the stressful event(s), given that prenatal life, infancy, childhood and adolescence are critical periods characterized by increased vulnerability to stressors. The developing brain undergoes rapid growth and is characterized by high turnover of neuronal connections during the prenatal and early postnatal life. These processes and, hence, brain plasticity, slow down during childhood and puberty, and plateau in young adulthood. Hormonal actions in early life, and to a much lesser extent later, can be organizational, i.e., can have effects that last for long periods of time, often for the entire life of the individual. Hormones of the stress system and sex steroids have such effects, which influence the behavior and certain physiologic functions of individuals for life. Exposure of the developing brain to severe and/or prolonged stress may result in hyperactivity/hyperreactivity of the stress system, with resultant amygdala hyperfunction (fear reaction), decreased activity of the hippocampus (defective glucocorticoid-negative feedback, cognition), and the mesocorticolimbic dopaminergic system (dysthymia, novelty-seeking, addictive behaviors), hyperactivation of the HPA axis (hypercortisolism), suppression of reproductive, growth, thyroid and immune functions, and changes in pain perception. These changes may be accompanied by abnormal childhood, adolescent and adult behaviors, including excessive fear ('inhibited child syndrome') and addictive behaviors, dysthymia and/or depression, and gradual development of components of the metabolic syndrome X, including visceral obesity and essential hypertension. Prenatal stress exerted during the period of sexual differentiation may be accompanied by impairment of this process with behavioral and/or somatic sequelae. The vulnerability of individuals to develop varying degrees and/or components of the above life-long syndrome is defined by as yet unidentified genetic factors, which account for up to 60% of the variance. CRH has marked kindling and glucocorticoids have strong consolidating properties, hence both of these hormones are crucial in development and can alone produce the above syndrome. CRH and glucocorticoids may act in synergy, as in acoustic startle, while glucocorticoids may suppress or stimulate CRH, as in the hypothalamus and amygdala, respectively. A CRH type 1 receptor antagonist, antalarmin, inhibits both the development and expression of conditioned fear in rats, and has anxiolytic properties in monkeys. Profound stressors, such as those from sexual abuse, may elicit the syndrome in older children, adolescents and adults. Most frequently, chronic dysthymia and/or depression may develop in association with gastrointestinal complaints and/or the premenstrual tension syndrome. A lesser proportion of individuals may develop the classic posttraumatic stress disorder, which is characterized by hypocortisolism and intrusive and avoidance symptoms; in younger individuals it may present as dissociative personality disorder. Copyright (C) 2003 S. Karger AG, Basel. C1 NICHHD, Pediat & Repord Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Charmandari, E (reprint author), NICHHD, Pediat & Repord Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Suite 9D42, Bethesda, MD 20892 USA. RI Charmandari, Evangelia/B-6701-2011 NR 126 TC 187 Z9 199 U1 5 U2 47 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2003 VL 59 IS 4 BP 161 EP 179 DI 10.1159/000069325 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 664VP UT WOS:000182083500001 PM 12649570 ER PT J AU Kumar, M Bradow, BP Zimmerberg, J AF Kumar, M Bradow, BP Zimmerberg, J TI Large-scale production of pseudotyped lentiviral vectors using baculovirus GP64 SO HUMAN GENE THERAPY LA English DT Article ID EFFICIENT GENE-TRANSFER; VIRUS-G GLYCOPROTEIN; PACKAGING CELL-LINE; LEUKEMIA-VIRUS; IN-VIVO; HIGH-TITER; MAMMALIAN-CELLS; MEMBRANE-FUSION; INSECT CELLS; HUMAN SERUM AB Unlike oncoretroviruses, lentiviral vectors can insert large genes and can target both dividing and nondividing cells; thus they hold unique promise as gene transfer agents. To enhance target range, the native lentiviral envelope glycoprotein is replaced (pseudotyped) with vesicular stomatitis virus G (VSVG), and the genes of interest are packaged in nonreplicating vectors by transient transfection with three plasmids. However, because of cytotoxic effects of VSVG expression in producer cells (293T cells) it has been difficult to generate a packaging cell line, required for even modest scale-up of vector production. Here we introduce a pseudotyped lentivirus vector using the baculovirus GP64 envelope glycoprotein. Compared with VSVG, GP64 vectors exhibited a similar broad tropism and similar native titers. GP64-pseudotyped vectors were usually highly concentrated without much loss of titer. Because, unlike VSVG, GP64 expression does not kill cells, we generated 293T-based cell lines constitutively expressing GP64. Our results demonstrate that the baculovirus GP64 protein is an attractive alternative to VSVG for viral vectors used in the large-scale production of high-titer virus required for clinical and commercial applications. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHD, NIH, Room 10D14,Bldg 10, Bethesda, MD 20892 USA. NR 47 TC 50 Z9 52 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2003 VL 14 IS 1 BP 67 EP 77 DI 10.1089/10430340360464723 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 636CM UT WOS:000180437000007 PM 12573060 ER PT J AU Kimchi-Sarfaty, C Arora, M Sandalon, Z Oppenheim, A Gottesman, MM AF Kimchi-Sarfaty, C Arora, M Sandalon, Z Oppenheim, A Gottesman, MM TI High cloning capacity of in vitro packaged SV40 vectors with no SV40 virus sequences SO HUMAN GENE THERAPY LA English DT Article ID MULTIDRUG-RESISTANCE GENE; HEMATOPOIETIC-CELLS; VIRAL VECTORS; INSECT CELLS; THERAPY; PSEUDOVIRIONS; EXPRESSION; MDR1; RESOLUTION; PHENOTYPE AB In vitro packaging of plasmid DNA using recombinant SV40 capsid proteins is a potentially useful procedure that overcomes some restrictions of the other SV40 systems such as the requirement for SV40 sequences and the limitation in size of DNA that can be packaged. The in vitro packaging system uses the four SV40 proteins (VP1, VP2, VP3, and agno) or VP1 only. The ability to confer drug resistance by three ABC transporter genes (MDR1, MRP1, or MXR) was determined using the surrogate fluorescent substrates rhodamine-123 or calcein AM and their specific inhibitors, or by using specific antibodies to the transporters to detect cell surface expression by fluorescence-activated cell sorter analysis (FACS). A green fluorescent protein plasmid (EGFP-C1) was also used to monitor gene transfer. The packaged plasmids ranged in size from 4.2 to 17.6 kb, and only slightly affected particle size as determined by electron microscopy. When 9.5 kb and larger plasmids were packaged using all SV40 proteins, MDR1 expression was decreased compared to VP1 alone. The size of the 15.2 kb DNA after packaging was the same as the original DNA. Packaging with SV40 capsid proteins in vitro does not require any SV40 sequences. Using either the MDR1 or the GFP gene we could demonstrate enhanced expression when cells were pretreated with phorbol 12-myristate 13-acetate (PMA) at low concentrations. Interferon-gamma did not alter expression. We conclude that in vitro packaging is more flexible then previously realized, permitting packaging of at least 17 kb plasmid DNA without the requirement for any viral sequences. This system combines efficient gene delivery of the SV40 viral vector with the presumed safety of nonviral vectors. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1A09,37 Convent Dr,MSC 4254, Bethesda, MD 20892 USA. NR 40 TC 33 Z9 36 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2003 VL 14 IS 2 BP 167 EP 177 DI 10.1089/104303403321070865 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 642AD UT WOS:000180778500008 PM 12614568 ER PT S AU Nabel, GJ AF Nabel, GJ BE Rubanyi, GM YlaHerttuala, S TI The future of gene therapy SO HUMAN GENE THERAPY: CURRENT OPPORTUNITIES AND FUTURE TRENDS SE ERNST SCHERING RESEARCH FOUNDATION WORKSHOP LA English DT Proceedings Paper CT Workshop on Human Gene Therapy - Current Opportunities and Future Trends CY OCT 02-04, 2002 CL BERKELEY, CA SP Ernst Schering Fdn ID MEF2 TRANSCRIPTION FACTOR; ENDOTHELIAL GROWTH-FACTOR; IMMUNE-RESPONSES; IN-VIVO; RECOMBINANT ADENOVIRUSES; MYOCARDIAL-ISCHEMIA; CARDIAC-HYPERTROPHY; RNA INTERFERENCE; ARTERIAL-WALL; MOUSE-LIVER C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. NR 62 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-00413-0 J9 E SCHERING RES FDN W PY 2003 VL 43 BP 1 EP 16 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA BX54G UT WOS:000185644200001 ER PT S AU Nabel, GJ AF Nabel, GJ BE Rubanyi, GM YlaHerttuala, S TI Cancer gene therapy: Present status and future directions SO HUMAN GENE THERAPY: CURRENT OPPORTUNITIES AND FUTURE TRENDS SE ERNST SCHERING RESEARCH FOUNDATION WORKSHOP LA English DT Proceedings Paper CT Workshop on Human Gene Therapy - Current Opportunities and Future Trends CY OCT 02-04, 2002 CL BERKELEY, CA SP Ernst Schering Fdn ID AUTOLOGOUS MELANOMA-CELLS; COLONY-STIMULATING-FACTOR; FAS LIGAND CD95L; TUMOR-REGRESSION; IMMUNE-RESPONSE; PHASE-I; IMMUNOTHERAPY AB In recent years, considerable progress has been made towards understanding the molecular basis of the progression and pathogenesis of various human cancers. Several lines of evidence now clearly show that malignant cells exhibit considerable genetic instability, and that progressive genetic changes occur during the course of tumorigenesis (for review, see Vogelstein and Kinzier 2002). In order to develop molecular genetic interventions to treat malignancy, it is critical to understand the relevant underlying genetic abnormalities and to develop appropriate strategies for these genetic lesions (Chaux et al. 1996; Gore and Collins 1994; Kirn 2001; Roth and Cristiano 1997; Seliger et al. 1996; Vile et al. 2000). The most promising approach is to design a therapy that can catalyze antitumor responses without the need to complement missing or defective genes in each cell within the tumor population (Nabel et al. 1994). Genetic interventions that can facilitate the development of immunity against mutant gene products arising within the tumor would be most desirable (Vieweg and Gilboa 1995). One way to achieve this goal is to design therapies that enhance immunologic recognition within specific tumor nodules (Abdel-Wahab et al. 1997; Blankenstein 1994; Dranoff et al. 1997; Ellem et al. 1997; Ohno et al. 1997). C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-00413-0 J9 E SCHERING RES FDN W PY 2003 VL 43 BP 81 EP 88 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA BX54G UT WOS:000185644200006 ER PT J AU Freidlin, B Zheng, G Li, ZH Gastwirth, JL AF Freidlin, B Zheng, G Li, ZH Gastwirth, JL TI Efficiency robust tests for mapping quantitative trait loci using extremely discordant sib pairs SO HUMAN HEREDITY LA English DT Article DE MAX; MERT; restricted likelihood ratio test; robustness; score test; triangle constraint ID HASEMAN-ELSTON METHOD; LINKAGE ANALYSIS; ASYMPTOTIC PROPERTIES; SIBLING PAIRS; POWER; SURVIVAL; HUMANS AB In 1972, Haseman and Elston proposed a pioneering regression method for mapping quantitative trait loci using randomly selected sib pairs. Recently, the statistical power of their method was shown to be increased when extremely discordant sib pairs are ascertained. While the precise genetic model may not be known, prior information that constrains IBD probabilities is often available. We investigate properties of tests that are robust against model uncertainty and show that the power gain from further constraining IBD probabilities is marginal. The additional linkage information contained in the trait values can be incorporated by combining the Haseman-Elston regression method and a robust allele sharing test. Copyright (C) 2003 S. Karger AG, Base. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Biostat Branch, Bethesda, MD 20892 USA. NCI, Off Biostat Res, NHLBI, Bethesda, MD 20892 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. RP Freidlin, B (reprint author), NCI, Biometr Res Branch, MSC 7334, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY14478] NR 25 TC 3 Z9 3 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2003 VL 55 IS 2-3 BP 117 EP 124 DI 10.1159/000072316 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 720UV UT WOS:000185279100006 PM 12931050 ER PT J AU Consolandi, C Busti, E Pera, C Delfino, L Ferrara, GB Bordoni, R Castiglioni, B Bernardi, LR Battaglia, C De Bellis, G AF Consolandi, C Busti, E Pera, C Delfino, L Ferrara, GB Bordoni, R Castiglioni, B Bernardi, LR Battaglia, C De Bellis, G TI Detection of HLA polymorphisms by ligase detection reaction and a universal array format: A pilot study for low resolution genotyping SO HUMAN IMMUNOLOGY LA English DT Article DE LDR; HLA typing; universal array ID DENSITY OLIGONUCLEOTIDE ARRAYS; SEQUENCE-ANALYSIS; MUTATIONS; IDENTIFICATION; HYBRIDIZATION; BRCA1 AB We present our results in the identification of polymorphic sites within the second exon of the human leukocyte antigen A (HLA-A) region using the DNA microarray technology. Allele specific detection was performed by polymerase chain reaction followed by ligase detection reaction (LDR) in combination with a universal array, a powerful method for high throughput DNA sequence analysis. By this approach we confirmed 32 human samples previously characterized by direct DNA sequencing, thus demonstrating the interest of this approach. (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Science Inc. C1 CNR, Ist Tecnol Biomed, I-20090 Segrate, Italy. Univ Milan, Dipartimento Sci & Tecnol Biomed, Segrate, Italy. Univ Milan, CISI, Segrate, Italy. Natl Canc Inst, Adv Biotechnol Ctr, IST, Genoa, Italy. Univ Genoa, Dept Oncol, Genoa, Italy. Univ Genoa, Dept Biol & Genet, Genoa, Italy. IBBA, Segrate, Italy. RP De Bellis, G (reprint author), CNR, Ist Tecnol Biomed, Via Flli Cervi 93, I-20090 Segrate, Italy. RI Castiglioni, Bianca/G-9856-2013; De Bellis, Gianluca/H-9725-2013; Battaglia, Cristina /E-5166-2017; OI De Bellis, Gianluca/0000-0002-1622-4477; Battaglia, Cristina /0000-0003-3025-9657; Castiglioni, Bianca/0000-0003-2326-6701 NR 17 TC 25 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JAN PY 2003 VL 64 IS 1 BP 168 EP 178 AR PII S0198-8859(02)00685-7 DI 10.1016/S0198-8859(02)00685-7 PG 11 WC Immunology SC Immunology GA 636EU UT WOS:000180442200020 PM 12507828 ER PT J AU Kondrashov, AS AF Kondrashov, AS TI Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases SO HUMAN MUTATION LA English DT Review DE mutation rate; human; target size; hot spot; mutation analysis ID FAMILIAL ADENOMATOUS POLYPOSIS; CHRONIC GRANULOMATOUS-DISEASE; X-LINKED AGAMMAGLOBULINEMIA; DREIFUSS MUSCULAR-DYSTROPHY; HIPPEL-LINDAU-DISEASE; SEVERE COMBINED IMMUNODEFICIENCY; GENOTYPE-PHENOTYPE CORRELATIONS; PROTEIN TRUNCATION TEST; ORNITHINE TRANSCARBAMYLASE DEFICIENCY; NEPHROGENIC DIABETES-INSIPIDUS AB I estimate per nucleotide rates of spontaneous mutations of different kinds in human's directly from the data on per locus mutation. rates and on sequences of de novo nonsense nucleotide substitutions, deletions, insertions, and complex events at eight loci causing autosomal dominant diseases and 12 loci causing X-linked diseases. The results are in good agreement with indirect estimates, obtained by Comparison of orthologous human and chimpanzee pseudogenes. The average direct estimate of the combined rate of all mutations is 1.8 x 10(-8) per nucleotide per generation, and the coefficient of variation of this rate across the 20 loci is 0.53. Single nucleotide substitutions are similar to25 times more common than all other mutations, deletions are similar tothree times more common than insertions, complex mutations are very rare, and CpG context increases Substitution rates by an order of magnitude. There is only a moderate tendency for loci with high er locus mutation rates to also have higher per nucleotide substitution rates, and per nucleotide rates of deletions and insertions are statistically independent on the per lotus mutation rate. Rates of different kinds of mutations are strongly correlated Across loci. Mutational hot spots with per nucleotide rates above 5 x 10(-7) make only a minor contribution to human mutation. In the next decade, direct measurements will produce a rather precise, quantitative description Of human spontaneous mutation at the DNA level. C1 Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Kondrashov, AS (reprint author), Natl Ctr Biotechnol Informat, NIH, 45 Ctr Dr,MSC 6510, Bethesda, MD 20892 USA. NR 151 TC 203 Z9 206 U1 1 U2 17 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2003 VL 21 IS 1 BP 12 EP 27 DI 10.1002/humu.10147 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 630RK UT WOS:000180122500004 PM 12497628 ER PT J AU Roberts, JM Pearson, GD Cutler, JA Lindheimer, MD AF Roberts, JM Pearson, GD Cutler, JA Lindheimer, MD TI Summary of the NHLBI Working Group on research on hypertension during pregnancy SO HYPERTENSION IN PREGNANCY LA English DT Article DE hypertension; pregnancy; preeclampsia; research; oxidative stress; pathophysiology ID OXIDATIVE STRESS; PREECLAMPTIC PREGNANCIES; REMOTE PROGNOSIS; ANTIHYPERTENSIVE TREATMENT; ENDOTHELIAL DYSFUNCTION; PEROXYNITRITE FORMATION; SUBSEQUENT PREGNANCY; ACUTE ATHEROSIS; BLOOD-PRESSURE; WOMEN AB A Working Group on Research in Hypertension in Pregnancy was recently convened by the National Heart Lung and Blood Institute to determine the state of knowledge in this area and suggest appropriate directions for research. Hypertensive disorders in pregnancy, especially preeclampsia, are a leading cause of maternal mortality worldwide and even in developed countries increase perinatal mortality five-fold. Much has been learned about preeclampsia but gaps in the knowledge necessary to direct therapeutic strategies remain. Oxidative stress is a biologically plausible contributor to the disorder that may be amenable to intervention. Hypertension that antedates pregnancy (chronic hypertension) bears many similarities to hypertension in nonpregnant women but the special setting of pregnancy demands information to guide evidence based therapy. The recommendations of the Working Group are to attempt a clinical trial of antioxidant therapy to prevent preeclampsia that is be complemented by mechanistic research to increase understanding of the genetics and pathogenesis of the disorder. For chronic hypertension clinical trials are recommended to direct choice of drugs, evaluate degree of control and assess implications to the mother and fetus. Recommendations to increase participation in this research are also presented. C1 Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. NHLBI, NIH, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Chicago, Pritzker Sch Med, Dept Obstet & Gynecol & Med, Div Biol Sci, Chicago, IL 60637 USA. Magee Womens Res Inst, Pittsburgh, PA USA. RP Roberts, JM (reprint author), 204 Craft Ave,Suite 610, Pittsburgh, PA 15213 USA. NR 74 TC 123 Z9 134 U1 3 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2003 VL 22 IS 2 BP 109 EP 127 DI 10.1081/PRG-120016792 PG 19 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 699FC UT WOS:000184045200001 PM 12908996 ER PT J AU Zhang, J Meikle, S Trumble, A AF Zhang, J Meikle, S Trumble, A TI Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States SO HYPERTENSION IN PREGNANCY LA English DT Article DE eclampsia; maternal morbidity; preeclampsia ID RISK-FACTORS; PREECLAMPSIA; ECLAMPSIA; HEALTHY; EPIDEMIOLOGY; WOMEN AB Objectives: This study was to report the incidence of severe maternal morbidity associated with hypertensive disorders of pregnancy in the United States. Study Design: We used data from the National Hospital Discharge Survey, a nationally representative sample of discharge records, from 1988 to 1997. The database consisted of approximately 300,000 deliveries, which represented 39 million births during the 10-year period. Results: The overall incidence of hypertensive disorders in pregnancy was 5.9% [95% confidence interval (CI): 5.2 to 6.5%]. Eclampsia was reported at 1.0 per 1000 deliveries (95% CI: 0.8 to 1.2). The incidence of eclampsia, severe preeclampsia, and superimposed preeclampsia remained unchanged during the 10-year period. Women with preeclampsia and eclampsia had a 3- to 25-fold increased risk of severe complications, such as abruptio placentae, thrombocytopenia, disseminated intravascular coagulation, pulmonary edema, and aspiration pneumonia. More than half of women with preeclampsia and eclampsia had cesarean delivery. African American women not only had higher incidence of hypertensive disorders in pregnancy but also tended to have a greater risk for most severe complications. Preeclamptic and eclamptic women younger than 20 years or older than 35 years had substantially higher morbidity. Conclusion: Preeclampsia and eclampsia carry a high risk for severe maternal morbidity. Compared to Caucasians, African Americans have higher incidence of hypertensive disorders in pregnancy and suffer from more severe complications. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. RP NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth & Human Serv, NIH Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM jim_zhang@nih.gov NR 21 TC 121 Z9 131 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1064-1955 EI 1525-6065 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2003 VL 22 IS 2 BP 203 EP 212 DI 10.1081/PRG-120021066 PG 10 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 699FC UT WOS:000184045200010 PM 12909005 ER PT J AU Min, BK McHugh, R Sempowski, GD Mackall, C Foucras, G Paul, WE AF Min, BK McHugh, R Sempowski, GD Mackall, C Foucras, G Paul, WE TI Neonates support lymphopenia-induced proliferation SO IMMUNITY LA English DT Article ID NAIVE T-CELLS; HOMEOSTATIC PROLIFERATION; LYMPHOCYTES-T; MEMORY CELLS; IN-VIVO; SURVIVAL; EXPANSION; INTERLEUKIN-7; IMMUNITY; LIGANDS AB T cells expand without intentional antigen stimulation when transferred into adult lymphopenic environments. In this study, we show that the physiologic lymphopenic environment existing in neonatal mice also supports CD4 T cell proliferation. Strikingly, naive CD4 T cells that proliferate within neonates acquire the phenotypic and functional characteristics of memory cells. Such proliferation is inhibited by the presence of both memory and naive CD4 T cells, is enhanced by 3-day thymectomy, is independent of IL-7, and requires a class If MHC-TCR interaction and a CD28mediated signal. CD44(bright) CD4 T cells in neonates have a wide repertoire as judged by the distribution of VP expression. Thus, lymphopenia-induced T cell proliferation is a physiologic process that occurs during the early postnatal period. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Med, Human Vaccine Inst, Durham, NC 27710 USA. NCI, Pediat Oncol Branch, NCI, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 50 TC 171 Z9 173 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2003 VL 18 IS 1 BP 131 EP 140 DI 10.1016/S1074-7613(02)00508-3 PG 10 WC Immunology SC Immunology GA 643KN UT WOS:000180860600013 PM 12530982 ER PT J AU Wahl, SA Chen, WJ AF Wahl, SA Chen, WJ TI TGF-beta - How tolerant can it be? SO IMMUNOLOGIC RESEARCH LA English DT Article DE Tr1; Th3; CD4(+)CD25(+) anergic/suppressor; IL-2; CTLA-4; autoimmunity ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; IMMUNOLOGICAL SELF-TOLERANCE; MYELIN BASIC-PROTEIN; DENDRITIC CELLS; IN-VITRO; TRANSFORMING GROWTH-FACTOR-BETA-1; ANTIGEN 4; PERIPHERAL-BLOOD; ORAL ANTIGEN AB A balance between an adequate immune response to an antigen or pathogen and tolerance is a prerequisite for normal immune homeostasis and the well-being of the host. In this complex self-regulation, multiple mechanisms have been implicated as contributing to the immune tolerance network, including apoptosis, anergy, and active suppression. Current excitement focuses on active suppression and new regulatory T cell-mediated pathways of immunosuppression that are being unraveled. Central to several of these pathways is transforming growth factor-beta (TGF-beta), a potent immunoregulatory cytokine that contributes to the function and generation of regulatory T cells. C1 NIDCR, Cellular Immunol Sect, OIIB, NIH, Bethesda, MD 20892 USA. RP Wahl, SA (reprint author), NIDCR, Cellular Immunol Sect, OIIB, NIH, Bldg 30,Room 320,30 Convent Dr, Bethesda, MD 20892 USA. NR 98 TC 32 Z9 39 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2003 VL 28 IS 3 BP 167 EP 179 DI 10.1385/IR:28:3:167 PG 13 WC Immunology SC Immunology GA 754XE UT WOS:000187357900001 PM 14713712 ER PT J AU Howcroft, TK Singer, DS AF Howcroft, TK Singer, DS TI Expression of nonclassical MHC class Ib genes - Comparison of regulatory elements SO IMMUNOLOGIC RESEARCH LA English DT Review DE MHC; class Ib; promoter; gene expression; HLA; H2; SLA ID MAJOR HISTOCOMPATIBILITY COMPLEX; TISSUE-SPECIFIC EXPRESSION; RNA-POLYMERASE-II; HLA-G EXPRESSION; CELL-SURFACE EXPRESSION; TATA-BINDING PROTEIN; G MESSENGER-RNA; DELTA T-CELLS; PREIMPLANTATION MOUSE EMBRYOS; DOWNSTREAM PROMOTER ELEMENT AB Peptide binding proteins of the major histocompatibility complex consist of the "classical" class la and "nonclassical" class Ib genes. The gene organization and structure/function relationship of the various exons comprising class I proteins are very similar among the class la and class Ib genes. Although the tissue-specific patterns of expression of these two gene families are overlapping, many class Ib genes are distinguished by relative low abundance and/or limited tissue distribution. Further, many of the class Ib genes serve specialized roles in immune responses. Given that the coding sequences of the class la and class Ib genes are highly homologous we sought to examine the promoter regions of the various class Ib genes by comparison to the well characterized promoter elements regulating expression of the class la genes. This analysis revealed a surprising complexity of promoter structures among all class I genes and few instances of conservation of class la promoter regulatory elements among the class Ib genes. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Howcroft, TK (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 5B09, Bethesda, MD 20892 USA. EM HowcrofK@Exchange.nih.gov NR 252 TC 18 Z9 18 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2003 VL 27 IS 1 BP 1 EP 29 DI 10.1385/IR:27:1:1 PG 29 WC Immunology SC Immunology GA 659BR UT WOS:000181757700001 PM 12637766 ER PT J AU Caspi, RR AF Caspi, RR TI Regulation, counter-regulation, and immunotherapy of autoimmune responses to immunologically privileged retinal antigens SO IMMUNOLOGIC RESEARCH LA English DT Article DE uveitis; autoimmune disease; T cells; Th1/Th2; tolerance ID ALTERED PEPTIDE LIGAND; ORAL TOLERANCE; GENETIC SUSCEPTIBILITY; MULTIPLE-SCLEROSIS; PROTECTIVE ROLE; MURINE MODEL; IFN-GAMMA; UVEITIS; UVEORETINITIS; INDUCTION AB Our interests revolve around the study of biological mechanisms regulating self-tolerance to immunologically privileged retinal proteins that serve as targets in sight-threatening autoimmune uveitic disease. These studies are aimed at understanding how self-tolerance to these antigens develops during ontogeny and is maintained during adulthood, the processes involved in its pathological breakdown, the regulatory mechanisms that bring about remission and recovery, and, finally, how we can utilize knowledge of these processes for therapeutic restoration of tolerance. To answer these questions, we use the experimental autoimmune uveitis (EAU) model in rats and mice. Because of the commonality of underlying immunological mechanisms, lessons and concepts learned in experimental ocular models are applicable to other disease entities, and, conversely, data gleaned from other autoimmune diseases are applicable to the study of uveitis. C1 NEI, Lab Immunol, Sect Immunoregulat, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Caspi, RR (reprint author), NEI, Lab Immunol, Sect Immunoregulat, NIH, Bg 10,Rm 10N222,10 Ctr Dr MSC 1857, Bethesda, MD 20892 USA. NR 42 TC 16 Z9 17 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2003 VL 27 IS 2-3 BP 149 EP 159 DI 10.1385/IR:27:2-3:149 PG 11 WC Immunology SC Immunology GA 706WF UT WOS:000184477500004 PM 12857964 ER PT J AU Germain, RN AF Germain, RN TI Ligand-dependent regulation of T cell development and activation SO IMMUNOLOGIC RESEARCH LA English DT Article DE T lymphocyte; T cell receptor; MHC molecule; antigen; thymus; CD4; CD8; signaling; vaccines; autoimmunity; tolerance ID RECEPTOR SIGNAL-TRANSDUCTION; POSITIVE SELECTION; CD8 LINEAGE; HOMEOSTATIC PROLIFERATION; IMMUNOLOGICAL SYNAPSE; THYMIC SELECTION; CUTTING EDGE; LYMPH-NODE; TCR-ZETA; IN-VIVO AB Mature CD4+ and CD8(+) T lymphocytes develop in the thymus from precursors with diverse clonally distributed receptors, possessing binding sites with negligible, intermediate, or high affinity for self-peptide: major histocompatibility complex (MHC) ligands. Positive- and negative-selection processes acting on this precursor pool yield a peripheral T cell population comprised of cells with receptors (TCR) capable of self-peptide: MHC ligand recognition, but largely depleted of those able to mediate overt self-responsiveness. The Lymphocyte Biology Section of the Laboratory of Immunology studies how self-ligand recognition guides T cell development in the thymus and influences the functionality of naive and activated T cells in the periphery. It also seeks to define the molecular basis for the discrimination between self-ligands and foreign antigens that controls T cell activation to effector function. Finally, it uses a combination of conventional cellular immunological methods, biochemical and biophysical studies, and advanced imaging techniques to visualize, quantitate, and model the various steps in the development of primary and memory T cell immune responses. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bldg 10,Rm11N311,10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. NR 53 TC 9 Z9 9 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2003 VL 27 IS 2-3 BP 277 EP 286 DI 10.1385/IR:27:2-3:277 PG 10 WC Immunology SC Immunology GA 706WF UT WOS:000184477500014 PM 12857974 ER PT J AU Lenardo, MJ AF Lenardo, MJ TI Molecular regulation of T lymphocyte homeostasis in the healthy and diseased immune system SO IMMUNOLOGIC RESEARCH LA English DT Article DE human immunodeficiency virus; apoptosis; autoimmunity; lymphoproliferation; Fas; tumor necrosis factor ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; IMMUNODEFICIENCY-VIRUS TYPE-1; FAS GENE-MUTATIONS; DEFECTIVE LYMPHOCYTE; APOPTOSIS; DEATH; DISORDER; CASPASE; DOMAIN AB Lymphocyte homeostasis is achieved by a balance between the production and death of lymphocytes. In particular, T lymphocytes differentiate and mature in the thymus and are released into the peripheral circulation, where they can travel to sites of encounter with antigen. Once in the circulation, T lymphocytes have varying life spans depending on whether they remain resting, become activated by antigen and replicate, or they become memory cells. The regulation of lymphocyte fate, especially the induction of programmed cell death, or apoptosis, has become a focus of intense molecular research, and much has been learned. In particular, the Fas receptor and other members of the tumor necrosis factor receptors, as well as their respective ligands, have emerged as key regulators of T lymphocyte apoptosis. We are studying genetic abnormalities of this death pathway, which we have found to underlie the human disease, autoimmune lymphoproliferative syndrome (ALPS). The study of ALPS has revealed that inhibiting the death of lymphocytes can lead to autoimmune consequences. Also, the homeostasis of T lymphocytes can be powerfully affected by viruses and other infectious agents. In particular, the human immunodeficiency virus can cause the attrition of CD4+ Tlymphocytes by inducing the premature death of such cells. We are studying the molecular mechanism by which the HIV causes CD4+ T cell destruction. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 33 Z9 35 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2003 VL 27 IS 2-3 BP 387 EP 397 DI 10.1385/IR:27:2-3:387 PG 11 WC Immunology SC Immunology GA 706WF UT WOS:000184477500023 PM 12857983 ER PT J AU Schwartzberg, PL AF Schwartzberg, PL TI Genetic approaches to tyrosine kinase signaling pathways in the immune system SO IMMUNOLOGIC RESEARCH LA English DT Article DE Tec kinases; phospholipase-C-gamma actin cytoskeleton; T helper cell differentiation; SAP; X-linked proliferative syndrome ID LINKED LYMPHOPROLIFERATIVE DISEASE; TEC FAMILY; CELL-DIFFERENTIATION; T-LYMPHOCYTES; ITK; IMMUNODEFICIENCY; AGAMMAGLOBULINEMIA; RESPONSES; PROTEIN; DOMAIN AB The development of a productive immune response requires the carefully coordinated activation of lymphocytes through their cell-surface antigen receptors, surface immunoglobulin (Ig) on B cells and the T cell receptor (TCR) on T cells. Studies of mutant cell lines, gene-targeted mice and humans with inherited immunodeficiencies have demonstrated that tyrosine kinases are critical components of lymphocyte antigen-receptor-signaling pathways. Our laboratory is interested in the mechanisms by which modulation of signaling pathways involving tyrosine kinases and related signaling molecules can influence cell function and development. We have concentrated our attention on the genetic and biochemical dissection of signaling pathways in the immune system, and how altering these pathways can change responses to infectious disease. As a model system, we are examining the Tec family kinases and their roles in T lymphocyte development and function. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg 49,4A38,49 Convent Dr, Bethesda, MD 20892 USA. NR 24 TC 3 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2003 VL 27 IS 2-3 BP 481 EP 488 DI 10.1385/IR:27:2-3:481 PG 8 WC Immunology SC Immunology GA 706WF UT WOS:000184477500031 PM 12857991 ER PT J AU Siegel, RM Muppidi, J Roberts, M Porter, M Wu, ZQ AF Siegel, RM Muppidi, J Roberts, M Porter, M Wu, ZQ TI Death receptor signaling and autoimmunity SO IMMUNOLOGIC RESEARCH LA English DT Article DE apoptosis; autoimmunity; lymphoproliferation; Fas; tumor necrosis factor ID DOMAIN-CONTAINING RECEPTOR; TUMOR-NECROSIS-FACTOR; MATURE T-LYMPHOCYTES; INDUCED CELL-DEATH; NF-KAPPA-B; FAS-LIGAND; LYMPHOPROLIFERATIVE SYNDROME; DENDRITIC CELLS; INDUCED APOPTOSIS; ANTIGEN RECEPTOR AB In recent years, it has become clear that self-nonself discrimination by the immune system is driven not so much by the specificities of the antigen receptors themselves, but by ligand-receptor systems that sense the presence of foreign pathogens (toll-like receptors) and those that regulate the balance between cellular proliferation and programmed cell death (tumor necrosis factor [TNF] family ligands and receptors). Interestingly, these two receptor families share a number of common signaling pathways, mediated by the cytoplasmic proteins containing death domains and TRAF domains, which trigger the complementary processes of programmed cell death and inflammation. Both humans and mice with genetic defects in the TNF-receptor family member Fas accumulate abnormal lymphocytes and develop systemic autoimmunity. These findings highlighted the importance of this TNF-receptor family member in the homeostasis of the immune system. In particular, the Fas receptor has been shown to be important in immunoreceptor-mediated apoptosis of activated T and B lymphocytes. Six members of the TNF-receptor superfamily share a common signaling domain with Fas, termed the death domain, that directly links these receptors to the apoptotic machinery of the cell, and, collectively, these receptors have been designated as "death receptors." We are currently investigating a number of important unresolved issues in this field, including: (1) how susceptibility to apoptosis through death receptors is regulated, (2) how Fas and related death receptors function in the maintenance of self-tolerance and homeostasis in the major cell types of the immune system, and (3) recently described nonapoptotic lymphocyte activation signals that use components of death receptor signaling. C1 NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Siegel, RM (reprint author), NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bldg 10,Rm 9N238, Bethesda, MD 20892 USA. RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 84 TC 16 Z9 17 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2003 VL 27 IS 2-3 BP 499 EP 512 DI 10.1385/IR:27:2-3:499 PG 14 WC Immunology SC Immunology GA 706WF UT WOS:000184477500033 PM 12857993 ER PT J AU Sher, A Collazzo, C Scanga, C Jankovic, D Yap, G Aliberti, J AF Sher, A Collazzo, C Scanga, C Jankovic, D Yap, G Aliberti, J TI Induction and regulation of IL-12-dependent host resistance to Toxoplasma gondii SO IMMUNOLOGIC RESEARCH LA English DT Article DE Toxoplasma gondii; host resistance; IL-12; IFN-gamma; dendritic cells; IGTP ID DENDRITIC CELLS; INTRACELLULAR PATHOGEN; IL-12 PRODUCTION; CUTTING EDGE; INFECTION; INTERLEUKIN-12; SIGNAL AB Resistance to the intracellular protozoan parasite Toxoplasma gondii is initiated by the induction of interleukin-12 (IL-12), which stimulates interferon (IFN)-gamma synthesis by natural killer (NK) cells and T lymphocytes. This review summarizes the work of our laboratory on the mechanisms by which the parasite triggers IL-12 synthesis, and how this response is regulated to avoid the lethal effects of excessive tissue inflammation. In addition, we present an overview of our studies investigating the mechanisms by which the IFN-gamma-produced as a consequence of IL-12 stimulation controls intracellular replication of the parasite in host cells. C1 NIH, Bethesda, MD 20892 USA. Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA. RP Sher, A (reprint author), NIAID, Parasit Dis Lab, Bldg 50,Room 6140, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 12 TC 43 Z9 56 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2003 VL 27 IS 2-3 BP 521 EP 527 DI 10.1385/IR:27:2-3:521 PG 7 WC Immunology SC Immunology GA 706WF UT WOS:000184477500035 PM 12857995 ER PT J AU Sun, PD AF Sun, PD TI Structure and function of natural-killer-cell receptors SO IMMUNOLOGIC RESEARCH LA English DT Article DE KIR; NKG2D; Fc receptors; crystal structure; immunoreceptors; NK receptors ID FC-GAMMA RECEPTOR; CLASS-I MOLECULES; CRYSTAL-STRUCTURE; IMMUNOGLOBULIN-SUPERFAMILY; INHIBITORY RECEPTORS; NKG2D RECEPTOR; T-CELLS; NK CELLS; COMPLEX; CLONING AB The function of natural-killer (NK) cells is modulated by the balance between a number of activating and inhibitory receptors. Killer immunoglobulinlike receptors (KIRs) are mostly inhibitory receptors. They play a critical role in recognizing self-class-I major histocompatibility complex (MHC) molecules and thus protect healthy host cells from NK-targeted lysis. In contrast, both NKG2D and CD 16 are activating NK receptors that trigger the NK-cell lysis of various tumor and virally infected cells through either direct ligand engagement or antibody-dependent cellular cytotoxicity (ADCC). Through structural studies of members of these distinct receptor families, in particular, the structure and recognition between KIR2DL2 and HLA-Cw3, that between NKG2D and ULBP3, and that between CD 16 and IgG Fc, considerable understandings have been achieved about their function and their ligand recognition. C1 NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 48 TC 25 Z9 28 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2003 VL 27 IS 2-3 BP 539 EP 548 DI 10.1385/IR:27:2-3:539 PG 10 WC Immunology SC Immunology GA 706WF UT WOS:000184477500037 PM 12857997 ER PT J AU Buggage, RR Matteson, DM Shen, DF Sun, B Tuaillon, N Chan, CC AF Buggage, RR Matteson, DM Shen, DF Sun, B Tuaillon, N Chan, CC TI Effect of sex hormones on experimental autoimmune uveoretinitis (EAU) SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Article DE experimental autoimmune uveoretinitis (EAU); estrogen; progesterone; testosterone; Th1 & Th2 cytokines ID RETINOID-BINDING PROTEIN; IMMUNE-RESPONSES; T-LYMPHOCYTES; MECHANISMS; DISEASES; UVEITIS; IMMUNODOMINANT; SUSCEPTIBILITY; TESTOSTERONE; EXPRESSION AB Purpose: Sex hormones have been associated with the prevalence, susceptibility, and severity of autoimmune disease. Although the exact mechanism is unknown, sex hormones are reported to influence cytokine production, specifically by affecting the balance of Th1 and Th2 effector cells. We evaluated the effect of estrogen, progesterone, and testosterone in autoimmune uveoretinitis (EAU), a rodent model of human ocular autoimmune disease. Methods: Lewis rats implanted with either beta-estradiol (estrogen), 5-dihydrotestosterone (5-DHT), norgestrel (progesterone), or estrogen plus progesterone were immunized with the retinal antigen interphotoreceptor retinoid binding protein (IRBP) peptide. Evaluation of EAU was based on histology of the eyes and measurement of peripheral immunological responses of DTH and lymphocyte proliferation to S-antigen. Quantitative RT-PCR was used to measure IFN-gamma and IL-10 mRNA in the eyes. Results: In female rats 5-DHT significantly decreased, estrogen slightly enhanced, but progesterone or estrogen + progesterone did not affect EAU. In contrast, in male rats 5-DHT slightly decreased, estrogen moderately decreased, progesterone did not effect, but, estrogen + progesterone slightly decreased EAU. The results correlated with the ocular levels of Th1 (IFN-gamma) and Th2 (IL-10) cytokine messengers. Conclusion: The data support the hypothesis that sex hormones may affect autoimmune diseases by inducing changes in the cytokine balance. This suggests that sex hormone therapy could be considered as an adjunct to anti-inflammatory agents to treat ocular autoimmune diseases in humans. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Buggage, RR (reprint author), 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20892 USA. NR 33 TC 17 Z9 20 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PY 2003 VL 32 IS 4 BP 259 EP 273 DI 10.1081/IMM-120025105 PG 15 WC Immunology SC Immunology GA 738MV UT WOS:000186293200004 PM 14603994 ER PT J AU Sundstrom, M Vliagoftis, H Karlberg, P Butterfield, JH Nilsson, K Metcalfe, DD Nilsson, G AF Sundstrom, M Vliagoftis, H Karlberg, P Butterfield, JH Nilsson, K Metcalfe, DD Nilsson, G TI Functional and phenotypic studies of two variants of a human mast cell line with a distinct set of mutations in the c-kit proto-oncogene SO IMMUNOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; CONSTITUTIVELY ACTIVATING MUTATIONS; GASTROINTESTINAL STROMAL TUMORS; LIGAND-INDEPENDENT ACTIVATION; BLOOD MONONUCLEAR-CELLS; FC-EPSILON-RI; HIGH-AFFINITY; PERIPHERAL-BLOOD; HEMATOPOIETIC-CELLS; CATALYTIC DOMAIN AB The human mast cell line (HMC)-1 cell line is growth-factor independent because of a constitutive activity of the receptor tyrosine kinase Kit. Such deregulated Kit activity has also been suggested causative in gastrointestinal stromal tumours (GISTs) and mastocytosis. HMC-1 is the only established continuously growing human mast cell line and has therefore been widely employed for in vitro studies of human mast cell biology. In this paper we describe two sublines of HMC-1, named HMC-1(560) and HMC-1(560,816) , with different phenotypes and designated by the locations of specific mutations in the c-kit proto-oncogene. Activating mutations in the Kit receptor were characterized using the pyrosequencing(TM) method. Both sublines have a heterozygous T to G mutation at codon 560 in the juxtamembrane region of the c-kit gene causing an amino acid substitution of Gly-560 for Val. In contrast, only HMC-1(560,816) cells have the c-kit (V816) mutation found in mast cell neoplasms causing an Asp-->Val substitution in the intracellular kinase domain. Kit was constitutively phosphorylated on tyrosine residues and associated with phosphatidylinositol 3'-kinase (PI 3-kinase) in both variants of HMC-1, but this did not lead to a constitutive phosphorylation of Akt or extracellular regulated protein kinase (ERK), which are signalling molecules normally activated by the interaction of stem cell factor (SCF) with Kit. The documentation and characterization of two sublines of HMC-1 cells provides both information on the biological consequences of mutations in Kit and recognition of the availability of what in reality are two distinct cultured human mast cell lines. C1 Univ Uppsala, Dept Genet & Pathol, Lab Tumor Biol, S-75185 Uppsala, Sweden. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Pyrosequencing AB, Uppsala, Sweden. Mayo Clin, Dept Allerg Dis, Rochester, MN USA. RP Nilsson, G (reprint author), Univ Uppsala, Dept Genet & Pathol, Lab Tumor Biol, S-75185 Uppsala, Sweden. RI Vliagoftis, Harissios/C-6480-2013 NR 52 TC 52 Z9 52 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JAN PY 2003 VL 108 IS 1 BP 89 EP 97 DI 10.1046/j.1365-2567.2003.01559.x PG 9 WC Immunology SC Immunology GA 634RL UT WOS:000180354400013 PM 12519307 ER PT J AU De Lorenzo, MS Ripoll, GV Yoshiji, H Yamazaki, M Thorgeirsson, UP Alonso, DF Gomez, DE AF De Lorenzo, MS Ripoll, GV Yoshiji, H Yamazaki, M Thorgeirsson, UP Alonso, DF Gomez, DE TI Altered tumor angiogenesis and metastasis of B16 melanoma in transgemc mice overexpressing tissue inhibitor of metalloproteinases-1 SO IN VIVO LA English DT Article DE TIMP-1; angiogenesis; metastasis; transgenic animal ID MATRIX METALLOPROTEINASES; MAMMARY-CARCINOMA; EXPRESSION; GROWTH; MODEL; CELLS; SUPPRESSES; APOPTOSIS; INVASION; TIMP-1 AB Tissue inhibitor of metalloproteinases-1 (TIMP-1) has emerged as a multifunctional protein that plays contrasting roles during angiogenesis and cancer spread. We have investigated the growth, vascularization and metastasis of B16 melanoma cells in a transgenic mouse model with elevated TIMP-1 levels in the systemic circulation. Transgenic C57BL/6j-CBA mice overexpressing human TIMP-1 in the liver under the control of the mouse albumin promoter / enhancer were employed. An early subcutaneous growth advantage and an increased tumor angiogenic response were observed in transgenic animals with respect to wild-type hybrid mice. On the contrary, there was a dramatic decrease in the lung colonizing ability of B16 melanoma cells in TIMP-1 transgenic mice. No significant effect on metastasis formation was observed in another transgenic mouse model with increased TIMP-1 expression in lungs but low plasma levels, where the transgene was placed under the control of the murine mammary tumor virus promoter. These results support the notion that TIMP-1 displays paradoxical effects on tumor progression and suggest that circulating TIMP-1 is efficient in suppressing lung colonization of melanoma cells. C1 Univ Nacl Quilmes, Oncol Mol Lab, Dept Sci & Technol, Buenos Aires, DF, Argentina. Nara Med Univ, Dept Internal Med 3, Nara, Japan. NCI, Div Basic Sci, Cellular Carcinogenesis & Tumor Promot Lab, Tumor Biol & Carcinogenesis Sect,NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Med, New York Presbyterian Hosp, New York, NY USA. RP Gomez, DE (reprint author), Univ Nacl Quilmes, Oncol Mol Lab, Dept Sci & Technol, R Saenz Pena 180,B1876BXD, Buenos Aires, DF, Argentina. NR 23 TC 18 Z9 19 U1 1 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JAN-FEB PY 2003 VL 17 IS 1 BP 45 EP 50 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 655EB UT WOS:000181537400008 PM 12655789 ER PT J AU Mash, C Keen, R Berthier, NE AF Mash, C Keen, R Berthier, NE TI Visual access and attention in two-year-olds' event reasoning and object search SO INFANCY LA English DT Article ID YOUNG-CHILDREN; LOCATION; INFANTS; TASK; STRATEGIES; KNOWLEDGE; MEMORY; CUES AB Several recent studies have revealed substantial limitations in 2-year-olds' ability to search accurately for objects that have undergone unseen movement, even along highly constrained paths. In many of these studies, children observed a ball as it rolled down a track and behind an occluding panel that contained 4 doors. The track had a barrier that was partly visible and could be placed in locations corresponding to the doors. When the ball came to a rest against the barrier and behind the occluder, the child's task was to find the ball by opening the correct door. The search accuracy of 2-year-olds has not differed from chance across several variations of this task. This research was conducted to identify the source of 2-year-olds' limitation in this domain. Children were granted a full view of the event before the ball was occluded with a door panel. Children's performance was better under this condition, but was still not systematically accurate unless their gaze remained locked onto the correct location. Two-year-olds' weak performance in these search tasks appears to be more a consequence of limitations in spatial integration than in their representation of unseen movement. C1 Univ Massachusetts, Amherst, MA 01003 USA. RP Mash, C (reprint author), NICHD, Sect Child & Family Res, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. NR 29 TC 21 Z9 21 U1 2 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1525-0008 J9 INFANCY JI Infancy PY 2003 VL 4 IS 3 BP 371 EP 388 DI 10.1207/S15327078IN0403_04 PG 18 WC Psychology, Developmental SC Psychology GA 739XN UT WOS:000186372200004 ER PT J AU Segal, BH Ding, L Holland, SM AF Segal, BH Ding, L Holland, SM TI Phagocyte NADPH oxidase, but not inducible nitric oxide synthase is essential for early control of Burkholderia cepacia and Chromobacterium violaceum infection in mice SO INFECTION AND IMMUNITY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; RECOMBINANT INTERFERON-GAMMA; RESPIRATORY BURST ACTIVITY; HOST-DEFENSE; REACTIVE NITROGEN; POLYMORPHONUCLEAR LEUKOCYTES; ANTIMICROBIAL ACTIVITY; PSEUDOMONAS-CEPACIA; HYDROGEN-PEROXIDE; CYSTIC-FIBROSIS AB Reactive oxygen and nitrogen intermediates have critical, partially overlapping roles in host defense against a variety of pathogens. Using mice deficient in generating phagocyte superoxide (p47(phox-/-)) and mice deficient in generating inducible nitric oxide synthase (iNOS(-/-)), we examined the roles of these reactive species in host defense against Burkholderia cepacia and Chromobacterium violaceum, organisms known to have unusual virulence in chronic granulomatous disease. Intraperitoneal B. cepacia challenge (4.0 X 10(3) to 4.0 X 10(5) organisms/mouse) resulted in mortality in all p47(phox-/-) mice, with the survival interval being inversely proportionate to the amount of inoculum. Pretreatment with gamma interferon did not affect survival. C. violaceum was strikingly virulent in p47(phox-/-) mice (the 50% lethal dose [LD50] was < 13 organisms). iNOS(-/-)and wild-type mice were resistant to B. cepacia challenges of at least 106 organisms per mouse, and the LD50 of C. violaceum was between 10(6) and 10(7) organisms per mouse. Consistent with the survival data, numbers of organisms in cultures of B. cepacia from multiple sites were higher for p47(phox-/-) mice than for iNOS(-/-) and wild-type mice at day 4 after challenge, but numbers of organisms for different B. cepacia strains varied. The recovery of C. violaceum was strikingly greater at 18 h after challenge for p47(phox-/-) mice than for iNOS(-/-) and wild-type mice, in which the organism burdens were virtually nil. In vitro, both B. cepacia and C. violaceum were sensitive to H2O2 and to reactive nitrogen intermediates but the sensitivities of different strains varied significantly. Host defense against B. cepacia and C violaceum is critically dependent in vivo on reactive oxygen intermediates, and these species are model organisms to further dissect host and pathogen interactions related to the generation and scavenging of microbicidal reactive intermediates. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 37 TC 16 Z9 18 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2003 VL 71 IS 1 BP 205 EP 210 DI 10.1128/IAI.71.1.205-210.2003 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 632EZ UT WOS:000180212000025 PM 12496167 ER PT J AU Jeevan, A Yoshimura, T Lee, KE McMurray, DN AF Jeevan, A Yoshimura, T Lee, KE McMurray, DN TI Differential expression of gamma interferon mRNA induced by attenuated and virulent Mycobacterium tuberculosis in guinea pig cells after Mycobacterium bovis BCG vaccination SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; BACILLUS-CALMETTE-GUERIN; IFN-GAMMA; PULMONARY TUBERCULOSIS; T-CELLS; PROTEIN-DEFICIENT; MOLECULAR-CLONING; AVIUM COMPLEX; FACTOR-ALPHA; INFECTION AB To determine whether Mycobacterium bovis BCG vaccination would alter gamma interferon (IFN-gamma) mRNA expression in guinea pig cells exposed to Mycobacterium tuberculosis, we cloned a cDNA encoding guinea pig IFN-gamma from a spleen cell cDNA library. The cDNA is composed of 1,110 bp, with an open reading frame encoding a 166-amino-acid protein which shows 56 and 41% amino acid sequence homology to human and mouse IFN-gamma respectively. Spleen or lymph node cells from naive and BCG-vaccinated guinea pigs were stimulated with purified protein derivative (PPD) or M. tuberculosis H37Ra or H37Rv, and the total RNA was subjected to Northern blot analysis with a P-32-labeled probe derived from the cDNA clone. Compared to the IFN-gamma mRNA expression in cells of naive animals, that in spleen and lymph node cells exposed to various stimuli was enhanced after BCG vaccination. However, there was a significant reduction in IFN-gamma mRNA levels when cells were stimulated with a multiplicity of infection of greater than 1 virulent M. tuberculosis bacterium per 10 cells. The enhanced IFN-gamma mRNA response in BCG-vaccinated animals was associated with an increase in the proportions of CD4(+) T cells in the spleens, as determined by fluorescence-activated cell sorter analysis. Furthermore, the nonadherent population in the spleens enriched either by panning with anti-guinea pig immunoglobulin G-coated plates or by purification on nylon wool columns produced more IFN-gamma mRNA than whole spleen cells following stimulation with concanavalin A or PPD. This indicates that T cells are principally responsible for the upregulation of IFN-gamma mRNA expression following BCG vaccination. The mechanism by which virulent mycobacteria suppress IFN-gamma mRNA accumulation is currently under investigation. C1 Texas A&M Univ, Syst Hlth Sci Ctr, Dept Immunol & Med Microbiol, College Stn, TX 77843 USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Jeevan, A (reprint author), Texas A&M Univ, Syst Hlth Sci Ctr, Dept Immunol & Med Microbiol, 407 Reynolds Med Bldg, College Stn, TX 77843 USA. FU NIAID NIH HHS [R01 AI015495, R01AI 15495] NR 49 TC 28 Z9 28 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2003 VL 71 IS 1 BP 354 EP 364 DI 10.1128/IAI.71.1.354-364.2003 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 632EZ UT WOS:000180212000043 PM 12496185 ER PT J AU Shreedhar, VK Kelsall, BL Neutra, MR AF Shreedhar, VK Kelsall, BL Neutra, MR TI Cholera toxin induces migration of dendritic cells from the subepithelial dome region to T- and B-cell areas of Peyer's patches SO INFECTION AND IMMUNITY LA English DT Article ID EPITHELIAL M-CELLS; SALMONELLA-TYPHIMURIUM; IN-VIVO; DIFFERENTIATION; CD8-ALPHA(+); LYMPHOCYTES; PARTICLES; REOVIRUS; SUBSETS; ENTRY AB Intestinal M cells deliver macromolecules, particles, and pathogens into the subepithelial dome (SED) region of Peyer's patch mucosa, an area rich in dendritic cells (DCs). We tested whether uptake of the mucosal adjuvant cholera toxin (CT) or live Salmonella bacteria can induce DC migration within Peyer's patches. Virus-sized, fluorescent polystyrene microparticles were efficiently transported by M cells and ingested by CD11c(+), CD11b(-), and CD8a(-) DCs in the SED region. DCs loaded with microparticles remained in the SED for up to 14 days. CT (but not the CT B subunit) and live attenuated Salmonella enterica serovar Typhimurium bacteria induced migration of the microparticle-loaded DCs from the SED region into underlying B-cell follicles and adjacent parafollicular T-cell zones. Our data provide the first demonstration that DCs move in response to enterotoxin adjuvants and live bacteria that enter the mucosa via M cells. C1 Childrens Hosp, GI Cell Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Clin Invest Lab, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. RP Neutra, MR (reprint author), Childrens Hosp, GI Cell Biol Lab, Enders 1220,300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI35365, AI34757, P01 AI035365, U01 AI035365]; NICHD NIH HHS [R01 HD017557, HD17557]; NIDDK NIH HHS [P30 DK034854, DK34854] NR 30 TC 105 Z9 115 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2003 VL 71 IS 1 BP 504 EP 509 DI 10.1128/IAI.71.1.504-509.2003 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 632EZ UT WOS:000180212000059 PM 12496201 ER PT J AU Kutty, G Kovacs, JA AF Kutty, G Kovacs, JA TI A single-copy gene encodes kex1, a serine endoprotease of Pneumocystis jiroveci SO INFECTION AND IMMUNITY LA English DT Article ID MAJOR SURFACE GLYCOPROTEIN; MOLECULAR CHARACTERIZATION; DIHYDROPTEROATE SYNTHASE; DIHYDROFOLATE-REDUCTASE; CARINII; PROTEASE; FAMILY AB We have cloned and characterized the kex1 gene of Pneumocystis jiroveci. Unlike the case for Pneumocystis carinii, in which the homologous PRT-1 genes are multicopy, kex1 is a single-copy gene encoding a protein homologous to fungal serine endoproteases, which localize to the Golgi apparatus. Thus, substantial biological differences can be seen among Pneumocystis species. C1 Warren G Magnuson Clin Ctr, Crit Care Med Dept, NIH, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), Bldg 10,Rm 7D43,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@nih.gov NR 24 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2003 VL 71 IS 1 BP 571 EP 574 DI 10.1128/IAI.71.1.571-574.2003 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 632EZ UT WOS:000180212000072 PM 12496214 ER PT J AU Kirman, JR Turon, T Su, H Li, A Kraus, C Polo, JM Belisle, J Morris, S Seder, RA AF Kirman, JR Turon, T Su, H Li, A Kraus, C Polo, JM Belisle, J Morris, S Seder, RA TI Enhanced immunogenicity to Mycobacterium tuberculosis by vaccination with an alphavirus plasmid replicon expressing antigen 85A SO INFECTION AND IMMUNITY LA English DT Article ID REPLICATING RNA VACCINE; DOUBLE-STRANDED-RNA; DENDRITIC CELLS; DNA VACCINES; PROTECTIVE EFFICACY; VIRUS; IMMUNIZATION; VECTORS; HEAT-SHOCK-PROTEIN-70; ACTIVATION AB The immunogenicity of a plasmid DNA vaccine incorporating Sindbis virus RNA replicase functions (pSINCP) and expressing antigen 85A (Ag85A) from Mycobacterium tuberculosis was compared with a conventional plasmid DNA vector encoding Ag85A. pSINCP-85A was highly immunogenic in mice and gave enhanced long-term protection against M. tuberculosis compared with the conventional vector. C1 Vaccine Res Ctr, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Natl Allergy & Infect Dis, Immunogenet Lab, NIH, Bethesda, MD USA. Food & Drug Adm, Bethesda, MD USA. Chiron Corp, Vaccines Res, Emeryville, CA USA. Colorado State Univ, Dept Microbiol, Ft Collins, CO USA. RP Seder, RA (reprint author), Vaccine Res Ctr, Cellular Immunol Sect, NIH, 40 Convent Dr,Rm 40-3512, Bethesda, MD 20892 USA. RI Belisle, John/B-8944-2017 OI Belisle, John/0000-0002-2539-2798 NR 19 TC 48 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2003 VL 71 IS 1 BP 575 EP 579 DI 10.1128/IAI.71.1.575-579.2003 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 632EZ UT WOS:000180212000073 PM 12496215 ER PT S AU Marquez, VE AF Marquez, VE BE Pankiewicz, KW Goldstein, BM TI The discovery of thiazole-4-carboxamide adenine dinucleotide (TAD) and a recent synthetic approach for the construction of a hydrolytically resistant surrogate SO INOSINE MONOPHOSPHATE DEHYDROGENASE: A MAJOR THERAPEUTIC TARGET SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT 1st National Symposium on Inosine Monophosphate Dehydrogenase CY AUG 20-21, 2000 CL WASHINGTON, D.C. SP Amer Chem Soc, Div Carbohydrate Chem ID INOSINE MONOPHOSPHATE DEHYDROGENASE; IMP DEHYDROGENASE; 5'-MONOPHOSPHATE DEHYDROGENASE; TIAZOFURIN METABOLISM; MITSUNOBU REACTION; BENZYL-ESTERS; ANALOGS; 2-BETA-D-RIBOFURANOSYLTHIAZOLE-4-CARBOXAMIDE; INHIBITORS; MECHANISM AB A short account of the mechanism of action of the oncolytic nucleoside, tiazofurin, and the discovery of its active metabolite, TAD, is described. The chapter also includes a brief history of the early chemical approaches used for the synthesis of TAD and other analogues, including the phosphodiesterase-resistant beta-methylene TAD phosphonate. A new synthetic approach to the latter compound is highlighted as a viable way to obtain this class of compounds in larger quantities. U.S. government work. Published 2003 American Chemical Society. C1 NCI, NIH, Med Chem Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Marquez, VE (reprint author), NCI, NIH, Med Chem Lab, Ctr Canc Res, Bldg 376,Boyles St,Room 104,POB B, Ft Detrick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov NR 32 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3780-8 J9 ACS SYM SER PY 2003 VL 839 BP 198 EP 210 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Genetics & Heredity SC Biochemistry & Molecular Biology; Chemistry; Genetics & Heredity GA BW37A UT WOS:000181756900010 ER PT J AU Veenstra, T Conrads, TP Issaq, HJ AF Veenstra, T Conrads, TP Issaq, HJ TI An accurate mass tag strategy for quantitative and high throughput proteome measurements SO INSTRUMENTATION SCIENCE & TECHNOLOGY LA English DT Letter C1 NCI, Frederick, MD 21701 USA. RP Veenstra, T (reprint author), NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1073-9149 J9 INSTRUM SCI TECHNOL JI Instrum. Sci. Technol. PY 2003 VL 31 IS 1 BP 103 EP 103 DI 10.1081/CI-120018412 PG 1 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA 653ET UT WOS:000181422800011 ER PT J AU Sarpong, SB Zhang, LY Kleeberger, SR AF Sarpong, SB Zhang, LY Kleeberger, SR TI A novel mouse model of experimental asthma SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE recombinant cockroach; dust mite; novel mouse model; inner city asthma ID HOUSE-DUST MITE; INNER-CITY CHILDREN; COCKROACH ALLERGEN; RISK-FACTORS; EXPOSURE; RESPONSES; SENSITIZATION; MICE; INFLAMMATION; INDUCTION AB Background: Animal models that mimic the pulmonary features observed in human asthma are important tools to study the mechanism(s) of allergen-induced asthma. Cockroach and dust mite allergens are two common allergens found in the 'inner city' environment. In this study, we examined the interaction between recombinant cockroach (r Bla g 2) and dust mite (r Der f 1) allergens in inbred mouse strain (A/J). The tested hypothesis was that there are enhanced effects of exposure to r Bla g 2 and r Der f 1 allergens in the airway inflammatory response in A/J mice. Methods: Five groups of mice (male, 6-8 weeks) were examined: vehicle (saline) controls; adjuvant ( alum) controls; r Bla g 2 immunized (0.01-10 mug/mouse), r Der f 1 immunized (0.01-10 mug/mouse), and combined immunization with r Der f 1 (0.05 mug/mouse) and r Bla g 2 (0.0 5 mug/mouse). Mice were immunized at days 0 and 7, challenged by orotracheal inhalation with r Der f 1 and/or r Bla g 2 allergen at day 14, and were studied and sacrificed on day 17. Airway hyperreactivity was measured by peak airway pressure and airway pressure time index (APTI). Differential cell analysis and total proteins in bronchoalveolar lavage returns were used to assess airway inflammation and epithelial injury. Results: Dose-related statistically significant increases in peak pressure, APTI, total cells, eosinophils, epithelial cells, but not total proteins, were induced by r Bla g 2 challenge in r Bla g 2-immunized mice. Similar allergen-induced dose-related increases in airway total cells, eosinophils, epithelial cells and total proteins were observed in r Der f 1 immunized mice. Compared to either allergen alone, enhanced airway inflammation and epithelial damage, but not airway reactivity, were detected in the combined group. Conclusion: This novel mouse model will allow investigation of the immunopathogenesis of human asthma and should provide insight into the common form of 'inner city asthma'. Copyright (C) 2003 S. Karger AG, Basel. C1 Howard Univ, Natl Human Genome Ctr, Dept Pediat & Child Hlth, Washington, DC 20060 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. NIEHS, Pulm Branch, Res Triangle Pk, NC 27709 USA. RP Sarpong, SB (reprint author), Howard Univ, Natl Human Genome Ctr, Dept Pediat & Child Hlth, Towers 4112,2041 Georgia Ave, Washington, DC 20060 USA. FU NHLBI NIH HHS [UO1 HL 72433]; NIAID NIH HHS [K08 AI 01450]; NIEHS NIH HHS [ES 03819] NR 29 TC 22 Z9 26 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2003 VL 132 IS 4 BP 346 EP 354 DI 10.1159/000074902 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 760CW UT WOS:000187794600007 PM 14707466 ER PT J AU Kondraganti, SR Fernandez-Saluguero, P Gonzalez, FJ Ramos, KS Jiang, WW Moorthy, H AF Kondraganti, SR Fernandez-Saluguero, P Gonzalez, FJ Ramos, KS Jiang, WW Moorthy, H TI Polycyclic aromatic hydrocarbon-inducible DNA adducts: Evidence by P-32-postlabeling and use of knockout mice for AH receptor-independent mechanisms of metabolic activation in vivo SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE DNA adducts; AH receptor; P-32-postlabeling; polycyclic aromatic hydrocarbons; knockout mice; cytochrome P4501A; cytochrome P4501B1 ID RAT-LIVER; BENZOPYRENE METABOLISM; MUTATIONAL HOTSPOTS; MESSENGER-RNA; CELL-CULTURES; I-COMPOUNDS; EXPRESSION; CYTOCHROME-P450; INDUCTION; CYP1B1 AB There is significant human exposure to polycyclic aromatic hydrocarbons (PAHs), many of which are potent carcinogens in laboratory animals and are suspected human carcinogens. The PAHs are bioactivated by cytochrome P450 (CYP)IAI/ I B I enzymes to reactive intermediates that bind to DNA, a critical step in the initiation of carcinogenesis. The Ah receptor (AHR) plays a critical role in the induction of CYPI enzymes (i.e., I I A 1, IA2 and I B 1) by PAHs such as benzo[a]pyrene (BP) and 3-methylcholanthrene (MC). In our investigation, we tested the hypothesis that AHR-null animals are less susceptible to PAH-induced DNA adduct formation than wild-type animals. Wild-type [AHR (+/+)] mice or mice lacking the gene for the AHR were treated with a single dose (100 mumol/kg) of BP or MC, and hepatic DNA adducts were analyzed by P-32-postlabeling. BP induced multiple hepatic DNA adducts in wild-type as well as AHR-null animals, suggesting the existence of AHR-independent mechanisms for BP metabolic activation. On the other hand, DNA adduct formation was markedly suppressed in AHR-null animals exposed to MC, although the major MC-DNA adduct was produced in these animals. Hepatic activities and apoprotein contents of 7-ethoxyresorufln O-deethylase (EROD) (CYPIAI) and 7-methoxyresorufin O-demethylase (MROD) (CYPIA2) activities were markedly induced by BP and MC in the wild-type, but not, in AHR-null animals. CYP I B I expression was also induced, albeit to a lesser extent by the PAH MC, but not BP, in the wild-type animals. In conclusion, these results demonstrate the existence of AHR-and CYPIAI-independent mechanisms of PAH metabolic activation in mouse liver, a phenomenon that may have important implications for PAH-mediated carcinogenesis. (C) 2002 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Univ Extremadura, Dept Bioquim & Biol Mol & Genet, Badajoz, Spain. NCI, Canc Res Ctr, Bethesda, MD USA. Texas A&M Univ, Coll Vet Med, Fac Toxicol, College Stn, TX 77843 USA. Texas A&M Univ, Coll Vet Med, Dept Physiol & Pharmacol, College Stn, TX 77843 USA. RP Baylor Coll Med, Dept Pediat, Baylor Plaza 1, Houston, TX 77030 USA. EM bmoorthy@bcm.tmc.edu OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 FU NIEHS NIH HHS [ES 09132] NR 59 TC 49 Z9 49 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2003 VL 103 IS 1 BP 5 EP 11 DI 10.1002/ijc.10784 PG 7 WC Oncology SC Oncology GA 623GZ UT WOS:000179696100002 PM 12455047 ER PT J AU Kawakami, M Kawakami, K Puri, RK AF Kawakami, M Kawakami, K Puri, RK TI Tumor regression mechanisms by IL-13 receptor-targeted cancer therapy involve apoptotic pathways SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE IL-13 receptor; head-and-neck squamous cell carcinoma; cytotoxin; apoptosis; athymic nu/nu mice ID CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; INTERLEUKIN-13 RECEPTOR; CYTOCHROME-C; NECK-CANCER; HUMAN HEAD; PROTEIN; MITOCHONDRIA; RELEASE; GROWTH AB IL-13 cytotoxin, composed of IL-13 and a truncated form of Pseudomonas exotoxin, targets IL-13R-overexpressing tumor cell lines in vitro and in vivo. To reveal the molecular mechanism of IL-13 cytotoxin-induced cell death in vivo, we demonstrate activation of apoptotic pathways in 2 s.c. growing human SCCHN tumor models in immunodeficient mice after i.t. administration of IL-13 cytotoxin. Treatment of HN 12 tumor bearing mice with Lp. or i.t. administration of IL-13 cytotoxin mediated marked regression of established tumors with complete remission. Interestingly, after a single i.t. administration, IL-13 cytotoxin disappeared within 6 hr but accumulation of caspase-3, -8 and -9 and cleavage of procaspase-3 and PARP continued within the tumors for a prolonged period. We further demonstrate that IL-13 cytotoxin also utilizes an alternate pathway of cell death via the release of cytochrome c from mitochondria to the cytosol. Our results indicate that IL-13 cytotoxin induces 2 major pathways of apoptosis, which may play a role in tumor regression. In addition, apoptotic molecules may serve as surrogate molecular markers of tumor response to IL-13R-directed cytotoxin therapy. (C) 2002 Wiley-Liss, Inc. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bldg 29B,Rm 2NN10,29 Lincoln Dr,MSC4555, Bethesda, MD 20892 USA. NR 31 TC 13 Z9 14 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 JAN 1 PY 2003 VL 103 IS 1 BP 45 EP 52 DI 10.1002/ijc.10778 PG 8 WC Oncology SC Oncology GA 623GZ UT WOS:000179696100007 PM 12455052 ER PT J AU Otte, JM Otte, C Beckedorf, S Schmitz, F Vonderhaar, BK Folsch, UR Kloehn, S Herzig, KH Monig, H AF Otte, JM Otte, C Beckedorf, S Schmitz, F Vonderhaar, BK Folsch, UR Kloehn, S Herzig, KH Monig, H TI Expression of functional prolactin and its receptor in human colorectal cancer SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE LA English DT Article DE prolactin; prolactin receptor; human colorectal cancer; normal intestinal mucosa; colorectal cancer cell lines ID HUMAN-BREAST-CANCER; POLYMERASE CHAIN-REACTION; VIVO PERFUSION TECHNIQUE; GROWTH-HORMONE; ECTOPIC PRODUCTION; PLASMA PROLACTIN; EPITHELIAL-CELLS; GENE-EXPRESSION; MESSENGER-RNA; CARCINOMA AB Background and aims: Ectopic production of prolactin has been reported for several tumors, and elevated prolactin plasma levels have been detected in colorectal cancer patients. However, the role of prolactin in colorectal cancer remains unclear. We therefore compared expression patterns of prolactin and its receptor in normal and neoplastic colonic mucosa of the same patient with noncancer controls and determined mitogenic effects in vitro. Materials and methods: mRNA and protein expression was analyzed by semiquantitative RT-PCR and western blotting. Localization of ligand and receptor in tissues was investigated by immunohistochemistry. Mitogenic effects of prolactin on colorectal cancer cell lines (Caco-2. HT-29, LoVo) were assayed by [H-3]thymidine incorporation, Results: mRNA expression of prolactin was detected in 13% of normal and 27% of cancer specimens, with the highest levels seen in moderately differentiated tumors. Receptor mRNA was amplified from the majority of normal (96%) and cancer (94%) samples with an overexpression seen in tumor tissues. Protein expression of prolactin was detected in cancer tissues only. with the highest levels seen in moderately differentiated tumors. Receptor protein expression was correlated with the RT-PCR data, showing up to four-fold overexpression in tumor tissues. Staining for both ligand and receptor Was observed in epithelial cells. DNA synthesis was significantly stimulated by prolactin in all cell lines reaching 167-197% of unstimulated controls. Conclusion: Expression of prolactin, overexpression of prolactin receptors in colorectal cancers, and mitogenic effects of prolactin suggests a role for this hormone in a subgroup of colorectal cancers, which is presumably mediated by paracrine/autocrine pathways. C1 Univ Kiel, Dept Internal Med 1, D-24105 Kiel, Germany. NCI, Bethesda, MD 20892 USA. RP Monig, H (reprint author), Univ Kiel, Dept Internal Med 1, Schittenhelmstr 12, D-24105 Kiel, Germany. NR 48 TC 12 Z9 14 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0179-1958 J9 INT J COLORECTAL DIS JI Int. J. Colorectal Dis. PD JAN PY 2003 VL 18 IS 1 BP 86 EP 94 DI 10.1007/s00384-002-0414-7 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 628KV UT WOS:000179994700014 PM 12458387 ER PT J AU Yanovski, SZ AF Yanovski, SZ TI Binge eating disorder and obesity in 2003: Could treating an eating disorder have a positive effect on the obesity epidemic? SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE binge eating; compensatory behaviors; early intervention; obesity ID COGNITIVE-BEHAVIORAL THERAPY; WEIGHT-LOSS; PREVALENCE; TRENDS; INDIVIDUALS; OVERWEIGHT; MULTISITE; PATTERNS; EATERS AB Objective: The purpose of this paper is to explore the relationship between binge eating disorder (BED) and obesity. Methods: Recent literature relating to the etiology, risk factors, pathophysiology, and treatment of binge eating disorder was reviewed. Results: The data suggest that binge eating may be a contributor to the development of obesity in susceptible individuals. Although eating disorders treatment in the absence of obesity treatment does not result in large weight losses, amelioration of binge eating does result in small weight losses and decreased weight regain over time. Discussion: Our challenge in the future is to understand better the ways in which BED and obesity co-exist, and to find treatment strategies that will relieve the distress and dysfunction due to this disordered eating while enhancing appropriate weight loss or preventing further weight gain. Published 2003 by Wiley Periodicals, Inc.(dagger). C1 NIDDKD, Div Disgest Dis & Nutr, Bethesda, MD 20892 USA. RP Yanovski, SZ (reprint author), NIDDKD, Div Disgest Dis & Nutr, 6707 Democracy Blvd,Room 665, Bethesda, MD 20892 USA. EM sy29f@nih.gov NR 23 TC 83 Z9 85 U1 6 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PY 2003 VL 34 SU S BP S117 EP S120 DI 10.1002/eat.10211 PG 4 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 708UL UT WOS:000184587900012 PM 12900992 ER PT J AU Nishi, H Neta, G Nishi, KH Akers, LM Rikiyama, T Proctor, KN Murphy, BA Johnson, AC AF Nishi, H Neta, G Nishi, KH Akers, LM Rikiyama, T Proctor, KN Murphy, BA Johnson, AC TI Analysis of the epidermal growth factor receptor promoter: The effect of nuclear factor-kappa B SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE EGFR promoter; transcription factor; NF-kappa B; DNA binding protein ID DNA-BINDING PROTEIN; NF-KAPPA; GENE-EXPRESSION; TRANSCRIPTIONAL REPRESSOR; IDENTIFICATION; ACTIVATION; CELLS; SEQUENCE; CLONING; SITE AB The epidermal growth factor receptor gene is highly regulated and responsive to extracellular stimuli that control cell growth. We have identified five putative nuclear factor-kappaB (NF-kappaB) binding sites within the epidermal growth factor receptor (EGFR) promoter region by sequence analysis. We have analyzed the potential role of NF-kappaB family members in the regulation of the EGFR transcription. Electrophoretic mobility shift analysis demonstrated that the p50 and p49, subunit proteins of the NF-kappaB, bound to the EGFR promoter at four out of five of these sites. However, it was found that NF-kappaB could not transactivate the EGFR by cotransfection experiments with each NF-kappaB subunit, using p50, p65 and c-Rel and an EGFR promoter luciferase reporter. Treatment of cells with tumor necrosis factor (TNF)-alpha, which could degrade the I-kappaB and then result in translocation of NF-kappaB to nucleus, did not enhance EGFR promoter reporter gene transcription. Also, TNF-alpha did not induce EGFR expression at the protein level. These results indicate that even though purified NF-kappaB can bind to the putative sites, there is no evidence that NF-kappaB transactivates the EGFR promoter region. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Johnson, AC (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5002,37 Convent Dr,MSC-4264, Bethesda, MD 20892 USA. NR 44 TC 22 Z9 24 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD JAN PY 2003 VL 11 IS 1 BP 49 EP 55 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 626XK UT WOS:000179899000009 PM 12469217 ER PT J AU Graham-Evans, B Tchounwou, PB Cohly, HHP AF Graham-Evans, B Tchounwou, PB Cohly, HHP TI Cytotoxicity and proliferation studies with arsenic in established human cell lines: Keratinocytes, melanocytes, dendritic cells, dermal fibroblasts, microvascular endothelial cells, monocytes and T-cells SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE arsenic; cytotoxicity; mitogenicity; skin cells ID SODIUM ARSENITE; APOPTOSIS; EXPRESSION; EXPOSURE AB Based on the hypothesis that arsenic exposure results in toxicity and mitogenecity, this study examined the dose-response of arsenic in established human cell lines of keratinocytes (HaCaT), melanocytes (1675), dendritic cells (THP-1/A23187), dermal fibroblasts (CRL1904), microvascular endothelial cells (HMEC), monocytes (THP-1), and T cells ( Jurkat). Cytotoxicity was determined by incubating THP-1, THP-1+ A23187 and JKT cells in RPMI 1640, 1675 in Vitacell, HMEC in EBM, and dermal fibroblasts and HaCaT in DMEM with 10% fetal bovine serum, 1% streptomycin and penicillin for 72 hrs in 96-well microtiter plates, at 37degreesC in a 5% CO2 incubator with different concentrations of arsenic using fluorescein diacetate (FDA). Cell proliferation in 96-well plates was determined in cultured cells starved by prior incubation for 24 hrs in 1% FBS and exposed for 72 hours, using the 96 cell titer proliferation solution (Promega) assay. Cytotoxicity assays yielded LD50s of 9 mug/mL for HaCaT, 1.5 mug/mL for CRL 1675, 1.5 mug/mL for dendritic cells, 37 mug/mL for dermal fibroblasts, 0.48 mug/mL for HMEC, 50 mug/mL for THP-1 cells and 50 mug/mL for JKT-T cells. The peak proliferation was observed at 6 mug/mL for HaCaT and THP-1 cells, 0.19 mug/mL for CRL 1675, dendritic cells, and HMEC, and 1.5 mug/mL for dermal fibroblasts and Jurkat T cells. These results show that arsenic is toxic at high doses to keratinocytes, fibroblasts, monocytes and T cells, and toxic at lower doses to melanocytes, microvascular endothelial cells and dendritic cells. Proliferation studies showed sub-lethal doses of arsenic to be mitogenic. C1 Jackson State Univ, Sch Sci & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. Univ Mississippi, Med Ctr, Dept Surg, Jackson, MS 39216 USA. RP Graham-Evans, B (reprint author), Jackson State Univ, Sch Sci & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Box 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu; hcohly@surgery.umsmed.edu NR 18 TC 15 Z9 17 U1 0 U2 9 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 JAN PY 2003 VL 4 IS 1 BP 13 EP 21 DI 10.3390/i4010013 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 746UR UT WOS:000186766500002 ER PT J AU Huff, J AF Huff, J TI Industry influences IARC carcinogenesis evaluations SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Letter ID MONOGRAPHS C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JAN-MAR PY 2003 VL 9 IS 1 BP 83 EP 84 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 669EW UT WOS:000182339800015 PM 16304740 ER PT J AU Melnick, RL AF Melnick, RL TI Suppression of crucial information in the IARC evaluation of DEHP SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Letter ID PEROXISOME PROLIFERATOR WY-14,643; DIETARY GLYCINE PREVENTS; HEPATOCYTE PROLIFERATION; KUPFFER CELLS; MECHANISM C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Melnick, RL (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. NR 8 TC 11 Z9 11 U1 0 U2 0 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JAN-MAR PY 2003 VL 9 IS 1 BP 84 EP 85 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 669EW UT WOS:000182339800016 PM 12749639 ER PT J AU Neammanee, P Randhawa, SU AF Neammanee, P Randhawa, SU TI Integrated methodology for board assignment and component allocation in printed circuit board assembly SO INTERNATIONAL JOURNAL OF PRODUCTION RESEARCH LA English DT Article ID MACHINES; SETUP; SYSTEMS AB An approach to minimize makespan for assigning boards to production lines is described. Because of sequence-dependent set-up times, board assignment and component allocation have to be performed concurrently. An integrated methodology is developed to obtain a solution to these two problems. The methodology consists of seven phases: printed circuit board grouping, family decomposition, subfamily sequencing, Keep Tool Needed Soonest (KTNS) procedure, component set-up determination, component allocation and board assignment. Application of the methodology to industrial problems demonstrates that it can solve large-scale problems efficiently. In addition, the effect of two key parameters, feeder capacity and threshold value, on the performance of the solution procedure was examined. The results indicate that feeder capacity has an impact on total workload imbalance but not on the global makespan. Threshold value, a measure of effectiveness of joining a component type to a component group for a printed circuit board family, has a significant effect on the global makespan. The interactions of threshold value, and variations in printed circuit board requirement and component usage also affect global makespan. C1 Oregon State Univ, Corvallis, OR 97331 USA. NIDA, Sch Appl Stat, Bangkok 10240, Thailand. RP Randhawa, SU (reprint author), Oregon State Univ, Corvallis, OR 97331 USA. NR 22 TC 7 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0020-7543 J9 INT J PROD RES JI Int. J. Prod. Res. PY 2003 VL 41 IS 5 BP 919 EP 937 DI 10.1080/0020754021000036938 PG 19 WC Engineering, Industrial; Engineering, Manufacturing; Operations Research & Management Science SC Engineering; Operations Research & Management Science GA 663QR UT WOS:000182016700005 ER PT J AU Karimpour, S Gius, D AF Karimpour, S Gius, D TI The holy grail of radiation oncology: Lessons learned from hyperthermia SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID THERAPY C1 NCI, Radiat Oncol Branch, ROSP, NIH, Bethesda, MD 20892 USA. RP Gius, D (reprint author), NCI, Radiat Oncol Branch, ROSP, NIH, Bldg 10,B3B69, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2003 VL 55 IS 1 BP 3 EP 4 AR PII S0360-3016(02)03861-0 DI 10.1016/S0360-3016(02)03861-0 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 647BD UT WOS:000181070600002 PM 12504029 ER PT B AU Robinson, J Beattie, G AF Robinson, J Beattie, G GP NRC TI Nonhuman primate resource needs: A moving target SO INTERNATIONAL PERSPECTIVES: THE FUTURE OF NONHUMAN PRIMATE RESOURCES LA English DT Proceedings Paper CT Workshop on the Future of Nonhuman Primate Resources CY APR 17-19, 2002 CL Washington, DC SP Inst Lab Anim Res C1 NIH, Natl Primate Res Ctr Program, Natl Ctr Res Resources, Div Comparat Med, Washington, DC USA. RP Robinson, J (reprint author), NIH, Natl Primate Res Ctr Program, Natl Ctr Res Resources, Div Comparat Med, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 0-309-08945-X PY 2003 BP 72 EP 80 PG 9 WC Genetics & Heredity; Medicine, Research & Experimental; Microbiology; Zoology SC Genetics & Heredity; Research & Experimental Medicine; Microbiology; Zoology GA BBO05 UT WOS:000226538400012 ER PT B AU Garnett, N AF Garnett, N GP NRC TI OLAW perspective on transportation of nonhuman primates SO INTERNATIONAL PERSPECTIVES: THE FUTURE OF NONHUMAN PRIMATE RESOURCES LA English DT Proceedings Paper CT Workshop on the Future of Nonhuman Primate Resources CY APR 17-19, 2002 CL Washington, DC SP Inst Lab Anim Res C1 NIH, Off Lab Anim Welfare, Bethesda, MD USA. RP Garnett, N (reprint author), NIH, Off Lab Anim Welfare, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 0-309-08945-X PY 2003 BP 181 EP 182 PG 2 WC Genetics & Heredity; Medicine, Research & Experimental; Microbiology; Zoology SC Genetics & Heredity; Research & Experimental Medicine; Microbiology; Zoology GA BBO05 UT WOS:000226538400023 ER PT J AU Launer, LJ AF Launer, LJ TI Epidemiology of white-matter lesions SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article; Proceedings Paper CT Conference on Vascular Burden of the Brain: New therapeutic Directions CY NOV, 2001 CL MADRID, SPAIN DE epidemiology; white-matter lesions; risk factors ID AUSTRIAN STROKE PREVENTION; BLOOD-PRESSURE; CAROTID ATHEROSCLEROSIS; ROTTERDAM-SCAN; CEREBROVASCULAR-DISEASE; CARDIOVASCULAR HEALTH; COGNITIVE FUNCTION; OLDER-ADULTS; MRI FINDINGS; FOLLOW-UP AB White-matter lesions (WML) detected on MRI may reflect different pathologies, but, in older persons, are thought to be mainly of ischemic origin. WML increase in prevalence with age. Several cardiovascular risk factors and cognitive, emotional, and physical function consequences of WML have been identified. These are reviewed briefly in this report. C1 NIA, LEDB, NIH, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, LEDB, NIH, Gateway Bldg 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 23 TC 11 Z9 14 U1 0 U2 1 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2003 VL 15 SU 1 BP 99 EP 103 DI 10.1017/S1041610203009037 PG 5 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 727RJ UT WOS:000185672000015 PM 16191224 ER PT J AU Launer, LJ AF Launer, LJ TI Alzheimer's disease and cardiovascular disease: An old disease with young origins factors SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 NIA, Lab Epidemiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2003 VL 15 SU 2 BP 110 EP 110 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 831QJ UT WOS:000222209400259 ER PT J AU Razin, SV Farrell, CM Recillas-Targa, F AF Razin, SV Farrell, CM Recillas-Targa, F TI Genomic domains and regulatory elements operating at the domain level SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 226 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review DE genomic domains; LCR; beta-globin genes; insulators; replication timing ID BETA-GLOBIN LOCUS; ORIGIN RECOGNITION COMPLEX; RNA-POLYMERASE-II; DOMINANT CONTROL REGION; KRUPPEL-LIKE FACTOR; HYPERSENSITIVE SITE 2; DROSOPHILA HETEROCHROMATIN PROTEIN-1; PROPER DEVELOPMENTAL CONTROL; YEAST ARTIFICIAL CHROMOSOME; ENHANCER BLOCKING ACTIVITY C1 Russian Acad Sci, Lab Struct & Funct Org Chromosomes, Inst Gene Biol, Moscow 117334, Russia. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Mol Genet, Mexico City 04510, DF, Mexico. RP Razin, SV (reprint author), Russian Acad Sci, Lab Struct & Funct Org Chromosomes, Inst Gene Biol, Moscow 117334, Russia. RI Razin, Sergey/M-6701-2015 OI Razin, Sergey/0000-0003-1976-8661 NR 268 TC 35 Z9 39 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2003 VL 226 BP 63 EP 125 DI 10.1016/S0074-7696(03)01002-7 PG 63 WC Cell Biology SC Cell Biology GA BX38U UT WOS:000185102600002 PM 12921236 ER PT B AU McMahon, FJ AF McMahon, FJ BE Ragaini, R TI Genetics and the global health burden of mood disorders SO INTERNATIONAL SEMINAR ON NUCLEAR WAR AND PLANETARY EMERGENCIES - 27TH SESSION SE SCIENCE AND CULTURE SERIES: NUCLEAR STRATEGY AND PEACE TECHNOLOGY LA English DT Proceedings Paper CT 27th Session of the International Seminar on Nuclear War and Planetary Emergencies CY AUG 18-26, 2002 CL Erice, ITALY SP E Majorana Ctr Sci Culture ID BIPOLAR AFFECTIVE-DISORDER; MANIC-DEPRESSIVE ILLNESS; PSYCHIATRIC-DISORDERS; SUSCEPTIBILITY; PREVALENCE; LIFETIME; LINKAGE AB Mood disorders encompass a large and heterogeneous group of mental illnesses ranging from chronic mild depression to manic-depressive disorder, also known as bipolar disorder. Mood disorders account for substantial economic losses due to medical costs, lost productivity, and premature death; and are the main cause of suicide, itself the leading medical cause of death among young people in developed countries. Family, twin, and adoption studies indicate a substantial genetic contribution to mood disorders, particularly the bipolar types, but non-genetic factors still account for 30% to 50% of the variance in individual risk. Molecular studies aimed at identifying the specific genes involved in susceptibility to mood disorders have been underway for close to 20 years, but comparatively few resources have been devoted to this problem and definitive findings have not yet emerged. The identification of all of the important genetic variation that increases individual risk for mood disorders will require a much larger commitment of resources. Such a commitment is needed to support systematic collection of larger study samples, complete characterization of genetic markers covering the entire human genome, and management of the resulting data. The impact of any genetic discoveries is expected to be large, but will depend on the proportion of mood disorders that can be attributed to the discovered genetic variation (attributable risk) and on the degree to which this genetic information can be used to develop novel diagnostic and treatment approaches. Genetically-based improvements in diagnosis, drug development, and preventive strategies, would have major implications for global public health. C1 NIMH, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-238-361-1 J9 SCI CULT NUCL STRAT PY 2003 BP 599 EP 612 DI 10.1142/9789812705150_0068 PG 14 WC Environmental Sciences; International Relations; Clinical Neurology; Political Science SC Environmental Sciences & Ecology; International Relations; Neurosciences & Neurology; Government & Law GA BCI39 UT WOS:000229579100068 ER PT J AU Bhatti, RA Yu, S Boulanger, A Fariss, RN Guo, Y Bernstein, SL Gentleman, S Redmond, TM AF Bhatti, RA Yu, S Boulanger, A Fariss, RN Guo, Y Bernstein, SL Gentleman, S Redmond, TM TI Expression of beta-carotene 15,15 ' monooxygenase in retina and RPE-choroid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EPITHELIAL-CELL LINE; PIGMENT-EPITHELIUM; IN-VITRO; MICROSOMAL PROTEIN; MACULAR PIGMENT; VISUAL CYCLE; MOUSE MODEL; 15,15'-DIOXYGENASE; CLONING; ENZYME AB PURPOSE. beta-Carotene 15,15' monooxygenase (beta-CM) catalyzes the central cleavage of beta-carotene to all-trans-retinal, the first step in vitamin A synthesis. This study was conducted to determine the expression of beta-CM in the mammalian retina and RPE, to assess its relevance in carotenoid-retinoid metabolism in the retina and RPE. METHODS. RT-PCR was used to detect expression of P-CM mRNA in the retina and RPE-choroid of the mouse, cow, human, and monkey and in RPE cells and other cell lines' Immunofluorescence microscopy was used to localize beta-CM in mouse and monkey retina with an anti-peptide antibody specific for beta-CM. RESULTS. By RT-PCR, beta-CM mRNA was detected at a low level in mouse and monkey retina and in the RPE-choroid of the monkey but not of the mouse. Conversely, beta-CM mRNA was expressed at a low level in both human and bovine RPE-choroid, but not in the retina of either. RPE primary cultured cells of the monkey also showed beta-CM mRNA expression, although the three human lines did not. In addition, of nine other cell lines tested, only COS-7 was positive for beta-CM. Immunofluorescence microscopy showed weak immunoreactivity in the inner retina in both the mouse and monkey. beta-CM immunoreactivity was not detectable in RPE of the mouse. Use of a long-wavelength exciting and emitting secondary probe to mitigate lipofuscin autofluorescence, facilitated the detection of a low level of beta-CM immunoreactivity in monkey RPE. CONCLUSIONS. beta-CM mRNA and protein are expressed at low levels in the mammalian retina and RPE-choroid. Given the low and variable expression of beta-CM in the retina and RPE, it can be concluded that beta-CM is not necessary for a conserved retina or RPE-specific function, but may be necessary for a species- C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA. RP Redmond, TM (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, 6 Ctr Dr,MSC 2740,Bldg 6,Room 339, Bethesda, MD 20892 USA. OI Redmond, T. Michael/0000-0002-1813-5291 NR 34 TC 25 Z9 28 U1 0 U2 7 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 JAN PY 2003 VL 44 IS 1 BP 44 EP 49 DI 10.1167/iovs.02-0167 PG 6 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300009 PM 12506054 ER PT J AU Marin-Castano, ME Elliot, SJ Potier, M Karl, M Striker, LJ Striker, GE Csaky, KG Cousins, SW AF Marin-Castano, ME Elliot, SJ Potier, M Karl, M Striker, LJ Striker, GE Csaky, KG Cousins, SW TI Regulation of estrogen receptors and MMP-2 expression by estrogens in human retinal pigment epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 29-MAY 04, 2001 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID HORMONE REPLACEMENT THERAPY; NF-KAPPA-B; TYPE-1 MATRIX-METALLOPROTEINASE; CHROMOSOMAL LOCALIZATION; GENE-EXPRESSION; MESANGIAL CELLS; GELATINASE-A; ACTIVATION; BETA; EYE AB PURPOSE. Age-related macular degeneration (ARMD) is characterized by progressive thickening and accumulation of various lipid-rich extracellular matrix (ECM) deposits under the retinal pigment epithelium (RPE). ECM dysregulation probably contributes to the pathologic course of ARMD. By activating estrogen receptors (Elks), estrogens regulate the expression of genes relevant in the turnover of ECM, among them matrix metalloproteinase (MMP)-2. Estrogen deficiency may predispose to dysregulated synthesis and degradation of ECM, leading to accumulation of collagens and other proteins between the RPE and its basement membrane. The purposes in the current study were to confirm the expression of ERs in human RPE, to elucidate whether these ERs are functional, and to test whether 17beta-estradiol (E-2) regulates expression of ERs and MMP-2. METHODS. Expression of ERs was examined in freshly isolated human RPE monolayer and in cultured human RPE cells, by using total RNA for RT-PCR and protein extracts for Western blot analysis. Supernatants were collected from freshly isolated human RPE and from cultured human RPE to assess MMP-2 activity by zymography and protein expression by Western blot. The transcriptional activity of ERs was studied in transfection experiments with an estrogen-responsive reporter construct. All these studies were preformed in the presence or absence of E-2 (10(-11) and 10(-7) M). RESULTS. Human RPE isolated from female and male individuals expressed both ER subtypes alpha and beta at the mRNA and protein levels. Treatment of cultured RPE cells with 10(-10) M E-2 increased expression of mRNA and protein of both receptor subtypes. E-2 (10(-10) M) also increased MMP-2 activity (similar to2.2-fold) and protein expression (similar to2.5-fold). In contrast, there was no change in ER levels and MMP-2 activity at higher E-2 concentrations (10(-8) M), compared with baseline. Preincubation of cells with 10(-7) M pyrrolidinedithiocarbamate (PDTC), an inhibitor of nuclear factor (NF)-kappaB, abolished the increase in MMP-2 activity and protein expression induced by E-2 at 10(-10) M. CONCLUSIONS. Both ER subtypes are expressed in RPE and regulated in a dose-dependent fashion by E-2. Estrogens similarly regulate MMP-2. This estrogen-induced effect is, at least in part, mediated through NF-kappaB. These data support the hypothesis that estrogens may exert biological function in RPE through ERs and that estrogen deficiency or excess may cause dysregulation of molecules that influence the turnover of ECM in Bruch's membrane associated with ARMD. C1 Univ Miami, Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA. Univ Miami, Sch Med, Vasc Biol Inst, Miami, FL 33136 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Cousins, SW (reprint author), Univ Miami, Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA. NR 49 TC 78 Z9 84 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 JAN PY 2003 VL 44 IS 1 BP 50 EP 59 DI 10.1167/iovs.01-1276 PG 10 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300010 PM 12506055 ER PT J AU Bettelheim, FA Lizak, MJ Zigler, JS AF Bettelheim, FA Lizak, MJ Zigler, JS TI Syneretic response of aging normal human lens to pressure SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; FREEZING-THAWING HYSTERESIS; SENILE CATARACTOUS LENSES; HYPERBARIC-OXYGEN; EYE LENSES; LIGHT-SCATTERING; WATER FRACTIONS; STATE; AGE; NMR AB PURPOSE. The study was designed to observe whether a reversible syneretic response to pressure is operative in normal human lenses and whether such a response demonstrates a uniform age dependence. METHODS. Seven sections (from the anterior outer cortex to the posterior outer cortex) of 10 human lenses were imaged at 2 atmospheres (atm) pressure and the T, (spin-lattice) and T-2 (spin-spin) relaxation data on each section were collected. The pressure was then released and NMR relaxographic data were collected under I atm. RESULTS. Both T-1 and T-2 relaxation times were at their minimum in the nuclear region and at their maximum at the two outer cortexes. With increasing pressure, T-2 relaxation times decreased. The pressure-dependent change in T-2 relaxation times decreased with age. Changes in T-1 relaxation times showed no consistent pressure or age dependence. The population index of T-2 relaxation, M-2, had a maximum in the nucleus and a minimum in the two cortexes. The population index of T-1 relaxation, M-1, was minimal in the nucleus and maximal at the two cortexes. M-2 increased with increasing pressure, whereas M-1 did not show consistent pressure dependence. The percentage of change in M-2 (DeltaM(2)) showed a statistically significant increase with increasing age, whereas the %DeltaM(1) showed no significant age-dependent trend. CONCLUSIONS. The positional dependence of relaxation times and the population indexes indicated that spin-spin relaxation represents the behavior of the bound water and the spin-lattice relaxation that of total water. As pressure increases, the strength of hydrogen bonding as well as the amount of bound water increases. The pressure-induced change in the total water is minimal. Thus, the free water-to-bound water ratio decreases with increasing pressure, demonstrating a significant syncretic response. The extent of reversible syneretic response decreases with age and is actually reversed in older lenses. The implication is that the ability of the human lens to respond reversibly to pressure decreases with the decrease in accommodation, and, when the ability is lost altogether, an increase in free water, a possible source of cataract formation, may ensue. C1 NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. Adelphi Univ, Dept Chem, Garden City, NY USA. Natl Inst Neurol Disorder & Stroke, Bethesda, MD USA. RP Bettelheim, FA (reprint author), NEI, Lab Mech Ocular Dis, NIH, 6 Ctr Dr,MSC 2735, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY 12496] NR 34 TC 11 Z9 14 U1 0 U2 2 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 JAN PY 2003 VL 44 IS 1 BP 258 EP 263 DI 10.1167/iovs.02-0422 PG 6 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300038 PM 12506083 ER PT J AU Rohrer, B Goletz, P Znoiko, S Ablonczy, Z Ma, JX Redmond, TM Crouch, RK AF Rohrer, B Goletz, P Znoiko, S Ablonczy, Z Ma, JX Redmond, TM Crouch, RK TI Correlation of regenerable opsin with rod ERG signal in Rpe65(-/-) mice during development and aging SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LEBER CONGENITAL AMAUROSIS; MOUSE MODEL; RETINITIS-PIGMENTOSA; BINDING PROTEIN; RHODOPSIN; MUTATIONS; PHOTORESPONSE; RETINOL; RATS; AGE AB PURPOSE. RPE65 has been shown to be essential for the production of 11-cis retinal by the retinal pigment epithelium. Mutations in RPE65 are known to be associated with severe forms of early-onset retinal dystrophy. This project was designed to determine the amount of regenerable opsin in Rpe65(-/-) mice during development and aging, and to examine the function of this rhodopsin by electroretinography (ERG). METHODS. Young and aged Rpe65(-/-) and wild-type (WT) mice. p were dark adapted. Endogenous rhodopsin and regenerable opsin were measured using absorption-difference spectrophotometry. Photoreceptor function was assessed with scotopic single-flash ERGS and photoreceptors were counted in histologic sections. Opsin's primary structure was analyzed by mass-spectrometric mapping. RESULTS. Unlike WT mice, amounts of regenerable opsin in RPe65(-/-) mice decreased significantly with age, which correlated with a decrease in the number of photoreceptors and a decline in ERG amplitudes. Opsin structure, however, did not change. No endogenous levels of rhodopsin were measurable in the RPe65(-/-) mice (detection limit: 0.225 pmol). 11-cis Retinal injections resulted in the regeneration of similar amounts of rhodopsin and improved rod function in a comparable way, irrespective of age. CONCLUSIONS. In the aged Rpe65(-/-) mouse, opsin levels decrease because of the loss of photoreceptors. The remaining opsin is structurally intact, and the components of the phototransduction cascade and the retinal circuitry remain functional, despite the absence of normal photoreceptor activity. C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Physiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. RI Znoyko, Sergey/E-1294-2013; OI Znoyko, Sergey/0000-0003-1265-328X; Redmond, T. Michael/0000-0002-1813-5291 FU NEI NIH HHS [EY 13520, EY 04939] NR 24 TC 44 Z9 44 U1 1 U2 2 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 JAN PY 2003 VL 44 IS 1 BP 310 EP 315 DI 10.1167/iovs.02-0567 PG 6 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300045 PM 12506090 ER PT J AU Huang, XH Wu, DY Chen, G Manji, H Chen, DF AF Huang, XH Wu, DY Chen, G Manji, H Chen, DF TI Support of retinal ganglion cell survival and axon regeneration by lithium through a Bcl-2-dependent mechanism SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ELEMENT-BINDING PROTEIN; AMP-RESPONSIVE ELEMENT; NITRIC-OXIDE SYNTHASE; TRANSGENIC MICE; BCL-2 EXPRESSION; NERVOUS-SYSTEM; NEURONS; GROWTH; DEATH; OVEREXPRESSION AB PURPOSE. To explore whether lithium, a long-standing mood-stabilizing drug, can be used to induce expression of Bcl-2 and support the survival and regeneration of axons of retinal ganglion cells (RGCs). METHODS. Levels of expression of Bcl-2 in the retina were assessed with quantitative reverse transcription-polymerase chain reaction. To determine whether lithium directly supports the survival of and axon-regenerative functions of RGCs, various amounts of lithium were added to cultures of isolated RGCs. Anti-Thy1.2 antibodies-conjugated to magnetic beads were used to isolate the RGCs. In addition, retina-brain slice cocultures were prepared from tissues of Bcl-2-deficient or Bcl-2-transgenic mice and treated with various amounts of lithium. The effects of the expression of Bcl-2 on lithium-mediated functions were then analyzed. RESULTS. Normal mouse retina expressed very low levels of Bcl-2 after birth. Addition of lithium in the culture increased mRNA levels of Bcl-2 in retinas of postnatal mice in a dose-dependent manner. Moreover, lithium promoted not only the survival of RGCs but also the regeneration of their axons. Depleting or forcing the expression of Bcl-2 in RGCs eliminated the effects of lithium. CONCLUSIONS. Lithium supports both the survival and regeneration of RGC axons through a Bcl-2-dependent mechanism. This suggests that lithium may be used to treat glaucoma, optic nerve neuritis, the degeneration of RGCs and their nerve fibers, and other brain and spinal cord disorders involving nerve damage and neuronal cell loss. To achieve full regeneration of the severed optic nerve, it may be essential to combine lithium therapy with other drugs that mediate induction of a permissive environment in the mature central nervous system. C1 Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Program Neurosci, Boston, MA 02115 USA. Univ So Calif, Kech Sch Med, Dept Cell & Neurobiol, Los Angeles, CA USA. Univ So Calif, Kech Sch Med, Dept Ophthalmol, Los Angeles, CA USA. NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RP Chen, DF (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. RI Chen, Guang/A-2570-2017 FU NEI NIH HHS [R01 EY 012983] NR 43 TC 55 Z9 65 U1 0 U2 2 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 JAN PY 2003 VL 44 IS 1 BP 347 EP 354 DI 10.1167/iovs.02-0198 PG 8 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300050 PM 12506095 ER PT J AU Basser, PJ Pajevic, S AF Basser, PJ Pajevic, S TI Dealing with uncertainty in diffusion tensor MR data SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Review ID ECHO-PLANAR IMAGES; NUCLEAR-MAGNETIC-RESONANCE; MATTER TRACT INTEGRITY; WHITE-MATTER; HUMAN BRAIN; WATER DIFFUSION; WEIGHTED MRI; DT-MRI; SELF-DIFFUSION; FIELD GRADIENT AB This paper explains how radio frequency (RF) background noise produces uncertainty in measured diffusion tensor MRI (DT-MRI) data, how this noise can be modeled, and how its effects can be mitigated. DT-MRI data are derived from a series of magnitude diffusion-weighted images (DWI) in which RF noise is rectified. A new Gaussian distribution is proposed that describes the variability of the estimated diffusion tensor, D, in an ideal experiment in which RF noise is the only artifact present. We show how to improve the design of DT-MRI experiments by requiring that the statistical distribution of D be independent of the laboratory coordinate system. Non-parametric empirical methods of analyzing uncertainty in DT-MRI experiments are also described. Monte Carlo simulations are useful in designing and interpreting DT-MRI experiments. Bootstrap methods help us measure the true variability of D (and quantities derived from it), and assess the quality of DT-MRI data. Matrix Perturbation techniques predict how the uncertainty in D propagates to its eigenvalues and eigenvectors. A method for obtaining a continuous diffusion tensor field from the measured discrete noisy DT-MRI data also reduces the uncertainty of D and quantities derived from it. Finally, we describe schemes that use wavelets to remove noise from DWI and DT-MRI data while preserving boundaries between different tissue regions. Collectively, these parametric and nonparametric methods provide a unified statistical framework to improve the design of DT-MRI experiments and their subsequent analysis. C1 NICHD, Sect Tissue Biophys & Biomimet, LIMB, NIH, Bethesda, MD 20892 USA. CIT, Math & Stat Comp Lab, NIH, Bethesda, MD 20892 USA. RP Basser, PJ (reprint author), NICHD, Sect Tissue Biophys & Biomimet, LIMB, NIH, 13 S Dr,Bldg 13,Rm 3W16, Bethesda, MD 20892 USA. EM pjbasser@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 134 TC 9 Z9 10 U1 0 U2 4 PU LASER PAGES PUBL LTD PI JERUSALEM PA MERKAZ SAPIR 6/36, GIVAT SHAUL, PO BOX 35409, JERUSALEM 91352, ISRAEL SN 0021-2148 J9 ISRAEL J CHEM JI Isr. J. Chem. PY 2003 VL 43 IS 1-2 BP 129 EP 144 DI 10.1560/8P01-8RMA-B9EH-6F4W PG 16 WC Chemistry, Multidisciplinary SC Chemistry GA 762NZ UT WOS:000187990200013 ER PT J AU Contopoulos-Ioannidis, DG O'Brien, TR Goedert, JJ Rosenberg, PS Ioannidis, JPA AF Contopoulos-Ioannidis, DG O'Brien, TR Goedert, JJ Rosenberg, PS Ioannidis, JPA TI Effect of CCR5-Delta 32 heterozygosity on the risk of perinatal HIV-1 infection: A meta-analysis SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CCR5-Delta 32; HIV-1; perinatal infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; CHEMOKINE RECEPTOR GENE; MUTANT CCR5 ALLELE; DISEASE PROGRESSION; VERTICAL TRANSMISSION; INFANT TRANSMISSION; TYPE-1 INFECTION; DENDRITIC CELLS; EXPOSED INFANTS AB Several studies have investigated whether heterozygosity for a 32-basepair deletion in the CC chemokine receptor 5 gene (CCR5-Delta32) affects susceptibility to perinatal HIV-1 infection, but results have been inconclusive. We performed a meta-analysis of published data from 11 studies of HIV-1 perinatally exposed children who were genotyped for the CCR5-Delta32 polymorphism. The crude overall HIV-1 infection rates, by simple data pooling, were 20% (one of five) among CCR5-Delta32 homozygote children, 39% (131 of 335) among CCR5-Delta32 heterozygote children, and 40% (1408 of 3526) among wild-type CCR5 homozygote children. Compared with wild-type CCR5 homozygotes, the random effects risk ratio for CCR5-Delta32 heterozygotes was 1.04 (95% confidence interval [CI], 0.92-1.17) among all children (N = 3861) and 1.03 (95% CI, 0.90-1.17) among those of European descent (n = 2890). Results were similar when adjusted for the available data on the CCR2-641 polymorphism (n = 1542). The meta-analysis clarifies that perinatal infection is not significantly altered by heterozygosity for CCR5-Delta32 in the child. C1 Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece. Univ Ioannina, Sch Med, Dept Pediat, GR-45110 Ioannina, Greece. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. RP Ioannidis, JPA (reprint author), Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. RI Ioannidis, John/G-9836-2011 NR 45 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS JI JAIDS PD JAN PY 2003 VL 32 IS 1 BP 70 EP 76 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 635PH UT WOS:000180407600010 PM 12514416 ER PT J AU Gollust, SE Hull, SC Wilfond, B AF Gollust, SE Hull, SC Wilfond, B TI Direct-to-consumer advertising of genetic testing - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Gollust, SE (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 1 PY 2003 VL 289 IS 1 BP 46 EP 46 DI 10.1001/jama.289.1.46-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 630XL UT WOS:000180136600023 ER PT J AU Judd, LL Akiskal, HS Schettler, PJ Coryell, W Maser, J Rice, JA Solomon, DA Keller, MB AF Judd, LL Akiskal, HS Schettler, PJ Coryell, W Maser, J Rice, JA Solomon, DA Keller, MB TI The comparative clinical phenotype and long term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders? SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar spectrum; bipolar I; bipolar II; depression; anxiety disorder co-morbidity; episode course ID BRANCH COLLABORATIVE PROGRAM; FAMILIAL TRANSMISSION; DEPRESSIVE SYMPTOMS; UNIPOLAR; ILLNESS; PSYCHOBIOLOGY AB Background: The present analyses were designed to compare the clinical characteristics and long-term episode course of Bipolar-I and Bipolar-II patients in order to help clarify the relationship between these disorders and to test the bipolar spectrum hypothesis. Methods: The patient sample consisted of 135 definite RDC Bipolar-I (BP-I) and 71 definite RDC Bipolar-II patients who entered the NIMH Collaborative Depression Study (CDS) between 1978 and 1981; and were followed systematically for up to 20 years. Groups were compared on demographic and clinical characteristics at intake, and lifetime comorbidity of anxiety and substance use disorders. Subsets of patients were compared on the number and type of affective episodes and the duration of inter-episode well intervals observed during a 10-year period following their resolution of the intake affective episode. Results: BP-I and BP-II had similar demographic characteristics and ages of onset of their first affective episode. Both disorders had more lifetime comorbid substance abuse disorders than the general population. BP-II had a significantly higher lifetime prevalence of anxiety disorders in general, and social and simple phobias in particular, compared to BP-L Intake episodes of BP-I were significantly more acutely severe. BP-II patients had a substantially more chronic course, with significantly more major and minor depressive episodes and shorter inter-episode well intervals. BP-II patients were prescribed somatic treatment a substantially lower percentage of time during and between affective episodes. Limitations: BP-l patients with severe manic course are less likely to be retained in long-term follow-up, whereas the reverse might be true for BP-II patients who are significantly more prone to depression (i.e., patients with less inclination to depression and with good prognosis may have dropped out in greater proportions); this could increase the gap In long term course characteristics between the two samples. The greater chronicity of BP-II may be due, in part, to the fact that the patients were prescribed somatic treatments substantially less often both during and between affective episodes. Conclusions: The variety in severity of the affective episodes shows that bipolar disorders, similar to unipolar disorders, are expressed longitudinally during their course as a dimensional illness. The similarities of the clinical phenotypes of BP-I and BP-II, suggest that BP-I and BP-II are likely to exist in a disease spectrum. They are, however, sufficiently distinct in terms of long-term course (i.e., BP-I with more severe episodes. and BP-II more chronic with a predominantly depressive course), that they are best classified as two separate subtypes in the official classification systems. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved. C1 Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. NIMH, Collaborat Program Psychobiol Depress Clin Studie, Bethesda, MD USA. Vet Adm Hosp, San Diego, CA USA. RP Judd, LL (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NIMH NIH HHS [R01 MH025478] NR 43 TC 182 Z9 185 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN PY 2003 VL 73 IS 1-2 BP 19 EP 32 AR PII S0165-0327(02)00324-5 DI 10.1016/S0165-0327(02)00324-5 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 638VX UT WOS:000180593900003 PM 12507734 ER PT J AU Arking, R Butler, B Chiko, B Fossel, M Gavrilov, LA Morley, JE Olshansky, SJ Perls, T Walker, RF AF Arking, R Butler, B Chiko, B Fossel, M Gavrilov, LA Morley, JE Olshansky, SJ Perls, T Walker, RF TI Anti-aging teleconference: What is anti-aging medicine? SO JOURNAL OF ANTI-AGING MEDICINE LA English DT Editorial Material AB The concepts of "anti-aging" and "anti-aging medicine" in particular are hotly debated now, both in the mass media and among some researchers. This paper represents an open discussion of anti-aging terms and related ideas by nine leading experts in the field of aging studies, and it describes in detail the arguments presented by both supporters and opponents of these concepts. Candid exchange of opinions makes it clear that more efforts are required before a consensus on these issues can be reached. The paper also presents evidence that the term "anti-aging" is routinely used now in scientific literature as a legitimate scientific term, including even the titles of publications in reputable scientific journals, written by established researchers. C1 Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. Int Longev Ctr, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. NIA, Bethesda, MD 20892 USA. Michigan State Univ, E Lansing, MI 48824 USA. Univ Chicago, Natl Opin Res Ctr, Ctr Aging, Chicago, IL 60637 USA. Univ Witwatersrand, Johannesburg, South Africa. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Univ Chicago, Ctr Aging, Chicago, IL 60637 USA. Univ Chicago, London Sch Hyg & Trop Med, Chicago, IL 60637 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ S Florida, Tampa, FL 33620 USA. RP Arking, R (reprint author), Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 NR 6 TC 11 Z9 11 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1094-5458 J9 J ANTI-AGING MED JI J. Anti-Aging Med. PY 2003 VL 6 IS 2 BP 91 EP 106 DI 10.1089/109454503769684775 PG 16 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 729DL UT WOS:000185756500004 PM 14614799 ER PT J AU Johnsen, BH Thayer, JF Laberg, JC Wormnes, B Raadal, M Skaret, E Kvale, G Berg, E AF Johnsen, BH Thayer, JF Laberg, JC Wormnes, B Raadal, M Skaret, E Kvale, G Berg, E TI Attentional and physiological characteristics of patients with dental anxiety SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE dental anxiety; heart rate variability; attentional bias ID HEART-RATE-VARIABILITY; FEAR; DISORDER; SCALE; POPULATION; THREAT; NORWAY AB Twenty patients with dental anxiety were investigated while seated in a dental chair in a dental clinic. Heart rate (HR), heart rate variability (HRV), and skin conductance level (SCL) were recorded while the patients were exposed to scenes of dental treatment as well as a Stroop attentional task. Results showed an attentional bias with longer manual reaction times (RT's) to the incongruent compared to the congruent color words as well as the threat compared to the neutral words. Longer RT's to the incongruent and the threat words were found in the low HRV patients compared to the high HRV patients. Furthermore, all patients showed an increase in HR during exposure and the Stroop, task compared to baseline. The HRV showed a decrease during the exposure and the S troop task compared to baseline. HR and HRV did not differ between exposure and the Stroop task. Moreover, HR and HRV did not return to baseline levels during the recovery period. The SCL showed an increase from baseline to exposure, from exposure to the Stroop task and a decrease in the recovery phase. Results showed the importance of vagal cardiac control in attentional, emotional, and physiological processes in patients suffering from dental fear. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Bergen, Dept Clin Psychol, N-5015 Bergen, Norway. Univ Bergen, Dept Odontol, Bergen, Norway. NIA, Baltimore, MD 21224 USA. Univ Bergen, Dept Psychosocial Sci, Bergen, Norway. RP Johnsen, BH (reprint author), Univ Bergen, Dept Clin Psychol, N-5015 Bergen, Norway. NR 35 TC 94 Z9 94 U1 4 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PY 2003 VL 17 IS 1 BP 75 EP 87 AR PII S0887-6185(02)00178-0 DI 10.1016/S0887-6185(02)00178-0 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 632CF UT WOS:000180205600005 PM 12464290 ER PT J AU Burnett, TA Mann, EA Cornell, SA Ludlow, CL AF Burnett, TA Mann, EA Cornell, SA Ludlow, CL TI Laryngeal elevation achieved by neuromuscular stimulation at rest SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE larynx; swallowing; kinematics ID AIRWAY PROTECTION; COORDINATION; ASPIRATION; MECHANISM; DYSPHAGIA; MOVEMENT; SWALLOW; HEAD AB During swallowing, airway protection is achieved in part by laryngeal elevation. Although multiple muscles are normally active during laryngeal elevation, neuromuscular stimulation of select muscles was evaluated to determine which single muscle or muscle pair best elevates the larynx and should be considered during future studies of neuromuscular stimulation in dysphagic patients. Hooked-wire monopolar electrodes were inserted into mylohyoid, thyrohyoid, and geniohyoid muscle regions in 15 healthy men selected for having a highly visible thyroid prominence for videotaping. During trials of single, bilateral, and combined muscle stimulations, thyroid prominence movements were video recorded, digitized, and normalized relative to elevation during a 2-ml water swallow. Individual muscle stimulation induced similar to30% of the elevation observed during a swallow and similar to50% of swallow velocity, whereas paired muscle stimulation resulted in similar to50% of the elevation and similar to80% of the velocity produced during a swallow. Paired muscle stimulation produced significantly greater elevation than single muscle stimulation and could assist with laryngeal elevation in dysphagic patients with reduced or delayed laryngeal elevation. C1 NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Burnett, TA (reprint author), NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, 10 Ctr Dr,Rm 5D38, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 FU NINDS NIH HHS [Z01 NS-02980] NR 22 TC 49 Z9 62 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 2003 VL 94 IS 1 BP 128 EP 134 DI 10.1152/japplphysiol.00406.2002 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 625KM UT WOS:000179815700018 PM 12486019 ER PT J AU Goodwin, RD Pine, DS Hoven, CW AF Goodwin, RD Pine, DS Hoven, CW TI Asthma and panic attacks among youth in the community SO JOURNAL OF ASTHMA LA English DT Article DE asthma; youth; epidemiology; respiratory disease; anxiety; panic ID PSYCHIATRIC MORBIDITY; ANXIETY DISORDERS; PREVALENCE; CHILDREN; EMERGENCY; SYMPTOMS; SAMPLE AB Objective. To determine the association between asthma and panic attacks among youth in the community. Method. Data were drawn from the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study (n = 1285), a community-based sample of youth age 9-17 in the United States. Multivariate logistic regression analyses were used to determine the association between asthma and both panic attacks and panic disorder, adjusting for differences in sociodemographic characteristics and comorbid mental disorders. Results. Asthma was associated with a significantly increased likelihood of panic attacks [OR = 1.5 (1.01, 2.2)]. This effect was specific and persisted after adjusting for differences in demographics and psychiatric comorbidity. Severe asthma was associated with an even greater likelihood of panic attacks [OR = 2.2 (1.3, 4.0)]. There was a dose-response relationship between number of panic symptoms during a panic attack and the likelihood of asthma [OR = 1.2 (1.1, 1.3)] and severe asthma [OR 1.3 (1.1, 1.4)], which remained significant after adjusting for differences in sociodemographic characteristics and comorbid mental disorders. Conclusions. These data suggest a significant association between asthma, severe asthma, and panic attacks among youth in the community. Replication of these findings is needed, as are future studies that investigate the nature of these links. In light of the increasing prevalence of asthma and hospitalization for asthma among youth in the United States and worldwide, these associations may be worthwhile to consider in future investigations. C1 Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. NIMH, Bethesda, MD 20892 USA. RP Goodwin, RD (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 1051 Riverside Dr,Unit 43, New York, NY 10032 USA. OI Hoven, Christina/0000-0003-1274-2936 NR 28 TC 57 Z9 57 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PY 2003 VL 40 IS 2 BP 139 EP 145 DI 10.1081/JAS-120017984 PG 7 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 680CR UT WOS:000182959200005 PM 12765315 ER PT J AU Boss, LP Wheeler, LSM Williams, PV Bartholomew, LK Taggart, VS Redd, SC AF Boss, LP Wheeler, LSM Williams, PV Bartholomew, LK Taggart, VS Redd, SC TI Population-based screening or case detection for asthma: Are we ready? SO JOURNAL OF ASTHMA LA English DT Review ID UNITED-STATES; CHILDREN; PREVALENCE; GUIDELINES; EXERCISE; SYMPTOMS; CARE AB Asthma is a prevalent health problem for which there are effective treatments. By identifying people with asthma and treating them effectively, the burden of asthma in the United States should be reduced. Detecting people with asthma through screening programs seems a logical approach to the problem. This article assesses our readiness for population-based screening and case detection programs for asthma and examines these activities in relation to World Health Organization criteria for determining the appropriateness of screening programs. Given that, at this time, a number of the criteria have not been met, we conclude that population-based approaches to screening and case detection of asthma are of unproven benefit and need further research. A more appropriate focus may be to ensure that all people who are diagnosed with asthma receive appropriate medical care. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Anne Arundel Cty Dept Hlth, Annapolis, MD USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Texas, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Houston, TX USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Boss, LP (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. OI Williams, Paul/0000-0003-3300-1328 NR 26 TC 15 Z9 15 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PY 2003 VL 40 IS 4 BP 335 EP 342 DI 10.1081/JAS-120018627 PG 8 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 701MX UT WOS:000184172300001 PM 12870828 ER PT J AU Zhulin, IB Nikolskaya, AN Galperin, MY AF Zhulin, IB Nikolskaya, AN Galperin, MY TI Common extracellular sensory domains in transmembrane receptors for diverse signal transduction pathways in Bacteria and Archaea SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; SP STRAIN PCC-7120; ACCEPTING CHEMOTAXIS PROTEINS; ASPARTATE RECEPTOR; HISTIDINE KINASE; MYCOBACTERIUM-TUBERCULOSIS; PSEUDOMONAS-AERUGINOSA; BACILLUS-SUBTILIS; ADENYLYL-CYCLASE; GGDEF DOMAIN AB Transmembrane receptors in microorganisms, such as sensory histidine kinases and methyl-accepting chemotaxis proteins, are molecular devices for monitoring environmental changes. We report here that sensory domain sharing is widespread among different classes of transmembrane receptors. We have identified two novel conserved extracellular sensory domains, named CHASE2 and CHASE3, that are found in at least four classes of transmembrane receptors: histidine kinases, adenylate cyclases, predicted diguanylate cyclases, and either serine/threonine protein kinases (CHASE2) or methyl-accepting chemotaxis proteins (CHASE3). Three other extracellular sensory domains were shared by at least two different classes of transmembrane receptors: histidine kinases and either diguanylate cyclases, adenylate cyclases, or phosphodiesterases. These observations suggest that microorganisms use similar conserved domains to sense similar environmental signals and transmit this information via different signal transduction pathways to different regulatory circuits: transcriptional regulation (histidine kinases), chemotaxis (methyl-accepting proteins), catabolite repression (adenylate cyclases), and modulation of enzyme activity (diguanylate cyclases and phosphodiesterases). The variety of signaling pathways using the CHASE-type domains indicates that these domains sense some critically important extracellular signals. C1 Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Zhulin, IB (reprint author), Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. RI Zhulin, Igor/A-2308-2012; Galperin, Michael/B-5859-2013 OI Zhulin, Igor/0000-0002-6708-5323; Galperin, Michael/0000-0002-2265-5572 NR 71 TC 85 Z9 93 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2003 VL 185 IS 1 BP 285 EP 294 DI 10.1128/JB.185.1.285-294.2003 PG 10 WC Microbiology SC Microbiology GA 629LJ UT WOS:000180050900032 PM 12486065 ER PT J AU Dzioba, J Hase, CC Gosink, K Galperin, MY Dibrov, P AF Dzioba, J Hase, CC Gosink, K Galperin, MY Dibrov, P TI Experimental verification of a sequence-based prediction: F1F0-Type ATPase of Vibrio cholerae transports protons, not Na+ ions SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COUPLED OXIDATIVE-PHOSPHORYLATION; VIRULENCE GENE-EXPRESSION; H+-TRANSLOCATING ATPASE; SUBUNIT-C; PROPIONIGENIUM-MODESTUM; ACETOBACTERIUM-WOODII; ESCHERICHIA-COLI; DNA-SEQUENCE; ALGINOLYTICUS CELLS; PROTEOLIPID SUBUNIT AB The membrane energetics of the intestinal pathogen Vibrio cholerae involves both H+ and Na+ as coupling ions. The sequence of the c subunit of V cholerae F0F1 ATPase suggested that this enzyme is H+ specific, in contrast to the results of previous studies on the Na+-dependent ATP synthesis in closely related Vibrio spp. Measurements of the pH gradient and membrane potential in membrane vesicles isolated from wild-type and DeltaatpE mutant V cholerae show that the F1F0 ATPase of V. cholerae is an H+, not Na+, pump, confirming the bioinformatics assignments that were based on the Na+-binding model of S. Rahlfs and V. Muller (FEBS Lett. 404:269-271, 1999). Application of this model to the AtpE sequences from other bacteria and archaea indicates that Na+-specific F1F0 ATPases are present in a number of important bacterial pathogens. C1 Univ Manitoba, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Dibrov, P (reprint author), Univ Manitoba, Dept Microbiol, Ft Garry Campus,Rm 425,Buller Bldg, Winnipeg, MB R3T 2N2, Canada. EM dibrovp@ms.umanitoba.ca RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU NCI NIH HHS [CA 21765, P30 CA021765] NR 36 TC 18 Z9 19 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2003 VL 185 IS 2 BP 674 EP 678 DI 10.1128/JB.185.2.674-678.2003 PG 5 WC Microbiology SC Microbiology GA 633FV UT WOS:000180272600035 PM 12511516 ER PT J AU Neuveut, C Scoggins, RM Camerini, D Markham, RB Jeang, KT AF Neuveut, C Scoggins, RM Camerini, D Markham, RB Jeang, KT TI Requirement for the second coding exon of Tat in the optimal replication of macrophage-tropic HIV-1 SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE HIV; macrophage tropism; Tat; AIDS pathogenesis; SCID mouse ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; MONOCYTE-DERIVED MACROPHAGES; RNA-POLYMERASE-II; SCID-HU MICE; T-CELLS; TYPE-1 TAT; TRANSCRIPTION PREINITIATION; CELLULAR PROTEIN; GENE-EXPRESSION AB HIV-1 Tat is essential for virus replication and is a potent transactivator of viral gene expression. Evidence suggests that Tat also influences virus infectivity and cytopathicity. Here, we find that the second coding exon of Tat contributes a novel function for the replication/infectivity of macrophage-tropic HIV-1. We show that macrophage-tropic HIV-1 which expresses the full-length two-exon form of Tat replicates better in monocyte-derived macrophages (MDM) than an otherwise isogenic virus which expresses only the one-exon form of Tat. Similarly, two-exon Tat expressing HIV-1 also replicates better than one-exon Tat expressing HIV-1 in two different models of human cells/tissue reconstituted SCID mice. Copyright (C) 2003 National Science Council, ROC and S. Karger AG, Basel. C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Univ Virginia, Hlth Sci Ctr, Myles H Thaler Ctr AIDS & Human Retrovirus Res, Charlottesville, VA USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 66 TC 14 Z9 14 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PY 2003 VL 10 IS 6 SI SI BP 651 EP 660 DI 10.1159/000073531 PN 1 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 739WG UT WOS:000186369300012 PM 14576468 ER PT J AU Traicoff, JL De Marchis, L Ginsburg, BL Zamora, RE Khattar, NH Blanch, VJ Plummer, S Bargo, SA Templeton, DJ Casey, G Kaetzel, CS AF Traicoff, JL De Marchis, L Ginsburg, BL Zamora, RE Khattar, NH Blanch, VJ Plummer, S Bargo, SA Templeton, DJ Casey, G Kaetzel, CS TI Characterization of the human polymeric immunoglobulin receptor (PIGR) 3 ' UTR and differential expression of PIGR mRNA during colon tumorigenesis SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE polymeric immunoglobulin receptor; 3 ' UTR; RNA stability; mRNA differential display; colon cancer; adenoma; neoplastic cell transformation ID TRANSMEMBRANE SECRETORY COMPONENT; POLY-IG RECEPTOR; GENE-EXPRESSION; COLORECTAL-CARCINOMA; MOLECULAR-CLONING; INTERFERON-GAMMA; LARGE EXON; PROTEIN; CANCER; REPEATS AB The human cell lines VACO-235 and VACO-411 constitute a novel in vitro model of colon adenoma to carcinoma progression. By differential display RT-PCR we identified a transcript that is expressed in the parental nontumorigenic adenoma line (VACO-235E), but is not expressed in the tumorigenic daughter (VACO-235L) or granddaughter (VACO-411) lines. This cDNA represents a previously uncharacterized portion of the 3' UTR of human PIGR. Human PIGR mRNA was found to be highly expressed in normal colon epithelium, but was decreased in 6 of 8 colon tumors and was negligible in 8 of 10 colon tumor cell lines. We sequenced the entire 1.8 kb 3' UTR of human PIGR, and found it to contain multiple repetitive elements as well as elements that could affect the processing and stability of PIGR mRNA. We hypothesize that differential regulation of PIGR mRNA stability may contribute to its downregulation in colon cancer. Copyright (C) 2003 National Science Council, ROC and S. Karger AG, Basel. C1 Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. NCI, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. Univ Kentucky, Dept Pathol, Lexington, KY USA. RP Traicoff, JL (reprint author), 2020 GeneSyst Inc, 9700 Great Seneca Highway, Rockville, MD 20850 USA. RI Templeton, Dennis/F-7695-2011; OI Kaetzel, Charlotte/0000-0001-7546-0085 FU NCI NIH HHS [CA 51998, CA 67409, CA 72160, P01 CA 51883, P30 CA 43703] NR 53 TC 16 Z9 18 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PY 2003 VL 10 IS 6 BP 792 EP 804 DI 10.1159/000073967 PN 2 PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 748YJ UT WOS:000186888500015 PM 14631119 ER PT J AU Mesleh, MF Valentine, KG Opella, SJ Louis, JM Gronenborn, AM AF Mesleh, MF Valentine, KG Opella, SJ Louis, JM Gronenborn, AM TI Myristoylation as a general method for immobilization and alignment of soluble proteins for solid-state NMR structural studies SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE lipid bilayer; myristoylation; orientational restraints; PISEMA; protein GB1; solid-state NMR ID CHEMICAL-SHIFT TENSORS; MEMBRANE-PROTEIN; PHOSPHOLIPID-BILAYERS; SPECTROSCOPY; DIPOLAR; RESOLUTION; TOPOLOGY; PEPTIDES AB N-terminal myristoylation of the immunoglobulin-binding domain of protein G (GB1) from group G Streptococcus provides the means to bind the protein to aligned phospholipid bilayers for solid-state NMR structural studies. The myristoylated protein is immobilized by its interactions with bilayers, and the sample alignment enables orientationally dependent N-15 chemical shifts and H-1-N-15-dipolar couplings to be measured. Spectra calculated for the average solution NMR structure of the protein at various orientations with respect to the magnetic field direction were compared to the experimental spectrum. The best fit identified the orientation of the myristoylated protein on the lipid bilayers, and demonstrated that the protein adopts a similar structure in both its myristoylated and non-myristoylated forms, and that the structure is not grossly distorted by its interaction with the phosholipid bilayer surface or by its location in the restricted aqueous space between bilayer leaflets. The protein is oriented such that its charged sides face the phosphatidylcholine headgroups of the lipids with the single amphiphilic helix running parallel to the bilayer surface. C1 Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Opella, SJ (reprint author), Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. FU NCRR NIH HHS [P41RR09731]; NIGMS NIH HHS [P01GM56538, R01GM29754, R37GM24266] NR 18 TC 5 Z9 5 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JAN PY 2003 VL 25 IS 1 BP 55 EP 61 DI 10.1023/A:1021964314987 PG 7 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 634EQ UT WOS:000180327400005 PM 12566999 ER PT J AU Hatakeyama, Y Nguyen, J Wang, XB Nuckolls, GH Shum, L AF Hatakeyama, Y Nguyen, J Wang, XB Nuckolls, GH Shum, L TI Smad signaling in mesenchymal and chondroprogenitor cells SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article; Proceedings Paper CT 4th International Conference on Bone Morphogenetic Proteins CY OCT 17-21, 2002 CL SACRAMENTO, CALIFORNIA SP Medtronic Sofamor Danek, Stryker Biotech ID BONE MORPHOGENETIC PROTEIN-2; OSTEOBLASTIC DIFFERENTIATION; I RECEPTORS; CHONDROGENIC DIFFERENTIATION; SOMITIC CHONDROGENESIS; BMP; CHONDROCYTES; EXPRESSION; C2C12; CONVERGENCE AB Background: Bone morphogenetic proteins (BMPs) are pleiotropic differentiation factors that regulate cell fate determination by orchestrating the activities of downstream signal transducers. Although BMP ligands can elicit signal transduction from heterodimeric combinations of several typed and type-II receptors, cytoplasmic transducers of the BMP signal include only three known BIVIP-specific regulatory Smad proteins: Smad1, 5, and 8. In order to determine the combination of signals that regulate chondrogenesis by BMPs, we analyzed the functions of BMP Smad subtypes. Methods: Multipotential mesenchymal C3H10T1/2 cells and monopotential chondroprogenitor MC615 cells were placed in micromass culture in the presence or absence of BMP4. Chondrogenic differentiation was assayed by measuring Sox9 and type-II collagen gene expression and by alcian blue staining. Transactivation of type-II collagen by regulatory Smads singly, or in combination with Smad4, which partners with regulatory Smads, was assayed by luciferase activity. Results: In the absence of BMP4, mesenchymal cells did not exhibit chondrogenic differentiation, whereas chondroprogenitor cells showed increased cartilage marker expression. In the presence of BMP4, the rate and extent of chondrogenesis increased in a dose-dependent manner for both cell types. We further determined that Smad1 or Smad5, but not Smad8, synergized with Smad4 in the transactivation of the type-II collagen promoter in chondroprogenitor cells. In contrast, Smad8 and Smad4 presented modest synergy in mesenchymal cells. Conclusions: Taken together, our data suggest that uncommitted mesenchymal cells do not have the cellular competence to respond to the rate-limiting chondroincluctive factor BMP However, in chondroprogenitor cells, BMP stimulates differentiation through mechanisms mediated by Smad1 or Smad5 in combination with Smad4. Clinical Relevance: Our functional studies of these mesenchymal and chondroprogenitor cells will establish the mechanisms of lineage commitment and provide a platform for molecular manipulations with predictable lineage outcome. Therefore, our knowledge base can provide the molecular basis for stem/progenitor cell differentiation and a paradigm for tissue engineering. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Shum, L (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, 6 Ctr Dr, MSC 2745,Bldg 6,Room 324, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [Z01 AR41114] NR 25 TC 39 Z9 42 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PY 2003 VL 85A SU 3 BP 13 EP 18 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 710KZ UT WOS:000184680500004 PM 12925604 ER EF