FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hoppin, JA AF Hoppin, JA TI Integrating exposure measurements into epidemiologic studies in agriculture SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article; Proceedings Paper CT International Symposium on Agricultural Exposures and Cancer CY NOV 19-22, 2002 CL Oxford Univ Green Coll, Oxford, ENGLAND SP CropLife Int, CropLife Amer, European Crop Protect Assoc, Int Agcy Res Canc HO Oxford Univ Green Coll DE epidemiology; exposure assessment; farming; pesticides ID PESTICIDE USE; HEALTH AB Agricultural epidemiology studies frequently rely on questionnaires to assess pesticide exposure. Farmers can provide accurate information regarding their pesticide use history. However, pesticide exposure is influenced not only by the pesticide, but also by factors related to pesticide application and behavior; estimates of exposure can be improved by incorporating data on these factors. Exposure measurement studies help to elucidate influential factors with regard to pesticide dose. These factors can be incorporated into exposure estimates to reduce measurement error and allow for better resolution of the exposure distribution. In the Agricultural Health Study, two exposure algorithms were developed to evaluate exposure intensity; this exposure intensity score was used to modify the lifetime days of pesticide application. This metric, along with additional refinement as a result of on-going field studies, will allow better assignment of exposure levels in the cohort. Future work to develop exposure metrics that incorporate both chemical and behavior characteristics for all farmworkers and farm residents will further improve epidemiologic studies in agriculture. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov NR 11 TC 6 Z9 6 U1 0 U2 1 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PY 2005 VL 31 SU 1 BP 115 EP 117 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 966HI UT WOS:000232010300018 PM 16190158 ER PT J AU Ito, Y AF Ito, Y TI Origin and evolution of the coil planet centrifuge: A personal reflection of my 40 years of CCC research and development SO SEPARATION AND PURIFICATION REVIEWS LA English DT Article DE countercurrent chromatography; coil planet centrifuge; liquid stationary phase; history ID PREPARATIVE COUNTERCURRENT CHROMATOGRAPHY; LIQUID PARTITION CHROMATOGRAPHY; ROTATING SEALS; SOLID SUPPORT; SEPARATION; APPARATUS; ACCELERATION; COLUMNS; DESIGN; SERIES AB The view by its founder of countercurrent chromatography history through the evolution of the coil planet centrifuge hydrodynamic chromatograph. Originally built for the separation of lymphocytes, the coil planet centrifuge took an unexpected course to become an efficient instrument that is currently widely used for separation and purification of natural and synthetic products. C1 NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 28 TC 31 Z9 31 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1542-2119 J9 SEP PURIF REV JI Sep. Purif. Rev. PY 2005 VL 34 IS 2 BP 131 EP 154 DI 10.1080/15422110500322883 PG 24 WC Chemistry, Applied; Chemistry, Analytical; Engineering, Chemical SC Chemistry; Engineering GA 051WH UT WOS:000238191900001 ER PT J AU Subbarao, K AF Subbarao, Kanta BE Peiris, M Anderson, LJ Osterhaus, AD Stohr, K Yuen, KY TI Vaccines SO SEVERE ACUTE RESPIRATORY SYNDROME LA English DT Article; Book Chapter ID ACUTE-RESPIRATORY-SYNDROME; FELINE INFECTIOUS PERITONITIS; ANTIBODY-DEPENDENT ENHANCEMENT; SARS-ASSOCIATED CORONAVIRUS; CRITICALLY-ILL PATIENTS; REVERSE GENETICS; HONG-KONG; SPIKE PROTEIN; PROTECTIVE IMMUNITY; GENOME SEQUENCE C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 63 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47075-595-2 PY 2005 BP 203 EP 212 D2 10.1002/9780470755952 PG 10 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA BZM56 UT WOS:000302029300022 ER PT J AU Kiddugavu, MG Kiwanuka, N Wawer, MJ Serwadda, D Sewankambo, NK Wabwire-Mangen, F Makumbi, F Li, XB Reynolds, SJ Quinn, TC Gray, RH AF Kiddugavu, MG Kiwanuka, N Wawer, MJ Serwadda, D Sewankambo, NK Wabwire-Mangen, F Makumbi, F Li, XB Reynolds, SJ Quinn, TC Gray, RH CA Rakai Study Grp TI Effectiveness of syphilis treatment using azithromycin and/or benzathine penicillin in Rakai, Uganda SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; COMMUNITY TRIAL; AIDS-PREVENTION; HIV-INFECTION; THERAPY; MANIFESTATIONS AB Objective: The goal of this study was to assess azithromycin and/or benzathine penicillin for treatment of syphilis. Methods: In a population-based study, participants with serologic syphilis (TRUST with TPHA confirmation) were offered 2.4 MU benzathine penicillin intramuscularly. Intervention arm participants received 1 g presumptive oral azithromycin. We assessed cure rates with penicillin or azithromycin given alone and in combination. Cure assessed after 10 months was defined as seroreversion or a 4-fold decrease in titer. The rate ratio (RR) of cure and 95% confidence intervals (95% CIs) were estimated by log binomial regression. Results: Among 952 cases with syphilis, 18% received penicillin alone, 17% azithromycin only, and 65% dual treatment. The overall cure rate was 61%. Cure rates were lower in males compared with females (RR, 0.89; 95% CI, 0.80-0.99) and in subjects with initial titers greater than or equal to1:4 compared with less than or equal to1:2 (RR, 0.77; 95% CI, 0.69-0.86). There was no significant differences in cure rates among HIV-positive and HIV-negative persons. With initial titers less than or equal to1:2, there were no differences in cure rates by treatment regimen. However, with initial titers greater than or equal to1:4, significantly higher cure rates were observed with azithromycin alone (adjusted RR, 1.38; 95% CI, 0.97-1.96), and with dual treatment of azithromycin and benzathine penicillin (RR, 1.38; 95% CI, 1.03-1.87) compared with penicillin alone. Conclusion: Azithromycin alone or in combination with penicillin achieved higher cure rates than penicillin alone in cases with a high initial TRUST titer. In low-titer infections, the 3 drug combinations were equally effective. HIV status did not affect cure rates. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. NIAID, NIH, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Makerere Univ, Fac Med, Kampala, Uganda. Makerere Univ, Fac Med, Clin Epidemiol Unit, Kampala, Uganda. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda. RP Gray, RH (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 615 N Wolfe St,Room W4030, Baltimore, MD 21205 USA. EM rgray@jhsph.edu OI Sewankambo, Nelson/0000-0001-9362-053X FU NIAID NIH HHS [AI34826, R01AI34826S]; NICHD NIH HHS [5P30HD06826] NR 24 TC 47 Z9 51 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JAN PY 2005 VL 32 IS 1 BP 1 EP 6 DI 10.1097/01.olq.0000148297.48590.d8 PG 6 WC Infectious Diseases SC Infectious Diseases GA 885XZ UT WOS:000226192000001 PM 15614114 ER PT J AU Valappil, T Kelaghan, J Macaluso, M Artz, L Austin, H Fleenor, ME Robey, L Hook, EW AF Valappil, T Kelaghan, J Macaluso, M Artz, L Austin, H Fleenor, ME Robey, L Hook, EW TI Female condom and male condom failure among women at high risk of sexually transmitted diseases SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; LATEX CONDOM; CONTRACEPTIVE EFFICACY; POLYURETHANE CONDOM; VAGINAL INTERCOURSE; HIV TRANSMISSION; HOMOSEXUAL MEN; UNITED-STATES; SEX WORKERS AB Objective: The objective of this study was to study the frequency and determinants of breakage and slippage during female and male condom use. Goal: The goal of this study was to determine condom breakage and slippage rate. Study: We conducted a 6-month prospective follow-up study of women attending 2 sexually transmitted disease clinics. Breakage and slippage rates were computed. Logistic regression was used to evaluate baseline characteristics and time-dependent behaviors. Results: A total of 869 women used condoms in 20,148 acts of intercourse. Breakage was less common for female condoms (0.1%; 95% confidence interval [CI], 0.05-0.21) than for male condoms (3.1%; 95% CI, 2.80-3.42). Slippage was more common for female condoms (5.6%; 95% CI, 5.10-6.13) than for male condoms (1.1%; 95% CI, 0.90-1.28). Rates significantly decreased with use and increased with number of previous failures. From first use to >15 uses, combined failure rate fell from 20% to 1.2% for female condoms (P <0.0001) and 9% to 2.3% for male condoms (P <0.01). Conclusions: Both condoms may provide good protection against sexually transmitted diseases. Experience determines success with either condom. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA. NICHHD, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Emory Univ, Atlanta, GA 30322 USA. Jefferson Cty Dept Hlth, Birmingham, AL USA. Madison Cty Hlth Dept, Huntsville, AL USA. RP Valappil, T (reprint author), US FDA, Ctr Drug Evaluat & Res, HFD-725,9201 Corp Blvd, Rockville, MD 20850 USA. EM valappilt@cder.fda.gov RI Macaluso, Maurizio/J-2076-2015 OI Macaluso, Maurizio/0000-0002-2977-9690 FU NICHD NIH HHS [N01-HD-1-3,135] NR 51 TC 39 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JAN PY 2005 VL 32 IS 1 BP 35 EP 43 DI 10.1097/01.olq.0000148295.60514.0b PG 9 WC Infectious Diseases SC Infectious Diseases GA 885XZ UT WOS:000226192000006 PM 15614119 ER PT J AU Nikonova, EV Vijayasarathy, C Zhang, L Cater, JR Galante, RJ Ward, SE Avadhani, NG Pack, AI AF Nikonova, EV Vijayasarathy, C Zhang, L Cater, JR Galante, RJ Ward, SE Avadhani, NG Pack, AI TI Differences in activity of cytochrome C oxidase in brain between sleep and wakefulness SO SLEEP LA English DT Article DE mitochondria; sleep; sleep deprivation; cytochrome c oxidase; oxidative phosphorylation ID CENTRAL NERVOUS-SYSTEM; GENE-EXPRESSION; ENERGY-METABOLISM; DROSOPHILA-MELANOGASTER; PROLONGED WAKEFULNESS; NEURONAL-ACTIVITY; RAT-BRAIN; TRANSCRIPTION; DEPRIVATION; ADENOSINE AB Study Objectives: Increased mRNA level of subunit 1 cytochrome c oxidase (COXI) during wakefulness and after short-term sleep deprivation has been described in brain. We hypothesized that this might contribute to increased activity of cytochrome oxidase (COX) enzyme during wakefulness, as part of the mechanisms to provide sufficient amounts of adenosine triphosphate to meet increased neuronal energy demands. Design: COX activity was measured in isolated mitochondria from different brain regions in groups of rats with 3 hours of spontaneous sleep, 3 hours of spontaneous wake, and 3 hours of sleep deprivation. The group with 3 hours of spontaneous wake was added to delineate the circadian component of changes in the enzyme activity. Northern blot analysis was performed to examine the mRNA levels of 2 subunits of the enzyme COXI and COXIV, encoded by mitochondrial and nuclear DNA, respectively. Setting: Laboratory of Biochemistry, Department of Animal Biology, and Center for Sleep and Respiratory Neurobiology, University of Pennsylvania. Participants: 2-month-old male Fischer rats (N = 21) implanted for polygraphic recording. Measurements and Results: For COX activity, there was a main effect by analysis of variance of experimental group (P < .0001) with significant increases in COX activity in wake and sleep-deprived groups as compared to the sleep group. A main effect of brain region was also significant (P < .001). There was no difference between brain regions in the degree of increase in enzyme activity in wakefulness. Both COXI and COXIV mRNA were increased with wakefulness as compared to sleep. Conclusions: There is an increase in COX activity after both 3 hours of spontaneous wake and 3 hours of sleep deprivation as compared with 3 hours of spontaneous sleep in diverse brain regions, which could be, in part, explained by the increased levels of bigenomic transcripts of the enzyme. This likely contributes to increased adenosine triphosphate production during wakefulness. C1 Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Biochem Lab, Philadelphia, PA 19104 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Nikonova, EV (reprint author), Hosp Univ Penn, Ctr Sleep & Resp Neurobiol, 991 Maloney Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM elenan@mail.med.upenn.edu RI Sanguansri, Luz/B-6630-2011 OI Sanguansri, Luz/0000-0003-1908-7604 FU NHLBI NIH HHS [P50 HL60287]; NIA NIH HHS [P01 AG17628] NR 62 TC 19 Z9 21 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JAN 1 PY 2005 VL 28 IS 1 BP 21 EP 27 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 911TN UT WOS:000228028000006 PM 15700717 ER PT J AU Arand, D Bonnet, M Hurwitz, T Mitler, M Rosa, R Sangal, RB AF Arand, D Bonnet, M Hurwitz, T Mitler, M Rosa, R Sangal, RB TI The clinical use of the MSLT and MWT SO SLEEP LA English DT Review ID EXCESSIVE DAYTIME SLEEPINESS; POSITIVE AIRWAY PRESSURE; LATENCY TEST MSLT; CONTROLLED CROSSOVER TRIAL; SIMULATED DRIVING PERFORMANCE; HUMAN BRAIN POTENTIALS; WAKEFULNESS TEST; APNOEA/HYPOPNOEA SYNDROME; APNEA/HYPOPNEA SYNDROME; NARCOLEPSY-CATAPLEXY C1 Kettering Med Ctr, Dayton, OH USA. Dayton Vet Affairs Med Ctr, Dayton, OH USA. Wright State Univ, Dayton, OH 45435 USA. Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. NINDS, Ctr Neurosci, Bethesda, MD 20892 USA. NIOSH, Washington, DC USA. Sleep Disorders Inst, Troy, MI USA. RP Arand, D (reprint author), Kettering Med Ctr, Dayton, OH USA. NR 181 TC 126 Z9 127 U1 1 U2 5 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JAN 1 PY 2005 VL 28 IS 1 BP 123 EP 144 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 911TN UT WOS:000228028000017 PM 15700728 ER PT J AU Hall, M Naydeck, BL Stone, KL Rubin, S Visser, M Satterfield, S Harris, T Newman, AB AF Hall, M Naydeck, BL Stone, KL Rubin, S Visser, M Satterfield, S Harris, T Newman, AB TI Association between sleep duration and mortality is partly mediated by higher levels of inflammation in older adults SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VU Univ Med Ctr, Inst Res Extramural Med, Amsterdam, Netherlands. Vrije Univ Amsterdam, Amsterdam, Netherlands. Univ Tennessee, Memphis, TN USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 348 BP A118 EP A118 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100349 ER PT J AU Hening, W Mathias, R Washburn, M Lesage, S Earley, CJ Wilson, AF AF Hening, W Mathias, R Washburn, M Lesage, S Earley, CJ Wilson, AF TI A segregation analysis of the restless legs syndrome (RLS) based on age-of-onset models SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 UMDNJ, RWJohnson Med Sch, New York, NY USA. NHRGI, Ctr Inherited Dis Res, IDRB, NIH, Baltimore, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 815 BP A274 EP A274 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101323 ER PT J AU Valladares, EM Motivala, SJ O'Neal, IC Thayer, JF Irwin, MR AF Valladares, EM Motivala, SJ O'Neal, IC Thayer, JF Irwin, MR TI Gender differences in heart rate variability during nocturnal wakefulness and sleep SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Univ Calif Los Angeles, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA. NIA, Lab Personal & Cognit, Bethesda, MD 20892 USA. RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 129 BP A43 EP A43 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100130 ER PT J AU Vgontzas, AN Pejovic, S Lin, H Bixler, EO Basta, M Chrousos, GP AF Vgontzas, AN Pejovic, S Lin, H Bixler, EO Basta, M Chrousos, GP TI Regular exercise is associated with significant reduction of sleepiness in men with sleep Apnea SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Penn State Coll Med, Sleep Res & Treatment Ctr, Hershey, PA USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 602 BP A202 EP A203 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101111 ER PT J AU Dreer, LE Jackson, WT Elliott, TR AF Dreer, Laura E. Jackson, Warren T. Elliott, Timothy R. BE McMurran, M McGuire, J TI SOCIAL PROBLEM SOLVING, PERSONALITY DISORDER, AND SUBSTANCE ABUSE SO SOCIAL PROBLEM SOLVING AND OFFENDING: EVIDENCE, EVALUATION AND EVOLUTION SE Wiley Series in Forensic Clinical Psychology LA English DT Article; Book Chapter ID ANTISOCIAL PERSONALITY; DRUG-ABUSERS; MENTAL-DISORDERS; BIRTH COHORT; ALCOHOL-USE; PSYCHOLOGICAL DISTRESS; MMPI CHARACTERISTICS; BEHAVIORAL TREATMENT; PSYCHIATRIC-PATIENTS; UNIPOLAR DEPRESSION C1 [Dreer, Laura E.] Univ Alabama Birmingham, Dept Psychol, NIH, Birmingham, AL 35294 USA. [Jackson, Warren T.] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Sch Med, Birmingham, AL 35294 USA. RP Dreer, LE (reprint author), Univ Alabama Birmingham, Dept Psychol, NIH, 415 Campbell Hall,Room233,1300 Univ Blvd, Birmingham, AL 35294 USA. RI Elliott, Timothy/I-5301-2012 OI Elliott, Timothy/0000-0002-6608-7714 NR 159 TC 6 Z9 6 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-0-470-71348-8 J9 WILEY SER FOREN CLIN PY 2005 BP 67 EP 89 DI 10.1002/9780470713488.ch4 PG 23 WC Psychology, Clinical; Criminology & Penology SC Psychology; Criminology & Penology GA BZE32 UT WOS:000301236500006 ER PT J AU Govender, T Hariprakasha, HK Kruger, HG Raasch, T AF Govender, T Hariprakasha, HK Kruger, HG Raasch, T TI Synthesis of trishomocubane amino acid derivatives SO SOUTH AFRICAN JOURNAL OF CHEMISTRY-SUID-AFRIKAANSE TYDSKRIF VIR CHEMIE LA English DT Article DE trishomocubane amino acid; hydantoin; Fmoc protection; t-Boc protection; acid fluoride; esterification ID PHASE PEPTIDE-SYNTHESIS; PROTECTING GROUP; FLUORIDES; ADAMANTANE; RESIDUES; FLUORINATION; HYDANTOINS; CONVENIENT; AMANTADINE; CHLORIDES AB The synthesis of four novel trishomocubane amino acid derivatives is described. The hydantoin precursor and bis-Boc protected hydantoin (>95% yield) were previously reported. A mild hydrolysis of the bis-Boc hydantoin with lithium hydroxide at room temperature quantitatively yielded the corresponding novel cage amino acid. The cage amino acid was characterized as the Fmoc derivative. Although the Fmoc amino acid is partially deprotected after three weeks in a refrigerator, it is stable enough for use in Solid Phase Peptide Synthesis (SPPS). The Fmoc cage amino acid was converted to the acid fluoride with cyanuric fluoride. The acid fluoride is required for activation of the cage amino acid in SPPS. Esterification of the sterically hindered trishomocubane amino acid is also reported, indicating sufficient reactivity of the acid function for potential use in SPPS. C1 Univ KwaZulu Natal, Sch Chem, ZA-4041 Durban, South Africa. NCI, Frederick, MD 21702 USA. RP Kruger, HG (reprint author), Univ KwaZulu Natal, Sch Chem, ZA-4041 Durban, South Africa. EM kruger@ukzn.ac.za RI Govender, Thavendran/H-6838-2013 OI Govender, Thavendran/0000-0003-2511-2503 NR 52 TC 16 Z9 16 U1 0 U2 4 PU BUREAU SCIENTIFIC PUBL PI PRETORIA PA P O BOX 1758, PRETORIA 0001, SOUTH AFRICA SN 0379-4350 J9 S AFR J CHEM-S-AFR T JI South Afr. J. Chem.-Suid-Afr. Tydskr. Chem. PY 2005 VL 58 BP 37 EP 40 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 897SU UT WOS:000227026200003 ER PT J AU Bhargava, R Levin, IW AF Bhargava, Rohit Levin, Ira W. BE Bhargava, R Levin, IW TI Fourier transform mid-infrared spectroscopic imaging Microspectroscopy with multichannel detectors SO SPECTROCHEMICAL ANALYSIS USING INFRARED MULTICHANNEL DETECTORS SE Sheffield Analytical Chemistry Series LA English DT Article; Book Chapter ID PLANE ARRAY DETECTION; INFRARED MICROSCOPY; SPATIAL-RESOLUTION; TIME; SPECTROMETER; PERFORMANCE; SYSTEMS; TISSUE; ROUTE; NOISE C1 [Bhargava, Rohit] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Bhargava, Rohit] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Levin, Ira W.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bhargava, R (reprint author), Univ Illinois, Dept Bioengn, 405 N Mathews Ave, Urbana, IL 61801 USA. NR 61 TC 5 Z9 5 U1 2 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98854-1 J9 SHEFF ANALY CHEM PY 2005 BP 1 EP 24 D2 10.1002/9780470988541 PG 24 WC Chemistry, Analytical SC Chemistry GA BAD15 UT WOS:000303834200002 ER PT J AU Bhargava, R Levin, IW AF Bhargava, Rohit Levin, Ira W. BE Bhargava, R Levin, IW TI Spectrochemical Analysis using Infrared Multichannel Detectors Preface SO SPECTROCHEMICAL ANALYSIS USING INFRARED MULTICHANNEL DETECTORS SE Sheffield Analytical Chemistry Series LA English DT Editorial Material; Book Chapter C1 [Bhargava, Rohit] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Bhargava, Rohit] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Levin, Ira W.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bhargava, R (reprint author), Univ Illinois, Dept Bioengn, 405 N Mathews Ave, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98854-1 J9 SHEFF ANALY CHEM PY 2005 BP XV EP XVI D2 10.1002/9780470988541 PG 2 WC Chemistry, Analytical SC Chemistry GA BAD15 UT WOS:000303834200001 ER PT J AU Huffman, SW Brown, CW AF Huffman, Scott W. Brown, Chris W. BE Bhargava, R Levin, IW TI Multivariate analysis of infrared spectroscopic image data SO SPECTROCHEMICAL ANALYSIS USING INFRARED MULTICHANNEL DETECTORS SE Sheffield Analytical Chemistry Series LA English DT Article; Book Chapter ID MODELING MIXTURE ANALYSIS; CURVE RESOLUTION; MULTICOMPONENT ANALYSIS; SPECTRAL DATA; LIQUID-CHROMATOGRAPHY; KEY SET; DIFFERENTIATION; VECTORS C1 [Huffman, Scott W.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Brown, Chris W.] Univ Rhode Isl, Dept Chem, Kingston, RI 02881 USA. RP Huffman, SW (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,B1-38, Bethesda, MD 20892 USA. NR 36 TC 5 Z9 5 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98854-1 J9 SHEFF ANALY CHEM PY 2005 BP 85 EP 114 D2 10.1002/9780470988541 PG 30 WC Chemistry, Analytical SC Chemistry GA BAD15 UT WOS:000303834200005 ER PT S AU Nossal, R AF Nossal, R BE Uribe, FJ Scherer, LGC DiazHerrera, E TI Applications of statistical physics in cell biology SO Statistical Physics and Beyond SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 2nd Mexican Meeting on Mathematical and Experimental Physics CY SEP 06-10, 2004 CL Mexico City, MEXICO SP Univ Autonoma Metropoitana, Consejo Nacl Ciencia Tecnol, Colegio Nacl ID ELECTRON CRYOMICROSCOPY; CLATHRIN; COATS; FLUCTUATIONS; RIGIDITY; MODEL AB The use of statistical physics and thermodynamics in cell biology is illustrated with examples relating to 1) membrane-embedded, switchable ion transport channels and 2) clathrin coats, which play a central role in receptor-mediated endocytosis and other cellular transport processes. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Nossal, R (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 23 TC 0 Z9 0 U1 2 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0242-6 J9 AIP CONF PROC PY 2005 VL 757 BP 104 EP 111 PG 8 WC Physics, Multidisciplinary SC Physics GA BCB22 UT WOS:000228485400010 ER PT J AU Mezey, E AF Mezey, Eva TI Bone marrow and brain - Unexpected allies or accidental acquaintances? SO STEM CELL REVIEWS LA English DT Review DE bone marrow; stem cell; transdifferentiation; fusion; Y chromosome; neuronal repair ID STROMAL CELLS DIFFERENTIATE; ADULT MICE; IN-VIVO; MICROGLIA; FUSION; EXPRESSION; NEURONS; ORIGIN; RAT AB Almost 10 yr have passed since we first entertained the idea that circulating blood cells originating in the bone marrow might contribute to central nervous system (CNS) cell lineages. Initially, we showed that microgalia are derived from bone marrow stem cells (BMSCs). Later, we found that BMSCs might also give rise to other neural cells-even neurons. We made our first observations in rodents, and then we examined human samples. In the brains of female patients who received bone marrow from male donors there are cells with neurons-specific markers together with the Y chromosome suggesting that they are the progeny donor bone marrow cells. All of our data and numerous recent experiments in the field suggest that circulating BM cells are quite plastic. Thus, they might be used in regenerative medicine to help heal or replace lost tissue in many different organs. C1 NIDCR, NIH, Bethesda, MD USA. RP Mezey, E (reprint author), NIDCR, NIH, Bethesda, MD USA. EM mezeye@ninds.nih.gov NR 22 TC 4 Z9 6 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1550-8943 J9 STEM CELL REV JI Stem Cell Rev. PY 2005 VL 1 IS 1 BP 15 EP 19 DI 10.1385/SCR:1:1:015 PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 083BD UT WOS:000240430000003 PM 17132870 ER PT J AU Turksen, K Rao, M AF Turksen, K. Rao, M. TI Issues in human embryonic stem cell biology SO STEM CELL REVIEWS LA English DT Article DE human embryonic stem cells (hESCs); self renewal; pluripotent; commitment; differentiation; regenerative medicine ID DIVERGENT PATHS; BLASTOCYSTS; MAINTAIN AB Human embryonic stem cells(hESC) derived from frozen unused blastocytes from in vitro fertilization clinics exhibit unlimited proliferative capacity, and are pluripotent. The ability to maintain hESCs cultures in an undifferentiated state in vitro and differentiate them along a given lineage in a controlled manner make these cells potentially invaluable in regenerative medicine. Recent developments in the generation of patient specific hESCs as well as animal product free culture systems are some of the latest developments in the field; however great challenges lie ahead before the theraoeutic application of hESCs becomes a reality. This article addresses some of the successes and roadblocks concerning the hESCs field; including various political, ethical and scientific obstacles. C1 Ottawa Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. NIA, Baltimore, MD 21224 USA. RP Turksen, K (reprint author), Ottawa Hlth Res Inst, 725 Parkdale Ave, Ottawa, ON K1Y 4E9, Canada. EM kturksen@ohri.ca NR 10 TC 1 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1550-8943 J9 STEM CELL REV JI Stem Cell Rev. PY 2005 VL 1 IS 2 BP 79 EP 81 DI 10.1385/SCR:1:2:079 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 083OT UT WOS:000240468800001 PM 17142841 ER PT J AU Zerhouni, EA Battey, JF AF Zerhouni, Elias A. Battey, James F., Jr. TI National Institutes of Health (NIH) - Progress on stem cell research SO STEM CELL REVIEWS LA English DT Article DE stem cell research; cell differentiation AB Human embryonic stem cell research offers the promise to eludicate some of the molecular mechanisms that underlie differentiation into specialized types. This knowledge may someday be used to develop new treatments for cellular degenerative diseases. National Institutes of Health has taken several steps to expidate progress in this new field. C1 NIH, Bethesda, MD 20892 USA. RP Battey, JF (reprint author), NIH, Bldg 31,Rm 3602 31 Ctr Dr,MSC 2320,9000 Rockville, Bethesda, MD 20892 USA. EM batteyj@ms.nidcd.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1550-8943 J9 STEM CELL REV JI Stem Cell Rev. PY 2005 VL 1 IS 2 BP 83 EP 85 DI 10.1385/SCR:1:2:083 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 083OT UT WOS:000240468800002 PM 17142842 ER PT J AU Smith, GH AF Smith, Gibert H. TI Stem cells and mammary cancer in mice SO STEM CELL REVIEWS LA English DT Article DE stem cells; MMTV; mammary; cancer; transplantation; mice ID TEMPLATE DNA STRANDS; CHEMICAL CARCINOGENESIS; TGF-BETA-1 EXPRESSION; EPITHELIAL-CELLS; TUMOR VIRUS; GLAND; TUMORIGENESIS; SENESCENCE; RENEWAL; DIFFERENTIATION AB I have used the paradigm of mammary cancer induction by the mouse mammary tumor virus (MMTV) to illustrate the body of evidence that supports the hypothesis that mammary epithelial stem/progenitor cells represent targets for oncogenic transformation. Further, it is argued that this is not a special case applicable only to MMTV-induced mammary cancer, because MMTV acts as an environmental mutagen producing random interruptions in the somatic DNA of infected cells by insertion of proviral DNA copies. In addition to disrupting the host genome, the proviral DNA also influences gene expression through its associated enhancer sequences over significant inter-genome distances. Genes commonly affected by MMTV insertion in multiple individual tumors include the Wnt genes, the fibroblast growth factor (FGF) gene family, and the Notch gene family. All of these gene families are known to play essential roles in stem cell maintenance and behavior in a variety of organs. The MMTV-induced mutations accumulate in cells that are long-lived and possess the properties of stem cells, namely, self-renewal and the capacity to produce divergent epithelial progeny through asymmetric division. The evidence shows that epithelial cells with these properties are present in normal mammary glands, may be infected with MMTV, and become transformed to produce epithelial hyperplasia through MMTV-induced mutagenesis and progress to frank mammary malignancy. Retroviral marking via MMTV proviral insertion demonstrates that this process progresses from a single mammary epithelial cell that possesses all that features ascribed to tissue-specific stem cells. C1 NCI, Ctr Canc Res, Mammary Bioll & Tumorigenesis Lab, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), Bldg 37,Room 1106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gs4d@nih.gov NR 37 TC 12 Z9 12 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1550-8943 J9 STEM CELL REV JI Stem Cell Rev. PY 2005 VL 1 IS 3 BP 215 EP 223 DI 10.1385/SCR:1:3:215 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 083OU UT WOS:000240468900006 PM 17142858 ER PT J AU Gerdes, MJ Yuspa, SH AF Gerdes, Michael J. Yuspa, Stuart H. TI The contribution of epidermal stem cells to skin cancer SO STEM CELL REVIEWS LA English DT Article DE stem cells; skin; squamous cell cancer; basal cell cancer; sebaceous adenoma ID HAIR FOLLICLE MORPHOGENESIS; LABEL-RETAINING CELLS; MOUSE SKIN; TRANSGENIC MICE; BETA-CATENIN; C-MYC; TELOMERASE ACTIVITY; CLONAL ORIGIN; P53 MUTATIONS; ULTRAVIOLET-RADIATION AB Tumors arising from the skin are of multiple phenotypes, with differing degrees of malignant potential. In mouse models of skin carcinogenesis, tumors of squamous phenotype are the most common; however, human disease indicates that multiple phenotypes may arise from a common pool of stem cells that are then influenced by epigenetic factors. The use of transgenic and knockout gene technologies with mice is unraveling some of the specific genes regulating fate determination in stem cells other than squamous lineage, including basal cell carcinoma and sebaceous adenomas. The following review examines the evidence for the stem cell origin of epidermal tumors and the contribution of some specific gene families toward stem cell fate decisions during epidermal tumor progression. C1 NCI, Lab Cellular Carcinogenesis & Tumor Promot, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Lab Cellular Carcinogenesis & Tumor Promot, Ctr Canc Res, Bldg 37,Room 4068A, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov FU Intramural NIH HHS NR 92 TC 30 Z9 31 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1550-8943 J9 STEM CELL REV JI Stem Cell Rev. PY 2005 VL 1 IS 3 BP 225 EP 231 DI 10.1385/SCR:1:3:225 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 083OU UT WOS:000240468900007 PM 17142859 ER PT J AU Lennartsson, J Jelacic, T Linnekin, D Shivakrupa, R AF Lennartsson, J Jelacic, T Linnekin, D Shivakrupa, R TI Normal and oncogenic forms of the receptor tyrosine kinase kit SO STEM CELLS LA English DT Review DE kit; signal transduction; hematopoiesis; oncogene; cancer ID STEM-CELL-FACTOR; GASTROINTESTINAL STROMAL TUMORS; COLONY-STIMULATING FACTOR; PROTOONCOGENE C-KIT; SRC FAMILY KINASES; ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC PROGENITOR CELLS; ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR; JUVENILE MYELOMONOCYTIC LEUKEMIA AB Kit is a receptor tyrosine kinase (RTK) that binds stem cell factor. This receptor ligand combination is important for normal hematopoiesis, as well as pigmentation, gut function, and reproduction. Structurally, Kit has both an extracellular and intracellular region. The intracellular region is comprised of a juxtamembrane domain (JMD), a kinase domain, a kinase insert, and a carboxyl tail. Inappropriate expression or activation of Kit is associated with a variety of diseases in humans. Activating mutations in Kit have been identified primarily in the JMD and the second part of the kinase domain and have been associated with gastrointestinal stromal cell tumors and mastocytosis, respectively. There are also reports of activating mutations in some forms of germ cell tumors and core binding factor leukemias. Since the cloning of the Kit ligand in the early 1990s, there has been an explosion of information relating to the mechanism of action of normal forms of Kit as well as activated mutants. This is important because understanding this RTK at the biochemical level could assist in the development of therapeutics to treat primary and secondary defects in the tissues that require Kit. Furthermore, understanding the mechanisms mediating transformation of cells by activated Kit mutants will help in the design of interventions for human disease associated with these mutations. The objective of this review is to summarize what is known about normal and oncogenic forms of Kit. We will place particular emphasis on recent developments in understanding the mechanisms of action of normal and activated forms of this RTK and its association with human disease, particularly in hematopoietic cells. C1 NCI, Basic Res Lab, Canc Res Ctr, Frederick, MD 21701 USA. RP Lennartsson, J (reprint author), Ludwig Inst Canc Res, Biomed Ctr, Box 595, SE-75124 Uppsala, Sweden. EM Johan.Lennartsson@LICR.uu.se NR 269 TC 172 Z9 182 U1 1 U2 7 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JAN PY 2005 VL 23 IS 1 BP 16 EP 43 DI 10.1634/stemcells.2004-0117 PG 28 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 886UY UT WOS:000226259400003 PM 15625120 ER PT S AU Antani, S Long, LR Thoma, GR AF Antani, S Long, LR Thoma, GR BE Lienhart, RW Babaguchi, N Chang, EY TI Applying vertebral boundary semantics to CBIR of digitized spine X-ray images SO Storage and Retrieval Methods and Applications for Multimedia 2005 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Storage and Retrieval Methods and Applications for Multimedia 2005 CY JAN 18-19, 2005 CL San Jose, CA SP Soc Imaging Sci & Technol, SPIE DE semantics; content-based image retrieval; biomedical image databases; shape matching; NHANES II ID OSTEOPHYTES AB There is a growing research interest in reliable content-based image retrieval (CBIR) techniques specialized for biomedical image retrieval. Applicable feature representation and similarity algorithms have to balance conflicting goals of efficient and effective retrieval while allowing queries on important and often subtle biomedical features. In a collection of digitized X-rays of the spine, such as that from the second National Health and Nutrition Examination Survey (NHANES II) maintained by the National Library of Medicine, a typical user may be interested in only a small region of the vertebral boundary pertinent to the pathology: for this experiment, the Anterior Osteophyte (AO). A previous experiment in pathology-based retrieval using partial shape matching (PSM) on a subset from the above collection; about 89% normal vertebrae were correctly retrieved. In contrast only 45% of moderate and severe cases were correctly retrieved, and on the average only 46% of the pathology classes were correctly determined. Further analysis revealed that mere shape matching is insufficient for semantically correct retrieval of pathological cases. This paper describes an automatic 9 point localization algorithm that incorporates reasoning about boundary semantics equivalent to that applied by the content-expert as a step in our enhancements to PSM, and results from initial experiments. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD 20894 USA. RP Antani, S (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 9 TC 5 Z9 5 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5655-1 J9 P SOC PHOTO-OPT INS PY 2005 VL 5682 BP 98 EP 107 DI 10.1117/12.588467 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Software Engineering; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BCD73 UT WOS:000228758500010 ER PT J AU Longstreth, WT Arnold, AM Beauchamp, NJ Manolio, TA Lefkowitz, D Jungreis, C Hirsch, CH O'Leary, DH Furberg, CD AF Longstreth, WT Arnold, AM Beauchamp, NJ Manolio, TA Lefkowitz, D Jungreis, C Hirsch, CH O'Leary, DH Furberg, CD TI Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly - The Cardiovascular Health Study SO STROKE LA English DT Article DE incidence; leukoaraiosis; magnetic resonance imaging ID AUSTRIAN STROKE PREVENTION; BLOOD-PRESSURE; FOLLOW-UP; BRAIN; LESIONS; MRI; HYPERINTENSITIES; PROGRESSION; VOLUMES; DISEASE AB Background and Purpose-Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging. Methods-The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade. Results-Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both Pless than or equal to0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk. Conclusion-Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors. C1 Univ Washington, Harborview Med Ctr, Dept Neurol, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. Univ Washington, Dept Biostat, Seattle, WA 98104 USA. Univ Washington, Dept Radiol, Seattle, WA 98104 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Dept Radiol, Neuroradiol Div, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Neurol Surg, Neuroradiol Div, Pittsburgh, PA USA. Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. Tufts New England Med Ctr, Dept Radiol, Boston, MA USA. Wake Forest Univ, Dept Neurol, Winston Salem, NC 27109 USA. Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Longstreth, WT (reprint author), Univ Washington, Harborview Med Ctr, Dept Neurol, Box 359775,325 9th Ave, Seattle, WA 98104 USA. EM wl@u.washington.edu FU NHLBI NIH HHS [N01-HC-85084, N01-HC-85080, N01-HC-85083, N01-HC-15103, N01-HC-35129, N01-HC-85082, N01-HC-85081, N01-HC-85085, N01-HC-85086, N01-HC-85079] NR 19 TC 214 Z9 227 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2005 VL 36 IS 1 BP 56 EP 61 DI 10.1161/01.STR.0000149625.99732.69 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 882NE UT WOS:000225944800016 PM 15569873 ER PT J AU Hacke, W Albers, G Al-Rawi, Y Bogousslavsky, J Davalos, A Eliasziw, M Fischer, M Furlan, A Kaste, M Lees, KR Soehngen, M Warach, S AF Hacke, W Albers, G Al-Rawi, Y Bogousslavsky, J Davalos, A Eliasziw, M Fischer, M Furlan, A Kaste, M Lees, KR Soehngen, M Warach, S CA DIAS Study Grp TI The Desmoteplase In Acute Ischemic Stroke Trial (DIAS) - A phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase SO STROKE LA English DT Article DE desmoteplase; magnetic resonance imaging; stroke; thrombolytic therapy ID TISSUE-PLASMINOGEN ACTIVATOR; PERFUSION MRI; ECASS II; DIFFUSION; ALTEPLASE; ATLANTIS; THERAPY AB Background and Purpose-Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI. Methods-DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale ( IHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 mug/kg, 90 mug/kg, and 125 mug/kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days. Results-Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012) were observed with desmoteplase (125 mug/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 mug/kg; P=0.757) and 60.0% (125 mug/kg; P=0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion. Conclusions-Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 mug/kg. C1 Univ Heidelberg, Dept Neurol, D-69120 Heidelberg, Germany. PAION GmbH, Aachen, Germany. ClinRes GmbH, Cologne, Germany. CHU Vaudois, Dept Neurol, Lausanne, Switzerland. Hosp Univ Dr Josep Trueta, Girona, Spain. Univ Calgary, Calgary, AB, Canada. Univ Helsinki, Cent Hosp, Dept Clin Neurosci, Helsinki, Finland. Univ Glasgow, Western Infirm, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland. Stanford Stroke Ctr, Palo Alto, CA USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Hacke, W (reprint author), Univ Heidelberg, Dept Neurol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany. EM werner_hacke@med.uni-heidelberg.de OI Kaste, Markku/0000-0001-6557-6412 NR 13 TC 651 Z9 688 U1 0 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2005 VL 36 IS 1 BP 66 EP 73 DI 10.1161/01.STR.0000149938.08731.2c PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 882NE UT WOS:000225944800018 PM 15569863 ER PT J AU Wood, MJ Storz, G AF Wood, MJ Storz, G TI Oxygen, metabolism, and gene expression: The T-Rex connection SO STRUCTURE LA English DT Editorial Material ID DNA-BINDING C1 NICHHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Wood, MJ (reprint author), NICHHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 8 TC 1 Z9 1 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JAN PY 2005 VL 13 IS 1 BP 2 EP 4 DI 10.1016/j.str.2004.12.002 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 893SW UT WOS:000226740500002 PM 15642255 ER PT J AU Moolchan, ET Zimmerman, D Sehnert, SS Zimmerman, D Huestis, MA Epstein, DH AF Moolchan, ET Zimmerman, D Sehnert, SS Zimmerman, D Huestis, MA Epstein, DH TI Recent marijuana blunt smoking impacts carbon monoxide as a measure of adolescent tobacco abstinence SO SUBSTANCE USE & MISUSE LA English DT Article DE adolescent; marijuana; carbon monoxide; smoking cessation ID CANNABIS USE; CESSATION; BEHAVIOR AB Adolescent tobacco smokers have a higher prevalence of marijuana (MJ) smoking than adolescents who do not smoke tobacco. As part of all adolescent smoking cessation trial, we examined whether MJ smoking, and specifically "blunt" (gutted cigars filled with MJ) smoking, elevated participants' likelihood of a false indication of cigarette smoking on the basis of breath carbon monoxide (CO) testing. Using clinical data from 37 adolescents (mean age 15.1 +/- 1.4 years, 78% female) who participated in a smoking-cessation trial in Baltimore between 1999 and 2002, and who on at least one occasion, reported abstinence from tobacco smoking for at least 7 days, we analyzed 146 cigarette-abstinent-visit exhaled CO concentrations classified into blunt occasions (12 participants, 33 visits), nonblunt MJ occasions (seven participants, 20 visits), and non-MJ occasions (27 paricipants, 93 visits). Repeated-measures logistic regression revealed that blunt occasions were associated with CO >= 8 ppm, compared to nonblunt occasions (p = 0.013). Blunt occasions also tended to be associated with the more youth-appropriate cutoff CO >= 6 ppm, compared to non-MJ occasions (p = 0.054). Blunt smoking impacted the interpretation of measures of exhaled CO for tobacco cessation. C1 NIDA, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program, Dept HHS,NIH, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program, Dept HHS,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov NR 27 TC 12 Z9 12 U1 2 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2005 VL 40 IS 2 BP 231 EP 240 DI 10.1081/JA-200048461 PG 10 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 906CU UT WOS:000227618900006 PM 15770886 ER PT J AU Flanzer, J AF Flanzer, J TI The status of health services research on adjudicated drug-abusing juveniles: Selected findings and remaining questions SO SUBSTANCE USE & MISUSE LA English DT Review DE adolescents; "drug abuse"; juvenile justice; health services; recovery; relapse; treatment effectiveness ID ADOLESCENT SUBSTANCE USE; HIGH-RISK YOUTHS; COST-BENEFIT; OUTCOMES; BEHAVIOR; OFFENDERS; ALCOHOL; INTERVENTIONS; DISORDERS; ALLIANCE AB This article focuses on the factors that affect the availability, accessibility, and opportunity of effective treatment for the adjudicated adolescent drug user The social and developmental context of "drug abuse" and its treatment in adolescents, and particularly in adjudicated adolescents, is reviewed and compared with that in adults. Selected health services research findings on this population are discussed in terms of the effectiveness of delivering treatment services; the organization, management, and financing of services; and adoption of best practices (technology transfer). C1 NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Flanzer, J (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd,Room 5153,MSC 9589, Bethesda, MD 20892 USA. EM JF1991@nih.gov NR 101 TC 11 Z9 11 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2005 VL 40 IS 7 SI SI BP 887 EP 911 DI 10.1081/JA-200058862 PG 25 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 943UA UT WOS:000230378900002 PM 16021921 ER PT J AU Thomas, Y Lambert, EY AF Thomas, Y Lambert, EY TI Special issue on club drug epidemiology - Foreward SO SUBSTANCE USE & MISUSE LA English DT Editorial Material C1 NIDA, Epidemiol Res Branch, Div Epidemiol & Prevent Res, Lexington, KY 40583 USA. RP Thomas, Y (reprint author), NIDA, Epidemiol Res Branch, Div Epidemiol & Prevent Res, Lexington, KY 40583 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2005 VL 40 IS 9-10 BP 1185 EP 1187 DI 10.1081/JA-200066724 PG 3 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 952RC UT WOS:000231022200002 ER PT S AU Moczydiowski, W Geser, A AF Moczydiowski, W Geser, A BE Giesl, J TI Termination of single-threaded one-rule Semi-Thue Systems SO TERM REWRITING AND APPLICATIONS, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 16th International Conference on Rewriting Technique and Application (RAT 2005) CY APR 19-21, 2005 CL Nara, JAPAN SP Fdn Nara Inst Sci & Technol, Informat Proc Soc Japan, Japan Soc Promot Sci, Kayamori Fdn Informat Sci Adv, Nara Convent Bureau, Telecomm Adv Fdn DE string rewriting; semi-Thue system; uniform termination; termination; one-rule; single-rule; single-threaded; well-behaved AB This paper is a contribution to the long standing open problem of uniform termination of Semi-Thue Systems that consist of one rule s -> t. McNaughton previously showed that rules incapable of (1) deleting t completely from both sides, (2) deleting t completely from the left, and (3) deleting t completely from the right, have a decidable uniform termination problem. We use a novel approach to show that Premise (2) or, symmetrically, Premise (3), is inessential. Our approach is based on derivations in which every pair of successive steps has an overlap. We call such derivations single-threaded. C1 Cornell Univ, Dept Comp Sci, Ithaca, NY 14853 USA. NIA, Hampton, VA 23666 USA. RP Moczydiowski, W (reprint author), Cornell Univ, Dept Comp Sci, 5162 Upson Hall, Ithaca, NY 14853 USA. EM wojtek@cs.cornell.edu; geser@nianet.org NR 12 TC 3 Z9 3 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-25596-6 J9 LECT NOTES COMPUT SC PY 2005 VL 3467 BP 338 EP 352 PG 15 WC Computer Science, Theory & Methods SC Computer Science GA BCH40 UT WOS:000229314100024 ER PT S AU Cho-Chung, YS Nesterova, MV AF Cho-Chung, YS Nesterova, MV BE ChoChung, YS Gerwirtz, AM Stein, CA TI Tumor reversion: Protein kinase A isozyme switching SO THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th NIH Symposium on Therapeutic Oligonucleotides CY DEC 13-14, 2004 CL NIH, Bethesda, MD HO NIH DE protein kinase A; antisense; gene transfer; gene therapy; site-selective cAMP analog; tumor reversion ID RI-ALPHA-SUBUNIT; CYCLIC-AMP ANALOGS; CANCER CELL-GROWTH; RII(BETA) REGULATORY SUBUNIT; HL-60 LEUKEMIA-CELLS; CAMP-BINDING-SITES; ANTISENSE OLIGODEOXYNUCLEOTIDE; BETA-SUBUNIT; AUTOPHOSPHORYLATION SITE; GENE-EXPRESSION AB The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in the isoforms RI and RII, which distinguish PKA isozymes type I (PKA-I) and type II (PKA-II). Evidence obtained from different experimental approaches-such as site-selective cAMP analogs, antisense oligonucleotides, transcription factor decoys, cDNA microarrays, and gene transfer-has shown that PKA-I and -II are expressed in a balance of cell growth and differentiation. Loss of this balance may underlie cancer genesis and progression. DNA microarrays demonstrate that antisense suppression of the Ri alpha, which upregulates RII beta, downregulates a wide range of genes involved in cell proliferation and transformation while upregulating cell differentiation and reverse transformation genes in PC3M prostate tumors that undergo regression. Conversely, the vector-mediated overexpression of RII beta, as opposed to those of RI alpha and Cot, exhibits induction of differentiation genes along with suppression of cell proliferation and transformation genes leading to reversion of tumor pheno-type. Thus, switching of PKA isozyme can cause tumor cells to undergo pheno-typic reversion of the malignancy. C1 NCI, Cellular Biochem Sect, BRL, CCR, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, BRL, CCR, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yc12b@nih.gov NR 60 TC 34 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 1-57331-608-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1058 BP 76 EP 86 DI 10.1196/annals.1359.014 PG 11 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BEA63 UT WOS:000236466000007 PM 16394127 ER PT S AU Zheng, ZM Tang, SA Tao, MF AF Zheng, ZM Tang, SA Tao, MF BE ChoChung, YS Gerwirtz, AM Stein, CA TI Development of resistance to RNAi in mammalian cells SO THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th NIH Symposium on Therapeutic Oligonucleotides CY DEC 13-14, 2004 CL NIH, Bethesda, MD HO NIH DE RNA interference; siRNA; miRNA; gene expression; viral inhibitors; gene therapies ID DOUBLE-STRANDED-RNA; SMALL INTERFERING RNAS; DEPENDENT PROTEIN-KINASE; ADENOVIRUS VAI-RNA; DELTA-VIRUS RNAS; GENE-EXPRESSION; MESSENGER-RNA; NS1 PROTEIN; CAENORHABDITIS-ELEGANS; SILENCING SUPPRESSOR AB The discovery of RNA interference (RNAi) in C. elegans and in plants has revolutionized current approaches to biology and medicine. RNAi silences genes in a sequence-specific manner through the actions of small pieces of double-stranded RNAs (siRNAs and miRNAs). RNAi has been found as a widespread natural phenomenon in eukaryotic cells and is also being used as a powerful experimental tool to explore gene function. Most importantly, it has many potential therapeutic applications. Viral gene-specific siRNAs are theoretically very promising antiviral inhibitors and have been examined in a broad range of medically important viruses. However, many RNA viruses escape RNAi-mediated suppression by counteracting the RNAi machinery through mutation of the targeted region, by encoding viral suppressors, or both. DNA viruses also counteract the RNAi machinery, preferentially using viral suppressors. Cellular factors may also contribute to RNAi resistance; ADAR1 was the first cellular factor found to be responsible for editing-mediated RNAi resistance. Because siRNAs can be used as potent small-molecule inhibitors of any cellular gene, the best way for a cell to maintain expression of essential genes for its long-term survival is to develop a program to resist the detrimental effects of RNAi. C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 10S 255, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov RI Tang, Shuang/F-9115-2014 OI Tang, Shuang/0000-0002-3084-0903 FU NCI NIH HHS [Z01 SC010357-06] NR 76 TC 30 Z9 30 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 1-57331-608-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1058 BP 105 EP 118 DI 10.1196/annals.1359.019 PG 14 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BEA63 UT WOS:000236466000010 PM 16394130 ER PT S AU Seidman, MM Puri, N Majumdar, A Cuenoud, B Miller, PS Alam, R AF Seidman, MM Puri, N Majumdar, A Cuenoud, B Miller, PS Alam, R BE ChoChung, YS Gerwirtz, AM Stein, CA TI The development of bioactive triple helix-forming oligonucleotides SO THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th NIH Symposium on Therapeutic Oligonucleotides CY DEC 13-14, 2004 CL NIH, Bethesda, MD HO NIH DE triple helix-forming oligonucleotide; gene targeting ID DOUBLE-STRANDED DNA; 2'-AMINOETHOXY-MODIFIED OLIGONUCLEOTIDES; DUAL RECOGNITION; CHROMATIN; STABILITY; NUCLEUS AB We are developing triple helix-forming oligonucleotides (TFOs) as gene targeting reagents in mammalian cells. We have described psoralen-conjugated TFOs containing 2'-O-methyl (2'OMe) and 2'-O-aminoethoxy (AE) ribose substitutions. TFOs with a cluster of 3-4 AE residues, with all other sugars as 2'OMe, were bioactive in a gene knockout assay in mammalian cells. In contrast, TFOs with one or two clustered, or three dispersed, AE residues were inactive. Thermal stability analysis of the triplexes indicated that there were only incremental differences between the active and inactive TFOs. However the active and inactive TFOs could be distinguished by their association kinetics. The bioactive TFOs showed markedly greater on-rates than the inactive TFOs. It appears that the on-rate is a better predictor of TFO bioactivity than thermal stability. Our data are consistent with a model in which a cluster of 34 AE residues stabilizes the nucleation event that precedes formation of a complete triplex. It is likely that triplexes in cells are much less stable than triplexes in vitro probably as a result of elation by chromatin-associated translocases and helicases. Consequently the biologic assay will favor TFOs that can bind and rebind genomic targets quickly. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA. Nova Pharmaceut Ltd, CH-4002 Basel, Switzerland. RP Seidman, MM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM seidmanm@grc.nia.nih.gov NR 17 TC 22 Z9 22 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 1-57331-608-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1058 BP 119 EP 127 DI 10.1196/annals.1359.020 PG 9 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BEA63 UT WOS:000236466000011 PM 16394131 ER PT S AU Panyutin, IV Sedelnikova, OA Bonner, WM Panyutin, IG Neumann, RD AF Panyutin, IV Sedelnikova, OA Bonner, WM Panyutin, IG Neumann, RD BE ChoChung, YS Gerwirtz, AM Stein, CA TI DNA damage produced by I-125-triplex-forming oligonucleotides as a measure of their succesful delivery into cell nuclei SO THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th NIH Symposium on Therapeutic Oligonucleotides CY DEC 13-14, 2004 CL NIH, Bethesda, MD HO NIH DE targeted radiotherapy; DNA triplex; antigene therapy; Auger emitters ID TRIPLEX-FORMING-OLIGONUCLEOTIDES; MAMMALIAN-CELLS; GENE; RADIOTHERAPY; PEPTIDE AB Decay of an Auger-electron-emitting radioisotope can knock out a targeted gene by producing DNA strand breaks within its sequence. For delivery of Auger emitters to genomic targets we used triplex-forming oligonucleotides (TFOs) that bind specifically to their target sequences by forming hydrogen bonds within the major groove of the target duplex. We named this approach antigene radiotherapy. In our previous studies, we demonstrated that I-125-labeled TFOs targeted against the human MDR1 gene produced sequence-specific double strand breaks (DSBs) within this gene in live cultured cells. We also found that conjugation of TFO with nuclear localization signal peptide significantly increased the efficiency of targeting. To screen the wide variety of possible TFO modifications a sensitive and robust assay of DNA damage produced by such I-125-TFOs would be highly desirable. Recently we showed a direct correspondence between the number of decays of I-125 incorporated into DNA as I-125-UdR and the number of histone gamma-H2AX foci per cell revealed by staining with gamma-H2AX antibodies. The technique is 100-fold more sensitive than other DSB-detection methods, thus it is possible to detect as few as an average of 0.5 DSBs per cell in a population of cultured cells. Here we applied this method to evaluate the intracellular DNA damage produced by two I-125-TFOs, the first targeted to the single-copy HPRT gene (I-125-TFO-HPRT) and second to a multicopy repeated sequence (GA)(n) that occurs almost 7000 times in the human genome (I-125-TFO-GA). DNA damage produced by I-125-TFO was assessed by staining the cells with gamma-H2AX antibody followed by either direct counting gamma-H2AX foci or by measuring the gamma-H2AX signal using flow cytometry. Both methods produced quantitatively close results; I-125-TFO-GA with multiple nuclear targets produced on average 1.93 times more gamma-H2AX foci per cell and generated 1.96 times increase in gamma-H2AX antibody staining signal than I-125-TFO-HPRT with a single target. The gamma-112AX-based assay requires considerably less time and effort than the direct measurement of DSB by Southern hybridization applied previously. Therefore, we believe that gamma-H2AX-based measurement of DNA damage could be useful for evaluation and cellular DNA accessibility by I-121-labeled DNA targeting agents. C1 NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Panyutin, IV (reprint author), NIH, Dept Nucl Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM igorp@helix.nih.gov NR 15 TC 5 Z9 9 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-608-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1058 BP 140 EP 150 DI 10.1196/annals.1359.022 PG 11 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BEA63 UT WOS:000236466000013 PM 16394133 ER PT S AU Cheadle, C Fan, J Cho-Chung, YS Werner, T Ray, J Do, L Gorospe, M Becker, KG AF Cheadle, C Fan, J Cho-Chung, YS Werner, T Ray, J Do, L Gorospe, M Becker, KG BE ChoChung, YS Gerwirtz, AM Stein, CA TI Stability regulation of mRNA and the control of gene expression SO THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th NIH Symposium on Therapeutic Oligonucleotides CY DEC 13-14, 2004 CL NIH, Bethesda, MD HO NIH DE nuclear run-on; microarray; transcription; mRNA turnover; T cell ID T-CELLS; TRANSCRIPTION; CDNA; ACTIVATION; MICROARRAY; ARRAYS AB Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. Standard techniques measure changes in total cellular poly(A) mRNA levels. The assumption that changes in gene expression as measured by these techniques are directly and well correlated with changes in rates of new gene synthesis form the basis of attempts to connect coordinated changes in gene expression with shared transcription regulatory elements. Yet systematic attempts at this approach remain difficult to demonstrate convincingly. One reason for this difficulty may result from the intricate convergence of both transcriptional and mRNA turnover events which, together, directly influence steady-state mRNA levels. Recent technical advances have led to the successful scale-up and application of nuclear run-on procedures directly to microarrays. This development has allowed a gene-by-gene comparison between new gene synthesis in the nucleus and measured changes in total cellular polyA mRNA. Results from these studies have begun to challenge the strict interpretation of changes in gene expression measured by conventional microarrays as being closely correlated with changes in mRNA transcription rate, but rather they tend to support the significant expansion of the role played by changes in mRNA stability regulation to standard analyses of gene expression. Gene expression profiles obtained from both polyA mRNA (whole-cell) and nuclear run-on (newly transcribed) RNA across a time course of one hour following the activation of human Jurkat T cells with PMA plus ionomycin revealed that regulation of mRNA stability may account for as much as 50% of all measurements of changes in total cellular polyA mRNA in this system. Stability regulation was inferred by the absence of corresponding regulation of nuclear gene transcription activity for groups of genes strongly regulated at the whole cell level and which were also resistant to inhibition by Actinomycin D pre-treatment. Consistent patterns across the time course were observed for both transcribed and stability-regulated genes. It is proposed that the regulation of mRNA stability in response to external stimuli contributes significantly to observed changes in gene expression as measured by high throughput systems. C1 NCI, CCR, NIH, Basic Res Labs,Cellular Biochem Sect, Bethesda, MD 20892 USA. NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Genomatix Software GmbH, D-80339 Munich, Germany. Capital Genomix, Gaithersburg, MD 20877 USA. NIA, DNA Array Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Cheadle, C (reprint author), NCI, CCR, NIH, Basic Res Labs,Cellular Biochem Sect, Bldg 10,Room 5B05, Bethesda, MD 20892 USA. EM cheadlec@mail.nih.gov OI Becker, Kevin/0000-0002-6794-6656 NR 18 TC 69 Z9 71 U1 0 U2 9 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-608-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1058 BP 196 EP 204 DI 10.1196/annals.1359.026 PG 9 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BEA63 UT WOS:000236466000017 PM 16394137 ER PT S AU Marquez, VE Kelley, JA Agbaria, R Ben-Kasus, T Cheng, JC Yoo, CB Jones, PA AF Marquez, VE Kelley, JA Agbaria, R Ben-Kasus, T Cheng, JC Yoo, CB Jones, PA BE ChoChung, YS Gerwirtz, AM Stein, CA TI Zebularine: A unique molecule for an epigenetically based strategy in cancer chemotherapy SO THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th NIH Symposium on Therapeutic Oligonucleotides CY DEC 13-14, 2004 CL NIH, Bethesda, MD HO NIH DE zebularine; cytidine deaminase inhibition; DNA methyltrasferase inhibition; antitumor activity; gene reactivation ID NUCLEIC-ACID COMPONENTS; DNA METHYLATION INHIBITOR; CYTIDINE DEAMINASE; 2-PYRIMIDINONE NUCLEOSIDES; RIBOSIDE ZEBULARINE; ANALOGS; ENZYME; 5-AZA-2'-DEOXYCYTIDINE; METHYLTRANSFERASE; CYTOSINE AB 1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) corresponds structurally to cytidine minus the exocyclic 4-amino group. The increased electrophilic character of its simple aglycon endows the molecule with unique biologic properties as a potent inhibitor of both cytidine deaminase and DNA cytosine methyltransferase. The latter activity makes zebularine a promising antitumor agent that is hydrolytically stable, preferentially targets cancer cells, and shows activity both in vitro and in experimental animals, even after oral administration. C1 NCI, Canc Res Ctr, Med Chem Lab, NIH, Frederick, MD 21702 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biochem, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biol Mol, Los Angeles, CA 90089 USA. RP Marquez, VE (reprint author), NCI, Canc Res Ctr, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov NR 27 TC 53 Z9 58 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 1-57331-608-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1058 BP 246 EP 254 DI 10.1196/annals.1359.037 PG 9 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BEA63 UT WOS:000236466000021 PM 16394141 ER PT S AU Nesterova, MV Cho-Chung, YS AF Nesterova, MV Cho-Chung, YS BE ChoChung, YS Gerwirtz, AM Stein, CA TI Chemoprevention with protein kinase A RI alpha antisense in DMBA-mammary carcinogenesis SO THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th NIH Symposium on Therapeutic Oligonucleotides CY DEC 13-14, 2004 CL NIH, Bethesda, MD HO NIH DE antisense; protein kinase A; carcinogenesis; chemoprevention; phase II enzymes; DNA repair; transcription factors ID XENOBIOTIC-METABOLIZING ENZYMES; TRANSCRIPTION FACTOR DECOY; EMBRYO CELL-CULTURES; CYCLIC-AMP; TUMOR-GROWTH; REGULATORY SUBUNIT; PHASE-I; NAD(P)H-QUINONE REDUCTASE; DIETARY ANTIOXIDANTS; CANCER AB Cancer is potentially preventable disease. A surprising variety of intracellular pathways can be a target for chemoprevention. Earlier it was discovered that cAMP-mediated system can play important role in prevention of DMBA-mammary carcinogenesis. There are two types of cAMP-dependent protein kinases (PKA), type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunits, but contain distinct regulatory (R) ones, RI versus RII, respectively. Evidence suggests that increased expression of PKA-I and its regulatory subunit (RI alpha) correlates with tumorogenesis and tumor growth. It was found that downregulation of RI alpha by 21-mer antisense oligonucleotide led to growth arrest of cancer cells. The effect of RI alpha antisense oligonucleotide correlated with a decrease in RI alpha protein and a concomitant increase in RII beta protein level. It was shown that antisense RI alpha can protect in a sequence-specific manner from 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis. At 90 days after DMBA intubation, RI alpha-antisense-treated rats exhibited significantly lower number of tumors per rat, than untreated control animals. The antisense also delayed the first tumor appearance. An increase in RI alpha and PKA-I levels in the mammary gland and liver preceded tumor production, and antisense downregulation of RI alpha restored normal levels of PKA-I and PKA-II in these tissues. Antisense RI alpha in the liver induced the phase H enzymes, glutathione S-transferase and quinone oxidoreductase, c-fos protein, and activator protein-1 (AP-1)- and cAMP response element (CRE)-directed transcription. In the mammary gland, antisense RI alpha promoted DNA repair processes. In contrast, the CRE transcription-factor decoy could not mimic these effects of antisense RI alpha. The results demonstrate that RI alpha antisense produces dual anticarcinogenic effects : (a) increasing DMBA detoxification in the liver by increasing phase 11 enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing CRE- and AP-1 directed transcription; and (b) activating DNA repair processes in the mammary gland by downregulating of PKA-1. C1 NCI, CCR, Basic Res Lab, Cellular Biochem Sect, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, CCR, Basic Res Lab, Cellular Biochem Sect, Bldg 10,Rm 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yc12b@nih.gov NR 57 TC 7 Z9 8 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-608-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1058 BP 255 EP 264 DI 10.1196/annals.1359.038 PG 10 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BEA63 UT WOS:000236466000022 PM 16394142 ER PT J AU Williams, C Walther, M AF Williams, Christopher Walther, McClellan TI Metastatic renal cell carcinoma versus pancreatic neuroendocrine tumor in von Hippel-Lindau disease: Treatment with interleukin-2 SO THESCIENTIFICWORLDJOURNAL LA English DT Article DE von Hippel-Lindau; neuroendocrine tumor; pancreas; renal cell carcinoma; metastases AB Differentiating between clear cell neuroendocrine tumor (NET) of the pancreas and renal cell carcinoma (RCC) metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL). The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies. C1 NCI, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Williams, C (reprint author), NCI, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA. EM willichr@mail.nih.gov; waltherm@mail.nih.gov NR 3 TC 5 Z9 5 U1 0 U2 0 PU THESCIENTIFICWORLD LTD PI NEWBURY PA 29-34, VENTURE WEST, NEW GREENHAM PARK, NEWBURY, BERKSHIRE RG19 6HX, ENGLAND SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PD JAN PY 2005 VL 5 BP 9 EP 10 DI 10.1100/tsw.2005.5 PG 2 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 109NF UT WOS:000242314300003 PM 15674444 ER PT J AU Horne, M AF Horne, M TI Overview of hemostasis and thrombosis; current status of antithrombotic therapies SO THROMBOSIS RESEARCH LA English DT Article; Proceedings Paper CT Conference on Dietary Supplements, Coagulation and Antithrombotic Therapies CY JAN 13-14, 2005 CL NIH, Bethesda, MD HO NIH C1 NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Horne, M (reprint author), NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov NR 3 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 117 IS 1-2 SI SI BP 15 EP 17 DI 10.1016/j.thromres.2005.05.007 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 987AM UT WOS:000233490800003 PM 16055174 ER PT J AU Desai, D Hasan, A Wesley, R Sunderland, E Pucino, F Csako, G AF Desai, D Hasan, A Wesley, R Sunderland, E Pucino, F Csako, G TI Effects of dietary supplements on aspirin and other antiplatelet agents: An evidence-based approach SO THROMBOSIS RESEARCH LA English DT Article; Proceedings Paper CT Conference on Dietary Supplements, Coagulation and Antithrombotic Therapies CY JAN 13-14, 2005 CL NIH, Bethesda, MD HO NIH ID LOW-DOSE ASPIRIN; N-3 FATTY-ACIDS; CORONARY-ARTERY-DISEASE; INHIBITS PLATELET ACTIVITY; VITAMIN-E; EICOSAPENTAENOIC ACID; FISH-OIL; MYOCARDIAL-INFARCTION; HEALTHY-VOLUNTEERS; PRIMARY-PREVENTION C1 NIH, Dept Pharm, Ctr Clin, DHHS, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, DHHS, Bethesda, MD 20892 USA. NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, DHHS, Bethesda, MD 20892 USA. NIH, Off Res Serv, Off Director, DHHS, Bethesda, MD 20892 USA. NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. RP Desai, D (reprint author), NIH, Dept Pharm, Ctr Clin, DHHS, Bldg 10,Room 1N-257, Bethesda, MD 20892 USA. EM ravald@cc.nih.gov NR 61 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 117 IS 1-2 SI SI BP 87 EP 101 DI 10.1016/j.thromres.2005.06.017 PG 15 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 987AM UT WOS:000233490800016 PM 16115664 ER PT J AU Bussey, H Tapson, V Cannon, RO Nolan, PE Gage, B Penzak, SR Spinler, SA De Smet, P Wittkowsky, A Lee, AP Ernst, E Marder, VJ AF Bussey, H Tapson, V Cannon, RO Nolan, PE Gage, B Penzak, SR Spinler, SA De Smet, P Wittkowsky, A Lee, AP Ernst, E Marder, VJ TI Opinions and research priorities SO THROMBOSIS RESEARCH LA English DT Editorial Material ID DIAGNOSED ATRIAL-FIBRILLATION; ALTERNATIVE MEDICINE; STROKE PREVENTION; HERBAL MEDICINES; RISK-FACTORS; COMPLEMENTARY; TRIALS; XIMELAGATRAN; THERAPIES; ADULTS C1 Univ Texas, Coll Pharm, Austin, TX 78712 USA. Univ Texas, Hlth Sci Ctr, Clin Pharm Programs, San Antonio, TX 78229 USA. Duke Univ, Med Ctr, Div Pulm & Crit Care Med, Durham, NC 27706 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Arizona, Coll Pharm, Dept Pharm & Sci, Tucson, AZ 85721 USA. Washington Univ, Sch Med, St Louis, MO USA. NIH, Ctr Clin, Dept Pharm, Cli Pharmacokinet Res Lab, Bethesda, MD 20892 USA. Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA USA. Sci Inst Dutch Phamacists, The Hague, Netherlands. Univ Washington, Med Ctr, Anticoagulat Serv, Seattle, WA 98195 USA. Peninsula Med Sch, Exeter, Devon, England. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Bussey, H (reprint author), Univ Texas, Coll Pharm, Austin, TX 78712 USA. EM Bussey@uthscsa.edu NR 53 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 117 IS 1-2 SI SI BP 155 EP 169 DI 10.1016/j.thromres.2005.05.030 PG 15 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 987AM UT WOS:000233490800024 PM 16099491 ER PT J AU Costello, R Young, J Burkholder, R Cranston, J Ortel, TL Dentali, S Cotter, R Maillet, JOS Hawkins, B Hooper, WC AF Costello, R Young, J Burkholder, R Cranston, J Ortel, TL Dentali, S Cotter, R Maillet, JOS Hawkins, B Hooper, WC TI Dialogue with patient care organizations SO THROMBOSIS RESEARCH LA English DT Article; Proceedings Paper CT Conference on Dietary Supplements, Coagulation and Antithrombotic Therapies CY JAN 13-14, 2005 CL NIH, Bethesda, MD HO NIH ID ST-JOHNS-WORT; VITAMIN-K INTAKE; DIETARY-SUPPLEMENTS; NUTRITIONAL SUPPLEMENTS; HERBAL MEDICINES; PRODUCTS; THERAPIES; MORTALITY; REMEDIES; GINSENG C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Platelet Disorder Support Assoc, Rockville, MD USA. Natl Consumers League, Washington, DC USA. Amer Med Assoc, Chicago, IL 60610 USA. Amer Soc Hematol, Washington, DC USA. Amer Herbal Prod Assoc, Silver Spring, MD USA. Amer Soc Clin Nutr, Bethesda, MD USA. Amer Dietet Assoc, Chicago, IL USA. Amer Soc Hlth Syst Pharmacists, Bethesda, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Costello, R (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,3B01, Bethesda, MD 20892 USA. EM CostellB@od.nih.gov NR 42 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 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 117 IS 1-2 SI SI BP 211 EP 222 DI 10.1016/j.thromres.2005.07.004 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 987AM UT WOS:000233490800031 PM 16125754 ER PT J AU Hasan, AAK Marder, VJ AF Hasan, AAK Marder, VJ TI Conference summary and recommendations for research SO THROMBOSIS RESEARCH LA English DT Editorial Material C1 Univ Calif Los Angeles, Los Angeles Orthopaed Hosp, David Geffen Sch Med, Dept Med,Div Hematol Med Oncol, Los Angeles, CA 90007 USA. NHLBI, Thrombosis & Hemostasis Program, Div Blood Dis & Resources, Bethesda, MD 20892 USA. RP Marder, VJ (reprint author), Univ Calif Los Angeles, Los Angeles Orthopaed Hosp, David Geffen Sch Med, Dept Med,Div Hematol Med Oncol, 2400 S Flower St, Los Angeles, CA 90007 USA. EM vmarder@laoh.ucla.edu 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 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 117 IS 1-2 SI SI BP 229 EP 230 DI 10.1016/j.thromres.2005.09.003 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 987AM UT WOS:000233490800033 PM 16225912 ER PT J AU Wang, WL Merchlinsky, M Inman, J Golding, B AF Wang, WL Merchlinsky, M Inman, J Golding, B TI Identification of a novel immunodominant cytotoxic T lymphocyte epitope derived from human factor VIII in a murine model of hemophilia A SO THROMBOSIS RESEARCH LA English DT Article DE factor VIII; CTL epitope; hemophilia A; gene therapy; animal model ID COAGULATION-FACTOR-VIII; GENE-TRANSFER; IN-VIVO; IMMUNE-RESPONSES; FLOW-CYTOMETRY; CELL EPITOPE; EFFECTOR; VECTOR; MICE; RECOGNITION AB Gene therapy of hemophilia A could be complicated by the development of immune responses against the vector as well as the Factor VIII (FVIII) transgene. Previous efforts have been focused on identifying FVIII inhibitor antibody epitopes, whereas the cytotoxic T lymphocyte (CTL) epitopes have not been characterized. CTL would kill cells expressing such epitopes and thus limit the efficacy of gene therapy. To investigate CTL responses against human FVIII in a mouse model of hemophilia A, a computer algorithm program (BIMAS) was employed to predict CTL epitopes of human FVIII. The potential binding of these predicted peptides to MHC class I K-b was evaluated in a TAP-deficient cell line. When recombinant vaccinia virus expressing B domain-deleted human FVIII (vv-FVIII) was used to immunize E16 hemophilia A mice, a specific CTL response against FVIII152-159 was generated. In contrast, a CTL response to four other FVIII peptides was not detected. Therefore, FVIII152-159 represents a dominant CTL epitope. Identification of this epitope raises the possibility that CTL response to FVIII gene-transduced cells can be diminished by deliberatively mutating the dominant CTL epitope white retaining the biologic function of FVIII for hemophilia A gene therapy. Published by Elsevier Ltd. C1 US FDA, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Review, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. RP Wang, WL (reprint author), US FDA, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM wangw@cber.fda.gov NR 41 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 116 IS 4 BP 335 EP 344 DI 10.1016/j.thromres.2004.12.011 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 955DQ UT WOS:000231205900010 PM 16038719 ER PT J AU Horne, MK Merryman, PK Cullinane, AM AF Horne, MK Merryman, PK Cullinane, AM TI Plasminogen interaction with platelets: The importance of carboxyterminal lysines SO THROMBOSIS RESEARCH LA English DT Article DE plasminogen; platelets; carboxypeptidase; lysine ID BINDING SITES; ACTIVATION; FIBRIN; MECHANISM; THROMBIN; SURFACE; PLASMA; AFFINITY; KINETICS; TPA AB Introduction: Thrombin stimulation enhances plasminogen binding to platelets and promotes platelet-dependent plasmin generation. The objective of this study was to determine whether carboxyterminal lysines (C-lysines) are important for these processes, as they are in other cell types. Materials and methods: (125)l-plasminogen and varying concentrations of unlabeled plasminogen were added to washed platelets that were either resting or stimulated with thrombin, thrombin receptor activating peptide, or ADP. In some experiments the platelets were digested with carboxypeptidase B to remove C-lysines. Platelet-dependent plasmin generation was also studied by adding plasminogen and tissue plasminogen activator to platelet suspensions and monitoring the conversion of a plasmin specific chromogenic substrate. The cells were either resting or stimulated with thrombin, thrombin receptor activating peptide, or ADP The effect of the thrombin inhibitor lepirudin and the plasmin inhibitor aprotinin on plasminogen binding and the appearance of C-lysines was also investigated. Results: Thrombin, but not thrombin receptor activating peptide or ADP, stimulated high-affinity binding of plasminogen and greatly promoted platelet-dependent plasmin generation. Digestion with carboxypeptidase B eliminated thrombin-induced high-affinity binding and reduced thrombin-induced plasmin generation by increasing the Michaelis constant. Lepirudin, but not aprotinin, inhibited thrombin-stimulated plasminogen binding to platelets. Conclusion: C-terminal lysines are necessary for high-affinity binding of plasminogen to platelets and for platelet-supported plasmin generation. The origin of the C-lysines is not clear, but they may result from a direct effect of thrombin, rather than an intermediate enzyme such as plasmin. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIH, Hematol Serv, Dept Lab Med, WG Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Hematol Serv, Dept Lab Med, WG Magnuson Clin Ctr, Rm 2C306,Bldg 10, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov NR 25 TC 3 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 116 IS 6 BP 499 EP 507 DI 10.1016/j.thromes.2005.03.021 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 972HF UT WOS:000232444200007 PM 15894352 ER PT J AU Hollowell, JG LaFranchi, S Smallridge, RC Spong, CY Haddow, JE Boyle, CA AF Hollowell, JG LaFranchi, S Smallridge, RC Spong, CY Haddow, JE Boyle, CA TI 2004 where do we go from here? - Summary of working group discussions on thyroid function and gestational outcomes SO THYROID LA English DT Editorial Material AB A workshop entitled, "The Impact of Maternal Thyroid Diseases on the Developing Fetus: Implications for Diagnosis, Treatment, and Screening," was held in Atlanta, Georgia, January 12-13,2004. This paper reports points of agreement among the attendees based on the scientific rigor of material presented. At the end of the workshop, participants were divided into four smaller groups to discuss and determine areas of agreement on issues associated with thyroid insufficiency, identify research needs and gaps, and recommend research strategies and policy needs. Discussion included: problems for the mother and the pregnancy; neuropsychological/developmental performance in offspring of women with thyroid deficiency; issues of diagnosis and treatment for the pregnant women with overt and subclinical hypothyroidism; the issues involved with screening women who are pregnant or who are planning pregnancy; and the status of Iodine Nutrition in the United States. The group then identified research needs and gaps. The results of these discussions are outlined in the paper with recommended research strategies and public health action. C1 Univ Kansas, Med Ctr, Dept Pediat, Kansas City, KS 66049 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Fdn Blood Res, Scarborough, ME 04074 USA. Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. RP Hollowell, JG (reprint author), Univ Kansas, Med Ctr, Dept Pediat, 435 N 1500 Rd, Kansas City, KS 66049 USA. EM jgh3@mindspring.com NR 6 TC 14 Z9 23 U1 2 U2 2 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD JAN PY 2005 VL 15 IS 1 BP 72 EP 76 DI 10.1089/thy.2005.15.72 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 896FX UT WOS:000226921100012 PM 15687826 ER PT J AU Tran, SD Wang, J Bandyopadhyay, BC Redman, RS Dutra, A Pak, E Swaim, WD Gerstenhaber, JA Bryant, JM Zheng, C Goldsmith, CM Kok, MR Wellner, RB Baum, BJ AF Tran, SD Wang, J Bandyopadhyay, BC Redman, RS Dutra, A Pak, E Swaim, WD Gerstenhaber, JA Bryant, JM Zheng, C Goldsmith, CM Kok, MR Wellner, RB Baum, BJ TI Primary culture of polarized human salivary epithelial cells for use in developing an artificial salivary gland SO TISSUE ENGINEERING LA English DT Article ID ACINAR-CELLS; PAROTID-GLAND; GENE-THERAPY; DENTISTRY; IMPACT; LINE; DIFFERENTIATION; LOCALIZATION; MATRIX; GROWTH AB Therapeutic irradiation for head and neck cancer, and the autoimmune disease Sjogren's syndrome, lead to loss of salivary parenchyma. They are the two main causes of irreversible salivary gland hypofunction. Such patients cannot produce adequate levels of saliva, leading to considerable morbidity. We are working to develop an artificial salivary gland for such patients. A major problem in this endeavor has been the difficulty in obtaining a suitable autologous cellular component. This article describes a method of culturing and expanding primary salivary cells obtained from human submandibular glands ( huSMGs) that is serum free and yields cells that are epithelial in nature. These include morphological ( light and transmission electron microscopy [TEM]), protein expression (immunologically positive for ZO-1, claudin-1, and E-cadherin), and functional evidence. Under confocal microscopy, huSMG cells show polarization and appropriately localize tight junction proteins. TEM micrographs show an absence of dense core granules, but confirm the presence of tight and intermediate junctions and desmosomes between the cells. Functional assays showed that huSMG cells have high transepithelial electrical resistance and low rates of paracellular fluid movement. Additionally, huSMG cells show a normal karyotype without any morphological or numerical abnormalities, and most closely resemble striated and excretory duct cells in appearance. We conclude that this culture method for obtaining autologous human salivary cells should be useful in developing an artificial salivary gland. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Oral Pathol Res Lab, Washington, DC 20422 USA. NHGRI, NIH, Bethesda, MD 20892 USA. McGill Univ, Fac Dent, Montreal, PQ, Canada. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, Bldg 10,Rm 1N113,MSC-1190, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov RI Liu, Yifei/L-7828-2014 OI Liu, Yifei/0000-0002-1087-9827 NR 28 TC 46 Z9 51 U1 0 U2 9 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JAN PY 2005 VL 11 IS 1-2 BP 172 EP 181 DI 10.1089/ten.2005.11.172 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 904QU UT WOS:000227513600016 PM 15738672 ER PT J AU Malarkey, DE Johnson, K Ryan, L Boorman, G Maronpot, RR AF Malarkey, DE Johnson, K Ryan, L Boorman, G Maronpot, RR TI New insights into functional aspects of liver morphology SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver; rodent; architecture; gradients; phenotypic anchoring; genomics; pathology; review; anatomy; magnetic resonance imaging; histology ID RAT-LIVER; COPPER DISTRIBUTION; GENE-EXPRESSION; NEWBORN LIVER; PORTAL BLOOD; DISEASE; FLOW; UNIT; REEVALUATION; SCINTIGRAPHY AB The liver is structurally and functionally complex and has been considered second only to brain in its complexity. Many mysteries still exist in this heterogeneous tissue whose functional unit of the lobule has continued to stump morphologists for over 300 years. The primary lobule, proposed by Matsumoto in 1979, has been gaining acceptance as the functional unit of the liver over other conceptual views because it's based on vessel architecture and includes the classic lobule as a secondary feature. Although hepatocytes comprise almost 80% of the liver, there are at least another dozen cell types. many of which provide "cross-talk" and play important functional roles in the normal and diseased liver. The distribution and functional roles of all cells in the liver must be carefully considered in both the analysis and interpretation of research data, particularly data in the area of genomics and "phenotypic anchoring" of gene expression results. Discoveries regarding the functional heterogeneity of the various liver cell types, including hepatocytes, hepatic stellate cells, sinusoidal endothelia, and Kupffer cells, are providing new insights into our understanding of the development, prevention and treatment of liver disease. For example, functional differences along zonal patterns (centrilobular or periportal) have been demonstrated for sinusoidal endothelium, Kupffer Cells, and hepatocytes and can explain the gradients and manifestations of disease observed within lobules. Intralobular gradients of bile uptake, glycogen depletion, glutamine synthetase, and carboxylesterase by hepatocytes; widened fenestrations in centrilobular sinusoidal lining cells; and differences in the components of centrilobular extracellular matrix or function of Kupffer cells have been demonstrated. Awareness of the complexities and heterogeneity of the liver will add to a greater understanding of liver function and disease processes that lead to toxicity, cancer, and other diseases. C1 NIEHS, Res Triangle Pk, NC 27709 USA. MRPath, Durham, NC 27707 USA. RP Malarkey, DE (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM rnalarkey@niehs.nih.gov NR 63 TC 67 Z9 69 U1 3 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 27 EP 34 DI 10.1080/01926230590881826 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300005 PM 15805053 ER PT J AU Boorman, GA Irwin, RD Vallant, MK Gerken, DK Lobenhofer, EK Hejtmancik, MR Hurban, P Brys, AM Travlos, GS Parker, JS Portier, CJ AF Boorman, GA Irwin, RD Vallant, MK Gerken, DK Lobenhofer, EK Hejtmancik, MR Hurban, P Brys, AM Travlos, GS Parker, JS Portier, CJ TI Variation in the hepatic gene expression in individual male Fischer rats SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver; rat; mRNA; differential gene expression; microarray; variation; transcriptome; controls ID STRESS-LIKE RESPONSES; DNA MICROARRAY; COMMON PROCEDURES; GLUTATHIONE; LIVER; MOUSE; HEPATOTOXICANTS; METHAPYRILENE; CONSEQUENCES; PROTEINS AB A new tool beginning to have wider application in toxicology studies is transcript profiling using microarrays. Microarrays provide an opportunity to directly compare transcript populations in the tissues of chemical-exposed and unexposed animals. While several studies have addressed variation between microarray platforms and between different laboratories, much less effort has been directed toward individual annual differences especially among control animals where RNA samples are usually pooled. Estimation of the variation in gene expression in tissues from untreated animals is essential for the recognition and interpretation of subtle changes associated with chemical exposure. In this study hepatic gene expression as well as standard toxicological parameters were evaluated in 24 rats receiving vehicle only in 2 independent experiments. Unsupervised clustering demonstrated some individual variation but supervised clustering, suggested that differentially expressed genes were generally random. The level of hepatic gene expression under carefully controlled study conditions is less than 1.5-fold for most genes. The impact of individual annual variability on microarray data call be minimized through experimental design. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Battelle Sci & Technol Int, Columbus, OH 43201 USA. Paradigm Genet Inc, Res Triangle Pk, NC 27709 USA. Constella Grp Inc, Res Triangle Pk, NC 27709 USA. RP Boorman, GA (reprint author), NIEHS, Environm Toxicol Program, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM boornian@niehs.nih.gov RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 47 TC 7 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 102 EP 110 DI 10.1080/01926230590522211 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300013 PM 15805061 ER PT J AU Irwin, RD Parker, JS Lobenhofer, EK Burka, LT Blackshear, PE Vallant, MK Lebetkin, EH Gerken, DF Boorman, GA AF Irwin, RD Parker, JS Lobenhofer, EK Burka, LT Blackshear, PE Vallant, MK Lebetkin, EH Gerken, DF Boorman, GA TI Transcriptional profiling of the left and median liver lobes of male F344/N rats following exposure to acetaminophen SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver; rat; mRNA; differential gene expression; microarray; variation; transcriptome; lobe differences; left lobe; median lobe ID COPPER DISTRIBUTION; NEWBORN LIVER; DISEASE; BLOOD; IRON AB The liver is a common organ for transcriptional profiling because of its role in xenobiotic metabolism and because hepatotoxicity is a common response to chemical exposure. To explore the impact that sampling different lobes may have on transcriptional profiling experiments we have examined and compared gene expression profiles of the left and median lobes of fivers front male F344 rats exposed to toxic and nontoxic doses of acetaminophen. Transcript profiling using microarrays revealed clear differences in the response of the left and median liver lobes of F344 rats to acetaminophen exposure both at low doses as well as doses that caused hepatotoxicity. Differences were found in the total number of differentially expressed genes in the left and median lobes, the number and identity of genes that were differentially expressed uniquely only in the left or median lobe, and in the patterns of gene expression. While it is not possible to generalize these results to compounds other than acetaminophen or other strains of rat, these results highlight the potential impact of sampling differences on the interpretation of gene expression profiles in the liver. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Constella Grp Inc, Res Triangle Pk, NC 27709 USA. Paradigm Genet Inc, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. Battelle Sci & Technol Int, Columbus, OH 43201 USA. RP Irwin, RD (reprint author), NIEHS, Environm Toxicol Program, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM irwin@niehs.nih.gov NR 20 TC 16 Z9 18 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 111 EP 117 DI 10.1080/01926230590522257 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300014 PM 15805062 ER PT J AU Malarkey, DE Parker, JS Turman, CA Scott, AM Paules, RS Collins, J Maronpot, RR AF Malarkey, DE Parker, JS Turman, CA Scott, AM Paules, RS Collins, J Maronpot, RR TI Microarray data analysis of mouse neoplasia SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver; lung; mammary gland; rodent; microarray gene expression analysis; genomics; cancer; review; gene expression profiling; neoplasia ID GLYCOGEN-SYNTHASE KINASE-3-BETA; DIFFERENTIALLY EXPRESSED GENES; HUMAN HEPATOCELLULAR-CARCINOMA; SPONTANEOUS REGRESSION; LIVER-TUMORS; BREAST-CANCER; GROWTH-FACTOR; PEROXISOME PROLIFERATOR; LUNG ADENOCARCINOMAS; RAS PROTOONCOGENE AB Microarray gene expression analysis offers great promise to help us understand the molecular events of experimental carcinogenesis, but have such promises been fulfilled? Studies of gene expression profiles of rodent are being published and demonstrate that yes, indeed, gene array data is furthering our understanding of tumor biology. Recent studies have identified differentially expressed genes in rodent mammary, colon, lung, and liver tumors. Although relatively few genes on the rodent arrays have been fully characterized, information has been generated to better identify signatures of histologic type and grade, understand invasion and metastasis, identify candidate biomarkers of early development, identify gene networks in carcinogenesis, understand responses to therapy, and decifer overlap with molecular events in human cancers. Data from mouse lung, mammary gland, and liver tumor studies are reviewed as examples of how to approach and interpret gene array data. Methods of gene array data analysis were also applied for discovery of genes involved in the regression of mouse fiver tumors induced by chlordane, a nongenotoxic murine hepatocarcinogen. Promises are beginning to be fulfilled and it is clear that pathologists and toxicologists, in collaboration with molecular biologists, bioinformatists, and other scientists are making great strides in the design, analysis, and interpretation of microarray data for cancer studies. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogen, Res Triangle Pk, NC 27709 USA. Constella Grp, Durham, NC 27707 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. RP Malarkey, DE (reprint author), NIEHS, Lab Expt Pathol, Maildrop B3-06,111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM malarkey@niehs.nih.gov NR 75 TC 5 Z9 5 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 127 EP 135 DI 10.1080/01926230590888315 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300016 PM 15805064 ER PT J AU Morgan, KT Jayyosi, Z Hower, MA Pino, MV Connolly, TM Kotlenga, K Lin, JY Wang, M Schmidts, HL Bonnefoi, MS Elston, TC Boorman, GA AF Morgan, KT Jayyosi, Z Hower, MA Pino, MV Connolly, TM Kotlenga, K Lin, JY Wang, M Schmidts, HL Bonnefoi, MS Elston, TC Boorman, GA TI The hepatic transcriptome as a window on whole-body physiology and pathophysiology SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver; rat; fasting; circadian; gene expressions; microarray; toxicogenomics; toxicology; rodent; pathology ID CIRCADIAN GENE-EXPRESSION; MOUSE-LIVER; DNA MICROARRAY; PROTEIN; CLOCK; TOXICOGENOMICS; IDENTIFICATION; CHOLESTEROL; CELLS; MICE AB Transcriptomics can be a valuable aid to pathologists. The information derived from microarray Studies may soon include the entire transcriptomes of most cell types, tissues and organs for the major species used for toxicology and human disease risk assessment. Gene expression changes observed ill Such Studies relate to every aspect of normal physiology and pathophysiology. When interpreting such data, one is forced to look "far from the lamp post," and in so doing, face one's ignorance of many areas of biology. The central role of the liver in toxicology, as well as in many aspects of whole-body physiology, makes the hepatic transcriptome all excellent place to start your studies. This article provides data that reveals the effects of fasting and circadian rhythm on the rat hepatic transcriptome, both of which need to be kept in mind when interpreting large-scale gene expression in the liver. Once you become comfortable with evaluating mRNA expression profiles and learn to correlate these data with your clinical and morphological observations, you may wonder why you did not start your studies of transcriptomics sooner. Additional study data call be viewed at the journal website at (www.toxpath.org). Two data files are provided in Excel format, which contain the control annual data from each of the studies referred to in the text, including normalized signal intensity data for each animal (n = 5) in the 6-hour, 24-hour, and 5-day time points. These files are briefly described in the associated 'Readme' file, and the complete list of GenBank numbers and Affymetrix IDs are provided in a separate txt file. These files are available at http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233. Click on the issue link for 33(1), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have all individual subscription or a member subscription accessed through (www.toxpath.org). C1 Aventis Inc, Bridgewater, NJ 08876 USA. Aventis Inc, Cambridge, MA 02139 USA. Aventis Inc, Frankfurt, Germany. Univ N Carolina, Dept Math, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Morgan, KT (reprint author), Aventis Inc, US Highway 202-206 N, Bridgewater, NJ 08876 USA. EM Kevin.Morgan@aventis.com NR 43 TC 10 Z9 11 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 136 EP 145 DI 10.1080/01926230590522149 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300017 PM 15805065 ER PT J AU Hailey, JR Walker, NJ Sells, DM Brix, AE Jokinen, MP Nyska, A AF Hailey, JR Walker, NJ Sells, DM Brix, AE Jokinen, MP Nyska, A TI Classification of proliferative hepatocellular lesions in Harlan Sprague-Dawley rats chronically exposed to dioxin-like compounds SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver; hepatocyte; nodular hyperplasia; proliferative; hyperplasia; regenerative hyperplasia; adenoma ID ADENOMATOUS HYPERPLASIA; CELL-PROLIFERATION; LIVER; CIRRHOSIS; PROMOTION; APOPTOSIS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; HEPATOCARCINOGENESIS; CARCINOGENESIS; TOXICOLOGY AB Over the years, the most appropriate classification scheme for nodular proliferative lesions of the hepatocyte has been heavily debated. In the most recent guidelines there appears to be a consensus for classifying these lesions as hepatocellular adenoma, hepatocellular carcinoma, or regenerative hyperplasia. Also, large foci of cellular alteration may appear somewhat nodular. Some nodular hepatocellular lesions from a group of 7 studies of dioxin and dioxin-like compounds conducted by the National Toxicology Program did not readily fit into these categories. Some of these lesions had morphologic features consistent with hyperplasia. However, there was not sufficient morphological or biological evidence to conclude that the entire response was regenerative. In other instances, these lesions had sonic features resembling adenoma, but contained a prominent component of biliary epithelium and/or oval cells. This component does not appear to be well described in the literature, and while its presence suggested a nodule to be nonneoplastic, this is inconclusive. This paper describes the morphology of these lesions, as well as the diagnostic approach taken in this series of studies. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Battelle Columbus Operat, Columbus, OH 43201 USA. Expt Pathol Labs, Res Triangle Pk, NC 27709 USA. Pathol Associates Inc, Res Triangle Pk, NC 27713 USA. RP Hailey, JR (reprint author), S Campus,MD-B3-08, Res Triangle Pk, NC 27709 USA. EM Hailey@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 35 TC 29 Z9 29 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 165 EP 174 DI 10.1080/01926230590888324 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300020 PM 15805068 ER PT J AU Kim, Y Sills, RC Houle, CD AF Kim, Y Sills, RC Houle, CD TI Overview of the molecular biology of hepatocellular neoplasms and hepatoblastomas of the mouse liver SO TOXICOLOGIC PATHOLOGY LA English DT Article DE mouse; hepatocellular carcinoma; hepatocellular adenoma; hepatoblastoma; liver; hepatocarcinogenesis ID POLYMERASE CHAIN-REACTION; BETA-CATENIN MUTATIONS; GROWTH-FACTOR-ALPHA; B6C3F1 MICE; GENETIC ALTERATIONS; P53 GENE; HUMAN HEPATOCARCINOGENESIS; SOMATIC MUTATIONS; RAS MUTATIONS; FACTOR-II AB The molecular pathogenesis of chemically induced hepatocellular neoplasms and hepatoblastomas in the B6C3F1 mouse is unclear but may involve alterations in the beta-catenin/Wnt signaling pathway as was recently described for human liver neoplasms. The objectives of this research were to characterize the Mutation frequency and spectrum of beta-catenin mutations and the intracellular localization of beta-catenin protein accumulation in chemically induced hepatoblastomas and hepatocellular neoplasms. In the majority of the hepatoblastomas examined by immunohistochemical methods, both nuclear and cytoplasmic localization of beta-catenin protein were detected, whereas in hepatocellular adenomas and carcinomas and normal liver only membrane staining was observed. Genomic DNA was isolated from paraffin sections of each liver tumor. beta-catenin exon 2 (corresponds to exon 3 in humans) genetic alterations were identified in the majority of hepatoblastomas from exposed mice. Deletion mutations were identified more frequently than point mutations in hepatoblastomas. Hepatocellular adenomas and carcinomas from treated mice had mutations in exon 2 of the beta-catenin gene which ranged from 32-43%, while 10% beta-catenin mutations were detected in spontaneous neoplasms. By immunohistochemical methods cyclin D1 was observed in Most nuclei of hepatoblastomas and strong expression of cyclin D1 was confirmed by Western analysis regardless of treatment. The cumulative data suggests that beta-catenin mutations with upregulation of the beta-catenin protein and Wnt signaling most likely increased cyclin D1 expression. Cyclin D1 may provide an advantage during tumor progression of hepatocellular neoplasms and hepatoblastomas. The review will also focus on other genes which are important in mouse and human liver tumors. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. RP Sills, RC (reprint author), NIEHS, Lab Expt Pathol, MD B3-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM sills@niehs.nih.gov NR 73 TC 21 Z9 22 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 175 EP 180 DI 10.1080/01926230590522130 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300021 PM 15805069 ER PT J AU Calvisi, DF Thorgeirsson, SS AF Calvisi, DF Thorgeirsson, SS TI Molecular mechanisms of hepatocarcinogenesis in transgenic mouse models of liver cancer SO TOXICOLOGIC PATHOLOGY LA English DT Article DE c-myc; TGF-alpha; transgenic mice; HCC; genomic instability; beta-catenin ID GROWTH-FACTOR-ALPHA; COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN HEPATOCELLULAR CARCINOMAS; BETA-CATENIN MUTATIONS; EXPRESSING C-MYC; NF-KAPPA-B; ACCELERATED HEPATOCARCINOGENESIS; FACTOR (TGF)-ALPHA; MICE; DISRUPTION AB Overexpression of c-myc and transforming growth factor-alpha (TGF-alpha) has been frequently observed in human hepatocellular carcinoma (HCC). suggesting a pivotal role played by these protooncogenes in liver oncogenesis. In order to investigate the molecular events underlying human hepatic malignant transformation, we have generated c-myc and c-myc/TGF-alpha transgenic mice that are prone to liver cancer. These transgenic mice develop HCCs with different incidence, kinetics and histopathological features. Indeed, co-expression of c-myc and TGF-alpha transgenes results in a dramatic synergistic effect on liver turner development when compared with respective single transgenic lines, including a shorter latency period and a more aggressive phenotype. The more malignant histopathological features characteristic of c-myc/TGF-alpha HCCs are the result of the increased proliferation and reduced apoptosis in this model of liver cancer when compared with single parental lines. Accordingly, c-myc and c-myc/TGF-alpha transgenic mice display a different molecular pathogenesis of HCC. Importantly, the genetic and molecular mechanisms that are involved in c-myc and c-myc/TGF-alpha liver cancer development are major oncogenic events in human hepatocarcinogenesis, indicating that these mouse models represent a useful tool to dissect and elucidate the molecular basis of human HCC. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 27 TC 54 Z9 56 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 181 EP 184 DI 10.1080/01926230590522095 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300022 PM 15805070 ER PT J AU Lewis, DN Nyska, A Johnson, K Malarkey, DE Ward, S Streicker, M Shabat, S Peddada, S Nyska, M AF Lewis, DN Nyska, A Johnson, K Malarkey, DE Ward, S Streicker, M Shabat, S Peddada, S Nyska, M TI 2-butoxyethanol female-rat model of hemolysis and disseminated thrombosis: X-ray characterization of osteonecrosis and growth-plate suppression SO TOXICOLOGIC PATHOLOGY LA English DT Article DE 2-butoxyethanol; hemolysis; thrombosis; osteonecrosis; growth plate; ischemia ID SICKLE-CELL-ANEMIA; EXTREMITY REPLANT MODEL; AVASCULAR NECROSIS; EPIPHYSEAL GROWTH; F344 RATS; INHALATION EXPOSURE; REPERFUSION INJURY; BONE; ISCHEMIA; DISEASE AB We recently proposed a chemically induced rat model for human hemolytic disorders associated with thrombosis. The objective of the present investigation was to apply a noninvasive, high-magnification X-ray analysis, the Faxitron radiography system, to characterize the protracted bone damage associated with this 2-butoxyethanol model and to validate it by histopathology. Groups of female Fischer 344 rats were given 0, 250, or 300 mg of 2-butoxyethanol/kg body weight daily for 4 consecutive days. Groups were then sacrificed 2 hours or 26 days after the final treatment. The treated animals displayed a darkened purple-red discoloration on the distal tail. Histopathological evaluation, including phosphotungstic acid-hematoxylin staining of animals sacrificed 2 hours after the final treatment, revealed disseminated thrombosis and infarction in multiple organs, including bones. The Faxitron MX-20 specimen radiography system was used to image selected bones of rats sacrificed 26 days posttreatment. Premature thinning of the growth plate occurred in the calcaneus, lumbar and coccygeal vertebrae, femur, and ilium of the treated animals. Areas of decreased radiographic densities were seen in the diaphysis of the femur of all treated animals. The bones were then examined histologically and showed a range of changes, including loss or damage to growth plates and necrosis of cortical bone. No thrombi were seen in the animals sacrificed at 30 days, but bone and growth plate changes consistent with prior ischemia were noted. The Faxitron proved to be an excellent noninvasive tool that can be used in future studies with this animal model to examine treatment modalities for the chronic effects of human thrombotic disorders. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Integrated Syst Lab, Res Triangle Pk, NC USA. Sapir Med Ctr, Dept Orthopaed Surg, Kefar Sava, Israel. RP Nyska, M (reprint author), NIEHS, Lab Expt Pathol, MD B3-06,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 NR 62 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 2 BP 272 EP 282 DI 10.1080/019262390908362 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 903PN UT WOS:000227438200009 PM 15902971 ER PT J AU Lambertini, L Surin, K Ton, TVT Clayton, N Dunnick, JK Kim, Y Hong, HHL Devereux, TR Sills, RC AF Lambertini, L Surin, K Ton, TVT Clayton, N Dunnick, JK Kim, Y Hong, HHL Devereux, TR Sills, RC TI Analysis of p53 tumor suppressor gene, H-ras protooncogene and proliferating cell nuclear antigen (PCNA) in squamous cell carcinomas of HRA/Skh mice following exposure to 8-methoxypsoralen (8-MOP) and UVA radiation (PUVA therapy) SO TOXICOLOGIC PATHOLOGY LA English DT Article DE PUVA; p53; PCNA mutation; skin squamous cell carcinoma (SCC); thymine ID NONMELANOMA SKIN-CANCER; DNA-BINDING DOMAIN; MOUSE SKIN; PSORIASIS PATIENTS; MOLECULAR EPIDEMIOLOGY; METHOXSALEN PSORALEN; MUTATIONAL SPECTRUM; TREATED PATIENTS; EPIDERMAL-CELLS; HIGH-FREQUENCY AB Treatment with 8-methoxypsoralen (8-MOP) and ultraviolet radiation (primarily UVA), called PUVA therapy, has been used to treat different chronic skin diseases but led to a significant increased risk for skin cancer. The National Toxicology Program (NTP) performed a study in mice treated with PUVA that showed a significant increase in squamous cell carcinomas of the skin. In the present study, we evaluated the protein expression of p53 and PCNA and DNA mutations of p53 and H-ras genes in both hyperplastic and neoplastic squamous cell lesions from the NTP study. By immunohistochemical staining, protein expression of both p53 and PCNA was detected in 3/16 (19%) of hyperplastic lesions and 14/17 (82%) of SCCs in groups treated with both 8-MOP and UVA. The mutation frequency of p53 in SCCs from mice administered 8-MOP plus UVA was 15/17 (88%) with a predominant distribution of mutations in exon 6 (14/15 - 93%). No H-ras mutations were detected in the hyperplastic lesions/tumors. The mutagenic effect of PUVA on the p53 tumor suppressor gene may lead to a conformational modification and inactivation of the p53 protein, which are considered critical steps in PUVA-induced skin carcinogenesis. The p53 mutational frequency and patterns from our study were different from those reported in human PUVA-type tumors. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Sills, RC (reprint author), NIEHS, Lab Expt Pathol, NIH, 111 TW Alexander Dr,POB 12233,Mail Drop B3-08, Res Triangle Pk, NC 27709 USA. EM sills@niehs.nih.gov NR 59 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 2 BP 292 EP 299 DI 10.1080/019262390908380 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 903PN UT WOS:000227438200011 PM 15902973 ER PT J AU Kim, Y Hong, HHL Lachat, Y Clayton, NP Devereux, TR Melnick, RL Hegi, ME Sills, RC AF Kim, Y Hong, HHL Lachat, Y Clayton, NP Devereux, TR Melnick, RL Hegi, ME Sills, RC TI Genetic alterations in brain tumors following 1,3-butadiene exposure in B6C3F1 mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE B6C3F1 mouse; 1,3-butadiene brain tumors; p53; Ink4a/Arf; mutation; loss of heterozygosity; neurocarcinogenesis ID MAMMARY ADENOCARCINOMAS; EGF RECEPTOR; RAS GENES; P53; MUTATIONS; CARCINOGENICITY; NEUROBLASTOMA; LUNG; CELL; OVEREXPRESSION AB The nervous system of the B6C3F1 mouse has rarely been a target for chemical carcinogenesis in the National Toxicology program (NTP) bioassays. However. 6 malignant gliomas and 2 neuroblastomas were observed in B6C3F1 mice exposed to 625 ppm 1,3-butadiene (NTP technical reports 288 and 434). These mouse brain tumors were evaluated with regard to the profile of genetic alterations [fiat are observed in human brain tumors. Alterations in the p53 tumor suppressor gene were common. Missense Mutations were observed in 3/6 malignant gliomas and 2/2 neuroblastomas and were associated with loss of heterozygosity. Most of the Mutations occurred tit exons 5-8 of the p53 gene and were G --> A transitions, and did not involve CpG sites. Lose. of heterozygosity at the Ink4a/Arf gene locus W is observed in 515 malignant gliomas and 1/1 neuroblastoma. while the PTEN (phosphatase and tensin homologue) gene locus was unaffected by deletions. One of 2 neuroblastomas had a mutation in codon 61 of H-ras, while H-ras mutations were not observed in the malignant gliomas examined. Only I brain tumor has been reported from control mice of over 500 NTP studies. This malignant glioma showed no evidence of alterations tit the p53 gene or K- and H-ras mutations. It is likely that the specific genetic alterations observed were induced or selected for by 1,3-butadiene treatment that contributed to the development of mouse brain tumors. The observed findings are similar tit part to the genetic alterations reported in human brain tumors. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Univ Lausanne Hosp, Dept Neurosurg, Lab Tumor Biol & Genet, Lausanne, Switzerland. RP Sills, RC (reprint author), NIEHS, Lab Expt Pathol, MD B3-08,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM sills@niehs.nih.gov RI Hegi, Monika/O-4796-2015 OI Hegi, Monika/0000-0003-0855-6495 NR 37 TC 6 Z9 7 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 3 BP 307 EP 312 DI 10.1080/01926230590922848 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 922KE UT WOS:000228836000001 PM 15814359 ER PT J AU Tani, Y Foster, PN Sills, RC Chan, PC Peddada, SD Nyska, A AF Tani, Y Foster, PN Sills, RC Chan, PC Peddada, SD Nyska, A TI Epididymal sperm granuloma induced by chronic administration of 2-methylimidazole in B6C3F(1) mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE 2-methylimidazole; epididymis; sperm granuloma; testis; germinal epithelium; mice ID INHALED METHYL-CHLORIDE; F344 RATS; TOXICITY; CARCINOGENICITY; BIOSYNTHESIS; KETOCONAZOLE; INHIBITION; SYSTEM AB Two-year mouse and rat bioassay Studies of 2-methylimidazole (2-MI) conducted by the National Toxicology program revealed that epididymal sperm granuloma(SG)s occurred only in male B6C3F(1) mice in a dose-related manner. The present Study characterized 2-MI-induced SGs in these epididymides. Groups of 50 male B6C3F(1) mice were fed diets containing 0.625, 1250, or 2500 ppm 2-MI lot 105 weeks the closes were equivalent to average daily, doses of approximately 13. 40, or 130 mg/kg. Testes and epididymides were histopathologically reexamined. 2-Methylimidazole increased the incidence of epididymal SGs (0%, 0%, 6%. 12%, respectively). Histologically, most of the SGs exhibited rupture of epididymal ducts with focal aggregations of macrophages in interstitia. Lesions occurred in the proximal caput of the epididymis and/or efferent ducts. not ill the corpus and cauda. In the testis. incidences of germinal epithelial atrophy (GEA) increased dose-relatedly (2%, 8% 16%, 28%. respectively). All mice with epididymal SG developed testicular GEA. The grading scores of testicular GEA tended to be more severe in mice with SGs than those without. No epididymal SG or testicular GEA was observed in 6-month-interim-sacrificed mice. The results imply that 2-year treatment of B6C3F(1) mice with 2-MI can induce epididymal SGs, primarily followed by more severe testicular GEA. The potential mechanism of SG induction by 2-MI is discussed. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Operat Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, NIH, POB 12233,Mail Drop B3-06, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 NR 35 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 3 BP 313 EP 319 DI 10.1080/01926230590922866 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 922KE UT WOS:000228836000002 PM 15814360 ER PT J AU Nyska, A Yoshizawa, K Jokinen, MP Brix, AE Sells, DM Wyde, ME Orzech, DP Kissling, GE Walker, NJ AF Nyska, A Yoshizawa, K Jokinen, MP Brix, AE Sells, DM Wyde, ME Orzech, DP Kissling, GE Walker, NJ TI Olfactory epithelial metaplasia and hyperplasia in female Harlan Sprague-Dawley rats following chronic treatment with polychlorinated biphenyls SO TOXICOLOGIC PATHOLOGY LA English DT Article DE dioxin; furans; polychlorinated biphenyls; nasal cavity; olfactory epithelium; metaplasia; hyperplasia; toxic equivalency factor ID SUBCHRONIC EXPOSURE; BRAIN-TISSUES; NASAL-MUCOSA; B6C3F1 MICE; F344 RATS; TCDD; CARCINOGENICITY; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; TOXICOLOGY; TOXICITY AB The National Toxicology Program recently completed a series of studies to evaluate the relative potency for toxicity and carcinogenicity of several polyhalogenated aromatic hydrocarbons including dioxin-like compounds (DLCs) and polychlorinated biphenyls. Female Sprague-Dawley rats were administered by gavage for up to 2 years with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 3,3',4,4',5-pentachlorobiphenyl (PCB126) 2.3,4,7,8-pentachlorodibenzofuran (PeCDF)- 2,2',4,4'.5,5'-hexachlorobiphenyl (PCB153); a tertiary Mixture of TCDD, PCB126, and PeCDF; a binary mixture of PCB126 and 153: or a binary mixture of PCB126 and 2,3',4,4',5-pentachlorobiphenyl (PCB118); control animals received corn oil-acetone vehicle (99: 1) alone. Nasal epithelial changes were observed only in animals exposed for 2 years to the higher doses of the binary mixtures of PCB126 + PCB153 (1000 ng/kg and 1000 ug/kg) and PCB126 + PCB118 (216 and 360 ng TCDD equivalents/kg). In both studies, the changes were of the same nonneoplastic nature. localized to nasal sections II and III located. respectively, at the level of the incisive papilla anterior to the first palatial ridge (section II) and through the middle of the second molar teeth (section III). The changes consisted of hyperplasia of the respiratory epithelium (level II) and metaplasia of olfactory epithelium to respiratory epithelium with further hyperplasia of the metaplastic respiratory epithelium (levels II and III). Variable amounts of acute inflammatory exudate appeared within the lumen of the nasal cavity, overlying the affected epithelium. Occasionally, the inflammation eroded through the skull and into the adjacent olfactory bulbs. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. Pathol Associates Inc, Durham, NC USA. Expt Pathol Labs, Res Triangle Pk, NC USA. Battelle Columbus Labs, Columbus, OH USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, MD B3-06,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 33 TC 12 Z9 13 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 3 BP 371 EP 377 DI 10.1080/01926230590930209 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 922KE UT WOS:000228836000010 PM 15805076 ER PT J AU Suttie, AW Dinse, GE Nyska, A Moser, GJ Goldsworthy, TL Maronpot, RR AF Suttie, AW Dinse, GE Nyska, A Moser, GJ Goldsworthy, TL Maronpot, RR TI An investigation of the effects of late-onset dietary restriction on prostate cancer development in the TRAMP mouse SO TOXICOLOGIC PATHOLOGY LA English DT Article DE diet-restriction; prostate cancer; TRAMP; neuroendocrine ID LARGE T-ANTIGEN; PROBASIN GENE PROMOTER; TRANSGENIC MOUSE; MICE; MODEL; CARCINOGENESIS; ADENOCARCINOMA; PROGRESSION; CARCINOMA; CELLS AB In our previous work we showed that dietary restriction initiated at puberty reduced prostate cancer development in the TRAMP mouse model. The current study was conducted to ascertain whether a dietary restriction regime would similarly reduce lesion development if imposed once turner development was well established. Male TRAMP mice were maintained on an ad libitum diet until 20 weeks of age when proliferative prostate lesions are clearly evident. Mice were then subjected to a 20% restriction in dietary calories compared to matched controls. which were continued on ad libitum feeding. Mice were sacrificed at 20. 24, 32. and 39 weeks of age and proliferative epithelia] lesions of the prostate were assessed using an established grading scheme. In this study, although dietary restriction reduced mean sex pluck weight (prostate and seminal vesicles), and mean grade of epithelial proliferative lesions in the dorsal and lateral lobes of the prostate, the effect was not as pronounced as was the case with dietary restriction from puberty. There was no relationship between serum insulin like growth factor (IGF-I) and prostate lesion grade. Additionally, we also report the relationship between lobe specific lesion development and SV40 immunostaining and, the occurance of neuroendocrine tumors (NETs) in the ventral prostate and urethra of the TRAMP mouse. NETs stained with high specificity and sensitivity for the neuroendocrine markers, synaptophysin and neuron-specific enolase (NSE), less for serotonin, but not for chromogranin A. NETs did not stain for cyclo-oxygenase-2 (COX-2) nor androgen receptor (AR). SV40 positive tubulo-acinar tumors seen occasionally in the kidney, did not stain for synaptophysin nor NSE. C1 Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Suttie, AW (reprint author), Integrated Lab Syst Inc, POB 13501, Res Triangle Pk, NC 27709 USA. EM asuttie@ils-inc.com FU NIEHS NIH HHS [N01-ES-95434, N01-ES-95446] NR 38 TC 25 Z9 25 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 3 BP 386 EP 397 DI 10.1080/01926230590930272 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 922KE UT WOS:000228836000012 PM 15805078 ER PT J AU Haley, P Perry, R Ennulat, D Frame, S Johnson, C Lapointe, JM Nyska, A Snyder, PW Walker, D Walter, G AF Haley, P Perry, R Ennulat, D Frame, S Johnson, C Lapointe, JM Nyska, A Snyder, PW Walker, D Walter, G CA STP Immunotoxicology Working Grp TI STP position paper: Best practice guideline for the routine pathology evaluation of the immune system SO TOXICOLOGIC PATHOLOGY LA English DT Article ID IMMUNOTOXICITY; RATS C1 AstraZeneca, Wilmington, DE 19850 USA. Wyeth Res, Chazy, NY 12921 USA. GlaxoSmithKline, King Of Prussia, PA 19406 USA. DuPont Co Inc, Haskell Lab Environm Sci Toxicol & Ind Med, Newark, DE 19714 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Pfizer Inc, Global Res & Dev, Groton, CT 06340 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Purdue Univ, Sch Vet Med, W Lafayette, IN 47907 USA. RP Haley, P (reprint author), Care of Klaunig J, Toxicol Pathol Editorial Off, 199 Grassmur Turn, Pine Hill, NJ 08021 USA. NR 9 TC 73 Z9 78 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 3 BP 404 EP 407 DI 10.1080/01926230590934304 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 922KE UT WOS:000228836000014 PM 15805080 ER PT J AU Regan, KS Cline, JM Creasy, D Davis, B Foley, GL Lanning, L Latendresse, JR Makris, S Morton, D Rehm, S Stebbins, K AF Regan, KS Cline, JM Creasy, D Davis, B Foley, GL Lanning, L Latendresse, JR Makris, S Morton, D Rehm, S Stebbins, K CA STP Ovary Evaluation Working Grp TI STP position paper: Ovarian follicular counting in the assessment of rodent reproductive toxicity SO TOXICOLOGIC PATHOLOGY LA English DT Article ID OOCYTE DESTRUCTION; FOLLICLES; RATS; TUMORIGENESIS; MICE C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Otsuka Maryland Res Inst, Rockville, MD USA. NCTR, Jefferson, AR USA. US EPA, OPPTS, Washington, DC 20460 USA. Dow Chem Co USA, Midland, MI 48674 USA. RP Regan, KS (reprint author), Care of Klaunig J, Toxicol Pathol Editorial Off, 199 Grassmur Turn, Pine Hill, NJ 08021 USA. RI Latendresse, John/A-9215-2009 NR 30 TC 24 Z9 25 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 3 BP 409 EP 412 DI 10.1080/01926230490515355 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 922KE UT WOS:000228836000016 PM 15805082 ER PT J AU Brix, AE Nyska, A Haseman, JK Sells, DM Jokinen, MP Walker, NJ AF Brix, AE Nyska, A Haseman, JK Sells, DM Jokinen, MP Walker, NJ TI Incidences of selected lesions in control female Harlan Sprague-Dawley rats from two-year studies performed by the National Toxicology Program SO TOXICOLOGIC PATHOLOGY LA English DT Article DE spontaneous lesions; Harlan SD rats; 2-year study ID HISTORICAL CONTROL DATA; CHRONIC EXPOSURE; NEOPLASMS; CARCINOGENICITY; TRITIUM; DIET AB The NTP has a long history of using Fischer rats and has compiled a large database of incidences of lesions seen in control animals. Such a database is lacking for Harlan Sprague - Dawley (SD) rats. The intention of this paper is to report spontaneous lesions observed in female vehicle control Harlan SD rats, and to compare the incidence in 2 strains of rats ( Fischer and Harlan SD) used in NTP studies. Female Harlan SD rats served as the test animals for a special series of 2-year studies. Male rats were not used in these studies. Complete histopathology was performed on all animals, and the pathology results underwent comprehensive NTP pathology peer review. The most commonly observed neoplasms in these female control Harlan SD rats were mammary gland fibroadenoma (71%), tumors of the pars distalis of the pituitary (41%) and thyroid gland C-cell tumors (30%). Female Fischer rats had incidences of 44% for mammary gland fibroadenomas, 34% for tumors of the pars distalis, and 16% for thyroid gland C-cell tumors. Fischer rats had a 15% incidence of clitoral gland tumors, while the Harlan SD rats had an incidence of < 1%. In contrast to Fischer F344 rats, the Harlan SD rats had a high incidence of squamous metaplasia of the uterus (44.2%). Squamous metaplasia is not a lesion commonly observed in NTP control Fischer rats. The Harlan SD rats had a very low incidence of mononuclear cell leukemia (0.5%), compared with an incidence of 24% in female Fischer rats. C1 Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Battelle Mem Inst, Columbus Labs, Columbus, OH 43201 USA. Pathol Associates Inc, Durham, NC 27713 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Brix, AE (reprint author), Expt Pathol Labs Inc, POB 12766, Res Triangle Pk, NC 27709 USA. EM brix@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 17 TC 27 Z9 28 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 4 BP 477 EP 483 DI 10.1080/01926230590961836 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 947CK UT WOS:000230620100005 PM 16036865 ER PT J AU Yoshizawa, K Kissling, GE Johnson, JA Clayton, NP Flagler, ND Nyska, A AF Yoshizawa, K Kissling, GE Johnson, JA Clayton, NP Flagler, ND Nyska, A TI Chemical-induced atrial thrombosis in NTP rodent studies SO TOXICOLOGIC PATHOLOGY LA English DT Review DE heart; left atrium; atrial thrombosis; F344 rats; B6C3F1 mice; chemical-induced; NTP studies ID TRANS-RETINOIC ACID; NECROSIS-FACTOR-ALPHA; FEMALE F344 RATS; NITRIC-OXIDE; SWISS MICE; 2-BUTOXYETHANOL-INDUCED HEMOLYSIS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; INDUCED METHEMOGLOBINEMIA; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS AB Cardiac thrombosis, one of the causes of sudden death throughout the world, plays a principal role in several cardiovascular diseases, such as myocardial infarction and stroke in humans. Data from studies of induction of chemical thrombosis in rodents help to identify substances in our environment that may contribute to cardiac thrombosis. Results for more than 500 chemicals tested in rodents in 2-year bioassays have been published as Technical Reports of the National Toxicology Program (NTP) < http://ntp-server.niehs.nih.gov/index >. We evaluated atrial thrombosis induced by these chemical exposures and compared it to similarly induced lesions reported in the literature. Spontaneous rates of cardiac thrombosis were determined for control Fischer 344 rats and B6C3F1 mice: 0% in rats and mice in 90-day studies and, in 2-year studies, 0.7% in both genders of mice, 4% in male rats, and 1% in female rats. Incidences of atrial thrombosis were increased in high-dosed groups involving 13 compounds ( incidence rate: 20-100%): 2-butoxyethanol, C. I. Direct Blue 15, bis(2-chloroethoxy) methane, diazoaminobenzene, diethanolamine, 3,3'-dimethoxybenzidine dihydrochloride, hexachloroethane, isobutene, methyleugenol, oxazepam, C. I. Pigment Red 23, C. I. Acid Red 114, and 4,4'-thiobis(6-t-butyl-m-cresol). The main localization of spontaneously occurring and chemically induced thromboses occurred in the left atrium. The literature survey suggested that chemical-induced atrial thrombosis might be closely related to myocardial injury, endothelial injury, circulatory stasis, hypercoagulability, and impaired atrial mechanical activity, such as atrial fibrillation, which could cause stasis of blood within the left atrial appendage, contributing to left atrial thrombosis. Supplementary data referenced in this paper are not printed in this issue of Toxicologic Pathology. They are available as downloadable files at http:taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233. To access them, click on the issue link for 33( 5), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath.org. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, POB 12233, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov NR 155 TC 3 Z9 3 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 5 BP 517 EP 532 DI 10.1080/01926230591034429 PG 16 WC Pathology; Toxicology SC Pathology; Toxicology GA 950HD UT WOS:000230847300001 PM 16048847 ER PT J AU Doi, AM Hailey, JR Hejtmancik, M Toft, JD Vallant, M Chhabra, RS AF Doi, AM Hailey, JR Hejtmancik, M Toft, JD Vallant, M Chhabra, RS TI Topical application of representative multifunctional acrylates produced proliferative and inflammatory lesions in F344/N rats and B6C3F(1) mice, and squamous cell neoplasms in Tg.AC mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE dermal; multifunctional acrylates; transgenic mouse; toxicity; carcinogenicity; squamous cell papillomas; inflammation ID DERMAL ONCOGENICITY BIOASSAYS; ALLERGIC CONTACT-DERMATITIS; ULTRAVIOLET CURING INKS; ZERO DOSE CONTROL; TRANSGENIC MOUSE; ETHYL ACRYLATE; SKIN TUMORS; RAS GENE; CARCINOGENICITY; CANCER AB Widespread human exposure to multifunctional acrylates is of concern, due to their inherent reactivity and irritating properties. Trimethylolpropane triacrylate (TMPTA) and pentaerythritol triacrylate (PETA) are industrially important representatives of multifunctional acrylates. The current studies characterized the toxicity of 3-month topical administration of technical grade TMPTA and PETA in F344/N rats and B6C3F(1) mice, and evaluated the carcinogenic potential of TMPTA and PETA in hemizygous Tg.AC (v-Ha-ras) transgenic mice. Administration of 0.75, 1.5, 3, 6, and 12 mg/kg TMPTA and PETA for 3 months resulted in hyperplastic, degenerative, and necrotic lesions, accompanied by chronic inflammation of the skin, with severities generally increasing with dose. Lesions were slightly more severe in rats, when compared with mice, and illustrate the irritant potential of TMPTA and PETA. A similar dosage regimen was used for the 6-month study with Tg.AC mice. Topical application of TMPTA and PETA to Tg.AC mice showed dose-dependent increases in squamous cell papillomas at the site of application, with decreases in the latency of their appearance in mice receiving 3 mg/kg or greater. Papillomas, the reporter phenotype in Tg.AC mice, were accompanied by a few squamous cell carcinomas, along with hyperplastic and inflammatory lesions. Although chronic inflammation might have contributed to the development of the skin lesions, the dose-related nature of the induction of the skin papillomas in Tg.AC mice by TMPTA and PETA may reflect a potential for carcinogenicity. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Battelle Mem Inst, Columbus, OH 43201 USA. RP Chhabra, RS (reprint author), NIEHS, POB 12233,Mail Drop EC-35, Res Triangle Pk, NC 27709 USA. EM chhabrar@niehs.nih.gov NR 38 TC 3 Z9 3 U1 4 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 6 BP 631 EP 640 DI 10.1080/01926230500295615 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 986UV UT WOS:000233476100002 PM 16176922 ER PT J AU Yoshizawa, K Matsumoto, M Oishi, Y Nyska, A AF Yoshizawa, K Matsumoto, M Oishi, Y Nyska, A TI Extraskeletal osteosarcoma with cystic appearance in an aged Sprague-Dawley rat SO TOXICOLOGIC PATHOLOGY LA English DT Article DE spontaneous tumor; extraskeletal osteosarcoma; cystic appearance; myositis ossificans; rat ID TELANGIECTATIC OSTEOSARCOMA; OSTEOGENIC-SARCOMA; TUMORS; BONE; MICE AB Extraskeletal osteosarcoma, arising spontaneously from the subcutis of the left abdomen and having it cystic appearance, was found in an untreated male Sprague-Dawley rat during a carcinogenicity study. At 76 weeks of age, the tumor mass had grown to 50 x 110 x 140 mm, and the animal exhibited severe anemia related to the complication of ulceration with hemorrhage. The tumor displayed irregular ossification at the walls of a cyst-like space filled with much yellowish fluid and necrotic cellular debris. Histopathologically, the tumor consisted of sheets of large, plump osteoblast-like cells, which produced broad irregular trabeculae of osteoid and calcified osseous tissue. Since extraskeletal osteosarcoma with a cystic appearance. has not been reported in animals, except for the telangiectatic type, our case shows an extremely rare type. C1 Astellas Pharma Inc, Drug Safety Res Labs, Toxicol Pathol, Osaka 5328514, Japan. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Yoshizawa, K (reprint author), Astellas Pharma Inc, Drug Safety Res Labs, Toxicol Pathol, Kashima 2-1-, Osaka 5328514, Japan. EM katsuhiko.yoshizawu@jp.astellas.com NR 25 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 7 BP 760 EP 763 DI 10.1080/01926230500417052 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 004JF UT WOS:000234748400003 PM 16306029 ER PT J AU Shan, L Yu, MS Snyderwine, EG AF Shan, L Yu, MS Snyderwine, EG TI Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas SO TOXICOLOGIC PATHOLOGY LA English DT Article DE mammary gland; rat pathology; carcinogenesis; microarray; tumorigenesis; molecular pathology; adenoma; gene-expression profiling ID FOOD-DERIVED CARCINOGEN; SPRAGUE-DAWLEY RATS; TUMORS; TUMORIGENESIS; CANCER; CLASSIFICATION; PROLACTIN; PATHWAY; FAT AB Chemical carcinogens induce both benign and malignant mammary gland tumors in female Sprague-Dawley rats. To identify gene expression profiles associated with malignancy, cDNA microarray analysis was used to compare gene expression profiles in rat mammary gland carcinomas, adenomas, and normal mammary gland. Tumors were induced with various chemical carcinogens including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 7-12- dimethylbenz[a]anthracene (DMBA), N-nitrosomethylurea (NMU), and 4- aminobiphenyl. The global gene expression profiles in carcinomas and adenomas were distinguishable by hierarchical clustering and multi-dimensional scaling analyses. Permutation analysis revealed 110 clones statistically differentially expressed between benign and malignant tumors (p < 0.0005). Carcinomas showed relatively high expression of several genes associated with mammary epithelial cell growth and proliferation (e.g., cyclin D1. PDGF alpha) and relatively low expression of differentiation marker genes (e.g., beta-casein, whey acidic protein, transferrin). Other categories of genes showing differential expression between carcinomas and adenomas were associated with protein homeostasis. cytoskeleton, extracellular matrix, and cell metabolism (fatty acid metabolism. oxidative phosphorylation, and glycolysis), Major gene families implicated in malignancy by over-expression in carcinomas included the annexins (annexin A1 and A4) and Stat family of transcription factors (Stat3 and Stat5a). The elevated expression of the prolactin receptor in carcinomas concomitant with several components of the mitogenic prolactin signaling pathway implicated prolactin/prolactin receptor/Stat5a/cyclin D1 in rat mammary gland malignancy. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bldg 37,Room 4146, Bethesda, MD 20892 USA. EM elizabeth_snyderwine@nih.gov FU Intramural NIH HHS NR 29 TC 11 Z9 11 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 7 BP 768 EP 775 DI 10.1080/01926230500437027 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 004JF UT WOS:000234748400005 PM 16316942 ER PT J AU Eastin, WC AF Eastin, WC TI National Toxicology Program's updated website http ://ntp.niehs.nih.gov SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Eastin, WC (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM eastin@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 7 BP 800 EP 801 DI 10.1080/01926230500377124 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 004JF UT WOS:000234748400009 ER PT J AU Yoshizawa, K Walker, NJ Jokinen, MP Brix, AE Sells, DM Marsh, T Wyde, ME Orzech, D Haseman, JK Nyska, A AF Yoshizawa, K Walker, NJ Jokinen, MP Brix, AE Sells, DM Marsh, T Wyde, ME Orzech, D Haseman, JK Nyska, A TI Gingival carcinogenicity in female Harlan Sprague-Dawley rats following two-year oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds SO TOXICOLOGICAL SCIENCES LA English DT Review DE gingival squamous hyperplasia; squamous cell carcinoma; rat; dioxin; dioxin-like compounds ID ARYL-HYDROCARBON RECEPTOR; EMBRYONIC PALATAL SHELVES; SUBCHRONIC DIETARY EXPOSURE; SQUAMOUS-CELL CARCINOMA; MOLAR TOOTH DEVELOPMENT; POLYCHLORINATED-BIPHENYLS; AH RECEPTOR; JUNCTIONAL EPITHELIUM; LACTATIONAL EXPOSURE; MACACA-FASCICULARIS AB We evaluated gingival toxicities induced by chronic exposure of female Harlan Sprague-Dawley rats to dioxin and dioxin-like compounds (DLCs) and compared them to similarly induced oral lesions reported in the literature. This investigation represents part of an ongoing initiative of the National Toxicology Program to determine the relative potency of chronic toxicity and carcinogenicity of polychlorinated dioxins, furans, and biphenyls. For two years, animals were administered by gavage 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 3,3',4,4',5-pentachlorobiphenyl (PCB126); 2,3,4,7,8-pentachlorodibenzofuran (PeCDF); 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153); a tertiary mixture of TCDD, PCB126, and PeCDF; a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and 2,3',4,4',5-pentachlorobiphenyl (PCB118); control animals received corn oil-acetone vehicle (99:1) alone. A full complement of tissues, including the palate with teeth, was examined microscopically. In the groups treated with TCDD and the mixtures of TCDD, PCB126, and PeCDF; PCB126 and 153; and PCB126 and 118, the incidences of gingival squamous hyperplasia increased significantly. Moreover, in the groups treated with TCDD, PCB126, and the mixture of PCB126 and 153, squamous cell carcinoma (SCC) in the oral cavity increased significantly. This investigation constitutes the first report documenting that chronic administration of dioxin-like PCBs can induce gingival SCC in rats. These results indicate that dioxin and DLCs target the gingiva of the oral cavity, in particular the junctional epithelium of molars. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. Pathol Associates Inc, Durham, NC 27713 USA. Expt Pathol Labs, Res Triangle Pk, NC 27709 USA. Battelle Mem Inst, Columbus Labs, Columbus, OH 43201 USA. NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, POB 12233,Mail Drop B3-06,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 104 TC 17 Z9 18 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2005 VL 83 IS 1 BP 64 EP 77 DI 10.1093/toxsci/kfi016 PG 14 WC Toxicology SC Toxicology GA 878WJ UT WOS:000225677700007 PM 15509667 ER PT J AU Stansbury, LG Hess, JR AF Stansbury, LG Hess, JR TI Putting the pieces together: Roger I. Lee and modern transfusion medicine SO TRANSFUSION MEDICINE REVIEWS LA English DT Biographical-Item AB Roger Irving Lee (1881-1964) played significant scientific and leadership roles in overcoming the clinical impediments to blood transfusion in the 1910s. He developed the first successful anticoagulant system, paraffinized glass, and the first sterile system for indirect transfusion without defibrination, the Lee-Vincent flask. He used citrate as an anticoagulant before those generally credited with its discovery did. He introduced surgical antisepsis of the donor site and a practical system for maintaining typed blood for a large hospital donor and transfusion service. He was Oswald Robertson's mentor at Harvard as well as his commanding officer in the Harvard Medical Unit on the Western Front during World War I. Lee sent Robertson to perform "his preserved blood cells transfusion" in the casualty clearing stations of the British Third Army and provided Robertson's group with 0 donors, enabling the most important medical development of the war. Lee put the pieces of modern blood banking and transfusion together. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Maryland, Med Ctr, Blood Bank, Dept Pathol, Baltimore, MD 21201 USA. NIH, Occupat Med Serv, Bethesda, MD 20892 USA. RP Hess, JR (reprint author), Univ Maryland, Med Ctr, Blood Bank, Dept Pathol, N2W50a,22 S Greene St, Baltimore, MD 21201 USA. EM jhess@umm.edu FU NHLBI NIH HHS [HL072359] NR 0 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 2005 VL 19 IS 1 BP 81 EP 84 DI 10.1016/j.tmrv.2004.09.003 PG 4 WC Hematology SC Hematology GA 903EB UT WOS:000227407200006 PM 15830330 ER PT J AU Kirk, AD Mannon, RB Swanson, SJ Hale, DA AF Kirk, AD Mannon, RB Swanson, SJ Hale, DA TI Strategies for minimizing immunosuppression in kidney transplantation SO TRANSPLANT INTERNATIONAL LA English DT Review DE immunosuppression; tolerance; transplant ID RENAL-ALLOGRAFT RECIPIENTS; DONOR BONE-MARROW; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; ACUTE REJECTION EPISODES; LONG-TERM IMPROVEMENT; MYCOPHENOLATE-MOFETIL; GRAFT-SURVIVAL; T-CELLS; DIABETES-MELLITUS; RANDOMIZED-TRIAL AB Immunosuppression remains the cause of most morbidity following organ transplantation. However, its use is also responsible for the outstanding graft and patient survival rates commonplace in modern transplantation. Thus, the predominant challenge for transplant clinicians is to provide a level of immunosuppression that prevents graft rejection while preserving immunocompetence against environmental pathogens. This review will outline several strategies for minimizing or tailoring the use of immunosuppressive drugs. The arguments for various strategies will be based on clinical trial data rather than animal studies. A distinction will be made between conventional immunosuppressive drug reduction based on over-immunosuppression, and newer induction methods specifically designed to lessen the need for chronic immunosuppression. Based on the available data we suggest that most patients can be transplanted with less immunosuppression than is currently standard. C1 NIDDKD, Transplantat Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), NIDDKD, Transplantat Branch, Dept Hlth & Human Serv, NIH, Room 11S-219,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 NR 112 TC 34 Z9 37 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD JAN PY 2005 VL 18 IS 1 BP 2 EP 14 DI 10.1111/j.1432-2277.2004.00019.x PG 13 WC Surgery; Transplantation SC Surgery; Transplantation GA 896IM UT WOS:000226927800001 PM 15612977 ER PT J AU Qasba, PK Ramakrishnan, B Boeggeman, E AF Qasba, PK Ramakrishnan, B Boeggeman, E TI Substrate-induced conformational changes in glycosyltransferases SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID ALPHA-LACTALBUMIN LA; CRYSTAL-STRUCTURE; N-ACETYLGLUCOSAMINE; STRUCTURAL BASIS; BLOOD-GROUP; HUMAN GLUCURONOSYLTRANSFERASE; SULFATE BIOSYNTHESIS; CONGENITAL DISORDERS; CATALYTIC MECHANISM; DONOR SPECIFICITY AB Oligosaccharide chains of glycoproteins, glycolipids and glycosaminoglycans are synthesized by glycosyltransferases by the transfer of specific glycosyl moieties from activated sugar-nucleotide donors to specific acceptors. Structural studies on several of these enzymes have shown that one or two flexible loops at the substrate-binding site of the enzymes undergo a marked conformational change from an open to a closed conformation on binding the donor substrate. This conformational change, in which the loop acts as a lid covering the bound donor substrate, creates an acceptor-binding site. After the glycosyl unit is transferred from the donor to the acceptor, the saccharide product is ejected and the loop reverts to its native conformation, thereby releasing the remaining nucleotide moiety. The specificity of the sugar donor is determined by a few residues in the sugar-nucleotide-binding pocket of the enzyme that are conserved among the family members from different species. C1 NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, CCR, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick, Lab Expt & Computat Biol,CCR, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, CCR, Frederick, MD 21702 USA. EM qasba@helix.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 71 TC 153 Z9 156 U1 3 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JAN PY 2005 VL 30 IS 1 BP 53 EP 62 DI 10.1016/j.tibs.2004.11.005 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 894BR UT WOS:000226765400010 PM 15653326 ER PT J AU Khil, PP Oliver, B Camerini-Otero, RD AF Khil, PP Oliver, B Camerini-Otero, RD TI X for intersection: retrotransposition both on and off the X chromosome is more frequent SO TRENDS IN GENETICS LA English DT Article ID HUMAN Y-CHROMOSOME; PROCESSED PSEUDOGENES; SEX-CHROMOSOMES; BIASED EXPRESSION; GENE-EXPRESSION; GENOME; EVOLUTION; DROSOPHILA; SPERMATOGENESIS; INACTIVATION AB As the heteromorphic sex chromosomes evolved from a pair of autosomes, the sex chromosomes became increasingly different in gene content and structure from each other and from the autosomes. Although recently there has been progress in documenting and understanding these differences, the molecular mechanisms that have fashioned some of these changes remain unclear. A new study addresses the differential distribution of retroposed genes in human and mouse genomes. Surprisingly, chromosome X is a major source and a preferred target for retrotransposition. C1 NIDDKD, Genet & Biochem Branch, Bethesda, MD 20892 USA. NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Camerini-Otero, RD (reprint author), NIDDKD, Genet & Biochem Branch, Bethesda, MD 20892 USA. EM camerini@ncifcrf.gov OI Khil, Pavel/0000-0002-4903-8777 NR 45 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JAN PY 2005 VL 21 IS 1 BP 3 EP 7 DI 10.1016/j.tig.2004.11.005 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 890BD UT WOS:000226485800002 PM 15680505 ER PT J AU Kolenbrander, PE Egland, PG Diaz, PI Palmer, RJ AF Kolenbrander, PE Egland, PG Diaz, PI Palmer, RJ TI Genome-genome interactions: bacterial communities in initial dental plaque SO TRENDS IN MICROBIOLOGY LA English DT Editorial Material ID ACTINOMYCES-VISCOSUS T14V; FIMBRIA-ASSOCIATED ADHESINS; BACTEROIDES-LOESCHEII; ORAL BACTERIA; STREPTOCOCCI; BIOFILMS; IDENTIFICATION; MICROFLORA; NAESLUNDII; LECTINS AB The usual context for genome-genome interactions is DNA-DNA interactions, but the manifestation of the genome is the cell. Here we focus on cell-cell interactions and relate them to the process of building multispecies biofilm communities. We propose that dental plaque communities originate as a result of intimate interactions between cells (genomes) of different species and not through clonal growth of genetically identical cells. Although DNA exchange might occur between cells within these communities, we limit our opinions to discussions of the spatiotemporal and metabolic relationships that exist here. We believe the multi-species interactions occurring during the early stages of biofilm formation determine the species composition and nature of the mature biofilm. The human oral cavity provides easy access to natural biofilms on a retrievable enamel chip, which is an excellent model for the study of genome-genome interactions. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20902 USA. RP Kolenbrander, PE (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20902 USA. EM pkolenbrander@dir.nider.nih.gov RI Diaz, Patricia/E-9465-2012 NR 30 TC 51 Z9 55 U1 3 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JAN PY 2005 VL 13 IS 1 BP 11 EP 15 DI 10.1016/j.tim.2004.11.005 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 893KG UT WOS:000226717200004 PM 15639626 ER PT J AU Drenth, JPH Martina, JA van de Kerkhof, R Bonifacino, JS Jansen, JBMJ AF Drenth, JPH Martina, JA van de Kerkhof, R Bonifacino, JS Jansen, JBMJ TI Polycystic liver disease is a disorder of cotranslational protein processing SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID KIDNEY-DISEASE; MOLECULAR CHARACTERIZATION; ENDOPLASMIC-RETICULUM; 2-HIT MODEL; MUTATIONS; PRKCSH; GENES; CYSTOGENESIS; HEPATOCYSTIN; SEC63P AB Autosomal-dominant polycystic liver disease (PCLD) is a rare disorder that is characterized by the progressive development of fluid-filled biliary epithelial cysts in the liver. Positional cloning has identified two genes that are mutated in patients with polycystic liver disease, PRKCSH and SEC63, which encode the beta-subunit of glucosidase II and Sec63, respectively. Both proteins are components of the molecular machinery involved in the translocation, folding and quality control of newly synthesized glycoproteins in the endoplasmic reticulum. Most mutations are truncating and probably lead to a complete loss of the corresponding proteins and the defective processing of a key regulator of biliary cell growth. The finding that PCLD is caused by proteins involved in oligosaccharide processing was unexpected and implicates a new avenue for research into neocystogenesis, and might ultimately result in the identification of novel therapeutic drugs. C1 Univ Nijmegen, Med Ctr St Radboud, Dept Med, Div Gastroenterol & Hepatol, NL-6500 HB Nijmegen, Netherlands. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Drenth, JPH (reprint author), Univ Nijmegen, Med Ctr St Radboud, Dept Med, Div Gastroenterol & Hepatol, NL-6500 HB Nijmegen, Netherlands. EM JoostPHDrenth@CS.com RI Drenth, J.P.H./H-8025-2014; OI Bonifacino, Juan S./0000-0002-5673-6370 NR 30 TC 56 Z9 57 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD JAN PY 2005 VL 11 IS 1 BP 37 EP 42 DI 10.1016/j.molmed.2004.11.004 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 894BQ UT WOS:000226765300007 PM 15649821 ER PT J AU Abbracchio, MP Burnstock, G Boeynaems, JM Barnard, EA Boyer, JL Kennedy, C Miras-Portugal, MT King, BF Gachet, C Jacobson, KA Weisman, GA AF Abbracchio, MP Burnstock, G Boeynaems, JM Barnard, EA Boyer, JL Kennedy, C Miras-Portugal, MT King, BF Gachet, C Jacobson, KA Weisman, GA TI The recently deorphanized GPR80 (GPR99) proposed to be the P2Y(15) receptor is not a genuine P2Y receptor SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Letter ID ADENOSINE AB The P2Y receptor family currently encompasses eight members (P2Y(1,2,4,6,11,12,13,14) receptors) that are activated by extracellular adenine and/or uracil nucleotides, or, in the case of the P2Y(14) receptor, by sugar-nucleotides, and are each characterized by the typical seven-transmembrane domain topology of G-protein-coupled receptors (GPCRs) [1]. For several years, it has been known that a series of 'orphan' GPCRs (i.e. cloned receptors available in the public database for which a natural ligand has not yet been identified) share significant sequence identity with the eight genuine P2Y receptors [1,2] and thus putatively represent novel members of the P2Y receptor family. C1 Royal Free & Unvi Coll Med Sch Sch, Auton Neurosci Inst, London NW3 2PF, England. Univ Milan, Dept Pharmacol Sci, I-20133 Milan, Italy. Free Univ Brussels, IRIBHM, B-1070 Brussels, Belgium. Free Univ Brussels, Erasme Hosp, Dept Med Chem, B-1070 Brussels, Belgium. Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England. Inspire Pharmaceut Inc, Mol Pharmacol, Durham, NC 27703 USA. Univ Strathclyde, Dept Physiol & Pharmacol, Glasgow G4 0NR, Lanark, Scotland. Univ Complutense Madrid, Dept Bioquim, E-28040 Madrid, Spain. EFS Alsace, INSERM, U311, F-67065 Strasbourg, France. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Univ Missouri, Dept Biochem, Columbia, MO 65212 USA. RP Burnstock, G (reprint author), Royal Free & Unvi Coll Med Sch Sch, Auton Neurosci Inst, Rowland Hill St, London NW3 2PF, England. EM g.burnstock@ucl.ac.uk RI Jacobson, Kenneth/A-1530-2009; Miras-Portugal, Maria Teresa/L-7137-2014; Abbracchio, Maria Pia/B-9342-2014; Gachet, Christian/H-9156-2016 OI Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388; FU Intramural NIH HHS [Z01 DK031116-20] NR 8 TC 31 Z9 35 U1 2 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JAN PY 2005 VL 26 IS 1 BP 8 EP 9 DI 10.1016/j.tips.2004.10.010 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 892WN UT WOS:000226680800003 PM 15629198 ER PT J AU Moro, S Spalluto, G Jacobson, KA AF Moro, S Spalluto, G Jacobson, KA TI Techniques: Recent developments in computer-aided engineering of GPCR ligands using the human adenosine A(3) receptor as an example SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID PROTEIN-COUPLED RECEPTORS; AGONIST BINDING-SITE; ANTAGONISTS; DERIVATIVES; RHODOPSIN; POTENT; MODEL; PHOSPHORYLATION; IDENTIFICATION; PHARMACOPHORE AB G-protein-coupled receptors (GPCRs) represent the largest known family of signal-transducing molecules, and convey signals for light and many extracellular regulatory molecules. GPCRs are dysfunctional or dys-regulated in several human diseases and are estimated to be the targets of >40% of the drugs used in clinical medicine today. The crystal structure of rhodopsin provides the first information on the three-dimensional structure of GPCRs, which now supports homology modeling studies and structure-based drug-design approaches. In this article, we review recent work on adenosine receptors, a family of GPCRs, and, in particular, on adenosine A(3) receptor antagonists. We focus on an iterative, bi-directional approach in which models are used to generate hypotheses that are tested by experimentation; the experimental findings are, in turn, used to refine the model. The success of this approach is due to the synergistic interaction between theory and experimentation. C1 Univ Padua, Dipartimento Sci Farmaceut, Mol Modeling Sect, I-35131 Padua, Italy. Univ Trieste, Dipartimento Sci Farmaceut, I-34127 Trieste, Italy. NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Moro, S (reprint author), Univ Padua, Dipartimento Sci Farmaceut, Mol Modeling Sect, Via Marzolo 5, I-35131 Padua, Italy. EM stefano.moro@unipd.it RI Jacobson, Kenneth/A-1530-2009; Moro, Stefano/A-2979-2012 OI Jacobson, Kenneth/0000-0001-8104-1493; Moro, Stefano/0000-0002-7514-3802 NR 45 TC 65 Z9 66 U1 1 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JAN PY 2005 VL 26 IS 1 BP 44 EP 51 DI 10.1016/j.tips.2004.11.006 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 892WN UT WOS:000226680800010 PM 15629204 ER PT J AU Gonzales, NR De Pascalis, R Schlom, J Kashmiri, SVS AF Gonzales, NR De Pascalis, R Schlom, J Kashmiri, SVS TI Minimizing the immunogenicity of antibodies for clinical application SO TUMOR BIOLOGY LA English DT Review DE complementarity-determining region grafting; human anti-murine antibody; humanized antibodies; immunogenicity; specificity-determining residue; serum reactivity; surface plasmon resonance ID SPECIFICITY-DETERMINING RESIDUES; HUMANIZED MONOCLONAL-ANTIBODY; COMPLEMENTARITY-DETERMINING REGIONS; AFFINITY HUMAN-ANTIBODIES; NON-HODGKINS-LYMPHOMA; ANTICARCINOMA ANTIBODY; ANTIGEN-BINDING; PHASE-I; HYPERVARIABLE LOOPS; FRAMEWORK RESIDUES AB The clinical utility of murine monoclonal antibodies has been greatly limited by the human anti-murine antibody responses they effect in patients. To make them less immunogenic, murine antibodies have been genetically engineered to progressively replace their murine content with that of their human counterparts. This review describes the genetic approaches that have been used to humanize murine antibodies, including the generation of mouse-human chimeric antibodies, veneering of the mouse variable regions, and the grafting of murine complementarity-determining regions (CDRs) onto the variable light ( V L) and variable heavy ( V H) frameworks of human immunoglobulin molecules, while retaining only those murine framework residues deemed essential for the integrity of the antigen-binding site. To minimize the anti-idiotypic responses that could still be evoked by the murine CDRs in humanized antibodies, two approaches have also been described. These are based on grafting onto the human frameworks the 'abbreviated' CDRs or only the specificity-determining residues (SDRs), the CDR residues that are involved in antigen interaction. The SDRs are identified through the help of the database of three-dimensional structures of antibody: antigen complexes or by mutational analysis of the antibody-combining site. In addition, we also describe the use of in vitro affinity maturation to enhance the binding affinity of humanized antibodies, as well as the manipulation of framework residues to maximize their human content and minimize their immunogenic potential. Copyright (C) 2005 S. Karger AG, Basel. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kashmiri, SVS (reprint author), 10 Ctr Dr,Bldg 10,Rm 5B38, Bethesda, MD 20892 USA. EM sk85f@nih.gov NR 50 TC 26 Z9 32 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2005 VL 26 IS 1 BP 31 EP 43 DI 10.1159/000084184 PG 13 WC Oncology SC Oncology GA 912JF UT WOS:000228073300005 PM 15741769 ER PT J AU Urzua, U Frankenberger, C Gangi, L Mayer, S Burkett, S Munroe, DJ AF Urzua, U Frankenberger, C Gangi, L Mayer, S Burkett, S Munroe, DJ TI Microarray comparative genomic hybridization profile of a murine model for epithelial ovarian cancer reveals genomic imbalances resembling human ovarian carcinomas SO TUMOR BIOLOGY LA English DT Article DE DNA microarray; ovarian cancer; mouse model; chromosomal aberrations ID CDNA MICROARRAYS; TUMORS; DNA; INSTABILITY; OVULATION; EVOLUTION; DISTINCT; BUB1 AB Microarray comparative genomic hybridization (mCGH) is emerging as a high-resolution technology to detect gene dosage alterations in numerous pathologies, including cancer. We optimized cDNA microarrays to identify genome-wide imbalances in spontaneously transformed mouse ovarian surface epithelial cell lines, an in vitro murine model for ovarian cancer. Amplification of chromosome 19 and a more variable gain pattern of chromosomes 15 and 5 were detected and independently validated using conventional metaphase CGH. In addition, cryptic aberrations in segments of chromosomes 4, 7, 8, 9, 11, 17, and X, allowed identification of 2 related genomic variants among six cell lines studied. Mouse-human synteny revealed an overall early transformation stage with approximately 80% conservation relative to human ovarian malignancies of epithelial origin including low malignant potential tumors, serous carcinoma, and carcinoma cell lines. Importantly, three of the cells bear gained segments 13 and 41 Mbp length of chromosomes 5 and 15, respectively, which are syntenic to human 22q11-13, 8q24 and 12p11-q24, the two latter chromosomal regions thought to define one pathway of karyotypic changes in the development of human ovarian tumors. Our findings support the utility of mouse ovarian surface epithelial (MOSE) cells in studying initiation and progression of human ovarian cancer and as a suitable model to evaluate therapeutic approaches. Copyright (C) 2005 S. Karger AG, Basel. C1 NCI, Lab Mol Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Lab Comparat Cytogenet, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Urzua, U (reprint author), Univ Chile, Fac Med, Programa Biol Celular & Mol, Inst Ciencias Biomed, Independencia 1027, Santiago 7, Chile. EM uurzua@med.uchile.cl RI Urzua, Ulises/A-3982-2013; OI Urzua, Ulises/0000-0003-0522-5754 FU PHS HHS [N01-C0-12400] NR 25 TC 17 Z9 20 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2005 VL 26 IS 5 BP 236 EP 244 DI 10.1159/000087378 PG 9 WC Oncology SC Oncology GA 962TT UT WOS:000231756600003 PM 16103745 ER PT S AU Greenwald, P AF Greenwald, P BE Senn, HJ Morant, R TI Lifestyle and medical approaches to cancer prevention SO TUMOR PREVENTION AND GENETICS III SE Recent Results in Cancer Research LA English DT Proceedings Paper CT Pediatric Psycho-Oncology Research Summit CY OCT, 2001 CL San Antonio, TX SP Childhood Canc Grp, NCI ID PROSTATE-CANCER; BREAST-CANCER; SELENIUM SUPPLEMENTATION; CONTROLLED-TRIAL; UNITED-STATES; US ADULTS; CHEMOPREVENTION; COHORT; MORTALITY; RISK AB Cancer risk can be reduced by adopting a healthy lifestyle and by medical means. Tobacco control is central to public policies for cancer prevention. Overweight and obesity in the United States may contribute to 20% of cancer deaths in women and 14% in men. Cancer prevention strategies have progressed from a predominant lifestyle approach to a model that combines clinical investigations in a medical setting with public health interventions. This change stems from advances in identifying, developing, and testing agents with the potential either to prevent cancer initiation, or to inhibit or reverse the progression of premalignant lesions to invasive cancer. Encouraging laboratory and epidemiologic studies, along with secondary endpoints in treatment trials, have provided a strong scientific rationale for the hypothesis that a pharmacologic approach - chemoprevention - can reduce cancer risk. Numerous chemopreventive agents, including naturally occurring vitamins, minerals, phytochemicals, and synthetic compounds, have proved to be safe and effective in preclinical and clinical studies. Promising results have been reported for cancers of the prostate, breast, colon, lung, bladder, cervix, oral cavity, esophagus, skin, and liver. The use of emerging technologies, identification of biomarkers of risk, and advances in genetic research are being applied to chemoprevention research. An interdisciplinary research approach to investigate molecular and genetic markers-as well as chemoprevention and lifestyle strategies-that affect cancer risk is being applied to the most common types of cancer in the United States in women (breast) and men (prostate). C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Greenwald, P (reprint author), NCI, Div Canc Prevent, NIH, 6130 Execut Blvd,Suite 2040, Bethesda, MD 20892 USA. EM pg37g@nih.gov NR 51 TC 22 Z9 22 U1 4 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-22228-6 J9 RECENT RES CANCER PY 2005 VL 166 BP 1 EP 15 PG 15 WC Oncology SC Oncology GA BBN83 UT WOS:000226377400001 PM 15648179 ER PT S AU Hawk, ET Umar, A Lubet, RA Kopelovich, L Viner, JL AF Hawk, ET Umar, A Lubet, RA Kopelovich, L Viner, JL BE Senn, HJ Morant, R TI Can animal models help us select specific compounds for cancer prevention trials? SO TUMOR PREVENTION AND GENETICS III SE Recent Results in Cancer Research LA English DT Proceedings Paper CT Pediatric Psycho-Oncology Research Summit CY OCT, 2001 CL San Antonio, TX SP Childhood Canc Grp, NCI ID FAMILIAL ADENOMATOUS POLYPOSIS; INDUCED COLON CARCINOGENESIS; SPRAGUE-DAWLEY RATS; GENETICALLY-ENGINEERED MICE; MAMMARY-CARCINOMA MODEL; BREAST-CANCER; RANDOMIZED-TRIAL; BETA-CAROTENE; POSTMENOPAUSAL WOMEN; PROSTATE CARCINOGENESIS AB Animal models provide unparalleled mechanistic insights into cancer development and potential opportunity for cancer prevention. Nevertheless, species differ markedly with regard to dietary exposures, cancer development, drug effects, and toxicity thresholds; therefore, testing in a single animal system may not predict human responses. Although replication of human cancer in animal models remains inexact, more than two decades of research have clearly yielded significant gains, as is evident in agents tested - and in certain cases, approved - for the prevention of epithelial cancers. Research efficiencies achievable through preliminary testing in genetically engineered and carcinogen-induced animal models enable us to probe genetic and signaling pathways that drive normal and neoplastic processes, and thereby figure prominently in decision trees for agent development. C1 NCI, GI & Other Canc Res Grp, Bethesda, MD 20892 USA. RP Hawk, ET (reprint author), NCI, GI & Other Canc Res Grp, Suite 2141,6130 Execut Blvd, Bethesda, MD 20892 USA. EM hawke@mail.nih.gov NR 86 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-22228-6 J9 RECENT RES CANCER PY 2005 VL 166 BP 71 EP 87 PG 17 WC Oncology SC Oncology GA BBN83 UT WOS:000226377400006 PM 15648184 ER PT S AU Schatzkin, A AF Schatzkin, A BE Senn, HJ Morant, R TI Problems with using biomarkers as surrogate end points for cancer: A cautionary tale SO TUMOR PREVENTION AND GENETICS III SE Recent Results in Cancer Research LA English DT Proceedings Paper CT Pediatric Psycho-Oncology Research Summit CY OCT, 2001 CL San Antonio, TX SP Childhood Canc Grp, NCI ID BREAST-CANCER; POSTMENOPAUSAL WOMEN; COLON-CANCER; RISK; ALCOHOL AB Investigations employing surrogate cancer end points are especially attractive because they may be smaller, shorter, and cheaper than comparable studies with explicit cancer outcomes. For many potential surrogate end points - epithelial cell proliferation will be taken as an example - inferences are problematic because of the existence of alternative causal pathways to cancer that bypass the surrogate end point. Evaluating potential surrogates requires information on the following three questions: (1) What is the relation of the surrogate end point to cancer? (2) What is the relation of the intervention (or exposure) to the surrogate? (3) To what extent does the surrogate end point mediate the relation between intervention (exposure) and cancer? Data for these questions may derive from animal experiments, human metabolic studies, observational epidermologic investigations (including ecologic studies), and randomized trials. Inferences to cancer from such downstream markers as colorectal adenomatous polyps and persistent human papillomavirus infection of the cervix are strong, though not absolutely unassailable. For all but these very-close-to-cancer markers, considerable caution is warranted in extrapolating from surrogate effects or associations to cancer. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20592 USA. RP NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320,Room 3040, Rockville, MD 20592 USA. EM as17h@nih.gov NR 13 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-22228-6 J9 RECENT RESULTS CANC JI Rec. Res. Camcer Res. PY 2005 VL 166 BP 89 EP 98 PG 10 WC Oncology SC Oncology GA BBN83 UT WOS:000226377400007 PM 15648185 ER PT S AU Meyskens, FL Szabo, E AF Meyskens, FL Szabo, E BE Senn, HJ Morant, R TI How should we move the field of chemopreventive agent development forward in a productive manner? SO TUMOR PREVENTION AND GENETICS III SE Recent Results in Cancer Research LA English DT Proceedings Paper CT Pediatric Psycho-Oncology Research Summit CY OCT, 2001 CL San Antonio, TX SP Childhood Canc Grp, NCI ID SURROGATE END-POINTS; ALPHA-DIFLUOROMETHYLORNITHINE; COLORECTAL ADENOMAS; CANCER PREVENTION; VITAMIN-A; RECURRENCE; TRIALS; DRUGS AB Epidemiologic observations and preclinical experimental investigations suggest that the prevention or reversal of precancers should be an effective strategy in humans to control cancer. Although "proof of principle" has been established in humans, the results of randomized trials have not been confirmatory in most cases. Toxicity in normal or near-normal populations has also been greater than anticipated. We examine the problems associated with testing chemoprevention agents in humans and offer a process and guidelines that may better inform the logical development of this relatively young clinical field. C1 Univ Calif Irvine, Dept Internal Med Hematol Oncol, Orange, CA 92868 USA. Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92868 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Meyskens, FL (reprint author), Univ Calif Irvine, Dept Internal Med Hematol Oncol, Orange, CA 92868 USA. EM flmeyske@msx.ndc.mc.uci.edu FU NCI NIH HHS [CA 62203] NR 25 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-22228-6 J9 RECENT RES CANCER PY 2005 VL 166 BP 113 EP 124 PG 12 WC Oncology SC Oncology GA BBN83 UT WOS:000226377400009 PM 15648187 ER PT S AU Brooks, AD Ramirez, T Toh, U Onksen, J Elliott, PJ Murphy, WJ Sayers, TJ AF Brooks, AD Ramirez, T Toh, U Onksen, J Elliott, PJ Murphy, WJ Sayers, TJ BE ElDeiry, WS TI The proteasome inhibitor bortezomib (Velcade) sensitizes some human tumor cells to Apo2L/TRAIL-mediated apoptosis SO TUMOR PROGRESSION AND THERAPEUTIC RESISTANCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Tumor Progression and Therapeutic Resistance CY NOV 08-09, 2004 CL Philadelphia, PA SP Univ Penn, Abramson Canc Ctr, Global Technol Comm LLC, Pfizer Inc, Fels Inst Canc Res, Thomas Jefferson Univ, Kimmel Canc Ctr, Wistar Inst DE apoptosis; bortezomib; velcade; Apo2L/TRAIL ID SIGNALING PATHWAYS; RENAL-CANCER; TRAIL; DEATH; RESISTANCE; INDUCTION; BAX; P53 AB On testing a panel of different human cancer cell lines, we observed that the proteasome inhibitor bortezomib could dramatically sensitize some lines to the apoptotic effects of Apo2L/TRAIL. Certain renal, colon, or breast tumor cell lines were dramatically sensitized, whereas other tumor lines from the same tissue of origin remained resistant. This sensitization did not correlate with either the p53 status of the individual tumor cell lines or their intrinsic sensitivity to Apo2L/TRAIL. Colon cancer cell lines lacking p53 or Bax were sensitized by bortezomib, suggesting that neither p53 nor Bax levels were crucial for sensitization. Although the molecular basis of bortezomib sensitization of tumor cells to Apo2L/TRAIL remains to be determined, this combination can have an enhanced apoptotic effect over either agent alone for certain human cancer cells. C1 NCI, SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. Kurume Univ, Dept Surg, Kurume, Fukuoka 830, Japan. Combinatorex, Boston, MA USA. Univ Nevada, Reno, NV USA. RP Sayers, TJ (reprint author), NCI, SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. EM sayers@mail.ncifcrf.gov FU NCI NIH HHS [R01 CA102282, R01 CA102282-03]; PHS HHS [N01-C0-12400] NR 13 TC 33 Z9 35 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 1-57331-543-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1059 BP 160 EP 167 DI 10.1196/annals.1339.042 PG 8 WC Oncology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Oncology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BDZ00 UT WOS:000236279200015 PM 16382051 ER PT J AU Calis, I Kirmizibekmez, H Beutler, JA Donmez, AA Yalcin, FN Kilic, E Ozalp, M Ruedi, P Tasdemir, D AF Calis, I Kirmizibekmez, H Beutler, JA Donmez, AA Yalcin, FN Kilic, E Ozalp, M Ruedi, P Tasdemir, D TI Secondary metabolites of Phlomis viscosa and their biological activities SO TURKISH JOURNAL OF CHEMISTRY LA English DT Article DE Phlomis viscosa; iridoids; phenylethanoid glycosides; lignan glucosides; 8-O-4 '-oxylignan; neolignan glucosides; biological activity ID PHENYLPROPANOID GLYCOSIDES; NEOLIGNAN GLYCOSIDES; PHENOLIC GLYCOSIDES; CONSTITUENTS; GLUCOSIDES; LEAVES; GLANDULOSA; IRIDOIDS AB Further phytochemical studies on the aerial parts of Phlomis viscosa (Lamiaceae) led to the isolation of 24 compounds: 3 iridoid glycosides, 10 phenylethanoid glycosides, a megastigmane glycoside and a hydroquinone glycoside, as well as 2 lignan glucosides and 7 neolignan glucosides, I of which is new (17b). Compound 17b was obtained is a minor component of an inseparable mixture (2:1) of 2 neolignan glucosides (17a/b), and characterized as 3',4-O-dimethylcedrusin 9-O-beta-glucopyranoside. Full NMR data of the known 8-O-4' neolignan glucoside, etythro-1-(4-O-,beta-glucopyranosyl-3-methoxyphenyl)-2-{2-methoxyl-4-[1-(E)-propene-3-ol]-phenoxyl}-propane-1,3-diol (18) are also reported. All isolated compounds were screened for cell growth inhibition versus 3 tumor cell lines (MCF7, NCI-H460, and SF-268) and several phenylethanoid glycosides were found to possess weak antitumoral activity. The phenylethanoid glycosides were also evaluated for their free radical (DPPH) scavenging, antibacterial and antifungal activities. The free radical (DPPH) scavenging activities of verbascoside (4), isoacteoside (5), forsythoside B (10), myricoside (13) and samioside (14) were found to be comparable to that of dl-alpha-tocopherol. Compounds 4, 5, 10 and 14 (MIC: 500 mu g/mL) as well as Leucosceptoside A (8) and 13 (MIC:1000 mu g/mL) showed very weak activity against Gram (+) bacteria. C1 Hacettepe Univ, Fac Pharm, Dept Pharmacognosy, TR-06100 Ankara, Turkey. NCI, Mol Targets Dev Program, Frederick, MD 21702 USA. Hacettepe Univ, Fac Sci, Dept Biol, TR-06532 Ankara, Turkey. Hacettepe Univ, Fac Pharm, Dept Pharmaceut Microbiol, TR-06100 Ankara, Turkey. Univ Zurich, Inst Organ Chem, CH-8057 Zurich, Switzerland. RP Kirmizibekmez, H (reprint author), Hacettepe Univ, Fac Pharm, Dept Pharmacognosy, TR-06100 Ankara, Turkey. EM hasankbekmez@yahoo.com RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 25 TC 16 Z9 16 U1 2 U2 8 PU SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK PI ANKARA PA ATATURK BULVARI NO 221, KAVAKLIDERE, TR-06100 ANKARA, TURKEY SN 1300-0527 J9 TURK J CHEM JI Turk. J. Chem. PY 2005 VL 29 IS 1 BP 71 EP 81 PG 11 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA 906KT UT WOS:000227640300009 ER PT S AU Lorick, KL Jensen, JP Weissman, AM AF Lorick, KL Jensen, JP Weissman, AM BE Deshaies, RJ TI Expression, purification, and properties of the Ubc4/5 family of E2 enzymes SO UBIQUITIN AND PROTEIN DEGRADATION, PART A SE Methods in Enzymology LA English DT Review; Book Chapter ID UBIQUITIN-CONJUGATING ENZYME; ENDOPLASMIC-RETICULUM; DEGRADATION; RECEPTOR; IDENTIFICATION; PROTEIN AB Ubiquitin-conjugating enzymes (E2s) play a central role in ubiquitylation. They function to bridge the first, nonspecific step of ubiquitin activation by El with the transfer of activated ubiquitin to substrates by substrate-specific E3s. While sharing a common core UBC domain, members of this family exhibit significant specificity in their physical and functional interactions with E3s. Among the families of E2s, members of the yeast Ubc4/5 family are particularly well conserved in higher metazoans. In humans, these are represented by the UbcH5 family. Members of this ubiqutiously expressed family show a capacity to interact with a wide range of E3s from both HECT and RING finger families, making them particularly useful tools in the laboratory. Using the UbcH5 family as a prototype, this chapter describes methods for the expression, purification, and characterization of E2 enzymes in vitro and some of the basics for their use in experiments in cells. C1 NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, Frederick, MD 21702 USA. RP Lorick, KL (reprint author), NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, Frederick, MD 21702 USA. NR 14 TC 20 Z9 20 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182803-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 398 BP 54 EP 68 DI 10.1016/S0076-6879(05)98006-3 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDE02 UT WOS:000233007300006 PM 16275319 ER PT S AU Yang, YL Lorick, KL Jensen, JP Weissman, AM AF Yang, YL Lorick, KL Jensen, JP Weissman, AM BE Deshaies, RJ TI Expression and evaluation of RING finger proteins SO UBIQUITIN AND PROTEIN DEGRADATION, PART A SE Methods in Enzymology LA English DT Review; Book Chapter ID UBIQUITIN-CONJUGATING ENZYME; P53; MDM2 AB RING finger proteins represent the largest class of potential ubiquitin ligases. This chapter describes methods used to express and assess the activity of proteins containing RING fingers based on our experience with a number of different family members. In addition to general protocols for assessing activity, specific protocols are provided for evaluating the ubiquitylation of p53 by the RING finger E3 Hdm2/Mdm2. Use of these methods may help identify new E3s, dissect factors involved in ubiquitylation of substrates, and screen for molecules that affect ubiquitylation. C1 NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, Frederick, MD 21702 USA. RP Yang, YL (reprint author), NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, Frederick, MD 21702 USA. NR 13 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182803-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 398 BP 103 EP 112 DI 10.1016/S0076-6879(05)98010-5 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDE02 UT WOS:000233007300010 PM 16275323 ER PT S AU Anfinrud, P Schotte, F Wulff, M AF Anfinrud, P Schotte, F Wulff, M BE Kobayashi, T Okada, T Kobayashi, T Nelson, KA DeSilvestri, S TI Watching proteins function with picosecond time-resolved X-ray crystallography SO ULTRAFAST PHENOMENA XIV SE SPRINGER SERIES IN CHEMICAL PHYSICS LA English DT Proceedings Paper CT 14th International Conference on Ultrafast Phenomena CY JUL 25-30, 2004 CL Niigata, JAPAN SP Opt Soc Amer ID MYOGLOBIN AB We have developed the method of picosecond time-resolved crystallography and used this technique to investigate structural dynamics in biological macromolecules at ambient temperature. Time-resolved snapshots of myoglobin following flash photolysis of the CO adduct were determined with 150 ps time resolution and < 2 angstrom spatial resolution. The structures reveal numerous sites in which CO becomes transiently trapped, as well as correlated motion of the protein side chains. When a single point mutation was introduced in a position near the binding site (L29F), the departure of CO from the primary docking site was significantly accelerated. The dramatic differences in the correlated protein displacements provide a structural explanation for these kinetic differences. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Anfinrud, P (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0172-6218 BN 3-540-24110-8 J9 SPRINGER SERIES CHEM PY 2005 VL 79 BP 581 EP 585 PG 5 WC Optics SC Optics GA BBW62 UT WOS:000228159300177 ER PT J AU Goncalves, LF Espinoza, J Lee, W Romero, R AF Goncalves, LF Espinoza, J Lee, W Romero, R TI Should the frontal bone be visualized in midline sagittal views of the facial profile to assess the fetal nasal bones during the first trimester? SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Letter ID DOWN-SYNDROME; GESTATION; FETUSES; ULTRASOUND; ABSENCE; TRISOMY-21 C1 NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, 4707 St Antoine Blvd, Detroit, MI 48201 USA. EM warfiela@mail.nib.gov NR 15 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD JAN PY 2005 VL 25 IS 1 BP 90 EP 92 DI 10.1002/uog.1800 PG 3 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 891NI UT WOS:000226587400017 PM 15593318 ER PT S AU Kullman, L Winterhalter, M Bezrukov, SM AF Kullman, L Winterhalter, M Bezrukov, SM BE Reggiani, L Pennetta, C Akimov, V Alfinito, E Rosini, M TI Functional sub-conformations in protein folding: Evidence from single-channel experiments SO Unsolved Problems of Noise and Fluctuations SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 4th International Conference on Unsolved Problems of Noise and Fluctuations in Physics, Biology and High Technology CY JUN 06-10, 2005 CL Gallipoli, ITALY SP Lecce Univ & Dipartimento Ingegneria Innovazione, Off Naval Res Global, Inst Pure & Appl Phys, Italian Minist Univ & Res, European Commiss, CNR INFM, Nanotechnol Natl Lab, Prov Lecce, Momune Gallipoli, Hewlett Packard Invent, INFOTE, INTEL, Assoc Ind Lecce, Ind Liason Off Lecce, European Phys Soc, IEEE DE static disorder; fluctuations; noise analysis ID FACILITATED MEMBRANE-TRANSPORT; COLI OUTER-MEMBRANE; ESCHERICHIA-COLI; SUGAR TRANSLOCATION; INDIVIDUAL MOLECULES; LAMB CHANNEL; MALTOPORIN; FLUCTUATIONS; KINETICS; BINDING AB We study fluctuations in ion conductance and enzymatic activity of a channel-forming protein Maltoporin, at the single-molecular level. Specifically, we analyze time-persistent variability of these parameters from channel to channel and discuss our findings in the context of static disorder in protein folding. The natural function of Maltoporin is passive sugar translocation. Reconstituted into planar lipid bilayers this channel shows large fluctuations in both its ion conductance and sugar binding strength. The dynamic features of conductance fluctuations representing the dynamic disorder, were studied previously and showed a complex power-law behavior. In the present paper, trying to elucidate the impact of channel's static disorder on its enzymatic function, we have analyzed more than 130 single channels. We conclude that fluctuations of the binding strength in time (same single channel) are much smaller than its fluctuations in ensemble (different single channels). Importantly, the disorder in ion conductance shows no significant correlation with the disorder in the binding strength. Variations in protein folding that are responsible for variations in ion conductance do not seem to affect sugar binding. This leads us to a conclusion that Maltoporin and, generally, other proteins can exist in a wide set of fully functional (but distinctly different) sub-conformations. 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 27 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0289-2 J9 AIP CONF PROC PY 2005 VL 800 BP 343 EP 348 PG 6 WC Biology; Instruments & Instrumentation; Physics, Applied; Physics, Mathematical SC Life Sciences & Biomedicine - Other Topics; Instruments & Instrumentation; Physics GA BDP57 UT WOS:000234784700049 ER PT J AU Boyiadzis, M Nam, M Dahut, W AF Boyiadzis, M Nam, M Dahut, W TI Fulminant hepatic failure secondary to metastatic prostate cancer SO UROLOGIA INTERNATIONALIS LA English DT Article DE prostate cancer; metastasis; hepatic failure ID LIVER-DISEASE AB The most common sites of metastatic disease from prostate cancer include the bones, lymph nodes and less commonly the lungs, adrenal glands, brain and kidneys. Acute fulminant hepatic failure secondary to cancer metastasis is rare and has unique clinical presentation. We describe a case of fatal liver failure in a 71-year-old male due to metastases to the liver from a prostatic adenocarcinoma. Thus in patients with metastatic cancer and elevated liver function tests, the possibility of hepatic involvement by the cancer should be considered as a possible cause of hepatic failure. Copyright (C) 2005 S. Karger AG, Basel. C1 NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. RP Dahut, W (reprint author), NCI, Med Oncol Clin Res Unit, Bldg 10,Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM dahutw@mail.nih.gov NR 9 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-1138 J9 UROL INT JI Urol.Int. PY 2005 VL 74 IS 2 BP 185 EP 187 DI 10.1159/000083293 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 904IV UT WOS:000227490200019 PM 15756074 ER PT B AU Biesecker, LG AF Biesecker, Leslie G. BE Miller, RJ Brubaker, BH Peterson, JC TI Human genetic therapies and manipulations SO Viewing New Creations with Anabaptist Eyes: Ethics of Biotechnology LA English DT Proceedings Paper CT Conference on Ethics of Biotechnology - Viewing New Creations with Anabaptist Eyes CY NOV, 2003 CL Eastern Mennonite Univ, Harrisonburg, VA HO Eastern Mennonite Univ ID BARDET-BIEDL-SYNDROME C1 NIH, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU CASCADIA PUBLISHING HOUSE PI TELFORD PA 126 KLINGERMAN RD, TELFORD, PA 18969 USA BN 978-1-931038-32-4 PY 2005 BP 39 EP 57 PG 19 WC Biotechnology & Applied Microbiology; Ethics; Medical Ethics; Religion SC Biotechnology & Applied Microbiology; Social Sciences - Other Topics; Medical Ethics; Religion GA BGL32 UT WOS:000248149300003 ER PT J AU Purcell, RH Emerson, SU AF Purcell, Robert H. Emerson, Suzanne U. BE Thomas, H Lemon, S Zuckerman, A TI Natural history and experimental models SO VIRAL HEPATITIS, 3RD EDITION LA English DT Article; Book Chapter ID HEPATITIS-A-VIRUS; ACUTE VIRAL-HEPATITIS; CHRONIC LIVER-DISEASE; ANTHROPOSOPHIC LIFE-STYLE; MONKEYS AOTUS-TRIVIRGATUS; GUILLAIN-BARRE-SYNDROME; ACUTE-RENAL-FAILURE; DAY-CARE-CENTERS; FULMINANT-HEPATITIS; CELL-CULTURE C1 [Purcell, Robert H.; Emerson, Suzanne U.] NIAID, NIH, LID, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. RP Purcell, RH (reprint author), NIAID, NIH, LID, Hepatitis Viruses Sect, Bldg 50,Room 6523,50 S Dr, Bethesda, MD 20892 USA. NR 266 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98713-1 PY 2005 BP 109 EP 125 DI 10.1002/9780470987131.ch8 D2 10.1002/9780470987131 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BZS84 UT WOS:000302866100009 ER PT B AU Farci, P Bukh, J Purcell, RH AF Farci, Patrizia Bukh, Jens Purcell, Robert H. BE Thomas, H Lemon, S Zuckerman, A TI Natural history and experimental models SO VIRAL HEPATITIS, 3RD EDITION LA English DT Article; Book Chapter ID HEPATITIS-C-VIRUS; NON-B-HEPATITIS; NON-A-HEPATITIS; POST-TRANSFUSION HEPATITIS; HYPERVARIABLE REGION 1; POLYMERASE-CHAIN-REACTION; EXPERIMENTALLY INFECTED CHIMPANZEES; CONGENITAL COAGULATION DISORDERS; PRIMARY HEPATOCELLULAR-CARCINOMA; ENVELOPE GLYCOPROTEIN GP70 C1 [Farci, Patrizia] Univ Cagliari, Dipartimento Sci Med, Policlin Univ, I-09042 Cagliari, Italy. [Bukh, Jens] NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. [Purcell, Robert H.] NIAID, NIH, LID, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. RP Farci, P (reprint author), Univ Cagliari, Dipartimento Sci Med, Policlin Univ, SS 554 Biviosestu, I-09042 Cagliari, Italy. NR 293 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98713-1; 978-1-4051-3005-9 PY 2005 BP 439 EP 467 DI 10.1002/9780470987131.ch27 D2 10.1002/9780470987131 PG 29 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BZS84 UT WOS:000302866100028 ER PT J AU Purcell, RH Emerson, SU AF Purcell, Robert H. Emerson, Suzanne U. BE Thomas, H Lemon, S Zuckerman, A TI Prevention SO VIRAL HEPATITIS, 3RD EDITION LA English DT Article; Book Chapter ID HEPATITIS-E VIRUS; NON-B HEPATITIS; TRANSMITTED NON-A; LINKED-IMMUNOSORBENT-ASSAY; OPEN-READING FRAME-2; CAPSID PROTEIN; UNITED-STATES; RHESUS-MONKEYS; INSECT CELLS; E INFECTION C1 [Purcell, Robert H.] NIAID, NIH, LID, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. [Emerson, Suzanne U.] NIAID, NIH, LID, Mol Hepatitis Sect, Bethesda, MD 20892 USA. RP Purcell, RH (reprint author), NIAID, NIH, LID, Hepatitis Viruses Sect, Bldg 50,Room 6523,50 South Dr, Bethesda, MD 20892 USA. NR 125 TC 10 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98713-1 PY 2005 BP 635 EP 648 DI 10.1002/9780470987131.ch42 D2 10.1002/9780470987131 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BZS84 UT WOS:000302866100043 ER PT J AU Chakraborti, S Prabakaran, P Xiao, XD Dimitrov, DS AF Chakraborti, Samitabh Prabakaran, Ponraj Xiao, Xiaodong Dimitrov, Dimiter S. TI The SARS Coronavirus S Glycoprotein Receptor Binding Domain: Fine Mapping and Functional Characterization SO VIROLOGY JOURNAL LA English DT Article AB The entry of the SARS coronavirus (SCV) into cells is initiated by binding of its spike envelope glycoprotein (S) to a receptor, ACE2. We and others identified the receptor-binding domain (RBD) by using S fragments of various lengths but all including the amino acid residue 318 and two other potential glycosylation sites. To further characterize the role of glycosylation and identify residues important for its function as an interacting partner of ACE2, we have cloned, expressed and characterized various soluble fragments of S containing RBD, and mutated all potential glycosylation sites and 32 other residues. The shortest of these fragments still able to bind the receptor ACE2 did not include residue 318 (which is a potential glycosylation site), but started at residue 319, and has only two potential glycosylation sites (residues 330 and 357). Mutation of each of these sites to either alanine or glutamine, as well as mutation of residue 318 to alanine in longer fragments resulted in the same decrease of molecular weight (by approximately 3 kDa) suggesting that all glycosylation sites are functional. Simultaneous mutation of all glycosylation sites resulted in lack of expression suggesting that at least one glycosylation site (any of the three) is required for expression. Glycosylation did not affect binding to ACE2. Alanine scanning mutagenesis of the fragment S319-518 resulted in the identification of ten residues (K390, R426, D429, T431, I455, N473, F483, Q492, Y494, R495) that significantly reduced binding to ACE2, and one residue (D393) that appears to increase binding. Mutation of residue T431 reduced binding by about 2-fold, and mutation of the other eight residues -by more than 10-fold. Analysis of these data and the mapping of these mutations on the recently determined crystal structure of a fragment containing the RBD complexed to ACE2 (Li, F, Li, W, Farzan, M, and Harrison, S. C., submitted) suggested the existence of two hot spots on the S RBD surface, R426 and N473, which are likely to contribute significant portion of the binding energy. The finding that most of the mutations (23 out of 34 including glycosylation sites) do not affect the RBD binding function indicates possible mechanisms for evasion of immune responses. C1 [Chakraborti, Samitabh; Prabakaran, Ponraj; Xiao, Xiaodong; Dimitrov, Dimiter S.] NCI Frederick, Prot Interact Grp, LECB, CCR,NIH, Frederick, MD 21702 USA. RP Dimitrov, DS (reprint author), NCI Frederick, Prot Interact Grp, LECB, CCR,NIH, Frederick, MD 21702 USA. EM schakraborti@ncifcrf.gov; praba@ncifcrf.gov; xiaox@ncifcrf.gov; dimitrov@ncifcrf.gov NR 23 TC 29 Z9 32 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PY 2005 VL 2 AR 73 DI 10.1186/1743-422X-2-73 PG 10 WC Virology SC Virology GA V26AR UT WOS:000208519000073 PM 16122388 ER PT J AU De Silva, FS Moss, B AF De Silva, Frank S. Moss, Bernard TI Origin-independent plasmid replication occurs in vaccinia virus cytoplasmic factories and requires all five known poxvirus replication factors SO VIROLOGY JOURNAL LA English DT Article AB Background: Replication of the vaccinia virus genome occurs in cytoplasmic factory areas and is dependent on the virus-encoded DNA polymerase and at least four additional viral proteins. DNA synthesis appears to start near the ends of the genome, but specific origin sequences have not been defined. Surprisingly, transfected circular DNA lacking specific viral sequences is also replicated in poxvirus-infected cells. Origin-independent plasmid replication depends on the viral DNA polymerase, but neither the number of additional viral proteins nor the site of replication has been determined. Results: Using a novel real-time polymerase chain reaction assay, we detected a >400-fold increase in newly replicated plasmid in cells infected with vaccinia virus. Studies with conditional lethal mutants of vaccinia virus indicated that each of the five proteins known to be required for viral genome replication was also required for plasmid replication. The intracellular site of replication was determined using a plasmid containing 256 repeats of the Escherichia coli lac operator and staining with an E. coli lac repressor-maltose binding fusion protein followed by an antibody to the maltose binding protein. The lac operator plasmid was localized in cytoplasmic viral factories delineated by DNA staining and binding of antibody to the viral uracil DNA glycosylase, an essential replication protein. In addition, replication of the lac operator plasmid was visualized continuously in living cells infected with a recombinant vaccinia virus that expresses the lac repressor fused to enhanced green fluorescent protein. Discrete cytoplasmic fluorescence was detected in cytoplasmic juxtanuclear sites at 6 h after infection and the area and intensity of fluorescence increased over the next several hours. Conclusion: Replication of a circular plasmid lacking specific poxvirus DNA sequences mimics viral genome replication by occurring in cytoplasmic viral factories and requiring all five known viral replication proteins. Therefore, small plasmids may be used as surrogates for the large poxvirus genome to study trans-acting factors and mechanism of viral DNA replication. C1 [De Silva, Frank S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM fdesilva@niaid.nih.gov; bmoss@nih.gov NR 57 TC 18 Z9 18 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PY 2005 VL 2 AR 23 DI 10.1186/1743-422X-2-23 PG 12 WC Virology SC Virology GA V26AR UT WOS:000208519000023 PM 15784143 ER PT J AU Greenier, JL Van Rompay, KKA Montefiori, D Earl, P Moss, B Marthas, ML AF Greenier, Jennifer L. Van Rompay, Koen K. A. Montefiori, David Earl, Patricia Moss, Bernard Marthas, Marta L. TI Simian immunodeficiency virus (SIV) envelope quasispecies transmission and evolution in infant rhesus macaques after oral challenge with uncloned SIVmac251: increased diversity is associated with neutralizing antibodies and improved survival in previously immunized animals SO VIROLOGY JOURNAL LA English DT Article AB Background: Oral infection of infant macaques with simian immunodeficiency virus (SIV) is a useful animal model to test interventions to reduce postnatal HIV transmission via breast-feeding. We previously demonstrated that immunization of infant rhesus macaques with either modified vaccinia virus Ankara (MVA) expressing SIV Gag, Pol and Env, or live-attenuated SIVmac1A11 resulted in lower viremia and longer survival compared to unimmunized controls after oral challenge with virulent SIVmac251 (Van Rompay et al., J. Virology 77: 179-190, 2003). Here we evaluate the impact of these vaccines on oral transmission and evolution of SIV envelope variants. Results: Limiting dilution analysis of SIV RNA followed by heteroduplex mobility assays of the V1-V2 envelope (env) region revealed two major env variants in the uncloned SIVmac251 inoculum. Plasma sampled from all infants 1 week after challenge contained heterogeneous SIV env populations including one or both of the most common env variants in the virus inoculum; no consistent differences in patterns of env variants were found between vaccinated and unvaccinated infants. However, SIV env variant populations diverged in most vaccinated monkeys 3 to 5 months after challenge, in association with the development of neutralizing antibodies. Conclusions: These patterns of viral envelope diversity, immune responses and disease course in SIV-infected infant macaques are similar to observations in HIV-infected children, and underscore the relevance of this pediatric animal model. The results also support the concept that neonatal immunization with HIV vaccines might modulate disease progression in infants infected with HIV by breast-feeding. C1 [Greenier, Jennifer L.; Van Rompay, Koen K. A.; Marthas, Marta L.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Montefiori, David] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Earl, Patricia; Moss, Bernard] NIH, Lab Viral Dis, Bethesda, MD 20892 USA. [Marthas, Marta L.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. RP Marthas, ML (reprint author), Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. EM jlgreenier@yahoo.com; kkvanrompay@ucdavis.edu; monte@acpub.duke.edu; PEARL@niaid.nih.gov; BMOSS@niaid.nih.gov; mlmarthas@ucdavis.edu FU National Center for Research Resources [RR00169]; NIH/NIAID [AI39109, AI46320]; Elizabeth Glaser Pediatric AIDS Foundation [8-97] FX We thank D. Bennett, D. Brandt, I. Bolton, L. Brignolo, K. Christe, L. Hirst, A. Spinner, W. von Morgenland and the California National Primate Research Center Colony Services for expert technical assistance; M. Ma for assistance with image analysis of HMA gels; E. Delwart (Univ. of California, San Francisco) for useful discussions and suggestions. We thank Shilpa Hattangadi and Lynn Frampton for construction of recombinant MVAs. This work was supported by Public Health Science grant RR00169 from the National Center for Research Resources, NIH/NIAID grants AI39109 and AI46320 (MLM), and Elizabeth Glaser Scientist award #8-97 (MLM) from the Elizabeth Glaser Pediatric AIDS Foundation. NR 52 TC 16 Z9 17 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PY 2005 VL 2 AR 11 DI 10.1186/1743-422X-2-11 PG 15 WC Virology SC Virology GA V26AR UT WOS:000208519000011 PM 15710048 ER PT S AU Steven, AC Conway, JF Cheng, NQ Watts, NR Belnap, DM Harris, A Stahl, SJ Wingfield, PT AF Steven, AC Conway, JF Cheng, NQ Watts, NR Belnap, DM Harris, A Stahl, SJ Wingfield, PT BE Roy, P TI Structure, assembly, and antigenicity of hepatitis B virus capsid proteins SO VIRUS STRUCTURE AND ASSEMBLY SE Advances in Virus Research LA English DT Review; Book Chapter ID COMMON EVOLUTIONARY ORIGIN; SECRETORY CORE PROTEIN; HEPATOMA-CELL LINE; ESCHERICHIA-COLI; CRYOELECTRON MICROSCOPY; NUCLEOCAPSID ENVELOPMENT; ELECTRON CRYOMICROSCOPY; MONOCLONAL-ANTIBODY; SURFACE-ANTIGEN; 4-HELIX BUNDLE C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. Inst Biol Struct JP Ebel, Lab Microscopie Elect, F-38027 Grenoble, France. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. OI Conway, James/0000-0002-6581-4748 FU Intramural NIH HHS NR 90 TC 44 Z9 46 U1 2 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 BN 0-12-039863-X J9 ADV VIRUS RES JI Adv.Virus Res. PY 2005 VL 64 BP 125 EP 164 DI 10.1016/S0065-3527(05)64005-5 PG 40 WC Virology SC Virology GA BCS32 UT WOS:000231014200005 PM 16139594 ER PT S AU Ono, A Freed, EO AF Ono, A Freed, EO BE Roy, P TI Role of lipid rafts in virus replication SO VIRUS STRUCTURE AND ASSEMBLY SE Advances in Virus Research LA English DT Review; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; GPI-ANCHORED PROTEINS; SEMLIKI-FOREST-VIRUS; VESICULAR STOMATITIS-VIRUS; MURINE LEUKEMIA-VIRUS; RESPIRATORY SYNCYTIAL VIRUS; ROUS-SARCOMA-VIRUS; EPSTEIN-BARR-VIRUS; DETERGENT-RESISTANT MEMBRANE; HIV-1 ENVELOPE GLYCOPROTEIN C1 Natl Canc Inst Frederick, Virus Cell Interact Sect, HIV Drug Resistance Program, NIH, Ft Detrick, MD 21702 USA. RP Ono, A (reprint author), Natl Canc Inst Frederick, Virus Cell Interact Sect, HIV Drug Resistance Program, NIH, Ft Detrick, MD 21702 USA. OI Ono, Akira/0000-0001-7841-851X NR 264 TC 92 Z9 93 U1 1 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 BN 0-12-039863-X J9 ADV VIRUS RES JI Adv.Virus Res. PY 2005 VL 64 BP 311 EP 358 DI 10.1016/S0065-3527(05)64010-9 PG 48 WC Virology SC Virology GA BCS32 UT WOS:000231014200010 PM 16139599 ER PT J AU Lehky, SR Sejnowski, TJ Desimone, R AF Lehky, SR Sejnowski, TJ Desimone, R TI Selectivity and sparseness in the responses of striate complex cells SO VISION RESEARCH LA English DT Article DE vision; macaque monkey; modeling; information theory; sparse coding ID INFERIOR TEMPORAL CORTEX; PRIMARY VISUAL-CORTEX; NATURAL IMAGES; RECEPTIVE-FIELDS; SPATIAL-FREQUENCY; INFORMATION-TRANSMISSION; ASSOCIATIVE MEMORY; NEURONS; STATISTICS; FILTERS AB Probability distributions of macaque complex cell responses to a large set of images were determined. Measures of selectivity were based on the overall shape of the response probability distribution, as quantified by either kurtosis or entropy. We call this non-parametric selectivity, in contrast to parametric selectivity, which measures tuning curve bandwidths. To examine how receptive field properties affected non-parametric selectivity, two models of complex cells were created. One was a standard Gabor energy model, and the other a slight variant constructed from a Gabor function and its Hilbert transform. Functionally, these models differed primarily in the size of their DC responses. The Hilbert model produced higher selectivities than the Gabor model, with the two models bracketing the data from above and below. Thus we see that tiny changes in the receptive field profiles can lead to major changes in selectivity. While selectivity looks at the response distribution of a single neuron across a set of stimuli, sparseness looks at the response distribution of a population of neurons to a single stimulus. In the model, we found that on average the sparseness of a population was equal to the selectivity of cells comprising that population, a property we call ergodicity. We raise the possibility that high sparseness is the result of distortions in the shape of response distributions caused by non-linear, information-losing transforms, unrelated to information theoretic issues of efficient coding. (c) 2004 Elsevier Ltd. All rights reserved. C1 RIKEN, Brain Sci Inst, Cognit Brain Mapping Lab, Wako, Saitama 3510198, Japan. Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92037 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Lehky, SR (reprint author), Salk Inst Biol Studies, Computat Neurosci Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM sidney@salk.edu FU Howard Hughes Medical Institute NR 55 TC 33 Z9 33 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PY 2005 VL 45 IS 1 BP 57 EP 73 DI 10.1016/j.visres.2004.07.021 PG 17 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 908DH UT WOS:000227767000006 PM 15571738 ER PT J AU Barsony, J AF Barsony, Julia BE Feldman, D TI Vitamin D Receptor and Retinoid X Receptor Subcellular Trafficking SO VITAMIN D: VOLS 1 AND 2, 2ND EDITION LA English DT Article; Book Chapter ID NUCLEAR-LOCALIZATION SIGNAL; D-MEDIATED TRANSCRIPTION; GLUCOCORTICOID-RECEPTOR; DNA-BINDING; NUCLEOCYTOPLASMIC TRANSPORT; LIVING CELLS; IN-VIVO; INTERACTING PROTEIN; HORMONE-RECEPTORS; ANDROGEN RECEPTOR C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Barsony, J (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 92 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-252687-9 PY 2005 BP 363 EP 379 PG 17 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BCV82 UT WOS:000311626800024 ER PT S AU Aoyagi, S Trotter, KW Archer, TK AF Aoyagi, S Trotter, KW Archer, TK BE Litwack, G TI ATP-dependent chromatin remodeling complexes and their role in nuclear receptor-dependent transcription in vivo SO VITAMINS AND HORMONES SE Vitamins and Hormones LA English DT Review; Book Chapter ID THYROID-HORMONE RECEPTOR; MAMMALIAN SWI/SNF COMPLEXES; TUMOR VIRUS PROMOTER; GLUCOCORTICOID-RECEPTOR; HISTONE DEACETYLASE; MMTV PROMOTER; SACCHAROMYCES-CEREVISIAE; ESTROGEN-RECEPTOR; PROTEIN METHYLTRANSFERASE; NUCLEOSOMAL ARRAYS AB Nuclear receptors (NRs) are ligand-dependent transcription factors that mediate transcription of target genes in chromatin. Modulation of chromatin structure plays an important part in the NR-mediated transcription process. ATP-dependent chromatin remodeling complexes have been shown to be intimately involved in NR-mediated transcription. In this review, we examine the role of chromatin remodeling complexes in facilitating the recruitment of coregulators and basal transcription factors. In addition, the role of subunit specificity within the chromatin remodeling complexes, the complexes' influence on remodeling activity, and complexes' recruitment to the NR-responsive promoters are discussed. (c) 2005 Elsevier Inc. C1 NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Aoyagi, S (reprint author), NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 171 TC 24 Z9 24 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 0-12-709870-4 J9 VITAM HORM JI Vitam. Horm. PY 2005 VL 70 BP 281 EP 307 DI 10.1016/S0083-6729(05)70009-1 PG 27 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BCD20 UT WOS:000228718900009 PM 15727808 ER PT B AU Cybulski, W AF Cybulski, W BE Carignan, Y DuMerer, D Koutsky, SK Lindquist, EN McClurken, KM McElrath, DP TI Print collections and their possible futures SO Who Wants Yesterday's Paper?: Essays on the Research Value of Printed Materials in the Digital Age LA English DT Proceedings Paper CT Symposium on Who Wants Yesterdays Papers CY MAR 01, 2002 CL Univ Maryland, Coll Pk, MD SP Univ Maryland, Coll Informat Studies, Univ Maryland, Lib HO Univ Maryland C1 Univ Maryland, Coll Informat Studies, Qual Assurance Unit, Natl Lib Med, College Pk, MD 20742 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU SCARECROW PRESS PI METUCHEN PA 52 LIBERTY ST, PO BOX 656, METUCHEN, NJ 08840 USA BN 0-8108-5119-9 PY 2005 BP 99 EP 113 PG 15 WC Information Science & Library Science SC Information Science & Library Science GA BCQ39 UT WOS:000230719900012 ER PT B AU Le, DX Thoma, GR AF Le, Daniel X. Thoma, George R. BE Callaos, N Lesso, W TI Automatically creating biomedical bibliographic records from printed volumes of old indexes SO WMSCI 2005: 9th World Multi-Conference on Systemics, Cybernetics and Informatics, Vol 3 LA English DT Proceedings Paper CT 9th World Multi-Conference on Systemics, Cybernetics and Informatics CY JUL 10-13, 2005 CL Orlando, FL DE Quarterly Cumulative Index Medicus; document image analysis; document scanning; OLDMEDLINE database; National Library of Medicine AB To provide online access to citations from old hardeopy indexes published from 1879 through 1965, an R&D division of the National Library of Medicine (NLM) is developing an automated system to convert bibliographic information in volumes of the printed Quarterly Cumulative Index Medicus (QCIM) to machine-readable form for inclusion in the OLDMIEDLINE (R) database. The system processes images scanned from a QCIM volume, segments and labels the image Tecords, identifies multiple occurrences of the same record in the volume, and creates unique citation records. The record segmentation and labeling technology is based on a smearing bottom-up approach for text block segmentation, the document page layout formats, and a set of rules for record labeling that is derived from the QCIM document format guideline. Since bibliographic information can be arranged as both "author entries" and "subject entries" in a QCIM document, the duplicate records have to be detected and combined to create a single unique citation. The duplicate records are identified based on matching "cross-reference" information such as author names, journal title abbreviation, volume, pagination, month, and year among different entries of the same citation. The "cross-reference" information can also be used to correct OCR errors resulting in improving the quality of citations created. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Le, DX (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU INT INST INFORMATICS & SYSTEMICS PI ORLANDO PA 14269 LORD BARCLAY DR, ORLANDO, FL 32837 USA BN 978-980-6560-55-0 PY 2005 BP 269 EP 274 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Computer Science, Software Engineering; Computer Science, Theory & Methods; Telecommunications SC Computer Science; Telecommunications GA BFP83 UT WOS:000243670400050 ER PT B AU Kim, IC Le, DX Thoma, GR AF Kim, In Cheol Le, Daniel X. Thoma, George R. BE Callaos, N Lesso, W Palesi, M TI Automated cleanup processing for extracting bibliographic data from biomedical online journals SO WMSCI 2005: 9TH WORLD MULTI-CONFERENCE ON SYSTEMICS, CYBERNETICS AND INFORMATICS, VOL 4 LA English DT Proceedings Paper CT 9th World Multi-Conference on Systemics, Cybernetics and Informatics CY JUL 10-13, 2005 CL Orlando, FL DE automated cleanup processing; online biomedical journal; bibliographic information; rule-based approach; learning process; MEDLINE (R) database; National Library of Medicine AB An R&D division of the National Library of Medicine (NLM) has developed the Web-based Medical Article Records System (WebNLARS) to create citations from online biomedical journals. This paper presents one important part of this system, the automated cleanup module that extracts bibliographic information from HTML-formatted text based on a rule-based approach. A learning scheme comparing the output of the cleanup module to the verified processing result is newly introduced to create and update cleanup rules automatically, thereby minimizing the manual effort for rule setting and improving the performance of the cleanup processing. Experimental results show that the proposed automated cleanup module can effectively detect and extract the bibliographic data of interest from HTML-formatted online journal articles using relevant rules identified through the learning process. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Kim, IC (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM ickim@mail.nih.gov; daniel@mail.nih.gov; gthoma@mail.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU INT INST INFORMATICS & SYSTEMICS PI ORLANDO PA 14269 LORD BARCLAY DR, ORLANDO, FL 32837 USA BN 978-980-6560-56-7 PY 2005 BP 401 EP 405 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BFP96 UT WOS:000243684900072 ER PT B AU Kim, J Le, DX Thoma, GR AF Kim, Jongwoo Le, Daniel X. Thoma, George R. BE Callaos, N Lesso, W Palesi, M TI Automated labeling of biomedical online journal articles SO WMSCI 2005: 9TH WORLD MULTI-CONFERENCE ON SYSTEMICS, CYBERNETICS AND INFORMATICS, VOL 4 LA English DT Proceedings Paper CT 9th World Multi-Conference on Systemics, Cybernetics and Informatics CY JUL 10-13, 2005 CL Orlando, FL DE Automated Labeling; HTML; online journals; Labeling; Fuzzy Rule-Based Algorithm; statistics; WebMARS; NLM ID DOCUMENT IMAGES AB An automated labeling (AL) module has been developed to automate the extraction of bibliographic data (e.g., article title, authors, affiliation, abstract, and others) from online biomedical journals for the National Library of Medicine's MEDLINES database. The AL module employs string matching, statistics, and fuzzy rule-based algorithms to identify segmented zones in an article's HTML pages as specific bibliographic data. Experiments conducted with 1,267 medical articles from 64 journal issues show about 97.71% accuracy. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Kim, J (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 14 TC 0 Z9 0 U1 0 U2 1 PU INT INST INFORMATICS & SYSTEMICS PI ORLANDO PA 14269 LORD BARCLAY DR, ORLANDO, FL 32837 USA BN 978-980-6560-56-7 PY 2005 BP 406 EP 411 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BFP96 UT WOS:000243684900073 ER PT J AU Urizar, GG Hurtz, SQ Albright, CL Ahn, DK Atienza, AA King, AC AF Urizar, Guido G., Jr. Hurtz, Shannon Q. Albright, Cheryl L. Ahn, David K. Atienza, Audie A. King, Abby C. TI Influence of maternal stress on successful participation in a physical activity intervention: The IMPACT project SO WOMEN & HEALTH LA English DT Article DE physical activity; women; maternal stress; mothers; family ID CARDIORESPIRATORY FITNESS; MOTIVATIONAL READINESS; EUROPEAN-AMERICAN; RANDOMIZED-TRIAL; DECISION-MAKING; SOCIAL SUPPORT; LEISURE-TIME; AGED WOMEN; EXERCISE; MOTHERS AB Few studies have examined the impact of motherhood on successful participation in physical activity (PA) interventions. The current study focused on mothers in the Increasing Motivation for Physical Activity or IMPACT study, which aimed to promote PA in sedentary, low-income, ethnically diverse women (74% Latina). The aim of this study was to determine whether certain maternal variables (e.g., number of children, number and intensity of maternal stressors) influenced successful participation in an 8-week, class-based, PA intervention. PA consisted of accumulating 30 minutes or more of moderate-intensity activities (e.g., walking) five or more days a week. Sixty-eight mothers (average age = 32 years) were assessed at baseline and 10 weeks. Paired comparison t-tests demonstrated a significant increase in PA-related energy expenditure from baseline to 10 weeks 3 < 0.05). Furthermore, this increase in PA was significantly associated with a decrease in the number of maternal stressors reported over this time period (p < 0.01). Simultaneous regression analyses indicated that (1) having a higher number of maternal stressors at baseline was associated with lower class attendance (p <= 0.05) and (2) rating these maternal stressors (e.g., unable to control children's behavior) as being more stressful at baseline was associated with lower levels of PA at 10 weeks (p <= 0.01), independent of the number of children at home. These results Suggest that the number and intensity of perceived maternal stressors may negatively impact attempts to become more physically active. Interventions should address such stressors. C1 Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA. NCI, Hlth Promot Res Branch, Bethesda, MD 20892 USA. RP Urizar, GG (reprint author), Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Hoover Pavil,Room N229,211 Quarry Rd, Stanford, CA 94305 USA. EM urizar@stanford.edu FU NHLBI NIH HHS [HL58914, 5T32HL07034] NR 48 TC 23 Z9 23 U1 3 U2 5 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2005 VL 42 IS 4 BP 63 EP 82 DI 10.1300/J013v42n04_04 PG 20 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 093EE UT WOS:000241149800004 PM 16782676 ER PT J AU Johnson, DM Worell, J Chandler, RK AF Johnson, DM Worell, J Chandler, RK TI Assessing psychological health and empowerment in women: The personal progress scale revised SO WOMEN & HEALTH LA English DT Article DE empowerment; resilience; feminist therapy ID MENTAL-HEALTH; CONCEPTUALIZATION; TRAUMA AB Empowerment is a primary outcome of many health interventions with women. Typical outcome measures, however, focus exclusively on specific symptoms, neglecting the clinically important attitudes and behaviors associated with increased empowerment and well-being. Empowerment is conceptualized as enabling women to access skills and resources to cope more effectively with current as well as future stress and trauma. This study investigated a new measure of personal empowerment in women, the Personal Progress Scale-Revised (PPS-R). Results suggest that the PPS-R is a promising measure of empowerment in women, demonstrating excellent reliability and validity in diverse sample of women. Additionally, the PPS-R demonstrated preliminary utility with a subgroup of abused women, a vulnerable group of women for whom empowerment is a variable of high importance. C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. Univ Kentucky, Lexington, KY 40506 USA. RP Johnson, DM (reprint author), 444 N Main St,4th Floor Ambulatory Bldg, Akron, OH 44310 USA. EM johnsod@summahealth.org NR 38 TC 30 Z9 31 U1 6 U2 22 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2005 VL 41 IS 1 BP 109 EP 129 DI 10.1300/J013v41nm01_07 PG 21 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 959CX UT WOS:000231495600007 PM 16048871 ER PT J AU Warburton, G Nares, S Angelov, N Brahim, JS Dionne, RA Wahl, SM AF Warburton, G Nares, S Angelov, N Brahim, JS Dionne, RA Wahl, SM TI Transcriptional events in a clinical model of oral mucosal tissue injury and repair SO WOUND REPAIR AND REGENERATION LA English DT Article ID GENE-EXPRESSION; INHIBITOR; SKIN; ANGIOGENESIS; TARGETS; PROTEIN; FAMILY; EGR-1; PAIN AB Tissue injury in the oral mucosa activates a cascade of transcriptional events important during the healing process that are not yet clearly defined. To characterize these events and identify potential gene targets for 14 future studies, we used cDNA expression arrays in a clinical model of tissue injury, Mucosal biopsies were taken before third molar extraction, 2-4 hours postoperatively, or at 48 hours. Hybridization patterns were analyzed and validated using real-time polymerase chain reaction. Prior to extraction, the biopsied mucosal tissues were characterized by a panoply of genes that were constitutively expressed. After injury, analysis revealed differential expression of genes involved in transcription, inflammation, and remodeling. At 2-4 hours after injury, genes such as Fos, Jun, and early growth response protein were up-regulated, while genes responsible for intercellular adhesion were down-regulated. At 48 hours after injury, the gene profile had shifted toward tissue remodeling. Here we identify genes constitutively expressed in normal oral mucosa and transcriptional events following mucosal tissue injury, which may be useful in identifying new therapeutic targets. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD USA. RP Warburton, G (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM smwahl@dir.nidcr.nih.gov NR 27 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1067-1927 EI 1524-475X J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JAN-FEB PY 2005 VL 13 IS 1 BP 19 EP 26 DI 10.1111/j.1067-1927.2005.130104.x PG 8 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 897NU UT WOS:000227012700004 PM 15659033 ER PT J AU Kamei, M Weinstein, BM AF Kamei, Makoto Weinstein, Brant M. TI Long-Term Time-Lapse Fluorescence Imaging of Developing Zebrafish SO ZEBRAFISH LA English DT Article AB A variety of different transgenic zebrafish lines have been generated expressing green fluorescent protein (GFP) or other fluorescent proteins in different organs and tissues, permitting dynamic visualization of development of these organs and tissues in living animals via time-lapse imaging. Although methods have been devised for short- to medium-term time-lapse imaging of transgenic zebrafish, these methods are not suitable for longer term imaging because of poor control over temperature, evaporation, and anoxia. We describe a new imaging chamber that provides continuously circulating flow of warm, oxygenated aqueous media. We show that the chamber can be used for multiphoton time-lapse imaging of developing blood vessels in the trunk of Fli1-EGFP transgenic zebrafish for 5 days without developmental delay, loss of viability, or evident reduction in strength of circulatory flow. This imaging chamber provides an important new tool for long-term dynamic imaging of transgenic zebrafish. C1 [Kamei, Makoto; Weinstein, Brant M.] Natl Inst Child Hlth & Human Dev NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. RP Weinstein, BM (reprint author), NICHD, Mol Genet Lab, NIH, Bldg 6B,Room 309,6 Ctr Dr, Bethesda, MD 20892 USA. EM flyingfish@nih.gov OI Kamei, Makoto/0000-0002-1438-0783 FU NICHD FX B.M.W. is supported by the intramural program of the NICHD. NR 21 TC 28 Z9 29 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 J9 ZEBRAFISH JI Zebrafish PY 2005 VL 2 IS 2 BP 113 EP 123 DI 10.1089/zeb.2005.2.113 PG 11 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA V18DG UT WOS:000207984900005 PM 18248171 ER PT J AU Zhu, XX Greig, NH Yu, QS Utsuki, T Holloway, HW Lahiri, DK Brossi, A AF Zhu, XX Greig, NH Yu, QS Utsuki, T Holloway, HW Lahiri, DK Brossi, A TI Synthesis of 3-alkylidene-isoindolinones via sulphide contraction SO HETEROCYCLES LA English DT Article ID FRIEDEL-CRAFTS REACTIONS; NECROSIS-FACTOR-ALPHA; THALIDOMIDE; HETEROANNULATION; ANALOGS AB Isoindolinones are essential moieties in numerous natural products, chemical research tools and therapeutics. Syntheses of such isoindoline containing agents may occur through precursors, particularly via 3-alkylidene-isoindolinones. An alternate approach be can achieved via sulphide contraction, described herein. As an example, phthalimide was thionated with Lawesson's reagent to give monothiophthalimide (4), which on stirring with alpha-bromoketones in the presence of base led to the Eschenmoser coupling reaction. In this manner, compounds (5, 6a and 6b) were formed by alkylation of monothiophthalimide with various a-bromoketones, followed by elimination of sulfur. For the compounds (6a and 6b), (Z)-3-alkylidene-isoindolinones were generated as a single product and no (E)-isomer was separated from the reaction mixture. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM GreigN@grc.nia.nih.gov NR 12 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD DEC 31 PY 2004 VL 64 BP 93 EP 99 PG 7 WC Chemistry, Organic SC Chemistry GA 897UZ UT WOS:000227032200014 ER PT J AU Wong, EY Lin, J Forget, BG Bodine, DM Gallagher, PG AF Wong, EY Lin, J Forget, BG Bodine, DM Gallagher, PG TI Sequences downstream of the erythroid promoter are required for high level expression of the human alpha-spectrin gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; MEMBRANE SKELETAL PROTEINS; DIMER-DIMER ASSOCIATION; BETA-GLOBIN PROMOTER; HEREDITARY PYROPOIKILOCYTOSIS; CHROMATIN STRUCTURE; FUNCTIONAL DOMAINS; MAMMALIAN-CELLS; TRANSGENIC MICE; GAMMA-GLOBIN AB alpha-Spectrin is a membrane protein critical for the flexibility and stability of the erythrocyte. We are attempting to identify and characterize the molecular mechanisms controlling the erythroid-specific expression of the alpha-spectrin gene. Previously, we demonstrated that the core promoter of the human alpha-spectrin gene directed low levels of erythroid-specific expression only in the early stages of erythroid differentiation. We have now identified a region 3' of the core promoter that contains a DNase I hypersensitive site and directs high level, erythroid-specific expression in reporter gene/transfection assays. In vitro DNase I footprinting and electrophoretic mobility shift assays identified two functional GATA-1 sites in this region. Both GATA-1 sites were required for full activity, suggesting that elements binding to each site interact in a combinatorial manner. This region did not demonstrate enhancer activity in any orientation or position relative to either the alpha-spectrin core promoter or the thymidine kinase promoter in reporter gene assays. In vivo studies using chromatin immunoprecipitation assays demonstrated hyperacetylation of this region and occupancy by GATA-1 and CBP (cAMP-response element-binding protein (CREB)-binding protein). These results demonstrate that a region 3' of the alpha-spectrin core promoter contains a GATA-1-dependent positive regulatory element that is required in its proper genomic orientation. This is an excellent candidate region for mutations associated with decreased alpha-spectrin gene expression in patients with hereditary spherocytosis and hereditary pyropoikilocytosis. C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. RP Gallagher, PG (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St,POB 208064, New Haven, CT 06520 USA. EM patrick.gallagher@yale.edu FU NHLBI NIH HHS [HL 65448] NR 62 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 31 PY 2004 VL 279 IS 53 BP 55024 EP 55033 DI 10.1074/jbc.M408886200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 882TI UT WOS:000225960800007 PM 15456760 ER PT J AU Liu, JG Guan, XQ Tamura, T Ozato, K Ma, XJ AF Liu, JG Guan, XQ Tamura, T Ozato, K Ma, XJ TI Synergistic activation of interleukin-12 p35 gene transcription by interferon regulatory factor-1 and interferon consensus sequence-binding protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NATURAL-KILLER-CELLS; NF-KAPPA-B; PROINFLAMMATORY CYTOKINE; IL-12 PRODUCTION; DENDRITIC CELLS; P40 EXPRESSION; C-REL; IRF-1; PROMOTER; MACROPHAGES AB Interferon regulatory factor-1 (IRF-1) and interferon consensus sequence-binding protein (ICSBP or IRF-8) are two members of the IRF family of transcription factors that play critical roles in interferon signaling in a wide range of host responses to infection and malignancy. Interleukin-12 (IL-12) is a key factor in the induction of innate resistance and generation of T helper type 1 cells and cytotoxic T lymphocytes. In this work, we find that ICSBP-deficient macrophages are highly defective in the production of IL-12. The defect is also observed at the level of IL-12 p40 and p35 mRNA expression. Transcriptional analyses revealed that ICSBP is a potent activator of the IL-12 p35 gene. It acts through a site localized to -226 to -219, named ICSBP-response element (ICSBP-RE), in the human IL-12 p35 promoter through physical association with IRF-1 both in vitro and in vivo. Co-expression of ICSBP and IRF-1 synergistically stimulates the IL-12 p35 promoter activity. Mutations at the ICSBP-RE results in the loss of protein binding as well as transcriptional activation by ICSBP alone or together with IRF-1. This study provides novel mechanistic information on how signals initiated during innate and adaptive immune responses synergize to yield greater IL-12 production and sustained cellular immunity. C1 Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, 1300 York Ave, New York, NY 10021 USA. EM xim2002@med.cornell.edu FU NCI NIH HHS [CA 79772]; NIAID NIH HHS [AI 045899] NR 31 TC 68 Z9 69 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 31 PY 2004 VL 279 IS 53 BP 55609 EP 55617 DI 10.1074/jbc.M406565200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 882TI UT WOS:000225960800079 PM 15489234 ER PT J AU Barthelmes, HU Habermeyer, M Christensen, MO Mielke, C Interthal, H Pouliot, JJ Boege, F Marko, D AF Barthelmes, HU Habermeyer, M Christensen, MO Mielke, C Interthal, H Pouliot, JJ Boege, F Marko, D TI TDP1 overexpression in human cells counteracts DNA damage mediated by topoisomerases I and II SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRAND BREAK REPAIR; PHOSPHODIESTERASE TDP1; COVALENT COMPLEXES; SPINOCEREBELLAR ATAXIA; ENZYME; YEAST; CAMPTOTHECIN; MECHANISM; PATHWAYS; PROTEINS AB Tyrosyl DNA phosphodiesterase 1 (TDP1) is a repair enzyme that removes adducts, e. g. of topoisomerase I from the 3'-phosphate of DNA breaks. When expressed in human cells as biofluorescent chimera, TDP1 appeared more mobile than topoisomerase I, less accumulated in nucleoli, and not chromosome-bound at early mitosis. Upon exposure to camptothecin both proteins were cleared from nucleoli and rendered less mobile in the nucleoplasm. However, with TDP1 this happened much more slowly reflecting most likely the redistribution of nucleolar structures upon inhibition of rDNA transcription. Thus, a steady association of TDP1 with topoisomerase I seems unlikely, whereas its integration into repair complexes assembled subsequently to the stabilization of DNA.topoisomerase I intermediates is supported. Cells expressing GFP-tagged TDP1 > 100-fold in excess of endogenous TDP1 exhibited a significant reduction of DNA damage induced by the topoisomerase I poison camptothecin and could be selected by that drug. Surprisingly, DNA damage induced by the topoisomerase II poison VP-16 was also diminished to a similar extent, whereas DNA damage independent of topoisomerase I or II was not affected. Overexpression of the inactive mutant GFP-TDP1(H263A) at similar levels did not reduce DNA damage by camptothecin or VP-16. These observations confirm a requirement of active TDP1 for the repair of topoisomerase I-mediated DNA damage. Our data also suggest a role of TDP1 in the repair of DNA damage mediated by topoisomerase II, which is less clear. Since overexpression of TDP1 did not compromise cell proliferation, it could be a pleiotropic resistance mechanism in cancer therapy. C1 Univ Dusseldorf, Sch Med, Inst Clin Chem & Lab Diagnost, D-40225 Dusseldorf, Germany. Univ Kaiserslautern, Dept Chem, Div Food Chem & Environm Technol, D-67663 Kaiserslautern, Germany. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. NIMH, Mol Biol Lab, Bethesda, MD 20894 USA. RP Boege, F (reprint author), Univ Dusseldorf, Sch Med, Inst Clin Chem & Lab Diagnost, Moorenstr 5, D-40225 Dusseldorf, Germany. EM Boege@med.uni-duesseldorf.de RI Marko, Doris/B-9354-2014 OI Marko, Doris/0000-0001-6568-2944 NR 33 TC 68 Z9 70 U1 0 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 31 PY 2004 VL 279 IS 53 BP 55618 EP 55625 DI 10.1074/jbc.M405042200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 882TI UT WOS:000225960800080 PM 15494395 ER PT J AU Wong, DS Zhang, JY Awasthi, Y Sharma, A Rogers, L Matlock, EF Van Lint, C Karpova, T McNally, J Harrod, R AF Wong, DS Zhang, JY Awasthi, Y Sharma, A Rogers, L Matlock, EF Van Lint, C Karpova, T McNally, J Harrod, R TI Nerve growth factor receptor signaling induces histone acetyltransferase domain-dependent nuclear translocation of p300/CREB-binding protein-associated factor and hGCN5 acetyltransferases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CDK-INHIBITOR P21(WAF1/CIP1); TRANSCRIPTION FACTOR CREB; LONG-TERM FACILITATION; VIRUS TYPE-1 TAX; SYMPATHETIC NEURONS; PC12 CELLS; BINDING PROTEIN; PHOSPHATIDYLINOSITOL 3-KINASE; SYNAPTIC-TRANSMISSION; HIPPOCAMPAL-NEURONS AB The transcriptional coactivators, p300/CREB-binding protein-associated factor (PCAF) and hGCN5, are recruited to chromatin-remodeling complexes on enhancers of various gene promoters in response to growth factor stimulation. However, the molecular mechanisms by which surface receptor signals modulate the assembly of nuclear transcription complexes are not fully understood. Here we report that nerve growth factor receptor signaling induces nuclear translocation of PCAF and hGCN5 dependent upon the phosphorylation of Ser and Thr residues within their histone acetyltransferase domains, which requires activation of PI3K, Rsk2(pp90), and MSK-1. Neurotrophin stimulation induces p53(K320) acetylation by PCAF and transcriptionally activates p53-responsive enhancer elements within the p21(WAF/CIP1) promoter associated with G(1)/S arrest during neuronal differentiation. Most importantly, these findings represent the first evidence for signal-dependent nuclear translocation of PCAF and hGCN5 acetyltransferases and allude to a novel mechanism for ligand/receptor modulation of nuclear chromatin-remodeling complexes in neurons. C1 So Methodist Univ, Dept Biol Sci, Mol Virol Lab, Dallas, TX 75275 USA. Free Univ Brussels, Inst Biol & Med Mol, Chim Biol Lab, B-6041 Gosselies, Belgium. NCI, Lab Receptor Biol & Gene Express, Fluorescence Imaging Facil, Ctr Canc Res ,NIH, Bethesda, MD 20892 USA. RP Harrod, R (reprint author), So Methodist Univ, Dept Biol Sci, Mol Virol Lab, 334-DLS,6501 Airline Dr, Dallas, TX 75275 USA. EM rharrod@mail.smu.edu NR 61 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 31 PY 2004 VL 279 IS 53 BP 55667 EP 55674 DI 10.1074/jbc.M408174200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 882TI UT WOS:000225960800086 ER PT J AU He, LS Grammer, AC Wu, XL Lipsky, PE AF He, LS Grammer, AC Wu, XL Lipsky, PE TI TRAF3 forms heterotrimers with TRAF2 and modulates its ability to mediate NF-kappa B activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR RECEPTOR; RESONANCE ENERGY-TRANSFER; LYMPHOTOXIN-BETA-RECEPTOR; TERMINAL KINASE; C-JUN; SUBCELLULAR-LOCALIZATION; FLUORESCENT PROTEIN; SPLICE-VARIANT; SINGLE-LASER; RING FINGER AB FRET experiments utilizing confocal microscopy or flow cytometry assessed homo- and heterotrimeric association of human tumor necrosis factor receptor-associated factors (TRAF) in living cells. Following transfection of HeLa cells with plasmids expressing CFP- or YFP-TRAF fusion proteins, constitutive homotypic association of TRAF2, -3, and -5 was observed, as well as heterotypic association of TRAF1-TRAF2 and TRAF3-TRAF5. A novel heterotypic association between TRAF2 and -3 was detected and confirmed by immunoprecipitation in Ramos B cells that constitutively express both TRAF2 and -3. Experiments employing deletion mutants of TRAF2 and TRAF3 revealed that this heterotypic interaction minimally involved the TRAF-C domain of TRAF3 as well as the TRAF-N domain and zinc fingers 4 and 5 of TRAF2. A novel flow cytometric FRET analysis utilizing a two-step approach to achieve linked FRET from CFP to YFP to HcRed established that TRAF2 and -3 constitutively form homo- and heterotrimers. The functional importance of TRAF2-TRAF3 heterotrimerization was demonstrated by the finding that TRAF3 inhibited spontaneous NF-kappaB, but not AP-1, activation induced by TRAF2. Ligation of CD40 on Ramos B cells by recombinant CD154 caused TRAF2 and TRAF3 to dissociate, whereas overexpression of TRAF3 in Ramos B cells inhibited CD154-induced TRAF2-mediated activation of NF-kappaB. Together, these results reveal a novel association between TRAF2 and TRAF3 that is mediated by unique portions of each protein and that specifically regulates activation of NF-kappaB, but not AP-1. C1 NIAMS, NIH, US Dept HHS, Bethesda, MD 20892 USA. NIH, Glow Cytometry Sect, Off Sci & Technol, US Dept HHS, Bethesda, MD 20892 USA. NIH, Cell Biol Grp B, Autoimmun Branch, US Dept HHS, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMS, NIH, US Dept HHS, 9000 Rockville Pike,Bldg 10,Rm 9N228, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov NR 56 TC 48 Z9 54 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 31 PY 2004 VL 279 IS 53 BP 55855 EP 55865 DI 10.1074/jbc.M407284200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 882TI UT WOS:000225960800109 PM 15383523 ER PT J AU Chung, MC Kawamoto, S AF Chung, MC Kawamoto, S TI IRF-2 is involved in up-regulation of nonmuscle myosin heavy chain II-A gene expression during phorbol ester-induced promyelocytic HL-60 differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR IRF-2; IN-VITRO; FACTOR-2; CELLS; ACTIVATION; IDENTIFICATION; REQUIRES; FECHTNER; MUTATION; MUSCLE AB Transcription of the nonmuscle myosin heavy chain II-A (NMHC-A) gene is regulated by various factors, including cell type, proliferation and differentiation stage, and extracellular stimuli. We have identified an intronic region (designated 32kb-150), which is located 32 kb downstream of the transcription start sites in the human NMHC-A gene, as a transcriptional regulatory region. 32kb-150 contains an interferon-stimulated response element (ISRE). By using HeLa and NIH3T3 cells, in which NMHC-A is constitutively expressed, interferon regulatory factor (IRF)-2 was found to be the only major protein, among the IRF family proteins, that bound to the ISRE in 32kb-150 both in vitro and in intact cells. IRF-2, which is known to either repress or activate target gene expression, acts as a transcriptional activator in the context of the 32kb-150 reporter gene. The carboxyl-terminal basic region of IRF-2 serves as an activation domain in this context. This is in contrast to its acting as a repressor domain in the context of the synthetic core ISRE. Furthermore, after treatment of promyelocytic HL-60 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), which triggers differentiation into macrophages, both NMHC-A expression and IRF-2 expression were found to be up-regulated with a similar time course. TPA treatment leads to recruitment of IRF-2 to 32kb-150 of the endogenous NMHC-A gene and acetylation of the core histones surrounding this region. In addition, the ISRE in the 32kb-150 reporter gene recruits IRF-2 and mediates TPA-induced activation of a reporter gene in HL-60 cells. Together, these results indicate that IRF-2 contributes to transcriptional activation of the NMHC-A gene via 32kb-150 during TPA-induced differentiation of HL-60 cells. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Kawamoto, S (reprint author), Bldg 10,Rm 8N202,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. EM kawamots@mail.nih.gov NR 49 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 31 PY 2004 VL 279 IS 53 BP 56042 EP 56052 DI 10.1074/jbc.M404791200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 882TI UT WOS:000225960800128 PM 15496418 ER PT J AU Abul-Hassan, KS Lehnert, BE Guant, L Walmsley, R AF Abul-Hassan, KS Lehnert, BE Guant, L Walmsley, R TI Abnormal DNA repair in selenium-treated human cells SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE selenium; DNA repair; host cell reactivation assay; challenge assay ID NUCLEOTIDE EXCISION-REPAIR; TOXIC METAL-IONS; SERUM SELENIUM; VITAMIN-E; SUBSEQUENT RISK; LUNG-CANCER; DAMAGE; BRCA1; ZINC; SUPPLEMENTATION AB Selenium (Se), a micronutrient and an environmental, a chemical and an industrial agent in many products, can have genotoxic effects as well as antimutagenic and/or anticarcinogenic properties, depending on its concentration and oxidation state. We investigated the cytotoxic response of human osteosarcoma (U2OS) cells to low doses of sodium selenite and assayed their resistivity to cisplatin treatment and their capacity to reactivate cisplatin-treated reporter system, whose repair occurs through the transcription coupled repair (TCR) pathway, using the Host Cell Reactivation (HCR) Assay. In addition, we examined the ability of Se-treated human primary lymphocytes for normal double-strand breaks rejoining (DSBR) using the Challenge assay. Although, U2OS cells did not demonstrate cytotoxicity to all Se doses used, as measured by the cell proliferation MTT assay, their resistivity to cisplatin was significantly reduced. Moreover, Se-treated cells exhibited a significant reduction in their capacity for TCR as compared with untreated control cells. Primary human blood lymphocytes demonstrated cytotoxicity to Se treatment at only a concentration of 10 muM. There were no significant increases in chromosome-type deletions or chromatid breaks or in mitotic indices in cells treated with Se alone or Se plus ionizing irradiation. However, dicentric chromosomes significantly increased upon treatment with 1 muM Se plus irradiation as compared with Se-untreated irradiated control. These findings demonstrate direct evidence on the inhibitory effect of inorganic Se on cellular DNA repair capacity. (C) 2004 Published by Elsevier B.V. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. St Marys Hosp, Manchester M13 0JH, Lancs, England. UMIST, Dept Biomol Sci, Manchester M60 1QD, Lancs, England. RP Abul-Hassan, KS (reprint author), Univ Manchester, Dept Biomol Sci, G10 Manchester, Manchester M60 1QD, Lancs, England. EM khaled_abul_hassan@hotmail.com NR 49 TC 20 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD DEC 31 PY 2004 VL 565 IS 1 BP 45 EP 51 DI 10.1016/j.mrgentox.2004.09.004 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 881KZ UT WOS:000225867700005 PM 15576238 ER PT J AU Sarkar, TK Basak, S Wainer, I Moaddel, R Yamaguchi, R Jozwiak, K Chen, HT Link, CC AF Sarkar, TK Basak, S Wainer, I Moaddel, R Yamaguchi, R Jozwiak, K Chen, HT Link, CC TI Coaxing a pyridine nucleus to give up its aromaticity: Synthesis and pharmacological characterization of novel conformationally restricted analogues of nicotine and anabasine SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DIELS-ALDER REACTIONS; O-QUINODIMETHANE ANALOGS; ACETYLCHOLINE-RECEPTOR; CONSTRAINED NICOTINES; FUNCTIONALIZED O-BIS(CHLOROMETHYL)PYRIDINES; 1-ARYLNAPHTHALENE LIGNANS; HETEROCYCLIC-ANALOGS; ALKALOID SYNTHESIS; INDOLE ALKALOIDS; 4+2 CYCLOADDUCTS AB A series of novel nicotine and anabasine related conformationally restricted compounds including those with pi-bonds in the connecting tether were synthesized following the hitherto unprecedented phenylsulfanyl group assisted generation of pyridine o-quinodimethane intermediates and their trapping by an intramolecular Diels-Alder reaction. Pharmacological characterization of some of these analogues at activating alpha3beta4 nAChRs was investigated, and constrained anabasine analogues 35 and 43 as well as constrained nicotine analogue 42 were found to exhibit moderately potent nicotinic agonist activity. Of special note is the fact that the pyrrolidinic nitrogen in these compounds is bound to a carbomethoxy group and, therefore, is not free to be protonated unlike all the known analogues of nicotine and anabasine, specifically designed as nAChRs agonists/antagonists. The structure-activity relationship studies indicate that when pi-cation interaction is absent, the position of chlorine atom in the pyridine ring and steric bulk at the connecting tether between the pyridine and pyrrolidine ring of the constrained nicotinic ligands are important descriptors for their binding affinity at alpha4beta2 and alpha3beta4 nAChRs as well as the subtype selectivity issue. These findings are likely to improve our understanding of the structural requirements for selectivity, which, at present, is probably the most important goal in the field of nicotinic ligands. C1 Indian Inst Technol, Dept Chem, Kharagpur 721302, W Bengal, India. NIA, Gerontol Res Ctr, NIH, Baltimore, MD USA. Acad Sinica, Inst Chem, Taipei 115, Taiwan. RP Sarkar, TK (reprint author), Indian Inst Technol, Dept Chem, Kharagpur 721302, W Bengal, India. EM tksr@chem.iitkgp.ernet.in RI Chen, Hui-Ting/C-5520-2009 NR 69 TC 12 Z9 12 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 30 PY 2004 VL 47 IS 27 BP 6691 EP 6701 DI 10.1021/jm049707c PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 882QC UT WOS:000225952400008 PM 15615518 ER PT J AU Zhou, SM Kern, ER Gullen, E Cheng, YC Drach, JC Matsumi, S Mitsuya, H Zemlicka, J AF Zhou, SM Kern, ER Gullen, E Cheng, YC Drach, JC Matsumi, S Mitsuya, H Zemlicka, J TI (Z)- and (E)-[2-fluoro-2-(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines, a new class of methylenecyclopropane analogues of nucleosides: Synthesis and antiviral activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PURINE NUCLEOSIDES; VIRUS; SYNADENOL; GUANINE; AGENTS AB The Z- and E-isomers of fluoromethylenecyclopropane analogues 11a-d and 12a-d were synthesized, and their antiviral activities were evaluated. The purine (Z,E)-methylenecyclopropane carboxylates 13 and 24 were selectively fluorinated using lithium diisopropylamide, LiCl, and N-fluorobenzenesulfonimide to give (Z,E)-fluoroesters 22 and 25. Reduction with LiBH4 or diisobutylaluminum hydride gave after chromatographic separation Z-isomers 11a and 11e and E-isomers 12a and 12e. The O-demethylation of 11e and 12e afforded guanine analogues 11b and 12b. Fluorination of (Z,E)-cytosine and thymine esters 15 and 16 afforded (Z,E)-fluoroesters 26 and 27, which were resolved before the reduction to analogues 11c and 11d and 12c and 12d. Adenine Z-isomer 11a was the most effective against Towne and AD 169 strains of human cytomegalovirus (HCMV, EC50 3.6 and 6.0 muM, respectively), but it was less effective against murine virus (MCMV, EC50 69 muM). Thymine Z-isomer 11d was effective against HSV-1 in BSC-1 cells (ELISA, EC50 2.5 muM) but inactive against HSV-1 or HSV-2 in Vero or HFF cells. All of the analogues with the exception of 12d were effective at least in one of the assays against Epstein-Barr virus (EBV) in Daudi or H-1 cells in a micromolar or submicromolar range. Cytosine and thymine Z-isomers 11c and 11d were active against varicella zoster virus (VZV) with EC50 0.62 muM. Adenine Z- and E-isomers 11a and 12a were effective against HIV-1 in MT-2 or MT-4 cells with EC50 12-22 and 2.3-7.6 muM, respectively, whereas only 12a was effective against hepatitis B virus (HBV) with EC50 15 muM. Analogues 11a and 12a were weak substrates for adenosine deaminase. C1 Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Chem,Dev Therapeut Program, Detroit, MI 48201 USA. Univ Alabama, Sch Med, Dept Pediat, Birmingham, AL 35233 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48019 USA. Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 860, Japan. NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Zemlicka, J (reprint author), Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Chem,Dev Therapeut Program, Detroit, MI 48201 USA. EM zemlicka@kci.wayne.edu FU NCI NIH HHS [R01-CA32779, R01-CA44358]; NIAID NIH HHS [P01-AI46390] NR 29 TC 31 Z9 33 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 30 PY 2004 VL 47 IS 27 BP 6964 EP 6972 DI 10.1021/jm040093l PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 882QC UT WOS:000225952400035 PM 15615545 ER PT J AU Szapacs, ME Mathews, TA Tessarollo, L Lyons, WE Mamounas, LA Andrews, AM AF Szapacs, ME Mathews, TA Tessarollo, L Lyons, WE Mamounas, LA Andrews, AM TI Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article; Proceedings Paper CT 10th International Conference on In Vivo Methods CY JUN 24-27, 2003 CL Karolinska Inst, Stockholm, SWEDEN HO Karolinska Inst DE BDNF knockout mice; serotonin transporter knockout mice; depression; anxiety disorders; antidepressant; aging; neurodegeneration; micro-dialysis; ELISA ID KNOCK-OUT MICE; ELEMENT-BINDING PROTEIN; ADULT-RAT BRAIN; MESSENGER-RNA; IN-VIVO; QUANTITATIVE MICRODIALYSIS; ANTIDEPRESSANT DRUGS; GENE-EXPRESSION; ENVIRONMENTAL ENRICHMENT; EXTRACTION FRACTION AB Serotonin (5-HT) has been proposed to promote neuronal plasticity during the treatment of mood and anxiety disorders and following neurodegenerative insult by altering the expression of critical genes including brain-derived neurotrophic factor (BDNF). In this study mice with constitutive reductions in the serotonin transporter (SERT) or BDNF were investigated to further assess the functional relationship between serotonin neurotransmission and BDNF expression. Using a modified extraction procedure and a commercial enzyme-linked immunosorbant assay, 50% decreases in BDNF protein in hippocampus, frontal cortex and brain stem were confirmed in 4-month-old mice lacking one copy, of the BDNF gene (BDNF+/-). By contrast, 4-month-old male and female mice with partial (SERT+/-) or complete (SERT-/-) reductions in SERT expression showed no differences in BDNF protein levels compared to SERT+/+ mice. although male SERT knockout mice of all genotypes had higher BDNF levels in hippocampus, frontal cortex. and brain stern than female animals. Microdialysis also was performed in BDNF+/- mice. In addition to other phenotypic aspects suggestive of altered serotonin neurotransmission. BDNF+/- mice show, accelerated age-related degeneration of 5-HT forebrain innervation. Nevertheless. extracellular 5-HT levels determined by zero net flux microdialysis were similar between BDNF+/+ and BDNF+/- mice in striatum and frontal cortex at 8-12 months of age. These data illustrate that a 50%. decrease in BDNF does not appear to be sufficient to cause measurable changes in basal extracellular 5-HT concentrations and, furthermore. that constitutive reductions in SERT expression are not associated with altered BDNF protein levels at the ages and in the brain re-pons examined in this study. (C) 2004 Elsevier B.V. All rights reserved. C1 Penn State Univ, Dept Chem, University Pk, PA 16802 USA. Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA. NCI, Neurol Dev Grp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Mol Embryol Sect, Frederick Canc Res & Dev Ctr, ABL,Basic Res Program, Frederick, MD 21702 USA. NINDS, NIH, Sci Review Branch, Ctr Neurosci, Bethesda, MD 20892 USA. NINDS, NIH, Extramural Res Program, Ctr Neurosci, Bethesda, MD 20892 USA. RP Andrews, AM (reprint author), Penn State Univ, Dept Chem, 152 Davey Lab, University Pk, PA 16802 USA. EM ama11@psu.edu RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 FU NIMH NIH HHS [MH067713, MH064756] NR 78 TC 89 Z9 91 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD DEC 30 PY 2004 VL 140 IS 1-2 BP 81 EP 92 DI 10.1016/j.jneumeth.2004.03.026 PG 12 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 885TO UT WOS:000226180100013 PM 15589338 ER PT J AU Mathews, TA Fedele, DE Coppelli, FM Avila, AM Murphy, DL Andrews, AM AF Mathews, TA Fedele, DE Coppelli, FM Avila, AM Murphy, DL Andrews, AM TI Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expression SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article; Proceedings Paper CT 10th International Conference on In Vivo Methods CY JUN 24-27, 2003 CL Karolinska Inst, Stockholm, SWEDEN HO Karolinska Inst DE serotonin transporter; knockout; microdialysis; zero net flux; serotonin; 5-hydroxyindoteacetic acid; dopamine; 3-4-dihydroxyphenylacetic acid; monoamine oxidase ID CAPILLARY LIQUID-CHROMATOGRAPHY; 5-HT1A RECEPTOR ANTAGONISTS; MEDIAL PREFRONTAL CORTEX; IN-VIVO MICRODIALYSIS; KNOCK-OUT MICE; MONOAMINE-OXIDASE; QUANTITATIVE MICRODIALYSIS; NUCLEUS-ACCUMBENS; BRAIN-SEROTONIN; FRONTAL-CORTEX AB Serotonin (5-HT) plays an integral regulatory role in mood, anxiety, cognition. appetite and aggressive behavior. Many therapeutic and illicit drugs that modulate these functions act at the serotonin transporter (SERT), thus a mouse model with reduced transporter expression was created to further investigate the effects of differential serotonin reuptake. In the present study. in vivo microdialysis was used to determine homeostatic alterations in extracellular 5-HT levels in unanesthetized SERT knockout mice. SERT-/- mice had significantly higher levels of basal dialysate 5-HT than SERT+/+ mice in striatum and frontal cortex. In addition. although gene-specific increases in 5-HT were evident. neuroadaptive alterations in dialysate dopamine levels were not detected in striatum. Zero net flux microdialysis was utilized to further investigate alterations in extracellular 5-HT. Using this method, a gene dose-dependent increase in extraneuronal 5-HT was observed in striatum (2.8 +/- 1.9.4 +/- 1 and 18 +/- 3 nM) and frontal cortex (1.4 +/- 0.4, 3.5 +/- 0.9 and 14 +/- 1 nM) in SERT+/+, SERT+/- and SERT-/- mice. respectively. Potassium stimulation revealed greater depolarization-induced increases in striatal 5-HT but not dopamine in SERT-/- mice. Furthermore, dialysate 5-hydroxyindoleacetic acid (5-HIAA) levels were reduced in striatum in a gene dose-dependent manner. while DOPAC was unchanged in SERT knockout mice. Finally. determination of monoamine oxidase (MAO) activity revealed no significant differences in K-M or V-max of type-A or type-B isozymes indicating that alterations in SERT expression do not cause adaptive changes in the activities of these key catabolic enzymes. Overall, these results demonstrate that constitutive reductions in SERT are associated with increase's in 5-HT in the extracellular signaling space in the absence of changes in dopamine neurochemistry. Furthermore. use of zero net flux microdialysis appears warranted in investigations of serotonergic synaptic function where modest changes in extracellular 5-HT are. thought to occur in response to altered uptake. (C) 2004 Elsevier B.V. All rights reserved. C1 Penn State Univ, Dept Chem, University Pk, PA 16802 USA. Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Andrews, AM (reprint author), Penn State Univ, Dept Chem, 104 Chem Bldg, University Pk, PA 16802 USA. EM ama11@psu.edu RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 FU NIMH NIH HHS [R01MH64756, R03MH067713] NR 94 TC 156 Z9 157 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD DEC 30 PY 2004 VL 140 IS 1-2 BP 169 EP 181 DI 10.1016/j.jneumeth.2004.05.017 PG 13 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 885TO UT WOS:000226180100022 PM 15589347 ER PT J AU Paik, S Shak, S Tang, G Kim, C Baker, J Cronin, M Baehner, FL Walker, MG Watson, D Park, T Hiller, W Fisher, ER Wickerham, DL Bryant, J Wolmark, N AF Paik, S Shak, S Tang, G Kim, C Baker, J Cronin, M Baehner, FL Walker, MG Watson, D Park, T Hiller, W Fisher, ER Wickerham, DL Bryant, J Wolmark, N TI A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; GENE-EXPRESSION PATTERNS; SURGICAL ADJUVANT BREAST; PROGNOSTIC-FACTORS; COLORECTAL-CANCER; TUMOR-MARKERS; ESTROGEN; SURVIVAL; INTEROBSERVER; CHEMOTHERAPY AB BACKGROUND: The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. METHODS: We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. RESULTS: Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. CONCLUSIONS: The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer. C1 Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Div Pathol, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA USA. Genom Hlth, Redwood City, CA USA. Univ Pittsburgh, Dept Stat, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Paik, S (reprint author), BSABP, Div Pathol, 4 Allegheny Ctr,5th Fl,E Commons Profess Bldg, Pittsburgh, PA 15212 USA. EM spaik.nejm@nsabp.org NR 41 TC 2875 Z9 2968 U1 13 U2 115 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 30 PY 2004 VL 351 IS 27 BP 2817 EP 2826 DI 10.1056/NEJMoa041588 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 883IH UT WOS:000226004300006 PM 15591335 ER PT J AU Ferris, FL AF Ferris, FL TI A new treatment for ocular neovascularization SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ARGON-LASER PHOTOCOAGULATION; RANDOMIZED CLINICAL-TRIALS; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; CHOROIDAL NEOVASCULARIZATION; VERTEPORFIN; MACULOPATHY; THERAPY C1 NIH, Bethesda, MD 20892 USA. RP Ferris, FL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 14 TC 8 Z9 8 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 30 PY 2004 VL 351 IS 27 BP 2863 EP 2865 DI 10.1056/NEJMe048316 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 883IH UT WOS:000226004300014 PM 15625339 ER PT J AU Goldstein, DS AF Goldstein, DS TI Case 27-2004: Multiple-system atrophy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ORTHOSTATIC HYPOTENSION C1 NINDS, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 30 PY 2004 VL 351 IS 27 BP 2882 EP 2882 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 883IH UT WOS:000226004300030 ER PT J AU Woods, SC D'Alessio, DA Tso, P Rushing, PA Clegg, DJ Benoit, SC Gotoh, K Liu, M Seeley, RJ AF Woods, SC D'Alessio, DA Tso, P Rushing, PA Clegg, DJ Benoit, SC Gotoh, K Liu, M Seeley, RJ TI Consumption of a high-fat diet alters the homeostatic regulation of energy balance SO PHYSIOLOGY & BEHAVIOR LA English DT Article; Proceedings Paper CT Workshop on Dietary Fat and Energy Balance - Myths and Facts CY JUL 07-11, 2003 CL Ascona, SWITZERLAND SP Ctr Stefano Franscini, Masterfoods, Nestec AC, Proctor & Gamble, Swiss Natl Sci Fdn DE high-fat diet; homeostatic regulation; energy balance ID APOLIPOPROTEIN A-IV; CENTRAL-NERVOUS-SYSTEM; FOOD-INTAKE; BODY-WEIGHT; METABOLIC SYNDROME; RAT HYPOTHALAMUS; OBESITY EPIDEMIC; INSULIN; SIGNALS; LEPTIN AB Humans in many countries are currently experiencing what has been called an epidemic of obesity. That is, the average body weight (and amount of fat stored in the body) is increasing over years, carrying with it a multitude of associated medical, psychological, and economic problems. While there is no shortage of possible causes of this epidemic, increased availability and consumption of high-fat (HF), calorically dense and generally quite palatable food is often touted as a likely culprit. In order to better assess the impact of consuming a diet with those qualities, we have developed a well-controlled animal model in which the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Long-Evans rats are fed one of two semipurified pelleted diets, a HF diet that contains 20% fat by weight and a low-fat (LF) diet that contains 4% fat by weight. Pair-fed animals consume the HF diet but are limited to the daily caloric intake of LF rats. Another group receives pelleted chow. Relative to animals consuming diets low in fat, HF animals weigh more, have more carcass fat, are hyperinsulinemic and hyperleptinemic, and are insulin resistant. HF-fed animals, independent of whether they become obese or not, also have central insulin and MTII insensitivity. Finally, HF rats have a down-regulated hypothalamic apo A-IN system that could contribute to their hyperphagia. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45237 USA. Univ Cincinnati, Dept Med, Cincinnati, OH USA. Univ Cincinnati, Dept Pathol, Cincinnati, OH USA. NIDDK, Review Branch, NIH, Bethesda, MD USA. RP Woods, SC (reprint author), Univ Cincinnati, Dept Psychiat, 2170 E Galbraith Rd, Cincinnati, OH 45237 USA. EM steve.woods@psychiatry.uc.edu OI Seeley, Randy/0000-0002-3721-5625 NR 48 TC 94 Z9 99 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC 30 PY 2004 VL 83 IS 4 BP 573 EP 578 DI 10.1016/j.physbeh.2004.07.026 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 887AF UT WOS:000226273900005 PM 15621062 ER PT J AU Williams, W Reimold, M Kerich, M Hommer, D Bauer, M Heinz, A AF Williams, W Reimold, M Kerich, M Hommer, D Bauer, M Heinz, A TI Glucose utilization in the medial prefrontal cortex correlates with serotonin turnover rate and clinical depression in alcoholics SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE depression; serotonin turnover rate; cerebrospinal fluid; medial prefrontal cortex; positron emission tomography ID ANTERIOR CINGULATE CORTEX; METABOLISM; DISORDERS; PET AB We measured the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), regional cerebral glucose uptake (rCMRglc) as assessed with positron emission tomography in the medial prefrontal cortex (PFC) and severity of clinical depression (Beck's Depression Inventory, BDI) in detoxified male alcoholics and age-matched healthy men. In alcoholics, the severity of clinical depression was negatively correlated with rCMRglc in the medial PFC and positively with CSF 5-HIAA concentrations. A voxel-based analysis showed that the strongest correlation between CSF 5-HIAA levels and rCMRglc was found in alcoholics in the left orbitofrontal and medial PFC (BA10 and BA11); no significant correlations were observed among healthy control subjects. This pilot study indicates that a dysfunction of medial PFC may interact with central serotonin turnover and negative mood states during early abstinence. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Med Berlin, Dept Psychiat & Psychotherapy, Charite, D-10117 Berlin, Germany. Univ Tubingen, Dept Nucl Med, Tubingen, Germany. Univ Tubingen, PET Ctr, Tubingen, Germany. NIAAA, NIH, Bethesda, MD USA. RP Heinz, A (reprint author), Univ Med Berlin, Dept Psychiat & Psychotherapy, Charite, Charite Campus Mitte, D-10117 Berlin, Germany. EM andreas.heinz@charite.de NR 27 TC 6 Z9 6 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 30 PY 2004 VL 132 IS 3 BP 219 EP 224 DI 10.1016/j.pscyhresns.2004.07.004 PG 6 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 897HX UT WOS:000226995700003 PM 15664793 ER PT J AU Harry, GJ Harris, MW Burka, LT AF Harry, GJ Harris, MW Burka, LT TI Mercury concentrations in brain and kidney following ethylmercury, methylmercury and Thimerosal administration to neonatal mice SO TOXICOLOGY LETTERS LA English DT Article DE thimerosal; mercury; tissue distribution ID RAT-BRAIN; EXPOSURE; TISSUE; VACCINES; INFANTS AB The distribution of mercury to the brain following an injection of methylmercury (MeHg) or ethylmercury (EtHg) was examined in immature mice. Postnatal day (PND) 16 CD 1 mice received MeHg chloride either by IM injection or by gavage. At 24 h and 7 days post-injection, total mercury concentrations were determined in blood, kidney, brain, and muscle by cold vapor atomic fluorescence spectrometry. At 24 h, an IM injection of MeHg chloride (17.4 mug) produced total mercury concentrations in the blood (6.2 +/- 0.9 mug/g), brain (5.6 +/- 1.3 mug; 0.6% delivered dose), and kidney (25.2 +/- 5.6 mug; 1.1%), approximately 30% of that obtained from oral administration (blood: 17.9 +/- 1.0 mug; brain: 16.1 +/- 1.2 mug, 1.5%; kidney: 64.9 +/- 6.3 mug, 2.7%). For comparison, PND 16 mice received an IM injection of concentrated dosing suspensions (2 mul dosing vol.) for EtHg chloride (6 mug) or Thimerosal (15.4 mug). For EtHg, approximately 0.39 +/- 0.06% of the injected mercury was detected in the brain and 3.5 +/- 0.6% in the kidney at 24 h. Thimerosal IM injection resulted in 0.22 +/- 0.04% in the brain, and 1.7 +/- 0.3% in the kidney. By 7 days, mercury levels decreased in the blood but were unchanged in the brain. An acute IM injection to adult mice of each suspension at a 10-fold higher dose resulted an average 0.1% mercury in the brain, and higher levels in the blood, kidney, and muscle as compared to the young. In immature mice, MeHg delivered via oral route of administration resulted in significantly greater tissue levels as compared to levels from IM injection. Comparisons of tissue distribution following IM administration suggest that an oral route of administration for mercury is not comparable to an IM delivery and that MeHg does not appear to be a good model for EtHg-containing compounds. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NIEHS, Neurobiol Lab, Neurotoxicol Grp, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, NIH, Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, NIH, Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), NIEHS, Neurobiol Lab, Neurotoxicol Grp, POB 12233,MD C1-04, Res Triangle Pk, NC 27709 USA. EM harry@niesh.nih.gov NR 28 TC 43 Z9 44 U1 2 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 30 PY 2004 VL 154 IS 3 BP 183 EP 189 DI 10.1016/j.toxlet.2004.07.014 PG 7 WC Toxicology SC Toxicology GA 870QJ UT WOS:000225072600003 PM 15501610 ER PT J AU Zhou, T Jia, XD Chapin, RE Maronpot, RR Harris, MW Liu, J Waalkes, MP Eddy, EM AF Zhou, T Jia, XD Chapin, RE Maronpot, RR Harris, MW Liu, J Waalkes, MP Eddy, EM TI Cadmium at a non-toxic dose alters gene expression in mouse testes SO TOXICOLOGY LETTERS LA English DT Article DE cadmium; microarray; real-time RT-PCR; testes; mouse ID IN-VIVO; REPAIR INHIBITION; INDUCED APOPTOSIS; MAMMALIAN-CELLS; INJECTION SITE; DNA-DAMAGE; REAL-TIME; PROSTATE; RAT; SPERMATOGENESIS AB The testes are important targets of cadmium (Cd)-induced toxicity and carcinogenicity in rodents. Exposure to Cd at environmentally relevant low levels is a significant human health concern, but the effects of Cd on the rodent testes at doses that do not cause overt lesions are poorly defined. We used cDNA microarray and quantitative real-time RT-PCR assays to determine gene expression profiles in the testes of CD-1 mice 12-72 h after a single s.c. injection of 5 mumol/kg CdCl2. This dose of Cd did not produce overt histopathological changes, but clearly altered the expression of some genes that are likely to be important in toxicity responses. The most significant changes in gene expression occurred 24 h after treatment, corresponding to when the highest level of Cd was detected in the testes. Increased expression of the C-myc and Egr1 genes strongly suggests acute stress responses. Repressed expression of cell cycle-regulated cyclin B1 and CDC2 proteins indicates a potential for causing G2/M arrest and disturbance of meiosis. Decreased expression of pro-apoptotic genes, particularly Casp3, and DNA repair genes possibly contributes to Cd-induced carcinogenesis. These results indicate that changes in gene expression occur well before overt effects of Cd-induced testicular toxicity and carcinogenicity are apparent. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod Toxicol Grp, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI,NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM eddy@niehs.nih.gov OI Chapin, Robert/0000-0002-5997-1261 NR 32 TC 57 Z9 61 U1 0 U2 11 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 30 PY 2004 VL 154 IS 3 BP 191 EP 200 DI 10.1016/j.toxlet.2004.07.015 PG 10 WC Toxicology SC Toxicology GA 870QJ UT WOS:000225072600004 PM 15501611 ER PT J AU Kanwar, R Fortini, ME AF Kanwar, R Fortini, ME TI Notch signaling: A different sort makes the cut SO CURRENT BIOLOGY LA English DT Editorial Material ID UBIQUITIN LIGASE; ENDOCYTOSIS; DELTA; ACTIVATION; RECEPTOR; PROTEIN; PATHWAY; FATE AB Notch signaling is regulated by ubiquitination of the receptor and its extracellular ligands. New studies reveal distinct ubiquitination-dependent endosomal sorting pathways in which ligand-bound Notch is activated while unliganded Notch is recycled or degraded, facilitating signaling while preventing inappropriate activation of unstimulated receptors. C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RP Kanwar, R (reprint author), NCI, Lab Prot Dynam & Signaling, 1050 Boyles St, Frederick, MD 21701 USA. EM fortini@ncifcrf.gov NR 20 TC 15 Z9 15 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 29 PY 2004 VL 14 IS 24 BP R1043 EP R1045 DI 10.1016/j.cub.2004.11.041 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 884FE UT WOS:000226069400009 PM 15620635 ER PT J AU Sun, HY Nikolovska-Coleska, Z Yang, CY Xu, L Liu, ML Tomita, Y Pan, HG Yoshioka, Y Krajewski, K Roller, PP Wang, SM AF Sun, HY Nikolovska-Coleska, Z Yang, CY Xu, L Liu, ML Tomita, Y Pan, HG Yoshioka, Y Krajewski, K Roller, PP Wang, SM TI Structure-based design of potent, conformationally constrained Smac mimetics SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID APOPTOSIS; PROTEIN; XIAP; SMAC/DIABLO; CASPASE; INHIBITOR; BINDING; CANCER C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Natl Canc Inst Frederick, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. RP Wang, SM (reprint author), Univ Michigan, Dept Internal Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM shaomeng@med.umich.edu RI Wang, Shaomeng/E-9686-2010 FU NCI NIH HHS [R91 CA 109025] NR 14 TC 114 Z9 117 U1 0 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 29 PY 2004 VL 126 IS 51 BP 16686 EP 16687 DI 10.1021/ja047438+ PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 882AI UT WOS:000225910400001 PM 15612682 ER PT J AU Ratnasinghe, LD Abnet, C Qiao, YL Modali, R Stolzenberg-Solomon, R Dong, ZW Dawsey, SM Mark, SD Taylor, PR AF Ratnasinghe, LD Abnet, C Qiao, YL Modali, R Stolzenberg-Solomon, R Dong, ZW Dawsey, SM Mark, SD Taylor, PR TI Polymorphisms of XRCC1 and risk of esophageal and gastric cardia cancer SO CANCER LETTERS LA English DT Article DE esophageal cancer; gastric cardia cancer; polymorphism; XRCC1 ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; SQUAMOUS-CELL CARCINOMA; DNA-REPAIR PROFICIENCY; BREAST-CANCER; CASE-COHORT; GENE XRCC1; MINERAL SUPPLEMENTATION; CHINESE POPULATION; VITAMIN AB Background: Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma in the world. In a nested case-cohort study that originated from two cancer prevention trials in Linxian, we examined the relationship between these cancers and two polymorphisms in the DNA repair gene XRCC1. Methods: We conducted a case-cohort study among individuals in the cohort who were alive and cancer free in 199 1, and had blood samples for DNA extraction. Real time Taqman analyses were conducted to genotype incident cancer cases (n = 221, 131 esophageal and 90 gastric cardia cancer cases) that developed through May 1996, and on an age- and sex-matched reference cohort (n = 454). We used Cox proportional hazard models to estimate relative risks (RR) and 95% confidence intervals (95% CI). Results: We observed no association between the variant genotype in XRCC1 Arg194Trp (codon 194 arganine to tryptophan substitution) and esophageal or gastric cardia cancer. However, carrying at least one copy of the variant allele in XRCC1 Arg399Gln (codon 399 arganine to glutamine substitution) was associated with reduced risk of gastric cardia cancer (RR: 0.60, 95% CI: 0.37-0.97) and the combined category esophageal/gastric cancer (RR: 0.67, 95% CI: 0.48-0.95). In combined polymorphisms analyses, we observed a significant reduction in risk of combined esophageal/gastric cancer among individuals that had both the XRCC1 Arg194Trp and Arg399Gln variant genotyopes (RR: 0.47, 95% CI: 0.26-0.84). Conclusions: Our results suggest that the XRCC1 Arg399Gln variant genotype is associated with reduced risk of upper GI cancer and that individuals with both XRCC1 variant genotypes are also at significantly reduced risk of upper GI cancer in this high-risk Chinese population. (C) 2004 Published by Elsevier Ireland Ltd. C1 US FDA, Natl Ctr Toxicol Res, Ctr Struct Genomics, Jefferson, AR 72079 USA. NCI, Canc Prevent Studies Branch, Clin Res Ctr, Rockville, MD USA. Chinese Acad Med Sci, Beijing 100037, Peoples R China. BioServe Biotechnol Ltd, Laurel, MD USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Ratnasinghe, LD (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Struct Genomics, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM lratnasinghe@nctr.fda.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 29 TC 48 Z9 55 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 28 PY 2004 VL 216 IS 2 BP 157 EP 164 DI 10.1016/j.canlet.2004.03.012 PG 8 WC Oncology SC Oncology GA 875IY UT WOS:000225414900003 PM 15533591 ER PT J AU Michelman-Ribeiro, A Boukari, H Nossal, R Horkay, F AF Michelman-Ribeiro, A Boukari, H Nossal, R Horkay, F TI Structural changes in polymer gels probed by fluorescence correlation spectroscopy SO MACROMOLECULES LA English DT Article ID POLY(VINYL ALCOHOL); AQUEOUS-SOLUTIONS; DIFFUSION; HYDROGELS; DYNAMICS C1 NIH, LIMB, Bethesda, MD 20892 USA. Boston Univ, Dept Phys, Boston, MA 02215 USA. RP Boukari, H (reprint author), NIH, LIMB, Bldg 10, Bethesda, MD 20892 USA. EM boukarih@mail.nih.gov NR 13 TC 30 Z9 30 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD DEC 28 PY 2004 VL 37 IS 26 BP 10212 EP 10214 DI 10.1021/ma048043d PG 3 WC Polymer Science SC Polymer Science GA 882IP UT WOS:000225932900078 ER PT J AU Lewis, D Ashwal, S Hershey, A Hirtz, D Yonker, M Silberstein, S AF Lewis, D Ashwal, S Hershey, A Hirtz, D Yonker, M Silberstein, S TI Practice parameter: Pharmacological treatment of migraine headache in children and adolescents - Report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society SO NEUROLOGY LA English DT Article ID DOUBLE-BLIND; PEDIATRIC MIGRAINE; SUBCUTANEOUS SUMATRIPTAN; PROPHYLACTIC TREATMENT; PROPRANOLOL; FLUNARIZINE; CRITERIA; TRIAL; EPIDEMIOLOGY; PREVALENCE AB Objective: To review evidence on the pharmacologic treatment of the child with migraine headache. Methods: The authors reviewed, abstracted, and classified relevant literature. Recommendations were based on a four-tiered scheme of evidence classification. Treatment options were separated into medications for acute headache and preventive medications. Results: The authors identified and reviewed 166 articles. For acute treatment, five agents were reviewed. Sumatriptan nasal spray and ibuprofen are effective and are well tolerated vs placebo. Acetaminophen is probably effective and is well tolerated vs placebo. Rizatriptan and zolmitriptan were safe and well tolerated but were not superior to placebo. For preventive therapy, 12 agents were evaluated. Flunarizine is probably effective. The data concerning cyproheptadine, amitriptyline, divalproex sodium, topiramate, and levetiracetam were insufficient. Conflicting data were found concerning propranolol and trazodone. Pizotifen, nimodipine, and clonidine did not show efficacy. Conclusions: For children (>age 6 years), ibuprofen is effective and acetaminophen is probably effective and either can be considered for the acute treatment of migraine. For adolescents (>12 years of age), sumatriptan nasal spray is effective and should be considered for the acute treatment of migraine. For preventive therapy, flunarizine is probably effective and can be considered, but is not available in the United States. There are conflicting or insufficient data to make any other recommendations for the preventive therapy of migraine in children and adolescents. For a clinical problem so prevalent in children and adolescents, there is a disappointing lack of evidence from controlled, randomized, and masked trials. C1 Childrens Hosp Kings Daughters, Div Child Neurol, Dept Pediat, Eastern Virginia Med Sch, Norfolk, VA USA. Loma Linda Univ, Sch Med, Dept Pediat, Div Child Neurol, Loma Linda, CA 92350 USA. Childrens Hosp, Med Ctr, Dept Neurol, Cincinnati, OH 45229 USA. NINDS, NIH, Bethesda, MD USA. AI Dupont Hosp Children, Div Child Neurol, Dept Pediat, Wilmington, DE USA. Thomas Jefferson Univ, Jefferson Headache Ctr, Philadelphia, PA USA. RP Lewis, D (reprint author), Amer Acad Neurol, 1080 Montreal Ave, St Paul, MN 55116 USA. OI Hershey, Andrew/0000-0002-1598-7536 NR 45 TC 212 Z9 223 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 28 PY 2004 VL 63 IS 12 BP 2215 EP 2224 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 883KJ UT WOS:000226010000004 PM 15623677 ER PT J AU Kang, DW Latour, LL Chalela, JA Dambrosia, JA Warach, S AF Kang, DW Latour, LL Chalela, JA Dambrosia, JA Warach, S TI Early and late recurrence of ischemic lesion on MRI - Evidence for a prolonged stroke-prone state? SO NEUROLOGY LA English DT Article ID LONG-TERM RISK; CEREBRAL INFARCTION; COMMUNITY-STROKE; RANDOMIZED TRIAL; BRAIN INFARCTION; POPULATION; PROGNOSIS; SURVIVAL; SUBTYPE; DISEASE AB Background: Based on previous observations of a high rate of ischemic lesion recurrence on diffusion-weighted imaging (DWI) within 1 week after an acute ischemic stroke, the authors hypothesized that silent new ischemic lesions are common between 1 week and 90 days after index stroke and that early lesion recurrence may be associated with late lesion recurrence. Methods: The authors studied 80 acute ischemic stroke patients who had initial MRI performed within 48 hours, and follow-up scans at 5 days and at 30 or 90 days after onset. Early lesion recurrences were defined as new ischemic lesions on 5-day DWI, and late lesion recurrences were defined as those on 30- or 90-day DWI or fluid attenuation inversion recovery image. Early lesion recurrence occurring outside the initial perfusion deficit was termed distant lesion recurrence. Results: Late lesion recurrence occurred in 26%, more frequently observed on 30- day MRI than 90-day MRI (p = 0.016). Early lesion recurrence (OR 4.0; 95% CI 1.3 to 11.7) and distant early lesion recurrence (OR 6.9; 95% CI 1.5 to 32.2) were independently associated with late lesion recurrence by multiple logistic regression analyses. Conclusions: There may be a continued risk for recurrent ischemic lesions in the weeks following the clinically symptomatic stroke. Future studies are needed to investigate whether MRI-defined ischemic lesion recurrences predict subsequent clinical recurrence and thus may be a potential surrogate endpoint in stroke secondary prevention trials. C1 NINDS, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, Bethesda, MD 20892 USA. NINDS, Sect Stroke Diagnost & Therapeut, Biostat Branch, NIH, Bethesda, MD 20892 USA. Univ Ulsan, Dept Neurol, Asan Med Ctr, Seoul, South Korea. RP Warach, S (reprint author), NINDS, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, 10 Ctr Dr,Room B1D733, Bethesda, MD 20892 USA. EM WarachS@ninds.nih.gov NR 28 TC 45 Z9 45 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 28 PY 2004 VL 63 IS 12 BP 2261 EP 2265 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 883KJ UT WOS:000226010000011 PM 15623684 ER PT J AU Bruno, MK Hallett, M Gwinn-Hardy, K Sorensen, B Considine, E Tucker, S Lynch, DR Mathews, KD Swoboda, KJ Harris, J Soong, BW Ashizawa, T Jankovic, J Renner, D Fu, YH Ptacek, LJ AF Bruno, MK Hallett, M Gwinn-Hardy, K Sorensen, B Considine, E Tucker, S Lynch, DR Mathews, KD Swoboda, KJ Harris, J Soong, BW Ashizawa, T Jankovic, J Renner, D Fu, YH Ptacek, LJ TI Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia - New diagnostic criteria SO NEUROLOGY LA English DT Article ID HUMAN-CHROMOSOME 16; INFANTILE CONVULSIONS; CHOREOATHETOSIS; FAMILY; LOCUS; GENE; CLASSIFICATION; EPIDEMIOLOGY; DELINEATION; PEDIGREE AB Background: Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by short episodes of involuntary movement attacks triggered by sudden voluntary movements. Although a genetic basis is suspected in idiopathic cases, the gene has not been discovered. Establishing strict diagnostic criteria will help genetic studies. Methods: The authors reviewed the clinical features of 121 affected individuals, who were referred for genetic study with a presumptive diagnosis of idiopathic PKD. Results: The majority (79%) of affected subjects had a distinctive homogeneous phenotype. The authors propose the following diagnostic criteria for idiopathic PKD based on this phenotype: identified trigger for the attacks (sudden movements), short duration of attacks (<1 minute), lack of loss of consciousness or pain during attacks, antiepileptic drug responsiveness, exclusion of other organic diseases, and age at onset between 1 and 20 years if there is no family history ( age at onset may be applied less stringently in those with family history). In comparing familial and sporadic cases, sporadic cases were more frequently male, and infantile convulsions were more common in the familial kindreds. Females had a higher remission rate than males. An infantile-onset group with a different set of characteristics was identified. A clear kinesigenic trigger was not elicited in all cases, antiepileptic response was not universal, and some infants had attacks while asleep. Conclusions: The diagnosis of idiopathic paroxysmal kinesigenic dyskinesia ( PKD) can be made based on historical features. The correct diagnosis has implications for treatment and prognosis, and the diagnostic scheme may allow better focus in the search for the PKD gene(s). C1 Univ Calif San Francisco, Howard Hughes Med Inst, Dept Neurol, San Francisco, CA 94143 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA. NINDS, Parkinsons Unit, Div Neurogenet, NIH, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. Univ Iowa, Coll Med, Dept Pediat, Iowa City, IA 52242 USA. Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. Univ Texas, Med Branch, Dept Neurol, Galveston, TX 77550 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. Natl Yang Ming Univ, Sch Med, Dept Neurol, Taipei, Taiwan. Taipei Vet Gen Hosp, Neurol Inst, Taipei, Taiwan. RP Ptacek, LJ (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Neurol, 1550 4th St,Mission Bay 19B,Rm 546, San Francisco, CA 94143 USA. EM ptacek@itsa.ucsf.edu RI Gwinn, Katrina/C-2508-2009 FU NINDS NIH HHS [R01 NS43533] NR 32 TC 153 Z9 187 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 28 PY 2004 VL 63 IS 12 BP 2280 EP 2287 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 883KJ UT WOS:000226010000014 PM 15623687 ER PT J AU Hou, SB Saw, JH Lee, KS Freitas, TA Belisle, C Kawarabayasi, Y Donachie, SP Pikina, A Galperin, MY Koonin, EV Makarova, KS Omelchenko, MV Sorokin, A Wolf, YI Li, QX Keum, YS Campbell, S Denery, J Aizawa, SI Shibata, S Malahoff, A Alam, M AF Hou, SB Saw, JH Lee, KS Freitas, TA Belisle, C Kawarabayasi, Y Donachie, SP Pikina, A Galperin, MY Koonin, EV Makarova, KS Omelchenko, MV Sorokin, A Wolf, YI Li, QX Keum, YS Campbell, S Denery, J Aizawa, SI Shibata, S Malahoff, A Alam, M TI Genome sequence of the deep-sea gamma-proteobacterium Idiomarina loihiensis reveals amino acid fermentation as a source of carbon and energy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hydrothermal vent ID SP-NOV.; BACTERIA; HAWAII; GENE; PREDICTION; SEAMOUNT; DATABASE; VOLCANO; CYCLE AB We report the complete genome sequence of the deep-sea gamma-proteobacterium, Idiomarina loihiensis, isolated recently from a hydrothermal vent at 1,300-m depth on the L (o) over bar ihi submarine volcano, Hawaii. The I. loihiensis genome comprises a single chromosome of 2,839,318 base pairs, encoding 2,640 proteins, four rRNA operons, and 56 tRNA genes. A comparison of I. loihiensis to the genomes of other gamma-proteobacteria reveals abundance of amino acid transport and degradation enzymes, but a loss of sugar transport systems and certain enzymes of sugar metabolism. This finding suggests that I. loihiensis relies primarily on amino acid catabolism, rather than on sugar fermentation, for carbon and energy. Enzymes for biosynthesis of purines, pyrimidines, the majority of amino acids, and coenzymes are encoded in the genome, but biosynthetic pathways for Leu, Ile, Val, Thr, and Met are incomplete. Auxotrophy for Val and Thr was confirmed by in vivo experiments. The I. loihiensis genome contains a cluster of 32 genes encoding enzymes for exopolysaccharide and capsular polysaccharide synthesis. It also encodes diverse peptidases, a variety of peptide and amino acid uptake systems, and versatile signal transduction machinery. We propose that the source of amino acids for I. loihiensis growth are the proteinaceous particles present in the deep sea hydrothermal vent waters. I. loihiensis would colonize these particles by using the secreted exopolysaccharide, digest these proteins, and metabolize the resulting peptides and amino acids. In summary, the I. loihiensis genome reveals an integrated mechanism of metabolic adaptation to the constantly changing deep-sea hydrothermal ecosystem. C1 Univ Hawaii, Dept Microbiol, Honolulu, HI 96822 USA. Univ Hawaii, Ctr Genom Proteom & Bioinformat Res Initiat, Honolulu, HI 96822 USA. Maui High Performance Comp Ctr, Maui, HI 96753 USA. Natl Inst Adv Ind Sci & Technol, Ctr Glycosci, Tsukuba, Ibaraki 3058566, Japan. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Hawaii, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA. Japan Sci & Technol Corp, Soft Nano Machine Project, Takanezawa, Tochigi 3291206, Japan. Shizuoka Univ, Dept Agr, Shizuoka 4228529, Japan. Inst Geol & Nucl Sci, Lower Hutt, New Zealand. RP Alam, M (reprint author), Univ Hawaii, Dept Microbiol, Snyder Hall 111,2538 The Mall, Honolulu, HI 96822 USA. EM alam@hawaii.edu RI Galperin, Michael/B-5859-2013; Saw, Jimmy/A-9972-2009 OI Galperin, Michael/0000-0002-2265-5572; Saw, Jimmy/0000-0001-8353-3854 FU Intramural NIH HHS [Z99 LM999999] NR 27 TC 89 Z9 513 U1 3 U2 20 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 28 PY 2004 VL 101 IS 52 BP 18036 EP 18041 DI 10.1073/pnas.0407638102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 884RD UT WOS:000226102700029 PM 15596722 ER PT J AU Fong, LG Ng, JK Meta, M Cote, N Yang, SH Stewart, CL Sullivan, T Burghardt, A Majumdar, S Reue, K Bergo, MO Young, SG AF Fong, LG Ng, JK Meta, M Cote, N Yang, SH Stewart, CL Sullivan, T Burghardt, A Majumdar, S Reue, K Bergo, MO Young, SG TI Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Hutchinson-Gilford progeria syndrome; prelamin A ID ENCODING LAMIN A/C; MANDIBULOACRAL DYSPLASIA; MUSCULAR-DYSTROPHY; NUCLEAR LAMINS; A-FACTOR; PRELAMIN; ZMPSTE24; PROTEIN; METALLOPROTEINASE; MATURATION AB Zmpste24 is a metalloproteinase required for the processing of prelamin A to lamin A, a structural component of the nuclear lamina. Zmpste24 deficiency results in the accumulation of prelamin A within cells, a complete loss of mature lamin A, and misshapen nuclear envelopes. Zmpste24-deficient (Zmpste24(-/-)) mice exhibit retarded growth, alopecia, micrognathia, dental abnormalities, osteolytic lesions in bones, and osteoporosis, which are phenotypes shared with Hutchinson-Gilford progeria syndrome, a human disease caused by the synthesis of a mutant prelamin A that cannot undergo processing to lamin A. Zmpste24(-/-) mice also develop muscle weakness. We hypothesized that prelamin A might be toxic and that its accumulation in Zmpste24(-/-) mice is responsible for all of the disease phenotypes. We further hypothesized that Zmpste24(-/-) mice with half-normal levels of prelamin A (Zmpste24(-/-) mice with one Lmna knockout allele) would be subjected to less toxicity and be protected from disease. Thus, we bred and analyzed Zmpste24(-/-)Lmna(+/-) mice. As expected, prelamin A levels in Zmpste24(-/-)Lmna(+/-) cells were significantly reduced. Zmpste24(-/-)Lmna(+/-) mice were entirely normal, lacking all disease phenotypes, and misshapen nuclei were less frequent in Zmpste24(-/-)Lmna(+/-) cells than in Zmpste24(-/-) cells. These data suggest that prelamin A is toxic and that reducing its levels by as little as 50% provides striking protection from disease. C1 Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. NCI, Ft Detrick, MD 21702 USA. Univ Calif San Francisco, Musculoskeletal & Quantitative Res Grp, Dept Radiol, San Francisco, CA 94107 USA. RP Fong, LG (reprint author), Univ Calif Los Angeles, Dept Med, Div Cardiol, 650 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM lfong@mednet.ucla.edu FU NHLBI NIH HHS [HL076839, R01 HL076839]; NIAMS NIH HHS [AR050200, R01 AR050200] NR 24 TC 134 Z9 138 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 28 PY 2004 VL 101 IS 52 BP 18111 EP 18116 DI 10.1073/pnas.0408558102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 884RD UT WOS:000226102700042 PM 15608054 ER PT J AU Maswood, N Young, J Tilmont, E Zhang, ZM Gash, DM Gerhardt, GA Grondin, R Roth, GS Mattison, J Lane, MA Carson, RE Cohen, RM Mouton, PR Quigley, C Mattson, MP Ingram, DK AF Maswood, N Young, J Tilmont, E Zhang, ZM Gash, DM Gerhardt, GA Grondin, R Roth, GS Mattison, J Lane, MA Carson, RE Cohen, RM Mouton, PR Quigley, C Mattson, MP Ingram, DK TI Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE brain-derived neurotrophic factor; cell death; dopamine ID AGED RHESUS-MONKEYS; DIETARY RESTRICTION; SUBSTANTIA-NIGRA; DOPAMINERGIC-NEURONS; EXCITOTOXIC INSULTS; FUNCTIONAL RECOVERY; STRIATAL NEURONS; BRAIN-DAMAGE; LIMB-USE; GDNF AB We report that a low-calorie diet can lessen the severity of neurochemical deficits and motor dysfunction in a primate model of Parkinson's disease. Adult male rhesus monkeys were maintained for 6 months on a reduced-calorie diet [30% caloric restriction (CR)] or an ad libitum control diet after which they were subjected to treatment with a neurotoxin to produce a hemiparkinson condition. After neurotoxin treatment, CR monkeys exhibited significantly higher levels of locomotor activity compared with control monkeys as well as higher levels of dopamine (DA) and DA metabolites in the striatal region. Increased survival of DA neurons in the substantia nigra and improved manual dexterity were noted but did not reach statistical significance. Levels of glial cell line-derived neurotrophic factor, which is known to promote the survival of DA neurons, were increased significantly in the caudate nucleus of CR monkeys, suggesting a role for glial cell line-derived neurotrophic factor in the anti-Parkinson's disease effect of the low-calorie diet. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Univ Kentucky, Morris K Udall Parkinsons Dis Res Ctr Excellence, Lexington, KY 40536 USA. NIH, Warren G Magnuson Clin Ctr, PET Dept, Bethesda, MD 20892 USA. NIMH, Neuroimaging Sect, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 55 TC 194 Z9 199 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 28 PY 2004 VL 101 IS 52 BP 18171 EP 18176 DI 10.1073/pnas.0405831102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 884RD UT WOS:000226102700052 PM 15604149 ER PT J AU Henry, ER Eaton, WA AF Henry, ER Eaton, WA TI Combinatorial modeling of protein folding kinetics: free energy profiles and rates SO CHEMICAL PHYSICS LA English DT Review DE protein folding theory; statistical mechanics; two-state proteins ID NUCLEATION-CONDENSATION MECHANISM; INTRAMOLECULAR CONTACT FORMATION; TRANSITION-STATE; SH3 DOMAIN; CHYMOTRYPSIN INHIBITOR-2; ENGINEERING ANALYSIS; 2-STATE TRANSITION; MICROSCOPIC THEORY; LOCAL INTERACTIONS; DIFFUSION-MODEL AB A combinatorial approach has been used to determine the optimal assumptions and robustness of simple statistical mechanical models for protein folding. By combining alternative plausible assumptions and different enumeration schemes for constructing partition functions, 76 closely related Ising-like models were generated. These include various contiguous sequence approximations, the possibility of forming a disordered loop between ordered segments, the use of an atomstic or coarse-grained representation of the protein structure, and the choice of ordered residues or native contacts as a reaction coordinate. We also consider all 2(N) conformations of an N-residue protein (e.g., 10(30) conformations for a 100-residue protein). Although the number of configurations is much too large to list, a free energy profile can be calculated using a build-up procedure by accumulation and recombination of partial partition functions. The predictions of the 76 models were tested against two kinds of experimental data - folding rates and the determination of two-state behavior for 25 proteins. Two-state behavior was judged by the relative magnitude of the dominant relaxation calculated from the rate matrix for motion on the free energy profile. The relative performance of each assumption was evaluated using rank sum statistics which show, with the exception of the single sequence approximation, that this class of models is not sensitive to alternative assumptions. Two-state free energy profiles are calculated for almost all but the a-helical proteins, and surprisingly accurate rates are predicted in both the absence and presence of denaturant. The combinatorics also show that an a-carbon representation of the protein structure does nearly as well as atomistic descriptions, possibly reflecting partial interatomic interactions between native residues in structures of the transition state ensemble. With its coarse-grained description of both the energy and entropy, and only 3 or 4 adjustable parameters, the a-carbon version may be regarded as the simplest possible analytical model of protein folding capable of predicting experimental properties of specific proteins. (C) 2004 Elsevier B.V. All rights reserved. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Eaton, WA (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 104, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 101 TC 59 Z9 60 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD DEC 27 PY 2004 VL 307 IS 2-3 BP 163 EP 185 DI 10.1016/j.chemphys.2004.06.064 PG 23 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 872NZ UT WOS:000225215200009 ER PT J AU Moaddel, R Jozwiak, K Yamaguchi, R Cobello, C Whittington, K Sarkar, TK Basak, S Wainer, IW AF Moaddel, R Jozwiak, K Yamaguchi, R Cobello, C Whittington, K Sarkar, TK Basak, S Wainer, IW TI On-line screening of conformationally constrained nicotines and anabasines for agonist activity at the alpha 3 beta 4-and alpha 4 beta 2-nicotinic acetylcholine receptors using immobilized receptor-based liquid chromatographic stationary phases SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE on-line screening; immobilized nicotinic receptors; nicotinic agonists ID BINDING-SITES; AFFINITY-CHROMATOGRAPHY; ANALOGS; PHARMACOLOGY; SUBTYPES; PHARMACOPHORE; FLUORESCENCE; INHIBITORS; TARGETS AB Liquid chromatography columns containing stationary phases based upon immobilized nicotinic acetylcholine receptors (nAChRs) were used to screen a series of conformationally constrained nicotine and anabasine derivatives for agonist activity. The alpha3beta4 nAChR and alpha4beta2 nAChR subtypes were used to prepare the chromatographic columns and [H-3] epibatidine dihydrochloride ([H-3] EB) was used as the marker ligand. Single displacement experiments were conducted with the test ligands and with nicotine and carbachol. Nicotine was used as an internal control for compounds with agonist activity and carbachol was used as an internal control for compounds with very weak agonistic activity (K-d > 4700 nM for 0 04). The displacement of [3 H] EB by each of the test compounds and internal controls was calculated and expressed as Deltaml. Functional studies were then conducted using a stably transfected cell line that expresses the alpha3beta4 nAChR and EC50 values were determined for the test compounds and the internal controls. A comparison of the Deltaml and EC50 values indicated that 9/11 compounds had been correctly identified as agonists or non-agonists of the alpha3beta4 nAChR. A similar comparison could not be made for the alpha4beta2 nAChR, since the intact cell line was not available for testing. The results of the study suggest that the immobilized nAChR columns can be used for the rapid on-line screening of compounds for their relative affinities for the immobilized receptor and as an initial determination of quahtative functional activities. (C) 2004 Elsevier B.V. All rights reserved. C1 NIA, Bioanalyt & Drug Discovery Unit, Natl Inst Hlth, Gerontol Res Ctr, Baltimore, MD 21224 USA. Med Univ Lublin, PL-20081 Lublin, Poland. Shionogi & Co Ltd, Hyogo, Japan. Indian Inst Technol, Dept Chem, Kharagpur 721302, W Bengal, India. RP Wainer, IW (reprint author), NIA, Bioanalyt & Drug Discovery Unit, Natl Inst Hlth, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov NR 32 TC 23 Z9 24 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD DEC 25 PY 2004 VL 813 IS 1-2 BP 235 EP 240 DI 10.1016/j.jchromb.2004.09.042 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 875IH UT WOS:000225413200028 PM 15556538 ER PT J AU Kim, KS Yoon, JH Kim, JK Baek, SJ Eling, TE Lee, WJ Ryu, JH Lee, JG Lee, JH Yoo, JB AF Kim, KS Yoon, JH Kim, JK Baek, SJ Eling, TE Lee, WJ Ryu, JH Lee, JG Lee, JH Yoo, JB TI Cyclooxygenase inhibitors induce apoptosis in oral cavity cancer cells by increased expression of nonsteroidal anti-inflammatory. drug-activated gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE nonsteroidal anti-inflammatory drugs; oral cavity cancer; apoptosis; NSAID-activated gene-1; Drosophila ID BETA SUPERFAMILY MEMBER; ANTIINFLAMMATORY DRUGS; CARCINOMA-CELLS; NAG-1; P53; GROWTH; PROLIFERATION; PATHWAY; HEAD AB We have investigated whether NAGA is induced in oral cavity cancer cells by various NSAIDs and if apoptosis induced by NSAIDs can be linked directly with the induction of NAG-1. NAG-1 expression was increased by diclofenac, aceclofenac, indomethacin, ibuprofen, and sulindac sulfide, in the order of NAG-1 induction, but not by acetaminophen, piroxicam or NS-398. Diclofenac was the most effective NAG-1 inducer. Incubation with diclofenac inhibited cell proliferation and induced apoptosis. The expression of NAG-1 was observed in advance of the induction of apoptosis. Conditioned medium from NAG-1-overexpressing Drosophila cells inhibited SCC 1483 cells proliferation and induced apoptosis. In summary, some NSAIDs induce NAG-1 expression in oral cavity cancer cells and the induced NAG-1 protein appears to mediate apoptosis. Therefore, NSAIDs may be considered as a possible chemopreventive agent against oral cavity cancer. (C) 2004 Elsevier Inc. All rights reserved. C1 Yonsei Univ, Coll Med, Dept Otorhinolaryngol, Seoul 120749, South Korea. Yonsei Univ, Coll Med, Airway Mucus Inst, Seoul 120749, South Korea. Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120749, South Korea. Konkuk Univ, Coll Med, Dept Otorhinolaryngol, Seoul, South Korea. Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. RP Kim, KS (reprint author), Yonsei Univ, Coll Med, Dept Otorhinolaryngol, 134 Shinchon Dong, Seoul 120749, South Korea. EM ydrhinol@yumc.yonsei.ac.kr RI Yoon, Joo-Heon/E-5781-2016; OI Baek, Seung/0000-0001-7866-7778; Yoon, Joo-Heon/0000-0003-2404-7156 NR 20 TC 49 Z9 50 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 24 PY 2004 VL 325 IS 4 BP 1298 EP 1303 DI 10.1016/j.bbrc.2004.10.176 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 877HB UT WOS:000225557500026 PM 15555568 ER PT J AU Clark, AB Kunkel, TA AF Clark, AB Kunkel, TA TI Cadmium inhibits the functions of eukaryotic MutS complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA MISMATCH REPAIR; ESCHERICHIA-COLI MUTS; ATPASE DOMAINS; PROTEIN MUTS; CANCER; REPLICATION; MECHANISMS; MSH2-MSH6; EXCISION; AFFINITY AB Exposure of yeast cells to low concentrations of cadmium results in elevated mutation rates due to loss of mismatch repair (MMR), and cadmium inhibits MMR activity in extracts of human cells (1). Here we show that cadmium inhibits both Msh2-Msh6- and Msh2-Msh3-dependent human MMR activity in vitro. This inhibition, which occurs at a step or steps preceding repair DNA synthesis, is observed for repair directed by either a 3' or a 5' nick. In an attempt to identify the protein target(s) of cadmium inhibition, we show that cadmium inhibition of MMR is not reversed by addition of zinc to the repair reaction, suggesting that the target is not a zinc metalloprotein. We then show that cadmium inhibits ATP hydrolysis by yeast Msh2-Msh6 but has no effect on ATPase hydrolysis by yeast Mlh1-Pms1. Steady state kinetic analysis with wild type Msh2-Msh6, and with heterodimers containing subunit-specific Glu to Ala replacements inferred to inactivate the ATPase activity of either Msh2 or Msh6, suggest that cadmium inhibits ATP hydrolysis by Msh6 but not Msh2. Cadmium also reduces DNA binding by Msh2-Msh6 and more so for mismatched than matched duplexes. These data indicate that eukaryotic Msh2-Msh3 and Msh2-Msh6 complexes are targets for inhibition of MMR by cadmium, a human lung carcinogen that is ubiquitous in the environment. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 39 TC 34 Z9 39 U1 5 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2004 VL 279 IS 52 BP 53903 EP 53906 DI 10.1074/jbc.C400495200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600002 PM 15513922 ER PT J AU Tran, POT Parker, SM LeRoy, E Franklin, CC Kavanagh, TJ Zhang, T Zhou, HR Vliet, P Oseid, E Harmon, JS Robertson, RP AF Tran, POT Parker, SM LeRoy, E Franklin, CC Kavanagh, TJ Zhang, T Zhou, HR Vliet, P Oseid, E Harmon, JS Robertson, RP TI Adenoviral overexpression of the glutamylcysteine ligase catalytic subunit protects pancreatic islets against oxidative stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUTATHIONE SYNTHESIS; DIABETES-MELLITUS; GLUCOSE TOXICITY; GENE-EXPRESSION; BETA-CELLS; SYNTHETASE; INTERLEUKIN-1-BETA; INHIBITION; DEFENSE; ENZYMES AB The catalytic subunit of glutamylcysteine ligase (GCLC) primarily regulates de novo synthesis of glutathione (GSH) in mammalian cells and is central to the antioxidant capacity of the cell. However, GCLC expression in pancreatic islets has not been previously examined. We designed experiments to ascertain whether GCLC is normally expressed in islets and whether it is up-regulated by interleukin-1beta (IL-1beta). GCLC expression levels were intermediate compared with other metabolic tissues (kidney, liver, muscle, fat, and lung). IL-1beta up-regulated GCLC expression (10 ng/ml IL-1beta, 3.76+/-0.86; 100 ng/ml IL-1beta, 4.22+/-0.68-fold control) via the p38 form of mitogen-activated protein kinase and NFkappaB and also increased reactive oxygen species levels (10 ng/ml IL-1beta, 5.41+/-1.8-fold control). This was accompanied by an increase in intraislet GSH/GSSG ratio (control, 7.1+/-0.1; 10 ng/ml IL-1beta, 8.0+/-0.5; 100 ng/ml IL-1beta, 8.2+/-0.5-fold control; p<0.05). To determine whether overexpression of GCLC increases the antioxidant capacity of the islet and prevents the adverse effects of IL-1β on glucose-induced insulin secretion, islets were infected with an adenovirus encoding GCLC. IL-1β significantly decreased glucose-stimulated insulin secretion (control, 123.8&PLUSMN;17.7; IL-1β, 40.2&PLUSMN;3.9 microunits/ml insulin/islet). GCLC overexpression increased intraislet GSH levels and partially prevented the decrease in glucose-stimulated insulin secretion caused by IL-1β. These data provide the first report of GCLC expression in the islet and demonstrate that adenoviral overexpression of GCLC increases intracellular GSH levels and protects the beta cell from the adverse effects of IL-1β. C1 Pacific NW Res Inst, Seattle, WA 98122 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, NIEHS, Ctr Ecogenet & Environm Hlth, NIH,Dept Environm Hlth, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA. RP Robertson, RP (reprint author), Pacific NW Res Inst, 720 Broadway, Seattle, WA 98122 USA. EM rpr@pnri.org FU NCI NIH HHS [CA90473]; NIDDK NIH HHS [R01 DK38325] NR 21 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2004 VL 279 IS 52 BP 53988 EP 53993 DI 10.1074/jbc.M404809200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600013 PM 15485876 ER PT J AU Vazquez-Prado, J Miyazaki, H Castellone, MD Teramoto, H Gutkind, JS AF Vazquez-Prado, J Miyazaki, H Castellone, MD Teramoto, H Gutkind, JS TI Chimeric G alpha(i2)/G alpha(13) proteins reveal the structural requirements for the binding and activation of the RGS-like (RGL)-containing Rho guanine nucleotide exchange factors (GEFs) by G alpha(13) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA-ASSOCIATED RHO; HETEROTRIMERIC G-PROTEINS; PDZ-RHOGEF; TRANSITION-STATE; GTP HYDROLYSIS; RGRGS DOMAIN; P115 RHOGEF; LARG; RECEPTOR; LOCALIZATION AB The alpha-subunit of G proteins of the G(12/13) family stimulate Rho by their direct binding to the RGS-like (RGL) domain of a family of Rho guanine nucleotide exchange factors (RGL-RhoGEFs) that includes PDZ-RhoGEF (PRG), p115RhoGEF, and LARG, thereby regulating cellular functions as diverse as shape and movement, gene expression, and normal and aberrant cell growth. The structural features determining the ability of Galpha(12/13) to bind RGL domains and the mechanism by which this association results in the activation of RGL-RhoGEFs are still poorly understood. Here, we explored the structural requirements for the functional interaction between Galpha(13) and RGL-RhoGEFs based on the structure of RGL domains and their similarity with the area by which RGS4 binds the switch region of Galpha(i) proteins. Using Galpha(i2), which does not bind RGL domains, as the backbone in which Galpha(13) sequences were swapped or mutated, we observed that the switch region of Galpha(13) is strictly necessary to bind PRG, and specific residues were identified that are critical for this association, likely by contributing to the binding surface. Surprisingly, the switch region of Galpha(13) was not sufficient to bind RGL domains, but instead most of its GTPase domain is required. Furthermore, membrane localization of Galpha(13) and chimeric Galpha(i2) proteins was also necessary for Rho activation. These findings revealed the structural features by which Galpha(13) interacts with RGL domains and suggest that molecular interactions occurring at the level of the plasma membrane are required for the functional activation of the RGL-containing family of RhoGEFs. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Inst Politecn Nacl, CINVESTAV, Dept Pharmacol, Mexico City 07000, DF, Mexico. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Rm 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; VAZQUEZ-PRADO, JOSE/C-1630-2017; OI CASTELLONE, MARIADOMENICA/0000-0003-0507-8037 FU FIC NIH HHS [D43 TW06664] NR 39 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2004 VL 279 IS 52 BP 54283 EP 54290 DI 10.1074/jbc.M410594200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600049 PM 15485891 ER PT J AU Heydorn, A Sondergaard, BP Ersboll, B Holst, B Nielsen, FC Haft, CR Whistler, J Schwartz, TW AF Heydorn, A Sondergaard, BP Ersboll, B Holst, B Nielsen, FC Haft, CR Whistler, J Schwartz, TW TI A library of 7TM receptor C-terminal tails - Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID EXCHANGER REGULATORY FACTOR; METABOTROPIC GLUTAMATE RECEPTORS; 3RD INTRACELLULAR LOOP; GROWTH-FACTOR RECEPTOR; BETA-ARRESTIN; BETA(2)-ADRENERGIC RECEPTOR; BETA(1)-ADRENERGIC RECEPTOR; BETA-2-ADRENERGIC RECEPTOR; SYNAPTIC-TRANSMISSION; OPIOID RECEPTORS AB Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor sequestration through interactions, mainly with the C-terminal intracellular tails of the receptors. A library of tails from 59 representative members of the super family of seven-transmembrane receptors was probed as glutathione S-transferase fusion proteins for interactions with four different adaptor proteins previously proposed to be involved in post-endocytotic sorting of receptors. Of the two proteins suggested to target receptors for recycling to the cell membrane, which is the route believed to be taken by a majority of receptors, ERM (ezrin-radixin-moesin)binding phosphoprotein 50 (EBP50) bound only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein-coupled receptor-associated sorting protein bound 23 of the 59 tail proteins. Surface plasmon resonance analysis of the binding kinetics of selected hits from the glutathione S-transferase pull-down experiments, i.e. the tails of the virally encoded receptor US28 and the delta-opioid receptor, confirmed the expected nanomolar affinities for interaction with SNX1. Truncations of the NK1 receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded that the tail library provides useful information on the general importance of certain adaptor proteins, for example, in this case, ruling out EBP50 as being a broad spectrum-recycling adaptor. C1 Univ Copenhagen, Panum Inst, Dept Pharmacol, Mol Pharmacol Lab, DK-2200 Copenhagen, Denmark. Tech Univ Denmark, DK-2800 Lyngby, Denmark. Rigshosp, Dept Clin Biochem, DK-2200 Copenhagen, Denmark. NIDDK, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Ernest Gallo Res Ctr, San Francisco, CA 94608 USA. 7TM Pharma AS, DK-2970 Horsholm, Denmark. RP Schwartz, TW (reprint author), Univ Copenhagen, Panum Inst, Dept Pharmacol, Mol Pharmacol Lab, DK-2200 Copenhagen, Denmark. EM schwartz@molpharm.dk NR 112 TC 108 Z9 112 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2004 VL 279 IS 52 BP 54291 EP 54303 DI 10.1074/jbc.M406169200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600050 PM 15452121 ER PT J AU Srisodsai, A Kurotani, R Chiba, Y Sheikh, F Young, HA Donnelly, RP Kimura, S AF Srisodsai, A Kurotani, R Chiba, Y Sheikh, F Young, HA Donnelly, RP Kimura, S TI Interleukin-10 induces uteroglobin-related protein (UGRP) 1 gene expression in lung epithelial cells through homeodomain transcription factor T/EBP/NKX2.1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENHANCER-BINDING PROTEIN; FACTOR-I; CYTOKINE PRODUCTION; HOMEOBOX GENE; DNA-BINDING; B GENE; A GENE; IL-10; PROMOTER; RECEPTOR AB UGRP1 is a downstream target gene for homeodomain transcription factor T/EBP/NKX2.1, which is predominantly expressed in lung epithelial cells, and may play an anti-inflammatory role in lung inflammation. To understand the role of UGRP1 in inflammation, its expression was investigated in relation to cytokine signaling. In vivo experiments using mouse embryonic lung organ culture and intranasal administration of interleukin (IL) 10 revealed that constitutive expression of Ugrp1 mRNA is enhanced by IL-10. Increase of protein levels was also demonstrated by immunohistochemistry using embryonic lungs. This IL-10 induction of Ugrp1 gene expression occurs at the transcriptional level when examined using mouse embryonic lung primary cultures. In human lung NCI-H441 cells that in contrast to mouse lung cells, do not exhibit constitutive expression of the gene, expression of the UGRP1 gene was induced in a rapid and stable fashion. Two T/EBP, but not STAT3, binding sites located in the human UGRP1 gene promoter are responsible for IL-10 induction of the UGRP1 gene as judged by transfection, gel shift, and chromatin immunoprecipitation analyses. The IL-10 receptor chains, IL-10R1 and IL-10R2, are expressed in H441 cells, however, STAT3 was only weakly activated upon IL-10 treatment. In contrast, STAT3 was strongly activated when the cells were treated with other cytokines such as IL-22 and interferon-beta but UGRP1 expression was not increased. Together these results demonstrate that IL-10 induces UGRP1 gene expression in lung epithelial cells through a T/EBP/NKX2.1-dependent pathway. The results further suggest that UGRP1 might be a target for IL-10 anti-inflammatory activities in the lung. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 3112B,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 46 TC 15 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2004 VL 279 IS 52 BP 54358 EP 54368 DI 10.1074/jbc.M405331200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600058 PM 15485815 ER PT J AU Liu, MF Garges, S Adhya, S AF Liu, MF Garges, S Adhya, S TI LacP1 promoter with an extended-10 motif - Pleiotropic effects of cyclic AMP protein at different steps of transcription initiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAMP RECEPTOR PROTEIN; OPEN COMPLEX-FORMATION; COLI RNA-POLYMERASE; PHAGE-PHI-29 REGULATORY PROTEIN-P4; ESCHERICHIA-COLI; ACTIVATOR PROTEIN; ALPHA-SUBUNIT; GALACTOSE OPERON; 434 REPRESSOR; IN-VIVO AB The cyclic AMP receptor protein (CRP), which activates transcription from the wild-type lacP1 promoter and most of its mutants, represses productive RNA synthesis from a lacP1 promoter variant that contains an extended -10 element, although CRP enhances RNA polymerase binding as well as open complex formation in both promoters. Moreover, abortive RNA synthesis, which is already higher in the extended -10 variant compared with the parent promoter, was further enhanced by CRP. These results, together with the observed decrease in productive RNA synthesis, indicate that CRP, while facilitating the earlier steps of initiation, inhibits transcription from the extended -10 lacP1 by hindering promoter clearance. We propose that CRP decreases energetic barriers to RNA polymerase binding, isomerization, and abortive RNA synthesis but stabilizes the abortive RNA initiating complex, which results in increasing the activation energy of the transition state before the elongation complex. The results demonstrate for the first time that a DNA-binding regulatory protein acts as an activator or a repressor in different steps of the transcription initiation pathway because of the energetic differences of the intermediate complex in the same promoter. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 5138, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov NR 44 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2004 VL 279 IS 52 BP 54552 EP 54557 DI 10.1074/jbc.M408609200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600080 PM 15385551 ER PT J AU Vuong, C Kocianova, S Voyich, JM Yao, YF Fischer, ER DeLeo, FR Otto, M AF Vuong, C Kocianova, S Voyich, JM Yao, YF Fischer, ER DeLeo, FR Otto, M TI A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYSACCHARIDE INTERCELLULAR ADHESIN; STAPHYLOCOCCUS-EPIDERMIDIS; INFECTION; LOCUS; MODEL; PATHOGENESIS; AUTOLYSIN; MUTANTS; AUREUS; SYSTEM AB Biofilms play an important role in many chronic bacterial infections. Production of an extracellular mixture of sugar polymers called exopolysaccharide is characteristic and critical for biofilm formation. However, there is limited information about the mechanisms involved in the biosynthesis and modification of exopolysaccharide components and how these processes influence bacterial pathogenesis. Staphylococcus epidermidis is an important human pathogen that frequently causes persistent infections by biofilm formation on indwelling medical devices. It produces a poly-N-acetylglucosamine molecule that emerges as an exopolysaccharide component of many bacterial pathogens. Using a novel method based on size exclusion chromatography-mass spectrometry, we demonstrate that the surface-attached protein IcaB is responsible for deacetylation of the poly-N-acetylglucosamine molecule. Most likely due to the loss of its cationic character, non-deacetylated poly - acetylglucosamine in an isogenic icaB mutant strain was devoid of the ability to attach to the bacterial cell surface. Importantly, deacetylation of the polymer was essential for key virulence mechanisms of S. epidermidis, namely biofilm formation, colonization, and resistance to neutrophil phagocytosis and human antibacterial peptides. Furthermore, persistence of the icaB mutant strain was significantly impaired in a murine model of device-related infection. This is the first study to describe a mechanism of exopolysaccharide modification that is indispensable for the development of biofilm-associated human disease. Notably, this general virulence mechanism is likely similar for other pathogenic bacteria and constitutes an excellent target for therapeutic maneuvers aimed at combating biofilm-associated infection. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Microscopy Core Facil, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115 NR 28 TC 247 Z9 269 U1 5 U2 33 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2004 VL 279 IS 52 BP 54881 EP 54886 DI 10.1074/jbc.M411374200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600117 PM 15501828 ER PT J AU Wacholder, S Struewing, JP Hartge, P Greene, MH Tucker, MA AF Wacholder, S Struewing, JP Hartge, P Greene, MH Tucker, MA TI Breast cancer risks for BRCA1/2 carriers SO SCIENCE LA English DT Letter ID OVARIAN-CANCER; PENETRANCE; MUTATIONS; HISTORY C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, M-S 7244, Bethesda, MD 20892 USA. EM Wacholder@NIH.gov RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 9 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 24 PY 2004 VL 306 IS 5705 BP 2188 EP 2188 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 882PE UT WOS:000225950000016 ER PT J AU Gershengorn, MC Hardikar, AA Wei, CJ Geras-Raaka, E Marcus-Samuels, B Raaka, BM AF Gershengorn, MC Hardikar, AA Wei, CJ Geras-Raaka, E Marcus-Samuels, B Raaka, BM TI Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells SO SCIENCE LA English DT Article ID INSULIN-PRODUCING CELLS; PANCREATIC BETA-CELLS; ADULT-MOUSE PANCREAS; IN-VITRO; STEM-CELLS; DIABETES-MELLITUS; PROGENITOR CELLS; DIFFERENTIATION; GENE; LINEAGES AB Insulin-expressing beta cells, found in pancreatic islets, are capable of generating more beta cells even in the adult. We show that fibroblast-like cells derived from adult human islets donated postmortem proliferate readily in vitro. These mesenchymal-type cells, which exhibit no hormone expression, can then be induced to differentiate into hormone-expressing islet-like cell aggregates, which reestablishes the epithelial character typical of islet cells. Immunohistochemistry, in situ hybridization, and messenger RNA measurements in single cells and cell populations establish the transition of epithelial. cells within islets to mesenchymal cells in culture and then to insulin-expressing epithelial, cells. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Gershengorn, MC (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov NR 27 TC 289 Z9 305 U1 1 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 24 PY 2004 VL 306 IS 5705 BP 2261 EP 2264 DI 10.1126/science.1101968 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 882PE UT WOS:000225950000048 PM 15564314 ER PT J AU Baltimore, D Nossal, G Daley, G Friedman, L Buick, R Sharav, V Stein, J Rahmstorf, S Rapley, C Collins, F Wainwright, B Rose, S Fauci, A Tam, P Venter, C Willard, H Neher, E AF Baltimore, D Nossal, G Daley, G Friedman, L Buick, R Sharav, V Stein, J Rahmstorf, S Rapley, C Collins, F Wainwright, B Rose, S Fauci, A Tam, P Venter, C Willard, H Neher, E TI New Year's wishes: All I want for 2005 is... SO NATURE LA English DT Editorial Material C1 CALTECH, Pasadena, CA 91125 USA. Univ Melbourne, Parkville, Vic 3052, Australia. Columbia Univ, New York, NY USA. Harvard Univ, Cambridge, MA 02138 USA. Hebron Univ, Palestinian Author, Hebron, Israel. Stanford Univ, Stanford, CA 94305 USA. Planetary Soc, Washington, DC USA. Univ Washington, Seattle, WA 98195 USA. Alliance Human Res Protect, New York, NY USA. Univ Oxford, Oxford OX1 2JD, England. Potsdam Inst Climate Impact Res, Potsdam, Germany. Natl Human Genome Res Inst, Bethesda, MD USA. NIAID, Bethesda, MD 20892 USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Open Univ, Milton Keynes MK7 6AA, Bucks, England. J Craig Venter Sci Fdn, Rockville, MD USA. Duke Univ, Durham, NC USA. Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany. RP Baltimore, D (reprint author), CALTECH, Pasadena, CA 91125 USA. OI Buick, Roger/0000-0003-0139-1659 NR 0 TC 0 Z9 0 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 23 PY 2004 VL 432 IS 7020 BP 942 EP 948 DI 10.1038/432942a PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 881RL UT WOS:000225887000010 ER PT J AU Zhou, LQ Mitra, R Atkinson, PW Hickman, AB Dyda, F Craig, NL AF Zhou, LQ Mitra, R Atkinson, PW Hickman, AB Dyda, F Craig, NL TI Transposition of hAT elements links transposable elements and V(D)J recombination SO NATURE LA English DT Article ID SINGLE ACTIVE-SITE; MUTATIONAL ANALYSIS; MUSCA-DOMESTICA; SACCHAROMYCES-CEREVISIAE; TN5 TRANSPOSITION; STRAND TRANSFER; TRANSFER STEPS; RAG PROTEINS; AMINO-ACIDS; DNA AB Transposons are DNA sequences that encode functions that promote their movement to new locations in the genome. If unregulated, such movement could potentially insert additional DNA into genes, thereby disrupting gene expression and compromising an organism's viability. Transposable elements are classified by their transposition mechanisms and by the transposases that mediate their movement. The mechanism of movement of the eukaryotic hAT superfamily elements was previously unknown, but the divergent sequence of hAT transposases from other elements suggested that these elements might use a distinct mechanism. Here we have analysed transposition of the insect hAT element Hermes in vitro. Like other transposons, Hermes excises from DNA via double-strand breaks between the donor-site DNA and the transposon ends, and the newly exposed transposon ends join to the target DNA. Interestingly, the ends of the donor double-strand breaks form hairpin intermediates, as observed during V(D)J recombination, the process which underlies the combinatorial formation of antigen receptor genes. Significant similarities exist in the catalytic amino acids of Hermes transposase, the V( D) J recombinase RAG, and retroviral integrase superfamily transposases, thereby linking the movement of transposable elements and V( D) J recombination. C1 Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA. Univ Calif Riverside, Inst Integrat Genome Biol, Riverside, CA 92521 USA. NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. RP Craig, NL (reprint author), Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. EM ncraig@jhmi.edu OI Zhou, Li Qin/0000-0001-8900-2835 NR 50 TC 128 Z9 134 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 23 PY 2004 VL 432 IS 7020 BP 995 EP 1001 DI 10.1038/nature03157 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 881RL UT WOS:000225887000033 PM 15616554 ER PT J AU Chu, JW Brooks, BR Trout, BL AF Chu, JW Brooks, BR Trout, BL TI Oxidation of methionine residues in aqueous solutions: Free methionine and methionine in granulocyte colony-stimulating factor SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HYDROGEN-PEROXIDE; MOLECULAR-DYNAMICS; PROTEIN FORMULATIONS; DEPENDENT FRICTION; SN2 REACTIONS; WATER OXIDE; SIMULATIONS; COORDINATE; SOLVENT; MODEL AB The free energy barriers and a mechanism of the oxidation of the amino acid methionine in water and in granulocyte colony-stimulating factor (G-CSF) are analyzed via combined quantum mechanical and molecular mechanical (QM/MM) methods, constrained molecular dynamics, and committor probability calculations. The computed free energy barrier of free methionine amino acid is very close to the measured value (14.7 +/- 1.2 versus 15.5 +/- 0.02 kcal/mol). The reaction coordinate was found to be the difference between the O-O bond of H2O2 and the S-O bond, where the S is the sulfur atom of the methionine residue. It was confirmed by computing the committor probability distribution and the distribution of constrained forces that this coordinate is not coupled to the activation of other degrees of freedom. The computed free energies of the oxidation of methionine residues in G-CSF indicate that the protein environment has insignificant effects on the reaction barriers of oxidation. This result further validates our proposal that the access of solvent to methionine sites, as measured by the two-shell water coordination number, governs the kinetics of the oxidation reaction of methionine groups in a protein molecule. We also found that the number of hydrogen bonds between the distal oxygen of H2O2 and the water molecules near the methionine increases along the reaction coordinate as oxidation progresses, indicating that the charge separation developed during the oxidation by H2O2 is stabilized by specific interactions with water molecules, such as hydrogen bonding. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. NIH, Struct Biol Lab, Div Comp Res & Technol, Bethesda, MD 20892 USA. RP Trout, BL (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM trout@mit.edu RI Chu, Jhih-Wei/D-2257-2012; Chu, Jhih-Wei/M-2870-2013 OI Chu, Jhih-Wei/0000-0003-3842-2893 NR 46 TC 31 Z9 34 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 22 PY 2004 VL 126 IS 50 BP 16601 EP 16607 DI 10.1021/ja0467059 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 880RZ UT WOS:000225808200066 PM 15600366 ER PT J AU Unal, E Arbel-Eden, A Sattler, U Shroff, R Lichten, M Haber, JE Koshland, D AF Unal, E Arbel-Eden, A Sattler, U Shroff, R Lichten, M Haber, JE Koshland, D TI DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain SO MOLECULAR CELL LA English DT Article ID SISTER-CHROMATID COHESION; SACCHAROMYCES-CEREVISIAE; FISSION YEAST; G2/M ARREST; REPAIR; ATM; COMPLEX; RECRUITMENT; CHECKPOINT; PROTEIN AB The postreplicative repair of double-strand breaks (DSBs) is thought to require sister chromatid cohesion, provided by the cohesin complex along the chromosome arms. A further specialized role for cohesin in DSB repair is suggested by its de novo recruitment to regions of DNA damage in mammals. Here, we show in budding yeast that a single DSB induces the formation of a similar to100 kb cohesin domain around the lesion. Our analyses suggest that the primary DNA damage checkpoint kinases Mec1p and Tel1p phosphorylate histone H2AX to generate a large domain, which is permissive for cohesin binding. Cohesin binding to the phospho-H2AX domain is enabled by Mre11p, a component of a critical repair complex, and Scc2p, a component of the cohesin loading machinery that is necessary for sister chromatid cohesion. We also provide evidence that the DSB-induced cohesin domain functions in postreplicative repair. C1 Carnegie Inst Washington, Howard Hughes Med Inst, Dept Embryol, Baltimore, MD 21210 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biol, Waltham, MA 02454 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Koshland, D (reprint author), Carnegie Inst Washington, Howard Hughes Med Inst, Dept Embryol, 115 W Univ Pkwy, Baltimore, MD 21210 USA. EM koshland@ciwemb.edu RI Lichten, Michael/C-5795-2013; OI Lichten, Michael/0000-0001-9707-2956; Haber, James/0000-0002-1878-0610 FU NIGMS NIH HHS [GM20056, GM61766] NR 55 TC 343 Z9 351 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 22 PY 2004 VL 16 IS 6 BP 991 EP 1002 DI 10.1016/j.molcel.2004.11.027 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 882IR UT WOS:000225933100013 PM 15610741 ER PT J AU Gu, YJ Guo, JX Pal, A Pan, SS Zimniak, P Singh, SV Ji, XH AF Gu, YJ Guo, JX Pal, A Pan, SS Zimniak, P Singh, SV Ji, XH TI Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity SO BIOCHEMISTRY LA English DT Article ID REFINEMENT; SITE; ISOMERIZATION; CONJUGATE; EVOLUTION; MOLSCRIPT; ENZYMES; A1-1; BOND AB The crystal structure of human class alyha glutathione (GSH) S-transferase A3-3 (hGSTA3-3) in complex with GSH was determined at 2.4 A. Despite considerable amino acid sequence identity with other human class alpha GSTs (e.g., hGSTA1-1), hGSTA3-3 is unique due to its exceptionally high steroid double bond isomerase activity for the transformation of Delta(5)-androstene-3,17-dione (Delta(5)-AD) to Delta(4)-androstene-3,17-dione. A comparative analysis of the active centers of hGSTA1-1 and hGSTA3-3 reveals that residues in positions 12 and 208 may contribute to their disparate isomerase activity toward Delta(5)-AD. Substitution of these two residues of hGSTA3-3 with the corresponding residues in hGSTA1-1 followed by kinetic characterization of the wild-type and the mutant enzymes supported this prediction. On the basis of our model of the hGSTA3-3.GSH.Delta(5)-AD, ternary complex and available biochemical data, we propose that the thiolate group of deprotonated GSH (GS(-)) serves as a base to initiate the reaction by accepting a proton from the steroid and the nonionized hydroxyl group of catalytic residue Y9 (HO-Y9) functions as part of a proton-conducting wire to transfer a proton back to the steroid. Residue R15 may function to stabilize the deprotonated thiolate group of GSH (GS(-)), and a GSH-bound water molecule may donate a hydrogen bond to the 3-keto group of Delta(5)-AD and thus help the thiolate of GS(-) to initiate the proton transfer and the subsequent stabilization of the reaction intermediate. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Pittsburgh Canc Inst, Pittsburgh, PA 15260 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. RP Ji, XH (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM jix@ncifcrf.gov RI Gu, Yijun/B-6017-2012; Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [CA076348]; NIEHS NIH HHS [ES009140, ES07804] NR 31 TC 18 Z9 19 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 21 PY 2004 VL 43 IS 50 BP 15673 EP 15679 DI 10.1021/bi048757g PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880GE UT WOS:000225776200003 PM 15595823 ER PT J AU Souliotis, VL Sfikakis, PP Anderson, LM Kyrtopoulos, SA AF Souliotis, VL Sfikakis, PP Anderson, LM Kyrtopoulos, SA TI Intra- and intercellular variations in the repair efficiency of O-6-methylguanine, and their contribution to kinetic complexity SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE O-6-alkylguanine-DNA alkyltransferase; repair kinetics; alpha-amanitin ID NON-PARENCHYMAL CELLS; RAT-LIVER DNA; ESCHERICHIA-COLI; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; N-NITROSODIMETHYLAMINE; CONTINUOUS EXPOSURE; METHYLATED PURINES; NITROSO-COMPOUNDS; EXCISION-REPAIR; ALPHA-AMANITIN AB Following administration to rats of various doses of N-nitrosodimethylamine (NDMA), O-6-methylguanine (O-6-meG) was lost from the DNA of four tissues (liver, white blood cells, lymph nodes, bone marrow) over two, sharply demarcated phases with substantially differing repair rates. Repair during each phase followed approximately first-order kinetics in O-6-meG, even after a high dose of NDMA which caused substantial depletion of O-6-alkylguanine-DNA alkyltransferase (AGT), a suicide repair protein. This is compatible with rate-determining adduct repair being brought about by a distinct, minor pool of AGT molecules which is rapidly replenished by de novo AGT synthesis. Similar biphasic repair kinetics were also observed in HepG2 cells treated in vitro with NDMA. In this case, the first phase of repair was inhibited by alpha-amanitin, an inhibitor of RNA polymerase II-mediated transcription. However, no dependence on transcriptional activity was found when O-6-meG repair in specific gene sequences with different transcriptional status in rat liver was examined, suggesting that the effects of a-amanitin in HepG2 cells did not reflect inhibition of preferential repair of transcribed sequences. Repair was also examined in rat liver hepatocytes and non-parenchymal cells separately after administration of NDMA at non-AGT depleting doses. Within each cell-population, the repair followed single phase, first-order kinetics, with adduct loss from AGT-rich hepatocytes being significantly faster than from the relatively AGT-deficient non-parenchymal cells. In conclusion, differences in the AGT content of different cell subpopulations in the liver (and probably in other tissues), as well as additional cellular factors affecting repair efficiency, appear to determine the observed variation in the kinetics of repair of O-6-meG. The additional cellular factors involved appear not to be related to the transcriptional state of the sequences being repaired, but may reflect different states of chromatin condensation. (C) 2004 Elsevier B.V. All rights reserved. C1 Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, GR-11635 Athens, Greece. Univ Athens, Sch Med, Dept Propedeut Med 1, GR-11527 Athens, Greece. NCI, Canc Res Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Souliotis, VL (reprint author), Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, 48 Vas Constantinou Ave, GR-11635 Athens, Greece. EM vls@eie.gr NR 45 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 EI 1873-135X J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 21 PY 2004 VL 568 IS 2 BP 155 EP 170 DI 10.1016/j.mrfmmm.2004.07.009 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 877ZK UT WOS:000225614500002 PM 15542103 ER PT J AU Barrett, MT Scheffer, A Ben-Dor, A Sampas, N Lipson, D Kincaid, R Tsang, P Curry, B Baird, K Meltzer, PS Yakhini, Z Bruhn, L Laderman, S AF Barrett, MT Scheffer, A Ben-Dor, A Sampas, N Lipson, D Kincaid, R Tsang, P Curry, B Baird, K Meltzer, PS Yakhini, Z Bruhn, L Laderman, S TI Comparative genomic hybridization using oligonucleotide microarrays and total genomic DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; DNA microarrays; genome ID NUCLEOTIDE POLYMORPHISM ARRAYS; HIGH-RESOLUTION ANALYSIS; COPY NUMBER VARIATION; CANCER; AMPLIFICATION; CARCINOMAS AB Array-based comparative genomic hybridization (CGH) measures copy-number variations at multiple loci simultaneously, providing an important tool for studying cancer and developmental disorders and for developing diagnostic and therapeutic targets. Arrays for CGH based on PCR products representing assemblies of BAC or cDNA clones typically require maintenance, propagation, replication, and verification of large clone sets. Furthermore, it is difficult to control the specificity of the hybridization to the complex sequences that are present in each feature of such arrays. To develop a more robust and flexible platform, we created probe-design methods and assay protocols that make oligonucleotide microarrays synthesized in situ by inkjet technology compatible with array-based comparative genomic hybridization applications employing samples of total genomic DNA. Hybridization of a series of cell lines with variable numbers of X chromosomes to arrays designed for CGH measurements gave median ratios for X-chromosome probes within 6% of the theoretical values (0.5 for XY/XX, 1.0 for XX/XX, 1.4 for XXX/XX, 2.1 for XXXX/XX, and 2.6 for XXXXX/XX). Furthermore, these arrays detected and mapped regions of single-copy losses, homozygous deletions, and amplicons of various sizes in different model systems, including diploid cells with a chromosomal breakpoint that has been mapped and sequenced to a precise nucleotide and tumor cell lines with highly variable regions of gains and losses. Our results demonstrate that oligonucleotide arrays designed for CGH provide a robust and precise platform for detecting chromosomal alterations throughout a genome with high sensitivity even when using full-complexity genomic samples. C1 Agilent Technol, Palo Alto, CA 94304 USA. NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. RP Laderman, S (reprint author), Agilent Technol, 3500 Deer Creek Rd, Palo Alto, CA 94304 USA. EM steve_laderman@agilent.com RI Kincaid, Robert/B-6683-2009 OI Kincaid, Robert/0000-0002-4344-0853 NR 26 TC 242 Z9 254 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 21 PY 2004 VL 101 IS 51 BP 17765 EP 17770 DI 10.1073/pnas.0407979101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 882PT UT WOS:000225951500037 PM 15591353 ER PT J AU Huebner, RE Nicol, M Mothupi, R Kayhty, H Mbelle, N Khomo, E Klugman, KP AF Huebner, RE Nicol, M Mothupi, R Kayhty, H Mbelle, N Khomo, E Klugman, KP TI Dose response of CRM197 and tetanus toxoid-conjugated Haemophilus influenzae type b vaccines SO VACCINE LA English DT Article DE Haemophilus influenzae type b vaccine; Hib; fractionated doses ID RANDOMIZED TRIAL; CHILDREN; MENINGITIS; IMMUNOGENICITY; EPIDEMIOLOGY; VACCINATION; PREVENTION; INFANTS; FINLAND; DISEASE AB High vaccine cost has limited use of conjugate vaccines in the developing world where the disease burden is greatest. Fixed fractional doses of Haemophilus influenzae type b (Hib) vaccines have been shown to be immunogenic, but dose responses of these vaccines in humans are needed to determine the lowest immunogenic dose as an option for lowering vaccine cost. We randomized children to receive one of five doses (0.625, 1.25, 2.5, 5.0 and 10 mug) of either a diphtheria CRM197 or tetanus toxoid-conjugated Hib vaccine. The children received a primary three-dose series at 6, 10, and 14 weeks of age and a booster dose at 9 months. Anti-PRP IgG antibodies were measured at each vaccination, at 18 weeks, and at one week following the booster dose. Concentrations of >1.25 mug of HibCRM(197) vaccine produced mean anti-PRP responses at 18 weeks of greater than or equal to5.72 mug/ml and greater than or equal to0.15 mug/ml was achieved in >98% of the children with at least 79% reaching anti-PRP concentrations of greater than or equal to1.0 mug/ml. Concentrations of greater than or equal to1.25 mug of Hib-tetanus vaccine produced mean anti-PRP responses at 18 weeks of greater than or equal to8.63 mug/ml and greater than or equal to0.15 mug/ml was achieved in 100% of the children with at least 88.9% reaching anti-PRP concentrations of greater than or equal to1.0 mug/ml. While mean antibody concentrations after either vaccine decreased over time, the proportion of children with antibody levels of greater than or equal to0.15 mug/ml had not changed significantly at the 9 month measurement. Immunologic memory was demonstrated by significant increases in mean antibody concentrations one week after the booster dose for doses greater than or equal to1.25 mug of HibCRM(197) and Hib-tetanus to mean concentrations greater than or equal to37.71 and 16.07 mug/ml, respectively. There were no differences in antibody responses for vaccine doses greater than or equal to1.25 mug of the same vaccine or between the same concentrations of the two different vaccines. Our data suggest that doses of these vaccines of greater than or equal to1.25 mug may be sufficient to stimulate an immune response that offers both short and longer term protection from invasive Hib disease. (C) 2004 Elsevier Ltd. All rights reserved. C1 MRC, Natl Hlth Lab Serv, Resp & Meningeal Pathogens Res Unit, Johannesburg, South Africa. Univ Witwatersrand, Johannesburg, South Africa. Natl Publ Hlth Inst, Dept Vaccines, Helsinki, Finland. Dept Int Hlth, Atlanta, GA USA. RP Klugman, KP (reprint author), NIAID, Epidemiol Branch, Basic Sci Program,Div AIDS, NIH,DHHS, 6700-B Rockledge Dr, Bethesda, MD 20892 USA. EM kklugma@sph.emory.edu OI Nicol, Mark/0000-0002-1366-4805 NR 18 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 21 PY 2004 VL 23 IS 6 BP 802 EP 806 DI 10.1016/j.vaccine.2004.06.052 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 882KC UT WOS:000225936800011 PM 15542205 ER PT J AU Mihalyi, E AF Mihalyi, E TI Review of some unusual effects of calcium binding to fibrinogen SO BIOPHYSICAL CHEMISTRY LA English DT Article DE fibrinogen; fibrin; thrombin; clotting; calcium binding; calorimetry ID BOVINE FIBRINOGEN; TERMINAL PARTS; MOLECULE; POLYMERIZATION; LOCALIZATION; ORGANIZATION; THROMBIN; RELEASE; CHAIN AB Calcium binding curves of human and bovine fibrinogen were obtained by using a calcium sensitive electrode. The two were identical and showed 2 high, 2-3 medium and more than 15 low affinity sites. Differential scanning calorimetry at neutral pH demonstrated the presence of the D and E domains of fibrinogen; however, at pH 3.5 the D-domain was split into two. The presence of the subdomains was demonstrated also by digestion by pepsin at this pH. Combination of digestion of fibrinogen and of its fragments with different enzymes and temperatures identified up to 12 subdomains in the original molecule. Clotting of fibrinogen by thrombin at pH 7.0 was investigated also by differential scanning calorimetry. In the absence of Ca2+ clotting elicited a 40% increase in the enthalpy of thermal denaturation of the D domain of fibrinogen, but the position of the peak increased only by 0.4 degreesC. However, with clotting in the presence of 10(-3) M calcium the former increased by 70-75% and the latter by 11.0 degreesC, while these parameters of the E-domain remained unchanged. Changes of bound calcium during clotting were also measured with the calcium sensitive electrode. These had to be corrected. because the drop in five calcium was partly compensated by release of some calcium that was already bound to fibrinogen. Log of the half time of calcium uptake plotted against log thrombin concentration indicated a first order process with respect to thrombin concentration. moreover, the rate determined corresponded to that of the conformation change measured by calorimetry. The calcium uptake was correlated with release of the fibrinopeptides. Release of fibrinopeptide B follows parallel to binding of calcium and that of fibrinopeptide A is about fourfold faster. Polymerization and formation of thick bundles of fibrin is connected with release of fibrinopeptide A. Clotting with Anerod, an enzyme that releases only fibrinopeptide A, showed only minimal binding of calcium. The polymerization inhibiting tetrapeptide Gly-Pro-Arg-Pro also depressed binding of calcium. These data suggest that a calcium-binding site must be in the proximity of the site of release of fibrinopeptide B and of a polymerization site. Published by Elsevier B.V. C1 NIH, Dept Clin Pathol, Serv Hematol, Bethesda, MD 20892 USA. RP Mihalyi, E (reprint author), NIH, Dept Clin Pathol, Serv Hematol, Bethesda, MD 20892 USA. EM emihalyi@aol.com NR 23 TC 10 Z9 10 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC 20 PY 2004 VL 112 IS 2-3 BP 131 EP 140 DI 10.1016/j.bpc.2004.07.012 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 885YS UT WOS:000226193900006 PM 15572240 ER PT J AU Nossal, R AF Nossal, R TI Zoetic polymers SO BIOPHYSICAL CHEMISTRY LA English DT Article DE rheology; biopolymers; actin filaments; microtubules; cell mechanics ID LIVING CELLS; INTERMEDIATE-FILAMENTS; MECHANICAL-PROPERTIES; FIBRIN CLOTS; CYTOARCHITECTURE; MICRORHEOLOGY; MICROSCOPY AB Conditions mediating the formation of biological polymers in situ are reviewed, and terminology suggested to differentiate polymers found in living cells from synthetic materials and polymers derived from biological sources that are modified or Studied in a way that obscures their biological function. Methods currently used to characterize the mechanical properties of biopolymer networks in cells are briefly discussed. Published by Elsevier B.V. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Nossal, R (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bldg 9,Room 1E116, Bethesda, MD 20892 USA. EM nossalr@mail.nih.edu NR 37 TC 0 Z9 0 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. PD DEC 20 PY 2004 VL 112 IS 2-3 BP 219 EP 222 DI 10.1016/j.bpc.2004.07.022 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 885YS UT WOS:000226193900019 PM 15572252 ER PT J AU Paschall, JE Oleksiak, MF VanWye, JD Roach, JL Whitehead, JA Wyckoff, GJ Kolell, KJ Crawford, DL AF Paschall, JE Oleksiak, MF VanWye, JD Roach, JL Whitehead, JA Wyckoff, GJ Kolell, KJ Crawford, DL TI FunnyBase: a systems level functional annotation of Fundulus ESTs for the analysis of gene expression SO BMC GENOMICS LA English DT Article ID SEQUENCE TAGS; PHYLOGENETIC ANALYSIS; CARDIAC-HYPERTROPHY; NATURAL-POPULATIONS; ENERGY-METABOLISM; GENOME DATABASE; MICROARRAY; PATTERNS; BRAIN; CDNA AB Background: While studies of non-model organisms are critical for many research areas, such as evolution, development, and environmental biology, they present particular challenges for both experimental and computational genomic level research. Resources such as mass-produced microarrays and the computational tools linking these data to functional annotation at the system and pathway level are rarely available for non-model species. This type of "systems-level" analysis is critical to the understanding of patterns of gene expression that underlie biological processes. Results: We describe a bioinformatics pipeline known as FunnyBase that has been used to store, annotate, and analyze 40,363 expressed sequence tags (ESTs) from the heart and liver of the fish, Fundulus heteroclitus. Primary annotations based on sequence similarity are linked to networks of systematic annotation in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and can be queried and computationally utilized in downstream analyses. Steps are taken to ensure that the annotation is self-consistent and that the structure of GO is used to identify higher level functions that may not be annotated directly. An integrated framework for cDNA library production, sequencing, quality control, expression data generation, and systems-level analysis is presented and utilized. In a case study, a set of genes, that had statistically significant regression between gene expression levels and environmental temperature along the Atlantic Coast, shows a statistically significant (P<0.001) enrichment in genes associated with amine metabolism. Conclusion: The methods described have application for functional genomics studies, particularly among non-model organisms. The web interface for FunnyBase can be accessed at http://genomics.rsmas.miami.edu/funnybase/super_craw4/. Data and source code are available by request at jpaschall@bioinfobase.umkc.edu. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Univ Missouri, Div Mol Biol & Biochem, Kansas City, MO 64110 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Crawford, DL (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. EM jep67c@umkc.edu; mfoleksi@ncsu.edu; jvanwye@rsmas.miami.edu; jlroach@rsmas.miami.edu; awhitehead@rsmas.miami.edu; wyckoffg@umkc.edu; kolellk@umkc.edu; dcrawford@rsmas.miami.edu RI Whitehead, Andrew/G-2122-2012 FU NHLBI NIH HHS [R01 HL65470, R01 HL065470]; NIEHS NIH HHS [R01 ES011588, ES011588] NR 54 TC 25 Z9 25 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD DEC 20 PY 2004 VL 5 AR 96 DI 10.1186/1471-2164-5-96 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 891UY UT WOS:000226607700001 PM 15610557 ER PT J AU Xu, DL Hay, JC AF Xu, DL Hay, JC TI Reconstitution of COPII vesicle fusion to generate a pre-Golgi intermediate compartment SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; SNARE COMPLEX; LIVING CELLS; TRANSPORT; ER AB What is the first membrane fusion step in the secretory pathway? In mammals, transport vesicles coated with coat complex (COP) II deliver secretary cargo to vesicular tubular clusters (VTCs) that ferry cargo from endoplasmic reticulum exit sites to the Golgi stack. However, the precise origin of VTCs and the membrane fusion step(s) involved have remained experimentally intractable. Here, we document in vitro direct tethering and SNARE-dependent fusion of endoplasmic reticulum-derived COPII transport vesicles to form larger cargo containers. The assembly did not require detectable Golgi membranes, preexisting VTCs, or CON function. Therefore, COPII vesicles appear to contain all of the machinery to initiate VTC biogenesis via homotypic fusion. However, COPI function enhanced VTC assembly, and early VTCs acquired specific Golgi components by heterotypic fusion with Golgi-derived CON vesicles. C1 Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. Univ Montana, COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA. Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. RP Hay, JC (reprint author), Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. EM jesse.hay@mso.umt.edu FU NIGMS NIH HHS [GM59378, R01 GM059378] NR 13 TC 64 Z9 67 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 20 PY 2004 VL 167 IS 6 BP 997 EP 1003 DI 10.1083/jcb.200408135 PG 7 WC Cell Biology SC Cell Biology GA 883TE UT WOS:000226037800001 PM 15611329 ER PT J AU Kuznetsov, SA Riminucci, M Ziran, N Tsutsui, TW Corsi, A Calvi, L Kronenberg, HM Schipani, E Robey, PG Bianco, P AF Kuznetsov, SA Riminucci, M Ziran, N Tsutsui, TW Corsi, A Calvi, L Kronenberg, HM Schipani, E Robey, PG Bianco, P TI The interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; FIBROUS DYSPLASIA; IN-VIVO; METAPHYSEAL CHONDRODYSPLASIA; STROMAL FIBROBLASTS; GRAFT SUBSTITUTES; LOCALIZATION; MICE; PRECURSORS AB The ontogeny of bone marrow and its stromal compartment, which Is generated from skeletal stem/ progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/paratkyroid hormone-related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Aquila, Dipartimento Med Sperimentale, I-67010 Coppito, Italy. Parco Sci Biomed San Raffaele, I-00161 Rome, Italy. Univ Rome La Sapienza 3, Dipartimento Med Sperimentale & Pathol, I-00161 Rome, Italy. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Robey, PG (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. EM probey@dir.nidcr.nih.gov; p.bianco@flashnet.it RI Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Calvi, Laura Maria/0000-0001-6969-239X FU NIAMS NIH HHS [P50 AR044855, AR044855]; NIDCR NIH HHS [Z01 DE000380, Z01 DE00380-20]; NIDDK NIH HHS [K08 DK064381, K08 DK064381-02, R21 DK069563, R21 DK069563-01]; Telethon [E.1029] NR 42 TC 78 Z9 80 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 20 PY 2004 VL 167 IS 6 BP 1113 EP 1122 DI 10.1083/jcb.200408079 PG 10 WC Cell Biology SC Cell Biology GA 883TE UT WOS:000226037800012 PM 15611335 ER PT J AU Kong, XT Deng, FM Hu, P Liang, FX Zhou, G Auerbach, AB Genieser, N Nelson, PK Robbins, ES Shapiro, E Kachar, B Sun, TT AF Kong, XT Deng, FM Hu, P Liang, FX Zhou, G Auerbach, AB Genieser, N Nelson, PK Robbins, ES Shapiro, E Kachar, B Sun, TT TI Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PERMEABILITY BARRIER FUNCTION; EPIDERMAL-GROWTH-FACTOR; TYPE-2 RECEPTOR GENE; NUCLEAR-DNA CONTENT; BLADDER EPITHELIUM; VESICOURETERAL REFLUX; UROTHELIAL DIFFERENTIATION; TRANSITIONAL EPITHELIUM; TETRASPANIN PROTEINS; MONOCLONAL-ANTIBODY AB Rhe apical surface of mouse urothelium is covered by two-dimensional crystals (plaques) of uroplakin (UP) particles. To study uroplakin function, we ablated the mouse UPII gene. A comparison of the phenotypes of UPII- and UPIII-deficient mice yielded new insights into the mechanism of plaque formation and some fundamental features of urothelial differentiation. Although UPIII knockout yielded small plaques, UPII knockout abolished plaque formation, indicating that both uroplakin heterodimers (UPIa/II and UPIb/III or IIIb) are required for plaque assembly. Both knockouts had elevated UPIb gene expression, suggesting that this is a general response to defective plaque assembly. Both knockouts also had small superficial cells, suggesting that continued fusion of uroplakin-delivering vesicles with the apical surface may contribute to umbrella cell enlargement. Both knockouts experienced vesicoureteral reflux, hydronephrosis, renal dysfunction, and, in the offspring of some breeding pairs, renal failure and neonatal death. These results highlight the functional importance of uroplakins and establish uroplakin defects as a possible cause of major urinary tract anomalies and death. C1 NYU, Sch Med, Ronald O Perelman Dept Dermatol, Epithelial Biol Unit, New York, NY 10016 USA. NYU, Sch Med, Dept Urol, New York, NY 10016 USA. NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA. NYU, Sch Med, New York Canc Inst, New York, NY 10016 USA. Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RP Sun, TT (reprint author), NYU, Sch Med, Ronald O Perelman Dept Dermatol, Epithelial Biol Unit, New York, NY 10016 USA. EM sunt01@med.nyu.edu OI Robbins, Edith S/0000-0003-1035-0621 FU NIDDK NIH HHS [DK39753, DK52206, DK66491, P01 DK052206, R01 DK039753, R01 DK066491] NR 74 TC 101 Z9 101 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 20 PY 2004 VL 167 IS 6 BP 1195 EP 1204 DI 10.1083/jcb.200406025 PG 10 WC Cell Biology SC Cell Biology GA 883TE UT WOS:000226037800019 PM 15611339 ER PT J AU Suzuki, S Numakawa, T Shimazu, K Koshimizu, H Hara, T Hatanaka, H Mei, L Lu, B Kojima, M AF Suzuki, S Numakawa, T Shimazu, K Koshimizu, H Hara, T Hatanaka, H Mei, L Lu, B Kojima, M TI BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts: roles in synaptic modulation SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HIGH-FREQUENCY STIMULATION; FIBROBLAST-GROWTH-FACTOR; NEUROTROPHIC FACTOR; CORTICAL-NEURONS; NERVOUS-SYSTEM; HIPPOCAMPAL-NEURONS; SIGNAL-TRANSDUCTION; GLUTAMATE RELEASE; SURVIVAL; TRANSMISSION AB Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity but the underlying signaling mechanisms remain unknown. Here, we show that BDNF rapidly recruits full-length TrkB (TrkB-FL) receptor into cholesterol-rich lipid rafts from nonraft regions of neuronal plasma membranes. Translocation of TrkB-FL was blocked by Trk inhibitors, suggesting a role of TrkB tyrosine kinase in the translocation. Disruption of lipid rafts by depleting cholesterol from cell surface blocked the ligand-induced translocation. Moreover, disruption of lipid rafts prevented potentiating effects of BDNF on transmitter release in cultured neurons and synaptic response to tetanus in hippocampal slices. in contrast, lipid rafts are not required for BDNF regulation of neuronal survival. Thus, ligand-induced TrkB translocation into lipid rafts may represent a signaling mechanism selective for synaptic modulation by BDNF in the central nervous system. C1 Natl Inst Adv Ind Sci & Technol, Res Inst Cell Engn, Ikeda, Osaka 5638577, Japan. Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan. Japan Sci & Technol Agcy, Solut Oriented Res Sci & Technol, Kawaguchi, Saitama 3320012, Japan. Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Kodaira, Tokyo 1878502, Japan. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Kojima, M (reprint author), Natl Inst Adv Ind Sci & Technol, Res Inst Cell Engn, Ikeda, Osaka 5638577, Japan. EM bailu@mail.NIH.gov; m-kojima@aist.go.jp RI Koshimizu, Hisatsugu/G-5536-2010; Lu, Bai/A-4018-2012; Mei, Lin/G-8755-2012 NR 42 TC 101 Z9 102 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 20 PY 2004 VL 167 IS 6 BP 1205 EP 1215 DI 10.1083/jcb.200404106 PG 11 WC Cell Biology SC Cell Biology GA 883TE UT WOS:000226037800020 PM 15596541 ER PT J AU Von Sternberg, R Schotte, M AF Von Sternberg, R Schotte, M TI A new anchialine shrimp of the genus Procaris (Crustacea : Decapoda : Procarididae) from the Yucatan Peninsula SO PROCEEDINGS OF THE BIOLOGICAL SOCIETY OF WASHINGTON LA English DT Article ID MARINE CAVES; AGOSTOCARIDIDAE; SUPERFAMILY; ATLANTIC; FAMILY AB A fourth species of the anchialine shrimp genus Procaris is described from Cozumel Island, Quintana Roo, Mexico. The combination of character states observed for the abdomen, antennal scale/stylocerite, second antennular segment, carapace, eyes, rostrum, and telson is unique in the genus. The new species appears to be morphologically most closely related to P. ascensionis from Ascension Island. Cladistic analysis of differentiating character states supports a sister group relationship between P. ascensionis and the Mexican species, in two out of three most parsimonious hypotheses. In addition, the Bermudan P. chacei and Hawaiian P. hawaiiana are positioned as sister taxa in all minimal length trees. While the discovery of a new Procaris species adds to our biogeographical knowledge of the genus, it has pointed to the possibility that the Atlantic taxa may be a paraphyletic assemblage. C1 NCBI GenBank, NIH, Bethesda, MD 20892 USA. Smithsonian Inst, Dept Zool, Natl Museum Nat Hist, Washington, DC 20013 USA. RP Von Sternberg, R (reprint author), NCBI GenBank, NIH, Bldg 45,Room 6An,18D-30, Bethesda, MD 20892 USA. EM sternber@ncbi.nlm.nih.gov; Schottem@si.edu NR 15 TC 4 Z9 5 U1 0 U2 1 PU BIOL SOC WASHINGTON PI WASHINGTON PA NAT MUSEUM NAT HIST SMITHSONIAN INST, WASHINGTON, DC 20560 USA SN 0006-324X J9 P BIOL SOC WASH JI Proc. Biol. Soc. Wash. PD DEC 20 PY 2004 VL 117 IS 4 BP 514 EP 522 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 895RM UT WOS:000226880700004 ER PT J AU Ramirez, JM Houzet, L Koller, R Bies, J Wolff, L Mougel, M AF Ramirez, JM Houzet, L Koller, R Bies, J Wolff, L Mougel, M TI Activation of c-myb by 5 ' retrovirus promoter insertion in myeloid neoplasms is dependent upon an intact alternative splice donor site (SD') in gag SO VIROLOGY LA English DT Article DE MuLV; splicing; leukemia; c-myb; oncogene; tumorigenesis; myeloid neoplasm; lymphoma ID MURINE LEUKEMIA-VIRUS; AVIAN-LEUKOSIS VIRUS; B-CELL LYMPHOMA; PROMONOCYTIC LEUKEMIA; INTEGRATION SITES; BALB/C MICE; TUMORS; GENES; GENOME; CANCER AB Alternative splicing in Mo-MuLV recruits a splice donor site, SD', within the gag that is required for optimal replication in vitro. Remarkably, this SD' site was also found to be utilized for production of oncogenic gag-myb fusion RNA in 100% of murine-induced myeloid leukemia (MML) in pristane-treated BALB/c mice. Therefore, we investigated the influence of silent mutations of SD' in this model. Although there was no decrease in the overall incidence of disease, there was a decrease in the incidence of myeloid leukemia with a concomitant increase in lymphoid leukemia. Importantly, there was a complete lack of myeloid tumors associated with 5' insertional mutagenic activation of c-myb, suggesting the specific requirement of the SD' site in this mechanism. (C) 2004 Elsevier Inc. All rights reserved. C1 UMI, UMR5121, Inst Biol,CNRS, IFR122,Lab Infect Retrovirales & Signalisat Cellu, F-34960 Montpellier 2, France. NCI, Lab Clin Oncol, NIH, Bethesda, MD 20892 USA. Slovak Acad Sci, Canc Res Inst, Ctr Mol Med, Bratislava, Slovakia. RP Mougel, M (reprint author), UMI, UMR5121, Inst Biol,CNRS, IFR122,Lab Infect Retrovirales & Signalisat Cellu, 4 Bd Henri IV, F-34960 Montpellier 2, France. EM mmoungel@univ-montp1.fr RI Mougel, Marylene/K-7958-2013 OI Mougel, Marylene/0000-0002-0345-1427 NR 41 TC 6 Z9 6 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 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2004 VL 330 IS 2 BP 398 EP 407 DI 10.1016/j.virol.2004.09.038 PG 10 WC Virology SC Virology GA 880HK UT WOS:000225779400004 PM 15567434 ER PT J AU Szajner, P Jaffe, H Weisberg, AS Moss, B AF Szajner, P Jaffe, H Weisberg, AS Moss, B TI A complex of seven vaccinia virus proteins conserved in all chordopoxviruses is required for the association of membranes and viroplasm to forin immature virions SO VIROLOGY LA English DT Article DE chordopoxviruses; vaccinia virus proteins; immature virions ID INTRACELLULAR ENVELOPED VIRIONS; BACTERIOPHAGE-T7 RNA-POLYMERASE; A14 PHOSPHOPROTEIN; PROGENY VACCINIA; VIRAL MEMBRANES; DENSE VIROPLASM; A30L PROTEIN; F10 KINASE; MORPHOGENESIS; MOVEMENT AB Early events in vaccinia virus (VAC) morphogenesis, particularly the formation of viral membranes and their association with viroplasm, are poorly understood. Recently, we showed that repression of A30 or G7 expression results in the accumulation of normal viral membranes that form empty-looking immature virions (IV), which are separated from large masses of electron-dense viroplasm. In addition, A30 and G7 physically and functionally interact with each other and with the F10 protein kinase. To identify other proteins involved in early morphogenesis, proteins from cells that had been infected with vaccinia virus expressing an epitope-tagged copy of F10 were purified by immunoaffinity chromatography and analyzed by gel electrophoresis. In addition to F10, A30, and G7, viral proteins A15, D2, D3, and J1 were identified by mass spectrometry of tryptic peptides. Further evidence for the complex was obtained by immunopurification of proteins associated with epitope-tagged A 15, D2, and D3. The previously unstudied A 15, like other proteins in the complex, was expressed late in infection, associated with virus cores, and required for the stability and kinase activity of F10. Biochemical and electron microscopic analyses indicated that mutants in which A15 or D2 expression was regulated by the Escherichia coli lac operator system exhibited phenotypes characterized by the presence of large numbers of empty immature virions, similar to the results obtained with inducible A30 and G7 mutants. Empty immature virions were also seen by electron microscopy of cells infected with temperature-sensitive mutants of D2 or D3, though the numbers of membrane forms were reduced perhaps due to additional effects of high temperature. Published by Elsevier Inc. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NINDS, Prot Peptide Sequence Facil, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 45 TC 26 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 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2004 VL 330 IS 2 BP 447 EP 459 DI 10.1016/j.virol.2004.10.008 PG 13 WC Virology SC Virology GA 880HK UT WOS:000225779400008 PM 15567438 ER PT J AU Berger, VW Ioannidis, JPA AF Berger, VW Ioannidis, JPA TI The Decameron of poor research SO BRITISH MEDICAL JOURNAL LA English DT Article C1 Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. NCI, Biometry Res Grp, NIH, Bethesda, MD 20892 USA. RP Ioannidis, JPA (reprint author), Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. EM jioannid@cc.uoi.gr RI Ioannidis, John/G-9836-2011 NR 0 TC 3 Z9 3 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD DEC 18 PY 2004 VL 329 IS 7480 BP 1436 EP 1440 DI 10.1136/bmj.329.7480.1436 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 882VB UT WOS:000225965800020 PM 15604177 ER PT J AU Arndt, MAE Krauss, R Rybak, SM AF Arndt, MAE Krauss, R Rybak, SM TI Antigen binding and stability properties of non-covalently linked anti-CD22 single-chain Fv dimers SO FEBS LETTERS LA English DT Article DE CD22; single chain Fv; diabody; dimer; stability ID NEURAMINIDASE ANTIBODY NC10; SCFV MULTIMERS; V-H; FRAGMENTS; TRIABODIES; DIABODIES; CC49; CARCINOMA; LYMPHOMA; MOLECULE AB By varying linker length and domain orientation three multivalent derivatives of a monovalent anti-CD22 single-chain fragment variable (scFv) antibody were generated. Shortening the linker of the V-H-V-L oriented scFv to 5 or 0 residues resulted in the formation of diabodies or a mixture of tetramers and trimers, respectively. Unexpectedly, a V-L-0-V-H scFv assembled to homogenous dimers, remained substantially more stable than the V-H-5-V-L diabody when incubated in human serum at 37 degreesC, and retained its dimeric state when concentrated up to 4 mg/ml. These properties suggest the V-L-0-V-H scFv could become an attractive vehicle for the selective delivery of multiple effector molecules to CD22(+) tumor cells. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Univ Hosp Essen, Inst Immunol, D-45122 Essen, Germany. NCI, SAIC, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Arndt, MAE (reprint author), Univ Hosp Essen, Inst Immunol, Virchowstr 171, D-45122 Essen, Germany. EM michaela.arndt@medizin.uni-essen.de; juergen.krauss@uni-essen.de; rybak@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 31 TC 16 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 17 PY 2004 VL 578 IS 3 BP 257 EP 261 DI 10.1016/j.febslet.2004.11.011 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 882LH UT WOS:000225939900011 PM 15589829 ER PT J AU Ahn, B Harrigan, JA Indig, FE Wilson, DM Bohr, VA AF Ahn, B Harrigan, JA Indig, FE Wilson, DM Bohr, VA TI Regulation of WRN helicase activity in human base excision repair SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WERNER-SYNDROME PROTEIN; DNA-POLYMERASE-BETA; HUMAN APURINIC ENDONUCLEASE; AAA-ATPASE P97/VCP; FLAP ENDONUCLEASE-1; MAJOR HUMAN; BIOCHEMICAL-CHARACTERIZATION; FUNCTIONAL INTERACTION; SUBSTRATE-SPECIFICITY; AP ENDONUCLEASE-1 AB Werner syndrome patients are deficient in the Werner protein (WRN), which is a multifunctional nuclear protein possessing 3'- 5' exonuclease and ATP-dependent helicase activities. Studies of Werner syndrome cells and biochemical studies of WRN suggest that WRN plays a role in several DNA metabolic pathways. WRN interacts with DNA polymerase beta(pol beta) and stimulates pol beta strand displacement synthesis on a base excision repair (BER) intermediate in a helicase-dependent manner. In this report, we examined the effect of the major human apurinic/apyrimidinic endonuclease (APE1) and of pol beta on WRN helicase activity. The results show that WRN alone is able to unwind several single strand break BER intermediates. However, APE1 inhibits WRN helicase activity on these intermediates. This inhibition is likely due to the binding of APE1 to nicked apurinic/apyrimidinic sites, suggesting that APE1 prevents the promiscuous unwinding of BER intermediates. This inhibitory effect was relieved by the presence of pol beta. A model involving the pol beta-mediated hand-off of WRN protein is proposed based on these results. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Ulsan, Dept Life Sci, Ulsan 680749, South Korea. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov NR 45 TC 60 Z9 65 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 2004 VL 279 IS 51 BP 53465 EP 53474 DI 10.1074/jbc.M409624200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878XL UT WOS:000225680600081 PM 15385537 ER PT J AU Kumar, S Gupta, L Han, YS Barillas-Mury, C AF Kumar, S Gupta, L Han, YS Barillas-Mury, C TI Inducible Peroxidases mediate nitration of Anopheles midgut cells undergoing apoptosis in response to Plasmodium invasion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE; IN-VITRO; NITROTYROSINE FORMATION; EOSINOPHIL PEROXIDASE; OOKINETE INVASION; MYELOPEROXIDASE; PEROXYNITRITE; TYROSINE; MECHANISM; GAMBIAE AB Plasmodium berghei invasion of Anopheles stephensi midgut cells causes severe damage, induces expression of nitric-oxide synthase, and leads to apoptosis. The present study indicates that invasion results in tyrosine nitration, catalyzed as a two-step reaction in which nitric-oxide synthase induction is followed by increased peroxidase activity. Ookinete invasion induced localized expression of peroxidase enzymes, which catalyzed protein nitration in vitro in the presence of nitrite and H2O2. Histochemical stainings revealed that when a parasite migrates laterally and invades more than one cell, the pattern of induced peroxidase activity is similar to that observed for tyrosine nitration. In Anopheles gambiae, ookinete invasion elicited similar responses; it induced expression of 5 of the 16 peroxidase genes predicted by the genome sequence and decreased mRNA levels of one of them. One of these inducible peroxidases has a C-terminal oxidase domain homologous to the catalytic moiety of phagocyte NADPH oxidase and could provide high local levels of superoxide anion (O-2(radical anion)), that when dismutated would generate the local increase in H2O2 required for nitration. Chemically induced apoptosis of midgut cells also activated expression of four ookinete-induced peroxidase genes, suggesting their involvement in general apoptotic responses. The two-step nitration reaction provides a mechanism to precisely localize and circumscribe the toxic products generated by defense reactions involving nitration. The present study furthers our understanding of the biochemistry of midgut defense reactions to parasite invasion and how these may influence the efficiency of malaria transmission by anopheline mosquitoes. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. RP Barillas-Mury, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM cbarillas@niaid.nih.gov FU NIAID NIH HHS [R01AI45573] NR 33 TC 72 Z9 75 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 2004 VL 279 IS 51 BP 53475 EP 53482 DI 10.1074/jbc.M409905200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878XL UT WOS:000225680600082 PM 15456781 ER PT J AU Yarovinsky, F Andersen, JF King, LR Caspar, P Aliberti, J Golding, H Sher, A AF Yarovinsky, F Andersen, JF King, LR Caspar, P Aliberti, J Golding, H Sher, A TI Structural determinants of the anti-HIV activity of a CCR5 antagonist derived from Toxoplasma gondii SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYCLOPHILIN-A; CRYSTAL-STRUCTURE; CYCLOSPORINE-A; CELL LINE; INFECTION; RECEPTOR; BINDING; ENTRY; INHIBITION AB The protozoan parasite Toxoplasma gondii possesses a protein, cyclophilin-18 (C-18), which binds to the chemokine receptor CCR5, induces interleukin-12 production from murine dendritic cells, and inhibits fusion and infectivity of human immunodeficiency virus 1 (HIV-1) R5 viruses by co-receptor antagonism. Site-directed mutagenesis was employed to identify the domains in C-18 responsible for its CCR5 binding and antiviral functions. To do so we focused on amino acid differences with Plasmodium falciparum cyclophilin, which, although 53% identical with C-18, has minimal binding activity for CCR5, and we generated 22 mutants with substitutions in the regions of non-homology located on the putative surface of the molecule. Two mutations situated on the face of C-18, predicted to be involved in its interaction with the ligand cyclosporin A, were shown to be critical for CCR5-binding and the inhibition of HIV-1 fusion and infectivity. In contrast, four mutations in C-18 specifically designed to abolish the peptidylprolyl cis-trans-isomerase activity of the protein failed to inactivate its CCR5 binding and HIV inhibitory activities. Interleukin-12 induction by C-18, on the other hand, was abrogated by mutations effecting either the CCR5 binding or enzymatic function of the molecule. These findings shed light on the structural basis of the molecular mimicry of the chemokine function by a pathogen-derived protein and provide a basis for further modification of C-18 into an antiviral agent. C1 NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Sher, A (reprint author), NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. EM asher@mail.nih.gov RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 36 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 2004 VL 279 IS 51 BP 53635 EP 53642 DI 10.1074/jbc.M410550200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878XL UT WOS:000225680600100 PM 15469936 ER PT J AU Wang, Y Kedei, N Wang, M Wang, QJ Huppler, AR Toth, A Tran, R Blumberg, PM AF Wang, Y Kedei, N Wang, M Wang, QJ Huppler, AR Toth, A Tran, R Blumberg, PM TI Interaction between protein kinase C mu and the vanilloid receptor type 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATION LOOP SER(744); DIRECT PHOSPHORYLATION; D PKD; EPSILON; CELLS; VR1; IDENTIFICATION; EXPRESSION; SUBSTRATE; NEURONS AB The capsaicin receptor VR1 is a polymodal nociceptor activated by multiple stimuli. It has been reported that protein kinase C plays a role in the sensitization of VR1. Protein kinase D/PKCmu is a member of the protein kinase D serine/threonine kinase family that exhibits structural, enzymological, and regulatory features distinct from those of the PKCs, with which they are related. As part of our effort to optimize conditions for evaluating VR1 pharmacology, we found that treatment of Chinese hamster ovary (CHO) cells heterologously expressing rat VR1 (CHO/rVR1) with butyrate enhanced rVR1 expression and activity. The expression of PKCmu and PKCbeta1, but not of other PKC isoforms, was also enhanced by butyrate treatment, suggesting the possibility that these two isoforms might contribute to the enhanced activity of rVR1. In support of this hypothesis, we found the following. 1) Overexpression of PKCmu enhanced the response of rVR1 to capsaicin and low pH, and expression of a dominant negative variant of PKCmu reduced the response of rVR1. 2) Reduction of endogenous PKCmu using antisense oligonucleotides decreased the response of exogenous rVR1 expressed in CHO cells as well as of endogenous rVR1 in dorsal root ganglion neurons. 3) PKCmu localized to the plasma membrane when overexpressed in CHO/rVR1 cells. 4) PKCmu directly bound to rVR1 expressed in CHO cells as well as to endogenous rVR1 in dorsal root ganglia or to an N-terminal fragment of rVR1, indicating a direct interaction between PKCmu and rVR1. 5) PKCmu directly phosphorylated rVR1 or a longer N-terminal fragment ( amino acids 1-118) of rVR1 but not a shorter one (amino acids 1-99). 6) Mutation of S116A in rVR1 blocked both the phosphorylation of rVR1 by PKCmu and the enhancement by PKCmu of the rVR1 response to capsaicin. We conclude that PKCmu functions as a direct modulator of rVR1. C1 Peking Univ, Dept Neurobiol, Neurosci Res Inst, Beijing 100083, Peoples R China. NCI, NIH, Bethesda, MD 20892 USA. RP Wang, Y (reprint author), Peking Univ, Dept Neurobiol, Neurosci Res Inst, 38 Xue Yuan Rd, Beijing 100083, Peoples R China. EM wangy66@bjmu.edu.cn; blumberp@dc37a.nci.nih.gov RI Toth, Attila/F-4859-2010; Wang, Qiming/B-6064-2012 OI Toth, Attila/0000-0001-6503-3653; NR 23 TC 50 Z9 57 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 2004 VL 279 IS 51 BP 53674 EP 53682 DI 10.1074/jbc.M410331200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878XL UT WOS:000225680600104 PM 15471852 ER PT J AU He, YY Huang, JL Chignell, CF AF He, YY Huang, JL Chignell, CF TI Delayed and sustained activation of extracellular signal-regulated kinase in human keratinocytes by UVA - Implications in carcinogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR; DOWN-REGULATION; SINGLET OXYGEN; ERK; APOPTOSIS; PATHWAY; RAS; JNK; PHOSPHORYLATION; RADIATION AB Exposure to the sun's UV radiation appears to be the most important environmental factor involved in the development of skin cancer. UVA is the major portion of UV radiation in sunlight and is considered to be a human carcinogen. In this study, we have investigated the delayed and sustained activation of ERK MAPK by UVA exposure. In parallel, a delayed Ras activation with a similar time course was observed after UVA exposure. The activated Ras was found to be localized in endomembranes such as the Golgi apparatus instead of plasma membranes. Expression of dominant negative Ras (N17Ras) abolished ERK activation by UVA. The presence of AG1478, an epidermal growth factor (EGF) receptor ( EGFR) kinase inhibitor, had no effect on ERK or Ras activation, indicating that EGFR kinase activity is not involved in ERK activation by UVA. In contrast, protein kinase C (PKC) depletion by chronic 12-O-tetradecanoylphorbol-13-acetate treatment nearly abolished UVA-induced ERK and Ras activation. The presence of the Ca2+-dependent-PKC inhibitor Go6976 had a similar effect. These findings suggest that ERK activation by UVA is mediated by PKC in a Ras-dependent pathway. In addition, a gradual increase in intracellular calcium level after UVA exposure was detected by flow cytometry. The presence of the PLC inhibitor U73122 or the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N, N, N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA-AM) blocked both ERK and Ras activation, suggesting that both PLC and calcium are required for ERK activation. Our findings demonstrated that, different from UVC and UVB, UVA-induced delayed and sustained ERK activation is EGFR kinase activity-independent, but PLC/calcium/PKC-mediated. The delayed and sustained ERK activation provides a survival signal to human HaCaT keratinocytes, which may serve as an important mechanism for cell transformation and potential skin carcinogenesis in vivo caused by UVA exposure. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP He, YY (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, FO-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM he3@niehs.nih.gov NR 32 TC 63 Z9 67 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 2004 VL 279 IS 51 BP 53867 EP 53874 DI 10.1074/jbc.M405781200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878XL UT WOS:000225680600125 PM 15471881 ER PT J AU Ma, BY Nussinov, R AF Ma, BY Nussinov, R TI Release factors eRF1 and RF2 - A universal mechanism controls the large conformational changes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RIBOSOME RECYCLING FACTOR; TRANSFER-RNA HYDROLYSIS; POLYPEPTIDE RELEASE; CRYSTAL-STRUCTURE; TRANSLATION TERMINATION; HISTIDINE PROTONATION; STRUCTURALLY DISTINCT; ANGSTROM RESOLUTION; STOP CODONS; FACTOR RRF AB Class I release factors 1 and 2 (RF1 and RF2) terminate protein synthesis by recognizing stop codons on the mRNA via their conserved amino acid motifs (NIKS in eRF1 and SPF in RF2) and by the conserved tripeptide (GGQ) interactions with the ribosomal peptidyltransferase center. Crystal structures of eRF1 and RF2 do not fit their ribosomal binding pocket (similar to73 Angstrom). Cryoelectron microscopy indicates large conformational changes in the ribosome-bound RF2. Here, we investigate the conformational dynamics of the eRF1 and RF2 using molecular dynamics simulation, structural alignment, and electrostatic analysis of domain interactions. We show that relaxed eRF1 has a shape remarkably similar to the ribosome-bound RF2 observed by cryoelectron microscopy. The similarity between the two release factors is as good as between elongation factor G and elongation factor Tuguanosine-5'(beta,gamma-imido)triphosphate-tRNA. Further, the conformational transitions and dynamics of eRF1 and RF2 between the free and ribosome-bound states are most likely controlled by protonation of conserved histidines. For eRF1, the distance between the NIKS and GGQ motifs shrinks from 97.5 Angstromin the crystal to 70-80 Angstrom. For RF2, the separation between SPF and GGQ elongates from 32 Angstrom in the crystal to 50 Angstrom. Coulombic interaction strongly favors the open conformation of eRF1; however, solvation and histidine protonation modulate the domain interactions, making the closed conformation of eRF1 more accessible. Thus, RF1 and RF2 function like molecular machines, most likely fueled by histidine protonation. The unified conformational control and the shapes of eRF1 and RF2 support the proposition that the termination of protein synthesis involves similar mechanisms across species. C1 NCI, Basic Res Program, SAIC Frederick Inc, Lab Expt & Computat Biol,NIH, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Lab Expt & Computat Biol,NIH, Frederick, MD 21702 USA. EM mab@ncifcrf.gov; ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-12400] NR 35 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 2004 VL 279 IS 51 BP 53875 EP 53885 DI 10.1074/jbc.M407412200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878XL UT WOS:000225680600126 PM 15475364 ER PT J AU Meyron-Holtz, EG Ghosh, MC Rouault, TA AF Meyron-Holtz, EG Ghosh, MC Rouault, TA TI Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo SO SCIENCE LA English DT Article ID SULFUR CLUSTER; DEGRADATION; METABOLISM; CELLS; IRP2; HOMEOSTASIS; ACONITASE; TENSION; MUTANT; HEME AB The iron-regulatory proteins (IRPs) posttranscriptionally regulate expression of transferrin receptor, ferritin, and other iron metabolism proteins. Although both IRPs can regulate expression of the same target genes, IRP2(-/-) mice significantly misregulate iron metabolism and develop neurodegeneration, whereas IRP1(-/-) mice are spared. We found that IRP2(-/-) cells misregulated iron metabolism when cultured in 3 to 6% oxygen, which is comparable to physiological tissue concentrations, but not in 21% oxygen, a concentration that activated IRP1 and allowed it to substitute for IRP2. Thus, IRP2 dominates regulation of mammalian iron homeostasis because it alone registers iron concentrations and modulates its RNA-binding activity at physiological oxygen tensions. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. EM trou@helix.nih.gov RI Meyron-Holtz, Esther/B-5991-2013 NR 29 TC 138 Z9 145 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 17 PY 2004 VL 306 IS 5704 BP 2087 EP 2090 DI 10.1126/science.1103786 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 881CM UT WOS:000225841000061 PM 15604406 ER PT J AU Nemoto, S Fergusson, MM Finkel, T AF Nemoto, S Fergusson, MM Finkel, T TI Nutrient availability regulates SIRT1 through a forkhead-dependent pathway SO SCIENCE LA English DT Article ID CAENORHABDITIS-ELEGANS; LIFE-SPAN; TRANSCRIPTION FACTORS; CALORIE RESTRICTION; CELL-SURVIVAL; FHA DOMAIN; P53; DEACETYLASE; DEATH; MDC1 AB Nutrient availability regulates life-span in a wide range of organisms. We demonstrate that in mammalian cells, acute nutrient withdrawal simultaneously augments expression of the SIRT1 deacetylase and activates the Forkhead transcription factor Foxo3a. Knockdown of Foxo3a expression inhibited the starvation-induced increase in SIRT1 expression. Stimulation of SIRT1 transcription by Foxo3a was mediated through two p53 binding sites present in the SIRT1 promoter, and a nutrient-sensitive physical interaction was observed between Foxo3a and p53. SIRT1 expression was not induced in starved p53-deficient mice. Thus, in mammalian cells, p53, Foxo3a, and SIRT1, three proteins separately implicated in aging, constitute a nutrient-sensing pathway. C1 NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiovasc Branch, Bldg 10, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 23 TC 390 Z9 406 U1 1 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 17 PY 2004 VL 306 IS 5704 BP 2105 EP 2108 DI 10.1126/science.1101731 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 881CM UT WOS:000225841000066 PM 15604409 ER PT J AU Balboni, G Salvadori, S Dal Piaz, A Bortolotti, F Argazzi, R Negri, L Lattanzi, R Bryant, SD Jinsmaa, Y Lazarus, LH AF Balboni, G Salvadori, S Dal Piaz, A Bortolotti, F Argazzi, R Negri, L Lattanzi, R Bryant, SD Jinsmaa, Y Lazarus, LH TI Highly selective fluorescent analogue of the potent delta-opioid receptor antagonist Dmt-Tic SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY; PEPTIDE; BINDING; PROBES; PHARMACOPHORE; LIGAND; MU; DELTORPHINS; AGONISTS; CELLS AB A fluorescent tripeptide probe derived by coupling fluorescein to H-Dmt-Tic-Glu-NH2 was developed to interact with delta-opioid receptors with high affinity (K-i = 0.035 nM) and selectivity (K-i(mu)/K-i(delta) = 4371). It acts as an irreversible delta-opioid receptor antagonist, and binding to NG108-15 cells is blocked by the standard nonpeptidic delta-opioid receptor antagonist naltrindole. This probe should prove useful in the study of the distribution of delta-opioid receptors in tissues and the internalization of opioid peptides during signal transduction. C1 Univ Cagliari, Dept Toxicol, I-09126 Cagliari, Italy. Univ Ferrara, Dept Chem, I-44100 Ferrara, Italy. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Univ Roma La Sapienza, Dept Human Physiol & Pharmacol Vittorio Erspamer, I-00185 Rome, Italy. NIEHS, LCBRA, Med Chem Grp, Res Triangle Pk, NC 27709 USA. RP Lazarus, LH (reprint author), Univ Cagliari, Dept Toxicol, I-09126 Cagliari, Italy. EM lazarus@niehs.nih.gov RI Argazzi, Roberto/C-4819-2015; OI Argazzi, Roberto/0000-0002-2619-6860; LATTANZI, Roberta/0000-0002-6377-9256 NR 29 TC 19 Z9 20 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 16 PY 2004 VL 47 IS 26 BP 6541 EP 6546 DI 10.1021/jm040128h PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 879VZ UT WOS:000225748500016 PM 15588089 ER PT J AU Hassan, SA AF Hassan, SA TI Intermolecular potentials of mean force of amino acid side chain interactions in aqueous medium SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; PARTICLE MESH EWALD; PERIODIC BOUNDARY-CONDITIONS; SCREENED COULOMB POTENTIALS; GUANIDINIUM ION-PAIR; POLAR GROUP BURIAL; MONTE-CARLO; ELECTROSTATIC INTERACTIONS; PROTEIN STABILITY; SODIUM-CHLORIDE AB A systematic study of the potentials of mean force (PMF) of hydrogen-bonded amino acid side chains in water is reported. Hydrogen-bonding (HB) partners are classified according to the hybridization state of their donor and acceptor atoms, as well as the net charge of the interacting pairs. This classification leads to a total of 42 classes of representative HB interactions. Constrained molecular dynamics simulations are carried out to calculate the intermolecular mean force (MF) of the solute molecules in an explicit solvent composed of nonpolarizable TIP3P water. Long-range forces are calculated using particle mesh Ewald (PME) summation in a cubic lattice with periodic boundary conditions. The intermolecular PMF are obtained by integrating the MF along a specified reaction path. MF autocorrelation functions and correlation times are calculated for each HB class. Statistical errors in the MF and PMF are estimated and reported. The results are compared with those reported in the literature for simpler systems in the liquid phase. The implications of the results for the description of effective HB interactions in continuum approximations of solvent effects in mesoscopic systems are discussed. C1 DHHS, Ctr Mol Modeling, Div Computat Biosci, CIT,NIH, Bethesda, MD 20892 USA. RP DHHS, Ctr Mol Modeling, Div Computat Biosci, CIT,NIH, Bethesda, MD 20892 USA. EM mago@helix.nih.gov NR 89 TC 32 Z9 33 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 16 PY 2004 VL 108 IS 50 BP 19501 EP 19509 DI 10.1021/jp0468410 PG 9 WC Chemistry, Physical SC Chemistry GA 879CX UT WOS:000225695100065 ER PT J AU Landon, MB Hauth, JC Leveno, KJ Spong, CY Leindecker, S Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sibai, B Langer, O Thorp, JM Ramin, SM Mercer, BM Gabbe, SG Iams, J Johnson, F Meadows, S Walker, H Rouse, D Northen, A Tate, S Bloom, S McCampbell, J Bradford, D Belfort, M Porter, F Oshiro, B Anderson, K Guzman, A Hibbard, J Jones, P Ramos-Brinson, M Moran, M Scott, D Lain, K Cotroneo, M Fischer, D Luce, M Meis, P Swain, M Moorefield, C Lanier, K Steele, L Sciscione, A DiVito, M Talucci, M Pollock, M Dombrowski, M Norman, G Millinder, A Sudz, C Steffy, B Siddiqi, T How, H Elder, N Malone, F D'Alton, M Pemberton, V Carmona, V Husami, H Silver, H Tillinghast, J Catlow, D Allard, D Socol, M Gradishar, D Mallett, G Burkett, G Gilles, J Potter, J Doyle, F Chandler, S Mabie, W Ramsey, R Conway, D Barker, S Rodriguez, M Moise, K Dorman, K Brody, S Mitchell, J Gilstrap, L Day, M Kerr, M Gildersleeve, E Catalano, P Milluzzi, C Slivers, B Santori, C Thom, E Julienson-Stevenson, H Fischer, M Weiner, S McNellis, D Howell, K Pagliaro, S AF Landon, MB Hauth, JC Leveno, KJ Spong, CY Leindecker, S Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sibai, B Langer, O Thorp, JM Ramin, SM Mercer, BM Gabbe, SG Iams, J Johnson, F Meadows, S Walker, H Rouse, D Northen, A Tate, S Bloom, S McCampbell, J Bradford, D Belfort, M Porter, F Oshiro, B Anderson, K Guzman, A Hibbard, J Jones, P Ramos-Brinson, M Moran, M Scott, D Lain, K Cotroneo, M Fischer, D Luce, M Meis, P Swain, M Moorefield, C Lanier, K Steele, L Sciscione, A DiVito, M Talucci, M Pollock, M Dombrowski, M Norman, G Millinder, A Sudz, C Steffy, B Siddiqi, T How, H Elder, N Malone, F D'Alton, M Pemberton, V Carmona, V Husami, H Silver, H Tillinghast, J Catlow, D Allard, D Socol, M Gradishar, D Mallett, G Burkett, G Gilles, J Potter, J Doyle, F Chandler, S Mabie, W Ramsey, R Conway, D Barker, S Rodriguez, M Moise, K Dorman, K Brody, S Mitchell, J Gilstrap, L Day, M Kerr, M Gildersleeve, E Catalano, P Milluzzi, C Slivers, B Santori, C Thom, E Julienson-Stevenson, H Fischer, M Weiner, S McNellis, D Howell, K Pagliaro, S CA Natl Inst Child Hlth Human Dev Mat TI Maternal and perinatal outcomes associated with a trial of labor after prior cesarean delivery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID UTERINE RUPTURE; RISK; WOMEN AB BACKGROUND: The proportion of women who attempt vaginal delivery after prior cesarean delivery has decreased largely because of concern about safety. The absolute and relative risks associated with a trial of labor in women with a history of cesarean delivery, as compared with elective repeated cesarean delivery without labor, are uncertain. METHODS: We conducted a prospective four-year observational study of all women with a singleton gestation and a prior cesarean delivery at 19 academic medical centers. Maternal and perinatal outcomes were compared between women who underwent a trial of labor and women who had an elective repeated cesarean delivery without labor. RESULTS: Vaginal delivery was attempted by 17,898 women, and 15,801 women underwent elective repeated cesarean delivery without labor. Symptomatic uterine rupture occurred in 124 women who underwent a trial of labor (0.7 percent). Hypoxic-ischemic encephalopathy occurred in no infants whose mothers underwent elective repeated cesarean delivery and in 12 infants born at term whose mothers underwent a trial of labor (P<0.001). Seven of these cases of hypoxic-ischemic encephalopathy followed uterine rupture (absolute risk, 0.46 per 1000 women at term undergoing a trial of labor), including two neonatal deaths. The rate of endometritis was higher in women undergoing a trial of labor than in women undergoing repeated elective cesarean delivery (2.9 percent vs. 1.8 percent), as was the rate of blood transfusion (1.7 percent vs. 1.0 percent). The frequency of hysterectomy and of maternal death did not differ significantly between groups (0.2 percent vs. 0.3 percent, and 0.02 percent vs. 0.04 percent, respectively). CONCLUSIONS: A trial of labor after prior cesarean delivery is associated with a greater perinatal risk than is elective repeated cesarean delivery without labor, although absolute risks are low. This information is relevant for counseling women about their choices after a cesarean section. C1 Ohio State Univ, Coll Med & Publ Hlth, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Texas San Antonio SW, Dallas, TX USA. NICHHD, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Univ Utah, Salt Lake City, UT USA. Univ Chicago, Chicago, IL 60637 USA. Univ Pittsburgh, Pittsburgh, PA USA. Magee Womens Hosp, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Brown Univ, Providence, RI 02912 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Memphis, TN USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas San Antonio, Houston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Vanderbilt Univ, Nashville, TN USA. RP Landon, MB (reprint author), Ohio State Univ, Coll Med & Publ Hlth, Dept Obstet & Gynecol, 1654 Upham Dr,Means Hall,5th Fl, Columbus, OH 43210 USA. EM landon.1@osu.edu RI Sandall, Jane/D-4146-2009; Varner, Michael/K-9890-2013; OI Sandall, Jane/0000-0003-2000-743X; caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 14 TC 506 Z9 531 U1 3 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 16 PY 2004 VL 351 IS 25 BP 2581 EP 2589 DI 10.1056/NEJMoa040405 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 879OC UT WOS:000225726100005 PM 15598960 ER PT J AU Morgan, WJ Plaut, M Mitchell, H AF Morgan, WJ Plaut, M Mitchell, H TI Environment and asthma - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Univ Arizona, Coll Med, Tucson, AZ 85724 USA. NIAID, Bethesda, MD 20817 USA. Rho, Chapel Hill, NC 27514 USA. RP Morgan, WJ (reprint author), Univ Arizona, Coll Med, Tucson, AZ 85724 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 16 PY 2004 VL 351 IS 25 BP 2654 EP 2655 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 879OC UT WOS:000225726100021 ER PT J AU Raafat, A Bargo, S Anver, MR Callahan, R AF Raafat, A Bargo, S Anver, MR Callahan, R TI Mammary development and tumorigenesis in mice expressing a truncated human Notch4/Int3 intracellular domain (h-Int3sh) SO ONCOGENE LA English DT Article DE Notch4/Int3 signaling; mammary tumorigenesis; mammary gland development ID NEOPLASTIC TRANSFORMATION; GLAND TUMORIGENESIS; EPITHELIAL-CELLS; FVB/N MICE; INT3 GENE; NOTCH; DIFFERENTIATION; HYPERPLASIA; INTEGRATION; MEMBER AB Recently, we have identified a novel 1.8 kb human Notch4/Int3 RNA species (designated h-Int3sh). The h-Int3sh RNA encodes a protein that is missing the CBF1-binding region (RAM23) of the Notch 4/Int3 intracellular domain (ICD). Expression of h-Int3sh in the MCF10A 'normal' human mammary epithelial cell line has been previously shown to induce changes characteristic of oncogenic transformation, including anchorage-independent growth in soft agar. To study the consequences of h-Int3sh expression in vivo on mammary gland development and tumorigenesis, three transgenic mouse lines were established, in which the transgene is the Whey acidic protein (WAP) promoter linked to h-Int3sh. Expression of WAP-Int3sh was detectable in the mammary gland at day 15 of pregnancy in each transgenic line. Mammary gland development in all founder lines is normal and the females can lactate. WAP-h-Int3sh females from each of the founder lines develop mammary tumors, but with a long latency (average age of 18 months). Tumor development was associated with activation of Notch pathway, as evidenced by upregulation of Hes-1. The long latency of mammary tumors in WAP-h-Int3sh mice could be due in part to the subcellular localization of h-Int3sh. Immuno. fluorescence analysis of transfected COS-1 cells showed that h-Int3sh is localized in the cytoplasm and nucleus, while Int3-ICD is detected only in the nucleus. We speculate that the Notch4/Int3 ICD-induced block to mammary gland development and tumorigenesis are consequences of an increasing gradient of CBF1-dependent Notch4/Int3 signaling. C1 NCI, Mammary Biol & Tumorignesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol & Histotechnol Lab, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Callahan, R (reprint author), NCI, Mammary Biol & Tumorignesis Lab, NIH, Bldg 10 Room 5B50, Bethesda, MD 20892 USA. EM rc54d@nih.gov FU PHS HHS [N01-C0-12400] NR 22 TC 32 Z9 32 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 16 PY 2004 VL 23 IS 58 BP 9401 EP 9407 DI 10.1038/sj.onc.1208187 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 880BT UT WOS:000225764100011 PM 15531924 ER PT J AU Rosamond, WD Chambless, LE Sorlie, PD Bell, EM Weitzman, S Smith, JC Folsom, AR AF Rosamond, WD Chambless, LE Sorlie, PD Bell, EM Weitzman, S Smith, JC Folsom, AR TI Trends in the sensitivity, positive predictive value, false-positive rate, and comparability ratio of hospital discharge diagnosis codes for acute myocardial infarction in four US communities, 1987-2000 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE coronary disease; diagnosis; hospital records; myocardial infarction; population surveillance; validation studies [publication type] ID CORONARY-HEART-DISEASE; REGISTER DATA; SURVEILLANCE; VALIDITY; MORTALITY; ACCURACY; CRITERIA; PROJECT; RECORDS; CARE AB Variations in the validity of hospital discharge diagnoses can complicate the assessment of trends in incidence of acute myocardial infarction (AMI). To clarify trends in the validity of discharge codes, the authors compared event classification based on published Atherosclerosis Risk in Communities (ARIC) Study criteria with the presence or absence of an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge code for AMI (code 410). Between 1987 and 2000, 154,836 coronary heart disease events involving hospitalization in the four ARIC communities had ICD-9-CM codes screened for AMI. The sensitivity of ICD-9-CM code 410 for classifying AMI in men (sensitivity = 0.65, 95% confidence interval (CI): 0.63, 0.66) was statistically significantly greater than that found for women (sensitivity = 0.60, 95% CI: 0.58, 0.62) and was greater in Whites (sensitivity = 0.67, 95% CI: 0.65, 0.68) than in Blacks (sensitivity = 0.50, 95% CI: 0.47, 0.53). The ethnic difference was related to a greater frequency of hypertensive heart disease and congestive heart failure codes encompassing AMI among Blacks as compared with Whites. The authors found that although the validity of ICD-9-CM code 410 to identify AMI was generally stable from 1987 through 2000, differences between Blacks and Whites and across geographic locations support investment in validation efforts in ongoing surveillance studies. C1 Univ N Carolina, Cardiovasc Dis Epidemiol Program, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC 27514 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. SUNY Albany, Sch Publ Hlth, Dept Epidemiol, Albany, NY 12222 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Epidemiol & Hlth Serv Evaluat, Beer Sheva, Israel. Univ Mississippi, Sch Med, Dept Pediat, Jackson, MS 39216 USA. Univ Mississippi, Sch Publ Hlth, Div Epidemiol, Jackson, MS 39216 USA. RP Rosamond, WD (reprint author), Univ N Carolina, Cardiovasc Dis Epidemiol Program, Sch Publ Hlth, Dept Epidemiol, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA. EM wayne_rosamond@unc.edu FU NHLBI NIH HHS [N01 HC 55021, N01 HC 55018, N01 HC 55016, N01 HC 55015, N01 HC 55019, N01 HC 55020, N01 HC 55022] NR 28 TC 59 Z9 59 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2004 VL 160 IS 12 BP 1137 EP 1146 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 878RF UT WOS:000225663600001 PM 15583364 ER PT J AU Rosamond, WD Chambless, LE Sorlie, PD Bell, EM Weitzman, S Smith, JC Folsom, AR AF Rosamond, WD Chambless, LE Sorlie, PD Bell, EM Weitzman, S Smith, JC Folsom, AR TI Rosamond et al. Respond to "Are heart attacks gone with the century?" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material C1 Univ N Carolina, Cardiovasc Dis Epidemiol Program, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC 27514 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. SUNY Albany, Sch Publ Hlth, Dept Epidemiol, Albany, NY 12222 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Epidemiol & Hlth Serv Evaluat, Beer Sheva, Israel. Univ Mississippi, Sch Med, Dept Pediat, Jackson, MS 39216 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. RP Rosamond, WD (reprint author), Univ N Carolina, Cardiovasc Dis Epidemiol Program, Sch Publ Hlth, Dept Epidemiol, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA. EM wayne_rosamond@unc.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2004 VL 160 IS 12 BP 1150 EP 1151 DI 10.1093/aje/kwh343 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 878RF UT WOS:000225663600003 ER PT J AU Zhang, YW Wise, JP Holford, TR Xie, H Boyle, P Zahm, SH Rusiecki, J Zou, KY Zhang, B Zhu, Y Owens, PH Zheng, TZ AF Zhang, YW Wise, JP Holford, TR Xie, H Boyle, P Zahm, SH Rusiecki, J Zou, KY Zhang, B Zhu, Y Owens, PH Zheng, TZ TI Serum polychlorinated biphenyls, cytochrome P-450 1A1 polymorphisms, and risk of breast cancer in Connecticut women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; cytochrome P-450 enzyme system; genetics; polychlorinated biphenyls; polymorphism (genetics); risk factors; women ID ORGANOCHLORINE EXPOSURE; AFRICAN-AMERICAN; ADIPOSE-TISSUE; NURSES HEALTH; PESTICIDES; RESIDUES; CYP1A1; ASSOCIATION; METABOLISM; CONGENERS AB Recent epidemiologic studies have suggested that genetic polymorphisms in the cytochrome P-450 1A1 gene (CYP1A1) may affect the relation between environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk. The authors report results from a case-control study evaluating the potential effect of gene-environment interaction between CYP1A1 and serum PCB levels on breast cancer risk among Caucasian women in Connecticut. The study included 374 case women with histologically confirmed breast cancer and 406 noncancerous controls with information on both serum PCB level and CYP1A1 genotype (1999-2002). Compared with women who had the homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 variant genotype (odds ratio (OR) = 2.1, 95% confidence interval (CI): 1.1, 3.9), especially postmenopausal women (OR = 2.4, 95% CI: 1.1, 5.0). Risks associated with the CYP1A1 m2 variant genotype were highest for all women (OR = 3.6, 95% CI: 1.5, 8.2) and postmenopausal women (OR = 4.3, 95% CI: 1.6, 12.0) with higher serum PCB levels (611-2,600 ng/g). The CYP1A1 m1 and m4 genotypes were not associated with breast cancer risk independently or in combination with PCB exposure. In summary, the CYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer and may modify the relation between PCB exposure and breast cancer risk. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Univ So Maine, Sch Appl Sci Engn & Technol, Dept Appl Sci Med, Portland, ME 04103 USA. European Inst Oncol, Dept Epidemiol & Biostat, Milan, Italy. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. RP Zheng, TZ (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 129 Church St,Suite 700, New Haven, CT 06510 USA. EM tongzhang.zheng@yale.edu RI Boyle, Peter/A-4380-2014; Zahm, Shelia/B-5025-2015 OI Boyle, Peter/0000-0001-6251-0610; FU NCI NIH HHS [CA 62006-05] NR 33 TC 53 Z9 61 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2004 VL 160 IS 12 BP 1177 EP 1183 DI 10.1093/aje/kwh346 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 878RF UT WOS:000225663600007 PM 15583370 ER PT J AU Farr, SL Cooper, GS Cai, J Savitz, DA Sandler, DP AF Farr, SL Cooper, GS Cai, J Savitz, DA Sandler, DP TI Pesticide use and menstrual cycle characteristics among premenopausal women in the agricultural health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE agriculture; hormone antagonists; hormones; infertility; menstrual cycle; pesticides ID FEMALE SPRAGUE-DAWLEY; LIFE-STYLE FACTORS; THYROID-FUNCTION; OCCUPATIONAL EXPOSURES; PUBERTAL DEVELOPMENT; FISCHER-344 RATS; OVARIAN-FUNCTION; MALE-FERTILITY; RISK-FACTORS; WISTAR RATS AB Menstrual cycle characteristics may have implications for women's fecundability and risk of hormonally related diseases. Certain pesticides disrupt the estrous cycle in animals. The authors investigated the cross-sectional association between pesticide use and menstrual function among 3,103 women living on farms in Iowa and North Carolina. Women were aged 21-40 years, premenopausal, not pregnant or breastfeeding, and not taking oral contraceptives. At study enrollment (1993-1997), women completed two self-administered questionnaires on pesticide use and reproductive health. Exposures of interest were lifetime use of any pesticide and hormonally active pesticides. Menstrual cycle characteristics of interest included cycle length, missed periods, and intermenstrual bleeding. The authors used generalized estimating equations to assess the association between pesticide use and menstrual cycle characteristics, controlling for age, body mass index, and current smoking status. Women who used pesticides experienced longer menstrual cycles and increased odds of missed periods (odds ratio = 1.5, 95% confidence interval: 1.2, 1.9) compared with women who never used pesticides. Women who used probable hormonally active pesticides had a 60-100% increased odds of experiencing long cycles, missed periods, and intermenstrual bleeding compared with women who had never used pesticides. Associations remained after control for occupational physical activity. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. RP Farr, SL (reprint author), 4770 Buford Highway,Mail Stop K-34, Atlanta, GA 30341 USA. EM sherry@alumni.unc.edu OI Sandler, Dale/0000-0002-6776-0018 NR 60 TC 46 Z9 48 U1 3 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2004 VL 160 IS 12 BP 1194 EP 1204 DI 10.1093/aje/kwi006 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 878RF UT WOS:000225663600009 PM 15583372 ER PT J AU England, LJ Levine, RJ Qian, C Soule, LM Schisterman, EF Yu, KF Catalano, PM AF England, LJ Levine, RJ Qian, C Soule, LM Schisterman, EF Yu, KF Catalano, PM TI Glucose tolerance and risk of gestational diabetes mellitus in nulliparous women who smoke during pregnancy SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diabetes; gestational; glucose tolerance test; pregnancy; smoking ID CIGARETTE-SMOKING; INSULIN-RESISTANCE; MEN; PREECLAMPSIA; SENSITIVITY; COHORT; TRIAL; DETERMINANTS; HEMOGLOBIN; METABOLISM AB Gestational diabetes mellitus has been associated with adverse maternal and infant outcomes, including preeclampsia and fetal macrosomia. Although cigarette smoking has been associated with increased insulin resistance, its effect on gestational diabetes mellitus risk is uncertain. The authors evaluated the effects of smoking on glucose tolerance in a cohort of pregnant women who participated in the Calcium for Preeclampsia Prevention trial, a randomized study of nulliparous women conducted in five US medical centers from 1992 to 1995. Results of screening and diagnostic testing for gestational diabetes mellitus were analyzed. For 3,774 of the 4,589 women enrolled, plasma glucose concentration 1 hour after a 50-g oral glucose challenge and complete information on pregnancy outcome were available; for 3,602 of the women, gestational diabetes mellitus status was known. Adjusted mean 1-hour plasma glucose concentration (mg/dl) was elevated in women who smoked at study enrollment (112.6, 95% confidence interval: 110.0, 115.3) compared with women who had never smoked (108.3, 95% confidence interval: 106.7, 109.8; p < 0.01). Women who smoked were at increased risk of gestational diabetes mellitus when criteria proposed by the National Diabetes Data Group were used (adjusted odds ratio = 1.9, 95% confidence interval: 1.0, 3.6). These findings support an association between smoking and gestational diabetes mellitus. C1 NICHHD, Div Epidemiol Stat & Prevent Res, US Dept HHS, Bethesda, MD 20892 USA. Allied Technol Grp, Rockville, MD USA. Johns Hopkins Sch Med, Dept Gynecol & Obstet, Baltimore, MD USA. Case Western Reserve Univ, Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA. RP England, LJ (reprint author), Ctr Dis Control & Prevent, Maternal Infant Hlth Branch, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth,US Dept HHS, 4770 Buford Highway NE, MS K-23, Atlanta, GA 30341 USA. EM lbe9@cdc.gov OI Schisterman, Enrique/0000-0003-3757-641X FU NICHD NIH HHS [N01-HD-13123, N01-HD-13121, N01-HD-13122, N01-HD-13124, N01-HD-13125, N01-HD-13126, N01-HD-23154, N01-HD-53246] NR 46 TC 25 Z9 29 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2004 VL 160 IS 12 BP 1205 EP 1213 DI 10.1093/aje/kwh340 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 878RF UT WOS:000225663600010 PM 15583373 ER PT J AU Edison, RJ Muenke, M AF Edison, RJ Muenke, M TI Mechanistic and epidemiologic considerations in the evaluation of adverse birth outcomes following gestational exposure to statins SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE statins; cholesterol; HMG-CoA reductase; birth defects; embryonic development; teratogen; Sonic Hedgehog; morphogenesis ID HMG-COA REDUCTASE; LIPID-LOWERING DRUGS; COENZYME-A REDUCTASE; SONIC-HEDGEHOG; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE; CHOLESTEROL-BIOSYNTHESIS; VERATRUM-CALIFORNICUM; CONTROLLED-TRIAL; LIMB ANOMALIES; MEVALONIC ACID AB The cholesterol-lowering "statin" drugs are contraindicated in pregnancy, but few data exist on their safety in human gestation. We reviewed case reports for patterns suggesting drug-related effects on prenatal development and considered a variety of mechanisms by which such effects, if confirmed, might occur. This uncontrolled case series included all FDA reports of statin exposures during gestation, as well as others from the literature and from manufacturers. Exposures and outcomes were reviewed and were tabulated by individual drug. Age-specific rates of exposure to each drug among women of child-bearing age were estimated. Of 214 ascertained pregnancy exposures, 70 evaluable reports remained after excluding uninformative cases. Among 31 adverse outcomes were 22 cases with structural defects, 4 cases of intrauterine growth restriction, and 5 cases of fetal demise. There were two principal categories of recurrent structural defects: cerivastatin and lovastatin were associated with four reports of severe midline CNS defects; simvastatin, lovastatin, and atorvastatin were all associated with reports of limb deficiencies, including two similar complex lower limb defects reported following simvastatin exposure. There were also two cases of VACTERL association among the limb deficiency cases. All adverse outcomes were reported following exposure to cerivastatin, simvastatin, lovastatin, or atorvastatin, which are lipophilic and equilibrate between maternal and embryonic compartments. None were reported following exposure to pravastatin, which is minimally present in the embryo. Statins reaching the embryo may down-regulate biosynthesis of cholesterol as well as many important metabolic intermediates, and may have secondary effects on sterol-dependent morphogens such as Sonic Hedgehog. The reported cases display patterns consistent with dysfunction of cholesterol biosynthesis and Sonic Hedgehog activity. Controlled studies are needed to investigate the teratogenicity of individual drugs in this class. Published 2004 Wiley-Liss, Inc.(dagger) C1 NIH, NHGRI, MGB, DHHS, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NIH, NHGRI, MGB, DHHS, 35 Convent Dr,MSC 3717 Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov NR 80 TC 96 Z9 100 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 15 PY 2004 VL 131A IS 3 BP 287 EP 298 DI 10.1002/ajmg.a.30386 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 876WU UT WOS:000225530200009 PM 15546153 ER PT J AU Ferrucci, L Guralnik, JM Bandinelli, S Bartali, B Corsi, A Lauretani, F AF Ferrucci, L Guralnik, JM Bandinelli, S Bartali, B Corsi, A Lauretani, F TI Falls and mobility limitations in older people: Measures of higher cerebral integration are also important - The reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID PREDICTOR; GAIT C1 NIA, NIH, Bethesda, MD USA. INRCA, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. RP Ferrucci, L (reprint author), NIA, NIH, Bethesda, MD USA. NR 6 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 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 15 PY 2004 VL 117 IS 12 BP 971 EP 972 DI 10.1016/j.amjmed.2004.10.009 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 884SL UT WOS:000226106300016 ER PT J AU Scanlon, PD Connett, JE Wise, RA Tashkin, DP Madhok, T Skeans, M Carpenter, PC Bailey, WC Buist, AS Eichenhorn, M Kanner, RE Weinmann, G AF Scanlon, PD Connett, JE Wise, RA Tashkin, DP Madhok, T Skeans, M Carpenter, PC Bailey, WC Buist, AS Eichenhorn, M Kanner, RE Weinmann, G CA Lung Hlth Study Res Grp TI Loss of bone density with inhaled triamcinolone in Lung Health Study II SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE bone density; obstructive lung diseases; osteoporosis; randomized controlled trials; triamcinolone acetonicle ID OBSTRUCTIVE PULMONARY-DISEASE; TERM GLUCOCORTICOID THERAPY; RANDOMIZED CONTROLLED-TRIAL; MINERAL DENSITY; CORTICOSTEROID USE; FLUTICASONE PROPIONATE; HIP FRACTURE; BECLOMETHASONE DIPROPIONATE; ELDERLY-PATIENTS; ADRENAL-FUNCTION AB Inhaled glucocorticosteroids (ICS) are commonly prescribed for chronic obstructive pulmonary disease. No adverse effect on bone mineral density (BMD) has been proven. In a randomized double-blind, placebo-controlled trial at seven centers in North America, we recruited 412 current smokers or recent quitters with mild to moderate chronic obstructive pulmonary disease. They used inhaled triamcinolone acetonide, 600 mcg, or placebo, twice daily. We measured femoral neck and lumbar spine BMD at baseline and after 1 and 3 years, and serum osteocalcin at baseline, 3 months, 1 year, and 3 years. After 3 years, BMD at the femoral neck decreased 1.78% more with ICS than with placebo (p < 0.001). More participants in the ICS group experienced 6% or more loss of femoral neck BMD (p = 0.002). Lumbar spine BMD increased in the placebo group by 0.98% but decreased by 0.35% in the ICS group (a difference of 1.33%, p = 0.007). Changes in osteocalcin did not correlate with changes in BMD. Fractures, lost height, or osteoporosis diagnoses were not increased among ICS users compared with placebo users. In summary, the use of inhaled triamcinolone acetonicle was associated with loss of BMD at the femoral neck and lumbar spine after 3 years of treatment. C1 Univ Minnesota, Coordinating Ctr, Minneapolis, MN USA. Mayo Clin, Rochester, MN USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Alabama, Birmingham, AL USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Utah, Salt Lake City, UT USA. RP Connett, JE (reprint author), Lung Hlth Study Coordinating Ctr, 2221 Univ Ave SE,Suite 200, Minneapolis, MN 55414 USA. EM john-c@blueox.ccbr.umn.edu FU NHLBI NIH HHS [5U01-HL50267-05] NR 56 TC 49 Z9 52 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 15 PY 2004 VL 170 IS 12 BP 1302 EP 1309 DI 10.1164/rccm.200310-13490C PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 880HY UT WOS:000225780800008 PM 15374846 ER PT J AU Beigi, F Chakir, K Xiao, RP Wainer, IW AF Beigi, F Chakir, K Xiao, RP Wainer, IW TI G-protein-coupled receptor chromatographic stationary phases. 2. Ligand-induced conformational mobility in an immobilized beta(2)-adrenergic receptor SO ANALYTICAL CHEMISTRY LA English DT Article ID BETA(2) ADRENERGIC-RECEPTOR; AFFINITY-CHROMATOGRAPHY; AGONIST BINDING; P-GLYCOPROTEIN; SOLUBILIZATION; ADRENOCEPTOR; PHARMACOLOGY; ANTAGONISTS; EXPRESSION; DOMAIN AB Membranes from a HEK-293 cell line expressing the beta(2)-adrenergic receptor (beta(2)-AR) have been immobilized on an artificial membrane liquid chromatographic stationary phase. The resulting phase was packed into a glass column (1.8 x 0.5 (i.d.) cm) and used in on-line chromatographic system. Frontal displacement affinity chromatography was used to determine the dissociation constants (K-d) of CGP 12177A (552.6 nM) and (S)propranolol (84.3 nM). Zonal displacement chromatography using CGP 12177A as the marker and racemic mixtures of the antagonists nadolol and propranolol demonstrated that the immobilized beta(2)-AR retained its ability to specifically bind these compounds. Similar experiments with (R)- and (S)-propranolol demonstrated that the immobilized receptor retained its enantioselectivity as (S)-propranolol displaced the CGP 12177 marker to a great extent that the (R)-enantiomer. The addition of the agonist butoxamine to the mobile phase increased the retention of the CGP-12177A as did the addition of the agonist fenoterol. These results indicate that the immobilized beta(2)-AR retained its ability to undergo ligand-induced conformational changes. The data from this study suggest that the immobilized beta(2)-AR can be used to screen for ligand binding interactions in both the resting and active states of the receptor. C1 NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov NR 36 TC 36 Z9 36 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD DEC 15 PY 2004 VL 76 IS 24 BP 7187 EP 7193 DI 10.1021/ac048910c PG 7 WC Chemistry, Analytical SC Chemistry GA 880IH UT WOS:000225781700005 PM 15595859 ER PT J AU Novikov, A Caroff, M Della-Negra, S Lebeyec, Y Pautrat, M Schultz, JA Tempez, A Wang, HYJ Jackson, SN Woods, AS AF Novikov, A Caroff, M Della-Negra, S Lebeyec, Y Pautrat, M Schultz, JA Tempez, A Wang, HYJ Jackson, SN Woods, AS TI Matrix-implanted laser desorption/ionization mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID GOLD CLUSTERS; PEPTIDES; PROTEINS; IONS AB The implantation of low-velocity massive gold clusters is shown to be a method of choice for homogeneous incorporation of a metallic matrix into the near-surface region of a solid biopolymer for subsequent laser desorption/ionization (LDI) MS analysis. Matrix implanted (MI)LDI spectra from cluster-implanted pure test peptide or tissue exhibit molecular ion peaks similar to those observed by matrix-assisted LDI. Moreover, the ion emission is very reproducible from any spot on the surface of these test samples. MILDI promises to be a powerful technique for mass spectrometric analysis of native biological samples as demonstrated by the first results on rat brain tissues. C1 NIDA, IRP, Baltimore, MD 21224 USA. CNRS, IN2P3, Inst Nucl Phys, F-91406 Orsay, France. Univ Paris 11, CNRS, Equipe Endotoxines, UMR 8619,IBBMC, F-91405 Orsay, France. Ionwerks Inc, Houston, TX 77030 USA. RP Woods, AS (reprint author), NIDA, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov NR 13 TC 18 Z9 18 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD DEC 15 PY 2004 VL 76 IS 24 BP 7288 EP 7293 DI 10.1021/ac049123i PG 6 WC Chemistry, Analytical SC Chemistry GA 880IH UT WOS:000225781700017 PM 15595871 ER PT J AU Onuki, J Chen, YM Teixeira, PC Schumacher, RI Medeiros, MHG Van Houten, B Di Mascio, P AF Onuki, J Chen, YM Teixeira, PC Schumacher, RI Medeiros, MHG Van Houten, B Di Mascio, P TI Mitochondrial and nuclear DNA damage induced by 5-aminolevulinic acid SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE acute intermittent porphyria; 5-aminolevulinic acid; mitochondrial DNA damage; hepatocellular carcinoma; quantitative polymerase chain reaction ID DELTA-AMINOLEVULINIC-ACID; ACUTE INTERMITTENT PORPHYRIA; POLYMERASE-CHAIN-REACTION; HUMAN-CELLS; OXIDATIVE DAMAGE; HEPATOCELLULAR-CARCINOMA; 4,5-DIOXOVALERIC ACIDS; CYCLIC DIMERIZATION; NITRIC-OXIDE; REPAIR AB 5-Aminolevulinic acid (ALA) is a heme precursor accumulated in plasma and in organs in acute intermittent porphyria (AIP), a disease associated with neuromuscular dysfunction and increased incidence of hepatocellular carcinoma (HCC). Liver biopsies of AIP patients showed odd-shaped mitochondria and autophagic vacuoles containing well-preserved mitochondria. ALA yields reactive oxygen species upon metal-catalyzed oxidation and causes in vivo and in vitro impairment of rat liver mitochondria and DNA damage. Using a quantitative polymerase chain reaction assay, we demonstrated that ALA induces a dose-dependent damage in nuclear and mitochondrial DNA in human SVNF fibroblasts and rat PC12 cells. CHO cells treated with ALA also show nuclear DNA damage and human HepG2 cells entered in apoptosis and necrosis induced by ALA and its dimerization product, DHPY. The present data provide additional information on the genotoxicity of ALA, reinforcing the hypothesis that it may be involved in the development of HCC in AIP patients. (C) 2004 Elsevier Inc. All rights reserved. C1 NIEHS, Mol Genet Lab, NIH, BR-05513970 Sao Paulo, SP, Brazil. RP Di Mascio, P (reprint author), NIEHS, Mol Genet Lab, NIH, BR-05513970 Sao Paulo, SP, Brazil. EM pdmascio@iq.usp.br RI Teixeira, Priscila/D-7426-2013; Medeiros, Marisa/A-5212-2008; Di Mascio, Paolo/D-1264-2014 OI Medeiros, Marisa/0000-0002-5438-1174; Di Mascio, Paolo/0000-0003-4125-8350 NR 74 TC 35 Z9 36 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC 15 PY 2004 VL 432 IS 2 BP 178 EP 187 DI 10.1016/j.abb.2004.09.030 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 874GU UT WOS:000225339700006 PM 15542056 ER PT J AU Requena, JR Dimitrova, MN Legname, G Teijeira, S Prusiner, SB Levine, RL AF Requena, JR Dimitrova, MN Legname, G Teijeira, S Prusiner, SB Levine, RL TI Oxidation of methionine residues in the prion protein by hydrogen peroxide SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE prion; methionine; oxidation; hydrogen peroxide; mass spectrometry; circular dichroism ID MASS-SPECTROMETRY; SUPEROXIDE-DISMUTASE; COPPER-BINDING; N-TERMINUS; DISEASES; PLASTICITY; PEPTIDES; LOCATION; CLEAVAGE; EPITOPE AB Reaction of H2O2 with the recombinant SHa(29-231) prion protein resulted in rapid oxidation of multiple methionine residues. Susceptibility to oxidation of individual residues, assessed by mass spectrometry after digestion with CNBr and lysC, was in general a function of solvent exposure. Met 109 and Met 112, situated in the highly flexible amino terminus, and key residues of the toxic peptide PrP (106-126), showed the greatest susceptibility. Met 129, a residue located in a polymorphic position in human PrP and modulating risk of prion disease, was also easily oxidized, as was Met 134. The structural effect of H2O2-induced methionine oxidation on PrP was studied by CD spectroscopy. As opposed to copper catalyzed oxidation, which results in extensive aggregation of PrP, this reaction led only to a modest increase in beta-sheet structure. The high number of solvent exposed methionine residues in PrP suggests their possible role as protective endogenous antioxidants. (C) 2004 Elsevier Inc. All rights reserved. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Hosp Meixoeiro, Dept Pathol, Vigo, Spain. RP Requena, JR (reprint author), Univ Santiago, Dept Microbiol & Med, Prion Res Unit, E-15706 Santiago, Spain. EM requenaj@usc.es RI Levine, Rodney/D-9885-2011; OI Legname, Giuseppe/0000-0003-0716-4393 NR 37 TC 57 Z9 60 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC 15 PY 2004 VL 432 IS 2 BP 188 EP 195 DI 10.1016/j.abb.2004.09.012 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 874GU UT WOS:000225339700007 PM 15542057 ER PT J AU Cash, MT Miles, EW Phillips, RS AF Cash, MT Miles, EW Phillips, RS TI The reaction of indole with the aminoacrylate intermediate of Salmonella typhimurium tryptophan synthase: observation of a primary kinetic isotope effect with 3-[H-2]indole SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE tryptophan synthase; pyridoxal-5 '-phosphate; indole; kinetic isotope effect; monovalent cation; multienzyme complex ID BIENZYME COMPLEX; ESCHERICHIA-COLI; ALPHA(2)BETA(2) COMPLEX; MONOVALENT CATIONS; ALLOSTERIC LINKAGES; BETA-SUBUNITS; L-SERINE; ALPHA; CATALYSIS; LIGAND AB The bacterial tryptophan synthase alpha(2)beta(2) complex catalyzes the final reactions in the biosynthesis of L-tryptophan. Indole is produced at the active site of the alpha-subunit and is transferred through a 25-30 Angstrom tunnel to the beta-active site, where it reacts with an aminoacrylate intermediate. Lane and Kirschner [Eur. J. Biochem. 129 (1983) 571] proposed a two-step nucleophilic addition-tautomerization mechanism for the reaction of indole with the aminoacrylate intermediate, based on the absence of an observed kinetic isotope effect (KIE) when 3-[H-2]indole reacts with the aminoacrylate intermediate. We have now observed a KIE of 1.4-2.0 in the reaction of 3-[H-2]indole with the aminoacrylate intermediate in the presence of monovalent cations, but not when an alpha-subunit ligand, disodium alpha-glycerophosphate (Na(2)GP), is present. Rapid-scanning stopped flow kinetic studies were performed of the reaction of indole and 3-[H-2]indole with tryptophan synthase preincubated with L-serine, following the decay of the aminoacrylate intermediate at 350 nm, the formation of the quinonoid intermediate at 476 nm, and the formation of the L-Trp external aldimine at 423 nm. The addition of Na(2)GP dramatically slows the rate of reaction of indole with the alpha-aminoacrylate intermediate. A primary KIE is not observed in the reaction of 3-[H-2]indole with the aminoacrylate complex of tryptophan synthase in the presence of Na(2)GP, suggesting binding of indole with tryptophan synthase is rate limiting under these conditions. The reaction of 2-methylindole does not show a KIE, either in the presence of Na+ or Na(2)GP. These results support the previously proposed mechanism for the beta-reaction of tryptophan synthase, but suggest that the rate limiting step in quinonoid intermediate formation from indole and the aminoacrylate intermediate is deprotonation. Published by Elsevier Inc. C1 Univ Georgia, Dept Chem, Ctr Metalloenzyme Studies, Athens, GA 30602 USA. Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. Univ Georgia, Ctr Metalloenzyme Studies, Athens, GA 30602 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Phillips, RS (reprint author), Univ Georgia, Dept Chem, Ctr Metalloenzyme Studies, Athens, GA 30602 USA. EM rsphillips@chem.uga.edu OI Phillips, Robert/0000-0001-8710-562X FU NIGMS NIH HHS [GM-45288] NR 30 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC 15 PY 2004 VL 432 IS 2 BP 233 EP 243 DI 10.1016/j.abb.2004.09.027 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 874GU UT WOS:000225339700012 PM 15542062 ER PT J AU Chaplet, ML Detry, D Deroanne, C Fisher, LW Castronovo, V Bellahcene, A AF Chaplet, ML Detry, D Deroanne, C Fisher, LW Castronovo, V Bellahcene, A TI Zoledronic acid up-regulates bone sialoprotein expression in osteoblastic cells through Rho GTPase inhibition SO BIOCHEMICAL JOURNAL LA English DT Article DE bisphosphonate; bone sialoprotein; osteoblast-like cells; post-transcriptional regulation; Rho GTPase; zoledronic acid ID MINERALIZED-TISSUE FORMATION; NITROGEN-CONTAINING BISPHOSPHONATES; MESSENGER-RNA; RAT BONE; IN-VITRO; ALKALINE-PHOSPHATASE; OSTEOCLAST FORMATION; MEVALONATE PATHWAY; MATRIX DEPOSITION; MARROW CULTURES AB Clinical practice reveals that osteoporotic women treated with BPs (bisphosphonates) show an increased bone mass density and a reduced risk of fractures. However, the mechanisms leading to these beneficial effects of BPs are still poorly understood. We hypothesized that ZOL (zoledronic acid), a potent third-generation BP, may induce the expression of proteins associated with the bone-forming potential of osteoblastic cells such as BSP (bone sialoprotein). Expression of BSP gene is up-regulated by hormones that promote bone formation and has been associated with de novo bone mineralization. Using real-time reverse transcriptase-PCR and Western-blot analysis, we demonstrated that ZOL increased BSP expression in Saos-2 osteoblast-like cells. Nuclear run-on and mRNA decay assays showed no effect at the transcriptional level but a stabilization of BSP transcripts in ZOL-treated cells. ZOL effect on BSP expression occurred through an interference with the mevalonate pathway since it was reversed by either mevalonate pathway intermediates or a Rho GTPase activator. We showed that ZOL impaired membrane localization of RhoA in Saos-2 cells indicating reduced prenylation of this protein. By the use of small interfering RNAs directed to RhoA and Rac1, we identified both Rho GTPases as negative regulators of BSP expression in Saos-2 cells. Our study demonstrates that ZOL induces BSP expression in osteoblast-like cells through inactivation of Rho GTPases and provides a potential mechanism to explain the favourable effects of ZOL treatment on bone mass and integrity. C1 Univ Liege, Metastasis Res Lab, Ctr Expt Canc Res, B-4000 Liege, Belgium. Univ Liege, Ctr Expt Canc Res, Lab Connect Tissues Biol, B-4000 Liege, Belgium. NIDCR, NIH, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. RP Bellahcene, A (reprint author), Univ Liege, Metastasis Res Lab, Ctr Expt Canc Res, B-4000 Liege, Belgium. EM a.bellahcene@ulg.ac.be NR 54 TC 28 Z9 30 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 2004 VL 384 BP 591 EP 598 DI 10.1042/BJ20040380 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 884KQ UT WOS:000226084000016 PM 15324309 ER PT J AU Srivastava, P Schito, M Fattah, RJ Hara, T Hartman, T Buckheit, RW Turpin, JA Inman, JK Appella, E AF Srivastava, P Schito, M Fattah, RJ Hara, T Hartman, T Buckheit, RW Turpin, JA Inman, JK Appella, E TI Optimization of unique, uncharged thioesters as inhibitors of HIV replication SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE thioester; HIVNCp7; zinc finger ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN ZINC FINGERS; TYPE-1 NUCLEOCAPSID PROTEIN; ANTI-HIV; IN-VIVO; ANTIRETROVIRAL THERAPY; REVERSE TRANSCRIPTION; BIOLOGICAL-PROPERTIES; NONINFECTIOUS VIRUS; TRANSGENIC MICE AB A combinatorial chemistry approach was employed to prepare a restricted library of N-substituted S-acyl-2-mercapto-benzamide thioesters. It was shown that many members of this chemotype display anti-HIV activity via their ability to interact with HIV-1, HIV-2, SIV-infected cells, cell-free virus, and chronically and latently infected cells in a manner consistent with targeting of the highly conserved HIV-1 NCp7 zinc fingers. Compounds were initially screened using two different in vitro antiviral assays and evaluated for stability in neutral buffer containing 10% pooled human Serum using a spectrophotometric assay. These data revealed that there was no significant correlation between thioester stability and antiviral activity, however, a slight inverse correlation between serum stability and virucidal activity was noted. Based on the virucidal capability and the ability to select lead compounds to inhibit virus expression from latently infected TNFalpha-induced U1 cells, we next determined if these compounds could prevent HIV cell-to-cell transmission. Several thioesters demonstrated potent inhibition of HIV cell-to-cell transmission with EC50 values in the 80-100 nM range. Thus, we have optimized a series of restricted thioesters and provided evidence that serum stability is not required for antiviral activity. Moreover, selected compounds show potential for development as topical microbicides. (C) 2004 Elsevier Ltd. All rights reserved. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. ImQuest BioSci Inc, Anti Infect Res, Frederick, MD 21704 USA. Henry M Jackson Fdn, Bethesda, MD 20892 USA. RP Schito, M (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM schitom@mail.nih.gov; appellae@nih.gov NR 43 TC 31 Z9 33 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC 15 PY 2004 VL 12 IS 24 BP 6437 EP 6450 DI 10.1016/j.bmc.2004.09.032 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 876UK UT WOS:000225523200010 PM 15556761 ER PT J AU McAteer, K Aceves-Gaona, A Michalczyk, R Buchko, GW Isern, NG Silks, LA Miller, JH Kennedy, MA AF McAteer, K Aceves-Gaona, A Michalczyk, R Buchko, GW Isern, NG Silks, LA Miller, JH Kennedy, MA TI Compensating bends in a 16-base-pair DNA oligomer containing a T(3)A(3) segment: A NMR study of global DNA curvature SO BIOPOLYMERS LA English DT Article DE T(n)A(n) segment; TpA step; residual dipolar couplings; radius of curvature analysis ID MOLECULAR-DYNAMICS SIMULATIONS; RESIDUAL DIPOLAR COUPLINGS; DOUBLE-HELICAL DNA; MINOR-GROOVE; CURVED DNA; NUCLEIC-ACIDS; TRP PROMOTER; TPA STEPS; STRUCTURAL BASIS; BASE DYNAMICS AB In-phase ligated DNA containing T(n)A(n) segments fail to exhibit the retarded polyacrylamide gel electrophoresis (PAGE) migration observed for in-phase ligated A(n)T(n) segments, a behavior thought to be correlated with macroscopic DNA curvature. The lack of macroscopic curvature in ligated T(n)A(n) segments is thought to be due to cancellation of bending in regions flanking the TpA steps. To address this issue, solution-state NMR, including residual dipolar coupling (RDC) restraints, was used to determine a high-resolution structure of [d(CGAGGTTTAAACCTCG)(2)], a DNA oligomer containing a T(3)A(3) tract. The overall magnitude and direction of bending, including the regions flanking the central TpA step, was measured using a radius of curvature, R-c, analysis. The R-c for the overall molecule indicated a small magnitude of global bending (R-c = 138 +/- 23 nm) towards the major groove, whereas the R-c for the two halves (72 +/- 33 nm and 69 +/- 14 nm) indicated greater localized bending into the minor groove. The direction of bending in the regions flanking the TpA step is in partial opposition (109degrees), contributing to cancellation of bending. The cancellation of bending did not correlate with a pattern of roll values at the TpA step, or at the 5' and 3' junctions, of the T(3)A(3) segment, suggesting a simple junction/roll model is insufficient to predict cancellation of DNA bending in all T(n)A(n) junction sequence contexts. Importantly, R-c analysis of structures refined without RDC restraints lacked the precision and accuracy needed to reliably measure bending. (C) 2004 Wiley Periodicals, Inc. C1 Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. Los Alamos Natl Lab, Biosci Div, NIH, Stable Isotope Resource, Los Alamos, NM 87545 USA. Washington State Univ, Dept Comp Sci & Elect Engn, Richland, WA 99352 USA. RP Kennedy, MA (reprint author), Pacific NW Natl Lab, Div Biol Sci, POB 999,K8-98, Richland, WA 99352 USA. EM ma_kennedy@pnl.gov RI Isern, Nancy/J-8016-2013; Buchko, Garry/G-6173-2015; OI Buchko, Garry/0000-0002-3639-1061; Isern, Nancy/0000-0001-9571-8864; Michalczyk, Ryszard/0000-0001-8839-6473 NR 64 TC 11 Z9 11 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 PD DEC 15 PY 2004 VL 75 IS 6 BP 497 EP 511 DI 10.1002/bip.20168 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 877GT UT WOS:000225556600006 PM 15526287 ER PT J AU Tisdale, JF AF Tisdale, JF TI HSCs for muscular dystrophy: a paradigm shift, back SO BLOOD LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 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 DEC 15 PY 2004 VL 104 IS 13 BP 3847 EP 3848 DI 10.1182/blood-2004-09-3654 PG 2 WC Hematology SC Hematology GA 877VC UT WOS:000225601000010 ER PT J AU Allan, JM Smith, AG Wheatley, K Hills, RK Travis, LB Hill, DA Swirsky, DM Morgan, GJ Wild, CP AF Allan, JM Smith, AG Wheatley, K Hills, RK Travis, LB Hill, DA Swirsky, DM Morgan, GJ Wild, CP TI Genetic variation in XPD predicts treatment outcome and risk of acute myeloid leukemia following chemotherapy SO BLOOD LA English DT Review ID NUCLEOTIDE EXCISION-REPAIR; CHRONIC MYELOGENOUS LEUKEMIA; APOPTOTIC CELL-DEATH; COUNCIL AML11 TRIAL; XERODERMA-PIGMENTOSUM; BCR-ABL; MARROW TRANSPLANTATION; DNA-REPAIR; MUTATIONS; POLYMORPHISMS AB The xeroderma pigmentosum group D (XPD) gene encodes a DNA helicase that functions in nucleotide excision repair of chemotherapy-induced DNA damage, the efficiency of which is predicted to be affected by a lysine to glutamine variant at codon 751. We hypothesized that this constitutive genetic variant may modify clinical response to chemotherapy, and we have examined its association with outcome following chemotherapy for acute myeloid leukemia (AML) in 341 elderly patients entered into the United Kingdom Medical Research Council AML II trial, and with the risk of developing chemotherapy-related AML. Among subjects treated for AML, disease-free survival at one year was 44% for lysine homozygotes, compared with 36% for heterozygotes and 16% for glutamine homozygotes (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.01-1.70; P = .04). Similarly, overall survival at one year was 38% for lysine homozygotes, 35% for heterozygotes, and 23% for glutamine homozygotes (HR, 1.18; 95% Cl, 0.99-1.41; P = .07). Furthermore, homozygosity for the XPD codon 751 glutamine variant was associated with a significantly increased risk of developing AML after chemotherapy (odds ratio, 2.22 for Gln/Gln vs Lys/Lys; 95% Cl, 1.04-4.74). These data suggest that the XPD codon 751 glutamine variant protects against myeloid cell death after chemotherapy. (C) 2004 by The American Society of Hematology. C1 Univ York, Dept Biol, Epidemiol & Genet Unit, York YO10 5YW, N Yorkshire, England. Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5YW, N Yorkshire, England. Univ Birmingham, Birmingham Clin Trials Unit, Birmingham, W Midlands, England. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Leeds Gen Infirm, Haematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England. Royal Marsden Hosp, Canc Res Inst, Surrey, England. Univ Leeds, Sch Med, Mol Epidemiol Unit, Leeds, W Yorkshire, England. RP Allan, JM (reprint author), Univ York, Dept Biol, Epidemiol & Genet Unit, York YO10 5YW, N Yorkshire, England. EM jim.allan@egu.york.ac.uk RI Allan, James/B-4448-2009; OI Hills, Robert/0000-0003-0166-0062 NR 38 TC 85 Z9 88 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 DEC 15 PY 2004 VL 104 IS 13 BP 3872 EP 3877 DI 10.1182/blood-2004-06-2161 PG 6 WC Hematology SC Hematology GA 877VC UT WOS:000225601000015 PM 15339847 ER PT J AU Schulze, H Korpal, M Bergmeier, W Italiano, JE Wahl, SM Shivdasani, RA AF Schulze, H Korpal, M Bergmeier, W Italiano, JE Wahl, SM Shivdasani, RA TI Interactions between the megakaryocyte/platelet-specific beta 1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functions SO BLOOD LA English DT Article ID STABLE PROTEINASE-INHIBITOR; TRANSCRIPTION FACTOR NF-E2; AMINO-ACID-SEQUENCE; BACTERIAL LIPOPOLYSACCHARIDE; ELONGATION FACTOR-1-ALPHA; LEUKOPROTEASE INHIBITOR; ACTIVATED PLATELETS; BLOOD-PLATELETS; DISCOID SHAPE; BINDING-SITE AB Plate let-restricted beta1 tubulin is required for optimal thrombopoiesis and discoid cell shape. To identify interacting factors, we used the divergent beta1-tubulin C-terminus as the bait in a yeast 2-hybrid screen of megakaryocyte (MK) cDNAs. We isolated secretory leukocyte protease inhibitor (SLPI), a serine protease antagonist characterized principally as a secreted factor with multiple roles in inflammation. SLPI is expressed in MKs and platelets in 2 discrete compartments. One pool resides in punctate cytoplasmic structures, whereas a significant fraction localizes along peripheral microtubules (MTs) and is lost with cold-induced MT disruption or in beta1 tubulin(-/-) platelets. These findings reveal unexpected interaction between a prominent cytoskeletal protein and an inhibitor of proteolysis. SLPI-/- mice show intact proplatelet formation, platelet numbers and shape, and marginal MT bands; thus, SLPI is not essential for thrombopoiesis. However, SLPI is released upon platelet activation, which also reverses its association with the resting marginal band. Platelet SLPI inhibits neutrophil elastase, an activity that is reduced when beta1 tubulin is absent. We conclude that SLPI localizes in part along the MK and platelet MT cytoskeleton by virtue of specific interactions with beta1 tubulin. SLPI may thus have unanticipated roles in MK and platelet functions, including regulated proteolysis after activation. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Biomed Res, Ctr Blood Res, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NHLBI NIH HHS [P01HL56949, R01HL63163, R01HL68130] NR 56 TC 19 Z9 20 U1 0 U2 5 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 DEC 15 PY 2004 VL 104 IS 13 BP 3949 EP 3957 DI 10.1182/blood-2004-03-1179 PG 9 WC Hematology SC Hematology GA 877VC UT WOS:000225601000026 PM 15315966 ER PT J AU Jin, YZ Mazza, C Christie, JR Giliani, S Fiorini, M Mella, P Gandellini, F Stewart, DM Zhu, QL Nelson, DL Notarangelo, LD Ochs, HD AF Jin, YZ Mazza, C Christie, JR Giliani, S Fiorini, M Mella, P Gandellini, F Stewart, DM Zhu, QL Nelson, DL Notarangelo, LD Ochs, HD TI Mutations of the Wiskott-Aldfich syndrome protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation SO BLOOD LA English DT Article ID X-LINKED THROMBOCYTOPENIA; ALDRICH-SYNDROME PROTEIN; GENE-MUTATIONS; MISSENSE MUTATIONS; JAPANESE PATIENTS; CELL-LINES; IDENTIFICATION; EXPRESSION; LYMPHOCYTES; HETEROGENEITY AB The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immune deficiency disorder characterized by thrombocytopenia, small platelet size, eczema, recurrent infections, and increased risk of autoimmune disorders and malignancies. X-linked thrombocytopenia (XLT) is an allelic variant of WAS which presents with a milder phenotype, generally limited to thrombocytopenia. WAS and XLT are caused by mutations of the Wiskott-Aldrich syndrome protein (WASP) gene which encodes a 502-amino acid protein, named WASP. WASP is thought to play a role in actin cytoskeleton organization and cell signaling. Here, we report the identification of 141 unique mutations, 71 not previously reported, from 227 WAS/XLT families with a total of 262 affected members. When possible we studied the effects of these mutations on transcription, RNA splicing, and protein expression. By analyzing a large number of patients with WAS/XLT at the molecular level we identified 5 mutational hotspots in the WASP gene and have been able to establish a strong association between genotype and phenotype. (C) 2004 by The American Society of Hematology. C1 Childrens Hosp & Reg Med Ctr, Seattle, WA 98109 USA. Univ Brescia, Ist Med Mol Angelo Nocivelli, Dept Pediat, Brescia, Italy. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Ochs, HD (reprint author), Univ Washington, Sch Med, Dept Pediat, 307 Westlake Ave N,Ste 300, Seattle, WA 98109 USA. EM allgau@u.washington.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU NICHD NIH HHS [HD17427-33] NR 46 TC 139 Z9 156 U1 1 U2 6 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 DEC 15 PY 2004 VL 104 IS 13 BP 4010 EP 4019 DI 10.1182/blood-2003-05-1592 PG 10 WC Hematology SC Hematology GA 877VC UT WOS:000225601000034 PM 15284122 ER PT J AU Hitomi, T Zhang, J Nicoletti, LM Grodzki, ACG Jamur, MC Oliver, C Siraganian, RP AF Hitomi, T Zhang, J Nicoletti, LM Grodzki, ACG Jamur, MC Oliver, C Siraganian, RP TI Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation SO BLOOD LA English DT Article ID FC-EPSILON-RI; PROTEIN-KINASE-C; SIGNAL-TRANSDUCTION; CROSS-LINKING; RBL-2H3 CELLS; B-CELL; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; TYROSINE PHOSPHORYLATION; PHOSPHATIDIC-ACID; HISTAMINE-RELEASE AB To investigate the role of phospholipase D (PLD) in FcepsilonRI signaling, the wild-type or the catalytically inactive forms of PLD1 or PLD2 were stably overexpressed in RBL-2H3 mast cells. FcepsilonRI stimulation resulted in the activation of both PLD1 and PLD2. However, PLD1 was the source of most of the receptor-induced PLD activity. There was enhanced FcepsilonRI-induced degranulation only in cells that overexpressed the catalytically inactive PLD1. This dominant-negative PLD1 enhanced FcepsilonRI-induced tyrosine phosphorylations of early signaling molecules such as the receptor subunits, Sylk and phospholipase C-gamma which resulted in faster release of Ca2+ from intracellular sources. Therefore, PLD1 negatively regulates signals upstream of the Ca2+ response. However, FcepsilonRI-induced PLD activation required Sylk and was downstream of the Ca2+ response, suggesting that basal PLD1 activity rather than that activated by cell stimulation controlled these early signaling events. Dominant-negative PLD1 reduced the basal phosphatidic acid formation in unstimulated cells, which was accompanied by an increase in FcepsilonRI within the lipid rafts. These results indicate that constitutive basal PLD1 activity by regulating phosphaticlic acid formation controls the early signals initiated by FcepsilonRI aggregation that lead to mast cell degranulation. (C) 2004 by The American Society of Hematology. C1 NIDCR, RAST Sect, OIIB, NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil. RP Hitomi, T (reprint author), NIDCR, RAST Sect, OIIB, NIH, NIH Bldg 10,Rm 1N106, Bethesda, MD 20892 USA. EM thitomi@mail.nih.gov RI Jamur, Maria Celia/L-5520-2016 OI Jamur, Maria Celia/0000-0001-7065-8543 NR 55 TC 18 Z9 18 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2004 VL 104 IS 13 BP 4122 EP 4128 DI 10.1182/blood-2004-06-2091 PG 7 WC Hematology SC Hematology GA 877VC UT WOS:000225601000047 PM 15339843 ER PT J AU Munitic, I Williams, JA Yang, YL Bei, D Lucas, PJ El Kassar, N Gress, RE Ashwell, JD AF Munitic, I Williams, JA Yang, YL Bei, D Lucas, PJ El Kassar, N Gress, RE Ashwell, JD TI Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis SO BLOOD LA English DT Article ID T-CELL DEVELOPMENT; INTERLEUKIN-7 RECEPTOR; DEFICIENT MICE; TRANSGENIC MICE; THYMOCYTE DIFFERENTIATION; NEGATIVE SELECTION; UP-REGULATION; CUTTING EDGE; MEMORY CELLS; GAMMA-CHAIN AB Interleukin-7 receptor (IL-7R) levels are tightly controlled during ontogeny: high on double-negative (DN) cells, absent on double-positive (DP) cells, and high once again on thymocytes undergoing positive selection. To determine if loss of IL-7-mediated survival signals in DP cells is necessary for normal antigen-specific selection, we created T-lineage-specific lL-7R alpha chain (IL-7Ralpha) transgenic (Tg) mice in which IL-7R is expressed throughout ontogeny. There was no effect of the IL-7Ralpha Tg on negative selection. Surprisingly, however, although the thymi of IL-7Ralpha Tg mice were comparable at birth, there was a decrease in thymocyte number as the mice aged. This was found to be due to competition between DN and IL-7R-expressing DP cells for endogenous IL-7, which resulted in decreased levels of Bcl-2 in DIN cells, increased DIN apoptosis, and decreased DN cell number. Therefore, the down-regulation of IL-7R on DP cells is an "altruistic" act required for maintaining an adequate supply of local IL-7 for DN cells. (C) 2004 by The American Society of Hematology. C1 NCI, Lab Immune Cell Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Rockville, MD 20857 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, Natl Inst Hlth, Bldg 37,Rm 3002,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov NR 57 TC 69 Z9 70 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 DEC 15 PY 2004 VL 104 IS 13 BP 4165 EP 4172 DI 10.1182/blood-2004-06-2484 PG 8 WC Hematology SC Hematology GA 877VC UT WOS:000225601000053 PM 15328149 ER PT J AU Chen, GB Zeng, WH Miyazato, A Billings, E Maciejewski, JP Kajigaya, S Sloand, EM Young, NS AF Chen, GB Zeng, WH Miyazato, A Billings, E Maciejewski, JP Kajigaya, S Sloand, EM Young, NS TI Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; DNA MICROARRAY ANALYSIS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; HEMATOPOIETIC PROGENITOR CELLS; APLASTIC-ANEMIA; CYTOGENETIC ABNORMALITIES; BONE-MARROW; LINEAR AMPLIFICATION; SCORING SYSTEM; FANCONI-ANEMIA AB Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDSs). Patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization and a small-sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these 2 techniques. Microarray data were confirmed by gene amplification and flow cytometry using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. In trisomy 8, upregulated genes were primarily involved in immune and inflammatory responses, and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis and apoptosis and down-regulation of genes controlling cell growth and differentiation. These results imply distinct molecular mechanisms for monosomy 7 and trisomy 8 MDS and implicate specific pathogenic pathways. (C) 2004 by The American Society of Hematology. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Young, NS (reprint author), Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM youngns@nhlbi.nih.gov NR 86 TC 90 Z9 98 U1 0 U2 5 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 DEC 15 PY 2004 VL 104 IS 13 BP 4210 EP 4218 DI 10.1182/blood-2004-01-0103 PG 9 WC Hematology SC Hematology GA 877VC UT WOS:000225601000059 PM 15315976 ER PT J AU Zhang, SM Tsai, S Wu, TT Li, BJ Shih, JWK Lo, SC AF Zhang, SM Tsai, S Wu, TT Li, BJ Shih, JWK Lo, SC TI Mycoplasma fermentans infection promotes immortalization of human peripheral blood mononuclear cells in culture SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; LEUKAEMIC BONE-MARROW; MALIGNANT-TRANSFORMATION; PERSISTENT INFECTION; HELICOBACTER-PYLORI; LEUKOCYTE CULTURES; MAMMALIAN-CELLS; HUMAN LEUKEMIA; TELOMERASE AB Chronic infection or colonization by mycoplasma(s) could gradually and significantly alter many biologic properties of mammalian host cells in culture, including induction of malignant transformation. We examined effects of Mycoplasma fermentans infection on the continuing survival and immortality of human peripheral blood mononuclear cells (PBMCs) from healthy blood donors. Without specific supplemental growth factors, human PBMCs normally die rapidly, with few cells other than macrophages/monocytes surviving after 2 weeks in cultures. Only occasional Epstein-Barr virus (EBV)-positive B lymphocytes would continue to proliferate and undergo spontaneous immortalization. Our present study revealed that infection of human PBMCs in culture with the incognitus and PG18 strains of M fermentans, but surprisingly not with some other strains tested in parallel, markedly enhanced the rate of EBV-positive B lymphocytes to undergo immortalization (74% vs 17%). Compared with spontaneously immortalized PBMCs, the PBMCs immortalized in cultures infected with the mycoplasmas often had prominent karyotype changes with chromosomal loss, gain, or translocations. Furthermore, many of these immortalized B lymphocytes were found to be monoclonal in nature. The in vitro findings would be of relevance to lymphoproliferative disorders that occurred in patients with immune suppression. The mycoplasma-mediated promotional effect in cell immortalization and its potential clinical implications warrant further study. (C) 2004 by The American Society of Hematology. C1 Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Washington, DC 20306 USA. Amer Registry Pathol, Dept Infect & Parasit Dis Pathol, Washington, DC 20306 USA. Natl Inst Hlth, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD USA. RP Lo, SC (reprint author), Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, 14th St & Alaska Ave,NW, Washington, DC 20306 USA. EM los@afip.osd.mil NR 43 TC 16 Z9 20 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2004 VL 104 IS 13 BP 4252 EP 4259 DI 10.1182/blood-2004-04-1245 PG 8 WC Hematology SC Hematology GA 877VC UT WOS:000225601000064 PM 15331449 ER PT J AU Alkhalil, A Cohn, JV Wagner, MA Cabrera, JS Rajapandi, T Desai, SA AF Alkhalil, A Cohn, JV Wagner, MA Cabrera, JS Rajapandi, T Desai, SA TI Plasmodium falciparum likely encodes the principal anion channel on infected human erythrocytes SO BLOOD LA English DT Article ID RED-BLOOD-CELLS; MALARIA PARASITE; CALCIUM-TRANSPORT; CHLORIDE CHANNELS; MEMBRANE; PERMEATION; CL; PATHWAY; SURFACE; ENTRY AB Invasion by the human malaria parasite, Plasmodium falciparum, is associated with marked yet selective increases in red blood cell (RBC) membrane permeability. We previously identified an unusual voltage-dependent ion channel, the plasmodial surface anion channel (PSAC), which may account for these increases. Since then, controversy has arisen about whether there are additional parasite-induced anion channels on the RBC membrane and whether these channels are parasite-encoded proteins or the result of modifications of an endogenous host protein. Here, we used genetically divergent parasite isolates and quantitative transport measurements to examine these questions. Our studies indicate that PSAC alone can adequately account for the increased permeability of infected RBCs to key solutes. Two distinct parasite isolates, grown in RBCs from a single donor, exhibit channel activity with measurably different voltage-dependent gating, a finding difficult to reconcile with simple activation or modification of a host protein. Instead, this difference in channel gating can be conservatively explained by a small number of polymorphisms in a parasite gene that encodes PSAC. The absence of known eukaryotic ion channel homologues in the completed P falciparum genome suggests a novel channel gene, and substantiates PSAC as a target for antimalarial development. (C) 2004 by The American Society of Hematology. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rm 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov RI Desai, Sanjay/B-7110-2009 FU Intramural NIH HHS [Z01 AI000882-07] NR 34 TC 60 Z9 62 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 DEC 15 PY 2004 VL 104 IS 13 BP 4279 EP 4286 DI 10.1182/blood-2004-05-2047 PG 8 WC Hematology SC Hematology GA 877VC UT WOS:000225601000067 PM 15319279 ER PT J AU Rutter, JL Bromley, CM Goldstein, AM Elder, DE Holly, EA Guerry, D Hartge, P Struewing, JP Hogg, D Halpern, A Sagebiel, RW Tucker, MA AF Rutter, JL Bromley, CM Goldstein, AM Elder, DE Holly, EA Guerry, D Hartge, P Struewing, JP Hogg, D Halpern, A Sagebiel, RW Tucker, MA TI Heterogeneity of risk for melanoma and pancreatic and digestive malignancies - A melanoma case-control study SO CANCER LA English DT Article DE etiology; heterogeneity; melanoma; risk ID CUTANEOUS MELANOMA; FAMILY-HISTORY; GERMLINE MUTATIONS; DYSPLASTIC NEVI; CDKN2A MUTATION; PRONE FAMILIES; CANCER; DELETION; VALIDATION; BREAST AB BACKGROUND. Data addressing the interfamilial heterogeneity of melanoma are limited. In the current study, the authors assessed melanoma risk according to family history of melanoma and other melanoma-associated malignancies and evaluated the familial heterogeneity of melanomas, pancreatic malignancies, and gastrointestinal malignancies. METHODS. The authors obtained patient histories of malignancy in first-degree relatives as part of a clinic-based case-control study. The case group included 737 newly diagnosed patients with invasive melanoma, and the control group included 1021 outpatients from clinics at the same medical centers. To assess heterogeneity of risk among families affected by melanoma, a nonparametric method was used to detect extrabinomial variation. In addition, selected patients with melanoma (n = 133) were tested for germline mutations in CDKN2A. RESULTS. The adjusted odds ratio associated with a family history of melanoma was 1.7 (95% confidence interval, 1.1-2.7). Family histories of pancreatic, gastrointestinal, brain, breast, or lymphoproliferative disease did not increase the risk of melanoma significantly. Among case families, significant evidence of familial heterogeneity was found for melanomas, but not for pancreatic or gastrointestinal malignancies. Two mutations in CDKN2A previously associated with melanoma risk were identified among the 133 patients tested in the case group; mutation detection did not differ between families with low and high heterogeneity scores. CONCLUSIONS. Familial heterogeneity testing in the study population did not improve the selection of high-risk families for genetic study. Even in a large case-control study, few families that had multiple members with melanoma were identified, and family members with pancreatic malignancies were rare. Published 2004 by the American Cancer Society.* C1 NCI, Canc Res Ctr, Bethesda, MD 20892 USA. BioStat Solut LLC, Damascus, MD USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Med, Pigmented Lesion Study Grp, Philadelphia, PA 19104 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Toronto, Dept Med Biophys, Inst Med Sci, Toronto, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Univ Calif San Francisco, Melanoma Clin, San Francisco, CA USA. RP Tucker, MA (reprint author), Genet Epidemiol Branch, Executive Plaza S,Suite 7122,6120 Executive Blvd, Bethesda, MD 20892 USA. EM tuckerp@mail.nih.gov RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013; OI Struewing, Jeffery/0000-0002-4848-3334; Rutter, Joni/0000-0002-6502-2361 NR 37 TC 20 Z9 21 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2004 VL 101 IS 12 BP 2809 EP 2816 DI 10.1002/cncr.20669 PG 8 WC Oncology SC Oncology GA 878HK UT WOS:000225637200012 PM 15529312 ER PT J AU Vitale-Cross, L Amornphimoltham, P Fisher, G Molinolo, AA Gutkind, JS AF Vitale-Cross, L Amornphimoltham, P Fisher, G Molinolo, AA Gutkind, JS TI Conditional expression of K-ras in an epithelial compartment that includes the stem cells is sufficient to promote squamous cell carcinogenesis SO CANCER RESEARCH LA English DT Article ID CANCER; SKIN; TRANSGENE; ONCOGENES; TUMORS; GENE AB Ras genes are the most frequently mutated oncogenes in human cancer. However, the contribution of ras to tumor initiation still is unclear because ras expression in primary cells can cause cell cycle arrest and even cell death by apoptosis. Furthermore, when expressed in the epidermis of mice, mutant ras promotes the formation of benign papillomas, only few of which will progress into carcinomas. However, in these cases, ras-transgene expression often is restricted to suprabasal or follicular epithelial cells that may lack self-renewal capacity. Thus, it still is conceivable that expression of active ras in other epithelial compartments may exert a distinct ability to promote malignant progression. To address this possibility, transgenic mice carrying the tetracycline-inducible system (tet-on receptor) targeted to the basal layer of stratified epithelium, which includes the epithelial stem cells, were engineered and crossed with mice expressing the K-ras(G12D) oncogene under the control of tet-regulated responsive elements. On doxycycline administration, proliferative lesions ranging from hyperplasias, papillomas, and dysplasias to metastatic carcinomas developed in squamous epithelia of the skin, oral mucosa, salivary glands, tongue, esophagus, forestomach, and uterine cervix within just 10 to 20 days. The most noticeable lesions were invasive squamous carcinomas of the skin and oral mucosa. These findings suggest that the expression of oncogenes in an epithelial compartment that includes the stem cells may be sufficient to promote squamous carcinogenesis. They also provide a molecularly defined conditional animal model system in which the mechanisms responsible for cancer initiation, maintenance, and metastatic spread can be readily investigated. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Laser Skin & Surg Ctr New York, New York, NY USA. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 19 TC 80 Z9 80 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2004 VL 64 IS 24 BP 8804 EP 8807 DI 10.1158/0008-5472.CAN-04-2623 PG 4 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200003 PM 15604235 ER PT J AU Griffin, KJ Kirschner, LS Matyakhina, L Stergiopoulos, S Robinson-White, A Lenherr, S Weinberg, FD Claflin, E Meoli, E Cho-Chung, YS Stratakis, CA AF Griffin, KJ Kirschner, LS Matyakhina, L Stergiopoulos, S Robinson-White, A Lenherr, S Weinberg, FD Claflin, E Meoli, E Cho-Chung, YS Stratakis, CA TI Down-regulation of regulatory subunit type 1A of protein kinase A leads to endocrine and other tumors SO CANCER RESEARCH LA English DT Article ID CARNEY COMPLEX; PRKAR1A GENE; RI-ALPHA; I-ALPHA; MUTATIONS; EXPRESSION; GROWTH; CELLS; SYSTEM; PKA AB Mutations of the human type la regulatory subunit (RIalpha) of cyclic AMP-dependent protein kinase (PKA; PRKAR1A) lead to altered kinase activity, primary pigmented nodular adrenocortical disease, and tumors of the thyroid and other tissues. To bypass the early embryonic lethality of Prkar1a(-/-) mice, we established transgenic mice carrying an antisense transgene for Prkar1a exon 2 (X2AS) under the control of a tetracycline-responsive promoter. Down-regulation of Prkar1a by up to 70% was achieved in transgenic mouse tissues and embryonic fibroblasts, with concomitant changes in kinase activity and increased cell proliferation, respectively. Mice developed thyroid follicular hyperplasia and adenomas, adrenocortical hyperplasia, and other features reminiscent of primary pigmented nodular adrenocortical disease, histiocytic and epithelial hyperplasias, lymphomas, and other mesenchymal tumors. These were associated with allelic losses of the mouse chromosome II Prkar1a locus, an increase in total type II PKA activity, and higher RIIbeta protein levels. This mouse provides a novel, useful tool for the investigation of cyclic AMP, RIalpha, and PKA functions and confirms the critical role of Prkar1a in tumorigenesis in endocrine and other tissues. C1 NICHHD, Sect Genet & Endocrinol, Dev Endocrinol Branch, Clin Res Ctr,NIH, Bethesda, MD 20892 USA. NCI, Cellular Biochem Sect, Basic Res Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Genet & Endocrinol, Dev Endocrinol Branch, Clin Res Ctr,NIH, Room 1-1330,MSC 1103,10 Ctr Dr, Bethesda, MD 20892 USA. EM Stratakc@mail.nih.gov OI Lenherr, Sara/0000-0002-4162-1546 NR 20 TC 70 Z9 71 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2004 VL 64 IS 24 BP 8811 EP 8815 DI 10.1158/0008-5472.CAN-04-3620 PG 5 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200005 PM 15604237 ER PT J AU Gold, B Kalush, F Bergeron, J Scott, K Mitra, N Wilson, K Ellis, N Huang, H Chen, M Lippert, R Halldorsson, BV Woodworth, B White, T Clark, AG Parl, FF Broder, S Dean, M Offit, K AF Gold, B Kalush, F Bergeron, J Scott, K Mitra, N Wilson, K Ellis, N Huang, H Chen, M Lippert, R Halldorsson, BV Woodworth, B White, T Clark, AG Parl, FF Broder, S Dean, M Offit, K TI Estrogen receptor genotypes and haplotypes associated with breast cancer risk SO CANCER RESEARCH LA English DT Article ID BETA-GENE; ALPHA GENE; SEQUENCE VARIANTS; AMERICAN WOMEN; POLYMORPHISMS; SUSCEPTIBILITY; IDENTIFICATION; DISEASE; BRCA1; PHARMACOGENOMICS AB Nearly one in eight US women will develop breast cancer in their lifetime. Most breast cancer is not associated with a hereditary syndrome, occurs in postmenopausal women, and is estrogen and progesterone receptor-positive. Estrogen exposure is an epidemiologic risk factor for breast cancer and estrogen is a potent mammary mitogen. We studied single nucleotide polymorphisms (SNPs) in estrogen receptors in 615 healthy subjects and 1011 individuals with histologically confirmed breast cancer, all from New York City. We analyzed 13 SNPs in the progesterone receptor gene (PLR), 17 SNPs in estrogen receptor 1 gene (ESR1), and 8 SNPs in the estrogen receptor 2 gene (ESR2). We observed three common haplotypes in ESR1 that were associated with a decreased risk for breast cancer [odds ratio (OR), similar to 0.4; 95% confidence interval (CI), 0.2-0.8; P < 0.01]. Another haplotype was associated with an increased risk of breast cancer (OR, 2.1; 95% CI, 1.2-3.8; P < 0.05). A unique risk haplotype was present in similar to7% of older Ashkenazi Jewish study subjects (OR, 1.7; 95% CI, 1.2-2.4; P < 0.003). We narrowed the ESR1 risk haplotypes to the promoter region and first exon. We define several other haplotypes in Ashkenazi Jews in both ESR1 and ESR2 that may elevate susceptibility to breast cancer. In contrast, we found no association between any PGR variant or haplotype and breast cancer. Genetic epidemiology study replication and functional assays of the haplotypes should permit a better understanding of the role of steroid receptor genetic variants and breast cancer risk. C1 NCI, Frederick Canc Res & Dev Ctr, Human Genet Sect, Lab Genom Divers,Ctr Canc Res, Frederick, MD 21702 USA. Celera Diganost, Rockville, MD USA. SAIC Frederick Inc, Frederick, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Appl Biosyst Inc, Rockville, MD USA. MIT, Dept Math, Cambridge, MA 02139 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. RP Gold, B (reprint author), NCI, Frederick Canc Res & Dev Ctr, Human Genet Sect, Lab Genom Divers,Ctr Canc Res, Bldg 560,Room 21-21, Frederick, MD 21702 USA. EM goldb@ncifcrf.gov OI Dean, Michael/0000-0003-2234-0631; Halldorsson, Bjarni/0000-0003-0756-0767 FU NCI NIH HHS [N01-CO-12400] NR 59 TC 80 Z9 85 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2004 VL 64 IS 24 BP 8891 EP 8900 DI 10.1158/0008-5472.CAN-04-1256 PG 10 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200017 PM 15604249 ER PT J AU Oh, J Seo, DW Diaz, T Wei, BY Ward, Y Ray, JM Morioka, Y Shi, SL Kitayama, H Takahashi, C Noda, M Stetler-Stevenson, WG AF Oh, J Seo, DW Diaz, T Wei, BY Ward, Y Ray, JM Morioka, Y Shi, SL Kitayama, H Takahashi, C Noda, M Stetler-Stevenson, WG TI Tissue inhibitors of metalloproteinase 2 inhibits endothelial cell migration through increased expression of RECK SO CANCER RESEARCH LA English DT Article ID BREAST EPITHELIAL-CELLS; IN-VITRO; MATRIX METALLOPROTEINASES; TUMOR-GROWTH; FOCAL ADHESIONS; ANGIOGENESIS; TIMP-2; RAP1; VIVO; MECHANISM AB The antiangiogenic function of the tissue inhibitors of metalloproteinases (TIMPs) has been attributed to their matrix metalloproteinase inhibitory activity. Here we demonstrate that TIMP-1 but not Ala+TIMP-1 inhibits both basal and vascular endothelial growth factor (VEGF)-stimulated migration of human microvascular endothelial cells (hMVECs), suggesting that this effect is dependent on direct inhibition of matrix metalloproteinase (MMP) activity. In contrast, TIMP-2 and mutant Ala+TIMP-2, which is devoid of MMP inhibitory activity, block hMVEC migration in response to VEGF-A stimulation. TIMP-2 and Ala+TIMP-2 also suppress basal hMVEC migration via a time-dependent mechanism mediated by enhanced expression of RECK, a membrane-anchored MMP inhibitor, which, in turn, inhibits cell migration. TIMP-2 treatment of hMVECs increases the association of Crk with C3G, resulting in enhanced Rap1 activation. hMVECs stably expressing Rap1 have increased RECK expression and display reduced cell migration compared with those expressing inactive Rap1(38N). RECK-null murine embryo fibroblasts fail to demonstrate TIMP-2-mediated decrease in cell migration despite activation of Rap1. TIMP-2-induced RECK decreases cell-associated MMP activity. Anti-RECK antibody increases MMP activity and reverses the TIMP-2-mediated reduction in cell migration. The effects of TIMP-2 on BECK expression and cell migration were confirmed in A2058 melanoma cells. These results suggest that TIMP-2 can inhibit cell migration via several distinct mechanisms. First, TIMP-2 can inhibit cell migration after VEGF stimulation by direct inhibition of MMP activity induced in response to VEGF stimulation. Secondly, TIMP-2 can disrupt VEGF signaling required for initiation of hMVEC migration. Third, TIMP-2 can enhance expression of RECK via Rap1 signaling resulting in an indirect, time-dependent inhibition of endothelial cell migration. C1 NCI, Ctr Canc Res, Vasc Biol Fac, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. Kyoto Univ, Dept Mol Oncol, Grad Sch Med, Kyoto, Japan. RP Stetler-Stevenson, WG (reprint author), NCI, Ctr Canc Res, Vasc Biol Fac, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. EM sstevenw@mail.nih.gov RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 45 TC 82 Z9 85 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2004 VL 64 IS 24 BP 9062 EP 9069 DI 10.1158/0008-5472.CAN-04-1981 PG 8 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200041 PM 15604273 ER PT J AU Meng, LH Zhang, HL Hayward, L Takemura, H Shao, RG Pommier, Y AF Meng, LH Zhang, HL Hayward, L Takemura, H Shao, RG Pommier, Y TI Tetrandrine induces early G(1) arrest in human colon carcinoma cells by down-regulating the activity and inducing the degradation of G(1)-S-specific cyclin-dependent kinases and by inducing p53 and p21(Cip1) SO CANCER RESEARCH LA English DT Article ID RETINOBLASTOMA PROTEIN; BISBENZYLISOQUINOLINE ALKALOIDS; THERAPEUTIC TARGETS; CDK INHIBITORS; CANCER-THERAPY; HEPG2 CELLS; APOPTOSIS; PHOSPHORYLATION; MODULATORS; INDUCTION AB Tetrandrine is an antitumor alkaloid isolated from the root of Stephania tetrandra. We find that micromolar concentrations of tetrandrine irreversibly inhibit the proliferation of human colon carcinoma cells in MTT and clonogenic assays by arresting cells in G,. Tetrandrine induces G(1) arrest before the restriction point in nocodazole- and serum-starved osynchronized HT29 cells, without affecting the G(1)-S transition in aphidicolin-synchronized cells. Tetrandrine-induced G, arrest is followed by apoptosis as shown by fluorescence-activated cell sorting, terminal deoxynucleotidyl transferase-mediated nick end labeling, and annexin V staining assays. Tetrandrine-induced early G, arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A, CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively, these results show that tetrandrine arrests cells in G, by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1). C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Peking Union Med Coll, Beijing, Peoples R China. Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100037, Peoples R China. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov NR 37 TC 59 Z9 67 U1 2 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2004 VL 64 IS 24 BP 9086 EP 9092 DI 10.1158/0008-5472.CAN-04-0313 PG 7 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200045 PM 15604277 ER PT J AU Hui, AM Wei, Z Wei, C Xi, D Purow, B Friedman, GC Fine, HA AF Hui, AM Wei, Z Wei, C Xi, D Purow, B Friedman, GC Fine, HA TI Agents with selective estrogen receptor (ER) modulator activity induce apoptosis in vitro and in vivo in ER-negative glioma cells SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; MANGANESE SUPEROXIDE-DISMUTASE; HIGH-DOSE TAMOXIFEN; MULTIPLE-MYELOMA CELLS; NECROSIS-FACTOR-ALPHA; BREAST-CANCER-CELLS; HIGH-GRADE GLIOMAS; TRANSCRIPTION FACTOR; GENE-EXPRESSION; INTERLEUKIN-8 PRODUCTION AB Tamoxifen, a member of the selective estrogen receptor modulator (SERM) family, is widely used in the treatment of estrogen receptor (ER)-expressing breast cancer. It has previously been shown that high-dose tamoxifen has cytotoxic activity against glioma cells, but whether this effect is drug specific or represents a general property of SERMs is unknown. In this study, we demonstrate that tamoxifen and CC-8490, a novel benzopyranone with SERM activity, induce glioma cell apoptosis in a dose- and time-dependent manner. Moreover, administration of tamoxifen and CC-8490 suppresses tumor growth in vivo and extends animal survival in glioma xenograft models. None of the eight glioma cell lines examined express either ER-alpha or -beta, suggesting the mechanism for tamoxifen- and CC-8490-induced glioma cell apoptosis is independent of the ER signaling pathway. Complementary DNA microarray expression profiling allowed us to identify a subset of genes specifically regulated by tamoxifen and CC-8490, and not by other apoptotic stimuli, including nuclear factor (NF)-kappaB with its target genes IEX-3, SOD2, IL6, and IL8. We demonstrate that suppression of NF-kappaB activation markedly enhances SERM-induced apoptosis, suggesting a role for NF-kappaB in protecting glioma cells from SERM-induced cytotoxicity. These findings demonstrate for the first time that a SERM other than tamoxifen can induce glioma cell apoptosis in vitro and in vivo and that the clinical efficacy of SERMs for the treatment of malignant gliomas could potentially be enhanced by simultaneous inhibition of the NF-kappaB pathway. C1 NINDS, Neuro Oncol Branch, NCI, NIH, Bethesda, MD 20892 USA. Celgene, San Diego, CA USA. RP Fine, HA (reprint author), Room 225,Bloch Bldg,Bldg 82,9030 Georgetown Rd, Bethesda, MD 20814 USA. EM hfine@mail.nih.gov NR 59 TC 45 Z9 48 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2004 VL 64 IS 24 BP 9115 EP 9123 DI 10.1158/0008-5472.CAN-04-2740 PG 9 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200049 PM 15604281 ER PT J AU Shibata, H Yoshioka, Y Ikemizu, S Kobayashi, K Yamamoto, Y Mukai, Y Okamoto, T Taniai, M Kawamura, M Abe, Y Nakagawa, S Hayakawa, T Nagata, S Yamagata, Y Mayumi, T Kamada, H Tsutsumi, Y AF Shibata, H Yoshioka, Y Ikemizu, S Kobayashi, K Yamamoto, Y Mukai, Y Okamoto, T Taniai, M Kawamura, M Abe, Y Nakagawa, S Hayakawa, T Nagata, S Yamagata, Y Mayumi, T Kamada, H Tsutsumi, Y TI Functionalization of tumor necrosis factor-alpha using phage display technique and PEGylation improves its antitumor therapeutic window SO CLINICAL CANCER RESEARCH LA English DT Article ID ELECTRON-DENSITY MAPS; POLYETHYLENE-GLYCOL; TNF-ALPHA; PHASE-I; INTERFERON ALPHA-2A; RECEPTOR ACTIVATION; MUTATIONAL ANALYSIS; TARGETED DELIVERY; ANIMAL TOXICITY; SOLID TUMORS AB Purpose: In this study, the optimization of antitumor therapy with tumor necrosis factor-alpha (TNF-alpha) was attempted. Experimental Design: Using the phage display technique, we created a lysine-deficient mutant TNF-alpha (mTNF-K90R). This mutant had higher affinities to both TNF receptors, despite reports that certain lysine residues play important roles in trimer formation and receptor binding. Results: The mTNF-K90R showed an in vivo therapeutic window that was 13-fold higher than that of the wild-type TNF-alpha (wTNF-alpha). This was due to the synergistic effect of its 6-fold stronger in vitro bioactivity and its 2-fold longer plasma half-life derived from its surface negative potential. The reason why the mTNF-K90R showed a higher bioactivity was understood by a molecular modeling analysis of the complex between the wTNF-alpha and TNF receptor-I. The mTNF-K90R, which was site-specifically mono-PEGylated at the NH2 terminus (sp-PEG-mTNF-K90R), had a higher in vitro bioactivity and considerably longer plasma half-life than the wTNF-alpha, whereas the randomly mono-PEGylated wTNF-alpha had 6% of the bioactivity of the wTNF-alpha. With regard to effectiveness and safety, the in vivo antitumor therapeutic window of the sp-PEG-mTNF-K90R was 60-fold wider than that of the wTNF-alpha. Conclusions: These results indicated that this functionalized TNF-alpha may be useful not only as an antitumor agent but also as a selective enhancer of vascular permeability in tumors for improving antitumor chemotherapy. C1 Osaka Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, Suita, Osaka 5650871, Japan. Natl Inst Hlth Sci, Tokyo 158, Japan. Kumamoto Univ, Dept Biol Struct, Grad Sch Pharmaceut Sci, Kumamoto, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Kobe Gakuin Univ, Dept Cell Therapeut, Grad Sch Pharmaceut Sci, Kobe, Hyogo 65121, Japan. Natl Inst Hlth Sci, Osaka Branch, Fundamental Res Labs Dev Med, Osaka 540, Japan. RP Tsutsumi, Y (reprint author), Osaka Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan. EM ytsutsumi@nihs.go.jp RI Abe, Yasuhiro/F-5206-2016 OI Abe, Yasuhiro/0000-0002-5931-6590 NR 46 TC 60 Z9 62 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2004 VL 10 IS 24 BP 8293 EP 8300 DI 10.1158/1078-0432.CCR-04-0770 PG 8 WC Oncology SC Oncology GA 882SE UT WOS:000225957800022 PM 15623605 ER PT J AU Neelapu, SS Baskar, S Gause, BL Kobrin, CB Watson, TM Frye, AR Pennington, R Harvey, L Jaffe, ES Robb, RJ Popescu, MC Kwak, LW AF Neelapu, SS Baskar, S Gause, BL Kobrin, CB Watson, TM Frye, AR Pennington, R Harvey, L Jaffe, ES Robb, RJ Popescu, MC Kwak, LW TI Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; PULSED DENDRITIC CELLS; CLASS-II MOLECULES; IMMUNE-RESPONSES; SURFACE-IMMUNOGLOBULIN; IDIOTYPE VACCINATION; ACTIVE IMMUNIZATION; ENDOGENOUS PATHWAY; MYELOMA PROTEINS; INDUCTION AB Purpose: The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients. Experimental Design: Ten patients with advanced-stage follicular lymphoma were treated with five doses of this second generation vaccine after chemotherapy-induced clinical remission. All patients were evaluated for cellular and humoral immune responses. Results: Autologous tumor and Id-specific type I cytokine responses were induced by vaccination in 10 and 9 patients, respectively. Antitumor immune responses were mediated by both CD4(+) and CD8(+) T cells, were human lymphocyte antigen class I and 11 associated, and persisted 18 months beyond the completion of vaccination. Specific anti-Id antibody responses were detected in four patients. After a median follow-up of 50 months, 6 of the 10 patients remain in continuous first complete remission. Conclusions: This first clinical report of a liposomal cancer vaccine demonstrates that liposomal delivery is safe, induces sustained tumor-specific CD4(+) and CD8(+) T-cell responses in lymphoma patients, and may serve as a model for vaccine development against other human cancers and infectious pathogens. C1 NCI, Expt & Transplantat Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. Biomira USA Inc, Cranbury, NJ USA. RP Neelapu, SS (reprint author), MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 903, Houston, TX 77030 USA. EM sneelapu@mdanderson.org FU NCI NIH HHS [N01-CO-12400] NR 44 TC 45 Z9 46 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2004 VL 10 IS 24 BP 8309 EP 8317 DI 10.1158/1078-0432.CCR-04-1071 PG 9 WC Oncology SC Oncology GA 882SE UT WOS:000225957800024 PM 15623607 ER PT J AU Baker, SD van Schaik, RHN Rivory, LP ten Tije, AJ Dinh, K Graveland, WJ Schenk, PW Charles, KA Clarke, SJ Carducci, MA McGuire, WP Dawkins, F Gelderblom, H Verweij, J Sparreboom, A AF Baker, SD van Schaik, RHN Rivory, LP ten Tije, AJ Dinh, K Graveland, WJ Schenk, PW Charles, KA Clarke, SJ Carducci, MA McGuire, WP Dawkins, F Gelderblom, H Verweij, J Sparreboom, A TI Factors affecting cytochrome P-450 3A activity in cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article ID ERYTHROMYCIN BREATH TEST; BODY-SURFACE AREA; AFRICAN-AMERICAN; DRUG-METABOLISM; GENETIC VARIANT; HUMAN LIVER; INTERINDIVIDUAL VARIABILITY; CLINICAL PRESENTATION; EUROPEAN-AMERICAN; ALLELIC VARIANTS AB Purpose: The purpose is to identify the demographic, physiologic, and inheritable factors that influence CYP3A activity in cancer patients. Experimental Design: A total of 134 patients (62 females; age range, 26 to 83 years) underwent the erythromycin breath test as a phenotyping probe of CYP3A. Genomic DNA was screened for six variants of suspected functional relevance in CYP3A4 (CYP3A4*1B, CYP3A4*6, CYP3A4*17, and CYP3A4*18) and CYP3A5 (CYP3A5*3C and CYP3A5*6). Results: CYP3A activity (AUC(0-40min)) varied up to 14-fold in this population. No variants in the CYP3A4 and CYP3A5 genes were a significant predictor of CYP3A activity (P > 0.2954). CYP3A activity was reduced by similar to50% in patients with concurrent elevations in liver transaminases and alkaline phosphatase or elevated total bilirubin (P < 0.001). In a multivariate analysis, CYP3A activity was not significantly influenced by age, sex, and body size measures (P > 0.05), but liver function combined with the concentration of the acute-phase reactant, alpha-1 acid glycoprotein, explained similar to18% of overall variation in CYP3A activity (P < 0.001). Conclusions: These data suggest that baseline demographic, physiologic, and chosen genetic polymorphisms have a minor impact on phenotypic CYP3A activity in patients with cancer. Consideration of additional factors, including the inflammation marker C-reactive protein, as well as concomitant use of other drugs, food constituents, and complementary and alternative medicine with inhibitory and inducible effects on CYP3A, is needed to reduce variation in CYP3A and treatment outcome to anticancer therapy. C1 Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Erasmus Univ, Med Ctr, Dept Clin Chem, Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Biostat, Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Med Oncol, Rotterdam, Netherlands. Univ Sydney, Dept Pharmacol, Sydney, NSW 2006, Australia. Univ Sydney, Dept Med Oncol, Sydney, NSW 2006, Australia. Franklin Square Hosp Ctr, Baltimore, MD USA. Howard Univ, Ctr Canc, Washington, DC 20059 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. NCI, Clin Pharmacol Res Core, Bethesda, MD USA. RP Baker, SD (reprint author), Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Bunting Blaustein Canc Res Bldg,1650 Orleans St,R, Baltimore, MD 21231 USA. EM sdbaker@jhmi.edu RI Sparreboom, Alex/B-3247-2008; Charles, Kellie/A-6886-2012 NR 66 TC 93 Z9 95 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2004 VL 10 IS 24 BP 8341 EP 8350 DI 10.1158/1078-0432.CCR-04-1371 PG 10 WC Oncology SC Oncology GA 882SE UT WOS:000225957800028 PM 15623611 ER PT J AU Fisher, LW Jain, A Tayback, M Fedarko, NS AF Fisher, LW Jain, A Tayback, M Fedarko, NS TI Small integrin binding ligand N-linked glycoprotein gene family expression in different cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID MESSENGER-RNA EXPRESSION; HUMAN BREAST CARCINOMAS; HUMAN PROSTATE-CANCER; GELATINASE-A MMP-2; HUMAN COLON-CANCER; HUMAN LUNG-CANCER; BONE SIALOPROTEIN; MATRIX METALLOPROTEINASES; OSTEOPONTIN EXPRESSION; COLORECTAL-CANCER AB Purpose: Members of the small integrin binding ligand N-linked glycoprotein (SIBLING) gene family have the capacity to bind and modulate the activity of matrix metalloproteinases (MMPs). The expression levels of five SIBLING gene family members bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein 1 (DMP1), matrix extracellular phosphoglycoprotein (MEPE), and dentin sialophosphoprotein (DSPP)l and certain MMPs were determined using a commercial cancer array. Experimental Design: Cancer profiling arrays containing normalized cDNA from both tumor and corresponding normal tissues from 241 individual patients were used to screen for SIBLING and MMP expression in nine distinct cancer types. Results: Significantly elevated expression levels were observed for BSP in cancer of the breast, colon, stomach, rectum, thyroid, and kidney; OPN in cancer of the breast uterus, colon, ovary, lung, rectum, and thyroid; DMP1 in cancer of the breast, uterus, colon, and lung; and dentin sialophosphoprotein in breast and lung cancer. The degree of correlation between a SIBLING and its partner MMP was found to be significant within a given cancer type (e.g., BSP and MMP-2 in colon cancer, OPN and MMP-3 in ovarian cancer; DMP1 and MMP-9 in lung cancer). The expression levels of SIBLINGs were distinct within subtypes of cancer (e.g., breast ductal tumors compared with lobular tumors). In general, SIBLING expression increased with cancer stage for breast, colon, lung, and rectal cancer. Conclusions: These results suggest SIBLINGs as potential markers of early disease progression in a number of different cancer types, some of which currently lack vigorous clinical markers. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Johns Hopkins Univ, Dept Med, Div Geriatr Med, Baltimore, MD USA. RP Fedarko, NS (reprint author), Room 5A-64 JHAAC,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM ndarko@jhmi.edu FU NCI NIH HHS [CA 87311] NR 88 TC 66 Z9 77 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2004 VL 10 IS 24 BP 8501 EP 8511 DI 10.1158/1078-0432.CCR-04-1072 PG 11 WC Oncology SC Oncology GA 882SE UT WOS:000225957800049 PM 15623631 ER PT J AU Ricker, JL Chen, Z Yang, XP Pribluda, VS Swartz, GM Van Waes, C AF Ricker, JL Chen, Z Yang, XP Pribluda, VS Swartz, GM Van Waes, C TI 2-methoxyestradiol inhibits hypoxia-inducible factor lot, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squamous cell carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID ESTROGEN METABOLITE 2-METHOXYESTRADIOL; MULTIPLE-MYELOMA CELLS; DRUG-RESISTANCE; FACTOR 1-ALPHA; APOPTOSIS; CANCER; EXPRESSION; OVEREXPRESSION; FACTOR-1-ALPHA; HIF-1-ALPHA AB Purpose: Head and neck squamous cell carcinomas have been reported to overexpress hypoxia-inducible factor (HIF)-1alpha, a transcription factor that promotes expression of angiogenesis factors and resistance to programmed and therapy-induced cell death. 2-Methoxyestradiol (2ME2) is a natural compound with HIF-1alpha inhibitory activity that is currently being evaluated in phase 1 and 2 clinical trials for advanced solid tumors and multiple myeloma. To our knowledge, this is the first study to evaluate the effects of 2ME2 in head and neck squamous cell carcinoma. Experimental Design: In the present study, we investigated the effects of 2ME2 alone and in combination with paclitaxel, an active agent in recurrent or advanced head and neck squamous cell carcinoma. Results: 2ME2 exhibited antiproliferative and cytotoxic effects in a panel of five head and neck squamous cell carcinoma cell lines in the 0.5 to 10 mumol/L range, including induction of G(2)-M blockade, caspase-3/7 activation, and apoptosis at 48 hours. 2ME2 resulted in decreased nuclear HIF-1alpha-binding activity and affected the expression of downstream genes, such as bid, a proapoptotic bcl-2 family member, and vascular endothelial growth factor, a proangiogenic cytokine. The up-regulation of Bid (57.5% at 12 hours, P < 0.0006) and inhibition of vascular endothelial growth factor secretion (57.7% at 24 hours, P < 0.015; and 50.3% at 48 hours, P < 0.0006) could be partially attributed to the effects on HIF-1alpha, because HIF-1alpha small interfering RNAs produced similar effects. Finally, in vivo, in a xenograft model of head and neck squamous cell carcinoma using UM-SCC-11A cells, 2ME2 exhibited antitumor and antiangiogenic activity, as measured by CD31 immuno-staining. Conclusions: These results provide support for the use of 2ME2 in combination with paclitaxel for the treatment of recurrent or advanced head and neck squamous cell carcinoma. C1 NIDOCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. EntreMed Inc, Rockville, MD USA. RP Van Waes, C (reprint author), NIDOCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bldg 10,Room 5D55,10 Ctr Dr MSC-1419, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU NIDCD NIH HHS [DC-00016] NR 45 TC 93 Z9 101 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2004 VL 10 IS 24 BP 8665 EP 8673 DI 10.1158/1078-0432.CCR-04-1393 PG 9 WC Oncology SC Oncology GA 882SE UT WOS:000225957800069 PM 15623651 ER PT J AU Puppo, M Pastorino, S Melillo, G Pezzolo, A Varesio, L Bosco, MC AF Puppo, M Pastorino, S Melillo, G Pezzolo, A Varesio, L Bosco, MC TI Induction of apoptosis by flavopiridol in human neuroblastoma cells is enhanced under hypoxia and associated with N-myc proto-oncogene down-regulation SO CLINICAL CANCER RESEARCH LA English DT Article ID DEPENDENT KINASE INHIBITOR; BONE-MARROW-TRANSPLANTATION; ACTIVITY IN-VIVO; CARCINOMA-CELLS; MEDIATED APOPTOSIS; CASPASE ACTIVATION; GENE-EXPRESSION; LEUKEMIA-CELLS; PHASE-I; GROWTH AB Purpose: Neuroblastoma is the most common extracranial solid tumor of children that arises from the sympathetic nervous system. Survival rates for neuroblastoma patients is low despite intensive therapeutic intervention, and the identification of new effective drugs remains a primary goal. The cyclin-dependent kinase inhibitor, flavopiridol, has demonstrated growth-inhibitory and cytotoxic activity against various tumor types. Our aim was to investigate flavopiridol effects on advanced-stage, N-myc proto-oncogene (MYCN)-amplified human neuroblastomas and the modulation of its activity by hypoxia, a critical determinant of tumor progression and a major challenge of therapy. Experimental Design: Cell viability was monitored by 3-(4,5 dimethyl-2 thiazolyl)-2,5 diphenyl-2H tetrazolium bromide (MTT) and trypan blue dye exclusion assays; DNA synthesis was assessed with the brontodeoxyuridine pulse-labeling technique; apoptosis was studied by Giemsa staining, DNA fragmentation, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling reaction, flow cytometric determination of hypodiploid DNA content, and evaluation of caspase activity and cytochrome c (CytC) release; MYCN expression was determined by Northern and Western blotting. Results: Flavopiridol caused dose- and time-dependent decreases in neuroblastoma viability by inducing apoptosis, as confirmed by morphologic and biochemical criteria. Cell death was preceded by DNA synthesis inhibition and G(1)-G(2) arrest, reversed by the pancaspase inhibitor, zVAD-fmk, and associated with caspase-3 and -2 activation and CytC increase. Moreover, flavopiridol strongly down-regulated MYCN mRNA and protein expression. Exposure to hypoxia enhanced both the extent of apoptosis and flavopiridol effects on CytC, caspase 3, and MYCN. Conclusions: These results indicate that flavopiridol has growth-inhibitory and apoptotic activity against advanced-stage neuroblastomas in vitro and is worthy of further investigation for the treatment of this disease. C1 Ist Giannina Gaslini, Mol Biol Lab, I-16148 Genoa, Italy. Ist Giannina Gaslini, Lab Oncol, I-16148 Genoa, Italy. NCI, Dev Therapeut Program,Tumor Hypoxia Lab, Sci Applicat Int Corp Frederick Inc, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. RP Bosco, MC (reprint author), Ist Giannina Gaslini, Mol Biol Lab, Lgo Gerolamo Gaslini 5, I-16148 Genoa, Italy. EM mariacarlabosco@ospedale-gaslini.ge.it RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 NR 61 TC 13 Z9 13 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2004 VL 10 IS 24 BP 8704 EP 8719 DI 10.1158/1078-0432.CCR-03-0422 PG 16 WC Oncology SC Oncology GA 882SE UT WOS:000225957800074 PM 15623656 ER PT J AU Hassan, R Bera, T Ho, M Pastan, I AF Hassan, R Bera, T Ho, M Pastan, I TI Mesothelin: A new target for immunotherapy - In response SO CLINICAL CANCER RESEARCH LA English DT Letter ID MOLECULAR-CLONING; OVARIAN C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2004 VL 10 IS 24 BP 8752 EP 8752 PG 1 WC Oncology SC Oncology GA 882SE UT WOS:000225957800080 ER PT J AU Hughes, I Blasiole, L Huss, D Warchol, ME Rath, NP Hurle, B Ignatova, E Dickman, JD Thalmann, R Levenson, R Ornitz, DM AF Hughes, I Blasiole, L Huss, D Warchol, ME Rath, NP Hurle, B Ignatova, E Dickman, JD Thalmann, R Levenson, R Ornitz, DM TI Otopetrin 1 is required for otolith formation in the zebrafish Danio rerio SO DEVELOPMENTAL BIOLOGY LA English DT Article DE otolith; otoconia; Otopetrin 1 (Otop1); biomineralization; vestibular systems ID EAR DEVELOPMENT; INNER-EAR; OTOCONIAL AGENESIS; MATRIX PROTEIN; GUINEA-PIG; MICE; MUTATIONS; GENE; MEMBRANE; MUTANT AB Orientation with respect to gravity is essential for the survival of complex organisms. The gravity receptor is one of the phylogenetically oldest sensory systems, and special adaptations that enhance sensitivity to gravity aye highly conserved. The fish inner ear contains three large extracellular biomineral particles, otoliths, which have evolved to transduce the force of gravity into neuronal signals. Mammalian ears contain thousands of small particles called otoconia that serve a similar function. Loss or displacement of these structures can be lethal for fish and is responsible for benign paroxysmal positional vertigo (BPPV) in humans. The distinct morphologies of otoconial particles and otoliths suggest divergent developmental mechanisms. Mutations in a novel gene Otopetrin 1 (Otop1), encoding multi-transmembrane domain protein, result in nonsyndromic otoconial agenesis and a severe balance disorder in mice. Here, we show that the zebrafish, Danio rerio, contains a highly conserved gene, otop1, that is essential for otolith formation. Morpholino-mediated knockdown of zebrafish Otop1 leads to otolith agenesis without affecting the sensory epithelium or other structures within the inner ear. Despite lack of otoliths in early development, otolith formation partially recovers in some fish after 2 days. However, the otoliths are malformed, misplaced, lack an organic matrix, and often consist of inorganic calcite crystals. These studies demonstrate that Otop1 has an essential and conserved role in the timing of formation and the size and shape of the developing otolith. (C) 2004 Elsevier Inc. All rights reserved. C1 Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. Washington Univ, Dept Chem & Biochem, St Louis, MO 63110 USA. Univ Missouri, Dept Chem & Biochem, St Louis, MO USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Ornitz, DM (reprint author), Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, 660 S Euclid Ave,POB 8103, St Louis, MO 63110 USA. EM dornitz@molecool.wustl.edu OI Ornitz, David/0000-0003-1592-7629 FU NIDCD NIH HHS [DC02236, DC006283, R01 DC002236, R01 DC002236-11, R01 DC006283]; NIMH NIH HHS [MH068789, P50 MH068789]; NINDS NIH HHS [R01 NS065761] NR 44 TC 38 Z9 41 U1 1 U2 17 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 DEC 15 PY 2004 VL 276 IS 2 BP 391 EP 402 DI 10.1016/j.ydbio.2004.09.001 PG 12 WC Developmental Biology SC Developmental Biology GA 880GR UT WOS:000225777500012 PM 15581873 ER PT J AU Parlato, R Rosica, A Rodriguez-Mallon, A Affuso, A Postiglione, MP Arra, C Mansouri, A Kimura, S Di Lauro, R De Felice, M AF Parlato, R Rosica, A Rodriguez-Mallon, A Affuso, A Postiglione, MP Arra, C Mansouri, A Kimura, S Di Lauro, R De Felice, M TI An integrated regulatory network controlling survival and migration in thyroid organogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE morphogenesis; organogenesis; migration ID ENHANCER-BINDING PROTEIN; TRANSCRIPTIONAL REPRESSOR; ENDODERM DEVELOPMENT; GENE-FUNCTION; MOUSE EMBRYO; HEDGEHOG; DIFFERENTIATION; HEX; EXPRESSION; GLAND AB The thyroid gland originates from the ventral floor of the foregut as a thickening of the endodermal cell layer. The molecular mechanisms underlying the early steps of thyroid morphogenesis are not known. Gene targeting experiments have contributed to the identification of several transcription factors, in general playing a role in the proliferation, survival, and migration of the thyroid cell precursors. The experiments reported here analyze the expression of the transcription factors Titf1, Hhex, Pax8, and Foxe1 in the thyroid primordium of null mutants of each of them. We found that most of these transcription factors are linked in an integrated regulatory network, each of them controlling the presence of other members of the network. The expression of Foxe1 is regulated in an intriguing fashion as it is strongly dependent on the presence of Pax8 in thyroid precursor cells, while the expression of the same gene in the pharyngeal endoderm surrounding the primordium is dependent on Sonic hedgehog (Shh)-derived signaling. Moreover, by the generation of mouse mutants expressing Foxe1 exclusively in the thyroid primordium, we provide a better understanding of the role of Foxel in these cells in order to acquire the competence to migrate into the underlying mesenchyme. In conclusion, we provide the first evidence of gene expression programs, controlled by a hierarchy of transcription factors expressed in the thyroid presumptive gut domain and directing the progression of thyroid morphogenesis. (C) 2004 Elsevier Inc. All rights reserved. C1 CEINGE, Stn Zool A Dohrn, I-80145 Naples, Italy. Ist Nazl Studio & Cura Tumori, Fdn Pascale, Naples, Italy. MPI Biophys Chem, Abt Mol Zellbiol, Gottingen, Germany. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Univ Naples Federico II, Dipartimento Biol & Patol Mol & Cellulare, Naples, Italy. RP Di Lauro, R (reprint author), CEINGE, Stn Zool A Dohrn, Via Comunale Margherita 482, I-80145 Naples, Italy. EM rdilauro@unina.it RI Di Lauro, Roberto/A-2746-2012; Parlato, Rosanna/G-8768-2015; OI Di Lauro, Roberto/0000-0001-9493-3036; Arra, Claudio/0000-0003-3162-2091; Parlato, Rosanna/0000-0001-6682-9645 FU Telethon [D.067] NR 29 TC 79 Z9 85 U1 1 U2 10 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 DEC 15 PY 2004 VL 276 IS 2 BP 464 EP 475 DI 10.1016/j.ydbio.2004.08.048 PG 12 WC Developmental Biology SC Developmental Biology GA 880GR UT WOS:000225777500018 PM 15581879 ER PT J AU Otto, M AF Otto, M TI Quorum-sensing control in Staphylococci - a target for antimicrobial drug therapy? SO FEMS MICROBIOLOGY LETTERS LA English DT Review DE Staphylococcus; quorum-sensing; biofilm; infection; antibacterial ID RNAIII-INHIBITING PEPTIDE; QUANTITATIVE TRANSCRIPT ANALYSIS; ACCESSORY GENE REGULATOR; GRAM-POSITIVE BACTERIA; PHENOL-SOLUBLE MODULIN; IN-VIVO; BIOFILM FORMATION; SIGNAL-TRANSDUCTION; AUREUS PATHOGENESIS; EPIDERMIDIS AB Today, we find ourselves in an urgent need for novel antibacterial drugs, as many important human pathogens have acquired multiple antibiotic resistance factors. Among those, Staphylococcus aureus and S. epidermidis play a major role as the leading sources of nosocomial infections. Recently, it has been suggested to develop therapeutics that attack bacterial virulence rather than kill bacteria. Such drugs are called "antipathogenic" and are believed to reduce the development of antibiotic resistance. Specifically, cell-density-dependent gene regulation (quorum-sensing) in bacteria has been proposed as a potential target. While promising reports exist about quorum-sensing blockers in gram-negative bacteria, the use of the staphylococcal quorum-sensing system as a drug target is now seen in an increasingly critical way. Inhibition of quorum-sensing in Staphylococcus has been shown to enhance biofilm formation. Furthermore, down-regulation or mutation of the Staphylococcus quorum-sensing system increases bacterial persistence in device-related infection, suggesting that interference with quorum-sensing would enhance rather than suppress this important type of staphylococcal disease. The chemical nature and biological function of another proposed staphylococcal quorum-sensing inhibitor, named "RIP", are insufficiently characterized. Targeting quorum-sensing systems might in principle constitute a reasonable way to find novel antibacterial drugs. However, as outlined here, this approach requires careful investigation in every specific pathogen and type of infection. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 NR 50 TC 110 Z9 123 U1 1 U2 55 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD DEC 15 PY 2004 VL 241 IS 2 BP 135 EP 141 DI 10.1016/j.femsle.2004.11.016 PG 7 WC Microbiology SC Microbiology GA 885RG UT WOS:000226174000002 PM 15598524 ER PT J AU Lee, HY Xu, Y Huang, Y Ahn, AH Auburger, GWJ Pandolfo, M Kwiecinski, H Grimes, DA Lang, AE Nielsen, JE Averyanov, Y Servidei, S Friedman, A Van Bogaert, P Abramowicz, MJ Bruno, MK Sorensen, BF Tang, L Fu, YH Ptacek, LJ AF Lee, HY Xu, Y Huang, Y Ahn, AH Auburger, GWJ Pandolfo, M Kwiecinski, H Grimes, DA Lang, AE Nielsen, JE Averyanov, Y Servidei, S Friedman, A Van Bogaert, P Abramowicz, MJ Bruno, MK Sorensen, BF Tang, L Fu, YH Ptacek, LJ TI The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway SO HUMAN MOLECULAR GENETICS LA English DT Article ID FRONTAL-LOBE EPILEPSY; MULTIPLE SEQUENCE ALIGNMENT; HUMAN GLYOXALASE II; HUMAN-CHROMOSOME 16; DYSTONIC CHOREOATHETOSIS; BASAL GANGLIA; INFANTILE CONVULSIONS; FUNCTIONAL-ANATOMY; SACCHAROMYCES-CEREVISIAE; HETEROLOGOUS EXPRESSION AB Paroxysmal non-kinesigenic dyskinesia (PNKD) is characterized by spontaneous hyperkinetic attacks that are precipitated by alcohol, coffee, stress and fatigue. We report mutations in the myofibrillogenesis regulator 1 (MR-1) gene causing PNKD in 50 individuals from eight families. The mutations cause changes (Ala to Val) in the N-terminal region of two MR-1 isoforms. The MR-1L isoform is specifically expressed in brain and is localized to the cell membrane while the MR-1S isoform is ubiquitously expressed and shows diffuse cytoplasmic and nuclear localization. Bioinformatic analysis reveals that the MR-1 gene is homologous to the hydroxyacylglutathione hydrolase (HAGH) gene. HAGH functions in a pathway to detoxify methylglyoxal, a compound present in coffee and alcoholic beverages and produced as a by-product of oxidative stress. Our results suggest a mechanism whereby alcohol, coffee and stress may act as precipitants of attacks in PNKD. Stress response pathways will be important areas for elucidation of episodic disease genetics where stress is a common precipitant of many common disorders like epilepsy, migraine and cardiac arrhythmias. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT USA. JW Goethe Univ Hosp, Frankfurt, Germany. Free Univ Brussels, Erasme Hosp, B-1050 Brussels, Belgium. Med Acad Warsaw, Dept Neurol, Warsaw, Poland. Univ Ottawa, Ottawa Hosp, Div Neurol, Ottawa, ON, Canada. Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. Univ Copenhagen, Panum Inst, Inst Med Biochem & Genet, DK-2200 Copenhagen, Denmark. Moscow Med Acad, Clin Nervous Dis, Moscow, Russia. Catholic Univ, Inst Neurol, Rome, Italy. NINDS, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. RP Ptacek, LJ (reprint author), Univ Calif San Francisco, Dept Neurol, Box 2922,1550 4th St, San Francisco, CA 94143 USA. EM ptacek@itsa.ucsf.edu RI Pandolfo, Massimo/B-2853-2010; Xu, Ying/A-3009-2013; OI Xu, Ying/0000-0002-6689-7768; Ahn, Andrew H/0000-0003-1780-9300 FU NINDS NIH HHS [NS43533] NR 51 TC 90 Z9 98 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2004 VL 13 IS 24 BP 3161 EP 3170 DI 10.1093/hmg/ddh330 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 883ZT UT WOS:000226055100012 PM 15496428 ER PT J AU Boland, GM Perkins, G Hall, DJ Tuan, RS AF Boland, GM Perkins, G Hall, DJ Tuan, RS TI Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE Wnt; mesenchymal stem cell; osteogenesis; LRP5; frizzled; signaling ID RECEPTOR-RELATED PROTEIN-5; CONVERGENT EXTENSION MOVEMENTS; RECESSIVE ROBINOW-SYNDROME; HUMAN TRABECULAR BONE; CHICK LIMB BUD; BETA-CATENIN; SIGNALING PATHWAY; PROGENITOR CELLS; OSTEOBLAST DIFFERENTIATION; NEGATIVE REGULATOR AB Multipotential adult mesenchymal stem cells (MSCs) are able to differentiate along several known lineages, and lineage commitment is tightly regulated through specific cellular mediators and interactions. Recent observations of a low/high bone-mass phenotype in patients expressing a loss-/gain-of-function mutation in LRP5, a coreceptor of the Wilt family of signaling molecules, Suggest the importance of Writ signaling in bone formation, possibly involving MSCs. To analyze the role of Wilt signaling in mesenchymal osteogenesis, we have profiled the expression of WNTs and their receptors, FRIZZLEDs(FZDs), and several secreted Writ inhibitors, such as SFRPs, and examined the effect of Wnt 3a, as a representative canonical Wnt member, during MSC osteogenesis in vitro. WNT11, FZD6, SFRP2, and SFRP3 are upregulated during MSC osteogenesis, while WNT9A and FZD7 are downregulated. MSCs also respond to exogenous Wnt 3a, based oil increased beta-catenin nuclearization and activation of a Wnt-responsive promoter, and the magnitude of this response depends on the MSC differentiation state. Writ 3a exposure inhibits MSC osteogenic differentiation, with decreased matrix mineralization and reduced alkaline phosphatase mRNA and activity. Wnt 3a treatment of fully osteogenically differentiated MSCs also Suppresses osteoblastic marker gene expression. The Wilt 3a effect is accompanied by increased cell number, resulting from both increased proliferation and decreased apoptosis, particularly during expansion of undifferentiated MSCs. The osteo-suppressive effects of Writ 3a are fully reversible, i.e., treatment prior to osteogenic induction does not compromise subsequent MSC osteogenesis. The results also showed that sFRP3 treatment attenuates some of the observed Wnt 3a effects on MSCs, and that inhibition of canonical Wilt signaling using a dominant negative TCF1 enhances MSC osteogenesis. Interestingly, expression of Wnt 5a, a non-canonical Wilt member, appeared to promote osteogenesis. Taken together, these findings suggest that canonical Writ signaling functions in maintaining an undifferentiated, proliferating progenitor MSC population, whereas non-canonical Wilts facilitate osteogenic differentiation. Release from canonical Wnt regulation is a prerequisite for MSC differentiation. Thus, loss-/gain-of-function Mutations of LRP5 would perturb Writ signaling and depress/promote bone formation by affecting the progenitor cell pool. Elucidating Wnt regulation of MSC differentiation is important for their potential application in tissue regeneration. Published 2004 Wiley-Liss, Inc.(dagger) C1 NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, 50 S Dr,Rm 1503, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU NIAMS NIH HHS [Z0IAR41131] NR 77 TC 319 Z9 346 U1 3 U2 31 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC 15 PY 2004 VL 93 IS 6 BP 1210 EP 1230 DI 10.1002/jcb.20284 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 875JP UT WOS:000225416700013 PM 15486964 ER PT J AU Robbins, PF Dudley, ME Wunderlich, J El-Gamil, M Li, YF Zhou, JH Huang, JP Powell, DJ Rosenberg, SA AF Robbins, PF Dudley, ME Wunderlich, J El-Gamil, M Li, YF Zhou, JH Huang, JP Powell, DJ Rosenberg, SA TI Cutting edge: Persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTES; METASTATIC MELANOMA; ADOPTIVE TRANSFER; TUMOR-REGRESSION; CD8+T CELLS; ANTIGEN; RECOGNITION AB The lack of persistence of transferred autologous mature lymphocytes in humans has been a major limitation to the application of effective cell transfer therapies. The results of a pilot clinical trial in 13 patients with metastatic Melanoma suggested that conditioning with nonmyeloablative chemotherapy before adoptive transfer of activated tumor-reactive T cells enhances tumor regression and increases the overall rates of objective clinical responses. The present report examines the relationship between T cell persistence and tumor regression through analysis of the TCR beta-chain V region gene products expressed in samples obtained from 25 patients treated with this protocol. Sequence analysis demonstrated that there was a significant correlation between tumor regression and the degree of persistence in peripheral blood of adoptively transferred T cell clones, suggesting that inadequate T cell persistence may represent a major factor limiting responses to adoptive immunotherapy. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Robbins, PF (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. EM Paul_Robbins@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 15 TC 281 Z9 282 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2004 VL 173 IS 12 BP 7125 EP 7130 PG 6 WC Immunology SC Immunology GA 878RT UT WOS:000225665100004 PM 15585832 ER PT J AU Salcedo, R Stauffer, JK Lincoln, E Back, TC Hixon, JA Hahn, C Shafer-Weaver, K Malyguine, A Kastelein, R Wigginton, JM AF Salcedo, R Stauffer, JK Lincoln, E Back, TC Hixon, JA Hahn, C Shafer-Weaver, K Malyguine, A Kastelein, R Wigginton, JM TI IL-27 mediates complete regression of orthotopic primary and metastatic murine neuroblastoma tumors: Role for CD8(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IFN-GAMMA PRODUCTION; RECOMBINANT HUMAN INTERLEUKIN-12; PHASE-I TRIAL; LOW-DOSE INTERLEUKIN-2; INTERFERON-GAMMA; MONOCLONAL-ANTIBODIES; ANTITUMOR IMMUNITY; TH1 RESPONSES; IL-12; CYTOKINE AB We have shown previously that IFN-gamma-inducing cytokines such as IL-12 can mediate potent antitumor effects against murine solid tumors. IL-27 is a newly described IL-12-related cytokine that potentiates various aspects of T and/or NK cell function. We hypothesized that IL-27 might also mediate potent antitumor activity in vivo. TBJ neuroblastoma cells engineered to overexpress IL-27 demonstrated markedly delayed growth compared with control mice, and complete durable tumor regression was observed in >90% of mice bearing either s.c. or orthotopic intra-adrenal tumors, and 40% of mice bearing induced metastatic disease. The majority of mice cured of their original TBJ-IL-27 tumors were resistant to tumor rechallenge. Furthermore, TBJ-IL-27 tumors were heavily infiltrated by CD8+ T cells, and draining lymph node-derived lymphocytes from mice bearing s.c. TBJ-IL-27 tumors are primed to proliferate more readily when cultured ex vivo with anti-CD3/anti-CD28 compared with lymphocytes from mice bearing control tumors, and to secrete higher levels of IFN-gamma. In addition, marked enhancement of local IFN-gamma gene expression and potent up-regulation of cell surface MHC class I expression are noted within TBJ-IL-27 tumors compared with control tumors. Functionally, these alterations occur in conjunction with the generation of tumor-specific CTL reactivity in mice bearing TBJ-IL-27 tumors, and the induction of tumor regression via mechanisms that are critically dependent on CD8+, but not CD4+ T cells or NK cells. Collectively, these studies suggest that IL-27 could be used therapeutically to potentiate the host antitumor immune response in patients with malignancy. C1 NCI, Pediat Oncol Branch, Ctr Canc Res, Ft Detrick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Ft Detrick, MD 21702 USA. SAIC Frederick, Lab Cell Mediated Immun, Ft Detrick, MD 21702 USA. DNAX Res Inst Mol & Cellular Biol Inc, Dept Discovery Biol, Palo Alto, CA USA. RP Wigginton, JM (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, Bldg 560,Room 31-93, Ft Detrick, MD 21702 USA. EM jw121b@nih.gov FU PHS HHS [N01-C0-12400] NR 69 TC 98 Z9 110 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2004 VL 173 IS 12 BP 7170 EP 7182 PG 13 WC Immunology SC Immunology GA 878RT UT WOS:000225665100010 PM 15585838 ER PT J AU Palmer, DC Balasubramaniam, S Hanada, K Wrzesinski, C Yu, ZY Farid, S Theoret, MR Hwang, LN Klebanoff, CA Gattinoni, L Goldstein, AL Yang, JC Restifo, NP AF Palmer, DC Balasubramaniam, S Hanada, K Wrzesinski, C Yu, ZY Farid, S Theoret, MR Hwang, LN Klebanoff, CA Gattinoni, L Goldstein, AL Yang, JC Restifo, NP TI Vaccine-stimulated, adoptively transferred CD8(+) T cells traffic indiscriminately and ubiquitously while mediating specific tumor destruction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; METASTATIC MELANOMA; LYMPH-NODES; IFN-GAMMA; ANTIGEN; LYMPHOCYTES; MIGRATION; IMMUNOTHERAPY; RESPONSES; CANCER AB It has been suggested that antitumor T cells specifically traffic to the tumor site, where they effect tumor destruction. To test whether tumor-reactive CD8(+) T cells specifically home to tumor, we assessed the trafficking of gp100-specific pmel-1 cells to large, vascularized tumors that express or do not express the target Ag. Activation of tumor-specific CD8(+) pmel-1 T cells with IL-2 and vaccination with an altered peptide ligand caused regression of gp100-positive tumors (B16), but not gp100-negative tumors (methylcholanthrene 205), implanted on opposing flanks of the same mouse. Surprisingly, we found approximately equal and very large numbers of pmel-I T cells (>25% of all lymphocytes) infiltrating both Ag-positive and Ag-negative tumors. We also found evidence of massive infiltration and proliferation of activated antitumor pmel-1 cells in a variety of peripheral tissues, including lymph nodes, liver, spleen, and lungs, but not peripheral blood. Most importantly, evidence for T cell function, as measured by production of IFN-gamma, release of perforin, and activation of caspase-3 in target cells, was confined to Ag-expressing tumor. We thus conclude that CD8(+) T cell-mediated destruction of tumor is the result of specific T cell triggering at the tumor site. The ability to induce ubiquitous homing and specific tumor destruction may be important in the case of noninflammatory metastatic tumor foci. C1 NCI, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20815 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. RP Palmer, DC (reprint author), NCI, NIH, Clin Res Ctr, Room 3W 35816, Bethesda, MD 20892 USA. EM palmerd@mail.nih.gov RI Gattinoni, Luca/A-2281-2008; Wrzesinski, Claudia/A-3077-2008; Hanada, Ken-ichi/A-4642-2008; Restifo, Nicholas/A-5713-2008; Klebanoff, Christopher/B-8088-2008; Palmer, Douglas/B-9454-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580; Balasubramaniam, Sanjeeve/0000-0002-0643-2117 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 41 TC 76 Z9 77 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2004 VL 173 IS 12 BP 7209 EP 7216 PG 8 WC Immunology SC Immunology GA 878RT UT WOS:000225665100014 PM 15585842 ER PT J AU Inobe, M Schwartz, RH AF Inobe, M Schwartz, RH TI CTLA-4 engagement acts as a brake on CD4(+) T cell proliferation and cytokine production but is not required for tuning T cell reactivity in adaptive tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLATHRIN-ASSOCIATED PROTEIN; ANERGY IN-VIVO; SELF-TOLERANCE; ANTIGEN 4; CTLA-4-MEDIATED INHIBITION; TYROSINE PHOSPHORYLATION; CTLA-4-DEFICIENT MICE; TUMOR-IMMUNOTHERAPY; CYCLE PROGRESSION; ENTEROTOXIN-B AB Adaptive tolerance is the physiologic down-regulation of T cell responsiveness in the face of persistent antigenic stimulation. In this study, we examined the role of CTLA-4 in this process using CTLA-4-deficient and wild-type TCR transgenic, Rag2(-/-), CD4(+) T cells transferred into a T cell-deficient, Ag-expressing host. Surprisingly, we found that the tuning-process of adoptively transferred T cells could be induced and the hyporesponsive state maintained in the absence of CTLA-4. Furthermore, movement to a deeper state of anergy following restimulation in vivo in a second Ag-bearing host was also unaffected. In contrast, CTLA-4 profoundly inhibited late T cell expansion in vivo following both primary and secondary transfers, and curtailed IL-2 and IFN-gamma production. Removal of this braking function in CTLA-4-deficient mice following Ag stimulation may explain their lymphoproliferative dysregulation. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4-Room 111,4 Ctr Dr,MSC-0420, Bethesda, MD 20892 USA. EM rs34r@nih.gov RI INOBE, Manabu/D-8393-2015 NR 63 TC 20 Z9 21 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2004 VL 173 IS 12 BP 7239 EP 7248 PG 10 WC Immunology SC Immunology GA 878RT UT WOS:000225665100018 PM 15585846 ER PT J AU Winders, BR Schwartz, RH Bruniquel, D AF Winders, BR Schwartz, RH Bruniquel, D TI A distinct region of the murine IFN-gamma promoter is hypomethylated from early T cell development through mature naive and Th1 cell differentiation, but is hypermethylated in Th2 cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA; GENE-EXPRESSION; DNA METHYLATION; IMMUNE-SYSTEM; EPIGENETIC REGULATION; CUTTING EDGE; DEMETHYLATION; INDUCTION; INTERLEUKIN-2; LYMPHOCYTES AB Reports on the status of DNA methylation of the IFN-gamma gene during T cell development in human and mouse have presented somewhat contradictory results. In this study we demonstrate in the mouse that methylation of the IFN-gamma promoter inhibits its transcriptional activity, and define a small hypomethylated region in T cells that correlates with transcription. The IFN-gamma promoter was also hypomethylated in NK cells, but not in B cells or nonhemopoietic tissues. Surprisingly, unlike the promoters of the IL-2 and IL-4 genes, the IFN-gamma promoter was hypomethylated in naive CD4(+) and CD8(+) T cells, and in this form from very early in T cell development. A population of non-B, non-T, non-NK cells containing the hypomethylated promoter was also found in the bone marrow. The hypomethylated state appears stable until peripheral CD4(+) T cells differentiate in response to Ag and APC. After T cell stimulation in vitro under Th2 conditions, but far less so under Th1 conditions, CD4(+) cells display a more methylated IFN-gamma promoter, which may contribute to the lack of expression of IFN-gamma in these preactivated cells. Our experiments support a new model of IFN-gamma chromatin structural changes in murine T cell development that differs from what has been previously published for human T cells. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Room 111A,Mail Stop Code 0420,4 Ctr Dr, Bethesda, MD 20892 USA. EM rs34r@nih.gov NR 40 TC 51 Z9 53 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2004 VL 173 IS 12 BP 7377 EP 7384 PG 8 WC Immunology SC Immunology GA 878RT UT WOS:000225665100034 PM 15585862 ER PT J AU Zhou, JH Dudley, ME Rosenberg, SA Robbins, PF AF Zhou, JH Dudley, ME Rosenberg, SA Robbins, PF TI Selective growth, in vitro and in vivo, of individual T cell clones from tumor-infiltrating lymphocytes obtained from patients with melanoma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID METASTATIC MELANOMA; ADOPTIVE TRANSFER; INTERLEUKIN-2; REPERTOIRE; ANTIGEN; CHAIN; IMMUNOTHERAPY; VACCINATION; EXPANSION; THERAPY AB In recent clinical trials in patients with metastatic melanoma, adoptive transfer of tumor-reactive lymphocytes mediated the regression of metastatic tumor deposits. To better understand the role of individual T cell clones in mediating tumor regression, a 5' RACE technique was used to determine the distribution of TCR beta-chain V region sequences expressed in the transferred cells as well as in tumor samples and circulating lymphocytes from melanoma patients following adoptive cell transfer. We found that dominant T cell clones were present in the in vitro-expanded and transferred tumor-infiltrating lymphocyte samples and certain T cell clones including the dominant T cell clones persisted at relatively high levels in the peripheral blood of the patients that demonstrated clinical responses to adoptive immunotherapy. However, these dominant clones were either undetected or present at a very low level in the resected tumor samples used for tumor-infiltrating lymphocyte generation. These data demonstrated that there was selective growth and survival, both in vitro and in vivo, of individual T cell clones from a relatively small number of T cells in the original tumor samples. These results suggest that the persistent T cell clones played an active role in mediating tumor regression and that 5' RACE analysis may provide an important tool for the analysis of the role of individual T cell clones in mediating tumor regression. A similar analysis may also be useful for monitoring autoimmune responses. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Room 2B42,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sar@mail.nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 24 TC 36 Z9 37 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2004 VL 173 IS 12 BP 7622 EP 7629 PG 8 WC Immunology SC Immunology GA 878RT UT WOS:000225665100062 PM 15585890 ER PT J AU Engels, EA Switzer, WM Heneine, W Viscidi, RP AF Engels, EA Switzer, WM Heneine, W Viscidi, RP TI Serologic evidence for exposure to simian virus 40 in North American zoo workers SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th International Conference on Malignancies in AIDS and Other Immunodeficiencies CY APR 29-30, 2004 CL Bethesda, MD ID FOAMY VIRUS-INFECTION; NEUTRALIZING ANTIBODIES; HUMAN SERA; BK VIRUS; JC VIRUS; 40 SV40; HUMANS AB Some laboratories have detected DNA from the macaque polyomavirus simian virus 40 (SV40) in human tumors, but possible routes of infection remain unknown. In the present study, an enzyme immunoassay using viruslike particles (VLPs) was used to test 254 zoo workers for antibodies to SV40; 25 zoo workers with direct contact with nonhuman primates and 15 other zoo workers (23% vs. 10%, respectively; P = .01) were seropositive for SV40. Additionally, SV40 seroreactivity confirmed by competitive-inhibition experiments (i.e., blocked by addition of SV40 VLPs but not by VLPs for BK virus or JC virus, which are related human polyomaviruses) was increased in zoo workers with direct contact with nonhuman primates ( 10% vs. 3%, respectively; P = .04). SV40 seroreactivity therefore may reflect zoonotic exposure. C1 NCI, Rockville, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, 6120 Execut Blvd,EPS 9010, Bethesda, MD 20892 USA. EM engelse@exchange.nih.gov NR 15 TC 26 Z9 28 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2004 VL 190 IS 12 BP 2065 EP 2069 DI 10.1086/425997 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 873LK UT WOS:000225281600002 PM 15551203 ER PT J AU Belshe, RB Newman, FK Anderson, EL Wright, PF Karron, RA Tollefson, S Henderson, FW Meissner, HC Madhi, S Roberton, D Marshall, H Loh, R Sly, P Murphy, B Tatem, JM Randolph, V Hackell, J Gruber, W Tsai, TF AF Belshe, RB Newman, FK Anderson, EL Wright, PF Karron, RA Tollefson, S Henderson, FW Meissner, HC Madhi, S Roberton, D Marshall, H Loh, R Sly, P Murphy, B Tatem, JM Randolph, V Hackell, J Gruber, W Tsai, TF TI Evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TYPE-3 VIRUS; INFECTIONS; EPIDEMIOLOGY; GLYCOPROTEINS; REINFECTION; TRIVALENT; ASSAY AB We evaluated a combination respiratory syncytial virus (RSV) and parainfluenza 3 virus (PIV3) live, attenuated intranasal vaccine for safety, viral replication, and immunogenicity in doubly seronegative children 6 - 18 months old. RSV cpts-248/404 and PIV3-cp45 vaccines were combined in a dose of 10(5) plaque-forming units of each per 0.5-mL dose and compared with monovalent vaccines or placebo. The virus shedding pattern of RSV was not different between monovalent RSV cpts-248/404 vaccine and combination vaccine. Modest reductions in the shedding of PIV3-cp45 vaccine virus were found after the administration of RSV cpts-248/404 and PIV3-cp45 vaccine, relative to monovalent PIV3 vaccine; 16 (76%) of 21 children given combination vaccine shed PIV3-cp45 versus 11 (92%) of 12 of those given monovalent PIV3 vaccine. Both vaccines were immunogenic, and antibody responses were similar between the monovalent groups and the combination group. Combined RSV/ PV3 vaccine is feasible for simultaneous administration, and further studies are warranted. C1 St Louis Univ, Div Infect Dis & Immunol, St Louis, MO 63110 USA. Vanderbilt Univ, Nashville, TN USA. Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. Tufts New England Med Ctr, Boston, MA USA. Univ N Carolina, Chapel Hill, NC USA. Wyeth Vaccines Res, Pearl River, NY USA. Univ Witwatersrand, Johannesburg, South Africa. Univ Adelaide, Womens & Childrens Hosp, Adelaide, SA, Australia. New Childrens Hosp, Perth, WA, Australia. RP Belshe, RB (reprint author), St Louis Univ, Div Infect Dis & Immunol, 3635 Vista Ave FDT-8N, St Louis, MO 63110 USA. EM belsherb@slu.edu RI Sly, Peter/F-1486-2010; Marshall, Helen/G-3603-2013 OI Sly, Peter/0000-0001-6305-2201; FU NIAID NIH HHS [AI-0099, N01-AI-15444] NR 30 TC 39 Z9 41 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2004 VL 190 IS 12 BP 2096 EP 2103 DI 10.1086/425981 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 873LK UT WOS:000225281600006 PM 15551207 ER PT J AU Qiao, M Ashok, M Bernard, KA Palacios, G Zhou, ZH Lipkin, WI Liang, TJ AF Qiao, M Ashok, M Bernard, KA Palacios, G Zhou, ZH Lipkin, WI Liang, TJ TI Induction of sterilizing immunity against west nile virus (WNV), by immunization with WNV-like particles produced in insect cells SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SUBUNIT VACCINE; WILD-TYPE; MICE; ENCEPHALITIS; INFECTION; EFFICACY; IMMUNOGLOBULIN; CHALLENGE; RESPONSES; STRAIN AB No specific vaccine for West Nile virus (WNV) is currently available for human use. In the present study, we describe the generation of WNV-like particles (WNV-LPs) in insect cells by use of recombinant baculoviruses expressing the WNV structural proteins prME or CprME. BALB/c mice immunized with purified WNV-LPs developed WNV-specific antibodies that had potent neutralizing activities. Mice immunized with prME-like particles (prME-LPs) showed no morbidity or mortality after challenge with WNV. Immunization with prME-LPs can induce sterilizing immunity without producing any evidence of viremia or viral RNA in the spleen or brain. These results suggest that WNV-LPs hold promise as a vaccine candidate for WNV infection. C1 NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Columbia Univ, Mailman Sch Publ Hlth, Greene Infect Dis Lab, New York, NY USA. Columbia Univ, Dept Epidemiol, New York, NY USA. Columbia Univ, Dept Neurol, New York, NY USA. Columbia Univ, Dept Pathol, New York, NY USA. New York State Dept Hlth, Wadsworth Ctr, New York, NY USA. Univ Texas, Med Sch Houston, Dept Pathol & Lab Med, Houston, TX USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Bldg 10,Rm 9B16, Bethesda, MD 20892 USA. EM wil2001@columbia.edu; jliang@nih.gov RI Palacios, Gustavo/I-7773-2015 OI Palacios, Gustavo/0000-0001-5062-1938 FU NIAID NIH HHS [AI51292, U54 AI057158, U54AI57158] NR 20 TC 37 Z9 38 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2004 VL 190 IS 12 BP 2104 EP 2108 DI 10.1086/425933 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 873LK UT WOS:000225281600007 PM 15551208 ER PT J AU Wade, NA Unadkat, JD Huang, S Shapiro, DE Mathias, A Yasin, S Ciupak, G Watts, DH Delke, I Rathore, M Hitti, J Frenkel, L Samelson, R Smith, ME Mofenson, L Burchett, SK AF Wade, NA Unadkat, JD Huang, S Shapiro, DE Mathias, A Yasin, S Ciupak, G Watts, DH Delke, I Rathore, M Hitti, J Frenkel, L Samelson, R Smith, ME Mofenson, L Burchett, SK TI Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS Clinical Trials Group protocol 332 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 10th Conference on Retroviruses and Opportunistic Infections CY FEB 10-14, 2003 CL BOSTON, MA ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERINATAL TRANSMISSION; ZIDOVUDINE; DIDANOSINE; TYPE-1; PLASMA; 2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE; CHILDREN; RISK AB This study evaluates the safety, tolerance, and pharmacokinetics of stavudine (d4T) in human immunodeficiency virus (HIV) - infected zidovudine (ZDV) - intolerant/refusing pregnant women and of single-dose d4T in their infants. Women received d4T and lamivudine (3TC) from enrollment until labor. During labor, women received oral 3TC and either intravenous or oral d4T. Infants received ZDV and 3TC for 6 weeks and a single dose of oral d4T at weeks 1 and 6. Mean maternal antenatal d4T pharmacokinetics (terminal plasma half-life [T-1/2], 83.5 +/- 16.8 min; area under the plasma-concentration time curve [AUC(0-infinity)], 81.6 +/- 22.0 mug . min/mL n = 6) were not significantly different from those during labor (T-1/2, 87.3 +/- 24.7 min; AUC(0-infinity), 88.1 +/- 16.6 mug . min/ mL; n = 6). Umbilical-cord and maternal plasma concentrations were not significantly different from one another. The oral clearance of d4T in infants was significantly greater at week 6 versus week 1 ( vs. 6.8 +/- 1.0 vs. 5.6 +/- 1.2 mL/min/kg). There were no toxicities, in women or infants, that required discontinuation or modification of the study drug. No infants had positive HIV viral diagnostic tests. d4T with or without 3TC is a potential alternative to ZDV for HIV-infected pregnant women. C1 Childrens Hosp Albany Med Ctr, Dept Pediat, Albany, NY 12208 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Univ Washington, Sch Pharm, Dept Pharmaceut, Seattle, WA 98195 USA. Univ Washington, Dept Pediat & Obstet & Gynecol, Seattle, WA 98195 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Florida, Hlth Sci Ctr, Dept Pediat, Jacksonville, FL 32209 USA. Univ Florida, Hlth Sci Ctr, Dept Obstet & Gynecol, Jacksonville, FL 32209 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Rockville, MD USA. NIAID, Div Aids, Bethesda, MD 20892 USA. RP Wade, NA (reprint author), Childrens Hosp Albany Med Ctr, Dept Pediat, 43 New Scotland Ave, Albany, NY 12208 USA. EM drnancyw@yahoo.com OI Mofenson, Lynne/0000-0002-2818-9808 FU NICHD NIH HHS [HD44404] NR 21 TC 27 Z9 27 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2004 VL 190 IS 12 BP 2167 EP 2174 DI 10.1086/425903 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 873LK UT WOS:000225281600015 PM 15551216 ER PT J AU Cavanaugh, J Wurtz, RH AF Cavanaugh, J Wurtz, RH TI Subcortical modulation of attention counters change blindness SO JOURNAL OF NEUROSCIENCE LA English DT Article DE attention; change blindness; motion; saccades; superior colliculus; stimulation; visual ID FRONTAL EYE FIELD; COVERT SPATIAL ATTENTION; SUPERIOR COLLICULUS; VISUAL-CORTEX; NEURONAL-ACTIVITY; TARGET SELECTION; CORTICAL AREAS; MOVEMENTS; MT; RESPONSES AB Change blindness is the failure to see large changes in a visual scene that occur simultaneously with a global visual transient. Such visual transients might be brief blanks between visual scenes or the blurs caused by rapid or saccadic eye movements between successive fixations. Shifting attention to the site of the change counters this "blindness" by improving change detection and reaction time. We developed a change blindness paradigm for visual motion and then showed that presenting an attentional cue diminished the blindness in both humans and old world monkeys. We then replaced the visual cue with weak electrical stimulation of an area in the monkey's brainstem, the superior colliculus, to see if activation at such a late stage in the eye movement control system contributes to the attentional shift that counters change blindness. With this stimulation, monkeys more easily detected changes and had shorter reaction times, both characteristics of a shift of attention. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20817 USA. RP Cavanaugh, J (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20817 USA. EM jrc@lsr.nei.nih.gov NR 47 TC 146 Z9 146 U1 0 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2004 VL 24 IS 50 BP 11236 EP 11243 DI 10.1523/JNEUROSCI.3724-04.2004 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 880CK UT WOS:000225766200007 PM 15601929 ER PT J AU White, E Miglioretti, DL Yankaskas, BC Geller, BM Rosenberg, RD Kerlikowske, K Saba, L Vacek, PM Carney, PA Buist, DSM Oestreicher, N Bar-Low, W Ballard-Barbash, R Taplin, SH AF White, E Miglioretti, DL Yankaskas, BC Geller, BM Rosenberg, RD Kerlikowske, K Saba, L Vacek, PM Carney, PA Buist, DSM Oestreicher, N Bar-Low, W Ballard-Barbash, R Taplin, SH TI Biennial versus annual mammography and the risk of late-stage breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SERVICES TASK-FORCE; SCREENING MAMMOGRAPHY; REPLACEMENT THERAPY; COST-EFFECTIVENESS; WOMEN; AGE; INTERVAL; DENSITY; DIAGNOSIS; EFFICACY AB Background: Mammography screening may reduce breast cancer mortality by detecting cancers at an earlier stage. However, certain questions remain, including the ideal interval between mammograms. Methods: We conducted an observational study using information collected by seven mammography registries across the United States to investigate whether women diagnosed with breast cancer after having screening mammograms separated by a 2-year interval (n = 2440) are more likely to be diagnosed with late-stage disease (positive lymph nodes or metastases) than women diagnosed with breast cancer after having screening mammograms separated by a 1-year interval (n = 5400). Analyses were stratified by age and breast density to clarify whether groups that have the poorest mammography sensitivity (i.e., women under age 50 years and those with mammographically dense breasts) would benefit most from annual screening. The subjects were women diagnosed with breast cancer between 1996 and 2001 who were 40-89 years old at their index mammographic examination (i.e., the most recent screen at or before breast cancer diagnosis). Data were analyzed by logistic regression, adjusting for race, ethnicity, family history of breast cancer, and mammography registry. Results: Among women age 40-49 years at the index mammogram, those with a 2-year screening interval were more likely to have late-stage disease at diagnosis than those with a 1-year screening interval (28% versus 21%; odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.01 to 1.81). There was no increase in late-stage disease for women 50 years or older with a 2-year versus a 1-year screening interval (women age 50-59 years at index mammogram: OR = 0.97, 95% CI = 0.75 to 1.25; women age 60-69 years at index mammogram: OR = 0.99, 95% CI = 0.72 to 1.35; women age 70 years or older at index mammogram: OR = 0.88, 95% CI = 0.64 to 1.19). There was no indication that women with dense breasts would benefit more from a 1-year versus 2-year screening interval than women with fatty breasts. Conclusion: These findings may be useful for policy decisions about appropriate screening intervals and for use in statistical models that estimate the costs and benefits of mammography by age and screening interval. C1 Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. Univ Vermont, Coll Med, Hlth Promot Res, Burlington, VT USA. Univ Vermont, Coll Med, Dept Med Biostat, Burlington, VT USA. Univ New Mexico, Hlth Sci Ctr, Dept Radiol, Albuquerque, NM 87131 USA. NCI, Appl Res Program, Dept Canc Control & Populat Sci, Bethesda, MD 20892 USA. Norris Cotton Canc Ctr, Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Dartmouth Med Sch, Lebanon, NH USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Cooper Inst, Dept Biostat, Golden, CO USA. Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Canc Res & Biostat, Seattle, WA USA. Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA. RP White, E (reprint author), Fred Hutchinson Canc Res Ctr, MY-B402,POB 19034, Seattle, WA 98109 USA. EM ewhite@fhere.org OI Saba, Laura/0000-0001-9649-1294 FU NCI NIH HHS [U01CA63736, U01CA63731, U01CA63740, U01CA69976, U01CA70013, U01CA70040, U01CA86076, U01CA86082] NR 37 TC 62 Z9 63 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 15 PY 2004 VL 96 IS 24 BP 1832 EP 1839 DI 10.1093/jnci/djh337 PG 8 WC Oncology SC Oncology GA 879EW UT WOS:000225700200008 PM 15601639 ER PT J AU Kiyatkin, EA Brown, PL AF Kiyatkin, EA Brown, PL TI Modulation of physiological brain hyperthermia by environmental temperature and impaired blood outflow in rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE brain metabolism; brain and body temperature; environmental heating; blood flow; jugular vein occlusion AB To study the role of ambient temperature and brain blood outflow in modulating physiological brain hyperthermia, temperatures in two brain structures (nucleus accumbens or NAcc and hippocampus or Hippo) and a non-locomotor head muscle (musculus temporalis) were monitored in rats exposed to three arousing stimuli (placement in the cage or environmental change, 3-min social interaction with a female rat, 3-min innocuous tail-pinch) under three conditions (intact animals at 23 degreesC or control, intact animals at 29 degreesC, animals with chronically occluded jugular veins at 23 degreesC). While each stimulus in each condition induced hyperthermia, with more rapid and stronger changes in brain structures than muscle, there were significant differences between conditions. At 29 degreesC, animal placement in the cage resulted in stronger temperature increase and larger brain-muscle differentials, while basal temperatures in Hippo and muscle (but not in NAcc) were higher than control. At 29 degreesC, hyperthermia during social interaction was smaller but more prolonged, while the response to tail-pinch was similar to that seen at normal environmental temperatures. Animals with chronically occluded jugular veins had similar basal temperatures but showed much weaker hyperthermia than intact animals during each stimulus presentation; temperature increases in brain structures, however, were much stronger than in the muscle. Our data suggest that the brain is able to decrease neural activation induced by environmental challenges under conditions of impaired blood outflow and restricted heat dissipation to the external environment. Published by Elsevier Inc. C1 NIDA, Intramural Res Program, Behav Neurosci Branch, Dept HHS,NIH, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Intramural Res Program, Behav Neurosci Branch, Dept HHS,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov NR 18 TC 19 Z9 19 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC 15 PY 2004 VL 83 IS 3 BP 467 EP 474 DI 10.1016/j.physbeh.2004.08.032 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 881MO UT WOS:000225871800012 PM 15581669 ER PT J AU Moody, TW Czerwinski, G Tarasova, NI Moody, DL Michejda, CJ AF Moody, TW Czerwinski, G Tarasova, NI Moody, DL Michejda, CJ TI The development of VIP-ellipticine conjugates SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 6th International Symposium on VIP/PACAP CY SEP 01-04, 2003 CL Hakone, JAPAN DE VIP-ellipticine derivatives; VIP agonists; VPAC(1) receptor; lung cancer ID SMALL-CELL-CARCINOMA; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; CANCER GROWTH; RECEPTOR; PEPTIDE; POLYPEPTIDE; ANTAGONIST; LUNG; PROTEIN AB The mechanism by which vasoactive intestinal peptide (VIP)-ellipticine (E) conjugates are cytotoxic for human lung cancer cells was investigated. VIP-alanyl-leucyl-alanyl-leucyl-alanine (ALALA)-E and VIP-leucyl-alanyl-leucyl-alanine (LALA)-E inhibited I-125-VIP binding to NCI-H1299 cells with an IC50 values of 0.5 and 0.1 muM, respectively. VIP-ALALA-E and VIP-LALA-E caused elevation of cAMP in NCI-H1299 cells with ED50 values of 0.7 and 0.1 muM. Radiolabeled VIP-LALA-E was internalized at 37degreesC and delivered the cytotoxic E into NCI-H1299 cells. VIP-LALA-E inhibited the growth of NCI-H1299 cells in vitro. Three days after the addition of VIP LALA-E to NCI-HI299 cells, cell viability decreased based on trypan blue exclusion and reduced 3 H-thymidine uptake. These results suggest that VIP-E conjugates are internalized in lung cancer cells as a result of VPAC(1) receptor-mediated endocytosis. (C) 2004 Elsevier B.V. All rights reserved. C1 NCI, Off Director, CCR, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Adv Biosci Labs, Macromol Struct Lab, Mol Aspects Drug Design Sect, Ft Detrick, MD 21702 USA. RP Moody, TW (reprint author), NCI, Off Director, CCR, Dept Hlth & Human Serv, Bldg 31,Room 3A34,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov NR 21 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD DEC 15 PY 2004 VL 123 IS 1-3 BP 187 EP 192 DI 10.1016/j.regpep.2004.03.021 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 871ST UT WOS:000225154400027 PM 15518911 ER PT J AU Marder, SR Fenton, W AF Marder, SR Fenton, W TI Measurement and Treatment Research to Improve Cognition in Schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE functional outcome; functional capacity; cognition; schizophrenia ID NEUROCOGNITIVE DEFICITS AB The impairments in social and vocational outcome that are common in schizophrenia are strongly related to the severity of impaired neurocognition. This observation led to the initiation of The NIMH's Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, which supports the development of pharmacological agents to improve cognition in schizophrenia. MATRICS addresses barriers to drug development through a number of activities, including the development of a consensus battery for measuring cognition in schizophrenia; the development of a consensus regarding the most promising molecular targets that should be the focus of drug development; the use of a joint meeting with representatives from the industry, academia, NIMH, and the U.S. Food and Drug Administration (FDA) to clarify guidelines for the design of clinical trials for cognition enhancing agents; and finally, to assist NIMH in developing its research agenda in this area. (C) 2004 Published by Elsevier B.V. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90073 USA. W Los Angeles VA Healthcare Ctr, MIRECC 210A, VISN 22, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. NIH, Bethesda, MD 20892 USA. RP Marder, SR (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marder@ucla.edu NR 20 TC 202 Z9 213 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 2004 VL 72 IS 1 BP 5 EP 9 DI 10.1016/j.schres.2004.09.010 PG 5 WC Psychiatry SC Psychiatry GA 886FI UT WOS:000226211900002 PM 15531402 ER PT J AU Nuechterlein, KH Barch, DM Gold, JM Goldberg, TE Green, MF Heaton, RK AF Nuechterlein, KH Barch, DM Gold, JM Goldberg, TE Green, MF Heaton, RK TI Identification of separable cognitive factors in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE cognition; schizophrenia; factor analysis; neuropsychology; psychopharmacology ID CONTINUOUS PERFORMANCE-TEST; WORKING-MEMORY IMPAIRMENTS; NEUROPSYCHOLOGICAL DEFICITS; SOCIAL COGNITION; INFORMATION; DYSFUNCTION; DISORDERS; ATTENTION; BATTERY; 1ST-EPISODE AB One of the primary goals in the NIMH initiative to encourage development of new interventions for cognitive deficits in schizophrenia, Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), has been to develop a reliable and valid consensus cognitive battery for use in clinical trials. Absence of such a battery has hampered standardized evaluation of new treatments and, in the case of pharmacological agents, has been an obstacle to FDA approval of medications targeting cognitive deficits in schizophrenia. A fundamental step in developing such a battery was to identify the major separable cognitive impairments in schizophrenia. As part of this effort, we evaluated the empirical evidence for cognitive performance dimensions in schizophrenia, emphasizing factor analytic studies. We concluded that seven separable cognitive factors were replicable across studies and represent fundamental dimensions of cognitive deficit in schizophrenia: Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning and Memory, Visual Learning and Memory, Reasoning and Problem Solving, and Verbal Comprehension. An eighth domain, Social Cognition, was added due to recent increased interest in this area and other evidence of its relevance for clinical trials aiming to evaluate the impact of potential cognitive enhancers on cognitive performance and functional outcome. Verbal Comprehension was not considered appropriate for a cognitive battery intended to be sensitive to cognitive change, due to its resistance to change. The remaining seven domains were recommended for inclusion in the MATRICS-NIMH consensus cognitive battery and will serve as the basic structure for that battery. These separable cognitive dimensions also have broader relevance to future research aimed at understanding the nature and structure of core cognitive deficits in schizophrenia. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. Washington Univ, Dept Psychol, St Louis, MO USA. Univ Maryland Baltimore Cty, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. NIMH, Intramural Program, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Nuechterlein, KH (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 300 Med Plaza,Rm 2251, Los Angeles, CA 90095 USA. EM keithn@ucla.edu RI Barch, Deanna/G-8638-2013 FU NIMH NIH HHS [MH22006, MH66286] NR 67 TC 590 Z9 609 U1 15 U2 76 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 2004 VL 72 IS 1 BP 29 EP 39 DI 10.1016/j.schres.2004.09.007 PG 11 WC Psychiatry SC Psychiatry GA 886FI UT WOS:000226211900005 PM 15531405 ER PT J AU Daly, JW Noimai, N Kongkathip, B Kongkathip, N Wilham, JM Garraffo, HM Kaneko, T Spande, TF Nimit, Y Nabhitabhata, J Chan-Ard, T AF Daly, JW Noimai, N Kongkathip, B Kongkathip, N Wilham, JM Garraffo, HM Kaneko, T Spande, TF Nimit, Y Nabhitabhata, J Chan-Ard, T TI Biologically active substances from amphibians: preliminary studies on anurans from twenty-one genera of Thailand SO TOXICON LA English DT Review DE toxicity; bufadienolides; pumiliotoxins; amphibians; serotonin ID POISON FROGS DENDROBATIDAE; IMIDAZOLE-ALKYLAMINES; PHENYL-ALKYLAMINES; INDOLE-ALKYLAMINES; SKIN; ALKALOIDS; BUFO; BUFADIENOLIDES; TETRODOTOXIN; TOADS AB Amphibian skin has been the source of a wide variety of biologically active substances, but less than one-third of the known genera of amphibians have been probed for such active substances. Skins of 21 genera of anurans from Thailand have now been investigated for noxious secretions, toxic substances, and alkaloids. Four genera of bufonid toads (Bufo, Ansonia, Leptophryne, Pedostipes) were toxic due to the presence of bufadienolides or bufadienolide-like compounds. Two species of ranid frogs (Rana raniceps, Rana signata) were toxic, perhaps due to the presence of toxic peptide(s). Two species of rhacophorid frogs (Polypedates) were slightly noxious/toxic. One species of microhylid frog (Kaloula pulchra) was noxious. Trace amounts of pumiliotoxin alkaloids were detected in a ranid frog (Limnonectes kuhli). A further 18 species did not exhibit noxious or toxic properties to a significant extent. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. Kasetsart Univ, Fac Sci, Dept Chem, Bangkok 10900, Thailand. Nan Hua Univ, Chiayi 622, Taiwan. Natl Sci Museum, Khlong Luang 12120, Pathum Thani, Thailand. RP Daly, JW (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bldg 8,Rm 1A17, Bethesda, MD 20892 USA. EM jdaly@nih.gov NR 18 TC 41 Z9 42 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD DEC 15 PY 2004 VL 44 IS 8 BP 805 EP 815 DI 10.1016/j.toxicon.2004.08.016 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 878CS UT WOS:000225624700001 PM 15530960 ER PT J AU Martin, RCG Hughes, K Doll, MA Lan, Q Martini, BS Lissowska, J Rothman, N Hein, DW AF Martin, RCG Hughes, K Doll, MA Lan, Q Martini, BS Lissowska, J Rothman, N Hein, DW TI Method for determination of (-102C > T) single nucleotide polymorphism in the human manganese superoxide dismutase promoter SO BMC GENETICS LA English DT Article ID TRANSGENIC MICE; MITOCHONDRIAL SUPEROXIDE; DILATED CARDIOMYOPATHY; PARKINSONS-DISEASE; ESCHERICHIA-COLI; GENOTYPE METHOD; BREAST-CANCER; GENE; CELLS; RISK AB Background: Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species constituting a major cellular defense mechanism against agents that induce oxidative stress. The MnSOD promoter contains an activator protein-2 (AP-2) binding site that modifies transcription of MnSOD. Mutations have been identified in the proximal region of the promoter in human tumor cell lines. One of these mutations (- 102C> T) has been shown to change the binding pattern of AP-2 leading to a reduction in transcriptional activity. The aim of our study was to develop a method to identify and determine the frequency of this (102C> T) polymorphism in human tissues. Results: A new TaqMan allelic discrimination genotype method was successfully applied to genomic DNA samples derived from blood, buccal swabs, snap frozen tissue and paraffin blocks. The polymorphism was shown to be in Hardy-Weinberg Equilibrium in an evaluation of 130 Caucasians from Warsaw, Poland: 44 (33.8%) were heterozygous and 6 (4.6%) were homozygous for - 102T. Conclusion: This report represents the first description of the MnSOD - 102C> T polymorphism in human subjects by a novel Taqman allelic discrimination assay. This method should enable molecular epidemiological studies to evaluate possible associations of this polymorphism with malignancies and other diseases related to reactive oxygen species. C1 Univ Louisville, Sch Med, Dept Surg, Louisville, KY 40292 USA. Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. M Slodowska Curie Inst Oncol, Warsaw, Poland. RP Martin, RCG (reprint author), Univ Louisville, Sch Med, Dept Surg, Louisville, KY 40292 USA. EM robert.martin@louisville.edu; Kalista.hughes@louisville.edu; Mark.doll@louisville.edu; qingl@mail.nih.gov; martini@louisville.edu; lissowsj@coi.waw.pl; rothmann@exchange.nih.gov; david.hein@louisville.edu RI Hein, David/A-9707-2008 FU NCI NIH HHS [CA34627, CA97942, P20 CA097942, R01 CA034627, R01 CA034627-19] NR 30 TC 5 Z9 5 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 14 PY 2004 VL 5 AR 33 DI 10.1186/1471-2156-5-33 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 890QS UT WOS:000226526500001 PM 15598343 ER PT J AU Koh, KK Quon, MJ Han, SH Chung, WJ Ahn, JY Seo, YH Kang, MH Ahn, TH Choi, IS Shin, EK AF Koh, KK Quon, MJ Han, SH Chung, WJ Ahn, JY Seo, YH Kang, MH Ahn, TH Choi, IS Shin, EK TI Additive beneficial effects of Losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients SO CIRCULATION LA English DT Article DE angiotensin; endothelium; hypercholesterolemia; hypertension; insulin ID VASCULAR SMOOTH-MUSCLE; CORONARY-ARTERY-DISEASE; END-POINT REDUCTION; ANGIOTENSIN-II; ENDOTHELIAL DYSFUNCTION; POSTMENOPAUSAL WOMEN; RECEPTOR ANTAGONIST; CONTROLLED-TRIAL; BLOOD-PRESSURE; CELLS AB Background - Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients. Methods and Results - This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms ( each 2 months) and 2 washout periods ( each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone ( both P < 0.001 and P = 0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity ( determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone ( P < 0.001 for adiponectin, P = 0.029 for QUICKI by ANOVA). Conclusions - Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients. C1 Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, Inchon, South Korea. NIH, Diabet Unit, Clin Invest Lab, NCCAM, Bethesda, MD 20892 USA. RP Koh, KK (reprint author), Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon, South Korea. EM kwangk@ghil.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Chung, Wook-Jin/0000-0002-9767-7098; Quon , Michael /0000-0002-5289-3707 NR 33 TC 204 Z9 221 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 14 PY 2004 VL 110 IS 24 BP 3687 EP 3692 DI 10.1161/01.CIR.0000143085.86697.13 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879HI UT WOS:000225706600012 PM 15569835 ER PT J AU Lobachev, K Vitriol, E Stemple, J Resnick, MA Bloom, K AF Lobachev, K Vitriol, E Stemple, J Resnick, MA Bloom, K TI Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex SO CURRENT BIOLOGY LA English DT Article ID DNA-REPAIR; SACCHAROMYCES-CEREVISIAE; INDIVIDUAL NUCLEOSOMES; DICENTRIC CHROMOSOME; MRE11; RECOMBINATION; ANAPHASE; REVEALS; ROLES AB Chromosome aberrations are common outcomes of exposure to DNA-damaging agents or altered replication events and are associated with various diseases and a variety of carcinomas, including leukemias, lymphomas, sarcomas, and epithelial tumors [1, 2]. The incidence of aberrations can be greatly increased as a result of defects in DNA repair pathways [3]. Although there is considerable information about the molecular events associated with the induction and repair of a double-strand break (DSB), little is known about the events that ultimately lead to translocations or deletions through the formation of chromosome breaks or the dissociation of broken ends. We describe a system for visualizing DNA ends at the site of a DSB in living cells. After induction of the break, DNA ends flanking the DSB site in wild-type cells remained adjacent. Loss of a functional RMX complex (Rad50/Mre11/Xrs2) or a mutation in the Rad50 Zn-hook structure resulted in DNA ends being dispersed in approximately 10%-20% of cells. Thus, the RMX complex holds broken ends together and counteracts mitotic spindle forces that can be destructive to damaged chromosomes. C1 NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. Georgia Inst Technol, Sch Biol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. RP Bloom, K (reprint author), NIEHS, Genet Mol Lab, NIH, 101 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM resnick@niehs.nih.gov; kbloom@email.unc.edu OI Vitriol, Eric/0000-0003-3398-1450; Bloom, Kerry/0000-0002-3457-004X FU NIGMS NIH HHS [GM-32238] NR 19 TC 83 Z9 86 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 14 PY 2004 VL 14 IS 23 BP 2107 EP 2112 DI 10.1016/j.cub.2004.11.051 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 880TA UT WOS:000225810900019 PM 15589152 ER PT J AU Turner, JMA Aprelikova, O Xu, XL Wang, RH Kim, SS Chandramouli, GVR Barrett, JC Burgoyne, PS Deng, CX AF Turner, JMA Aprelikova, O Xu, XL Wang, RH Kim, SS Chandramouli, GVR Barrett, JC Burgoyne, PS Deng, CX TI BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome inactivation SO CURRENT BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; X-CHROMOSOME; DNA; PROTEIN; MOUSE; ATM; PROPHASE; CELLS; RNA; SPERMATOGENESIS AB In mammalian spermatogenesis, the X and Y chromosomes are transcriptionally silenced during the pachytene stage of meiotic prophase (meiotic sex chromosome inactivation, MSCI), forming a condensed chromatin domain termed the sex or XY body [1-3]. The nucleosomal core histone H2AX is phosphorylated within the XY chromatin domain just prior to MSCI, and it has been hypothesized that this triggers the chromatin condensation and transcriptional repression [4, 5]. Here, we show that the kinase ATR localizes to XY chromatin at the onset of MSCI and that this localization is disrupted in mice with a mutant form of the tumor suppressor protein BRCA1. In the mutant pachytene cells, ATR is usually present at nonsex chromosomal sites, where it colocalizes with aberrant sites of H2AX phosphorylation; in these cells, there is MSCI failure. In rare pachytene cells, ATR does locate to XY chromatin, H2AX is then phosphorylated, a sex body forms, and MSCI ensues. These observations highlight an important role for BRCA1 in recruiting the kinase ATR to XY chromatin at the onset of MSCI and provide compelling evidence that it is ATR that phosphorylates H2AX and triggers MSCI. C1 NIDDKD, Geent Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England. NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Geent Dev & Dis Branch, NIH, Bldg 10,9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 NR 27 TC 225 Z9 232 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 14 PY 2004 VL 14 IS 23 BP 2135 EP 2142 DI 10.1016/j.cub.2004.11.032 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 880TA UT WOS:000225810900024 PM 15589157 ER PT J AU O'Brien, SJ AF O'Brien, SJ TI Cats SO CURRENT BIOLOGY LA English DT Editorial Material C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. NR 7 TC 4 Z9 4 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 14 PY 2004 VL 14 IS 23 BP R988 EP R989 DI 10.1016/j.cub.2004.11.017 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 880TA UT WOS:000225810900005 PM 15589144 ER PT J AU Pearce, DA Atkinson, M Tagle, DA AF Pearce, DA Atkinson, M Tagle, DA TI Glutamic acid decarboxylase autoimmunity in Batten disease and other disorders SO NEUROLOGY LA English DT Review ID NEURONAL CEROID-LIPOFUSCINOSIS; MITOCHONDRIAL ATP SYNTHASE; SUBUNIT-C; MOUSE MODEL; AUTOANTIBODY; STORAGE; CLN3 AB Degenerative diseases of the CNS, such as stiff-person syndrome (SPS), progressive cerebellar ataxia, and Rasmussen encephalitis, have been characterized by the presence of autoantibodies. Recent findings in individuals with Batten disease and in animal models for the disorder indicate that this condition may be associated with autoantibodies against glutamic acid decarboxylase ( GAD), an enzyme that converts the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid ( GABA). Anti-GAD autoantibodies could result in excess excitatory neurotransmitters, leading to the seizures and other symptoms observed in patients with Batten disease. The pathogenic potential of GAD autoantibodies is examined in light of what is known for other autoimmune disorders, such as multiple sclerosis, SPS, Rasmussen encephalitis, and type 1 diabetes, and may have radical implications for diagnosis and management of Batten disease. C1 Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Ctr Aging & Dev Biol, Rochester, NY 14642 USA. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Pearce, DA (reprint author), Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Ctr Aging & Dev Biol, Box 645, Rochester, NY 14642 USA. EM david_pearce@urmc.rochester.edu NR 17 TC 32 Z9 32 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 14 PY 2004 VL 63 IS 11 BP 2001 EP 2005 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 879IX UT WOS:000225711400005 PM 15596740 ER PT J AU Crooks, DM Pacheco-Rodriguez, G DeCastro, RM McCoy, JP Wang, J Kumaki, F Darling, T Moss, J AF Crooks, DM Pacheco-Rodriguez, G DeCastro, RM McCoy, JP Wang, J Kumaki, F Darling, T Moss, J TI Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE loss of heterozygosity; metastasis; CD235a; angiomyolipoma; smooth muscle cells ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; LYMPHANGIOMYOMATOSIS; WOMEN; TSC2; ANGIOMYOLIPOMAS; HETEROZYGOSITY; EXPRESSION; MUTATIONS; ANTIGEN AB Lymphangioleiomyomatosis (LAM) is a multisystem disorder of women, characterized by cystic degeneration of the lungs, renal angiomyolipomas (AML), and lymphatic abnormalities. LAM lesions result from the proliferation of benign-appearing, smooth muscle-like LAM cells, which are characterized by loss of heterozygosity (LOH) of one of the tuberous sclerosis complex (TSC) genes. LAM cells are believed to migrate among the involved organs. Because of the apparently metastatic behaviour of LAM, we tried to isolate LAM cells from body fluids. A cell fraction separated by density gradient centrifugation from blood had TSC2 LOH in 33 of 60 (55%) LAM patients. Cells with TSC2 LOH were also found in urine from 11 of 14 (79%) patients with AML and in chylous fluid from 1 of 3 (33%) patients. Identification of LAM cells with TSC2 LOH in body fluids was not correlated with severity of lung disease or extrapulmonary involvement and was found in one patient after double lung transplantation. These studies are compatible with a multisite origin for LAM cells. They establish the existence of disseminated, potentially metastatic LAM cells through a relatively simple, noninvasive procedure that should be valuable for molecular and genetic studies of somatic mutations in LAM and perhaps other metastatic diseases. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov OI Darling, Thomas/0000-0002-5161-1974 NR 25 TC 100 Z9 114 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 14 PY 2004 VL 101 IS 50 BP 17462 EP 17467 DI 10.1073/pnas.0407971101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 880QD UT WOS:000225803400029 PM 15583138 ER PT J AU Gil-Da-Costa, R Braun, A Lopes, M Hauser, MD Carson, RE Herscovitch, P Martin, A AF Gil-Da-Costa, R Braun, A Lopes, M Hauser, MD Carson, RE Herscovitch, P Martin, A TI Toward an evolutionary perspective on conceptual representation: Species-specific calls activate visual and affective processing systems in the macaque SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE auditory; brain; evolution; vocalizations; concepts ID SUPERIOR TEMPORAL SULCUS; PRIMATE PREFRONTAL CORTEX; RANGING RHESUS-MONKEYS; MACACA-MULATTA; CORTICAL PROJECTIONS; NONHUMAN PRIMATE; BRAIN; OBJECTS; MEMORY; SOUNDS AB Non-human primates produce a diverse repertoire of species-specific calls and have rich conceptual systems. Some of their calls are designed to convey information about concepts such as predators, food, and social relationships, as well as the affective state of the caller. Little is known about the neural architecture of these calls, and much of what we do know is based on single-cell physiology from anesthetized subjects. By using positron emission tomography in awake rhesus macaques, we found that conspecific vocalizations elicited activity in higher-order visual areas, including regions in the temporal lobe associated with the visual perception of object form (TE/TEO) and motion (superior temporal sulcus) and storing visual object information into long-term memory (TE), as well as in limbic (the amygdala and hippocampus) and paralimbic regions (ventromedial prefrontal cortex) associated with the interpretation and memory-encoding of highly salient and affective material. This neural circuitry strongly corresponds to the network shown to support representation of conspecifics and affective information in humans. These findings shed light on the evolutionary precursors of conceptual representation in humans, suggesting that monkeys and humans have a common neural substrate for representing object concepts. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NIDCD, NIH, Bethesda, MD 20892 USA. NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. Gulbenkian Inst Sci, Program Biol & Med, P-2780 Oeiras, Portugal. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Martin, A (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C-104, Bethesda, MD 20892 USA. EM alexmartin@mail.nih.gov RI martin, alex/B-6176-2009; Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 54 TC 71 Z9 72 U1 0 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 14 PY 2004 VL 101 IS 50 BP 17516 EP 17521 DI 10.1073/pnas.0408077101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 880QD UT WOS:000225803400038 PM 15583132 ER PT J AU Wang, HF Cao, WW Zhou, QF Shung, KK Huang, YH AF Wang, HF Cao, WW Zhou, QF Shung, KK Huang, YH TI Silicon oxide colloidal/polymer nanocomposite films SO APPLIED PHYSICS LETTERS LA English DT Article ID MEDICAL IMAGING APPLICATIONS; THIN-FILMS; PIEZOELECTRIC PROPERTIES; ULTRASONIC TRANSDUCERS; MHZ AB The quarter-wavelength (lambda/4) acoustic matching layer, a vital component in medical ultrasonic transducer, can bridge the large acoustic impedance mismatch between the piezoelectric material and the human body. Composite materials are widely used as matching materials in order to cover the wide acoustic impedance range that cannot be accomplished by using a single-phase material. At high frequencies (>50 MHz), the lambda/4 matching layers become extremely thin so that the fabrication of homogeneous composite material matching layers becomes very challenging. A method is reported in this letter to fabricate sol-gel silicon oxide colloidal/polymer composite film on silicon substrate, in which the particle size of silicon oxide colloidal is between 10 and 40 nm. The acoustic impedance of the nanocomposite films versus aging temperature has been measured at the desired operating frequency. (C) 2004 American Institute of Physics. C1 Penn State Univ, Mat Res Inst, University Pk, PA 16802 USA. Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. Chemat Technol Inc, Northridge, CA 91324 USA. RP Wang, HF (reprint author), Siemens Med Solut USA Inc, Issaquah, WA 98027 USA. EM qifazhou@usc.edu RI Cao, Wenwu/F-6091-2012 OI Cao, Wenwu/0000-0002-2447-1486 NR 9 TC 16 Z9 16 U1 1 U2 10 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD DEC 13 PY 2004 VL 85 IS 24 BP 5998 EP 6000 DI 10.1063/1.1836018 PG 3 WC Physics, Applied SC Physics GA 878AZ UT WOS:000225620200061 ER PT J AU Siddiq, F Chowfin, A Tight, R Sahmoun, AE Smego, RA AF Siddiq, F Chowfin, A Tight, R Sahmoun, AE Smego, RA TI Medical vs surgical management of spinal epidural abscess SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 11th International Congress on Infectious Diseases CY MAR 04-07, 2004 CL Cancun, MEXICO ID PROGNOSTIC FACTORS AB Background: We compared the clinical features and outcomes of patients with spinal epidural abscess treated with prolonged parenteral antibiotics alone or combined with computed tomography-guided percutaneous needle aspiration drainage with those of patients undergoing surgical decompression. Methods: A retrospective analysis of 57 cases of spinal epidural abscess treated at an academic teaching hospital during a 14-year period. Results: The lumbar region was most frequently involved, and 46% of patients were immunocompromised. Staphylococcus aureus was the most frequently encountered pathogen. For 60 treatment courses, management included medical only (25 patients), medical plus computed tomography-guided percutaneous needle aspiration (7 patients), or surgical drainage approaches (28 patients). Prolonged use of parenteral antibiotics alone or combined with percutaneous needle drainage yielded clinical outcomes at least comparable with antibiotics plus surgical intervention, irrespective of patient age, presence of comorbid illness, disease onset, neurologic abnormality at time of presentation, or abscess size. Conclusion: Patients with spinal epidural abscess can be safely and effectively treated with conservative medical treatment without the need for surgery. C1 NIAID, NIH, TB Res Sect, Rockville, MD 20852 USA. N Dakota State Univ, Sch Med & Hlth Sci, Dept Med, Fargo, ND 58105 USA. RP Smego, RA (reprint author), NIAID, NIH, TB Res Sect, Twinbrook II,Room 2236,MSC 8180,12441 Parklawn Dr, Rockville, MD 20852 USA. EM rsmego@niaid.nih.gov NR 20 TC 74 Z9 74 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 13 PY 2004 VL 164 IS 22 BP 2409 EP 2412 DI 10.1001/archinte.164.22.2409 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 879FN UT WOS:000225701900002 PM 15596629 ER PT J AU Knox, SS Weidner, G Adelman, A Stoney, CM Ellison, C AF Knox, SS Weidner, G Adelman, A Stoney, CM Ellison, C CA Invest Natl Heart Lung Blood Inst TI Hostility and physiological risk in the National Heart, Lung, and Blood Institute Family Heart Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Psychosomatic-Society CY MAR 05-08, 2003 CL PHOENIX, AZ SP Amer Psychosomat Soc ID ACUTE MYOCARDIAL-INFARCTION; LONGITUDINAL DATA-ANALYSIS; METABOLIC SYNDROME; YOUNG-ADULTS; SOCIAL SUPPORT; DISEASE; MORTALITY; PLASMA; MEN; ATHEROSCLEROSIS AB Background: The present analyses investigated possible pathways for earlier reported associations in the National Heart, Lung, and Blood Institute Family Heart Study between hostility and coronary and carotid end points. Methods: The cross-sectional design recruited 535 women and 491 men with average familial risk for coronary heart disease and 1950 women and 1667 men with high familial coronary risk from 3 prospective ongoing studies at 4 sites. Recruitment of high-risk participants was based on family risk score. Average-risk participants came from a randomly selected group. Outcome measures were plasminogen activator inhibitor type 1 (PAI-1), homocysteine, fibrinogen, fasting glucose, blood pressure, high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol, and "lipid metabolic disorder" (LMD) (defined as systolic blood pressure greater than or equal to140 mm Hg or diastolic blood pressure greater than or equal to90 mm Hg); fasting glucose greater than or equal to126 mg/dL (greater than or equal to7.0 mmol/L) or the use of diabetes medications; body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than or equal to30; triglycerides greater than or equal to250 mg/dL (greater than or equal to2.8 mmol/L), high-density lipoprotein cholesterol <40 mg/dL (<1.0 mmol/L) in men and <50 mg/dL (<1.3 mmol/L) in women; and low-density lipoprotein cholesterol level greater than or equal to130 mg/dL (greater than or equal to3.4 mmol/L). Results: After adjustment for age and risk-related behaviors, hostility was significantly associated with glucose level and LMD in high-risk women, with LMD in average-risk women, with PAI-1 and LMD in high-risk men, and with fibrinogen level in average-risk men. Conclusions: Associations between hostility and physiological risk were only partially accounted for by health behaviors, suggesting that further investigation of mechanistic pathways is warranted. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Res Inst Prevent Med, Suasalito, CA USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RP Knox, SS (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd-5C01, Bethesda, MD 20892 USA. EM knoxss@mail.nih.gov NR 46 TC 10 Z9 10 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 13 PY 2004 VL 164 IS 22 BP 2442 EP 2448 DI 10.1001/archinte.164.22.2442 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 879FN UT WOS:000225701900007 PM 15596634 ER PT J AU Abbott, KC Trespalacios, FC Agodoa, LY Taylor, A Bakris, GL AF Abbott, KC Trespalacios, FC Agodoa, LY Taylor, A Bakris, GL TI beta-Blocker use in long-term dialysis patients - Association with hospitalized heart failure and mortality SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HEMODIALYSIS-PATIENTS; ADRENERGIC-BLOCKADE; CONTROLLED-TRIAL; UNITED-STATES; RISK-FACTORS; COMET TRIAL; THERAPY; SURVIVAL; DISEASE; HYPERTENSION AB Background: beta-Blockers have been shown to be beneficial in the treatment and prevention of heart failure (HF) in the general population, but they have not been assessed for their association with nonfatal HF in a nationally representative population of long-term dialysis patients. Methods: We conducted a retrospective cohort study of 2550 patients enrolled in the US Renal Data System (USRDS) Wave 2 who were Medicare eligible at the start of the study. Analysis was stratified by the presence or absence of a known diagnosis of HF, and patients followed up until December 31, 2000. Cox regression analysis, including propensity scores, was used to model adjusted hazard ratios for beta-blocker use (assessed separately by cardioselective activity and lipid solubility) with time to the first Medicare institutional claim for HF, cardiovascular-related death, or death from any cause. Results: In patients without a previous history of HF, beta-blocker use was significantly associated with a lower adjusted risk of HF (adjusted hazard ratio, 0.69; 95% confidence interval, 0.52-0.91; P=.008), with a similar reduction in risk of cardiac-related and all-cause death. beta-Blocker use had no statistically significant associations with outcomes in patients with previous HF. Conclusions: In dialysis patients without a previous documented history of HF, beta-blocker use was associated with a lower risk of new HF, cardiovascular death, and death from any cause. No such associations were seen for dialysis patients with a previous history of HF. These results are hypothesis generating only and should be confirmed in randomized trials. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Serv Cardiol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Div Nephrol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Div Cardiol, Bethesda, MD 20814 USA. Madigan Army Med Ctr, Serv Nephrol, Ft Lewis, WA USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Prevent Med Serv, Chicago, IL 60612 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 36 TC 71 Z9 77 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 13 PY 2004 VL 164 IS 22 BP 2465 EP 2471 DI 10.1001/archinte.164.22.2465 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 879FN UT WOS:000225701900010 PM 15596637 ER PT J AU Shih, JH Michalowska, AM Dobbin, K Ye, YM Qiu, TH Green, JE AF Shih, JH Michalowska, AM Dobbin, K Ye, YM Qiu, TH Green, JE TI Effects of pooling mRNA in microarray class comparisons SO BIOINFORMATICS LA English DT Article ID DESIGN AB Motivation: In microarray experiments investigators sometimes wish to pool RNA samples before labeling and hybridization due to insufficient RNA from each individual sample or to reduce the number of arrays for the purpose of saving cost. The basic assumption of pooling is that the expression of an mRNA molecule in the pool is close to the average expression from individual samples. Recently, a method for studying the effect of pooling mRNA on statistical power in detecting differentially expressed genes between classes has been proposed, but the different sources of variation arising in microarray experiments were not distinguished. Another paper recently did take different sources of variation into account, but did not address power and sample size for class comparison. In this paper, we study the implication of pooling in detecting differential gene expression taking into account different sources of variation and check the basic assumption of pooling using data from both the cDNA and Affymetrix GeneChip microarray experiments. Results: We present formulas for the required number of subjects and arrays to achieve a desired power at a specified significance level. We show that due to the loss of degrees of freedom for a pooled design, a large increase in the number of subjects may be required to achieve a power comparable to that of a non-pooled design. The added expense of additional samples for the pooled design may outweigh the benefit of saving on microarray cost. The microarray data from both platforms show that the major assumption of pooling may not hold. C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM jshih@mail.nih.gov NR 10 TC 40 Z9 42 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD DEC 12 PY 2004 VL 20 IS 18 BP 3318 EP 3325 DI 10.1093/bioinformatics/bth391 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 880JR UT WOS:000225786600004 PM 15247103 ER PT J AU Dorman, SE Picard, C Lammas, D Heyne, K van Dissel, JT Baretto, R Rosenzweig, SD Newport, M Levin, M Roesler, J Kumararatne, D Casanova, JL Holland, SM AF Dorman, SE Picard, C Lammas, D Heyne, K van Dissel, JT Baretto, R Rosenzweig, SD Newport, M Levin, M Roesler, J Kumararatne, D Casanova, JL Holland, SM CA IFNgammaR1 Deficiency Study Grp TI Clinical features of dominant and recessive interferon gamma receptor 1 deficiencies SO LANCET LA English DT Article ID INTERFERON-GAMMA-RECEPTOR; BACILLE CALMETTE-GUERIN; INHERITED INTERLEUKIN-12 DEFICIENCY; SMALL DELETION HOTSPOT; MYCOBACTERIAL INFECTION; IFN-GAMMA; IFN-GAMMA-R1 DEFICIENCY; CHILD; SUSCEPTIBILITY; MUTATION AB Background Interferon gamma receptor 1 (IFNgammaR1) deficiency is a primary immunodeficiency with allelic dominant and recessive mutations characterised clinically by severe infections with mycobacteria. We aimed to compare the clinical features of recessive and dominant IFNgammaR1 deficiencies. Methods We obtained data from a large cohort of patients worldwide. We assessed these people by medical histories, records, and genetic and immunological studies. Data were abstracted onto a standard form. Findings We identified 22 patients with recessive complete IFNgammaR1 deficiency and 38 with dominant partial deficiency. BCG and environmental mycobacteria were the most frequent pathogens. In recessive patients, 17 (77%) had environmental mycobacterial disease and all nine BCG-vaccinated patients had, BCG disease. In dominant patients, 30 (79%) had environmental mycobacterial disease and 11 (73%) of 15 BCG-vaccinated patients had BCG disease. Compared with dominant patients, those with recessive deficiency were younger at onset of first environmental mycobacterial disease (mean 3.1 years [SD 2.5] vs 13.4 years [14.3], p=0.001), had more mycobacterial disease episodes (19 vs 8 per 100 person-years of observation, p=0.0001), had more severe mycobacterial disease (mean number of organs infected by Mycobacterium avium complex 4.1 [SD 0.8] vs 2.0 [1.1], p=0.004), had shorter mean disease-free intervals (1.6 years [SD 1.4] vs 7.2 years [7.6], p<0.0001), and lower Kaplan-Meier survival probability (p<0.0001). M avium complex osteomyelitis was more frequent in dominant than in recessive patients (22/28 [79%] vs 1/8 [13%], p=0.002), and this disorder without other organ involvement arose only in dominant patients (9/28 [32%]). Disease caused by rapidly growing mycobacteria was present in more recessive than dominant patients (7/22 [32%] vs 1/38 [3%], p=0.002). Interpretation Recessive complete and dominant partial IFNgammaR1 deficiencies have related clinical phenotypes, but are distinguishable by age at onset, dissemination, and clinical course of mycobacterial diseases. A strong correlation exists between IFNGR1 genotype, cellular responsiveness to interferon gamma, and clinical disease features. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Univ Paris 05, Lab Human Genet Infect Dis, INSERM, U550,Necker Med Sch, Paris, France. Hop Necker Enfants Malad, Dept Paediat, Paediat Immunol Haematol Unit, Paris, France. Univ Birmingham, Div Immun & Infect, Birmingham, W Midlands, England. Illerweg, Kiel, Germany. Leiden Univ, Med Ctr, Leiden, Netherlands. Hosp Garrahan, Buenos Aires, DF, Argentina. Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England. Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Paediat, London, England. Univ Dresden, Dresden, Germany. Addenbrookes Hosp, Dept Clin Biochem & Immunol, Cambridge, England. RP Casanova, JL (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bldg 10,CRC B3-419,10 Ctr Dr,MSC 1684, Bethesda, MD 20892 USA. EM casanova@necker.fr; smh@nih.gov NR 41 TC 223 Z9 229 U1 0 U2 13 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 11 PY 2004 VL 364 IS 9451 BP 2113 EP 2121 DI 10.1016/S0140-6736(04)17552-1 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 879TR UT WOS:000225742300024 PM 15589309 ER PT J AU Leblais, V Jo, SH Chakir, K Maltsev, V Zheng, M Crow, MT Wang, W Lakatta, EG Xiao, RP AF Leblais, V Jo, SH Chakir, K Maltsev, V Zheng, M Crow, MT Wang, W Lakatta, EG Xiao, RP TI Phosphatidylinositol 3-kinase offsets cAMP-mediated positive inotropic effect via inhibiting Ca2+ influx in cardiomyocytes SO CIRCULATION RESEARCH LA English DT Article DE PI3K; PKA; cardiac contractility; L-type calcium current; beta(1)-adrenergic receptor ID COUPLED RECEPTOR KINASES; CARDIAC MYOCYTES; PHOSPHOINOSITIDE 3-KINASE; G-PROTEIN; PERTUSSIS-TOXIN; MYOCARDIAL-CONTRACTILITY; ADENYLYL-CYCLASE; UP-REGULATION; CELL-DEATH; RAT-HEART AB Phosphoinositide 3-kinase (PI3K) has been implicated in beta(2)-adrenergic receptor (beta(2)-AR)/G(i)-mediated compartmentation of the concurrent G(s)-cAMP signaling, negating beta(2)-AR-induced phospholamban phosphorylation and the positive inotropic and lusitropic responses in cardiomyocytes. However, it is unclear whether PI3K crosstalks with the beta(1)-AR signal transduction, and even more generally, with the cAMP/PKA pathway. In this study, we show that selective beta(1)-AR stimulation markedly increases PI3K activity in adult rat cardiomyocytes. Inhibition of PI3K by LY294002 significantly enhances beta(1)-AR-induced increases in L-type Ca2+ currents, intracellular Ca2+ transients, and myocyte contractility, without altering the receptor-mediated phosphorylation of phospholamban. The LY294002 potentiating effects are completely prevented by betaARK-ct, a peptide inhibitor of beta-adrenergic receptor kinase-1 (betaARK1) as well as G(betagamma) signaling, but not by disrupting G(i) function with pertussis toxin. Moreover, forskolin, an adenylyl cyclase activator, also elevates PI3K activity and inhibition of PI3K enhances forskolin-induced contractile response in a betaARK-ct sensitive manner. In contrast, PI3K inhibition affects neither the basal contractility nor high extracellular Ca2+-induced increase in myocyte contraction. These results suggest that beta(1)-AR stimulation activates PI3K via a PKA-dependent mechanism, and that G(betagamma) and the subsequent activation of betaARK1 are critically involved in the PKA-induced PI3K signaling which, in turn, negates cAMP-induced positive inotropic effect via inhibiting sarcolemmal Ca2+ influx and the subsequent increase in intracellular Ca2+ transients, without altering the receptor-mediated phospholamban phosphorylation, in intact cardiomyocytes. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. Peking Univ, Inst Cardiovasc Sci, Beijing 100871, Peoples R China. RP Xiao, RP (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM XiaoR@grc.nia.nih.gov OI Wang, Wang/0000-0001-9093-412X NR 41 TC 39 Z9 44 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC 10 PY 2004 VL 95 IS 12 BP 1183 EP 1190 DI 10.1161/01.RES.0000150049.74539.8a PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 878IT UT WOS:000225641000007 PM 15539636 ER PT J AU Akahane, T Akahane, M Shah, A Connor, CM Thorgeirsson, UP AF Akahane, T Akahane, M Shah, A Connor, CM Thorgeirsson, UP TI TIMP-1 inhibits microvascular endothelial cell migration by MMP-dependent and MMP-independent mechanisms SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE TIMP-1; MMP; microvascular; endothelium; focal adhesion; VE-cadherin; PECAM-1; cytoskeleton; FAK; paxillin; PTEN ID FOCAL ADHESION KINASE; TUMOR-SUPPRESSOR PTEN; TISSUE INHIBITOR; METALLOPROTEINASE INHIBITORS; INTERENDOTHELIAL JUNCTIONS; BETA-CATENIN; E-CADHERIN; ANGIOGENESIS; CANCER; GROWTH AB It was reported over a decade ago that tissue inhibitor of metal loproteinases- I (TIMP-1) suppresses angiogenesis in experimental models but the mechanism is still incompletely understood. This in vitro study focused on the molecular basis of TIMP-1-mediated inhibition of endothelial cell (EC) migration, a key step in the angiogenic process. Both recombinant human TIMP-1 and the synthetic MMP inhibitors, GM6001 and MMP-2-MMP-9 Inhibitor 111, suppressed migration of human dermal microvascular endothelial cells (HDMVEC) in a close-dependent fashion. The MMP-dependent inhibition of migration was associated with increased expression of the junctional adhesion proteins, VE-cadherin and PECAM-1, and VE-cadherin accumulation at cell-cell junctions. TIMP-1 also caused MMP-independent dephosphorylation of focal adhesion kinase (FAK) (pY397) and paxillin, which was associated with reduced number of F-actin stress fibers and focal adhesions. Moreover, TIMP-1 stimulated expression of PTEN that has been shown to reduce phosphorylation of FAK and inhibit cell migration. Our data suggest that TIMP-I inhibits HDMVEC migration through MMP-dependent stimulation of VE-cadherin and MMP-independent stimulation of PTEN with subsequent dephosphorylation of FAK and cytoskeletal remodeling. Published by Elsevier Inc. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, UP (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bldg 37,Room 4068,9000 Rockville Pike, Bethesda, MD 20892 USA. EM thorgeiu@mail.nih.gov NR 51 TC 58 Z9 66 U1 1 U2 5 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC 10 PY 2004 VL 301 IS 2 BP 158 EP 167 DI 10.1016/j.yexcr.2004.08.002 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 873DY UT WOS:000225260800006 PM 15530852 ER PT J AU Geiszt, M Leto, TL AF Geiszt, M Leto, TL TI The Nox family of NAD(P)H oxidases: Host defense and beyond SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID COLON EPITHELIAL-CELLS; SUPEROXIDE-GENERATING OXIDASE; RESPIRATORY BURST OXIDASE; SMOOTH-MUSCLE CELLS; NADPH-OXIDASE; HYDROGEN-PEROXIDE; REACTIVE OXYGEN; SIGNAL-TRANSDUCTION; KINASE ACTIVATION; EXPRESSION C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Fac Med, Dept Physiol, H-1444 Budapest, Hungary. RP Leto, TL (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tleto@nih.gov NR 61 TC 283 Z9 296 U1 1 U2 18 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 51715 EP 51718 DI 10.1074/jbc.R400024200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400001 PM 15364933 ER PT J AU Yu, DH Khan, E Khaleque, MA Lee, J Laco, G Kohlhagen, G Kharbanda, S Cheng, YC Pommier, Y Bharti, A AF Yu, DH Khan, E Khaleque, MA Lee, J Laco, G Kohlhagen, G Kharbanda, S Cheng, YC Pommier, Y Bharti, A TI Phosphorylation of DNA topoisomerase I by the c-Abl tyrosine kinase confers camptothecin sensitivity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVE-SITE TYROSINE; N-TERMINAL DOMAIN; CATALYTIC-ACTIVITY; APOPTOTIC RESPONSE; IONIZING-RADIATION; CLEAVAGE COMPLEXES; ANTITUMOR DRUGS; STRESS-RESPONSE; CYTO-TOXICITY; STRAND BREAKS AB DNA topoisomerase I ( topo I) is involved in the regulation of DNA supercoiling, gene transcription, recombination, and DNA repair. The anticancer agent camptothecin specifically targets topo I. The mechanisms responsible for the regulation of topo I in cells, however, are not known. This study demonstrates that c-Abl-dependent phosphorylation up-regulates topo I activity. The c-Abl SH3 domain bound directly to the N-terminal region of topo I. The results demonstrate that c-Abl phosphorylated topo I at Tyr(268) in core subdomain II. c-Abl-mediated phosphorylation of topo I Tyr(268) in vitro and in cells conferred activation of the topo I isomerase function. Moreover, activation of c-Abl by treatment of cells with ionizing radiation was associated with c-Abl-dependent phosphorylation of topo I and induction of topo I activity. The functional significance of the c-Abl/topo I interaction is supported by the findings that (i) mutant topo I(Y268F) exhibited loss of c-Abl-induced topo I activity, and (ii) c-Abl(-/-) cells were deficient in the accumulation of protein-linked DNA breaks. In addition, loss of topo I phosphorylation in c-Abl-deficient cells conferred resistance to camptothecin-induced apoptosis. These findings collectively support a model in which c-Abl-mediated phosphorylation of topo I is functionally important to topo I activity and sensitivity to topo I poisons. C1 Boston Univ, Sch Med, Dept Med, Ctr Mol Stress Response, Boston, MA 02118 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Bharti, A (reprint author), Boston Univ, Sch Med, Dept Med, Ctr Mol Stress Response, 650 Albany St,EBRC-311, Boston, MA 02118 USA. EM Bharti@bu.edu FU NCI NIH HHS [CA55241] NR 91 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 51851 EP 51861 DI 10.1074/jbc.M404396200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400018 PM 15448168 ER PT J AU Trosky, JE Mukherjee, S Burdette, DL Roberts, M McCarter, L Siegel, RM Orth, K AF Trosky, JE Mukherjee, S Burdette, DL Roberts, M McCarter, L Siegel, RM Orth, K TI Inhibition of MAPK signaling pathways by VopA from Vibrio parahaemolyticus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YERSINIA EFFECTOR YOPJ AB During infection, bacterial pathogens utilize a type III secretion system to inject effectors into the cytoplasm of a target cell where they disrupt the defense system of the host cell. Vibrio parahaemolyticus, a causative agent of gastroenteritis endemic in Southeast Asia, has a type III secretion system that encodes a novel member of the YopJ-like protein effector family, VopA ( Vibrio outer protein A). Our studies revealed that Vibrio VopA encodes an evolutionarily conserved activity that is extremely potent and requires an intact catalytic site to abrogate signaling pathways in a manner distinct from that of other YopJ-like effectors. We observed that VopA efficiently inhibits the MAPK signaling pathways but not the NFkappaB pathway in mammalian cells. When expressed in yeast, VopA induces a growth arrest phenotype and also blocks yeast MAPK signaling pathways. Our observations provide insight into the immense diversity of targets utilized by YopJ-like effectors to manipulate eukaryotic signaling machineries that are important for the response and survival of the host cell during infection and/or symbiosis. C1 Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA. NIAMS, Immunoregulat Unit, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. RP Orth, K (reprint author), Univ Texas, SW Med Ctr, Dept Mol Biol, 5323 Harry Hines Blvd,Room NA5-320, Dallas, TX 75390 USA. EM kimorth@hamon.swmed.edu OI Dinalo, Jennifer/0000-0001-5174-5756 FU NIAID NIH HHS [AI056404, Y2-AI-3739] NR 16 TC 69 Z9 71 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 51953 EP 51957 DI 10.1074/jbc.M407001200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400030 PM 15459200 ER PT J AU Katsafanas, GC Moss, B AF Katsafanas, GC Moss, B TI Vaccinia virus intermediate stage transcription is complemented by Ras-GTPase-activating protein SH3 domain-binding protein (G3BP) and cytoplasmic activation/proliferation-associated protein (p137) individually or as a heterodimer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LATE MESSENGER-RNAS; GENE-EXPRESSION; LATE PROMOTER; ENDORIBONUCLEASE G3BP; IN-VITRO; PURIFICATION; POLYMERASE; IDENTIFICATION; CELLS; SUBUNIT AB Transcription of the DNA genome of vaccinia virus occurs in the cytoplasm and is temporally programmed by early, intermediate, and late stage-specific transcription factors in conjunction with a viral multisubunit RNA polymerase. The RNA polymerase, capping enzyme, and three factors (VITF-1, VITF-2, and VITF-3) are sufficient for in vitro transcription of a DNA template containing an intermediate stage promoter. Vaccinia virus intermediate transcription factor (VITF)-1 and -3 are virus-encoded, whereas VITF-2 was partially purified from extracts of uninfected HeLa cells. Using purified and recombinant viral proteins, we showed that the HeLa cell factor was required for transcription of linear or nicked circular templates but not of super coiled DNA. HeLa cell polypeptides of similar to110 and 66 kDa co-purified with VITF-2 activity through multiple chromatographic steps. The polypeptides were separated by SDS-polyacrylamide gel electrophoresis and identified by mass spectrometry as Ras-GTPase-activating protein SH3 domain-binding protein (G3BP) and p137, recently named cytoplasmic activation/proliferation-associated protein-1. The co-purification of the two polypeptides with transcription-complementing activity was confirmed with specific antibodies, and their association with each other was demonstrated by affinity chromatography of tagged recombinant forms. Furthermore, recombinant G3BP and p137 expressed individually or together in mammalian or bacterial cells complemented the activity of the viral RNA polymerase and transcription factors. The involvement of cellular proteins in transcription of intermediate stage genes may regulate the transition between early and late phases of vaccinia virus replication. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 39 TC 48 Z9 50 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 52210 EP 52217 DI 10.1074/jbc.M411033200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400061 PM 15471883 ER PT J AU Anderson, SP Howroyd, P Liu, J Qian, X Bahnemann, R Swanson, C Kwak, MK Kensler, TW Corton, JC AF Anderson, SP Howroyd, P Liu, J Qian, X Bahnemann, R Swanson, C Kwak, MK Kensler, TW Corton, JC TI The transcriptional response to a peroxisome proliferator-activated receptor alpha agonist includes increased expression of proteome maintenance genes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PPAR-ALPHA; NULL MICE; DIFFERENTIAL EXPRESSION; PROTEASOME ACTIVITY; 20S PROTEASOME; PROTECTION; PROTEINS; DITHIOLETHIONES; CLOFIBRATE; APOPTOSIS AB The nuclear receptor peroxisome proliferator-activated receptor alpha(PPARalpha), in addition to regulating lipid homeostasis, controls the level of tissue damage after chemical or physical stress. To determine the role of PPARalpha in oxidative stress responses, we examined damage after exposure to chemicals that increase oxidative stress in wild-type or PPARalpha-null mice. Primary hepatocytes from wild-type but not PPARalpha-null mice pretreated with the PPAR pan-agonist WY-14,643 (WY) were protected from damage to cadmium and paraquat. The livers from intact wild-type but not PPARalpha-null mice were more resistant to damage after carbon tetrachloride treatment. To determine the molecular basis of the protection by PPARalpha, we identified by transcript profiling genes whose expression was altered by a 7-day exposure to WY in wild-type and PPARalpha-null mice. Of the 815 genes regulated by WY in wild-type mice ( p less than or equal to 0.001; greater than or equal to 1.5-fold or less than or equal to - 1.5-fold), only two genes were regulated similarly by WY in PPARalpha-null mice. WY increased expression of stress modifier genes that maintain the health of the proteome, including those that prevent protein aggregation (heat stress-inducible chaperones) and eliminate damaged proteins ( proteasome components). Although the induction of proteasomal genes significantly overlapped with those regulated by 1,2-dithiole-3-thione, an activator of oxidant-inducible Nrf2, WY increased expression of proteasomal genes independently of Nrf2. Thus, PPARalpha controls the vast majority of gene expression changes after exposure to WY in the mouse liver and protects the liver from oxidant-induced damage, possibly through regulation of a distinct set of proteome maintenance genes. C1 ToxicoGenom, Chapel Hill, NC 27514 USA. Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. BASF AG, D-67056 Ludwigshafen, Germany. NCI, NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Chem Ind Inst Toxicol, Ctr Hlth Res, Res Triangle Pk, NC 27709 USA. Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. GlaxoSmithKline Res & Dev, Invest Toxicol & Pathol Grp, Safety Assessment, Res Triangle Pk, NC 27709 USA. RP Corton, JC (reprint author), ToxicoGenom, 209 Silver Creek Tr, Chapel Hill, NC 27514 USA. EM ccorton@msn.com RI Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X FU NIEHS NIH HHS [ES09775-01] NR 38 TC 56 Z9 57 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 52390 EP 52398 DI 10.1074/jbc.M409347200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400083 PM 15375163 ER PT J AU Smith, AJ Sanders, MA Thompson, BR Londos, C Kraemer, FB Bernlohr, DA AF Smith, AJ Sanders, MA Thompson, BR Londos, C Kraemer, FB Bernlohr, DA TI Physical association between the adipocyte fatty acid-binding protein and hormone-sensitive lipase - A fluorescence resonance energy transfer analysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTORS; DIFFERENTIATION-RELATED PROTEIN; A-MEDIATED LIPOLYSIS; INSULIN-RESISTANCE; 3T3-L1 ADIPOCYTES; LIPID DROPLETS; ADIPOSE-TISSUE; PERILIPIN-A; KINASE; CELLS AB Previous in vitro studies have established that hormone sensitive lipase (HSL) and adipocyte fatty acid-binding protein (AFABP) form a physical complex that presumably positions the FABP to accept a product fatty acid generated during catalysis. To assess AFABP-HSL interaction within a cellular context, we have used lipocytes derived from 293 cells (C8PA cells) and examined physical association using fluorescence resonance energy transfer. Transfection of C8PA cells with cyan fluorescent protein (CFP)-HSL, yellow fluorescent protein (YFP)-adipocyte FABP, or YFP-liver FABP revealed that under basal conditions each protein was cytoplasmic. In the presence of 20 muM forskolin, CFP-HSL translocated to the triacylglycerol droplet, coincident with BODIPY-FA labeled depots. Fluorescence resonance energy transfer analysis demonstrated that CFP-HSL associated with YFP-adipocyte FABP in both basal and forskolin-treated cells. In contrast, little if any fluorescence resonance energy transfer could be detected between CFP-HSL and YFP-liver FABP. These results suggest that a pre-lipolysis complex containing at least AFABP and HSL exists and that the complex translocates to the surface of the lipid droplet. C1 Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. Univ Minnesota, Imaging Ctr, St Paul, MN 55108 USA. NIDDK, Membrane Regulat Sect, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Med, Div Endocrinol, Stanford, CA 94305 USA. Vet Adm Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. RP Bernlohr, DA (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, 321 Church St SE, Minneapolis, MN 55455 USA. EM bern1001@umn.edu FU NIDDK NIH HHS [DK 53189, DK 46942] NR 33 TC 41 Z9 43 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 52399 EP 52405 DI 10.1074/jbc.M410301200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400084 PM 15456755 ER PT J AU Liang, XD Young, JJ Boone, SA Waugh, DS Duesbery, NS AF Liang, XD Young, JJ Boone, SA Waugh, DS Duesbery, NS TI Involvement of domain II in toxicity of anthrax lethal factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TOXIN PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; ADENYLATE-CYCLASE; CRYSTAL-STRUCTURE; FACTOR CLEAVES; KINASE-KINASE; INHIBITORS; SEQUENCE; CELLS; MACROPHAGES AB Anthrax lethal factor (LF) is a Zn2+-metalloprotease that cleaves and inactivates mitogen-activated protein kinase kinases (MEKs). We have used site-directed mutagenesis to identify a cluster of residues in domain II of LF that lie outside the active site and are required for cellular proteolytic activity toward MEKs. Alanine substituted for Leu(293), Lys(294), Leu(514), Asn(516), or Arg(491) caused a 10-50-fold reduction in LF toxicity. Further, whereas pairwise substitution of alanine for Leu(514) and either Leu(293), Lys(294), or Arg(491) completely abrogated LF toxicity, pairwise mutation of Leu(514) and Asn(516) resulted in toxicity comparable with N516A alone. The introduction of these mutations reduced LF-mediated cleavage of MEK2 in cell-based assays but altered neither the ability of LF to bind protective antigen nor its ability to translocate across a membrane. Interestingly, direct in vitro measurement of LF activity indicated that decreased toxicity was not always accompanied by reduced proteolytic activity. However, mutations in this region significantly reduced the ability of LF to competitively inhibit B-Raf phosphorylation of MEK. These results provide evidence that elements of domain II are involved in the association of LF into productive complex with MEKs. C1 Van Andel Res Inst, Lab Canc & Dev Cell Biol, Grand Rapids, MI 49503 USA. NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Duesbery, NS (reprint author), Van Andel Res Inst, Lab Canc & Dev Cell Biol, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA. EM duesbery@vai.org OI DUESBERY, NICK/0000-0002-4258-5655 NR 39 TC 18 Z9 19 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 52473 EP 52478 DI 10.1074/jbc.M409105200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400092 PM 15465830 ER PT J AU Allende, ML Sasaki, T Kawai, H Olivera, A Mi, YD van Echten-Deckert, G Hajdu, R Rosenbach, M Keohane, CA Mandala, S Spiegel, S Proia, RL AF Allende, ML Sasaki, T Kawai, H Olivera, A Mi, YD van Echten-Deckert, G Hajdu, R Rosenbach, M Keohane, CA Mandala, S Spiegel, S Proia, RL TI Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; FUNCTIONAL-CHARACTERIZATION; VASCULAR MATURATION; MOLECULAR-CLONING; IMMUNOSUPPRESSANT FTY720; 1-PHOSPHATE RECEPTOR; ENDOTHELIAL-CELLS; SPHINGOSINE-1-PHOSPHATE; GROWTH; S1P(1) AB Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many cellular functions, is synthesized from sphingosine and ATP by the action of sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To begin to investigate the physiological functions of sphingosine kinase and S1P signaling, we generated mice deficient in SPHK1. Sphk1 null mice were viable, fertile, and without any obvious abnormalities. Total SPHK activity in most Sphk1-/- tissues was substantially, but not completely, reduced indicating the presence of multiple sphingosine kinases. S1P levels in most tissues from the Sphk1 -/- mice were not markedly decreased. In serum, however, there was a significant decrease in the S1P level. Although S1P signaling regulates lymphocyte trafficking, lymphocyte distribution was unaffected in lymphoid organs of Sphk1 -/- mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in the Sphk1 null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug. The results with these Sphk1 null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany. Virginia Commonwealth Univ, Dept Biochem, Sch Med, Richmond, VA 23298 USA. Merck & Co Inc, Res Labs, Dept Immunol & Rheumatol, Rahway, NJ 07065 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bldg 10,Rm 9N-314,10 Ctr Dr,MSC 1821, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 FU NCI NIH HHS [CA61774] NR 47 TC 264 Z9 275 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 52487 EP 52492 DI 10.1074/jbc.M406512200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400094 PM 15459201 ER PT J AU Rose, A Froment, P Perrot, V Quon, MJ LeRoith, D Dupont, J AF Rose, A Froment, P Perrot, V Quon, MJ LeRoith, D Dupont, J TI The luteinizing hormone-releasing hormone inhibits the anti-apoptotic activity of insulin-like growth factor-1 in pituitary alpha T3 cells by protein kinase C alpha-mediated negative regulation of Akt SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE-CELLS; PLECKSTRIN HOMOLOGY DOMAIN; GENE-EXPRESSION; IGF-I; PROSTATE-CANCER; MAP KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; MOLECULAR-CLONING; COUPLED RECEPTORS; TRANSGENIC MICE AB The luteinizing hormone-releasing hormone (LHRH) receptor is a G protein-coupled receptor involved in the synthesis and release of pituitary gonadotropins and in the proliferation and apoptosis of pituitary cells. Insulinlike growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor that has a mitogenic effect on pituitary cells. In this study, we used the alphaT3 gonadotrope cell line as a model to characterize the IGF-1R signaling pathways and to investigate whether this receptor interacts with the LHRH cascade. We found that IGF-1 activated the IGF-1R, insulin receptor substrate (IRS)-1, phosphatidylinositol 3-kinase, and Akt in a time-dependent manner in alphaT3 cells. The MAPK (ERK1/2, p38, and JNK) pathways were only weakly activated by IGF-1. In contrast, LHRH strongly stimulated the MAPK pathways but had no effect on Akt activation. Cotreatment with IGF-1 and LHRH had various effects on these signaling pathways. 1) It strongly increased IGF-1-induced tyrosine phosphorylation of IRS-1 and IRS-1-associated phosphatidylinositol 3-kinase through activation of the epidermal growth factor receptor. 2) It had an additive effect on ERK1/2 activation without modifying the phosphorylation of p38 and JNK1/2. 3) It strongly reduced IGF-1 activation of Akt. 3-(4,5-Dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide assays and cell cycle analysis revealed that, in addition to having an additive effect on ERK1/2 activation, cotreatment with IGF-1 and LHRH also had an additive effect on cell proliferation. The LHRH-induced inhibition of Akt stimulated by IGF-1 was completely blocked by Safingol, a protein kinase C (PKC) alpha-specific inhibitor, and by a dominant negative form of PKCalpha. Finally, we showed that the inhibitory effect of LHRH on IGF-1-induced PKCalpha-mediated Akt activation was associated with a marked reduction in Bad phosphorylation and a substantial decrease in the ability of IGF-1 to rescue alphaT3 cells from apoptosis induced by serum starvation. Our results demonstrate for the first time that several interactions take place between IGF-1 and LHRH receptors in gonadotrope cells. C1 NCCAM, Diabet Unit, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. INRA, Unite Physiol Reprod & Comportements, F-37380 Nouzilly, France. Univ Lyon 1, UMR INSERM U449 INRA 1235, RTH Laennec, Sch Med, F-69372 Lyon, France. NIDDK, Sect Mol & Cellular Physiol, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Dupont, J (reprint author), INRA, Unite Physiol Reprod & Comportements, F-37380 Nouzilly, France. EM jdupont@tours.inra.fr RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915 NR 86 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 52500 EP 52516 DI 10.1074/jbc.M404571200 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400096 PM 15448167 ER PT J AU Agniswamy, J Lei, BF Musser, JM Sun, PD AF Agniswamy, J Lei, BF Musser, JM Sun, PD TI Insight of host immune evasion mediated by two variants of group A Streptococcus Mac protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FC-GAMMA-RECEPTOR; CRYSTAL-STRUCTURE; COMPLEX; BINDING; SURFACE; OPSONOPHAGOCYTOSIS; IGG; IDENTIFICATION; RESOLUTION AB Group A Streptococcus has evolved numerous mechanisms to evade the host immune system to survive, disseminate, and cause disease. Recently a secreted protein named Mac-1 was identified and shown to enhance survival of the pathogen. A new variant of Mac-1 (designated Mac-2) also was recently described and shown to differ from Mac-1 by similar to50% amino acid sequence divergence in the middle one-third of the molecule. To gain new information about the role of Mac-1 and Mac-2 in host-pathogen interactions, solution binding experiments were performed using surface plasmon resonance and purified Mac proteins. Mac-1 bound the same lower hinge region of human IgG as Fc receptors with 2.5 muM affinity, which lead to proteolytic cleavage of the antibody. Similar K-m (6.8-18.9 muM) and k(cat) (0.02-0.13 s(-1)) values of the Mac-1 endopeptidase activity were obtained for IgG(1), IgG(2), IgG(3), and IgG(4). Mac-2 variant, in contrast, bound human IgG poorly (K-D = 16 mM) and had weak endopeptidase activity against IgG. Instead, Mac-2 bound FcgammaRII and FcgammaRIII with 5 and 75 muM affinity, respectively. This binding competitively blocked IgG from recognition by Fc receptors. Taken together, Mac proteins block immunoglobulin recognition by Fc receptors and degrade immunoglobulins, thereby enhancing survival of the pathogen through the inhibition of phagocytosis, endocytosis of IgG-opsonized particles, and antibody-dependent cell-mediated cytotoxicity. Consequently, these proteins may be potential therapeutic targets. C1 NIAAA, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59717 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Sun, PD (reprint author), NIAAA, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM psun@nih.gov NR 23 TC 38 Z9 40 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 52789 EP 52796 DI 10.1074/jbc.M410698200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400126 PM 15466462 ER PT J AU Pineda, M Gregory, BD Szczypinski, B Baxter, KR Hochschild, A Miller, ES Hinton, DM AF Pineda, M Gregory, BD Szczypinski, B Baxter, KR Hochschild, A Miller, ES Hinton, DM TI A family of anti-sigma(70) proteins in T4-type phages and bacteria that are similar to AsiA, a transcription inhibitor and co-activator of bacteriophage T4 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE phage; AsiA; Rsd; AlgQ; transcription ID COLI RNA-POLYMERASE; COMPLETE GENOME SEQUENCE; HOST-RANGE VIBRIOPHAGE; SIGMA FACTOR ASIA; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; ACTIVATOR MOTA; PROMOTER RECOGNITION; ANGSTROM RESOLUTION; STRUCTURAL BASIS AB Anti-sigma(70) factors interact with sigma(70) proteins, the specificity subunits of prokaryotic RNA polymerase. The bacteriophage T4 anti-sigma(70) protein, AsiA, binds tightly to regions 4.1 and 4.2 of the sigma(70) subunit of Escherichia coli RNA polymerase and inhibits transcription from sigma(70) promoters that require recognition of the canonical sigma(70) - 35 DNA sequence. In the presence of the T4 transcription activator MotA, AsiA also functions as a co-activator of transcription from T4 middle promoters, which retain the canonical sigma(70) - 10 consensus sequence but have a MotA box sequence centered at - 30 rather than the sigma(70) - 35 sequence. The E. coli anti-sigma(70) protein Rsd also interacts with region 4.2 of sigma(70) and inhibits transcription from sigma(70) promoters. Our sequence comparisons of T4 AsiA with Rsd, with the, predicted AsiA orthologs of the T4-type phages RB69, 44RR, KVP40, and, - Aeh1, and with AlgQ, a regulator of alginate production in Pseudomonas aeruginosa indicate that these proteins share conserved amino acid residues at positions known to be important for the binding of T4 AsiA to sigma(70) region 4. We show that, like T4 AsiA, Rsd binds to sigma(70) in a native protein gel and, as with T4 AsiA, a L18S substitution in Rsd disrupts this complex. Previous work has assigned sigma(70) amino acid F563, within region 4.1, as a critical determinant for AsiA binding. This residue is also involved in the binding of sigma(70) to the D-flap of core, suggesting that AsiA inhibits transcription by disrupting the interaction between sigma(70) region 4.1 and the beta-flap. We find that as with T4 AsiA, the interaction of KVP40 AsiA, Rsd, or AlgQ with sigma(70) region 4 is diminished by the substitution F563Y. We also demonstrate that like T4 AsiA and Rsd, KVP40 AsiA inhibits transcription from sigma(70)-dependent promoters. We speculate that the phage AsiA orthologs, Rsd, and AlgQ are members of a related family in T4-type phage and bacteria, which interact similarly with primary a factors. In addition, we show that even though a clear MotA ortholog has not been identified in the KVP40 genome and the phage genome appears to lack typical middle promoter sequences, KVP40 AsiA activates transcription from T4 middle promoters in the presence of T4 MotA. We speculate that KVP40 encodes a protein that is dissimilar in sequence, but functionally equivalent, to T4 MotA. Published by Elsevier Ltd. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. N Carolina State Univ, Dept Microbiol, Raleigh, NC 27695 USA. RP Hinton, DM (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 2A-13, Bethesda, MD 20892 USA. EM dhinton@helix.nih.gov FU NIGMS NIH HHS [R01 GM044025] NR 63 TC 31 Z9 31 U1 0 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 10 PY 2004 VL 344 IS 5 BP 1183 EP 1197 DI 10.1016/j.jmb.2004.10.003 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876NK UT WOS:000225503600003 PM 15561138 ER PT J AU Zerhouni, EA AF Zerhouni, EA TI Information access - NIH public access policy SO SCIENCE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 12 Z9 12 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 10 PY 2004 VL 306 IS 5703 BP 1895 EP 1895 DI 10.1126/science.1106929 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 879DC UT WOS:000225695600028 PM 15591188 ER PT J AU Corey, DP Garcia-Anoveros, J Holt, JR Kwan, KY Lin, SY Vollrath, MA Amalfitano, A Cheung, ELM Derfler, BH Duggan, A Geleoc, GSG Gray, PA Hoffman, MP Rehm, HL Tamasauskas, D Zhang, DS AF Corey, DP Garcia-Anoveros, J Holt, JR Kwan, KY Lin, SY Vollrath, MA Amalfitano, A Cheung, ELM Derfler, BH Duggan, A Geleoc, GSG Gray, PA Hoffman, MP Rehm, HL Tamasauskas, D Zhang, DS TI TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells SO NATURE LA English DT Article ID ION CHANNELS; INNER-EAR; MECHANOELECTRICAL TRANSDUCTION; MECHANOTRANSDUCER CHANNEL; TIP LINKS; ADAPTATION; MUTATIONS; GENE; CADHERIN-23; ADENOVIRUS AB Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. Although some protein constituents of the transduction apparatus are known, the mechanically gated transduction channels have not been identified in higher vertebrates. Here, we investigate TRP ( transient receptor potential) ion channels as candidates and find one, TRPA1 ( also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted. Inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Inst Neurosci, Dept Anesthesiol, Chicago, IL 60611 USA. Northwestern Univ, Inst Neurosci, Dept Neurol, Chicago, IL 60611 USA. Northwestern Univ, Inst Neurosci, Dept Physiol, Chicago, IL 60611 USA. Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Otolaryngol, Charlottesville, VA 22908 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Partners Genome Ctr, Mol Med Lab, Cambridge, MA 02139 USA. Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27705 USA. NIDCR, Matrix & Morphogenesis Unit, CDBRB, NIH, Bethesda, MD 20892 USA. RP Corey, DP (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM dcorey@hms.harvard.edu OI Corey, David/0000-0003-4497-6016 NR 42 TC 412 Z9 458 U1 4 U2 36 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 9 PY 2004 VL 432 IS 7018 BP 723 EP 730 DI 10.1038/nature03066 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 877UE UT WOS:000225597200040 PM 15483558 ER PT J AU Stratakis, CA Bertherat, J Carney, JA AF Stratakis, CA Bertherat, J Carney, JA TI Mutation of perinatal myosin heavy chain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CARNEY COMPLEX; DISEASE C1 NIH, Bethesda, MD 20892 USA. Hop Cochin, F-75014 Paris, France. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Stratakis, CA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 4 TC 8 Z9 8 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 9 PY 2004 VL 351 IS 24 BP 2556 EP 2556 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 877TE UT WOS:000225593100027 PM 15590965 ER PT J AU Haviernik, P Lahoda, C Bradley, HL Hawley, TS Ramezani, A Hawley, RG Stetler-Stevenson, M Stetler-Stevenson, WG Bunting, KD AF Haviernik, P Lahoda, C Bradley, HL Hawley, TS Ramezani, A Hawley, RG Stetler-Stevenson, M Stetler-Stevenson, WG Bunting, KD TI Tissue inhibitor of matrix metalloproteinase-1 overexpression in M1 myeloblasts impairs IL-6-induced differentiation SO ONCOGENE LA English DT Article DE tissue inhibitor of matrix metalloproteinase; myeloid leukemia; signal transducer and activator of transcription; retroviral vector ID ERYTHROID-POTENTIATING ACTIVITY; BREAST EPITHELIAL-CELLS; LEUKEMIA-CELLS; TUMOR-GROWTH; PANCREATIC-CANCER; SIGNALING PATHWAY; BONE-MARROW; NUDE-MICE; IN-VIVO; B-CELLS AB The balance between matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase ( TIMP) is important for extracellular matrix interactions of hematopoietic cells. MMP-independent growth modulating activity for TIMP-1 on B lymphocytes and erythroid progenitors has also been described, but a role for TIMP-1 in myelomonocytic differentiation has not been previously reported. In this study, we demonstrate that TIMP-1 overexpression impairs differentiation of the myeloblastic M1 cell line following interleukin (IL)-6 stimulation. We generated retroviral vectors coexpressing human TIMP-1 and the green fluorescent protein (GFP) and stably transduced murine M1 myeloid cells. TIMP-1 expressing cells showed a large reduction in IL-6-induced macrophage differentiation in vitro that was reversible with a specific monoclonal antibody. The differentiation delay in M1/TIMP-1 cells was also specifically reversible by pharmacologic phosphatidylinositol-3 kinase (PI3-K) inhibition. Additionally, overexpression of a TIMP-1/GFP fusion protein also impaired M1 differentiation and this protein was localized to the cell surface, consistent with an autocrine receptor-mediated mechanism. Surprisingly, TIMP-1 transduced cells had a selective advantage for growth in IL-6, indicating that functional effects on growth and differentiation of M1 cells were primarily through an autocrine mechanism. Intrinsic TIMP-1 expression in myeloid leukemia cells might thus impact upon survival or differentiation. C1 Amer Red Cross, Jerome H Holland Lab Biomed Sci, Hematopoiesis Dept, Rockville, MD 20855 USA. George Washington Univ, Inst Biomed Sci, Genet Program, Washington, DC 20037 USA. Amer Red Cross, Jerome H Holland Lab Biomed Sci, Flow Cytometry Facil, Rockville, MD 20855 USA. George Washington Univ, Dept Anat & Cell Biol, Washington, DC 20037 USA. NIH, Flow Cytometry Unit, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. NIH, Extracellular Matrix Sect, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. RP Bunting, KD (reprint author), Case Western Reserve Univ, Div Hematol Oncol, 10900 Euclid Ave WRB2, Cleveland, OH 44106 USA. EM kevin.bunting@case.edu RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NHLBI NIH HHS [R01HL073738, R21HL071171]; NIDDK NIH HHS [R01DK059380] NR 44 TC 10 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 9 PY 2004 VL 23 IS 57 BP 9212 EP 9219 DI 10.1038/sj.onc.1208096 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 878HR UT WOS:000225638000006 PM 15516987 ER PT J AU Kim, AJ Lee, CS Schlessinger, D AF Kim, AJ Lee, CS Schlessinger, D TI Bex3 associates with replicating mitochondria and is involved in possible growth control of F9 teratocarcinoma cells SO GENE LA English DT Article DE mitochondrial DNA; protein sorting signals; DNA replication; actin filaments; siRNA ID NUCLEAR EXPORT; DEATH EXECUTOR; MESSENGER-RNA; GENE FAMILY; NADE; SEQUENCE; IDENTIFICATION; EXPRESSION; PROTEINS; EMBRYOS AB Bex3 expression and possible function in growth control were studied. It was expressed in a limited number of organs, including gonads and hippocampal regions of the brain. Visualized by deconvolution microscopy as a GFP-fusion protein in F9 teratocarcinoma cells, Bex3 localized, along with concentrations of actin, at perinuclear mitochondria that were undergoing active DNA replication. Bex3 association with mitochondria required a nuclear export signal (NES) and the C-terminal four amino acids (CaaX box), and siRNA reduction of Bex3 levels led to slow or negligible growth rates of the F9 cells. Thus, Bex3 may be required in target tissues for mitochondrial function at a distinct phase of the cellular growth cycle. (C) 2004 Elsevier B.V. All rights reserved. C1 NIA, IRP, Genet Lab, Baltimore, MD 21224 USA. RP Schlessinger, D (reprint author), NIA, IRP, Genet Lab, Suite 3000,333 Cassell Dr, Baltimore, MD 21224 USA. EM schlessingerd@grc.nia.nih.gov NR 30 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 8 PY 2004 VL 343 IS 1 BP 79 EP 89 DI 10.1016/j.gene.2004.08.031 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 879PC UT WOS:000225728700007 PM 15563833 ER PT J AU Cai, DC McCarron, RM Hallenbeck, J AF Cai, DC McCarron, RM Hallenbeck, J TI Cloning and characterization of a forkhead transcription factor gene, FoxOla, from thirteen-lined ground squirrel SO GENE LA English DT Article DE hibernation; ischemic tolerance; cytoprotection; apoptosis; Akt ID CEREBRAL-ISCHEMIA; CELL-SURVIVAL; C-ELEGANS; LIFE-SPAN; PROTEIN; PHOSPHORYLATION; HIBERNATION; FUSION; FKHR; AKT AB This research analyzes the regulation of ischemic tolerance in hibernating thirteen-lined ground squirrels (Spermophilus tridecemlineatus). Hibernation is studied because it represents a unique state of reversible suspended animation associated with tolerance to an otherwise lethal reduction of core body temperature and metabolism. An integral aspect of hibernation is the profound decrease of cerebral perfusion without neurological damage. As such, hibernation serves as a model for studying natural tolerance to brain ischemia. Identification of regulatory mechanisms that control hibernation in ground squirrels may guide efforts to develop improved treatments for stroke and brain trauma. It was previously shown that phosphorylation of Akt (protein kinase 13), an insulin-like growth factor-regulated serine/threonine kinase, was significantly reduced as was its kinase activity in hibernating thirteen-lined ground squirrels. Here we studied the forkhead (FH) in rhabdomyosarcoma (FKHR) transcription factor, which is controlled by Akt signaling and is involved in regulating cell cycle progression and cell death. A cDNA derived from brains of S. tridecemlineatus, encoding a specific FKHR transcription factor, FoxO1a, was cloned and sequenced, and the amino acid sequence of the protein was deduced. FoxO1a is composed of 653 amino acids and has a predicted molecular mass of 69.4 kilodaltons (kDa). Here, for the first time, we report the contrary expression of phosphorylation of two members in the insulin-like growth factor signaling pathway during hibernation (i.e., phosphorylated FKHR was significantly up-regulated as phosphorylation of its upstream kinase, Akt, was significantly down-regulated). Further study is required to identify the possible connection between FoxO1a and Akt activity and the possible role of such interactions in hibernation. (C) 2004 Elsevier B.V. All rights reserved. C1 Natl Inst Neurol Disorders & Stroke, Stroke Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. USN, Med Res Ctr, Resuscitat Med Dept, Silver Spring, MD 20910 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. RP Hallenbeck, J (reprint author), Natl Inst Neurol Disorders & Stroke, Stroke Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM hallenbj@ninds.nih.gov NR 26 TC 10 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 8 PY 2004 VL 343 IS 1 BP 203 EP 209 DI 10.1016/j.gene.2004.09.003 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 879PC UT WOS:000225728700020 PM 15563846 ER PT J AU Cahill, K Parsegian, VA AF Cahill, K Parsegian, VA TI Rydberg-London potential for diatomic molecules and unbonded atom pairs SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ENERGY CURVES; ARGON AB We propose and test a pair potential that is accurate at all relevant distances and simple enough for use in large-scale computer simulations. A combination of the Rydberg potential from spectroscopy and the London inverse-sixth-power energy, the proposed form fits spectroscopically determined potentials better than the Morse, Varnshi, and Hulburt-Hirschfelder potentials and much better than the Lennard-Jones and harmonic potentials. At long distances, it goes smoothly to the London force appropriate for gases and preserves van der Waals's "continuity of the gas and liquid states," which is routinely violated by coefficients assigned to the Lennard-Jones 6-12 form. (C) 2004 American Institute of Physics. C1 Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA. NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20894 USA. RP Cahill, K (reprint author), Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA. EM cahill@unm.edu; aparsegi@helix.nih.gov NR 26 TC 23 Z9 23 U1 2 U2 11 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 8 PY 2004 VL 121 IS 22 BP 10839 EP 10842 DI 10.1063/1.1830011 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 875RS UT WOS:000225440000001 PM 15634034 ER PT J AU Dudko, OK Berezhkovskii, AM Weiss, GH AF Dudko, OK Berezhkovskii, AM Weiss, GH TI Diffusion in the presence of periodically spaced permeable membranes SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID SELF-DIFFUSION; FIELD GRADIENT; SPIN-ECHOES; WATER; NMR; BARRIERS; H-1-NMR; TIME AB The diffusion of molecules in biological tissues and some other microheterogeneous systems is affected by the presence of permeable barriers. This leads to the slowdown of diffusion at long times as compared to barrier-free diffusion. At short times the effect of barriers is weak. In consequence, the diffusion coefficient D(t) decreases as a function of time. We derive an exact solution for the Laplace transform of D(t) for diffusion in a space separated into layers by equally spaced, parallel identical planes of arbitrary permeability. Additionally, we give an approximation to D(t) which is reasonably accurate over the whole range of the partition permeability from zero (the case of isolated layers) to infinity (the case of no barriers). (C) 2004 American Institute of Physics. C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Dudko, OK (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 16 TC 29 Z9 29 U1 0 U2 3 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 8 PY 2004 VL 121 IS 22 BP 11283 EP 11288 DI 10.1063/1.1814055 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 875RS UT WOS:000225440000050 PM 15634083 ER PT J AU Berezhkovskii, AM Makhnovskii, YA Monine, MI Zitserman, VY Shvartsman, SY AF Berezhkovskii, AM Makhnovskii, YA Monine, MI Zitserman, VY Shvartsman, SY TI Boundary homogenization for trapping by patchy surfaces SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID CONTROLLED LIGAND-BINDING; DIFFUSION; RECEPTORS AB We analyze trapping of diffusing particles by nonoverlapping partially absorbing disks randomly located on a reflecting surface, the problem that arises in many branches of chemical and biological physics. We approach the problem by replacing the heterogeneous boundary condition on the patchy surface by the homogenized partially absorbing boundary condition, which is uniform over the surface. The latter can be used to analyze any problem (internal and external, steady state, and time dependent) in which diffusing particles are trapped by the surface. Our main result is an expression for the effective trapping rate of the homogenized boundary as a function of the fraction of the surface covered by the disks, the disk radius and trapping efficiency, and the particle diffusion constant. We demonstrate excellent accuracy of this expression by testing it against the results of Brownian dynamics simulations. (C) 2004 American Institute of Physics. C1 Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Moscow 119991, Russia. Russian Acad Sci, Inst High Temp, Thermophys Ctr, Moscow 125412, Russia. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Shvartsman, SY (reprint author), Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. EM stas@princeton.edu RI Makhnovskii, Yurii/B-1223-2014 OI Makhnovskii, Yurii/0000-0002-1517-536X NR 18 TC 53 Z9 54 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 8 PY 2004 VL 121 IS 22 BP 11390 EP 11394 DI 10.1063/1.1814351 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 875RS UT WOS:000225440000065 PM 15634098 ER PT J AU Riegel, AC Lupica, CR AF Riegel, AC Lupica, CR TI Independent presynaptic and postsynaptic mechanisms regulate endocannabinoid signaling at multiple synapses in the ventral tegmental area SO JOURNAL OF NEUROSCIENCE LA English DT Article DE marijuana; metabotropic glutamate receptors; S-K channels; bursting; mesolimbic; GABA; dopamine neuron; GABA-B receptors ID METABOTROPIC GLUTAMATE RECEPTORS; METHYL-D-ASPARTATE; MIDBRAIN DOPAMINERGIC-NEURONS; NUCLEUS-ACCUMBENS; SUBSTANTIA-NIGRA; CANNABINOID CB1; BASAL GANGLIA; RAT-BRAIN; PHENYLGLYCINE DERIVATIVES; AFFERENT MODULATION AB Dopamine (DA) neurons in the ventral tegmental area have been implicated in psychiatric disorders and drug abuse. Understanding the mechanisms through which their activity is regulated via the modulation of afferent input is imperative to understanding their roles in these conditions. Here we demonstrate that endocannabinoids liberated from DA neurons activate cannabinoid CB1 receptors located on glutamatergic axons and on GABAergic terminals targeting GABA(B) receptors located on these cells. Endocannabinoid release was initiated by inhibiting either presynaptic type-III metabotropic glutamate receptors or postsynaptic calcium-activated potassium channels, two conditions that also promote enhanced DA neuron excitability and bursting. Thus, activity-dependent release of endocannabinoids may act as a regulatory feedback mechanism to inhibit synaptic inputs in response to DA neuron bursting, thereby regulating firing patterns that may fine-tune DA release from afferent terminals. C1 NIDA, Cellular Neurobiol Branch, Electrophysiol Unit,Intramural Res Program, NIH,US Dept HHS, Baltimore, MD 21224 USA. RP Lupica, CR (reprint author), NIDA, Cellular Neurobiol Branch, Electrophysiol Unit,Intramural Res Program, NIH,US Dept HHS, Baltimore, MD 21224 USA. EM clupica@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000437-08] NR 63 TC 107 Z9 110 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 8 PY 2004 VL 24 IS 49 BP 11070 EP 11078 DI 10.1523/JNEUROSCI.3695-04.2004 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 878AI UT WOS:000225618300009 PM 15590923 ER PT J AU Deans, KJ Natanson, C Minneci, PC AF Deans, KJ Natanson, C Minneci, PC TI Dose effects of steroids on survival in sepsis - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID SEPTIC SHOCK; METAANALYSIS C1 NIH, Bethesda, MD 20892 USA. RP Deans, KJ (reprint author), NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 7 PY 2004 VL 141 IS 11 BP 892 EP 892 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 876WZ UT WOS:000225530700022 ER PT J AU Davis, BR Furberg, CD Wright, JT Cutler, JA Whelton, P AF Davis, BR Furberg, CD Wright, JT Cutler, JA Whelton, P TI Angiotensin-converting enzyme inhibitors and diuretics: Optimal combination therapy - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 Univ Texas, Sch Publ Hlth, Houston, TX 77030 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NHLBI, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA. RP Davis, BR (reprint author), Univ Texas, Sch Publ Hlth, Houston, TX 77030 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 7 PY 2004 VL 141 IS 11 BP 893 EP 893 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 876WZ UT WOS:000225530700024 ER PT J AU Erinoff, L Anthony, JC Brown, GK Caine, ED Dougherty, DM Glowinski, AL Goldston, DB Linehan, MM Mann, JJ Miczek, KA Ries, RK Roy, A Sher, KJ Tarter, RE Wilcox, HD Wines, JD Yen, S AF Erinoff, L Anthony, JC Brown, GK Caine, ED Dougherty, DM Glowinski, AL Goldston, DB Linehan, MM Mann, JJ Miczek, KA Ries, RK Roy, A Sher, KJ Tarter, RE Wilcox, HD Wines, JD Yen, S TI Overview of workshop on drug abuse and suicidal behavior SO DRUG AND ALCOHOL DEPENDENCE LA English DT Editorial Material ID NATIONAL COMORBIDITY SURVEY; AFRICAN-AMERICAN; SUBSTANCE USE; PERSONALITY-TRAITS; DEPENDENT PATIENTS; MAJOR DEPRESSION; IMPULSIVITY; RISK; DISORDERS; ADOLESCENTS C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. Michigan State Univ, E Lansing, MI 48824 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Rochester, Ctr Med, Rochester, NY 14627 USA. Univ Texas, Hlth Sci Ctr, Houston, TX 77030 USA. Washington Univ, St Louis, MO 63108 USA. Duke Child & Family Study Ctr, Durham, NC 27710 USA. Univ Washington, Seattle, WA 98195 USA. Columbia Univ, New York, NY 10032 USA. Tufts Univ, Medford, MA 02115 USA. Harborview Med Ctr, Seattle, WA 98104 USA. Univ Med & Dent New Jersey, E Orange, NJ 07018 USA. Univ Missouri, Columbia, MO 65211 USA. Univ Pittsburgh, Pittsburgh, PA 15261 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02478 USA. Brown Univ, Providence, RI 02912 USA. FedEx, Rockville, MD 20852 USA. RP Erinoff, L (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5153,MSC 9589, Bethesda, MD 20892 USA. EM le30q@nih.gov FU NIDA NIH HHS [K05 DA015799] NR 55 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 7 PY 2004 VL 76 SU S BP S3 EP S9 DI 10.1016/j.drugalcdep.2004.08.002 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 880XX UT WOS:000225824700002 PM 15555814 ER PT J AU Erinoff, L Compton, WM Volkow, ND AF Erinoff, L Compton, WM Volkow, ND TI Drug abuse and suicidal behavior SO DRUG AND ALCOHOL DEPENDENCE LA English DT Editorial Material C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Erinoff, L (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5153,MSC 9589, Bethesda, MD 20892 USA. EM le30q@nih.gov NR 11 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 7 PY 2004 VL 76 SU S BP S1 EP S2 DI 10.1016/j.drugalcdep.2004.08.001 PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 880XX UT WOS:000225824700001 PM 15555811 ER PT J AU Gaur, D Mayer, DCG Miller, LH AF Gaur, D Mayer, DCG Miller, LH TI Parasite ligand-host receptor interactions during invasion of erythrocytes by Plasmodium merozoites SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on Malaria CY MAR 24-26, 2004 CL Baltimore, MD SP Johns Hopkins Malaria Res Inst DE erythrocyte; Plasmodium; cell invasion; merozoite surface proteins; Duffy binding protein ID DUFFY-BLOOD-GROUP; APICAL MEMBRANE ANTIGEN-1; PAPUA-NEW-GUINEA; FALCIPARUM-MALARIA PARASITES; SOUTHEAST-ASIAN OVALOCYTOSIS; MOLECULAR-WEIGHT PRECURSOR; YOELII ADHESIVE PROTEINS; RED-CELL INVASION; SURFACE PROTEIN-1; GLYCOPHORIN-C AB Malaria parasites must recognise and invade different cells during their life cycle. The efficiency with which Plasmodium falciparum invades erythrocytes of all ages is an important virulence factor, since the ability of the parasite to reach high levels of parasitemia is often associated with severe pathology and morbidity. The merozoite invasion of erythrocytes is a highly complex, multi-step process Thai is dependent on a cascade of specific molecular interactions. Although many proteins are known to play an important role in invasion, their functional characteristics remain unclear. Therefore, a complete understanding of the molecular interactions that are the basis of the invasion process is absolutely crucial, not only in improving our knowledge about the basic biology of the malarial parasite, but also for the development of intervention strategies to counter the disease. Here we review the current state of knowledge about the receptor-ligand interactions that mediate merozoite invasion of erythrocytes. (C) 2004 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Miller, LH (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Bldg Twinbrook 3,Room 3E-32D, Bethesda, MD 20892 USA. EM lmiller@niaid.nih.gov NR 152 TC 148 Z9 151 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD DEC 7 PY 2004 VL 34 IS 13-14 BP 1413 EP 1429 DI 10.1016/j.ijpara.2004.10.010 PG 17 WC Parasitology SC Parasitology GA 880SV UT WOS:000225810400002 PM 15582519 ER PT J AU Vaitheeswaran, S Yin, H Rasaiah, JC Hummer, G AF Vaitheeswaran, S Yin, H Rasaiah, JC Hummer, G TI Water clusters in nonpolar cavities SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE grand canonical ensemble; hydrophobic interactions; fullerenes; free energy of transfer; configurational-specific heat ID HYDROPHOBIC CAVITIES; PROTON TRANSLOCATION; CREATING MUTATIONS; CYTOCHROME P450CAM; CARBON NANOTUBES; DISORDERED WATER; MODEL; MOLECULES; HYDRATION; BACTERIORHODOPSIN AB We explore the structure and thermodynamics of water clusters confined in nonpolar cavities. By calculating the grand-canonical partition function term by term, we show that small nonpolar cavities can be filled at equilibrium with highly structured water clusters. The structural and thermodynamic properties of these encapsulated water clusters are similar to those observed experimentally in the gas phase. Water filling is highly sensitive to the size of the cavity and the strength of the interactions with the cavity wall. Water penetration into pores can thus be modulated by small changes in the polarity and structure of the cavity. Implications on water penetration into proteins are discussed. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Maine, Dept Chem, Orono, ME 04469 USA. Univ Maine, Dept Phys & Astron, Orono, ME 04469 USA. RP Rasaiah, JC (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM rasaiah@maine.edu; gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 39 TC 138 Z9 140 U1 7 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 7 PY 2004 VL 101 IS 49 BP 17002 EP 17005 DI 10.1073/pnas.0407968101 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 879SV UT WOS:000225740100006 PM 15572444 ER PT J AU Wang, RH Yu, HT Deng, CX AF Wang, RH Yu, HT Deng, CX TI A requirement for breast-cancer-associated gene 1 (BRCA1) in the spindle checkpoint SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Mac2; p53; cell cycle; OCT-1; genetic instability ID MAMMALIAN-CELLS; CENTROSOME AMPLIFICATION; GENETIC INSTABILITY; PREMATURE ANAPHASE; TUMOR-FORMATION; PROTEIN BUBR1; MICE LACKING; MUTANT MICE; MAD2; TUMORIGENESIS AB BRCA1-associated breast cancer exhibits significantly higher levels of chromosomal abnormalities than sporadic breast cancers. However, the molecular mechanisms regarding the roles of BRCA1 in maintaining genome integrity remain elusive. By using a mouse model deficient for Brca1 full-length isoform (Brca1,(Delta11/Delta11)), we found that Brca1(Delta11/Delta11) cells displayed decreased expression of a number of genes that are involved in the spindle checkpoint, including Mad2, which is a key component of spindle checkpoint that inhibits anaphase-promoting complex. We showed that Brca1(Delta11/Delta11) cells failed to arrest at metaphase in the presence of nococlazole and underwent apoptosis because of activation of p53. Consistently, reconstitution of Mad2 in Brca1(Delta11/Delta11) cells partially restored the spindle checkpoint and attenuated apoptosis. By using UBR60 cells, which carry tetracycline-regulated expression of BRCA1, we demonstrated that BRCA1 binds to transcription factor OCT-1 and up-regulates the transcription of MAD2. Furthermore, we showed that the induction of BRCA1 to endogenous MAD2 or transfected MAD2 luciferase reporter in UBR60 cells was completely inhibited by acute suppression of BRCA1 by RNA interference. These data reveal a role of BRCA1 in maintaining genome integrity by interplaying with p53 and genes that are involved in the spindle checkpoint and apoptosis. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. RP Deng, CX (reprint author), NIDDKD, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 NR 34 TC 100 Z9 107 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 7 PY 2004 VL 101 IS 49 BP 17108 EP 17113 DI 10.1073/pnas.0407585101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 879SV UT WOS:000225740100025 PM 15563594 ER PT J AU Graveel, C Su, YL Koeman, J Wang, LM Tessarollo, L Fiscella, M Birchmeier, C Swiatek, P Bronson, R Woude, GV AF Graveel, C Su, YL Koeman, J Wang, LM Tessarollo, L Fiscella, M Birchmeier, C Swiatek, P Bronson, R Woude, GV TI Activating Met mutations produce unique tumor profiles in mice with selective duplication of the mutant allele SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PAPILLARY RENAL-CARCINOMAS; HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE DOMAIN; SCATTER FACTOR; EMBRYONIC LETHALITY; SOMATIC MUTATIONS; HUMAN CANCER; CELL TUMORS; RECEPTOR; PROTOONCOGENE AB Tyrosine kinase-activating mutations in Met have been observed in hereditary papillary renal carcinomas as well as in other cancers. These mutations have been examined in several in vitro systems, where they cause constitutive Met activation, focus formation, and cell motility, and are tumorigenic in xenografts. To study the influence of these mutations on tumorigenesis in vivo, we generated mice with targeted mutations in the murine met locus. The following five mouse lines with mutant Met were created: WT, D1226N, Y1228C, M1248T, and M1248T/L1193V. We observed that mice harboring D1226N, Y1228C, and M1248T/11193V mutations developed a high frequency of sarcomas and some lymphomas, whereas the M1248T mice developed carcinomas and lymphomas. Of considerable interest, we observed trisomy of chromosome 6 and duplication of the mutant met allele in a majority of the tumors, similar to what has been reported in patients with hereditary renal papillary carcinomas. These results demonstrate that activating Met mutations and met amplification play key roles in promoting tumorigenesis in vivo. Moreover, our findings show that different mutations in the Met kinase domain can influence the types of cancers that develop. C1 Van Andel Res Inst, Oncol Mol Lab, Grand Rapids, MI 49503 USA. Van Andel Res Inst, Cytogenet Program, Grand Rapids, MI 49503 USA. Natl Hlth Res Inst, Taipei 115, Taiwan. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. Human Genome Sci Inc, Rockville, MD 20850 USA. Max Delbruck Centrum Mol Med, Dept Neurosci, D-13122 Berlin, Germany. Tufts Univ, Dept Biomed Sci, North Grafton, MA 01536 USA. RP Woude, GV (reprint author), Van Andel Res Inst, Oncol Mol Lab, 333 Bostwick Ave, Grand Rapids, MI 49503 USA. EM george.vandewoude@vai.org NR 29 TC 74 Z9 75 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 7 PY 2004 VL 101 IS 49 BP 17198 EP 17203 DI 10.1073/pnas.0407651101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 879SV UT WOS:000225740100040 PM 15557554 ER PT J AU Kidd, SE Hagen, F Tscharke, RL Huynh, M Bartlett, KH Fyfe, M MacDougall, L Boekhout, T Kwon-Chung, KJ Meyer, W AF Kidd, SE Hagen, F Tscharke, RL Huynh, M Bartlett, KH Fyfe, M MacDougall, L Boekhout, T Kwon-Chung, KJ Meyer, W TI A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PCR fingerprinting; amplified fragment length polymorphism (AFLP); restriction fragment length polymorphism (RFLP); mating type ID NEOFORMANS VAR GATTII; DOLPHIN TURSIOPS-TRUNCATUS; PULMONARY CRYPTOCOCCOSIS; EPIDEMIOLOGY; INFECTIONS AB Cryptococcus gattii causes life-threatening infection of the pulmonary and central nervous systems in hosts with normal immunity and traditionally has been considered to be restricted geographically to tropical and subtropical climates. The recent outbreak of C. gattii in the temperate climate of Vancouver Island, BC, Canada, led to a collaborative investigation. The objectives of the current study were to ascertain the environmental source of the outbreak infections, survey the molecular types of the outbreak and environmental cryptococcal isolates, and determine the extent of genetic diversity among the isolates. PCR-fingerprinting and amplified fragment length polymorphism (AFLP) were used to examine the genotypes, and mating assays were performed to determine the mating type of the isolates. All outbreak and environmental isolates belonged to C. gattii. Concordant results were obtained by using PCR-fingerprinting and AFLP analysis. The vast majority of clinical and veterinary infections were caused by isolates of the molecular type VGII/AFLP6, but two were caused by molecular type VGI/AFLP4. All environmental isolates belonged to molecular type VGII/AFLP6. Two or three sub-types were observed within VGII/AFLP6 among outbreak and environmental isolates. All mating-competent isolates were of the alpha-mating type. The emergence of this usually tropical pathogen on Vancouver Island highlights the changing distribution of this genotype and emphasizes the importance of an ongoing collaborative effort to monitor the global epidemiology of this yeast. C1 Westmead Hosp, Inst Clin Pathol & Med Res, Mol Mycol Lab, Ctr Infect Dis & Microbiol, Westmead, NSW 2145, Australia. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. Cent Bur Schimmelcultures, NL-3508 AD Utrecht, Netherlands. Univ Utrecht, Med Ctr, Dept Med, Div Acute Med & Infect Dis, NL-3508 GA Utrecht, Netherlands. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. British Columbia Ctr Dis Control, Vancouver, BC V5Z 4R4, Canada. Univ British Columbia, Sch Occupat & Environm Hyg, Vancouver, BC V6T 1Z3, Canada. RP Meyer, W (reprint author), Westmead Hosp, Inst Clin Pathol & Med Res, Mol Mycol Lab, Ctr Infect Dis & Microbiol, Room 3114A,Level 3, Westmead, NSW 2145, Australia. EM w.meyer@usyd.edu.au RI Kidd, Sarah/A-1731-2009; Boekhout, Teun/F-1552-2010; Kidd, Sarah/N-1362-2013; Hagen, Ferry/B-9044-2009; Meyer, Wieland/G-1204-2015 OI Kidd, Sarah/0000-0002-5957-4178; Boekhout, Teun/0000-0002-0476-3609; Kidd, Sarah/0000-0002-5957-4178; Hagen, Ferry/0000-0002-5622-1916; Meyer, Wieland/0000-0001-9933-8340 NR 29 TC 402 Z9 420 U1 6 U2 36 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 7 PY 2004 VL 101 IS 49 BP 17258 EP 17263 DI 10.1073/pnas.0402981101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 879SV UT WOS:000225740100050 PM 15572442 ER PT J AU Vazquez, G Wedel, BJ Aziz, O Trebak, M Putney, JW AF Vazquez, G Wedel, BJ Aziz, O Trebak, M Putney, JW TI The mammalian TRPC cation channels SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article; Proceedings Paper CT 8th European Symposium on Calcium-Binding Proteins in Normal and Transformed Cells CY JUL 28-31, 2004 CL Hinxton Hall, Campus, Cambridge, ENGLAND SP European Calcium Soc, VisiTech Int, European Union, High Level Sci Conf, British Soc Cell Biol, Raytek, Leica Microsyst, Zeiss, Univ Imaging, Med Solut & Imp HO Hinxton Hall, Campus DE ion channel; calcium channel; non-selective cation channel; TRP channel; TRPC channel; capacitative calcium entry; store-operated channel; second messenger-operated channel; inositol trisphosphate receptor; diacylglycerol; phospholipase C ID CAPACITATIVE CA2+ ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; MOUSE TRANSIENT RECEPTOR; PROTEIN-KINASE-C; ENDOGENOUSLY EXPRESSED TRP1; OPERATED HTRP3 CHANNELS; PORTAL-VEIN MYOCYTES; SMOOTH-MUSCLE-CELLS; CALCIUM-ENTRY; HUMAN PLATELETS AB Transient Receptor Potential-Canonical (TRPC) channels are mammalian homologs of Transient Receptor Potential (TRP), a Ca2+-permeable channel involved in the phospholipase C-regulated photoreceptor activation mechanism in Drosophila. The seven mammalian TRPCs constitute a family of channels which have been proposed to function as store-operated as well as second messenger-operated channels in a variety of cell types. TRPC channels, together with other more distantly related channel families, make up the larger TRP channel superfamily. This review summarizes recent findings on the Structure, regulation and function of the apparently ubiquitous TRPC cation channels. Published by Elsevier B.V. C1 NIEHS, Calcium Regulat Sect, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Calcium Regulat Sect, NIH, Dept Hlth & Human Serv, 3 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Putney@niehs.nih.gov RI Trebak, Mohamed/E-7405-2014 NR 140 TC 175 Z9 190 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD DEC 6 PY 2004 VL 1742 IS 1-3 SI SI BP 21 EP 36 DI 10.1016/j.bbamer.2004.08.015 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 893XK UT WOS:000226754200004 PM 15590053 ER PT J AU Sikazwe, DMN Li, SM Mardenborough, L Cody, V Roth, BL Ablordeppey, SY AF Sikazwe, DMN Li, SM Mardenborough, L Cody, V Roth, BL Ablordeppey, SY TI Haloperidol: towards further understanding of the structural contributions of its pharmacophric elements at D2-like receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE haloperidol; SAR; pharmacophoric elements; D2-like receptors; dopamine receptors ID MONOCLONAL-ANTIBODIES; PHARMACOLOGY; BINDING; DRUG AB An attempt to understand the pharmacophore-relevant position of the alcoholic moiety in haloperidol and the contributions of other pharmacophoric elements led to the re-synthesis of its tropane analogue (compound 2). An analysis of the binding data suggests that haloperidol binds to the DA receptors with the OH group in the axial position and the OH group, while not essential for binding, enhances binding especially at the D2 receptor. It also became clear that shortening the butyrophenone chain not only reduces binding affinity at the DA receptors but eliminates subtype selectivity. (C) 2004 Published by Elsevier Ltd. C1 Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA. Hauptman Woodward Med Res Inst Inc, Buffalo, NY 14203 USA. Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, NIMH, Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RP Ablordeppey, SY (reprint author), Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA. EM seth.ablordeppey@famu.edu RI Roth, Bryan/F-3928-2010 FU NCRR NIH HHS [G12 RR 03020]; NIGMS NIH HHS [GM 08111] NR 11 TC 16 Z9 16 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 6 PY 2004 VL 14 IS 23 BP 5739 EP 5742 DI 10.1016/j.bmcl.2004.09.046 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 869AA UT WOS:000224953300004 PM 15501032 ER PT J AU Fukumoto, S Kiba, T Hall, B Iehara, N Nakamura, T Longenecker, G Krebsbach, PH Nanci, A Kulkarni, AB Yamada, Y AF Fukumoto, S Kiba, T Hall, B Iehara, N Nakamura, T Longenecker, G Krebsbach, PH Nanci, A Kulkarni, AB Yamada, Y TI Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TOOTH DEVELOPMENT; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; GENE; EXPRESSION; ENAMEL; MOUSE; AMELOGENIN; LAMININ; GROWTH AB Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin. During this process, epithelial cells differentiate into enamel-secreting ameloblasts. Ameloblastin, an enamel matrix protein, is expressed by differentiating ameloblasts. Here, we report the creation of ameloblastin-null mice, which developed severe enamel hypoplasia. In mutant tooth, the dental epithelium differentiated into enamel-secreting ameloblasts, but the cells were detached from the matrix and subsequently lost cell polarity, resumed proliferation, and formed multicell layers. Expression of Msx2, p27, and p75 were deregulated in mutant ameloblasts, the phenotypes of which were reversed to undifferentiated epithelium. We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation. The mutant mice developed an odontogenic tumor of dental epithelium origin. Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretary stage ameloblasts by binding to ameloblasts and inhibiting proliferation. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Kyushu Univ, Fac Dent Sci, Div Oral Hlth Growth & Dev, Sect Pediat Dent, Fukuoka 8128582, Japan. Univ Michigan, Sch Dent, Dept Oral Med Pathol & Oncol, Ann Arbor, MI 48109 USA. Univ Montreal, Fac Dent, Dept Stomatol, Montreal, PQ H3C 3J7, Canada. RP Yamada, Y (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. EM yoshi.yamada@nih.gov RI Nakamura, Takashi/P-7796-2016 OI Nakamura, Takashi/0000-0001-9904-1037 FU Canadian Institutes of Health Research [64178-1] NR 38 TC 203 Z9 216 U1 3 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 6 PY 2004 VL 167 IS 5 BP 973 EP 983 DI 10.1083/jcb.200409077 PG 11 WC Cell Biology SC Cell Biology GA 879FD UT WOS:000225700900017 PM 15583034 ER PT J AU Lee, JK Stewart-Jones, G Tao, D Harlos, K Di Gleria, K Dorrell, L Douek, DC van der Merwe, PA Jones, EY McMichael, AJ AF Lee, JK Stewart-Jones, G Tao, D Harlos, K Di Gleria, K Dorrell, L Douek, DC van der Merwe, PA Jones, EY McMichael, AJ TI T cell cross-reactivity and conformational changes during TCR engagement SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE HIV; CTL; HLA-A2; binding conformation; fine specificity ID MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN-IMMUNODEFICIENCY-VIRUS; PEPTIDE-MHC COMPLEXES; ELECTRON-DENSITY MAPS; PIGEON CYTOCHROME-C; REVERSE-TRANSCRIPTASE; LYMPHOCYTE RESPONSES; RECEPTOR RECOGNITION; POSITIVE SELECTION; CRYSTAL-STRUCTURES AB All thymically selected T cells are inherently cross-reactive, yet many data indicate a fine specificity in antigen recognition, which enables virus escape from immune control by mutation in infections such as the human immunodeficiency virus (HIV). To address this paradox, we analyzed the fine specificity of T cells recognizing a human histocompatibility leukocyte antigen (HLA)-A2-restricted, strongly immunodominant, HIV gag epitope (SLFNTVATL). The majority of 171 variant peptides tested bound HLA-A2, but only one third were recognized. Surprisingly, one recognized variant (SLYNTVATL) showed marked differences in structure when bound to HLA-A2. T cell receptor (TCR) recognition of variants of these two peptides implied that they adopted the same conformation in the TCR-peptide-major histocompatibility complex (MHC) complex. However, the on-rate kinetics of TCR binding were identical, implying that conformational changes at the TCR-peptide-MHC binding interface occur after an initial permissive antigen contact. These findings have implications for the rational design of vaccines targeting viruses with unstable genomes. C1 John Radcliffe Hosp, Human Immunol Unit, MRC, Weatherall Inst Mol Med, Oxford OX3 9DS, England. Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England. Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP McMichael, AJ (reprint author), John Radcliffe Hosp, Human Immunol Unit, MRC, Weatherall Inst Mol Med, Oxford OX3 9DS, England. EM andrew.mcmichael@ndm.ox.ac.uk RI van der Merwe, P. Anton/F-8539-2011; Stewart-Jones, Guillaume/E-7013-2013; Jones, Yvonne/J-2293-2016 OI Jones, Yvonne/0000-0002-3834-1893 NR 66 TC 108 Z9 111 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 6 PY 2004 VL 200 IS 11 BP 1455 EP 1466 DI 10.1084/jem.20041251 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 879RR UT WOS:000225737100010 PM 15583017 ER PT J AU Zhang, JQ Okumura, C McCarty, T Min, SS Mukhopadhyay, P Hori, M Torrey, TA Naghashfar, Z Zhou, JX Lee, CH Roopenian, DC Morse, HC Davidson, WF AF Zhang, JQ Okumura, C McCarty, T Min, SS Mukhopadhyay, P Hori, M Torrey, TA Naghashfar, Z Zhou, JX Lee, CH Roopenian, DC Morse, HC Davidson, WF TI Evidence for selective transformation of autoreactive immature plasma cells in mice deficient in Fasl SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE autoimmunity; B cell lymphoma ID HEPATITIS-C VIRUS; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; INDUCED CYTIDINE DEAMINASE; NON-HODGKIN LYMPHOMAS; ANTI-DNA ANTIBODIES; B-CELLS; SJOGRENS-SYNDROME; SOMATIC MUTATION; RECEPTOR REVISION; CLONAL EVOLUTION AB Germline mutations in Fas and Fasl induce nonmalignant T cell hyperplasia and systemic autoimmunity and also greatly increase the risk of B cell neoplasma. B lymphomas occuring in Fasl mutant (gld) mice usually are immunoglobulin (Ig) isotype switched, secrete Ig, and are plasmacytoid in appearance but lack Myc translocations characteristic of other plasma cell (PC) neoplasms. Here, we explore the relationship between B cell autoreactivity and transformation and use gene expression profiling to further classify gld plasmacytoid lymphomas (PLs) and to identify genes of potential importance in transformation. We found that the majority of PLs derive from antigen-experienced autoreactive B cells producing antinuclear antibody or rheumatoid factor and exhibit the skewed Ig V gene repertoire and Ig gene rearrangements patterns associated with these specificities. Gene expression profiling revealed that both primary and transplanted PLs share a transcriptional profile that places them at an early stage in PC differentiation and distinguishes them from other B cell neoplasms. In addition, genes were identified whose altered expression might be relevant in lymphomagenesis. Our findings provide a strong case for targeted transformation of autoreactive B cells in gld mice and establish a valuable model for understanding the relationship between systemic autoimmunity and B cell neoplasia. C1 Amer Red Cross, Jerome H Holland Lab, Dept Immunol, Rockville, MD 20855 USA. NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Ibaraki Cent Hosp, Ibaraki 3100815, Japan. Jackson Lab, Bar Harbor, ME 04609 USA. George Washington Univ, Inst Biol Sci, Dept Immunol, Washington, DC 20037 USA. RP Davidson, WF (reprint author), Univ Maryland, Sch Med, Greenebaum Canc Ctr, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM wdavi002@umaryland.edu RI MUKHOPADHYAY, PARTHA/G-3890-2010; OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA82872-02, R01 CA082872] NR 74 TC 17 Z9 17 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 6 PY 2004 VL 200 IS 11 BP 1467 EP 1478 DI 10.1084/jem.20041575 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 879RR UT WOS:000225737100011 PM 15583018 ER PT J AU Golech, SA McCarron, RM Chen, Y Bembry, J Lenz, F Mechoulam, R Shohami, E Spatz, M AF Golech, SA McCarron, RM Chen, Y Bembry, J Lenz, F Mechoulam, R Shohami, E Spatz, M TI Human brain endothelium: coexpression and function of vanilloid and endocannabinoid receptors SO MOLECULAR BRAIN RESEARCH LA English DT Article DE brain endothelium; endocannabinoids; receptors; Ca2+ influx; VASP ID CANNABINOID RECEPTORS; MESSENGER-RNA; RAT AORTA; CELLS; ANANDAMIDE; MODULATION; SYSTEM; VR1; CB2 AB The arachidonic acid derivative, 2-arachidonoyl-glycerol (2-AG), was initially isolated from gut and brain; it is also produced and released from blood and vascular cells. Many of the 2-AG-induced cellular responses (i.e., neuromodulation, cytoprotection and vasodilation) are mediated by cannabinoid receptors CB1 and CB2. The findings presented here demonstrate the expression of CB1, CB2 and TRPV1 receptors on cerebromicrovascular endothelial cells (HBEC). The expression of TRPV1, CB1 and CB2 receptor mRNA and proteins were demonstrated by RT-PCR and polyclonal antibodies, respectively. The endocannabinoid 2-AG, and other related compounds [anandamide (ANA), methanandamide (m-ANA), N-(4-hydroxyphenyl-arachidonyl-ethanolamide) (AM404) and capsaicin] dose-dependently stimulated Ca2+ influx in HBEC. The selective TRPV1 receptor antagonist (capsazepine), CB1 receptor antagonist (SR141716A) and CB2 receptor antagonist (SR144528) inhibited these responses. The effects of capsaicin, a specific agonist for TRPV1 receptors, were inhibited by capsazepine, but only weakly by CB1 or CB2 receptor antagonists. 2-AG also induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP); this response was mediated by VR1 receptors. These studies clearly indicate that 2-AG and other related compounds may function as agonists on VR1 receptors, as well as CB1 and CB2 receptors, and implicated these factors in various HBEC functions. Published by Elsevier B.V. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Naval Med Res Ctr, Resuscitat Med Dept, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Hebrew Univ Jerusalem, Jerusalem, Israel. RP Spatz, M (reprint author), NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. EM spatzm@ninds.nih.gov NR 31 TC 80 Z9 82 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 6 PY 2004 VL 132 IS 1 BP 87 EP 92 DI 10.1016/j.molbrainres.2004.08.025 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 876LX UT WOS:000225499500010 ER PT J AU Clemente, JT Parada, CA Veiga, MCA Gear, RW Tambeli, CH AF Clemente, JT Parada, CA Veiga, MCA Gear, RW Tambeli, CH TI Sexual dimorphism in the antinociception mediated by kappa opioid receptors in the rat temporomandibular joint SO NEUROSCIENCE LETTERS LA English DT Article DE temporomandibular joint; formalin test; nociception; sex differences; kappa opioid receptor; estrous cycle ID ESTROUS-CYCLE; PERIPHERAL MORPHINE; EXPERIMENTAL PAIN; SPINAL-CORD; ANALGESIA; MICE; FORMALIN; PROGESTERONE; MODEL; MU AB This study assessed the effect of the kappa opioid receptor agonist U50,488 administered into the rat temporomandibular joint (TMJ) on nociceptive behavioral responses evoked by formalin injected into the same site. Groups consisted of females, stratified into proestrus and diestrus phases of the estrous cycle, and males. Intra-TMJ formalin induced significantly different dose-dependent responses among the three groups, with diestrus females showing greater responses than males or proestrus females; therefore, equi-nociceptive formalin doses were chosen to test the effects of U50,488. U50,488 significantly reduced formalin-induced nociceptive behavior in all groups, but the reduction was significantly greater in females, especially those in diestrus. Pre-injection of the selective kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) into the same site significantly attenuated the effect of U50488; U50,488 injection into the contralateral TMJ failed to reduce nociceptive behavior. These findings support a role for kappa opioid receptors local to the site of inflammation to modulate inflammatory pain. Furthermore, since plasma levels of ovarian hormones are low during diestrus, these findings are consistent with the suggestion that sex hormones may play an antagonistic role in these peripheral kappa-mediated effects. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Campinas, Fac Dent Piracicaba, Dept Physiol, Lab Orofacial Pain, BR-13414900 Sao Paulo, SP, Brazil. Univ Sao Paulo, Dept Pharmacol, Fac Med Ribeirao Preto, Sao Paulo, SP, Brazil. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA USA. Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA USA. RP Tambeli, CH (reprint author), Univ Campinas, Fac Dent Piracicaba, Dept Physiol, Lab Orofacial Pain, Av Limeira 901, BR-13414900 Sao Paulo, SP, Brazil. EM tambeli@fop.unicamp.br RI Parada, Carlos Amilcar/C-3974-2012; Tambeli, Claudia/D-4356-2012; Clemente-Napimoga, Juliana/E-5163-2013 OI Clemente-Napimoga, Juliana/0000-0003-1068-3039 NR 36 TC 46 Z9 46 U1 2 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 6 PY 2004 VL 372 IS 3 BP 250 EP 255 DI 10.1016/j.neulet.2004.09.048 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 876BG UT WOS:000225469900015 PM 15542250 ER PT J AU Prabakaran, P Singarayan, MG AF Prabakaran, P Singarayan, MG TI Long-range ordering in water-halide ion interactions: A database study SO CHEMISTRY LETTERS LA English DT Article ID CAMBRIDGE STRUCTURAL DATABASE; MOLECULAR-CRYSTALS; AB-INITIO; CLUSTERS; ENERGETICS; HYDRATION; SPECTRA; N=1-6 AB A detailed analysis of water-halide ion interactions using the Cambridue Structural Database reveals predominant cyclic hydrogen-bonded ((H2OX-)-X-.)(2) Clusters and isostructural tapes of 4,5,6-membered rings leading to channel hydrates. C1 RIKEN, Tsukuba Inst, Tsukuba, Ibaraki 3050074, Japan. RP Singarayan, MG (reprint author), NCI, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. RI Ponraj, Prabakaran/D-6325-2011 NR 17 TC 4 Z9 4 U1 0 U2 2 PU CHEMICAL SOC JAPAN PI TOKYO PA 1-5 KANDA-SURUGADAI CHIYODA-KU, TOKYO, 101-8307, JAPAN SN 0366-7022 EI 1348-0715 J9 CHEM LETT JI Chem. Lett. PD DEC 5 PY 2004 VL 33 IS 12 BP 1640 EP 1641 DI 10.1246/cl.2004.1640 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 880AS UT WOS:000225761300052 ER PT J AU McAuliffe, J Vogel, L Roberts, A Fahle, G Fischer, S Shieh, WJ Butler, E Zaki, S Claire, MS Murphy, B Subbarao, K AF McAuliffe, J Vogel, L Roberts, A Fahle, G Fischer, S Shieh, WJ Butler, E Zaki, S Claire, MS Murphy, B Subbarao, K TI Replication of SARS coronavirus administered into the respiratory tract of African Green, rhesus and cynomolgus monkeys SO VIROLOGY LA English DT Article DE replication; SARS; respiratory tract ID FELINE INFECTIOUS PERITONITIS; VIRUS-INFECTION; PRIMATE MODEL; PATHOGENESIS; IDENTIFICATION; VACCINE AB SARS coronavirus (SARS-CoV) administered intranasally and intratracheally to rhesus, cynomolgus and African Green monkeys (AGM) replicated in the respiratory tract but did not induce illness. The titer of serum neutralizing antibodies correlated with the level of virus replication in the respiratory tract (AGM>cynomolgus>rhesus). Moderate to high titers of SARS-CoV with associated interstitial pneumonitis were detected in the lungs of AGMs on day 2 and were resolving by day 4 post-infection. Following challenge of AGMs 2 months later, virus replication was highly restricted and there was no evidence of enhanced disease. These species will be useful for the evaluation of the immunogenicity of candidate vaccines, but the lack of apparent clinical illness in all three species, variability from animal to animal in level of viral replication, and rapid clearance of virus and pneumonitis in AGMs must be taken into account by investigators considering the use of these species in efficacy and challenge studies. Published by Elsevier Inc. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Microbiol Serv, Ctr Clin, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Bioqual Inc, Rockville, MD 20852 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Room 6132,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov NR 21 TC 96 Z9 102 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2004 VL 330 IS 1 BP 8 EP 15 DI 10.1016/j.virol.2004.09.030 PG 8 WC Virology SC Virology GA 872GL UT WOS:000225195600002 PM 15527829 ER PT J AU Ahn, KS Ou, W Silver, J AF Ahn, KS Ou, W Silver, J TI Inhibition of certain strains of HIV-1 by cell surface polyanions in the form of cholesterol-labeled oligonucleotides SO VIROLOGY LA English DT Article DE cholesterol-labeled oligonucleotides; virus entry; membrane fusion; HIV-1; electrostatic interaction ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPARAN-SULFATE PROTEOGLYCAN; GP120 ENVELOPE GLYCOPROTEIN; DEXTRAN SULFATE; V3 LOOP; T-CELLS; INITIAL INTERACTION; TYPE-1 ATTACHMENT; PLASMA-MEMBRANE; INFECTION AB Cholesterol-labeled oligonucleotides were found several years ago to inhibit HIV-1 in tissue culture at nanomolar concentrations. We present evidence that this is mainly due to an electrostatic interaction between polyanionic oligonucleotide concentrated at the cell surface and a positively charged region in the V3 loop of the HIV-1 envelope protein. When added to tissue culture, cholesterol-labeled oligonucleotides became concentrated at the plasma membrane and potently inhibited virus entry and cell fusion mediated by the envelope protein of some X4 strains of HIV-1, but had little effect on fusion mediated by R5 strains of HIV-1, amphotropic MLV envelope protein, or VSV-G protein. Noncholesterol-labeled oligonucleotides did not bind to the cell surface or inhibit fusion. The pattern of susceptibility to cholesterol-labeled oligonucleotides among HIV-1 strains was the same as reported for nonmembrane-associating polyanions such as dextran sulfate, but the cholesterol-labeled oligonucleotides were effective at lower concentrations. Substitution of a basic 33 amino acid V3 loop sequence from the envelope protein of a resistant strain into a susceptible strain made the envelope protein resistant to inhibition. Inhibition by cholesterol-labeled oligonucleotides was abrogated by the polycation DEAE-dextran. Cholesterol-labeled oligonucleotides bound to nonraft regions of the plasma membrane and did not inhibit HIV virus binding to cells. Many infectious agents first associate with target cells via relatively nonspecific charge interactions; our data suggest that molecules that combine a membrane-targeting motif with multiple negative charges might be useful to modify these interactions. Published by Elsevier Inc. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Silver, J (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 336, Bethesda, MD 20892 USA. EM jsilver@nih.gov OI Silver, Jonathan/0000-0001-9231-6368 NR 53 TC 8 Z9 9 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 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2004 VL 330 IS 1 BP 50 EP 61 DI 10.1016/j.virol.2004.09.010 PG 12 WC Virology SC Virology GA 872GL UT WOS:000225195600006 PM 15527833 ER PT J AU Yuan, LJ Honma, S Ishida, SI Yan, XY Kapikian, AZ Hoshino, Y AF Yuan, LJ Honma, S Ishida, SI Yan, XY Kapikian, AZ Hoshino, Y TI Species-specific but not genotype-specific primary and secondary isotype-specific NSP4 antibody responses in gnotobiotic calves and piglets infected with homologous host bovine (NSP4[A]) or porcine (NSP4[B]) rotavirus SO VIROLOGY LA English DT Article DE rotavirus; NSP4; antibody response; NSP4 genotype/serotype; species specificity; protective immunity; gnotobiotic pigs/calves ID NONSTRUCTURAL GLYCOPROTEIN; SEQUENCE-ANALYSIS; IMMUNE-RESPONSES; PROTEINS; PATHOGENESIS; PROTECTION; RESISTANCE; VIRULENCE; MUTATIONS; DIARRHEA AB Using recombinant baculoviruses expressing rotavirus NSP4 [A], [B], [C], and [D] genotypes of bovine, porcine, human, simian, or murine origin, we analyzed serum antibody responses to NSP4s in gnotobiotic calves and piglets infected by the oral/alimentary or intraamniotic route with bovine (NSP4[A]) (Wyatt, R.G., Mebus, C.A., Yolken, R.H., Kalica, A.R., James, H.D., Jr., Kapikian, A.Z., Chanock, R.M., 1979. Rotaviral immunity in gnotobiotic calves: heterologous resistance to human virus induced by bovine virus. Science 203(4380), 548-550) or porcine (NSP4[B]) (Hoshino, Y., Saif, L.J., Sereno, M.M., Chanock, R.M., Kapikian, A.Z., 1988. Infection immunity of piglets to either VP3 or VP7 outer capsid protein confers resistance to challenge with a virulent rotavirus bearing the corresponding antigen. J. Virol. 62(3), 744-748) rotaviruses. Following primary infection and challenge with virulent rotaviruses, the animals developed higher or significantly higher antibody titers to homologous host homotypic NSP4s than to heterologous host homotypic or heterologous host heterotypic NSP4s, indicating that antibody responses were species specific rather than genotype specific. Antibody responses to NSP4s corresponded closely with the phylogenetic relationships of NSP4s within a species-specific region of amino acids (aa) 131-141. In contrast, NSP4 genotypes determined by amino acid full-length sequence identity predicted poorly their "serotypes". In piglets, antibodies to NSP4 induced by previous oral infection failed to confer protection against challenge from a porcine rotavirus bearing serotypically different VP4 and VP7 but essentially identical NSP4 to the porcine rotavirus in primary infection. Thus, in an approach to immunization with a live oral rotavirus vaccine, the NSP4 protein does not appear to play an important role in protection against rotavirus disease and infection. Published by Elsevier Inc. C1 NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, NIH, 50 South Dr,MSC 8026,Bldg 50,Room 6308, Bethesda, MD 20892 USA. EM yuan.21@osu.edu; thoshino@niaid.nih.gov RI Yuan, Lijuan/A-2468-2008 OI Yuan, Lijuan/0000-0003-0709-5228 NR 28 TC 13 Z9 15 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2004 VL 330 IS 1 BP 92 EP 104 DI 10.1016/j.virol.2004.09.021 PG 13 WC Virology SC Virology GA 872GL UT WOS:000225195600010 PM 15527837 ER PT J AU Schomacker, H Collins, PL Schmidt, AC AF Schomacker, H Collins, PL Schmidt, AC TI In silico identification of a putative new paramyxovirus related to the Henipavirus genus SO VIROLOGY LA English DT Article DE henipa-like virus; Nipah virus; Hendra virus; emerging virus; paramyxovirus; viral phylogeny; in silico ID HUMAN MESANGIAL CELLS; MULTIPLE SEQUENCE ALIGNMENT; NIPAH-VIRUS; MOLECULAR CHARACTERIZATION; ANGIOTENSIN-II; ANGREM104; SOFTWARE; DISEASE; BIOLOGY; HENDRA AB A database search for genes encoding paramyxoviral proteins revealed sequences that were designated as human but presented strong evidence of being of viral origin. The two cDNA-derived sequences designated AngRem104 and AngRem52 were originally described as human gene products that were upregulated by angiotensin II in primary mesangial kidney cells. However, their high degree of sequence relatedness to known viral proteins suggests that they represent the P/C/V, M, and F genes of a putative new member of family Paramyxoviridae. Comparison of deduced amino acid sequences and nucleotide motifs suggests that this putative virus is a divergent relative of the Hendra and Nipah viruses; hence, we suggest henipa-like virus or HNLV as a provisional name. Compared to Nipah virus, the percentage of identical (similar) amino acids varied from 19% (42%) for the C protein to 51% (75%) for the M protein. The presence and conservation of presumptive viral transcription start and stop signals and an apparent P editing motif also indicate a relationship of this putative virus to the henipaviruses. Given the highly pathogenic nature of the henipaviruses, the origin of these sequences is enigmatic, and attempts to identify and isolate HNLV are warranted. (C) 2004 Elsevier Inc. All rights reserved. C1 Charite Univ Med Berlin, Dept Pediat, D-13353 Berlin, Germany. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Schmidt, AC (reprint author), Charite Univ Med Berlin, Dept Pediat, Ostring 1,R 30073, D-13353 Berlin, Germany. EM alexander_c.schmidt@charite.de NR 33 TC 8 Z9 8 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 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2004 VL 330 IS 1 BP 178 EP 185 DI 10.1016/j.virol.2004.09.019 PG 8 WC Virology SC Virology GA 872GL UT WOS:000225195600017 PM 15527844 ER PT J AU Grundner, C Pancera, M Kang, JM Koch, M Sodroski, J Wyatt, R AF Grundner, C Pancera, M Kang, JM Koch, M Sodroski, J Wyatt, R TI Factors limiting the immunogenicity of HIV-1 gp120 envelope glycoproteins SO VIROLOGY LA English DT Article DE HIV-1; envelope glycoproteins; immunogenicity ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL-EPITOPE; MHC CLASS-II; NEUTRALIZING ANTIBODIES; 3-DIMENSIONAL STRUCTURE; VARIABLE REGIONS; RECEPTOR-BINDING; PEPTIDES; RESPONSES; PROTEIN AB Efficient immune responses to HIV-1 gene products are essential elements to the development and design of an effective vaccine. Ideally, both humoral and cellular responses will be optimally elicited. It is therefore important to elucidate any factors that might limit the immumogenicity of HIV-1 proteins that are likely to be included in an effective vaccine. Since the HIV-1 exterior envelope glycoprotein gp 120 is a major target for neutralizing antibodies, it is a virtual certainty that this gene product will be a component of any vaccine that seeks to elicit neutralizing antibody responses from the host humoral immune system. We report here the testing of several HIV-1 gp 120 variants derived from a primary isolate that appears deficient in eliciting immune responses at both the level of CD4+ help and consequently in the generation of high-affinity IgG antibody responses in small animals. Factors limiting an effective immune response include (a) envelope glycoprotein strain variation decreasing functional T-cell help, (b) alteration of the glycosylation patterns of gp 120 by expression in different cell types, and (c) the native structure of gp 120 itself, which may limit the elicitation of effective T-cell help during natural infection or during parenteral immunization in adjuvant. Such limiting factors and others should be considered in the design and testing of gpl20-based immumogens in small animals and possibly in primates as well. C1 NIH, Struct Virol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wyatt, R (reprint author), NIH, Struct Virol Sect, Vaccine Res Ctr, 40 Convent Dr,Bldg 40, Room 4512, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov FU NIAID NIH HHS [5 R21 AI-44328-02, 1 R21 AI-44328-02] NR 56 TC 38 Z9 39 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 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2004 VL 330 IS 1 BP 233 EP 248 DI 10.1016/j.virol.2004.08.037 PG 16 WC Virology SC Virology GA 872GL UT WOS:000225195600022 PM 15527849 ER PT J AU Milush, JA Kosub, D Marthas, M Schmidt, K Scott, F Wozniakowski, A Brown, C Westmoreland, S Sodora, DL AF Milush, JA Kosub, D Marthas, M Schmidt, K Scott, F Wozniakowski, A Brown, C Westmoreland, S Sodora, DL TI Rapid dissemination of SIV following oral inoculation SO AIDS LA English DT Article DE SIV; HIV; oral transmission; macaque; acute SIV infection ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; NEWBORN RHESUS MACAQUES; MONOCLONAL-ANTIBODIES; PASSIVE-IMMUNIZATION; INTRAVAGINAL INOCULATION; SEXUAL TRANSMISSION; NEONATAL MACAQUES; NONHUMAN-PRIMATES; VIRAL REPLICATION AB Objective: To assess the earliest events regarding transmission and dissemination of SIV following nontraumatic oral inoculation in macaques. Design: Juvenile and neonate rhesus macaques were orally inoculated with SIVmac251 and necropsied at 1, 2, 4, 7, or 14 days post-inoculation. Sites of transmission and the extent of viral spread were assessed by using molecular techniques and in situ hybridization to identify SIV nucleic acid in lymphoid and nonlymphoid tissues. Results: This study demonstrates that 1 day post-exposure, SIV nucleic acid was detected in the alimentary canal only in tissues proximal to the stomach, including the oral and esophageal mucosa as well as the tonsils. Following infection, virus was observed to spread rapidly to regional and peripheral lymph nodes by 1 and 2 days post-inoculation (dpi). Hundreds of copies of SIV-DNA were detected 4 dpi, increasing to > 10 000 copies/1 x 10(6) cells by 7 dpi. Identification of SIV positive T cells and macrophages implicates these cell types in viral spread, although dissemination of free virus is also likely. Conclusions: Here the oral and esophageal mucosa, as well as tonsils, are demonstrated to be potential sites for viral infection upon nontraumatic oral exposure to SIV in macaques. The rapid dissemination following oral transmission observed in this study is reflective of SIV transmission across other mucosal surfaces. The rapidity with which SIV, and probably HIV, spreads throughout the lymphatics indicates a major obstacle for a vaccine amnestic immune response to eliminate infected cells prior to dissemination. (C) 2004 Lippincott Williams Wilkins. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Calif Davis, California Natl Primate Res Ctr, Davis, CA 95616 USA. NIAID, Mol Microbiol Lab, NIH, Rockville, MD USA. Massachusetts Gen Hosp, Charlestown, MA USA. RP Sodora, DL (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM DonaId.Sodora@UTSouthwestern.edu FU NCRR NIH HHS [RR 00169, RR 000150, RR 00168, RR 017740]; NIAID NIH HHS [5T32 AI 005284, 5T32 AI 07520, AI 35522]; NIDCR NIH HHS [DE 12926] NR 50 TC 47 Z9 47 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD DEC 3 PY 2004 VL 18 IS 18 BP 2371 EP 2380 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 884BR UT WOS:000226060100004 PM 15622313 ER PT J AU Kamiya, A Inoue, Y Kodama, T Gonzalez, FJ AF Kamiya, A Inoue, Y Kodama, T Gonzalez, FJ TI Hepatocyte nuclear factors 1 alpha and 4 alpha control expression of proline oxidase in adult liver SO FEBS LETTERS LA English DT Article DE amino acid metabolism; liver-enriched; transcription factor; gene expression; proline oxidase ID CENTRAL REGULATOR; GENE-EXPRESSION; BILE-ACID; RECEPTOR; MICE; DIFFERENTIATION; FACTOR-4-ALPHA; HNF-1-ALPHA; COOPERATION; HOMEOSTASIS AB Adult liver functions are regulated by several hepatocyte nuclear factors (HNFs). HNF4alpha and HNF1alpha are involved in metabolic functions in the liver. The expression of proline oxidase (PO) and proline dehydrogenase was downregulated in the HNF4alpha liver-specific null mice. In addition, the expression of PO was also diminished in the liver derived from HNF1alpha-null mice. The -160 bp proximal promoter region of the PO gene has two HNF4alpha and HNF1alpha-binding consensus sites. Transactivation, electrophoretic mobility shift and chromatin immunoprecipitation studies revealed that these regions are important for PO promoter activity. These results suggested that HNF4alpha and HNF1alpha regulate proline metabolism in adult liver. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Lab Syst Biol & Med, RCAST 34, Tokyo 1538904, Japan. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 3106 B1,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 22 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 3 PY 2004 VL 578 IS 1-2 BP 63 EP 68 DI 10.1016/j.febslet.2004.10.070 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 878MI UT WOS:000225650500012 PM 15581617 ER PT J AU Fueger, PT Hess, HS Posey, KA Bracy, DP Pencek, RR Charron, MJ Wasserman, DH AF Fueger, PT Hess, HS Posey, KA Bracy, DP Pencek, RR Charron, MJ Wasserman, DH TI Control of exercise-stimulated muscle glucose uptake by GLUT4 is dependent on glucose phosphorylation capacity in the conscious mouse SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT SKELETAL-MUSCLE; TRANSGENIC MICE; HEXOKINASE-II; INSULIN-RESISTANCE; KNOCKOUT MICE; TRANSPORT; OVEREXPRESSION; GENE; HOMEOSTASIS; LIMITATIONS AB Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during exercise because GLUT4 overexpression does not increase exercise-stimulated MGU. Instead of glucose transport, glucose phosphorylation is a primary limitation of exercise-stimulated MGU. It was hypothesized that a partial ablation of GLUT4 would not impair exercise-stimulated MGU when glucose phosphorylation capacity is normal but would do so when glucose phosphorylation capacity was increased. Thus, C57BL/6J mice with hexokinase II (HKII) overexpression (HKTg), a GLUT4 partial knock-out (G4(+/-)), or both (HKTg + G4(+/-)) and wild-type (WT) littermates were implanted with carotid artery and jugular vein catheters for sampling and infusions at 4 months of age. After a 7-day recovery, 5-h fasted mice remained sedentary or ran on a treadmill at 0.6 mph for 30 min ( n = 9 - 12 per group) and received a bolus of 2-deoxy[H-3] glucose to provide an index of MGU (R-g). Arterial blood glucose and plasma insulin concentrations were similar in WT, G4(+/-), HKTg, and HKTg + G4(+/-) mice. Sedentary R-g values were the same in all genotypes in all muscles studied, confirming that glucose transport is a significant barrier to basal glucose uptake. Gastrocnemius and soleus Rg were greater in exercising compared with sedentary mice in all genotypes. During exercise, G4(+/-) mice had a marked increase in blood glucose that was corrected by the addition of HK II overexpression. Exercise R-g (mumol/100g/min) was not different between WT and G4(+/-) mice in the gastrocnemius ( 24 +/- 5 versus 21 +/- 2) or the soleus ( 54 +/- 6 versus 70 +/- 7). In contrast, the enhanced exercise R-g observed in HKTg mice compared with that in WT mice was absent in HKTg + G4(+/-) mice in both the gastrocnemius (39 +/- 7 versus 22 +/- 6) and the soleus ( 98 +/- 13 versus 65 +/- 13). Thus, glucose transport is not a significant barrier to exercise-stimulated MGU despite a 50% reduction in GLUT4 content when glucose phosphorylation capacity is normal. However, when glucose phosphorylation capacity is increased by HK II overexpression, GLUT4 availability becomes a marked limitation to exercise-stimulated MGU. C1 Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. RP Fueger, PT (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, 4321 Med Pk Dr,Suite 200, Durham, NC 27704 USA. EM patrick.fueger@duke.edu FU NIDDK NIH HHS [R01 DK-54902, R01 DK-47425, U24 DK-59637] NR 39 TC 29 Z9 30 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 3 PY 2004 VL 279 IS 49 BP 50956 EP 50961 DI 10.1074/jbc.M408312200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874MZ UT WOS:000225355800039 PM 15456776 ER PT J AU Chang, TS Jeong, W Woo, HA Lee, SM Park, S Rhee, SG AF Chang, TS Jeong, W Woo, HA Lee, SM Park, S Rhee, SG TI Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; HYDROGEN-PEROXIDE; THIOREDOXIN; PROTEIN; FAMILY; IDENTIFICATION; OVEROXIDATION; LOCALIZATION; INACTIVATION; MECHANISM AB Peroxiredoxins (Prxs) are a family of peroxidases that reduce hydroperoxides. The cysteine residue in the active site of certain eukaryotic Prx enzymes undergoes reversible oxidation to sulfinic acid (Cys-SO2H) during catalysis, and sulfiredoxin (Srx) has been identified as responsible for reversal of the resulting enzyme inactivation in yeast. We have now characterized mammalian orthologs of yeast Srx with an assay based on monitoring of the reduction of sulfinic Prx by immunoblot analysis with antibodies specific for the sulfinic state. Sulfinic reduction by mammalian Srx was found to be a slow process (k(cat) = 0.18/min) that requires ATP hydrolysis. ATP could be efficiently replaced by GTP, dATP, or dGTP but not by CTP, UTP, dCTP, or dTTP. Both glutathione and thioredoxin are potential physiological electron donors for the Srx reaction, given that their K-m values (1.8 mM and 1.2 muM, respectively) are in the range of their intracellular concentrations, and the V-max values obtained with the two reductants were similar. Although its pK(a) is relatively low ( similar to 7.3), the active site cysteine of Srx remained reduced even when the active site cysteine of most Prx molecules became oxidized. Finally, depletion of human Srx by RNA interference suggested that Srx is largely responsible for reduction of the Cys-SO2H of Prx in A549 human cells. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. RP Rhee, SG (reprint author), NIH, Bldg 50,Rm 3523,South Dr,MSC 8015, Bethesda, MD 20892 USA. EM sgrhee@nih.gov NR 30 TC 208 Z9 225 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 3 PY 2004 VL 279 IS 49 BP 50994 EP 51001 DI 10.1074/jbc.M409482200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874MZ UT WOS:000225355800044 PM 15448164 ER PT J AU Yahiro, K Wada, A Yamasaki, E Nakayama, M Nishi, Y Hisatsune, J Morinaga, N Sap, J Noda, M Moss, J Hirayama, T AF Yahiro, K Wada, A Yamasaki, E Nakayama, M Nishi, Y Hisatsune, J Morinaga, N Sap, J Noda, M Moss, J Hirayama, T TI Essential domain of receptor tyrosine phosphatase beta (RPTP beta) for interaction with Helicobacter pylori vacuolating cytotoxin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MOLECULE HB-GAM; VACA TOXIN; ZETA/RPTP-BETA; MICE DEFICIENT; PTP-ALPHA; PROTEIN; BINDING; CELLS; ACTIVATION AB Helicobacter pylori produces a potent exotoxin, VacA, which causes progressive vacuolation as well as gastric injury. Although VacA was able to interact with two receptor-like protein tyrosine phosphatases, RPTPbeta and RPTPalpha, RPTPbeta was found to be responsible for gastric damage caused by VacA. To define the region of RPTPbeta involved in VacA binding, we made mutants of human cDNA RPTPbeta-B, a short receptor form of RPTPbeta. Immunoprecipitation experiments to assess VacA binding to RPTPbeta-B mutants indicated that five residues (QTTQP) at positions 747 - 751 of the extracellular domain of RPTPbeta-B ( which is commonly retained in RPTPbeta-A, a long form of RPTPbeta) play a crucial role in its interaction with VacA, resulting in vacuolation as well as Git-1 phosphorylation. Transfected cells expressing deletion mutant Delta752, which lacks QTTQP, or the double point mutant Delta747 (T748A, T749A) had diminished vacuolation in response to VacA. Treatment of RPTPbeta-B and Delta747 ( which have QTTQP at 747 - 751) with neuraminidase and O-glycosidase diminished their VacA binding, whereas chondroitinase ABC did not have an effect. No inhibitory effect of pleiotrophin, a natural RPTPbeta ligand, on VacA binding to RPTPbeta-B or Delta747 was observed, supporting the conclusion that the extracellular region of RPTPbeta-B responsible for VacA binding is different from that involved in binding pleiotrophin. These data define the region in the RPTPbeta extracellular domain critical for VacA binding, in particular the sequence QTTQP at positions 747 - 751 with crucial threonines at positions 748 and 749 and are consistent with a role for terminal sialic acids possibly because of threonine glycosylation. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba 2608670, Japan. Japan Sci & Technol Corp, PRESTO, Saitama 3320012, Japan. NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. EM hirayama@net.nagasaki-u.ac.jp NR 51 TC 21 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 3 PY 2004 VL 279 IS 49 BP 51013 EP 51021 DI 10.1074/jbc.M406473200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874MZ UT WOS:000225355800046 PM 15383529 ER PT J AU Wilkinson, JC Richter, BWM Wilkinson, AS Burstein, E Rumble, JM Balliu, B Duckett, CS AF Wilkinson, JC Richter, BWM Wilkinson, AS Burstein, E Rumble, JM Balliu, B Duckett, CS TI VIAF, a conserved inhibitor of apoptosis (IAP)-interacting factor that modulates caspase activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; UBIQUITIN-PROTEIN LIGASE; X-LINKED INHIBITOR; CELL-DEATH; STRUCTURAL BASIS; BACULOVIRUS INHIBITOR; MEDIATED APOPTOSIS; ENDOTHELIAL-CELLS; BINDING-PROTEINS; MAMMALIAN-CELLS AB Inhibitor of apoptosis (IAP) proteins are involved in the suppression of apoptosis, signal transduction, cell cycle control and gene regulation. Here we describe the cloning and characterization of viral IAP-associated factor (VIAF), a highly conserved, ubiquitously expressed phosphoprotein with limited homology to members of the phosducin family that associates with baculovirus Op-IAP. VIAF bound Op-IAP both in vitro and in intact cells, with each protein displaying a predominantly cytoplasmic localization. VIAF lacks a consensus IAP binding motif, and overexpression of VIAF failed to prevent Op-IAP from protecting human cells from a variety of apoptotic stimuli, suggesting that VIAF does not function as an IAP antagonist. VIAF was unable to directly inhibit caspase activation in vitro and a reduction of VIAF protein levels by RNA interference led to a decrease in Bax-mediated caspase activation, suggesting that VIAF functions to co-regulate the apoptotic cascade. Finally, VIAF is a substrate for ubiquitination mediated by Op-IAP. Thus, VIAF is a novel IAP-interacting factor that functions in caspase activation during apoptosis. C1 Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Duckett, CS (reprint author), Med Sci 1,Room 5315,1301 Catherine St, Ann Arbor, MI 48109 USA. EM colind@umich.edu RI Burstein, Ezra/B-7247-2016; OI Burstein, Ezra/0000-0003-4341-6367; Rumble, Julie/0000-0001-7220-7631 FU NCI NIH HHS [T32 CA09676] NR 77 TC 19 Z9 28 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 3 PY 2004 VL 279 IS 49 BP 51091 EP 51099 DI 10.1074/jbc.M409623200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874MZ UT WOS:000225355800055 PM 15371430 ER PT J AU Skorvaga, M DellaVecchia, MJ Croteau, DL Theis, K Truglio, JJ Mandavilli, BS Kisker, C Van Houten, B AF Skorvaga, M DellaVecchia, MJ Croteau, DL Theis, K Truglio, JJ Mandavilli, BS Kisker, C Van Houten, B TI Identification of residues within UvrB that are important for efficient DNA binding and damage processing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; CRYSTAL-STRUCTURE; THERMUS-THERMOPHILUS; PROTEIN COMPLEX; RECOGNITION; HELICASE; ENZYME AB The UvrB protein is the central recognition protein in bacterial nucleotide excision repair. We have shown previously that the highly conserved beta-hairpin motif in Bacillus caldotenax UvrB is essential for DNA binding, damage recognition, and UvrC-mediated incision, as deletion of the upper part of the beta-hairpin ( residues 97 112) results in the inability of UvrB to be loaded onto damaged DNA, defective incision, and the lack of strand-destabilizing activity. In this work, we have further examined the role of the beta-hairpin motif of UvrB by a mutational analysis of 13 amino acids within or in the vicinity of the beta-hairpin. These amino acids are predicted to be important for the interaction of UvrB with both damaged and non-damaged DNA strands as well as the formation of salt bridges between the beta-hairpin and domain 1b of UvrB. The resulting mutants were characterized by standard functional assays such as oligonucleotide incision, electrophoretic mobility shift, strand-destabilizing, and ATPase assays. Our data indicated a direct role of Tyr(96), Glu(99), and Arg(123) in damage-specific DNA binding. In addition, Tyr(93) plays an important but less essential role in DNA binding by UvrB. Finally, the formation of salt bridges between the beta-hairpin and domain 1b, involving amino acids Lys(111) bound to Glu(307) and Glu(99) bound to Arg(367) or Arg(289), are important but not essential for the function of UvrB. C1 SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Slovak Acad Sci, Canc Res Inst, Dept Mol Genet, Bratislava 83391, Slovakia. Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA. RP Kisker, C (reprint author), SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. EM kisker@pharm.sunysb.edu; vanhout1@niehs.nih.gov NR 14 TC 25 Z9 25 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 3 PY 2004 VL 279 IS 49 BP 51574 EP 51580 DI 10.1074/jbc.M409266200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874MZ UT WOS:000225355800113 PM 15456749 ER PT J AU Kleinau, G Jaschke, H Neumann, S Lattig, J Paschke, R Krause, G AF Kleinau, G Jaschke, H Neumann, S Lattig, J Paschke, R Krause, G TI Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; THYROTROPIN TSH RECEPTOR; LEUCINE-RICH REPEATS; EXTRACELLULAR DOMAIN; LUTEINIZING-HORMONE; BETA-SUBUNIT; ALPHA-SUBUNIT; HUMAN CHORIOGONADOTROPIN; CONSTITUTIVE ACTIVATION; CRYSTAL-STRUCTURE AB Glycoprotein hormone receptors (GPHRs) differ from the other seven transmembrane receptors mainly through a complex activation mechanism that requires the binding of a large hormone toward a large N-terminal ectodomain. The intramolecular mechanism of the signal transduction to the serpentine domain upon hormone binding at the ectodomain is not understood. To identify determinants at the GPHR ectodomain that may be involved in signal transduction, we first searched for homologous structural features. Based on high sequence similarity to the determined structures of the Nogo-receptor ectodomain and the intermolecular complex of the Interleukin-8 ligand (IL8) and the N-terminal peptide of the IL8 receptor (IL8RA), the hypothesis was developed that portions of the intramolecular components, Cysteine-box-2 and Cysteine-box-3, of the GPHR ectodomain interact and localize at the interface between ectodomain and serpentine domain. Indeed, point mutations within the (DEFN406)-E-403 motif at Cysteine-box-3 of the thyrotropin receptor resulted in increased basal cAMP levels, suggesting that this motif may be important for transduction of the signal from the ectodomain to the transmembrane domain. New indications are provided about the tight spatial cooperation and relative location of the new epitope and other determinants at the thyrotropin receptor ectodomain, such as the leucine-rich repeat motif Ser(281) and the cysteine boxes. According to the high sequence conservation, the results are of general relevance for the signal transduction mechanism of other glycoprotein hormone receptors such as choriogonadotrophic/luteinizing hormone receptor and follicle-stimulating hormone receptor. C1 Forsch Inst Mol Pharmacol, D-13125 Berlin, Germany. Univ Leipzig Klinikum, Dept Med 3, D-04103 Leipzig, Germany. NIDDK, NIH, CEB, Bethesda, MD 20892 USA. RP Krause, G (reprint author), Forsch Inst Mol Pharmacol, Robert Rossle Str 10, D-13125 Berlin, Germany. EM GKrause@FMP-Berlin.de NR 52 TC 52 Z9 52 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 3 PY 2004 VL 279 IS 49 BP 51590 EP 51600 DI 10.1074/jbc.M404748200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874MZ UT WOS:000225355800115 PM 15345720 ER PT J AU Geiszt, M Lekstrom, K Leto, TL AF Geiszt, M Lekstrom, K Leto, TL TI Analysis of mRNA transcripts from the NAD(P)H oxidase 1 (Nox1) gene - Evidence against production of the NADPH oxidase homolog-1 short (NOH-1S) transcript variant SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLON EPITHELIAL-CELLS; H+ CHANNEL; SUPEROXIDE; CLONING; PROTON; CONDUCTANCE; GP91-PHOX; COMPONENT; CYTOCHROME-B558; FLAVOPROTEIN AB Recent reports indicate that NAD(P) H oxidase 1 (Nox1) mRNA undergoes alternative splicing, producing a short transcript (NOH-1S) encoding a novel H+ channel. Although the H+ transport properties of NOH-1S-transfected cells resemble those of many cells, the production of a NOH-1S protein was never documented. We characterized Nox1 transcripts in colon-derived cells and present evidence that mRNA splicing does not produce NOH-1S; rather, NOH-1S appears to be an artifact of template switching during cDNA synthesis. The NOH-1S transcript was not observed by Northern blotting, despite claims of its abundance based on RNase protection assays. The shortened cDNA was generated by avian myeloblastosis virus reverse transcriptase, but not by thermally stable reverse transcriptase under conditions that produce full-length Nox1. Analysis of shortened cDNAs detected NOH-1S sequence and other variants that differ at the alleged splice junction site. Although no appropriate RNA splicing sites were found within Nox1 to account for NOH-1S formation, we found repetitive sequence elements bordering the deleted region, which could promote intramolecular template switching during cDNA synthesis. Template switching was confirmed in vitro, where the deleted cDNA was generated by avian myeloblastosis virus reverse transcriptase from a synthetic, full-length Nox1 RNA template. A survey of the expressed sequence tags database suggests that similar switching phenomena occur between repetitive elements in other Nox family transcripts, indicating such cloning artifacts are common. In contrast, genuine RNA splicing does account for another Nox1 transcript lacking the entire exon 11, which is abundant in colon cells but encodes a protein incapable of supporting superoxide production. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Dept Physiol, Fac Med, H-1444 Budapest, Hungary. RP Leto, TL (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike,Bldg 10,Rm 11N106, Bethesda, MD 20892 USA. EM tleto@nih.gov NR 36 TC 32 Z9 33 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 3 PY 2004 VL 279 IS 49 BP 51661 EP 51668 DI 10.1074/jbc.M409325200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874MZ UT WOS:000225355800122 PM 15375166 ER PT J AU Coppola, V Tessarollo, L AF Coppola, V Tessarollo, L TI Control of hyperphagia prevents obesity in BDNF heterozygous mice SO NEUROREPORT LA English DT Article DE brain derived neurotrophic factor; diet; females; glucose; hyperphagia; males; metabolism ID NEUROTROPHIC FACTOR; ENERGY-BALANCE; REGULATES GLUCOSE; DIABETIC MICE; METABOLISM; ABNORMALITIES; DEFICIENT AB Reduced levels of BDNF in mice cause obesity and behavioral abnormalities including increased aggression and hyperactivity. While it has been shown that the obesity is in part caused by increased food consumption it is still not clear whether defects in other mechanisms involved in the control of body weight homeostasis can also affect this phenotype. Here we report that mice with reduced levels of BDNF do not develop obesity and have normal blood glucose levels if fed over a prolonged period of time the amount of food that control mice usually consume. Thus, hyperphagia appears to be the primary cause of obesity development rather than changes in mechanisms controlling metabolism. C1 NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Tessarollo, L (reprint author), NCI, Neural Dev Grp, Mouse Canc Genet Program, 7th St,Bldg 560 Rm 32-31D,POB B, Frederick, MD 21702 USA. EM tessarol@ncifcrf.gov RI Coppola, Vincenzo/E-2917-2011 OI Coppola, Vincenzo/0000-0001-6163-1779 NR 14 TC 28 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 3 PY 2004 VL 15 IS 17 BP 2665 EP 2668 DI 10.1097/00001756-200412030-00022 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 884EX UT WOS:000226068600022 PM 15570174 ER PT J AU Lan, Q Zhang, LP Li, GL Vermeulen, R Weinberg, RS Dosemeci, M Rappaport, SM Shen, M Alter, BP Wu, YJ Kopp, W Waidyanatha, S Rabkin, C Guo, WH Chanock, S Hayes, RB Linet, M Kim, S Yin, SN Rothman, N Smith, MT AF Lan, Q Zhang, LP Li, GL Vermeulen, R Weinberg, RS Dosemeci, M Rappaport, SM Shen, M Alter, BP Wu, YJ Kopp, W Waidyanatha, S Rabkin, C Guo, WH Chanock, S Hayes, RB Linet, M Kim, S Yin, SN Rothman, N Smith, MT TI Hematotoxicity in workers exposed to low levels of benzene SO SCIENCE LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; TOXICITY; BLOOD; RISK; NQ01 AB Benzene is known to have toxic effects on the blood and bone marrow, but its impact at levels below the U.S. occupational standard of 1 part per million (ppm) remains uncertain. in a study of 250 workers exposed to benzene, white blood cell and platelet counts were significantly lower than in 140 controls, even for exposure below 1 ppm in air. Progenitor cell colony formation significantly declined with increasing benzene exposure and was more sensitive to the effects of benzene than was the number of mature blood cells. Two genetic variants in key metabolizing enzymes, myeloperoxidase and NAD(P)H:quinone oxidoreductase, influenced susceptibility to benzene hematotoxicity. Thus, hematotoxicity from exposure to benzene occurred at air levels of 1 ppm or less and may be particularly evident among genetically susceptible subpopulations. C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. New York Blood Ctr, Clin Serv, White Plains, NY 10605 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Peking Union Med Coll, Beijing, Peoples R China. SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Ctr Canc Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Smith, MT (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. EM martynts@berkeley.edu RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU NIEHS NIH HHS [P30ES01896, P30ES10126, P42 ES004705, P42ES04705, P42ES05948, R01ES06721] NR 21 TC 277 Z9 303 U1 5 U2 43 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 3 PY 2004 VL 306 IS 5702 BP 1774 EP 1776 DI 10.1126/science.1102443 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 878FA UT WOS:000225630800052 PM 15576619 ER PT J AU Zhou, DP Mattner, J Cantu, C Schrantz, N Yin, N Gao, Y Sagiv, Y Hudspeth, K Wu, YP Yamashita, T Teneberg, S Wang, DC Proia, RL Levery, SB Savage, PB Teyton, L Bendelac, A AF Zhou, DP Mattner, J Cantu, C Schrantz, N Yin, N Gao, Y Sagiv, Y Hudspeth, K Wu, YP Yamashita, T Teneberg, S Wang, DC Proia, RL Levery, SB Savage, PB Teyton, L Bendelac, A TI Lysosomal glycosphingolipid recognition by NKT cells SO SCIENCE LA English DT Article ID T-CELLS; MICE LACKING; ANTIGEN PRESENTATION; RECEPTOR; SPECIFICITY; LYMPHOCYTE; EXPRESSION; ACTIVATION; SYNTHASE; DEFECTS AB NKT Celts represent a distinct lineage of T cells that coexpress a conserved alphabeta T cell receptor (TCR) and natural killer (NK) receptors. Although the TCR of NKT cells is characteristically autoreactive to CD1d, a lipid-presenting molecule, endogenous ligands for these cells have not been identified. We show that a lysosomal glycosphingolipid of previously unknown function, isoglobotrihexosylceramide (iGb3), is recognized both by mouse and human NKT cells. Impaired generation of lysosomal iGb3 in mice lacking beta-hexosaminidase b results in severe NKT cell deficiency, suggesting that this lipid also mediates development of NKT cells in the mouse. We suggest that expression of iGb3 in peripheral tissues may be involved in controlling NKT cell responses to infections and malignancy and in autoimmunity. C1 Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Gothenburg, Inst Med Biochem, SE-40530 Gothenburg, Sweden. Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China. Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. RP Zhou, DP (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM dzhou@midway.uchicago.edu; abendela@bsd.uchicago.edu RI Yin, NIng/C-8991-2011; Proia, Richard/A-7908-2012; Zhou, Dapeng/D-3059-2014 OI Zhou, Dapeng/0000-0003-1347-3811 FU NCRR NIH HHS [P20RR16459]; NIAID NIH HHS [AI50847, AI053725, R01 AI38339] NR 32 TC 698 Z9 727 U1 3 U2 23 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 3 PY 2004 VL 306 IS 5702 BP 1786 EP 1789 DI 10.1126/science/1103440 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 878FA UT WOS:000225630800056 PM 15539565 ER PT J AU Pirsel, M Chovanec, M Dudas, A Kleibl, K Van Houten, B AF Pirsel, M Chovanec, M Dudas, A Kleibl, K Van Houten, B TI Fourth DNA repair workshop on DNA damage and repair: mechanisms and biological consequences Smolenice Castle, 2-5 May 2004 SO DNA REPAIR LA English DT Editorial Material ID SYNDROME GROUP-B; NUCLEOTIDE EXCISION-REPAIR; INTERSTRAND CROSS-LINKS; TRANSCRIPTION-COUPLED REPAIR; COCKAYNE-SYNDROME PATIENTS; HUMAN BLADDER-CARCINOMA; BASAL-CELL CARCINOMAS; IN-SITU HYBRIDIZATION; DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE C1 Canc Res Inst, Genet Mol Lab, Bratislava 83391 37, Slovakia. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Canc Res Inst, Genet Mol Lab, Vlarska 7, Bratislava 83391 37, Slovakia. EM miroslav.pirsel@savba.sk RI Pirsel, Miroslav/A-9996-2008 NR 90 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD DEC 2 PY 2004 VL 3 IS 12 BP 1639 EP 1659 DI 10.1016/j.dnarep.2004.07.007 PG 21 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 865ZA UT WOS:000224741500008 PM 16170865 ER PT J AU Friedberg, EC Hanaoka, F Tanaka, K Yasui, A Wilson, SH AF Friedberg, EC Hanaoka, F Tanaka, K Yasui, A Wilson, SH TI The 2nd US-Japan DNA Repair Meeting, Honolulu, Hawaii, June 4-8, 2004 SO DNA REPAIR LA English DT Editorial Material AB The 2nd US-Japan DNA Repair Meeting convened at the JW Marriott Ihilani Hotel, outside Honolulu, Hawaii, from June 4-8, 2004. In keeping with the tradition of US-Japan conferences the meeting was modest in size comprising 25 participants from each country. The program featured platform presentations from each participant, with lots of time devoted to discussion of groups of related talks. A novel feature of the meeting was the absence of formally designated and previously announced titles for sessions and talks, providing a level of informality that promoted relaxed interactions. Discussion was gratifyingly brisk and informative throughout and was considered to be a highlight of the meeting. All sessions were chaired by the program planners Errol Friedberg and Sam Wilson, who did not present formal talks. The following pages comprise summations of the talks presented, organized into primary topic themes. C1 Univ Texas, SW Med Ctr, Dept Pathol, Lab Mol Pathol, Dallas, TX 75390 USA. Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan. Tohoku Univ, Inst Genet Mol, Inst Dev Aging & Canc, Aoba Ku, Sendai, Miyagi 9808575, Japan. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Friedberg, EC (reprint author), Univ Texas, SW Med Ctr, Dept Pathol, Lab Mol Pathol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM friedberg.errol@pathology.swmed.edu NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 2 PY 2004 VL 3 IS 12 BP 1661 EP 1674 DI 10.1016/j.dnarep.2004.07.005 PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 865ZA UT WOS:000224741500009 ER PT J AU De Martino, G La Regina, G Coluccia, A Edler, MC Barbera, MC Brancale, A Wilcox, E Hamel, E Artico, M Silvestri, R AF De Martino, G La Regina, G Coluccia, A Edler, MC Barbera, MC Brancale, A Wilcox, E Hamel, E Artico, M Silvestri, R TI Arylthioindoles, potent inhibitors of tubulin polymerization SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIMITOTIC AGENTS; CANCER; COLCHICINE; ANALOGS; BINDING AB Several arylthioindoles had excellent activity as inhibitors both of tubulin polymerization and of the growth of MCF-7 human breast carcinoma cells. Methyl 3-[(3,4,5-trimethoxyphenyl)thio]-5-methoxy-1H-indole-2-carboxylate (21), the most potent derivative, showed IC50 = 2.0 muM, 1.6 times more active than colchicine and about as active as combretastatin A-4 (CSA4). Compound 21 inhibited the growth of the MCF-7 cells at IC50 = 13 nM. Colchicine and CSA4 had 13 nM and 17 nM IC50 values, respectively, with these cells. C1 Univ Roma La Sapienza, Dipartimento Studi Farmaceut, I-00185 Rome, Italy. Univ Wales Coll Cardiff, Welsh Sch Pharm, Cardiff CF10 3XF, S Glam, Wales. NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. RP Silvestri, R (reprint author), Univ Roma La Sapienza, Dipartimento Studi Farmaceut, Piazzale Aldo Moro 5, I-00185 Rome, Italy. EM romano.silvestri@uniroma1.it RI La Regina, Giuseppe/I-2161-2012; De Martino, Maria Gabriella/I-2357-2012; Brancale, Andrea/N-9445-2014; OI La Regina, Giuseppe/0000-0003-3252-1161; Brancale, Andrea/0000-0002-9728-3419; Silvestri, Romano/0000-0003-2489-0178; /0000-0002-7940-8206 NR 19 TC 120 Z9 120 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 2 PY 2004 VL 47 IS 25 BP 6120 EP 6123 DI 10.1021/jm049360d PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 875GX UT WOS:000225409400003 PM 15566282 ER PT J AU Cao, JJ Lever, JR Kopajtic, T Katz, JL Pham, AT Holmes, ML Justice, JB Newman, AH AF Cao, JJ Lever, JR Kopajtic, T Katz, JL Pham, AT Holmes, ML Justice, JB Newman, AH TI Novel azido and isothiocyanato analogues of [3-(4-phenylalkylpiperazin-1-yl)propyl]bis(4-fluorophenyl)amines as potential irreversible ligands for the dopamine transporter SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MONOAMINE TRANSPORTERS; PHOTOAFFINITY LIGANDS; RIMCAZOLE ANALOGS; COCAINE RECEPTOR; BINDING DOMAINS; PROBES; RADIOSYNTHESIS; DESIGN; LABELS; SITES AB Potential irreversible ligands were prepared, based on a series of 3-(1-piperazinyl)propyl-N,N-bis(4-fluorophenyl)amines, as molecular probes for the dopamine transporter (DAT). Both azido and isothiocyanato-substituted phenylalkyl analogues were synthesized and evaluated for displacement of [H-3]WIN 35 428 in rat caudate putamen tissue. All of the analogues showed moderate binding potencies at the DAT. The azido analogue, 16b, was radiolodinated and used to photolabel human DAT-transfected HEK 293 cell membranes. [I-125] 16b irreversibly labeled an similar to80 kDa band corresponding to the DAT detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This radioligand provides a novel addition to the growing arsenal of structurally diverse irreversible ligands that are being used to identify binding domains on the DAT Characterizing points of attachment of these irreversible probes to the DAT protein will ultimately help elucidate the three-dimensional arrangement of the transmembrane domains, identify individual binding sites of the DAT inhibitors, and direct future drug design. C1 Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Psychobiol Sect, Intramural Res Program, Baltimore, MD 21224 USA. Univ Missouri, Dept Radiol, Columbia, MO 65201 USA. Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA. Emory Univ, Dept Chem, Atlanta, GA 30322 USA. RP Newman, AH (reprint author), Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [DA015805, DA15175, DA11176] NR 35 TC 8 Z9 8 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 2 PY 2004 VL 47 IS 25 BP 6128 EP 6136 DI 10.1021/jm049670w PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 875GX UT WOS:000225409400005 PM 15566284 ER PT J AU Bonner, WM AF Bonner, WM TI Phenomena leading to cell survival values which deviate from linear-quadratic models SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE non-targeted effects; bystander effects; low-dose hypersensitivity ID DOSE HYPER-RADIOSENSITIVITY; POTENTIALLY LETHAL DAMAGE; IONIZING-RADIATION; GENOMIC INSTABILITY; ATAXIA TELANGIECTASIA; BYSTANDER RESPONSE; ADAPTIVE RESPONSE; HUMAN-FIBROBLASTS; G(2)-PHASE CELLS; TISSUE-CULTURE AB For several decades, the prevailing paradigm for modeling the effects of ionizing radiation (IR) on living systems was the target model with its inherent assumptions-that only those cells in the radiation path whose molecules sustained collisions with high energy particles and rays were damaged, that the damage was proportional to the energy absorbed by each cell and to the number of cells absorbing energy, and that all cells had identical sensitivities to radiation. However, evidence has accumulated that cells exhibit phenomena at low radiation exposures that appear to contradict at least one of these assumptions. Some of these phenomena currently under active study include low-dose hypersensitivity (HRS), increased radiation radioresistance (IRR), the adaptive response (AR), the bystander effect (BE), and death-inducing factor (DIE). These effects may interact to give rise to other phenomena such as hormesis, in which small amounts of otherwise toxic agent appear to be beneficial. Elucidating the cellular and molecular bases for these phenomena will lead to greater understanding of the relationships of these processes, including hormesis, to human health. (C) 2004 Published by Elsevier B.V. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bonner, WM (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37 Rm 5050A MSC 4255, Bethesda, MD 20892 USA. EM bonnerw@mail.nih.gov NR 30 TC 26 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 2 PY 2004 VL 568 IS 1 BP 33 EP 39 DI 10.1016/j.mrfmmm.2004.06.044 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 873VO UT WOS:000225309600005 PM 15530537 ER PT J AU Emerson, SU Purcell, RH AF Emerson, SU Purcell, RH TI Global health - Running like water - The omnipresence of hepatitis E SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIAID, Mol Hepatitis Sect, NIH, Bethesda, MD 20892 USA. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 55 Z9 57 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 2 PY 2004 VL 351 IS 23 BP 2367 EP 2368 DI 10.1056/NEJMp048285 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 875OC UT WOS:000225429000003 PM 15575050 ER PT J AU Fenton, W James, R Insel, T AF Fenton, W James, R Insel, T TI Psychiatry residency training, the physician-scientist, and the future of psychiatry SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Fenton, W (reprint author), NIMH, Div Adult Translat Res & Treatment Dev, 6001 Execut Blvd,Room 6216,MSC 9621, Bethesda, MD 20892 USA. EM wfenton@mail.nih.gov NR 7 TC 18 Z9 19 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD WIN PY 2004 VL 28 IS 4 BP 263 EP 266 DI 10.1176/appi.ap.28.4.263 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 885RU UT WOS:000226175400002 PM 15673819 ER PT J AU Sen, HN Chan, CC Nussenblatt, RB Buggage, RR AF Sen, HN Chan, CC Nussenblatt, RB Buggage, RR TI Occult primary carcinoma metastatic to the iris SO ACTA OPHTHALMOLOGICA SCANDINAVICA LA English DT Article DE occult carcinoma; iris; metastasis C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sen, HN (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA. EM senh@nei.nih.gov NR 3 TC 4 Z9 5 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1395-3907 J9 ACTA OPHTHALMOL SCAN JI Acta Ophthalmol. Scand. PD DEC PY 2004 VL 82 IS 6 BP 746 EP 747 DI 10.1111/j.1600-0420.2004.00273.x PG 2 WC Ophthalmology SC Ophthalmology GA 884NT UT WOS:000226093000020 PM 15606475 ER PT J AU Grant, S AF Grant, S TI Let's not be impulsive: Comments on Lubman et al. (2004) SO ADDICTION LA English DT Editorial Material ID ORBITOFRONTAL CORTEX C1 NIDA, Clin Neurobiol Branch, Div Clin Neurobiol Dev & Treatment Res, NIH,HHS, Bethesda, MD 20892 USA. RP Grant, S (reprint author), NIDA, Clin Neurobiol Branch, Div Clin Neurobiol Dev & Treatment Res, NIH,HHS, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM sgrant@nida.nih.gov NR 5 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 2004 VL 99 IS 12 BP 1504 EP 1505 DI 10.1111/j.1360-0443.2004.00895.x PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 880LJ UT WOS:000225791000006 PM 15585040 ER PT J AU Miura, T Mattson, MP Rao, MS AF Miura, T Mattson, MP Rao, MS TI Cellular lifespan and senescence signaling in embryonic stem cells SO AGING CELL LA English DT Review DE aging; Akt signaling; cell cycle; ES cells; p53; Rb; senescence; telomerase; telomere ID REVERSE-TRANSCRIPTASE GENE; CATALYTIC SUBUNIT HTERT; HUMAN ENDOTHELIAL-CELLS; TUMOR-SUPPRESSOR P53; GROWTH-FACTOR-I; HUMAN-TELOMERASE; CANCER-CELLS; C-MYC; REPLICATIVE SENESCENCE; CAENORHABDITIS-ELEGANS AB Most mammalian cells when placed in culture will undergo a limited number of cell divisions before entering an unresponsive non-proliferating state termed senescence. However, several pathways that are activated singly or in concert can allow cells to bypass senescence at least for limited periods. These include the telomerase pathway required to maintain telomere ends, the p53 and Rb pathways required to direct senescence in response to DNA damage, telomere shortening and mitogenic signals, and the insulin-like growth factor - Akt pathway that may regulate lifespan and cell proliferation. In this review, we summarize recent findings related to these pathways in embryonic stem (ES) cells and suggest that ES cells are immortal because these pathways are tightly regulated. C1 NIA, Gerontol Res Ctr, Stem Cell Biol Unit, Neurosci Lab, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Cellular & Mol Neurosci Sect, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Rao, MS (reprint author), NIA, Gerontol Res Ctr, Stem Cell Biol Unit, Neurosci Lab, 5600 Nathan Shock Dr,Room 4E01, Baltimore, MD 21224 USA. EM raomah@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 125 TC 61 Z9 67 U1 0 U2 4 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD DEC PY 2004 VL 3 IS 6 BP 333 EP 343 DI 10.1111/j.1474-9728.2004.00134.x PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 878DL UT WOS:000225626600002 PM 15569350 ER PT J AU Santos, JH Meyer, JN Skorvaga, M Annab, LA Van Houten, B AF Santos, JH Meyer, JN Skorvaga, M Annab, LA Van Houten, B TI Mitochondrial hTERT exacerbates free-radical-mediated mtDNA damage SO AGING CELL LA English DT Article DE aging; DNA repair; hTERT; human mitochondria; mitochondrial DNA; oxidative DNA damage; telomerase ID NORMAL HUMAN-CELLS; TELOMERASE REVERSE-TRANSCRIPTASE; DNA-DAMAGE; HUMAN FIBROBLASTS; INDUCED APOPTOSIS; OXIDATIVE DAMAGE; NUCLEAR EXPORT; LIFE-SPAN; CANCER; MECHANISM AB Telomerase is often re-activated in human cancers and is widely used to immortalize cells in culture. in addition to the maintenance of telomeres, telomerase has been implicated in cell proliferation, genomic instability and apoptosis. Here we show that human telomerase reverse transcriptase (hTERT) is targeted to the mitochondria by an N-terminal leader sequence, and that mitochondrial extracts contain telomerase activity. In seven different human cell lines, mitochondrial telomerase increases hydrogen-peroxide-mediated mitochondrial DNA damage. hTERT expression did not alter the rate of hydrogen peroxide breakdown or endogenous cellular levels. Because the damaging effects of hydrogen peroxide are mediated by divalent metal ions (Fenton chemistry), we examined the levels of bioavailable metals. in all cases, higher levels of chelatable metals were found in hTERT-expressing cells. These results suggest that mitochondrial telomerase sensitizes cells to oxidative stress, which can lead to apoptotic cell death, and imply a novel function of telomerase in mitochondrial DNA transactions. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, NIH, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Slovak Acad Sci, Canc Res Inst, Mol Carcinogenesis Lab, Bratislava 83391, Slovakia. RP Van Houten, B (reprint author), NIEHS, Mol Genet Lab, NIH, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM vanhout1@niehs.nih.gov NR 55 TC 113 Z9 123 U1 1 U2 13 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD DEC PY 2004 VL 3 IS 6 BP 399 EP 411 DI 10.1111/j.1474-9728.2004.00124.x PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 878DL UT WOS:000225626600009 PM 15569357 ER PT J AU Smith, JM Amara, RR Campbell, D Xu, Y Patel, M Sharma, S Butera, ST Ellenberger, DL Yi, H Chennareddi, L Herndon, JG Wyatt, LS Montefiori, D Moss, B McClure, HM Robinson, HL AF Smith, JM Amara, RR Campbell, D Xu, Y Patel, M Sharma, S Butera, ST Ellenberger, DL Yi, H Chennareddi, L Herndon, JG Wyatt, LS Montefiori, D Moss, B McClure, HM Robinson, HL TI DNA/MVA vaccine for HIV type 1: Effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; IMMUNE-RESPONSES; AIDS VACCINE; CELL DIFFERENTIATION; MUCOSAL CHALLENGE; MAMMALIAN-CELLS; RHESUS-MONKEYS; VIRAL ESCAPE; MEMORY; PROTECTION AB Recently, a vaccine consisting of DNA priming followed by boosting with modified vaccinia Ankara (MVA) has provided long-term protection of rhesus macaques against a virulent challenge with a chimera of simian and human immunodeficiency viruses. Here, we report studies on the development of the DNA component for a DNA/MVA HIV vaccine for humans. Specifically, we assess the ability of a codon-optimized Gag-expressing DNA and two noncodon-optimized Gag - Pol - Env-expressing DNAs to prime the MVA booster dose. The codon-optimized DNA expressed virus-like particles (VLPs), whereas one of the noncodon-optimized DNAs expressed VLPs and the other expressed aggregates of HIV proteins. The MVA boost expressed Gag - Pol and Env and produced VLPs. Immunogenicity studies in macaques used one intramuscular prime with 600 mug of DNA and two intramuscular boosts with 1 x 10(8) pfu of MVA at weeks 8 and 30. The codon-optimized and noncodon-optimized DNAs proved similar in their ability to prime anti-Gag T cell responses. The aggregate and VLP-expressing Gag - Pol - Env DNAs also showed no significant differences in their ability to prime anti-Env Ab responses. The second MVA booster dose did not increase the peak CD4 and CD8 T cell responses, but increased anti-Env Ab titers by 40- to 90-fold. MVA-only immunizations elicited 10 - 100 times lower frequencies of T cells and 2 - 4 lower titers of anti-Env Ab than the Gag - Pol - Env DNA/MVA immunizations. Based on the breadth of the T cell response and a trend toward higher titers of anti-Env Ab, we are moving forward with human trials of the noncodon-optimized VLP-expressing DNA. C1 Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30329 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30329 USA. Ctr Dis Control & Prevent, HIV & Retrovirol Branch, Atlanta, GA 30333 USA. Emory Univ, Sch Med, Electron Microscope Core, Atlanta, GA 30329 USA. NIAID, Viral Dis Lab, Bethesda, MD USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30329 USA. RP Robinson, HL (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd,Box 129, Atlanta, GA 30329 USA. EM hrobins@rmy.emory.edu FU NCRR NIH HHS [RR-00165]; NIAID NIH HHS [P01 AI49364]; NIDA NIH HHS [P30 DA 12121] NR 30 TC 41 Z9 41 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 2004 VL 20 IS 12 BP 1335 EP 1347 DI 10.1089/aid.2004.20.1335 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 883XN UT WOS:000226049200008 PM 15650426 ER PT J AU Fox, E Harkins, D Taylor, H McMullan, M Han, H Samdarshi, T Garrison, R Skelton, T AF Fox, E Harkins, D Taylor, H McMullan, M Han, H Samdarshi, T Garrison, R Skelton, T TI Epidemiology of mitral annular calcification and its predictive value for coronary events in African Americans: The Jackson Cohort of the Atherosclerotic Risk in Communities study SO AMERICAN HEART JOURNAL LA English DT Article ID ANULAR CALCIUM; DISEASE; VALVE; INTERRELATIONSHIP; ECHOCARDIOGRAPHY; ASSOCIATION; PREVALENCE; SEVERITY; FAILURE; HEART AB Background Despite the potential link between mitral annular calcification (MAC) and atherosclerosis, there is limited data regarding the prevalence of MAC in African Americans and its relationship with coronary hear. disease (CHD) events in this high-risk population., Methods The study population included 2409 African American participants of the Artherosclerotic Risk in Communities study (ARIC) undergoing echo examinations between 1993-1996. The primary outcome was incident CHD events, [defined as fatal coronary event, hospitalized myocardial infarction or cardiac procedure]. MAC was considered a binary variable (yes/no). The Cox proportional hazard model was used for the analysis and the model was adjusted for gender, age, body mass index, hypertension, diabetes, smoking status, renal function (based on serum creatinine), high LDL and low HDL. Results Of. the 2409 in the study population, 1549 (64%) were women and the mean age was 59.2 +/- 5.8 years (range 49-75). MAC was positively associated with age and renal function. The overall prevalence of MAC was 4.6% for women and 5.6% for men. In participants aged greater than or equal to70, the prevalence of MAC was 10% in women and 15.2% in men. During a median follow-up of 4.8 years, there were 237 total incident CHD events recorded. After adjustment, the hazard ratio for CHID events among the MAC subgroup was 2.32 (95% Cl, 1.11-4.87). Conclusions In this relatively young population of middle-aged African Americans, the prevalence of MAC is low;. however, the presence of MAC incurs a significant risk for coronary events. C1 Univ Mississippi, Med Ctr, Div Cardiovasc Dis, Dept Med, Jackson, MS 39216 USA. Natl Heart Lung & Blood Inst Jacksons Heart Study, Jackson, MS USA. RP Fox, E (reprint author), Univ Mississippi, Med Ctr, Div Cardiovasc Dis, Dept Med, 2500 N State St, Jackson, MS 39216 USA. EM efox@medicine.umsmed.edu FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55022, N01-HC-55018, N01-HC-55016, N01-HC-55020, N01-HC-55019, N01-HC-55021] NR 27 TC 27 Z9 29 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2004 VL 148 IS 6 BP 979 EP 984 DI 10.1016/j.ahj.2004.05.048 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 882WF UT WOS:000225970400010 PM 15632881 ER PT J AU Cooper, HA Domanski, MJ Rosenberg, Y Norman, J Scott, JH Assmann, SF McKinlay, SM Hochman, JS Antman, EM AF Cooper, HA Domanski, MJ Rosenberg, Y Norman, J Scott, JH Assmann, SF McKinlay, SM Hochman, JS Antman, EM CA MAGIC Trial Investigators TI Acute ST-segment elevation myocardial infarction and prior stroke: An analysis from the Magnesium in Coronaries (MAGIC) trial SO AMERICAN HEART JOURNAL LA English DT Article ID CEREBROVASCULAR-DISEASE; THROMBOLYTIC THERAPY; ARTERY-DISEASE; PREDICTORS; MORTALITY; EVENTS; ERA AB Background Patients with prior stroke represent a substantial proportion of patients presenting with acute ST-segment elevation myocardial infarction (STEMI). However, the impact of prior stroke on prognosis has not been rigorously examined in the reperfusion era. Methods The baseline characteristics, treatments, and clinical outcomes of patients with prior stroke enrolled in the Magnesium in Coronaries (MAGIC) trial were evaluated and compared to those of patients without prior stroke. Results MAGIC enrolled 6213 patients with STEMI, of whom 558 (9.0%) had prior stroke. Patients with prior stroke were more likely to have a history of hypertension (88.0% vs 70.3%), diabetes (19.9% vs 14.5%), myocardial infarction (38.2% vs 25.1%), and congestive heart failure (15.6% vs 9.7%). The mean Thrombolysis in Myocardial Infarction Risk Score was higher in patients with prior stroke compared to those without prior stroke (4.37 vs 3.93, P<.0001). Patients with prior stroke were less likely to receive reperfusion therapy, even among those considered eligible at presentation (66.3% vs 80.6%, P<.0001). Compared to patients without prior stroke, inhospital stroke (3.0% vs 1.0%, P<.0001), severe congestive heart failure (23.3% vs 18.2%, P=.003), and 30-day mortality (21.0% vs 14.7%, P<.0001) were higher among patients with prior stroke. On multivariable analysis, prior stroke was independently associated with a significantly higher risk of death at 30 days (odds ratio 1.44, P=.0023). Conclusions Patients with prior stroke who present with STEMI are at very high risk for short-term morbidity and mortality. Aggressive treatment of these patients appears warranted. C1 Washington Hosp Ctr, Washington, DC 20010 USA. NHLBI, Bethesda, MD 20892 USA. New England Res Inst, Watertown, MA 02172 USA. NYU, Med Ctr, New York, NY 10016 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Cooper, HA (reprint author), Washington Hosp Ctr, 110 Irving St NW,Suite NA1103, Washington, DC 20010 USA. EM howord.a.cooper@medstar.net OI Hochman, Judith/0000-0002-5889-5981 FU PHS HHS [N01-8C-85155] NR 16 TC 8 Z9 9 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2004 VL 148 IS 6 BP 1012 EP 1019 DI 10.1016/j.ahj.2004.02.017 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 882WF UT WOS:000225970400016 PM 15632887 ER PT J AU Raiten, DJ Picciano, MF AF Raiten, DJ Picciano, MF TI Vitamin D and health in the 21st century: bone and beyond. Executive summary SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Conference on Vitamin D and Health in the 21st Century CY OCT 09-10, 2003 CL Bethesda, MD SP NCI, NIH, DHHS, US Ctr Dis Control & Prevent, USDA Agr Res Serv, NIAMS, DNRC, NIDDK, ORWH, Coca Cola N Amer, Natl Dairy Council DE vitamin D; National Institutes of Health conference ID NUTRITIONAL RICKETS; AFRICAN-AMERICAN AB Vitamin D is unique, in terms of its metabolism and physiologic features and the human reliance on both endogenous production (activation through exposure to ultraviolet light) and exogenous sources (diet, primarily fortified foods) to meet biological requirements. Recent evidence has indicated a reemergence of vitamin D-deficient rickets and an alarming prevalence of vitamin D insufficiency (ie, low circulating concentrations of 25-hydroxyvitamin D) in particular segments of the US population. Furthermore, evidence has emerged implicating vitamin D status in a range of adverse health conditions, including cancer and certain autoimmune diseases. Therefore, a conference organized by the National Institute of Child Health and Human Development and the National Institutes of Health Office of Dietary Supplements was held to explore current knowledge and to develop a research agenda to address the range of issues associated with vitamin D and health during the life cycle. These proceedings contain presentations about 1) existing data on vitamin D status in the United States and internationally, 2) the current state of knowledge regarding the biological functions of vitamin D, 3) the strength of evidence supporting reconsideration of current policies regarding vitamin D intake, 4) gaps in understanding of the factors affecting and current options for improving vitamin D status in the United States and internationally, and 5) research needs to address gaps in knowledge regarding vitamin D assessment, biological features, and requirements. This executive summary provides an overview of the conference and its conclusions. C1 NICHD, Office Prevent Res & Int Programs, Endocrinol Nutr & Growth Branch, Ctr Res Mothers & Children,NIH,DHHS, Rockville, MD 20852 USA. NIH Office Dietry Supplements, Rockville, MD 20852 USA. RP Raiten, DJ (reprint author), NICHD, Office Prevent Res & Int Programs, Endocrinol Nutr & Growth Branch, Ctr Res Mothers & Children,NIH,DHHS, 6100 Executive Blvd,Room 2A01, Rockville, MD 20852 USA. EM raitend@mail.nih.gov NR 20 TC 53 Z9 54 U1 1 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2004 VL 80 IS 6 SU S BP 1673S EP 1677S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 879ID UT WOS:000225708700001 PM 15585787 ER PT J AU Shaw, PA Etzioni, R Zeliadt, SB Mariotto, A Karnofski, K Penson, DF Weiss, NS Feuer, EJ AF Shaw, PA Etzioni, R Zeliadt, SB Mariotto, A Karnofski, K Penson, DF Weiss, NS Feuer, EJ TI An ecologic study of prostate-specific antigen screening and prostate cancer mortality in nine geographic areas of the United States SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE computer simulation; confounding factors (epidemiology); mass screening; mortality; prostate-specific antigen; prostatic neoplasms ID SURVEILLANCE SERIES; INTERPRETING TRENDS; WHITE MEN; DEATH; PATTERNS; SURVIVAL; THERAPY; DECLINE; KINGDOM; IMPACT AB Ecologic studies of cancer screening examine cancer mortality rates in relation to use of population screening. These studies can be confounded by treatment patterns or influenced by choice of outcome and time horizon. Interpretation can be complicated by uncertainty about when mortality differences might be expected. The authors examined these issues in an ecologic analysis of prostate-specific antigen (PSA) screening and prostate cancer mortality across nine cancer registries in the United States. Results suggested a weak trend for areas with greater PSA screening rates to have greater declines in prostate cancer mortality; however, the magnitude of this trend varied considerably with the time horizon and outcome measure. A computer model was used to determine whether divergence of mortality declines would be expected under an assumption of a clinically significant survival benefit due to screening. Given a mean lead time of 5 years, the model projected that differences in mortality between high- and low-use areas should be apparent by 1999 in the absence of other factors affecting mortality. The authors concluded that modest differences in PSA screening rates across areas, together with additional sources of variation, could have produced a negative ecologic result. Ecologic analyses of the effectiveness of PSA testing should be interpreted with caution. C1 Fred Hutchinson Canc Res Ctr, Program Biostat, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. NCI, Stat Res & Applicat Branch, Div Canc Control & Pupulat Sci, Bethesda, MD 20892 USA. Univ So Calif, Norris Canc Ctr, Keck Sch Med, Los Angeles, CA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. RP Etzioni, R (reprint author), Fred Hutchinson Canc Res Ctr, Program Biostat, 1100 Fairview Ave N,M2-B230, Seattle, WA 98109 USA. EM retzioni@fhcrc.org FU NCI NIH HHS [CA88160, CA92408] NR 37 TC 31 Z9 31 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2004 VL 160 IS 11 BP 1059 EP 1069 DI 10.1093/aje/kwh336 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 874PC UT WOS:000225361300004 PM 15561985 ER PT J AU Rossing, MA Tang, MTC Flagg, EW Weiss, LK Wicklund, KG AF Rossing, MA Tang, MTC Flagg, EW Weiss, LK Wicklund, KG TI A case-control study of ovarian cancer in relation to infertility and the use of ovulation-inducing drugs SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE infertility; ovarian neoplasms ID STATES CASE-CONTROL; COLLABORATIVE ANALYSIS; FERTILITY DRUGS; WHITE WOMEN; RISK; COHORT; TUMORS AB The authors conducted a population-based, case-control study among women aged 35-54 years to assess the influence of infertility and use of ovulation-inducing drugs on ovarian cancer risk. The study was conducted from 1994 to 1998 in three regions (metropolitan Atlanta, Georgia, Detroit, Michigan, and Seattle, Washington) and included 378 cases and 1,637 controls. Data were obtained through in-person interviews, and analysis was conducted using unconditional logistic regression. Among parous women, the authors observed no association of cancer risk with a history of infertility, medical evaluation for infertility, specific types of infertility, or use of ovulation-inducing drugs. Among nulliparous women, risk was increased among women with a history of infertility (odds ratio = 1.6, 95% confidence interval: 1.0, 2.6), particularly when infertility first became manifest relatively late in reproductive life (for first infertility at greater than or equal to30 years of age: odds ratio = 2.2, 95% confidence interval: 1.1, 4.5); risk was not associated with medical evaluation for infertility, specific types of infertility, or use of ovulation-inducing drugs. Findings were similar when borderline and invasive epithelial tumors were considered separately. While the results of this study support the hypothesis that a subset of nulliparous women who experience infertility may be at increased risk of ovarian cancer, the reasons for this increase in risk remain unclear. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Emory Univ, Sch Med, Div Gen Med, Atlanta, GA USA. NCI, Bethesda, MD 20892 USA. RP Rossing, MA (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1100 Fairview Ave N,POB 19024,MP-381, Seattle, WA 98109 USA. EM mrossing@fhcrc.org NR 19 TC 55 Z9 59 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2004 VL 160 IS 11 BP 1070 EP 1078 DI 10.1093/aje/kwh315 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 874PC UT WOS:000225361300005 PM 15561986 ER PT J AU Baumgartner, KB Hunt, WC Baumgartner, RN Crumley, DD Gilliland, FD McTiernan, A Bernstein, L Ballard-Barbash, R AF Baumgartner, KB Hunt, WC Baumgartner, RN Crumley, DD Gilliland, FD McTiernan, A Bernstein, L Ballard-Barbash, R TI Association of body composition and weight history with breast cancer prognostic markers: Divergent pattern for hispanic and non-hispanic white women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE anthropometry; biological markers; body composition; body constitution; breast neoplasms; Hispanic Americans; prognosis ID POSTMENOPAUSAL WOMEN; FAT DISTRIBUTION; UNITED-STATES; RACIAL/ETHNIC GROUPS; ESTROGEN-RECEPTOR; RELATIVE WEIGHT; SEX-HORMONES; MASS-INDEX; SURVIVAL; OBESITY AB Body composition and weight gain are breast cancer risk factors that may influence prognosis. The Health, Eating, Activity, and Lifestyle Study was designed to evaluate the relations of body composition, weight history, hormones, and lifestyle factors to prognosis for women with breast cancer. In the cross-sectional analysis of this cohort study specific to 150 Hispanic and 466 non-Hispanic White women in New Mexico diagnosed between 1996 and 1999, the authors hypothesized that obesity measures are associated with baseline prognostic markers and that these associations are modified by ethnicity. Ethnic-stratified multiple logistic regression analyses showed divergent results for a tumor size of 1.0 cm or more and, to a lesser extent, positive lymph node status. Among Hispanics, the highest quartile for body mass index (29.5 vs. <22.5 kg/m(2): odds ratio (OR) = 0.16, 95% confidence interval (CI): 0.03, 0.84) and for waist circumference (greater than or equal to95.0 vs. <78.5 cm: OR = 0.09, 95% CI: 0.01, 0.78) was significantly associated with a reduced tumor size. In contrast, for overweight and obese non-Hispanic White women, there was an increased association with obesity-related measures, particularly striking for the highest quartile of waist circumference (OR = 2.76, 95% CI: 1.45, 5.26). These findings suggest that Hispanics may have a different breast cancer phenotype than non-Hispanic Whites, which associates differently with body composition and weight history. C1 Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Div Epidemiol, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Canc Res & Treatment Ctr, Epidemiol & Canc Prevent Program, Albuquerque, NM 87131 USA. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. RP Baumgartner, KB (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Div Epidemiol, Canc Res Facil,G-18,2325 Camino Salud NE, Albuquerque, NM 87131 USA. EM kbaum@nmtr.unm.edu FU NCI NIH HHS [N01-CN-75036-20] NR 54 TC 27 Z9 27 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2004 VL 160 IS 11 BP 1087 EP 1097 DI 10.1093/aje/kwh313 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 874PC UT WOS:000225361300007 PM 15561988 ER PT J AU Harnack, L Himes, JH Anliker, J Clay, T Gittelsohn, J Jobe, JB Ring, K Snyder, P Thompson, J Weber, JL AF Harnack, L Himes, JH Anliker, J Clay, T Gittelsohn, J Jobe, JB Ring, K Snyder, P Thompson, J Weber, JL TI Intervention-related bias in reporting of food intake by fifth-grade children participating in an obesity prevention study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bias (epidemiology); intervention studies; nutrition assessment ID AMERICAN-INDIAN SCHOOLCHILDREN; PATHWAYS; PROGRAM; TRIAL AB Data collected as part of Pathways, a school-based trial for the primary prevention of obesity in American Indian children conducted between 1997 and 2000, were analyzed to examine possible intervention-related bias in food reporting. The authors hypothesized that children in the intervention schools may have systematically underreported their dietary intake relative to children in the control schools. Nutrient intake estimates for lunch derived from record-assisted 24-hour dietary recalls were compared with intake estimates from observed lunch intakes. Reported nutrient intakes were included in regression analyses as the dependent variables; observed intake, intervention condition, and age were included as independent variables. Results indicated that, among females, intervention condition was a significant predictor of reported energy, fat, and saturated fatty acid intakes. Independently of observed intake, reported lunch energy intake among females in the intervention schools was 66.8 calories lower than reported intake among females in the control schools (p = 0.03). These findings suggest that investigators should consider bias in reporting of dietary intake by intervention condition when conducting diet-focused intervention studies. Specifically, enhancing measures that rely on self-reports with objective measures of dietary intake would help investigators to evaluate whether differential reporting by treatment group has occurred. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Nutr, Amherst, MA 01003 USA. Univ New Mexico, Hlth Sci Ctr, Prevent Res Ctr, Albuquerque, NM 87131 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. Univ New Mexico, Hlth Sci Ctr, Off Native Amer Diabet Programs, Albuquerque, NM 87131 USA. Univ Arkansas Med Sci, Dept Pediat, Ctr Appl Res & Evaluat, Little Rock, AR 72205 USA. RP Harnack, L (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM harnack@epi.umn.edu NR 17 TC 16 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2004 VL 160 IS 11 BP 1117 EP 1121 DI 10.1093/aje/kwh328 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 874PC UT WOS:000225361300010 PM 15561991 ER PT J AU Arcos-Burgos, M Castellanos, FX Pineda, D Lopera, F Palacio, JD Palacio, LG Rapoport, JL Berg, K Bailey-Wilson, JE Muenke, M AF Arcos-Burgos, M Castellanos, FX Pineda, D Lopera, F Palacio, JD Palacio, LG Rapoport, JL Berg, K Bailey-Wilson, JE Muenke, M TI Attention-deficit/hyperactivity disorder in a population isolate: Linkage to loci at 4q13.2, 5q33.3, 11q22, and 17p11 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; FAMILY-BASED ASSOCIATION; PEDIGREE DISEQUILIBRIUM TEST; SEGREGATION ANALYSIS; BIPOLAR DISORDER; COMPLEX TRAITS; GENERAL-CLASS; ANTIOQUIA COLOMBIA; GENETIC-ANALYSIS; GENOMEWIDE SCAN AB Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is the most common behavioral disorder of childhood. Twin, adoption, segregation, association, and linkage studies have confirmed that genetics plays a major role in conferring susceptibility to ADHD. We applied model-based and model-free linkage analyses, as well as the pedigree disequilibrium test, to the results of a genomewide scan of extended and multigenerational families with ADHD from a genetic isolate. In these families, ADHD is highly comorbid with conduct and oppositional defiant disorders, as well as with alcohol and tobacco dependence. We found evidence of linkage to markers at chromosomes 4q13.2, 5q33.3, 8q11.23, 11q22, and 17p11 in individual families. Fine mapping applied to these regions resulted in significant linkage in the combined families at chromosomes 4q13.2 (two-point allele-sharing LOD score from LODPAL = 4.44 at D4S3248), 5q33.3 (two-point allele-sharing LOD score from LODPAL = 8.22 at D5S490), 11q22 (two-point allele-sharing LOD score from LODPAL = 5.77 at D11S1998; multipoint nonparametric linkage [NPL] - log [P value] = 5.49 at similar to128 cM), and 17p11 (multipoint NPL - log [P value] >12 at similar to12 cM; multipoint maximum location score 2.48 [alpha = 0.10] at similar to12 cM; two-point allele-sharing LOD score from LODPAL = 3.73 at D17S1159). Additionally, suggestive linkage was found at chromosome 8q11.23 (combined two-point NPL - log [P value] >3.0 at D8S2332). Several of these regions are novel (4q13.2, 5q33.3, and 8q11.23), whereas others replicate already-published loci (11q22 and 17p11). The concordance between results from different analytical methods of linkage and the replication of data between two independent studies suggest that these loci truly harbor ADHD susceptibility genes. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Antioquia, Populat Genet Mutacarcinogenesis & Genet Epidemio, Medellin, Colombia. Univ Antioquia, Neurosci Grp, Medellin, Colombia. NYU, Ctr Child Study, New York, NY USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920; Palacio, Juan David/0000-0002-1584-4391 NR 61 TC 126 Z9 135 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2004 VL 75 IS 6 BP 998 EP 1014 DI 10.1086/426154 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 867TW UT WOS:000224866400006 PM 15497111 ER PT J AU Morgan, DL Su, YF Dill, JA Turnier, JC Westerberg, RB Smith, CS AF Morgan, DL Su, YF Dill, JA Turnier, JC Westerberg, RB Smith, CS TI Chemical and physical characteristics of cellulose insulation particulates, and evaluation of potential acute pulmonary toxicity SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE cellulose insulation; chemical composition; particulates; fibers; instillation; rats; respiratory toxicity ID BORIC-ACID; DEVELOPMENTAL TOXICITY; RATS; WORKERS; BORON; DUST; MICE AB Background During installation of cellulose insulation (CI) in new and older houses, significant quantities of airborne material are generated. This study characterized the chemical and physical properties, and potential acute pulmonary toxicity of CI. Methods CI from four manufacturers was analyzed for inorganic additives and trace element impurities. Aerosols were generated and size fractionated. The number and size of fibrous and nonfibrous particles in the respirable fractions were determined. Respirable CI particulates were intratracheally instilled in rats (5 mg/kg) to evaluate potential pulmonary toxicity. Results CI samples were similar in composition with small differences due primarily to fire retardants. Less than 0.1% of CI was respirable and contained few fibers. Acute exposure to CI caused transient inflammation in the lungs and increased 4-hydroxyproline. Microscopic evaluation revealed a minimal to mild, non-progressing granulomatous pneumonitis. Conclusions Low concentrations of respirable particles were found in CI aerosols. Particles consisted primarily of fire retardants with few fibers, and caused mild pulmonary toxicity in rats. Published 2004 Wiley-Liss, Inc.(dagger) C1 Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Pacific NW Lab, Richland, WA USA. Pathol Associates Inc, Res Triangle Pk, NC USA. RP Morgan, DL (reprint author), Natl Inst Environm Hlth Sci, Mol Toxicol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM morgand@niehs.nih.gov NR 27 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 2004 VL 46 IS 6 BP 554 EP 569 DI 10.1002/ajim.20101 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 876XS UT WOS:000225532700002 PM 15551371 ER PT J AU Walker, LC Overstreet, MA Willing, MC Marini, JC Cabral, WA Pals, G Bristow, J Atsawasuwan, P Yamauchi, M Yeowell, HN AF Walker, LC Overstreet, MA Willing, MC Marini, JC Cabral, WA Pals, G Bristow, J Atsawasuwan, P Yamauchi, M Yeowell, HN TI Heterogeneous basis of the type VIB form of Ehlers-Danlos syndrome (EDS VIB) that is unrelated to decreased collagen lysyl hydroxylation SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 15-18, 2002 CL LOS ANGELES, CA SP Soc Investigat Dermatol DE skin fibroblasts; Ehlers-Danlos type VIB; lysyl hydroxylase isoforms; collagen cross-linking; genetic heterogeneity ID HUMAN-SKIN FIBROBLASTS; HYDROXYLYSINE-DEFICIENT COLLAGEN; CROSS-LINKING; I COLLAGEN; LYSINE HYDROXYLATION; MOLECULAR PACKING; MESSENGER-RNAS; ASCORBIC-ACID; GENE PLOD; CLONING AB Skin fibroblasts from the majority of patients with the clinical diagnosis of Ehlers-Danlos syndrome type VI (EDS VI; kyphoscoliosis type), have significantly decreased lysyl hydroxylase (LH) activity due to mutations in the LH1 gene (classified as EDS VIA: OMIM no. 225400). A rare condition exists in which patients are clinically similar but have normal levels of LH activity (designated EDS VIB: OMIM no. 229200). To define the biochemical defect, we have examined cultured fibroblasts from four EDS VIB patients for changes in the levels of the mRNAs for LH1, LH2, and LH3, collagen cross-linking patterns, and the extent of lysine hydroxylation of type I collagen a chains. Although normal levels of LH1 mRNA were observed in all four patients, in two patients the levels of LH2 mRNA were decreased by >50%, and a similar decrease was observed in LH3 mRNA in the other two patients. A distinct pattern of collagen cross-links, indicative of decreased lysyl hydroxylation, could be identified in EDS VIA patients, but there was no clear correlation between collagen cross-link pattern and changes in the individual LH mRNAs in EDS VIB patients. Linkage to tenascin-X was excluded in these patients. This study suggests that the basis for this form of EDS VI is genetically heterogeneous, and that alternative pathways in addition to lysine hydroxylation of collagen may be affected. (C) 2004 Wiley-Liss, Inc. C1 Duke Univ, Med Ctr, Div Dermatol, Durham, NC 27710 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. NICHD, Heritable Disorders Branch, Bethesda, MD USA. VU Med Ctr, Dept Human Genet, Amsterdam, Netherlands. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA. RP Yeowell, HN (reprint author), Duke Univ, Med Ctr, Div Dermatol, Box 3135, Durham, NC 27710 USA. EM yeowe001@mc.duke.edu RI Pals, Gerard/A-5198-2011; OI Atsawasuwan, Phimon/0000-0002-2576-060X FU NIA NIH HHS [AG10215] NR 52 TC 8 Z9 8 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2004 VL 131A IS 2 BP 155 EP 162 DI 10.1002/ajmg.a.30302 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 876WS UT WOS:000225530000008 PM 15523625 ER PT J AU Ho, NC Guarnieri, M Brant, LJ Park, SS Sun, B North, M Francomano, CA Carson, BS AF Ho, NC Guarnieri, M Brant, LJ Park, SS Sun, B North, M Francomano, CA Carson, BS TI Living with achondroplasia: Quality of life evaluation following cervico-medullary decompression SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE cervico-medullary compression; decompression; foramen magnum; mortality; quality of life ID CERVICOMEDULLARY-JUNCTION COMPRESSION; INFANTS; OUTCOMES; SF-36 AB Achondroplasia is the most common of the heritable skeletal dysplasias. Cervico-medullary compression is a frequently encountered and potentially lethal neurological complication. Cervico-medullary decompression (CMD) at the foramen magnum is often employed to relieve the pressure on the emerging cervical cord. Given the inherent risks associated with major surgery, there has been a substantial debate regarding the best criteria for CMD. Our objectives for this study are to explore the quality of life of patients who had undergone CMD, and to assess whether surgery is associated with mortality and increased long-term morbidity. A Medical Outcome Study 36-item Short Form General Health Survey designed to evaluate eight general health concepts as well as achondroplasia-related issues, was administered to patients assessed in the neurosurgery department in Johns Hopkins Hospital between 1977 and 1998. One hundred and sixty-seven patients were eligible for inclusion. Forty-three could not be contacted, and two refused consent. One hundred and twenty-two patients were assessed. Fifty-six (46%) individuals had CMD and 66 (54%) did not. There was 1 case of mortality in the CMD group and 12 cases in the non-CMD group. In the non-CMD group, all deaths, as far as we know, were unrelated to cervico-medullary compression. In this cohort of surviving patients (n = 109), the quality of life of the 55 (50.5%) who had undergone CMD is comparable to that of the 54 (49.5%) who did not have surgery, controlled for age and sex. CMD is indicated for patients with achondroplasia with significant symptomatic foramen magnum compression. It can be life saving. It can abolish profound central apnea that may cause sudden death and alleviate neurological complications associated with damage of the significantly compressed spinal cord. With regards to long-term outcome evaluation, the quality of life of individuals with achondroplasia who had CMD is similar to those age- and sex-matched patients who did not have this surgery. Moreover, CMD, with all its inherent surgical risks, does not appear to be associated with higher mortality or increased long-term morbidity. (C) 2004 Wiley-Liss, Inc. C1 Johns Hopkins Med Inst, Dept Neurol Surg, Baltimore, MD 21224 USA. NIA, Stat Methods & Expt Designs Sect, RRB, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Pediat, Baltimore, MD 21205 USA. NIA, Sect Human Genet & Integrat Med, LG, NIH, Baltimore, MD 21224 USA. RP Guarnieri, M (reprint author), Johns Hopkins Med Inst, Dept Neurol Surg, Baltimore, MD 21224 USA. EM mguarnie@jhmi.edu NR 29 TC 11 Z9 14 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2004 VL 131A IS 2 BP 163 EP 167 DI 10.1002/ajmg.a.30342 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 876WS UT WOS:000225530000009 PM 15487008 ER PT J AU Thadani, PV Strauss, JF Dey, SK Anderson, VM Audus, KL Coats, KS Cross, JC Erlebacher, A Ganapathy, V Linzer, DI Miller, RK Novak, DA Rapaka, RS Sadovsky, Y Salafia, CM Soares, M Unadkat, J AF Thadani, PV Strauss, JF Dey, SK Anderson, VM Audus, KL Coats, KS Cross, JC Erlebacher, A Ganapathy, V Linzer, DI Miller, RK Novak, DA Rapaka, RS Sadovsky, Y Salafia, CM Soares, M Unadkat, J TI National institute on drug abuse conference report on placental proteins, drug transport, and fetal development SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE drugs of abuse; placenta; fetal growth; transporters; proteins ID CANNABINOID RECEPTOR; BLOOD-FLOW; COCAINE; RAT; PREGNANCY; EXPOSURE; DIFFERENTIATION; IMPLANTATION; ALCOHOL; GROWTH AB The use of illicit and licit drugs during pregnancy is a major public health concern because of potential adverse effects on the fetus and the risk to maternal health. Because the placenta is the primary link between the mother and the conceptus and is essential for the growth and survival of the fetus, abnormalities in placental formation and function resulting from drug use could have a major influence on pregnancy outcome. At present, little information is available on the impact of abused drugs on placental biology alone or in combination with other "host" factors (eg, stress,infections). This prompted the National Institute on Drug Abuse (NIDA) to convene a meeting of experts in placental biology to review cutting-edge research with the mission to translate existing information to new clinical and research initiatives in the drug abuse field. This report Summarizes the presentations and research recommendations resulting front the workshop discussions. (C) 2004 Elsevier Inc. All rights reserved. C1 Natl Inst Drug Abuse, Div Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. Univ Penn, Med Ctr, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Vanderbilt Univ, Sch Med, Dept Pediat & Cell & Dev Biol & Pharmacol, Div Reprod & Dev Biol, Nashville, TN 37212 USA. Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66045 USA. Mississippi State Univ, Dept Sci Biol, Mississippi State, MS 39762 USA. Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 1N4, Canada. Univ Calgary, Dept Obstet & Gynecol, Calgary, AB T2N 1N4, Canada. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. Univ Rochester, Dept Obstet & Gynecol, Sch Med & Dent, Rochester, NY 14627 USA. Univ Florida, Dept Pediat, Gainesville, FL 32611 USA. Washington Univ, Dept Pediat, St Louis, MO 63130 USA. Washington Univ, Dept Gynecol, St Louis, MO 63130 USA. Washington Univ, Dept Cell Biol & Physiol, St Louis, MO 63130 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, EarlyPath Clin & Res Consultat Serv, New York, NY 10027 USA. Univ Kansas, Med Ctr, Inst Maternal Fetal Biol, Kansas City, KS 66103 USA. Univ Washington, Dept Pharmaceut & Res Affiliate, Seattle, WA 98195 USA. RP Thadani, PV (reprint author), Natl Inst Drug Abuse, Div Neurosci & Behav Res, NIH, 6001 Execut Blvd,Room 4282,MSC 9555, Bethesda, MD 20892 USA. EM pt24e@nih.gov RI Cross, James/F-4814-2011 OI Cross, James/0000-0003-0956-9378 NR 38 TC 10 Z9 10 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 BP 1858 EP 1862 DI 10.1016/j.ajog.2004.07.059 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FZ UT WOS:000225925800004 PM 15592265 ER PT J AU Alexander, J AF Alexander, J CA NICHD MFMU Network TI The MFMU units cesarean registry: Fetal injury associated with cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 543 BP S153 EP S153 DI 10.1016/j.ajog.2004.10.445 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500537 ER PT J AU Andrews, W Jeffcoat, M Schwebke, J Klebanoff, M Zhang, J Cliver, S AF Andrews, W Jeffcoat, M Schwebke, J Klebanoff, M Zhang, J Cliver, S TI Longitudinal Study of Vaginal Flora: Periodontal disease is significantly associated with bacterial vaginosis (BV) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Univ Alabama, Birmingham, AL USA. Univ Penn, Philadelphia, PA 19104 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 167 BP S55 EP S55 DI 10.1016/j.ajog.2004.10.072 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500169 ER PT J AU Bahado-Singh, RO Mahoney, MJ Zachary, J Wapner, RJ AF Bahado-Singh, RO Mahoney, MJ Zachary, J Wapner, RJ CA NICHD BUN Study Grp TI Contingency screening: Modeling of an alternate pathway for first trimester down syndrome risk assessment SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, BUN Study Grp, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 53 BP S25 EP S25 DI 10.1016/j.ajog.2004.09.088 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500055 ER PT J AU Chowdhury, M Tromp, G Kuivaniemi, H Edwin, S Romero, R AF Chowdhury, M Tromp, G Kuivaniemi, H Edwin, S Romero, R TI Novel functional sequence variants in the promoter of a gene downregulated in preterm prom: A possible genetic basis for the predisposition to membrane rupture? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. NICHHD, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 54 BP S25 EP S25 DI 10.1016/j.ajog.2004.09.089 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500056 ER PT J AU Church, MW AF Church, MW TI Auditory brainstem responses (ABRS) in neonates exposed to repeated courses of antenatal corticosteroids SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 408 BP S118 EP S118 DI 10.1016/j.ajog.2004.10.310 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500403 ER PT J AU Cotter, A Duthely, ML Gonzalez-Quintero, V Sullivan, MJO AF Cotter, A Duthely, ML Gonzalez-Quintero, V Sullivan, MJO TI Duration of membrane rupture and vertical transmission of HIV: Does the four hour rule still apply? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Georgetown Univ, Washington, DC 20057 USA. NICHD, UPDN, NIH, Bethesda, MD USA. NIMH, LMP, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 172 BP S56 EP S56 DI 10.1016/j.ajog.2004.10.077 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500174 ER PT J AU Endres, M Toso, L Roberson, R Park, J Dunlap, V Abebe, D Poggi, S Spong, C AF Endres, M Toso, L Roberson, R Park, J Dunlap, V Abebe, D Poggi, S Spong, C TI Prevention of alcohol-induced delays in developmental milestones and learning abnormalities in a model of fetal alcohol syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, UPDN, NIH, Bethesda, MD USA. Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 476 BP S137 EP S137 DI 10.1016/j.ajog.2004.10.378 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500470 ER PT J AU Gomez, R Schepeler, M Nien, JK Romero, R Medina, L Gonzalez, R Carstens, M Hassan, S Mazor, M Ortiz, JA AF Gomez, R Schepeler, M Nien, JK Romero, R Medina, L Gonzalez, R Carstens, M Hassan, S Mazor, M Ortiz, JA TI Is amniotic fluid interleukin-6 determination of value before the placement of a "rescue cerclage"? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 CEDIP, Sotero del Rio Hosp, Puente Alto, Chile. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Soroka Univ, Med Ctr, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 223 BP S71 EP S71 DI 10.1016/j.ajog.2004.10.127 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500223 ER PT J AU Haddad, R Tromp, G Kuivaniemi, H Chaiworapongsa, T Kim, YM Romero, R AF Haddad, R Tromp, G Kuivaniemi, H Chaiworapongsa, T Kim, YM Romero, R TI Spontaneous labor at term is characterized by a genomic signature of acute inflammation in the chorioamniotic membranes but not in the systemic circulation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Natl Inst Child Hlth & Human Dev, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. NR 0 TC 6 Z9 6 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 481 BP S138 EP S138 DI 10.1016/j.ajog.2004.10.383 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500475 ER PT J AU Hediger, M Luke, B Grainger, D Misiunas, R Anderson, E Witter, F Mauldin, J Newman, R Nugent, C O'Sullivan, MJ Hankins, G D'Alton, M AF Hediger, M Luke, B Grainger, D Misiunas, R Anderson, E Witter, F Mauldin, J Newman, R Nugent, C O'Sullivan, MJ Hankins, G D'Alton, M TI Suboptimal first-trimester growth and very preterm delivery of twins SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHHD, NIH, DESPR, Washington, DC USA. Univ Miami, Miami, FL 33152 USA. Univ Kansas, Wichita, KS 67214 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Baltimore, MD USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. Columbia Univ, New York, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 202 BP S65 EP S65 DI 10.1016/j.ajog.2004.10.106 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500203 ER PT J AU Hendler, I AF Hendler, I CA NICHD MFMU Network TI The effect of maternal obesity on the course of asthma during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 326 BP S96 EP S96 DI 10.1016/j.ajog.2004.10.230 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500326 ER PT J AU Hendler, I AF Hendler, I CA NICHD MFMU Network TI The relationship between resolution of asymptomatic bacterial vaginosis and spontaneous preterm birth in fetal fibronectin positive women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 355 BP S105 EP S105 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500353 ER PT J AU Hibbard, JU AF Hibbard, JU TI The MFMU cesarean registry: Impact of morbid obesity on trial of labor vs elective repeat cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 216 BP S69 EP S69 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500216 ER PT J AU Hibbard, JU AF Hibbard, JU TI The MFMU cesarean registry: Impact of obesity on trial of labor after previous cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 215 BP S69 EP S69 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500215 ER PT J AU Hong, JS Espinoza, J Goncalves, L Kim, YM Edwin, S Yoon, BH Nien, JK Hassan, S Mazor, M Romero, R AF Hong, JS Espinoza, J Goncalves, L Kim, YM Edwin, S Yoon, BH Nien, JK Hassan, S Mazor, M Romero, R TI Osteoprotegerin in maternal plasma during normal pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48202 USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 151, South Korea. Soroka Univ, Med Ctr, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 495 BP S141 EP S141 DI 10.1016/j.ajog.2004.10.397 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500489 ER PT J AU Hong, JS Hull, W Chaiworapongsa, T Whitsett, J Romero, R AF Hong, JS Hull, W Chaiworapongsa, T Whitsett, J Romero, R TI Spontaneous term parturition is associated with decreased amniotic fluid surfactant protein A concentration SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, Perinatol Res Branch, DHHS, NIH, Bethesda, MD USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 45 BP S21 EP S21 DI 10.1016/j.ajog.2004.09.080 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500047 ER PT J AU Kim, GJ Kuivaniemi, H Tromp, G Kim, YM Kim, MR Hong, JS Yoon, BH Kim, CJ Mazor, M Romero, R AF Kim, GJ Kuivaniemi, H Tromp, G Kim, YM Kim, MR Hong, JS Yoon, BH Kim, CJ Mazor, M Romero, R TI Evidence for the participation of bone morphogenetic protein-2 in normal spontaneous labor at term SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, DHHS, Perinatol Res Branch, NIH, Bethesda, MD USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pathol, Bethesda, MD USA. Seoul Natl Univ, Coll Med, Seoul, South Korea. Soroka Univ, Med Ctr, Dept Obstet & Gynecol, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 46 BP S21 EP S21 DI 10.1016/j.ajog.2004.09.081 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500048 ER PT J AU Kim, MR Nien, JK Kim, CJ Kim, YM Kim, GJ Goncalves, L Oh, SY Chaiworapongsa, T Mazor, M Romero, R AF Kim, MR Nien, JK Kim, CJ Kim, YM Kim, GJ Goncalves, L Oh, SY Chaiworapongsa, T Mazor, M Romero, R TI Villitis of unknown etiology as a placental counterpart of transplantation rejection: The demonstration of CD8(+) T lymphocyte and NK cell infiltration in this lesion SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Seoul Natl Univ, Seoul, South Korea. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Soroka Univ, Med Ctr, Beer Sheva, Israel. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 290 BP S87 EP S87 DI 10.1016/j.ajog.2004.10.194 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500290 ER PT J AU Kim, YM Kim, MR Kim, GJ Espinoza, J Gomez, R Kim, CJ Yoon, BH Mazor, M Satto, S Romero, R AF Kim, YM Kim, MR Kim, GJ Espinoza, J Gomez, R Kim, CJ Yoon, BH Mazor, M Satto, S Romero, R TI The placental bed of patients with preeclampsia has increased density of granulysin positive immunocytes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. NICHD, DHHS, Perinatol Res Branch, NIH, Bethesda, MD USA. Hosp Dr Sotero del Rio, CEDIP, Puente Alto, Chile. Seoul Natl Univ, Coll Med, Seoul, South Korea. Soroka Univ, Med Ctr, Beer Sheva, Korea, Israel. Toyama Med & Pharmaceut Univ, Dept Obstet & Gynecol, Toyama, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 71 BP S31 EP S31 DI 10.1016/j.ajog.2004.09.105 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500073 ER PT J AU Kim, YM Oh, SY Nien, JK Gomez, R Kim, CJ Mazor, M Abrahams, V Mor, G Saito, S Romero, R AF Kim, YM Oh, SY Nien, JK Gomez, R Kim, CJ Mazor, M Abrahams, V Mor, G Saito, S Romero, R TI Toll-like receptor 4: A link between "danger signals", the innate immune system, trophoblast apoptosis and preeclampsia? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, DHHS, NIH, Bethesda, MD USA. Hosp Dr Sotero del Rio, CEDIP, Puente Alto, Chile. Seoul Natl Univ, Seoul, South Korea. Soroka Univ, Med Ctr, Beer Sheva, Israel. Yale Univ, Dept Obstet & Gynecol, New Haven, CT USA. Toyama Med & Pharmaceut Univ, Dept Obstet & Gynecol, Toyama, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 9 BP S6 EP S6 DI 10.1016/j.ajog.2004.09.044 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500011 ER PT J AU Labarrere, C Romero, R Dicarlo, H Kim, YM Terry, C Chaiworapongsa, T Mazor, M AF Labarrere, C Romero, R Dicarlo, H Kim, YM Terry, C Chaiworapongsa, T Mazor, M TI Evidence that atherosis and atherosclerosis may have a common origin SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Clarian Hlth, Indianapolis, IN USA. NICHD, DHHS, Perinatol Res Branch, NIH, Bethesda, MD USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Soroka Univ, Med Ctr, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 84 BP S34 EP S34 DI 10.1016/j.ajog.2004.09.118 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500086 ER PT J AU Landon, M AF Landon, M TI The MFMU cesarean registry: Factors affecting the success of trial of labor following prior cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 38 BP S17 EP S17 DI 10.1016/j.ajog.2004.09.073 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500040 ER PT J AU Levine, R Thadhani, R Qian, C Lam, C Lim, KH Yu, K Blink, A Sachs, B Epstein, F Sibai, B Sukhatme, V Karumanchi, A AF Levine, R Thadhani, R Qian, C Lam, C Lim, KH Yu, K Blink, A Sachs, B Epstein, F Sibai, B Sukhatme, V Karumanchi, A TI Urinary placental growth factor (PGF) and the risk of preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHHD, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Allied Technol Grp, Rockville, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 10 BP S6 EP S6 DI 10.1016/j.ajog.2004.09.045 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500012 ER PT J AU Moldenhauer, J AF Moldenhauer, J CA NICHD MFMU Network TI Influence of maternal asthma and asthma severity on newborn morphometry SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 331 BP S98 EP S98 DI 10.1016/j.ajog.2004.10.234 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500330 ER PT J AU Nien, JK Gomez, R Espinoza, J Goncalves, L Hong, JS Edwin, S Hassan, S Mazor, M Romero, R AF Nien, JK Gomez, R Espinoza, J Goncalves, L Hong, JS Edwin, S Hassan, S Mazor, M Romero, R TI Resistin: A hormone which induces insulin resistance is increased in normal pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 48201 USA. Hosp Dr Sotero del Rio, CEDIP, Puente Alto, Chile. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. Soroka Univ, Med Ctr, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 156 BP S52 EP S52 DI 10.1016/j.ajog.2004.10.061 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500158 ER PT J AU Park, J Poggi, S Toso, L Abebe, D Einat, H Spong, C AF Park, J Poggi, S Toso, L Abebe, D Einat, H Spong, C TI No phenotype associated with established lipopolysaccharide model for cerebral palsy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, UPDN, NIH, Bethesda, MD USA. Georgetown Univ Hosp, Dept Obstet Gynecol, Washington, DC 20007 USA. NIMH, LMP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 52 BP S23 EP S23 DI 10.1016/j.ajog.2004.09.087 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500054 ER PT J AU Poggi, S Park, J Toso, L Einat, H Roberson, R Dunlap, V Woodard, J Abebe, D Spong, C AF Poggi, S Park, J Toso, L Einat, H Roberson, R Dunlap, V Woodard, J Abebe, D Spong, C TI Inflammatory-mediated model of cerebral palsy with developmental sequelae SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Georgetown Univ, Washington, DC 20057 USA. NICHD, UPDN, NIH, Bethesda, MD USA. NIMH, LMP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 169 BP S56 EP S56 DI 10.1016/j.ajog.2004.10.074 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500171 ER PT J AU Ramsey, P AF Ramsey, P TI Relationship of midtrimester fetal fibronectin (FFN) concentration to antibiotic efficacy for the prevention of spontaneous preterm birth in asymptomatic FFN positive women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, Maternal Fetal Med Units Network, NIH, Birmingham, AL USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 24 BP S11 EP S11 DI 10.1016/j.ajog.2004.09.059 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500026 ER PT J AU Richani, K Soto, E Espinoza, J Nien, JK Chaiworapongsa, T Refuerzo, J Blackwell, S Edwin, S Mazor, M Romero, R AF Richani, K Soto, E Espinoza, J Nien, JK Chaiworapongsa, T Refuerzo, J Blackwell, S Edwin, S Mazor, M Romero, R TI Unexplained intrauterine fetal death is accompanied by activation of complement SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Detroit, MI USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Soroka Univ, Med Ctr, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 568 BP S161 EP S161 DI 10.1016/j.ajog.2004.10.470 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500562 ER PT J AU Richani, K Soto, E Espinoza, J Nien, JK Chatworapongsa, T Edwin, S Mazor, M Romero, R AF Richani, K Soto, E Espinoza, J Nien, JK Chatworapongsa, T Edwin, S Mazor, M Romero, R TI Normal pregnancy is characterized by systemic activation of the complement system SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Soroka Univ, Med Ctr, Beer Sheva, Israel. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 487 BP S139 EP S139 DI 10.1016/j.ajog.2004.10.389 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500481 ER PT J AU Romero, R Gomez, R Nien, JK Yoon, BH Luo, R Beecher, C Mazor, M AF Romero, R Gomez, R Nien, JK Yoon, BH Luo, R Beecher, C Mazor, M TI Metabolomics in premature labor: A novel approach to identify patients at risk for preterm delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, DHHS, Perinatol Res Branch, NIH, Bethesda, MD USA. Hosp Dr Sotero del Rio, CEDIP, Puente Alto, Chile. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. Metabolin Inc, Durham, NC USA. Soroka Univ, Med Ctr, Beer Sheva, Israel. NR 0 TC 5 Z9 5 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 1 BP S2 EP S2 DI 10.1016/j.ajog.2004.09.036 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500003 ER PT J AU Rouse, D AF Rouse, D CA NICHD MFMU Network TI The MFMU cesarean registry: Predictability of uterine atony after primary cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 551 BP S155 EP S155 DI 10.1016/j.ajog.2004.10.453 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500545 ER PT J AU Sheffield, J AF Sheffield, J CA NICHD Maternal Fetal Med TI The effect of active and passive cigarette smoke on pregnant women with asthma SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 322 BP S95 EP S95 DI 10.1016/j.ajog.2004.10.226 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500322 ER PT J AU Sibai, B AF Sibai, B TI Plasma CRH levels at 16-20 weeks do not predict preterm delivery in women at high-risk for preterm delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 392 BP S114 EP S114 DI 10.1016/j.ajog.2004.10.295 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500390 ER PT J AU Silver, RM AF Silver, RM TI The MFMU cesaraean section registry: Maternal morbidity associated with multiple repeat cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 37 BP S17 EP S17 DI 10.1016/j.ajog.2004.09.072 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500039 ER PT J AU Sorokin, Y AF Sorokin, Y CA NICHD TI Effect of maternal BMI, number of courses and timing of antenatal corticosteroids: Association with neonatal anthropometric measurements SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 360 BP S106 EP S106 DI 10.1016/j.ajog.2004.10.263 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500358 ER PT J AU Soto, E Richani, K Espinoza, J Nien, JK Chaiworapongsa, T Edwin, S Mazor, M Romero, R AF Soto, E Richani, K Espinoza, J Nien, JK Chaiworapongsa, T Edwin, S Mazor, M Romero, R TI Anaphylatoxins in preterm and term labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Soroka Univ, Ctr Med, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 288 BP S87 EP S87 DI 10.1016/j.ajog.2004.10.192 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500288 ER PT J AU Spong, CY AF Spong, CY TI Progesterone for prevention of recurrent preterm birth: Impact of gestational age at prior delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 23 BP S11 EP S11 DI 10.1016/j.ajog.2004.09.058 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500025 ER PT J AU Toso, L Poggi, S Park, J Dunlap, V Roberson, R Abebe, D Spong, C AF Toso, L Poggi, S Park, J Dunlap, V Roberson, R Abebe, D Spong, C TI Alcohol brain NMDA subunit expression altered by in utero alcohol exposure SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHD, UPDN, NIH, Bethesda, MD USA. Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 448 BP S130 EP S130 DI 10.1016/j.ajog.2004.10.350 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500443 ER PT J AU Zhang, J Park, M Reddy, U AF Zhang, J Park, M Reddy, U TI Natural history of fetal position during pregnancy and risk of breech delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NIH, Epidemiol Branch, Bethesda, MD 20892 USA. NIH, Perinatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 601 BP S169 EP S169 DI 10.1016/j.ajog.2004.10.503 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500595 ER PT J AU Kercher, L Favara, C Chan, CC Race, R Chesebro, B AF Kercher, L Favara, C Chan, CC Race, R Chesebro, B TI Differences in scrapie-induced pathology of the retina and brain in transgenic mice that express hamster prion protein in neurons, astrocytes, or multiple cell types SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CREUTZFELDT-JAKOB DISEASE; DEVELOPMENTAL EXPRESSION; NATURAL SCRAPIE; MESSENGER-RNA; LYMPH-NODES; PRP; INFECTION; DEGENERATION; AGENT; GENE AB Prion protein (PrP) is expressed in many tissues and is required for susceptibility to scrapie and other prion diseases. To investigate the role of PrP expression in different cell types on pathology in retina and brain after scrapie infection, we examined transgenic mice expressing hamster PrP from the PrP promoter (tg7), the neuron-specific enolase promoter (tgNSE), or the astrocyte-specific glial fibrillary acidic protein promoter (tgGFAP). After intraocular inoculation with hamster scrapie, clinical disease developed in tg7 and tgNSE mice by 100 days and in tgGFAP mice by 350 days. Astrogliosis and scrapie-associated protease-resistant PrP (PrP-res) were detected in retina and brain before clinical onset. Retinal PrP-res was present in high amounts in both tg7 and tgNSE mice, however only tg7 mice developed retinal degeneration and extensive apoptosis. In contrast, in all three lines of mice high levels of brain PrP-res; accompanied by neurodegeneration were observed. Thus, PrP expression on neurons or astrocytes was sufficient for development of scrapie-induced degeneration in brain but not in retina. The combined effects of PrPres production in multiple cell types was required to produce retinal degeneration, whereas in brain PrPres; production by neurons or astrocytes alone was sufficient to cause neuronal damage via direct or indirect-mechanisms. C1 NIAID, NIH, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NIH, NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Chesebro, B (reprint author), NIAID, NIH, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM bchesebro@niaid.nih.gov NR 41 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2004 VL 165 IS 6 BP 2055 EP 2067 DI 10.1016/S0002-9440(10)63256-7 PG 13 WC Pathology SC Pathology GA 874WL UT WOS:000225381100020 PM 15579448 ER PT J AU Lievremont, JP Bird, GS Putney, JW AF Lievremont, JP Bird, GS Putney, JW TI Canonical transient receptor potential TRPC7 can function as both a receptor- and store-operated channel in HEK-293 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE calcium signaling; nonselective cation channels ID CA2+-PERMEABLE CATION CHANNEL; CAPACITATIVE CA2+ ENTRY; INOSITOL TRISPHOSPHATE RECEPTOR; CALCIUM-ENTRY; DROSOPHILA TRP; MOLECULAR-CLONING; HUMAN HOMOLOG; HEK293 CELLS; G-PROTEIN; EXPRESSION AB Previous studies on the activation mechanism of canonical transient receptor potential ( TRPC) channels have often produced conflicting conclusions. All seven have been shown to be activated by phospholipase C (PLC)-coupled receptors, but TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, and TRPC7 have also been proposed to function as store-operated channels. 1 In the case of TRPC3, the expression environment and the expression level appear to determine the mode of regulation. Evidence of a close structural relative of TRPC3, TRPC7, has been presented that this channel is activated by receptor activation or by store depletion. On the basis of previous findings for TRPC3, we reasoned that subtle differences in structure or expression conditions might account for the apparent distinct gating mechanisms of TRPC7. To reexamine the mode of activation of TRPC7, we stably and transiently transfected human embryonic kidney (HEK)-293 cells with cDNA encoding for human TRPC7. We examined the ability of a PLC-activating agonist and an intracellular Ca2+ store-depleting agent to activate these channels. Our findings demonstrate that when transiently expressed in HEK-293 cells, TRPC7 forms channels that are activated by PLC-stimulating agonists, but not by Ca2+ store depletion. However, when stably expressed in HEK-293 cells, TRPC7 can be activated by either Ca2+ store depletion or PLC activation. To our knowledge, this is the first demonstration of a channel protein that can be activated by both receptor- and store-operated modes in the same cell. In addition, the results reconcile the apparently conflicting findings of other laboratories regarding TRPC7 regulation. C1 NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov NR 47 TC 58 Z9 65 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 2004 VL 287 IS 6 BP C1709 EP C1716 DI 10.1152/ajpcell.00350.2004 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 867WV UT WOS:000224874400022 PM 15342342 ER PT J AU Esaki, T Suzuki, H Cook, M Shimoji, K Cheng, SY Sokoloff, L Nunez, J AF Esaki, T Suzuki, H Cook, M Shimoji, K Cheng, SY Sokoloff, L Nunez, J TI Cardiac glucose utilization in mice with mutated alpha- and beta-thyroid hormone receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE heart; thyroid hormone resistance syndrome; glucose metabolism; 2-deoxyglucose ID TARGETED MUTATION; GENE-EXPRESSION; RESISTANCE; MYOSIN; RAT; ISOFORMS; HEART; TEMPERATURE; PHENOTYPE; MECHANISM AB Abnormal thyroid function is usually associated with altered cardiac function. Mutations in the thyroid hormone (TH)-binding region of the TH beta-receptor (TRbeta) that eliminate its TH-binding ability lead to the thyroid hormone resistance syndrome (RTH) in humans, which is characterized by high blood TH levels, goiter, hyperactivity, and tachycardia. Mice with "knock-in" mutations in the TH beta-receptor (TRalpha) or TRbeta that remove their TH-binding ability have been developed, and those with the mutated TRbeta (TRbeta(PV/PV)) appear to provide a model for RTH. These two types of mutants show different effects on cerebral energy metabolism, e. g., negligible change in glucose utilization (CMRGlc) in TRbeta(PV/PV) mice and markedly reduced CMRGlc, like that found in cretinous rats, in the mice (TRalpha(PV/+)) with the knock-in mutation of the TRalpha gene. Studies in knockout mice have indicated that the TRalpha may also influence heart rate. Because mutations in both receptor genes appear to affect some parameters of cardiac function and because cardiac functional activity and energy metabolism are linked, we measured heart glucose utilization (HMRGlc) in both the TRbeta(PV/PV) and TRalpha(PV/+) mutants. Compared with values in normal wild-type mice, HMRGlc was reduced (-77 to -95%) in TRalpha(PV/+) mutants and increased (87 to 340%) in TRbeta(PV/PV) mutants, the degree depending on the region of the heart. Thus the TRalpha(PV/+) and TRbeta(PV/PV) mutations lead, respectively, to opposite effects on energy metabolism in the heart that are consistent with the bradycardia seen in hypothyroidism and the tachycardia associated with hyperthyroidism and RTH. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NCI, Positron Emiss Dept, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Rm 1A-07,36 Convent Dr MSC 4030, Bethesda, MD 20892 USA. EM louissokoloff@mail.nih.gov NR 29 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 2004 VL 287 IS 6 BP E1149 EP E1153 DI 10.1152/ajpendo.00078.2004 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 867WP UT WOS:000224873800015 PM 15304375 ER PT J AU Deem, S Kim, SS Min, JH Eveland, R Moulding, J Martyr, S Wang, XD Swenson, ER Gladwin, MT AF Deem, S Kim, SS Min, JH Eveland, R Moulding, J Martyr, S Wang, XD Swenson, ER Gladwin, MT TI Pulmonary vascular effects of red blood cells containing S-nitrosated hemoglobin SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE nitric oxide; hypoxic pulmonary vasoconstriction; erythrocytes ID NITRIC-OXIDE BIOAVAILABILITY; OXYGEN-BINDING; BIOCHEMICAL-CHARACTERIZATION; HUMAN CIRCULATION; NITROSOHEMOGLOBIN; VASOCONSTRICTION; ERYTHROCYTES; HEME; TRANSNITROSATION; NITROSOTHIOLS AB The role of S-nitrosated hemoglobin (SNO-Hb) in the regulation of blood flow is a central and controversial question in cardiopulmonary physiology. In the present study, we investigate whether intact human red blood cells (RBCs) synthesized to contain high SNO-Hb levels are able to export nitric oxide bioactivity and vasodilate the pulmonary circulation, and whether SNO-Hb dependent vasodilation occurs secondary to an intrinsic oxygen-linked, allosteric function of Hb. RBCs containing supraphysiological concentrations (100-1,000 x normal) of SNO-Hb (SNO-RBCs) were synthesized and added to isolated, perfused rat lungs during anoxic or normoxic ventilation, and during normoxic ventilation with pulmonary hypertension induced by the thromboxane mimetic U-46619. SNO-RBCs produced dose-dependent pulmonary vasodilation compared with control RBCs during conditions of both normoxic (U-46619) and hypoxic pulmonary vasoconstriction. These effects were associated with a simultaneous, rapid, and temperature-dependent loss of SNO from Hb. Both vasodilatory effects and the rate of SNO-Hb degradation were independent of oxygen tension and Hb oxygen saturation. Furthermore, these effects were not affected by inhibition of the RBC membrane band 3 protein (anion exchanger-1), a putative membrane facilitator of NO export from RBCs. Whereas these data support observations by multiple groups that synthesized SNO-Hb can vasodilate, this effect is not under intrinsic oxygen-dependent allosteric control, nor likely to be relevant in the pulmonary circulation at normal physiological concentrations. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Ctr, Dept Anesthesiol, Seattle, WA 98104 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Ctr, Dept Med, Seattle, WA 98104 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Ctr, Dept Pulm & Crit Care, Seattle, WA 98104 USA. Univ Ulsan, Asan Med Ctr, Coll Med, Dept Anesthesiol, Kangnung 682714, South Korea. Kwandong Univ, Myongji Hosp, Dept Anesthesiol, Kwandong 412270, South Korea. NIDDKD, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Deem, S (reprint author), Harborview Med Ctr, Dept Anesthesiol, POB 359724, Seattle, WA 98104 USA. EM sdeem@u.washington.edu FU NHLBI NIH HHS [HL-03796-01, HL-24613] NR 29 TC 17 Z9 19 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 2004 VL 287 IS 6 BP H2561 EP H2568 DI 10.1152/ajpheart.00310.2004 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 871VW UT WOS:000225165700024 PM 15297254 ER PT J AU Minneci, PC Deans, KJ Banks, SM Costello, R Csako, G Eichacker, PQ Danner, RL Natanson, C Solomon, SB AF Minneci, PC Deans, KJ Banks, SM Costello, R Csako, G Eichacker, PQ Danner, RL Natanson, C Solomon, SB TI Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE vasopressors and systemic perfusion; low cardiac output septic shock; vasopressors and acidosis; vasopressors and cardiac function ID LOW-DOSE VASOPRESSIN; REVERSIBLE MYOCARDIAL DEPRESSION; BETA-ADRENERGIC RECEPTORS; HEMODYNAMIC SUPPORT; HEART-FAILURE; SEPSIS; THERAPY; POLYSACCHARIDE; EPIDEMIOLOGY; DYSFUNCTION AB During sepsis, limited data on the survival effects of vasopressors are available to guide therapy. Therefore, we compared the effects of three vasopressors on survival in a canine septic shock model. Seventy-eight awake dogs infected with differing doses of intraperitoneal Escherichia coli to produce increasing mortality were randomized to receive epinephrine (0.2, 0.8, or 2.0 mug.kg(-1).min(-1)), norepinephrine (0.2, 1.0, or 2.0 mug.kg(-1).min(-1)), vasopressin (0.01 or 0.04 U/min), or placebo in addition to antibiotics and fluids. Serial hemodynamic and biochemical variables were measured. Increasing doses of bacteria caused progressively greater decreases in survival (P<0.06), mean arterial pressure (MAP) (P<0.05), cardiac index (CI) (P<0.02), and ejection fraction (EF) (P=0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin (P=0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose (P=0.02) but not bacterial dose. Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacteria doses. Compared with concurrent infected controls, epinephrine caused greater decreases in CI, EF, and pH, and greater increases in systemic vascular resistance and serum creatinine than norepinephrine and vasopressin. These epinephrine-induced changes were significantly related to the dose of epinephrine administered. In this study, the effects of vasopressors were independent of severity of infection but dependent on the type and dose of vasopressor used. Epinephrine adversely affected organ function, systemic perfusion, and survival compared with norepinephrine and vasopressin. In the ranges studied, norepinephrine and vasopressin have more favorable risk-benefit profiles than epinephrine during sepsis. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Minneci, PC (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, 10 Ctr Dr,Bldg 10,Rm 7D43, Bethesda, MD 20892 USA. EM pminneci@mail.cc.nih.gov NR 51 TC 15 Z9 16 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 2004 VL 287 IS 6 BP H2545 EP H2554 DI 10.1152/ajpheart.00450.2004 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 871VW UT WOS:000225165700022 PM 15319205 ER PT J AU Chiba, Y Kusakabe, T Kimura, S AF Chiba, Y Kusakabe, T Kimura, S TI Decreased expression of uteroglobin-related protein 1 in inflamed mouse airways is mediated by IL-9 SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE uteroglobin-related protein 1; interleukin-9; airway inflammation; allergic asthma ID BRONCHIAL HYPERRESPONSIVENESS; EPITHELIAL-CELLS; TRANSGENIC MICE; INTERLEUKIN 9; ASTHMA; INFLAMMATION; GENE; TRANSCRIPTION; SUSCEPTIBILITY; CYTOKINE AB Uteroglobin-related protein 1 (UGRP1) is a secretory protein, highly expressed in epithelial cells of airways. Although an involvement of UGRP1 in the pathogenesis of asthma has been suggested, its function in airways remains unclear. In the present study, a relationship between airway inflammation, UGRP1 expression, and interleukin-9 (IL-9), an asthma candidate gene, was evaluated by using a murine model of allergic bronchial asthma. A severe airway inflammation accompanied by airway eosinophilia and elevation of IL-9 in bronchoalveolar lavage (BAL) fluids was observed after ovalbumin ( OVA) challenge to OVA-sensitized mice. In this animal model of airway inflammation, lung Ugrp1 mRNA expression was greatly decreased compared with control mice. A significant inverse correlation between lung Ugrp1 mRNA levels and IL-9 levels in BAL fluid was demonstrated by regression analysis (r = 0.616, P = 0.023). Immunohistochemical analysis revealed a distinct localization of UGRP1 in airway epithelial cells of control mice, whereas UGRP1 staining was patchy and faint in inflamed airways. Intranasal administration of IL-9 to naive mice decreased the level of Ugrp1 expression in lungs. These findings suggest that UGRP1 is downregulated in inflamed airways, such as allergic asthmatics, and IL-9 might be an important mediator for modulating UGRP1 expression. C1 NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. RP Kimura, S (reprint author), NCI, NIH, Lab Metab, Bldg 37,Rm 3112B, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov NR 24 TC 21 Z9 23 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD DEC PY 2004 VL 287 IS 6 BP L1193 EP L1198 DI 10.1152/ajplung.00263.2004 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 869BI UT WOS:000224956900017 PM 15531759 ER PT J AU Daugherty, BL Mateescu, M Patel, AS Wade, K Kimura, S Gonzales, LW Guttentag, S Ballard, PL Koval, M AF Daugherty, BL Mateescu, M Patel, AS Wade, K Kimura, S Gonzales, LW Guttentag, S Ballard, PL Koval, M TI Developmental regulation of claudin localization by fetal alveolar epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE tight junction; endocytosis; lung development; epithelial barrier function; pneumocytes ID TIGHT JUNCTIONS; ENDOTHELIAL-CELLS; LUNG LIQUID; PERMEABILITY; PHOSPHORYLATION; EXPRESSION; PROTEINS; OCCLUDIN; PATHWAY; BARRIER AB Tight junction proteins in the claudin family regulate epithelial barrier function. We examined claudin expression by human fetal lung (HFL) alveolar epithelial cells cultured in medium containing dexamethasone, 8-bromo-cAMP, and isobutylmethylxanthanine (DCI), which promotes alveolar epithelial cell differentiation to a type II phenotype. At the protein level, HFL cells expressed claudin-1, claudin-3, claudin-4, claudin-5, claudin-7, and claudin-18, where levels of expression varied with culture conditions. DCI-treated differentiated HFL cells cultured on permeable supports formed tight transepithelial barriers, with transepithelial resistance ( TER)>1,700 ohm/cm(2). In contrast, HFL cells cultured in control medium without DCI did not form tight barriers (TER<250 ohm/cm(2)). Consistent with this difference in barrier function, claudins expressed by HFL cells cultured in DCI medium were tightly localized to the plasma membrane; however, claudins expressed by HFL cells cultured in control medium accumulated in an intracellular compartment and showed discontinuities in claudin plasma membrane localization. In contrast to claudins, localization of other tight junction proteins, zonula occludens (ZO)-1, ZO-2, and occludin, was not sensitive to HFL cell phenotype. Intracellular claudins expressed by undifferentiated HFL cells were localized to a compartment containing early endosome antigen-1, and treatment of HFL cells with the endocytosis inhibitor monodansylcadaverine increased barrier function. This suggests that during differentiation to a type II cell phenotype, fetal alveolar epithelial cells use differential claudin expression and localization to the plasma membrane to help regulate tight junction permeability. C1 Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Inst Environm Med, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Neonatol, Philadelphia, PA 19104 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Koval, M (reprint author), Univ Penn, Sch Med, Dept Physiol, B-400 Richards Bldg 6085,3700 Hamilton Walk, Philadelphia, PA 19104 USA. EM mkoval@mail.med.upenn.edu RI Guttentag, Susan/D-8705-2013; Koval, Michael/C-6366-2015 OI Guttentag, Susan/0000-0003-4420-5879; Koval, Michael/0000-0002-5422-5614 FU NHLBI NIH HHS [P01-HL-019737, P01 HL019737-290018, P01 HL019737, R01 HL059959]; NIGMS NIH HHS [R01 GM061012, R01-GM-61012, R01 GM061012-05] NR 39 TC 57 Z9 57 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD DEC PY 2004 VL 287 IS 6 BP L1266 EP L1273 DI 10.1152/ajplung.00423.2003 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 869BI UT WOS:000224956900026 PM 15347569 ER PT J AU Voynow, JA Fischer, BM Malarkey, DE Burch, LH Wong, T Longphre, M Ho, SB Foster, WM AF Voynow, JA Fischer, BM Malarkey, DE Burch, LH Wong, T Longphre, M Ho, SB Foster, WM TI Neutrophil elastase induces mucus cell metaplasia in mouse lung SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article; Proceedings Paper CT 100th International Conference of the American-Thoracic-Society CY MAY 21-26, 2004 CL Orlando, FL SP Amer Thorac Soc DE neutrophil elastase; goblet cell metaplasia; Muc5ac ID AIRWAY EPITHELIAL-CELLS; FACTOR RECEPTOR ACTIVATION; INDUCED MUC5AC EXPRESSION; RAT BRONCHIAL EPITHELIUM; MUCIN GENE-EXPRESSION; GLAND SEROUS CELLS; NASAL EPITHELIUM; PROTEIN EXPRESSION; MESSENGER-RNA; ASTHMA AB Goblet cell hyperplasia in the superficial airway epithelia is a signature pathological feature of chronic bronchitis and cystic fibrosis. In these chronic inflammatory airway diseases, neutrophil elastase (NE) is found in high concentrations in the epithelial lining fluid. NE has been reported to trigger mucin secretion and increase mucin gene expression in vitro. We hypothesized that chronic NE exposure to murine airways in vivo would induce goblet cell metaplasia. Human NE (50 mug) or PBS saline was aspirated intratracheally by male Balb/c (6 wk of age) mice on days 1, 4, and 7. On days 8, 11, and 14, lung tissues for histology and bronchoalveolar lavage (BAL) samples for cell counts and cytokine levels were obtained. NE induced Muc5ac mRNA and protein expression and goblet cell metaplasia on days 8, 11, and 14. These cellular changes were the result of proteolytic activity, since the addition of an elastase inhibitor, methoxysuccinyl Ala-Ala-Pro-Val chloromethylketone (AAPV-CMK), blocked NE-induced Muc5ac expression and goblet cell metaplasia. NE significantly increased keratinocyte-derived chemokine and IL-5 in BAL and increased lung tissue inflammation and BAL leukocyte counts. The addition of AAPV-CMK reduced these measures of inflammation to control levels. These experiments suggest that NE proteolytic activity initiates an inflammatory process leading to goblet cell metaplasia. C1 Duke Univ, Med Ctr, Div Pediat Pulm Med, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Bayer Biotechnol, Dept Cell & Analyt Biol, Berkeley, CA 94710 USA. Univ Minnesota, Vet Affairs Med Ctr, Dept Med, Minneapolis, MN 55417 USA. RP Voynow, JA (reprint author), Duke Univ, Med Ctr, Div Pediat Pulm Med, Dept Pediat, Box 2994, Durham, NC 27710 USA. EM voyno001@mc.duke.edu FU NHLBI NIH HHS [HL-65611, HL-62641] NR 65 TC 91 Z9 98 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD DEC PY 2004 VL 287 IS 6 BP L1293 EP L1302 DI 10.1152/ajplung.00140.2004 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 869BI UT WOS:000224956900029 PM 15273079 ER PT J AU Song, J Hu, XQ Shi, M Knepper, MA Ecelbarger, CA AF Song, J Hu, XQ Shi, M Knepper, MA Ecelbarger, CA TI Effects of dietary fat, NaCl, and fructose on renal sodium and water transporter abundances and systemic blood pressure SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE insulin resistance; natriuresis; diuresis; NaPi-2; sodium hydrogen exchanger 3; BSC1; TSC; epithelial sodium channel ID THICK ASCENDING LIMB; INDUCED INSULIN-RESISTANCE; HYPERTENSIVE-RATS; ARTERIAL-PRESSURE; NITRIC-OXIDE; FEMALE RATS; KIDNEY; VASOPRESSIN; COTRANSPORTER; MECHANISMS AB Dietary fructose, NaCl, and/or saturated fat have been correlated with mean arterial pressure ( MAP) rises in sensitive strains of rats. Dysregulation of sodium and/or water reabsorption by the kidney may contribute. Using radiotelemetry and parallel semiquantitative immunoblotting, we examined the effects of various diets on MAP and the regulation of abundance of the major renal sodium and water transport proteins in male Sprague-Dawley rats. In study 1, rats ( similar to 275 g) were fed one of four diets for 4 wk ( n = 6/group): 1) control, 2) 65% fructose, 3) control + added NaCl (2.59%), or 4) fructose + NaCl. In study 2, 5% butter ( fat) was added to the above four diets. Both fat and NaCl, but not fructose, caused modest rises in MAP ( 5 - 10 mmHg) and increased the day-to-night ratio in diastolic blood pressure. NaCl or fructose increased kidney size. Creatinine clearance was increased by salt or fat, and fractional excretion of sodium was decreased by fat. In study 1, high NaCl markedly reduced plasma renin and aldosterone and its regulated proteins in whole kidney, i.e., the thiazide-sensitive Na-Cl cotransporter and the alpha- and gamma (70-kDa band)-subunits of the epithelial sodium channel. These effects were blunted by fat. Fructose increased the abundance of the sodium phosphate cotransporter, whereas it decreased the bumetanide-sensitive Na-K-2Cl cotransporter and aquaporin-2. Overall, doubling of dietary fat appeared to impair dietary sodium adaptation, i.e., blunt the downregulation of aldosterone-mediated effects, thus allowing blood pressure to rise at an accelerated rate. C1 Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20057 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Ecelbarger, CA (reprint author), Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20057 USA. EM ecelbarc@georgetown.edu FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [R01 HL074142, HL-073193, HL-074142, ZO1-HL-01282] NR 50 TC 40 Z9 40 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2004 VL 287 IS 6 BP F1204 EP F1212 DI 10.1152/ajprenal.00063.2004 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 867PZ UT WOS:000224855800014 PM 15304371 ER PT J AU Reid, BC Warren, JL Rozier, G AF Reid, BC Warren, JL Rozier, G TI Comorbidity and early diagnosis of head and neck cancer in a medicare population SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID ORAL-CANCER; RISK; PRECANCER; ADULTS AB Background: This study assessed potential opportunities for an early diagnosis of head and neck cancers (HNCA), and the role played by comorbidity, among contacts by Medicare patients with the healthcare system before their diagnosis. Comorbidity was hypothesized to affect the relationship between use of healthcare services and stage of disease. Methods: The study database (n = 11,312) was constructed by linking files from the Surveillance, Epidemiology, and End Results Program 1991 through 1999 and those of the Center for Medicare and Medicaid Services Program. HNCA cases were comprised of the lip, oral cavity, pharynx, and larynx anatomic sites. Results: Among persons with no alcohol and tobacco-related comorbidities (ATC), increasing numbers of physician visits were independently associated with a reduced risk of advanced stage at diagnosis for all anatomic sites, but especially the pharynx and larynx. Among persons with one or more ATC, physician visits displayed no association with stage at diagnosis with the exception of laryngeal tumors, where physician visits were strongly associated with reduced risk of late stage at diagnosis. Over 46% of cases with advanced stage tumors, most of whom also had ATC disease, had greater than or equal to11 physician visits in the year preceding their diagnosis of HNCA. Conclusions: Potential opportunities for an earlier diagnosis of HNCA were found among the numerous contacts with the healthcare system that patients had prior to their cancer diagnosis. Such opportunities were especially numerous and relevant for persons with ATC and form the basis for combining high-risk with opportunistic screening approaches. (C) 2004 American journal of Preventive Medicine. C1 Univ Maryland, Sch Dent, Dept Hlth Promot & Policy, Hlth Serv Res Program, Baltimore, MD 21201 USA. Natl Canc Inst, Applied Res Program, Bethesda, MD USA. Univ N Carolina, Dept Hlth Policy & Adm, Sch Publ Hlth, Chapel Hill, NC USA. RP Reid, BC (reprint author), Univ Maryland, Sch Dent, Dept Hlth Promot & Policy, Hlth Serv Res Program, Room 3A-08,666 Baltimore St, Baltimore, MD 21201 USA. EM bcr001@dental.umaryland.edu FU NIDCR NIH HHS [5-K22-DE014341-02] NR 19 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD DEC PY 2004 VL 27 IS 5 BP 373 EP 378 DI 10.1016/j.amepre.2004.07.018 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 872KF UT WOS:000225205400003 PM 15556736 ER PT J AU Saraiya, M Glanz, K Briss, PA Nichols, P White, C Das, D Smith, SJ Tannor, B Hutchinson, AB Wilson, KM Gandhi, N Lee, NC Rimer, B Coates, RC Kerner, JF Hiatt, RA Buffler, P Rochester, P AF Saraiya, M Glanz, K Briss, PA Nichols, P White, C Das, D Smith, SJ Tannor, B Hutchinson, AB Wilson, KM Gandhi, N Lee, NC Rimer, B Coates, RC Kerner, JF Hiatt, RA Buffler, P Rochester, P TI Interventions to prevent skin cancer by reducing exposure to ultraviolet radiation - A systematic review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID SUN-PROTECTION BEHAVIORS; CUTANEOUS MALIGNANT-MELANOMA; RANDOMIZED CONTROLLED-TRIAL; HEALTH-EDUCATION PROGRAM; BASAL-CELL CARCINOMA; POOL COOL PROGRAM; SUNSCREEN USE; RISK-FACTORS; UNITED-STATES; OUTDOOR WORKERS AB The relationship between skin cancer and ultraviolet radiation is well established. Behaviors such as seeking shade, avoiding sun exposure during peak hours of radiation, wearing protective clothing, or some combination of these behaviors can provide protection. Sunscreen use alone is not considered an adequate protection against ultraviolet radiation. This report presents the results of systematic reviews of effectiveness, applicability, other harms or benefits, economic evaluations, and barriers to use of selected interventions to prevent skin cancer by reducing exposure to ultraviolet radiation. The Task Force on Community Preventive Services found that education and policy approaches to increasing sun-protective behaviors were effective when implemented in primary schools and in recreational or tourism settings, but found insufficient evidence to determine effectiveness when implemented in other settings, such as child care centers, secondary schools and colleges, and occupational settings. They also found insufficient evidence to determine the effectiveness of interventions oriented to healthcare settings and providers, media campaigns alone, interventions oriented to parents or caregivers of children, and community-wide multicomponent interventions. The report also provides suggestions for areas for future research. (C) 2004 American journal of Preventive Medicine. C1 Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Epidemiol Program Off, Atlanta, GA 30341 USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96822 USA. NCI, NIH, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Saraiya, M (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, 4770 Buford Highway,MS K55, Atlanta, GA 30341 USA. EM MSaraiya@cdc.gov OI Kerner, Jon/0000-0002-8792-3830 NR 252 TC 197 Z9 203 U1 12 U2 36 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD DEC PY 2004 VL 27 IS 5 BP 422 EP 466 DI 10.1016/j.amepre.2004.08.009 PG 45 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 872KF UT WOS:000225205400011 PM 15556744 ER PT J AU Schmidt, PJ Haq, N Rubinow, DR AF Schmidt, PJ Haq, N Rubinow, DR TI A longitudinal evaluation of the relationship between reproductive status and mood in perimenopausal women SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHOLOGIC DISTRESS; NATURAL MENOPAUSE; DEPRESSION; SYMPTOMS; DISORDERS; COMMUNITY; SAMPLE; SCALE AB Objective: Mood and reproductive function were prospectively evaluated in asymptomatic premenopausal women to determine whether the onset of depression was temporally linked to the perimenopause. Method: Twenty-nine asymptomatic, regularly cycling women were monitored longitudinally for an average of 5 years until at least 6 months of amenorrhea occurred. Outcome measures included mood ratings and menstrual diaries completed daily, the Structured Clinical Interview for DSM-IV, and plasma levels of follicle-stimulating hormone obtained at 3-6-month intervals. The number of episodes of depression an their timing relative to the final menstrua period were determined. Differences in outcome measures between women who did and did not become depressed during the perimenopause were determined by Student's t test, chi-square tests, and Fisher's exact test. Results: The authors observed 11 episodes of new-onset depression in nine of the 29 women. In the 24 months surrounding the last menstrual period nine episodes of depression were observed. Six of the nine women who became depressed during the study had no prior depressive episodes. For the 24 months surrounding the final menses, the risk for onset of depression was 14 times as high as for a 31-year premenopausal period of time. Women who developed depression during the perimenopause were not distinguished from those who remained asymptomatic on the basis of symptom profile, duration of the perimenopause, endocrine measures, or past historical variables. Conclusions: These preliminary data suggest that events related to the late perimenopause may be associated with an increased susceptibility to develop depression in some women. C1 NIMH, Behav Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, NIH, Dept Hlth & Human Serv, Rm 3N238,Bldg 10,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. EM peterschmidt@mail.nih.gov NR 28 TC 128 Z9 134 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2004 VL 161 IS 12 BP 2238 EP 2244 DI 10.1176/appi.ajp.161.12.2238 PG 7 WC Psychiatry SC Psychiatry GA 876NJ UT WOS:000225503500015 PM 15569895 ER PT J AU Wendler, D Emanuel, EJ Lie, RK AF Wendler, D Emanuel, EJ Lie, RK TI The standard of care debate: Conceptual clarifications - Wendler et al. respond SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Bergen, Dept Publ Hlth & Primary Hlth Care, N-5020 Bergen, Norway. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2004 VL 94 IS 12 BP 2048 EP 2049 DI 10.2105/AJPH.94.12.2048-a PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 877IF UT WOS:000225560800004 ER PT J AU Killian, JK Merino, M Bondy, C Bakalov, V Chow, C AF Killian, JK Merino, M Bondy, C Bakalov, V Chow, C TI MRI of angiolipoma of the breast in Turner's syndrome SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID CANCER C1 NIH, Bethesda, MD 20892 USA. RP Killian, JK (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2004 VL 183 IS 6 BP 1843 EP 1844 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 873KB UT WOS:000225277400059 PM 15547244 ER PT J AU Eskandari, F AF Eskandari, F TI Predictive value of gall bladder scan in management of classic biliary colic in the absence of cholelithiasis or acute inflammation SO AMERICAN JOURNAL OF SURGERY LA English DT Letter C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Eskandari, F (reprint author), NIMH, NIH, Bethesda, MD 20892 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 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 2004 VL 188 IS 6 BP 821 EP 822 DI 10.1016/j.amjsurg.2004.08.018 PG 2 WC Surgery SC Surgery GA 885UW UT WOS:000226183600063 PM 15619506 ER PT J AU Ozdemirli, M Cheson, B Jaffe, ES AF Ozdemirli, M Cheson, B Jaffe, ES TI What is anaplastic large cell lymphoma? SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter ID EPSTEIN-BARR-VIRUS; PYOTHORAX-ASSOCIATED LYMPHOMA; T-CELL; B-CELL; PHENOTYPE; TRANSPLANT; GENE C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Hematol, Washington, DC USA. NIH, Pathol Lab, Bethesda, MD USA. Georgetown Univ Hosp, Dept Pathol, Washington, DC 20007 USA. RP Ozdemirli, M (reprint author), Georgetown Univ Hosp, Dept Pathol, Washington, DC 20007 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2004 VL 28 IS 12 BP 1664 EP 1665 DI 10.1097/00000478-200412000-00019 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA 874VX UT WOS:000225379600019 PM 15577690 ER PT J AU Abbott, KC Lentine, KL Bucci, JR Agodoa, LY Peters, TG Schnitzler, MA AF Abbott, KC Lentine, KL Bucci, JR Agodoa, LY Peters, TG Schnitzler, MA TI The impact of transplantation with deceased donor hepatitis C-positive kidneys on survival in wait-listed long-term dialysis patients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE black; deceased donor; dialysis; donor; elderly; end-stage renal disease; expanded criteria donor; hepatitis C; kidney transplant; survival; USRDS; wait list ID RENAL-TRANSPLANTATION; VIRUS-INFECTION; PREVALENCE; RECIPIENTS AB Whether transplantation of deceased donor kidney allografts from donors with antibodies against hepatitis C virus (HCV) confers a survival advantage compared with remaining on the kidney transplant waiting list is not yet known. We studied 38,270 USRDS Medicare beneficiaries awaiting kidney transplantation who presented with end-stage renal disease from April 1, 1995 to July 31, 2000. Cox regression was used to compare the adjusted hazard ratios for death among recipients of kidneys from deceased donors, and donors with antibodies against hepatitis C (DHCV+), controlling for demographics and comorbidities. In comparison to staying on the waiting list, transplantation from DHCV+ was associated with improved survival among all patients (adjusted hazard ratio for death 0.76, 95% CI 0.60, 0.96). Of patients receiving DHCV+ kidneys, 52% were themselves hepatitis C antibody positive (HCV), so outcomes associated with use of these grafts may have particular implications for HCV transplant candidates. Recommendations for use of DHCV+ kidneys may require analysis of data not currently collected from either dialysis or transplant patients. However, transplantation of DHCV+ kidneys is associated with improved patient survival compared to remaining wait-listed and dialysis dependent. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Washington Univ, Sch Med, Serv Nephrol, St Louis, MO USA. NIDDK, NIH, Bethesda, MD USA. Univ Florida, Hlth Sci Ctr Jacksonville, Dept Surg, Jacksonville, FL 32209 USA. Jacksonville Transplant Ctr Shands, Jacksonville, FL USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 FU NIDDK NIH HHS [K25-DK-02916-01] NR 11 TC 55 Z9 57 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2004 VL 4 IS 12 BP 2032 EP 2037 DI 10.1111/j.1600-6143.2004.00606.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 876HM UT WOS:000225487400016 PM 15575906 ER PT J AU Blaney, JE Hanson, CT Firestone, CY Hanley, KA Murphy, BR Whitehead, SS AF Blaney, JE Hanson, CT Firestone, CY Hanley, KA Murphy, BR Whitehead, SS TI Genetically modified, live attenuated dengue virus type 3 vaccine candidates SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID RHESUS-MONKEYS; HEMORRHAGIC-FEVER; 3'-UNTRANSLATED REGION; UNTRANSLATED REGION; NONHUMAN-PRIMATES; CHIMERIC VACCINE; HUMAN VOLUNTEERS; VERO CELLS; IMMUNOGENICITY; REPLICATION AB Three novel recombinant dengue type 3 (DEN3) virus vaccine candidates have been generated from a DEN3 virus isolated from a mild outbreak of dengue fever in the Sleman area of central Java in Indonesia in 1978. Antigenic chimeric viruses were prepared by replacing the membrane precursor and envelope (ME) proteins of recombinant DEN4 (rDEN4) virus with those from DEN3 Sleman/78 in the presence (rDEN3/4Delta30(ME)) and the absence (rDEN3/4(ME)) of the 030 mutation, a previously described 30-nucleotide deletion in the 3' untranslated region. In addition, a full-length infectious cDNA clone was generated from the DEN3 isolate and used to produce rDEN3 virus and the vaccine candidate rDEN3Delta30. The chimeric viruses rDEN3/4(ME) and rDEN3/4Delta30(ME) appear to be acceptable vaccine candidates since they were restricted in replication in severe combined immune deficiency mice transplanted with human hepatoma cells, in rhesus monkeys, and in Aedes and Toxorynchites mosquitoes, and each was protective in rhesus monkeys against DEN3 virus challenge. The rDEN3/4(ME) and rDEN3/4Delta30(ME) viruses were comparable in all parameters evaluated, indicating that antigenic chimerization resulted in the observed high level of attenuation. Surprisingly, rDEN3Delta30 was not attenuated in any model tested when compared with wild-type rDEN3 and therefore, is not a vaccine candidate at present. Thus, the rDEN3/4(ME) and rDEN3/4Delta30(ME) antigenic chimeric viruses can be considered for evaluation in humans and for inclusion in a tetravalent dengue vaccine. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Blaney, JE (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM jblaney@niaid.nih.gov; chanson@niaid.nih.gov; efirestone@niaid.nih.gov; khanley@niaid.nih.gov; bmurphy@niaid.nih.gov; swhitehead@niaid.nih.gov NR 47 TC 68 Z9 75 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2004 VL 71 IS 6 BP 811 EP 821 PG 11 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 884ZN UT WOS:000226125300021 PM 15642976 ER PT J AU Costin, GE Vieira, WD Valencia, JC Rouzaud, F Lamoreux, ML Hearing, VJ AF Costin, GE Vieira, WD Valencia, JC Rouzaud, F Lamoreux, ML Hearing, VJ TI Immortalization of mouse melanocytes carrying mutations in various pigmentation genes SO ANALYTICAL BIOCHEMISTRY LA English DT Editorial Material ID OCULOCUTANEOUS ALBINISM; SENESCENCE; MELANOMA; CLONING; CULTURE; FAMILY; COLOR; LINE; SKIN C1 NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX 77843 USA. RP Hearing, VJ (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 18 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 1 PY 2004 VL 335 IS 1 BP 171 EP 174 DI 10.1016/j.ab.2004.07.035 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 870GK UT WOS:000225045400022 PM 15519586 ER PT J AU Gergen, PJ AF Gergen, PJ TI Promoting quality in asthma care: rewarding what we teach SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Editorial Material ID CHILDHOOD; CHILDREN; COHORT C1 NIH, Bethesda, MD 20892 USA. RP Gergen, PJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD DEC PY 2004 VL 93 IS 6 BP 510 EP 512 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 879WN UT WOS:000225750000003 PM 15609758 ER PT J AU Gruger, T Nitiss, JL Maxwell, A Zechiedrich, EL Heisig, P Seeber, S Pommier, Y Strumberg, D AF Gruger, T Nitiss, JL Maxwell, A Zechiedrich, EL Heisig, P Seeber, S Pommier, Y Strumberg, D TI A mutation in Escherichia coli DNA gyrase conferring quinolone resistance results in sensitivity to drugs targeting eukaryotic topoisomerase II SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID STAPHYLOCOCCUS-AUREUS; EFFLUX PUMPS; FLUOROQUINOLONE RESISTANCE; PSEUDOMONAS-AERUGINOSA; DETERMINING REGION; GENETIC-EVIDENCE; ENZYME-DNA; IV; INHIBITORS; CLEAVAGE AB Fluoroquinolones are broad-spectrum antimicrobial agents that target type II topoisomerases. Many fluoroquinolones are highly specific for bacterial type II topoisomerases and act against both DNA gyrase and topoisomerase IV. In Escherichia coli, mutations causing quinolone resistance are often found in the gene that encodes the A subunit of DNA gyrase. One common site for resistance-conferring mutations alters Ser(83), and mutations to Leu or Trp result in high levels of resistance to fluoroquinolones. In the present study we demonstrate that the mutation of Ser(83) to Trp in DNA gyrase (Gyr(S83W)) also results in sensitivity to agents that are potent inhibitors of eukaryotic topoisomerase II but that are normally inactive against prokaryotic enzymes. Epipodophyllotoxins, such as etoposide, teniposide and amino-azatoxin, inhibited the DNA supercoiling activity of Gyr(S83W), and the enzyme caused elevated levels of DNA cleavage in the presence of these agents. The DNA sequence preference for Gyr(S83W)-induced cleavage sites in the presence of etoposide was similar to that seen with eukaryotic type II topoisomerases. Introduction of the Gyr(S83W) mutation in E. coli strain RFM443-242 by site-directed mutagenesis sensitized it to epipodophyllotoxins and amino-azatoxin. Our results demonstrate that sensitivity to agents that target topoisomerase II is conserved between prokaryotic and eukaryotic enzymes, suggesting that drug interaction domains are also well conserved and likely occur in domains important for the biochemical activities of the enzymes. C1 Univ Hamburg, Inst Pharm, Dept Pharmaceut Biol & Microbiol, Hamburg, Germany. St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Univ Essen Gesamthsch, W German Canc Ctr, Dept Internal Med & Med Oncol, D-45122 Essen, Germany. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Strumberg, D (reprint author), Univ Essen Gesamthsch, Sch Med, Dept Internal Med, Hufelandstr 55, D-45122 Essen, Germany. EM dirk.strumberg@uni-essen.de RI Nitiss, John/E-9974-2010; OI Nitiss, John/0000-0002-1013-4972 FU NCI NIH HHS [R01 CA052814, CA21765, CA52814, P30 CA021765] NR 62 TC 14 Z9 14 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2004 VL 48 IS 12 BP 4495 EP 4504 DI 10.1128/AAC.48.13.4495-4504.2004 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 876CW UT WOS:000225474500001 PM 15561817 ER PT J AU Yeh, LH Alayash, AI AF Yeh, LH Alayash, AI TI Effects of cell-free hemoglobin on hypoxia-inducible factor (HIF-1 alpha) and heme oxygenase (HO-1) expressions in endothelial cells subjected to hypoxia SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID CROSS-LINKED HEMOGLOBIN; NITRIC-OXIDE SYNTHASE; REDOX SIDE REACTIONS; BLOOD SUBSTITUTES; FACTOR-I; SIGNAL-TRANSDUCTION; GENE; MECHANISMS; ACTIVATION; INDUCTION AB We have investigated the impact of diaspirin cross-linked hemoglobin (DBBF-Hb), a blood substitute, on cell signaling pathways that are modulated in part by biological peroxides (i.e., hydrogen peroxide, lipid peroxide, and peroxynitrite). Bovine aortic endothelial cells (BAECs) subjected to hypoxia expressed hypoxia-inducible factor (HIF-1alpha) in a time course that paralleled the expressions of heme oxygenase (HO-1). Co-incubation of the oxy form (HbFe(2+)) with hypoxic BAECs resulted in an increase in the expression of HIF-1alpha in a manner that corresponded linearly with the decay of HbFe(2+) and accumulation of the ferric form (HbFe(3+)). Inclusion of HbFe(3+) with hypoxic BAECs produced twice as much expression in the HIF-1alpha and HO-1 proteins as opposed to HbFe(2+) alone, or HbFe(2+) plus hypoxia. In addition, higher and more persistent levels of the ferryl form (HbFe(4+)), due to the consumption of endogenous peroxides, were found in the hypoxic media containing hemoglobin. Nitric oxide (NO) released from an NO donor reduced the levels of HIF-lalpha in the hypoxic cells treated with either HbFe(2+) or HbFe(3+), but had little or no effect on the levels of HO-1. DBBF-Hb modulates key cell-signaling pathways by competing with peroxides required for the deactivation of HIF-1alpha, which may modulate important physiological mediators. C1 US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bethesda, MD 20892 USA. RP US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, 8800 Rockville Pike,Bldg 29,Room 112, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 52 TC 21 Z9 21 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD DEC PY 2004 VL 6 IS 6 BP 944 EP 953 DI 10.1089/1523086042259850 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 869XZ UT WOS:000225019300002 PM 15548892 ER PT J AU Nagababu, E Rifkind, JM AF Nagababu, E Rifkind, JM TI Heme degradation by reactive oxygen species SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID RED-BLOOD-CELLS; HYDROGEN-PEROXIDE; CARBON-MONOXIDE; IRON RELEASE; CYTOCHROME-P-450 HEME; ACID HYDROPEROXIDE; LIPID-PEROXIDATION; OXIDATIVE STRESS; FENTON REAGENT; HUMAN-DISEASE AB Heme proteins play a major role in various biological functions, such as oxygen sensing, electron transport, signal transduction, and antioxidant defense enzymes. Most of these reactions are carried out by redox reactions of heme iron. As the heme is not recycled, most cells containing heme proteins have the microsomal mixed function oxygenase, heme oxygenase, which enzymatically degrades heme to biliverdin, carbon monoxide, and iron. However, the red cell with the largest pool of heme protein, hemoglobin, contains no heme oxygenase, and enzymatic degradation of the red cell heme occurs only after the senescent red cells are removed by the reticuloendothelial system. Therefore, only nonenzymatic heme degradation initiated when the heme iron undergoes redox reactions in the presence of oxygen-producing reactive oxygen species takes place in the red cell. Unlike enzymatic degradation, which specifically attacks the a-methene bridge, reactive oxygen species randomly attack all the carbon methene bridges of the tetrapyrrole rings, producing various pyrrole products in addition to releasing iron. This review focuses on the literature related to nonenzymatic heme degradation with special emphasis on hemoglobin, the dominant red cell heme protein. C1 NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. RP NIA, Mol Dynam Sect, NIH, 5600 Nathan Shock Dr,TRIAD Room 406A, Baltimore, MD 21224 USA. EM enikan@grc.nia.nih.gov NR 82 TC 106 Z9 107 U1 3 U2 23 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD DEC PY 2004 VL 6 IS 6 BP 967 EP 978 DI 10.1089/1523086042259823 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 869XZ UT WOS:000225019300004 PM 15548894 ER PT J AU Buehler, PW Alayash, AI AF Buehler, PW Alayash, AI TI Oxygen sensing in the circulation: "Cross talk" between red blood cells and the vasculature SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID HYPOXIA-INDUCIBLE FACTOR-1; ENDOTHELIAL GROWTH-FACTOR; ADVENTITIAL VASA VASORUM; FACTOR GENE-EXPRESSION; NITRIC-OXIDE; FACTOR-I; SIGNAL-TRANSDUCTION; S-NITROSOHEMOGLOBIN; ERYTHROPOIETIN GENE; CYTOCHROME-OXIDASE AB Oxygen (O-2) sensing in blood and regulation of microvascular tone appear to involve hemoglobin (Hb) conformational changes resulting from O-2 desaturation. This observation has prompted the thought that Hb functions as both an O-2 sensor and regulator of microvasular blood flow to meet local tissue oxygen demand. The mechanism(s) by which this is accomplished has recently been the subject of increasing debate. Three primary hypotheses are described within the literature and include release of adenosine 5'-triphosphate by red blood cells (RBCs), release of S-nitrosylated molecules from RBCs originally bound to beta93 cysteine residues of oxyHb, and nitrite conversion and storage of nitric oxide by Hb at the site of ferric (Fe3+) and ferrous (Fe2+) Hb. Within extravascular cells, the global regulator of oxygen homeostasis is hypoxia-inducible factor-1 (HIF-1). This transcriptional factor is tightly regulated by O-2 and cellular redox-sensitive mechanisms. HIF-1 activation is responsible for the up-regulation of proteins, which increase O-2 supply. We believe that there are important and yet unexplored mechanisms by which RBCs can directly or indirectly communicate via redox intermediates with extravascular sites as part of the global O-2 sensing mechanism. C1 US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bethesda, MD 20892 USA. RP US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bldg 29,Room 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 86 TC 21 Z9 21 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD DEC PY 2004 VL 6 IS 6 BP 1000 EP 1010 DI 10.1089/1523086042259814 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 869XZ UT WOS:000225019300007 PM 15548897 ER PT J AU Sklar, PA Grubb, JR Voell, JD Zalos, G Blackwelder, WC Metcalf, JA Rupert, A Gladwin, MT Witek, J Davey, RT Masur, H Cannon, RO AF Sklar, PA Grubb, JR Voell, JD Zalos, G Blackwelder, WC Metcalf, JA Rupert, A Gladwin, MT Witek, J Davey, RT Masur, H Cannon, RO TI Endothelial dysfunction in HIV-infected patients on CART does not improve even when lipid profiles improve on pravastatin SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY OCT 25-28, 2004 CL Washington, DC C1 Drexel Univ, Philadelphia, PA 19104 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD DEC PY 2004 VL 9 IS 6 MA 024 BP L15 EP L15 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 960TL UT WOS:000231616000053 ER PT J AU Bachrach, G Haake, SK Glick, A Hazan, R Naor, R Andersen, RN Kolenbrander, PE AF Bachrach, G Haake, SK Glick, A Hazan, R Naor, R Andersen, RN Kolenbrander, PE TI Characterization of the novel Fusobacterium nucleatum plasmid pKH9 and evidence of an addiction system SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID BACILLUS-SUBTILIS SPOIIIE; TOXIN-ANTITOXIN SYSTEM; ORAL EPITHELIAL-CELLS; PORPHYROMONAS-GINGIVALIS; PERIODONTAL BACTERIA; ESCHERICHIA-COLI; GENOME SEQUENCE; DNA; ALIGNMENT; DIVISION AB Fusobacterium nucleatum is an important oral anaerobic pathogen involved in periodontal and systemic infections. Studies of the molecular mechanisms involved in fusobacterial virulence and adhesion have been limited by lack of systems for efficient genetic manipulation. Plasmids were isolated from eight strains of F. nucleatum. The smallest plasmid, pKH9 (4,975 bp), was characterized and used to create new vectors for fusobacterial genetic manipulation. DNA sequence analysis of pKH9 revealed an open reading frame (ORF) encoding a putative autonomous rolling circle replication protein (Rep), an ORF predicted to encode a protein homologous to members of the FtsK/SpoIIIE cell division-DNA segregation protein family, and an operon encoding a putative toxin-antitoxin plasmid addiction system (txf-axf). Deletion analysis localised the pKH9 replication region in a 0.96-kbp fragment. The pKH9 rep gene is not present in this fragment, suggesting that pKH9 can replicate in fusobacteria independently of the Rep protein. A pKH9-based, compact Escherichia coli-F. nucleatum shuttle plasmid was constructed and found to be compatible with a previously described pFN1-based fusobacterial shuttle plasmid. Deletion of the pKH9 putative addiction system (txf-axf) reduced plasmid stability in fusobacteria, indicating its addiction properties and suggesting it to be the first plasmid addiction system described for fusobacteria. pKH9, its genetic elements, and its shuttle plasmid derivatives can serve as useful tools for investigating fusobacterial properties important in biofilm ecology and pathogenesis. C1 Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Inst Dent Sci, IL-91120 Jerusalem, Israel. Univ Calif Los Angeles, Sch Dent, Dent Res Inst, Sec Periodont & Oral Biol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Dent, Dent Res Inst, Med Sect, Los Angeles, CA USA. Natl Inst Dent & Craniofacial Res, NIH, Oral Infect & Immun Branch, Bethesda, MD USA. RP Bachrach, G (reprint author), Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Inst Dent Sci, POB 12272, IL-91120 Jerusalem, Israel. EM bgilad@md2.huji.ac.il FU NIDCR NIH HHS [DE12639] NR 31 TC 10 Z9 11 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 2004 VL 70 IS 12 BP 6957 EP 6962 DI 10.1128/AEM.70.12.6957-6962.2004 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 879LM UT WOS:000225719300002 PM 15574887 ER PT J AU Rickard, AH McBain, AJ Stead, AT Gilbert, P AF Rickard, AH McBain, AJ Stead, AT Gilbert, P TI Shear rate moderates community diversity in freshwater biofilms SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MULTISPECIES BIOFILMS; POTABLE WATER; RIBOSOMAL DNA; BACTERIA; COAGGREGATION; SURFACE; FLOW; HYDROPHOBICITY; VELOCITY; ADHESION AB The development of freshwater multispecies biofilms at solid-liquid interfaces occurs both in quiescent waters and under conditions of high shear rates. However, the influence of hydrodynamic shear rates on bacterial biofilm diversity is poorly understood. We hypothesized that different shear rates would significantly influence biofilm diversity and alter the relative proportions of coaggregating and autoaggregating community isolates. In order to study this hypothesis, freshwater biofilms were developed at five shear rates (<0.1 to 305 S-1) in a rotating concentric cylinder reactor fed with untreated potable water. Eubacterial diversity was assessed by denaturing gradient gel electrophoresis (DGGE) and culturing on R2A agar. Fifty morphologically distinct biofilm strains and 16 planktonic strains were isolated by culturing and identified by partial 16S rRNA gene sequencing, and their relatedness was determined by the construction of a neighbor-joining phylogenetic tree. Phylogenetic and DGGE analyses showed an inverse relationship between shear rate and bacterial diversity. An in vitro aggregation assay was used to assess the relative proportions of coaggregating and autoaggregating species from each biofilm. The highest proportion of autoaggregating bacteria was present at high shear rates (198 to 305 S-1). The intermediate shear rate (122 S-1) selected for the highest proportion of coaggregating bacteria (47%, or 17 of a possible 36 coaggregation interactions). Under static conditions (<0.1 S-1), 41 (33%) of a possible 125 coaggregation interactions were positive. Few coaggregation (3.3%) or autoaggregation (25%) interactions occurred between the 16 planktonic strains. In conclusion, these data show that shear rates affect biofilm diversity as well as the relative proportions of aggregating bacteria. C1 Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester, Lancs, England. RP Rickard, AH (reprint author), NIDCR, NIH, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. EM arickard@mail.nih.gov OI McBain, Andrew/0000-0002-5255-5425 NR 53 TC 77 Z9 81 U1 1 U2 25 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 2004 VL 70 IS 12 BP 7426 EP 7435 DI 10.1128/AEM.70.12.7426-7435.2004 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 879LM UT WOS:000225719300060 PM 15574945 ER PT J AU Ornstein, PA Elischberger, HB AF Ornstein, PA Elischberger, HB TI Studies of suggestibility: Some observations and suggestions SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Article ID FALSE CHILDHOOD MEMORIES; EVENT PLAUSIBILITY; CHILDRENS MEMORY; PRESCHOOLERS; TESTIMONY; SCALE C1 Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. NICHHD, Bethesda, MD 20892 USA. RP Ornstein, PA (reprint author), Univ N Carolina, Dept Psychol, CB 3270,Davie Hall, Chapel Hill, NC 27599 USA. EM pao@unc.edu NR 44 TC 6 Z9 6 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0888-4080 J9 APPL COGNITIVE PSYCH JI Appl. Cogn. Psychol. PD DEC PY 2004 VL 18 IS 8 SI SI BP 1129 EP 1141 DI 10.1002/acp.1081 PG 13 WC Psychology, Experimental SC Psychology GA 883RQ UT WOS:000226033800010 ER PT J AU Ruder, AM Waters, MA Butler, MA Carreon, T Calvert, GM Davis-King, KE Schulte, PA Sanderson, WT Ward, EM Connally, LB Heineman, EF Mandel, JS Morton, RF Reding, DJ Rosenman, KD Talaska, G AF Ruder, AM Waters, MA Butler, MA Carreon, T Calvert, GM Davis-King, KE Schulte, PA Sanderson, WT Ward, EM Connally, LB Heineman, EF Mandel, JS Morton, RF Reding, DJ Rosenman, KD Talaska, G CA Brain Canc Collaborative Study Grp TI Gliomas and farm pesticide exposure in men: The upper midwest health study SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article DE agricultural workers' diseases; case-control studies; glioma; pesticides; rural population ID BRAIN CANCER; OCCUPATIONAL EXPOSURE; PROXY RESPONDENTS; SURROGATE RESPONDENTS; PARKINSONS-DISEASE; LUNG-CANCER; NEW-ZEALAND; RISK; MORTALITY; COHORT AB The National Institute for Occupational Safety and Health evaluated farm pesticide exposure and glioma risk in a study that included 457 glioma cases and 648 population-based controls, all adult men (18-80 yr old) and nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. Multiple logistic regressions were used to control for farm residence, age, age group, education, and exposure to other pesticides. No associations were found between glioma and 12 specific pesticides. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) and found reduced glioma risk for insecticides (OR = 0.53, CI = 0.37-0.77), fumigants (OR = 0.57, CI = 0.34-0.95), and organochlorines (OR = 0.66, CI = 0.47-0.94). In analyses excluding proxy respondents (47% of cases) most CIs included 1.0. No positive association of farm pesticide exposure and glioma was found. Other farm exposures may explain the excess brain cancer risk seen in previous studies. C1 NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. NCI, Rockville, MD USA. Univ Minnesota, Minneapolis, MN 55455 USA. Mercy Fdn, Des Moines, IA USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. Michigan State Univ, E Lansing, MI 48824 USA. Univ Cincinnati, Cincinnati, OH USA. RP Ruder, AM (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Ctr Dis Control & Prevent, 4676 Columbia Pkwy,Mailstop R-16, Cincinnati, OH 45226 USA. RI Carreon, Tania/A-6548-2008; Waters, Martha/B-7441-2011; Ruder, Avima/I-4155-2012 OI Ruder, Avima/0000-0003-0419-6664 NR 73 TC 10 Z9 10 U1 3 U2 6 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD DEC PY 2004 VL 59 IS 12 BP 650 EP 657 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 052BA UT WOS:000238204300004 PM 16789473 ER PT J AU Grant, BF Stinson, FS Hasin, DS Dawson, DA Chou, SP Anderson, K AF Grant, BF Stinson, FS Hasin, DS Dawson, DA Chou, SP Anderson, K TI Immigration and lifetime prevalence of DSM-IV psychiatric disorders among Mexican Americans and non-Hispanic Whites in them United States - Results from the national epidemiologic survey on alcohol and related conditions SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; III-R; ICD-10 ALCOHOL; DRUG MODULES; NOSOLOGICAL COMPARISONS; CLINICAL DIAGNOSES; ABUSE DIAGNOSES; HEAVY DRINKERS; LOS-ANGELES AB Background: There exist no national prevalence data on specific DSM-IV Axis I psychiatric disorders among foreign-born and US-born Mexican Americans and non-Hispanic whites. Objective: To present nationally representative data on the prevalence of DSM-IV lifetime-psychiatric disorders among foreign-born and US-born Mexican Americans and non-Hispanic whites. Design: Face-to-face survey conducted in the 2001 2002 National Epidemiologic Survey on Alcohol and Related Conditions. Setting: The United States and District of Columbia, including Alaska and Hawaii. Participants: Household and group-quarters residents, aged 18 years and older (n = 43 093). Main Outcome Measures: Prevalence of DSM-IV substance use disorders and mood and anxiety disorders. Results: With few exceptions, foreign-born Mexican Americans and foreign-born non-Hispanic whites were at significantly lower risk (P<.05) of DSM-IV substance use. and mood and anxiety disorders compared with their US-born counterparts. Although the risk of specific psychiatric disorders was similar between foreign-born Mexican Americans and foreign-born non-Hispanic whites, US-born Mexican Americans were at significantly lower risk (P<.05), of psychiatric morbidity than US-born non-Hispanic whites. Conclusions: Data favoring foreign-born Mexican Americans with respect to mental health may extend to foreign-born non-Hispanic whites. Future research among foreign-born and US-born Mexican Americans and the foreign-born and US-born of other origins and descents is needed to understand what appears to be the protective effects of culture and the deleterious effects of acculturation on psychiatric morbidity in the United States. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Bethesda, MD USA. Columbia Univ, Dept Epidemiol, New York, NY USA. Columbia Univ, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, MS 9304,5635 Fishers Ln, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov NR 47 TC 272 Z9 274 U1 3 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2004 VL 61 IS 12 BP 1226 EP 1233 DI 10.1001/archpsyc.61.12.1226 PG 8 WC Psychiatry SC Psychiatry GA 877DU UT WOS:000225548800006 PM 15583114 ER PT J AU Ward, NS Cohen, LG AF Ward, NS Cohen, LG TI Mechanisms underlying recovery of motor function after stroke SO ARCHIVES OF NEUROLOGY LA English DT Review ID USE-DEPENDENT PLASTICITY; LONG-TERM POTENTIATION; PREMOTOR CORTEX; REPETITIVE TMS; STIMULATION; CONNECTIONS; FMRI; REORGANIZATION; AMPHETAMINE; MODULATION AB Stroke is the leading cause of long-term disability worldwide and a condition for which there is no universally accepted treatment. The development of new effective therapeutic strategies relies on a better understanding of the mechanisms underlying recovery of function. Noninvasive techniques to study brain function, including functional magnetic resonance imaging, positron emission tomography, transcranial magnetic stimulation, electroencephalography, and magneto encephalography, led to recent studies that identified some of these operating mechanisms, resulting in the formulation of novel approaches to motor rehabilitation. C1 NINDS, Human Cort Phsiol Sect, NIH, Bethesda, MD 20817 USA. UCL, Inst Neurol, Wellcome Dept Imaging Neurosci, London, England. RP Cohen, LG (reprint author), NINDS, Human Cort Phsiol Sect, NIH, Bldg 10,Room 5N226, Bethesda, MD 20817 USA. EM cohen@ninds.nih.gov FU Wellcome Trust [071398] NR 32 TC 290 Z9 317 U1 1 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 EI 1538-3687 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2004 VL 61 IS 12 BP 1844 EP 1848 DI 10.1001/archneur.61.12.1844 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 878OM UT WOS:000225656100003 PM 15596603 ER PT J AU Morris, HR Steele, JC Crook, R Wavrant-De Vrieze, F Onstead-Cardinale, L Gwinn-Hardy, K Wood, NW Farrer, M Lees, AJ McGeer, PL Siddique, T Hardy, J Perez-Tur, J AF Morris, HR Steele, JC Crook, R Wavrant-De Vrieze, F Onstead-Cardinale, L Gwinn-Hardy, K Wood, NW Farrer, M Lees, AJ McGeer, PL Siddique, T Hardy, J Perez-Tur, J TI Genome-wide analysis of the Parkinsonism-dementia complex of Guam SO ARCHIVES OF NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; LINKAGE DISEQUILIBRIUM; GENETIC INVESTIGATIONS; CLINICAL-FEATURES; ENDEMIC DISEASE; ISLAND; ALS; FREQUENCY; CHAMORROS; PATTERNS AB Background: Parkinsonism-dementia complex (PDC) is a neurofibrillary tangle degeneration involving the deposition of Alzheimer-type tau, predominantly in the mesial temporal cortex, brainstem, and basal ganglia. It occurs in focal geographic isolates, including Guam and the Kii peninsula of Japan. The familial clustering of the disease has suggested that a genetic factor could be important in its etiology. Objective: To determine whether a genetic locus could be identified, linked, or associated with PDC. Design and Patients: We performed a genome-wide association study of 22 Guamanian PDC and 19 control subjects using 834 microsatellite markers with an approximate genome-wide marker density of 4.4 centimorgans. Results: Two-point association analysis identified 17 markers (P<.015). Each of these markers then underwent conventional linkage analysis in 5 families with PDC. One marker, D20S103, generated a logarithm of odds score of greater than 1.5. Multipoint association analysis also highlighted 2 other areas on chromosome 14q (adjacent to D14S592, 59.2 megabases [M]) and chromosome 20 (adjacent to D20S470, 17.4 M) with multipoint association logarithm of the odds scores of greater than 2. The areas around D20S103, D14S592, and D20S470 were further analyzed by association using additional microsatellite markers and by conventional linkage analysis. This did not provide further evidence for the role of these areas in PDC. Conclusions: This study has not identified a single gene locus for PDC, confirming the impression of a geographic disease isolate with a complex genetic, a genetic/environmental etiology, or a purely environmental etiology. C1 UCL, Dept Mol Pathogenesis, London, England. UCL, Inst Neurol, Queen Sq Brain Bank Neurol Disorders, Sara Koe PSP Res Ctr, London, England. UCL, Reta Lila West Inst Neurol Sci, London, England. Micronesian Hlth Study 2, Tamuning, GU USA. Mayo Clin, Dept Neurosci, Jacksonville, FL USA. Univ British Columbia, Kinsmen Lab Neurol Res, Vancouver, BC, Canada. Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. CSIC, Inst biomed Valencia, Unitat Genet Mol, Valencia, Spain. Cardiff Univ, Coll Med, Dept Med, Neurol Sect, Cardiff, S Glam, Wales. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10,Room 6C103,MSC1589, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Morris, Huw/B-8527-2008; Gwinn, Katrina/C-2508-2009; Perez-Tur, Jordi/A-2143-2010; turton, miranda/F-4682-2011; Hardy, John/C-2451-2009; Lees, Andrew/A-6605-2009; Wood, Nicholas/C-2505-2009 OI Morris, Huw/0000-0002-5473-3774; Perez-Tur, Jordi/0000-0002-9111-1712; Wood, Nicholas/0000-0002-9500-3348 NR 43 TC 29 Z9 30 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2004 VL 61 IS 12 BP 1889 EP 1897 DI 10.1001/archneur.61.12.1889 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 878OM UT WOS:000225656100009 PM 15596609 ER PT J AU Rogaeva, E Johnson, J Lang, AE Gulick, C Gwinn-Hardy, K Kawarai, T Sato, C Morgan, A Werner, J Nussbaum, R Petit, A Okun, MS McInerney, A Mandel, R Groen, JL Fernandez, HH Postuma, R Foote, KD Salehi-Rad, S Liang, Y Reimsnider, S Tandon, A Hardy, J St George-Hyslop, P Singleton, AB AF Rogaeva, E Johnson, J Lang, AE Gulick, C Gwinn-Hardy, K Kawarai, T Sato, C Morgan, A Werner, J Nussbaum, R Petit, A Okun, MS McInerney, A Mandel, R Groen, JL Fernandez, HH Postuma, R Foote, KD Salehi-Rad, S Liang, Y Reimsnider, S Tandon, A Hardy, J St George-Hyslop, P Singleton, AB TI Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; EARLY-ONSET PARKINSONISM; MUTATIONS; FAMILIES; PATHWAY AB Background: Mutations in the PTEN-induced kinase (PINK1) gene located within the PARK6 locus on chromosome 1p35-p36 have recently been identified in patients with recessive early-onset Parkinson disease. Objective: To assess the prevalence of PINK1 mutations within a series of early- and late-onset Parkinson disease patients living in North America. Design: All coding exons of the PINK1 gene were sequenced in a series of 289 Parkinson disease patients and 80 neurologically normal control subjects; the mutation frequencies were evaluated in additional controls (100 white and 50 Filipino subjects). Results: We identified 27 variants, including the first reported compound heterozygous mutation (Glu240Lys and Leu489Pro) and a homozygous Leu347Pro mutation in 2 unrelated young-onset Parkinson disease patients. Conclusion: Autosomal recessive mutations in PINK1 are a rare cause of young-onset Parkinson disease. C1 NIA, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Hlth Network, Dept Med, Div Neurol, Toronto, ON, Canada. Univ Toronto, Toronto Western Hosp, Dept Med, Div Neurol, Toronto, ON, Canada. Univ Toronto, Toronto Western Hosp, Movement Disorders Ctr, Toronto, ON, Canada. Univ Toronto, Toronto Western Hosp, Ctr Res Neurodegenetat dis, Toronto, ON, Canada. Univ Florida, Movement Disorders Ctr, Dept Neurol, Gainesville, FL USA. Univ Florida, Movement Disorders Ctr, Dept Neurosurg, Gainesville, FL USA. Univ Florida, Movement Disorders Ctr, Dept Psychiat, Gainesville, FL USA. RP Singleton, AB (reprint author), NIA, Mol Genet Sect, NIH, 35 Convent Dr,Room 1A1015,Mail Stop Code 3707, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Johnson, Janel/A-7136-2010; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; OI Okun, Michael/0000-0002-6247-9358 NR 16 TC 113 Z9 123 U1 3 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2004 VL 61 IS 12 BP 1898 EP 1904 DI 10.1001/archneur.61.12.1898 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 878OM UT WOS:000225656100010 PM 15596610 ER PT J AU Maisto, SA Carey, MP Carey, KB Gordon, CM Schum, JL Lynch, KG AF Maisto, SA Carey, MP Carey, KB Gordon, CM Schum, JL Lynch, KG TI The relationship between alcohol and individual differences variables on attitudes and behavioral skills relevant to sexual health among heterosexual young adult men SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Article DE condom use; alcohol; risk behavior; men; attitudes ID AIDS-RISK BEHAVIOR; CONDOM USE; SENSATION SEEKING; HIV-INFECTION; SUBSTANCE USE; URBAN WOMEN; INTOXICATION; ASSOCIATION; MYOPIA; SCALE AB The purpose of this experiment was to investigate the effects of alcohol, alcohol sex expectancies, and sexual sensation seeking on determinants of sexual health behavior according to the Information Motivation - Behavioral Skills (IMB) model. The participants were 48 heterosexual young adultmales who attended 2 laboratory sessions. During Session 1, participants completed a set of screening and individual differences measures, and during Session 2 they were randomly assigned to 1 of 3 beverage conditions: control, alcohol (0.65 g alcohol/kg body weight), or placebo. Following the experimental manipulation, all participants completed measures regarding attitudes toward condom use, intention to engage in risky sex, and condom use negotiation skills. The results showed that participants who consumed alcohol had poorer negotiation skills and greater intention to engage in risky sex compared to participants who did not drink alcohol. Although alcohol did not affect any dimension of attitude regarding condom use, attitude about condoms' effects on sex, as well as sexual sensation seeking, were correlated with both intention ratings and skills. Multiple regression models, including both attitudes and sensation seeking, showed that attitudes accounted for 20 - 25% of variance independent of beverage condition in predicting intention ratings and skills. The findings were consistent with past research showing that alcohol consumption can have detrimental effects on determinants of sexual health behavior and that individual differences factors can enhance the power of models like the IMB to predict such behavior. C1 Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. Syracuse Univ, Ctr Hlth & Behav, Syracuse, NY USA. NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Maisto, SA (reprint author), Syracuse Univ, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA. EM samaisto@psych.syr.edu FU NIAAA NIH HHS [AA/MH11613]; NIMH NIH HHS [K02 MH001582, K02 MH001582-05, K02-MH01582, K02 MH001582-04] NR 49 TC 37 Z9 37 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0004-0002 J9 ARCH SEX BEHAV JI Arch. Sex. Behav. PD DEC PY 2004 VL 33 IS 6 BP 571 EP 584 DI 10.1023/B:ASEB.0000044741.09127.e6 PG 14 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 861RV UT WOS:000224437200006 PM 15483371 ER PT J AU Bentley, K Deacon, N Sonza, S Zeichner, S Churchill, M AF Bentley, K Deacon, N Sonza, S Zeichner, S Churchill, M TI Mutational analysis of the HIV-1 LTR as a promoter of negative sense transcription SO ARCHIVES OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; NATURAL ANTISENSE TRANSCRIPTS; IN-VITRO; T-CELLS; GENE-EXPRESSION; BINDING-SITES; HIGH-AFFINITY; PLUS STRAND; TAR RNA AB The HIV-1 gene promoter is a bi-directional promoter of transcription. We report the characterization of the negative sense promoter (NSP) by analysis of the effect on negative sense transcription of a series of LTR U3 region substitution mutants. Mutations in the region nt - 58 to - 183 ( positive sense transcription initiation nt +1) reduced transcription to < 15% of wild type NSP activity. This region, essential for NSP activity, was designated the core basal promoter. Over expression of NF-κB RelA(p65) and LEF-1 increased negative sense expression, as did over expression of H-ras oncogene, consistent with the presence of cognate sequence motifs for NF-κB, LEF-1 and RBF. We were also able to confirm that the NSP is a TATA-less promoter inhibited by HIV-1 Tat. Based on our findings, we propose a model for the interaction between the NSP and PSP, and the role of Tat in regulating the interaction. C1 Macfarlane Burnet Inst Med Res & Publ Hlth, Natl Ctr HIV Virol Res, AIDS Mol Biol Unit, Melbourne, Vic 3004, Australia. Macfarlane Burnet Inst Med Res & Publ Hlth, Natl Ctr HIV Virol Res, AIDS Pathogenesis Res Unit, Melbourne, Vic 3004, Australia. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Churchill, M (reprint author), Macfarlane Burnet Inst Med Res & Publ Hlth, Natl Ctr HIV Virol Res, AIDS Mol Biol Unit, Commercial Rd, Melbourne, Vic 3004, Australia. EM churchil@burnet.edu.au NR 55 TC 9 Z9 10 U1 2 U2 2 PU SPRINGER WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD DEC PY 2004 VL 149 IS 12 BP 2277 EP 2294 DI 10.1007/s00705-004-0386-8 PG 18 WC Virology SC Virology GA 873TF UT WOS:000225303200001 PM 15338321 ER PT J AU Okada, SK Fischer, R Yarboro, C Illei, G Lipsky, P Grammer, A AF Okada, SK Fischer, R Yarboro, C Illei, G Lipsky, P Grammer, A TI Peripheral B cell abnormalities in systemic lupus erythematosus: Comparative phenotypes assessed by polychromatic flow cytometry and effects of treatment with humanized anti-IL6R monoclonal antibody. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2004 VL 50 IS 12 BP 4081 EP 4081 PG 1 WC Rheumatology SC Rheumatology GA 879WP UT WOS:000225750200055 ER PT J AU Lapteva, L Roebuck-Spencer, TM Nowak, MS Yarboro, CH Takada, K Pao, M Rosenstein, D Jacobs, G Weickert, TW Bleiberg, J Volpe, B Diamond, B Lipsky, PE Illei, GG AF Lapteva, L Roebuck-Spencer, TM Nowak, MS Yarboro, CH Takada, K Pao, M Rosenstein, D Jacobs, G Weickert, TW Bleiberg, J Volpe, B Diamond, B Lipsky, PE Illei, GG TI Individual adjustment for expected level of cognitive functioning improves sensitivity of testing for cognitive dysfunction (CdysF) in patients with systemic lupus erythematosus (SLE). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol C1 NIAMSD, DHHS, NIH, Bethesda, MD 20892 USA. Natl Rehabil Hosp, Washington, DC USA. NIMH, DHHS, NIH, Bethesda, MD 20892 USA. Cornell Univ, New York, NY 10021 USA. Yeshiva Univ Albert Einstein Coll Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2004 VL 50 IS 12 BP 4092 EP 4092 PG 1 WC Rheumatology SC Rheumatology GA 879WP UT WOS:000225750200086 ER PT J AU Wolfe, F Nadareishvili, ZG Hallenbeck, JM Michaud, K AF Wolfe, F Nadareishvili, ZG Hallenbeck, JM Michaud, K TI Anti-tumor necrosis factor therapy with infliximab decreases the risk of stroke in patients with rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol C1 Natl Data Bank Rheumat Dis, Wichita, KS USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2004 VL 50 IS 12 BP 4099 EP 4099 PG 1 WC Rheumatology SC Rheumatology GA 879WP UT WOS:000225750200105 ER PT J AU Ryu, JK Song, SU Choi, HK Seong, DH Yoon, SM Kim, SJ Suh, JK AF Ryu, JK Song, SU Choi, HK Seong, DH Yoon, SM Kim, SJ Suh, JK TI Plasma transforming growth factor-beta(1) levels in patients with erectile dysfunction SO ASIAN JOURNAL OF ANDROLOGY LA English DT Article DE erectile dysfunction; transforming growth factor; fibrosis; diagnosis ID FACTOR-BETA; SMOOTH-MUSCLE; EXPRESSION; ATHEROSCLEROSIS; MECHANISMS; FIBROSIS; DISEASE; CELLS; MEN AB To evaluate the plasma TGF-beta(1), level in erectile dysfunction (ED) patients of various causes. Methods: Sixty-two patients with ED and 26 potent men were subjected to the study. Based on multidisciplinary work-ups, including medical history, physical examinations, blood tests with lipid profile and hormones, penile duplex Doppler ultrasonogram and neurophysiological tests, causes for ED were classified as psychogenic (n= 15), neurogenic (n= 16) and vasculogenic (n=31). The plasma TGF-beta(1), level was measured by the ELISA method. Results: The plasma TGFbeta(1), level was significantly increased in the ED group (6.7 +/- 4.9 ng/mL), compared to the control (4.0 +/- 2.1 ng/mL) (P <0.01). In the ED groups, there was a significant increase in the vasculogenic group (9.0 +/- 5.5 ng/mL), compared to the psychogenic (3.8 +/- 1.8 ng/mL) and neurogenic groups (4.8 +/- 3.2 ng/mL) (P<0.01). Of the vascular risk factors, both the smoking (7.5 +/- 4.7 ng/mL) and dyslipidemia groups (7.4 +/- 4.4 ng/mL) showed significantly increased plasma TGF-P, levels, compared to the non-smokers (5.5 +/- 2.8 ng/mL), and those without dyslipidernia (4.8 +/- 2.8 ng/mL) (P<0.05). Conclusion: Vascular risk factors are associated with an elevated plasma TGF-P, level, which may contribute to cavernous fibrosis and ED. C1 Inha Univ, Sch Med, Dept Urol, Inchon 400103, South Korea. Inha Univ, Sch Med, Clin Res Ctr, Inchon 400103, South Korea. Yonsei Univ, Sch Med, Dept Urol, Seoul, South Korea. NIH, NCI, Bethesda, MD USA. RP Suh, JK (reprint author), Inha Univ, Sch Med, Dept Urol, 7-206 3rd St, Inchon 400103, South Korea. EM jksuh@inha.ac.kr NR 20 TC 13 Z9 13 U1 0 U2 0 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1008-682X J9 ASIAN J ANDROL JI Asian J. Androl. PD DEC PY 2004 VL 6 IS 4 BP 349 EP 353 PG 5 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 877XB UT WOS:000225607300012 PM 15546028 ER PT J AU Jia, YP Ramasamy, S Wood, F Alayash, AI Rifkind, JM AF Jia, YP Ramasamy, S Wood, F Alayash, AI Rifkind, JM TI Cross-linking with O-raffinose lowers oxygen affinity and stabilizes haemoglobin in a non-cooperative T-state conformation SO BIOCHEMICAL JOURNAL LA English DT Article DE blood substitute; haemoglobin; modified Hb; oxygen transport; T state ID NITRIC-OXIDE; INOSITOL HEXAPHOSPHATE; FUNCTIONAL-PROPERTIES; QUATERNARY STRUCTURE; SH GROUPS; HEME; COOPERATIVITY; HISTIDINE; BINDING; DEOXYHEMOGLOBIN AB O-R-polyHbA(0) is an intra- and intermolecularly O-raffinose cross-linked derivative of deoxygenated human haemoglobin developed as an oxygen therapeutic. When compared with its native protein (HbA(0)), O-R-polyHbA(0) was found to be locked in the T (tense) quaternary conformation with a lower oxygen affinity, a reduced Bohr effect (50% of HbA(0)) and no measurable cooperativity (h = 1). The kinetics of oxygen and CO binding to the protein indicate lower 'on' rates and faster 'off' rates than HbA(0) and the absence of effects of inositol hexaphosphate (IHP) on the kinetics. Other properties consistent with a T-like conformation are inaccessibility of the betaCys-93 thiol group of O-R-polyHbA(0), the hyperfine splitting from nitrogen in the EPR spectrum of the Fe(II)NO complex of O-R-polyHbA(0) and decreased flexibility in the distal haem pocket, as indicated by low-spin bis-histidine complexes detected by EPR of oxidized chains. A comparison of the properties of O-R-polyHbA(0) with those of HbA(0) with and without IHP, as well as the reaction of nitrite with deoxygenated haemoglobin, provide additional insights into the variations in the conformation of T-state haemoglobin in solution (modifications of the T state produced by adding organic phosphates, like IHP and 2,3-diphosphoglycerate). Although the physiological ramifications of locking HbA0 in the T conformation with the O-raffinose are still unknown, valuable insights into haemoglobin function are provided by these studies of O-R-polyHbA(0). C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 48 TC 16 Z9 18 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 2004 VL 384 BP 367 EP 375 DI 10.1042/BJ20040612 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 879DP UT WOS:000225696900017 PM 15303971 ER PT J AU Yang, Q Gonzalez, FJ AF Yang, Q Gonzalez, FJ TI Peroxisome proliferator-activated receptor alpha regulates B lymphocyte development via an indirect pathway in mice SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE PPAR alpha; B lymphocyte; bone marrow ID FATTY-ACIDS; PPAR-ALPHA; LIPID-METABOLISM; IMMUNE-RESPONSES; BONE-MARROW; LOW-DENSITY; HYPOLIPIDEMIC DRUG; IN-VIVO; EXPRESSION; MECHANISM AB Peroxisome proliferator-activator receptor et (PPARalpha), a member of the nuclear receptor superfamily, has been implicated in the regulation of inflammation and immune response. Adaptive immune responses are suppressed by exposure to PPARalpha agonists, resulting in severe thymus and spleen atrophy. In addition, the decline in both T and B cells is due in part to the loss of splenocytes upon exposure to PPARalpha agonists. Thus, the current study was designed to examine the effect of Wy-14,643, a potent PPARalpha agonist, on B cell development in bone marrow from wild-type and PPARalpha-null mice. Significantly decrease in pro/pre-B cell and total B220(+) cell was observed in wild-type mice in bone marrow upon Wy-14,643 treatment, but not in PPARalpha-null mice. Immature and mature B cell populations are not affected. This suggests that PPARalpha is involved in the development of B cell during lymphoid lineage. However, surprisingly, PPARalpha mRNA was absent in bone marrow as revealed by RT-PCR. Therefore, the effect of PPARalpha on B cell development is by an indirect mechanism. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106B, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 46 TC 7 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 1 PY 2004 VL 68 IS 11 BP 2143 EP 2150 DI 10.1016/j.bcp.2004.08.016 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 868ZP UT WOS:000224952200005 PM 15498504 ER PT J AU Grillon, C Smith, K Haynos, A Nieman, LK AF Grillon, C Smith, K Haynos, A Nieman, LK TI Deficits in hippocampus-mediated Pavlovian conditioning in endogenous hypercortisolism SO BIOLOGICAL PSYCHIATRY LA English DT Article DE trace eyeblink conditioning; classical conditioning; Cushing's syndrome; hypercortisolism; glucocorticoids; verbal memory ID NICTITATING-MEMBRANE RESPONSE; CUSHINGS-SYNDROME; DECLARATIVE MEMORY; CORTISOL-LEVELS; COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; PYRAMIDAL NEURONS; FORMATION VOLUME; AGED RATS; STRESS AB Background Elevated endogenous levels of corticosteroids cause neural dysfunction and loss, especially within the hippocampus, as well as cognitive impairment in hippocampus-mediated tasks. Because Cushing's syndrome patients suffer from hypercortisolism, they represent a unique opportunity to study the impact of elevated glucocorticoids on cognitive functions. The ann of this study was to examine the performance of Cushing's syndrome patients on trace eyeblink conditioning, a cross-species, hippocampal-mediated test of learning and memory. Methods: Eleven Cashing's syndrome patients and 11 healthy control subjects participated in an eyeblink trace conditioning test (1000-msec trace) and a task of declarative memory for words. Salivary cortisol was collected in both the patients and the control subjects, and urinary free cortisol was collected in the patients only. Results: The patients exhibited fewer conditional responses and remembered fewer words, compared with the control subjects. Cortisol levels correlated with immediate and delayed declarative memory only. Conditional response correlated with delayed recall after controlling for the magnitude of unconditional response. Conclusions: The integrity of the hippocampus seems to be compromised in Cushing's syndrome patients. Trace eyeblink conditioning might be useful both as a clinical tool to examine changes in hippocampus function in Cushing's disease patients and as a translational tool of research on the impact of chronic exposure of glucocorticoids. C1 NIMH, Mood & Anxiety Disorders Program, NIH, US Dept HHS, Bethesda, MD USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH, NIH, DHHS, MAP, 15k North Dr,Bldg 15k,Room 113,MSC 2670, Bethesda, MD 20892 USA. EM Grillon.christian@nih.gov NR 56 TC 28 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2004 VL 56 IS 11 BP 837 EP 843 DI 10.1016/j.biopsych.2004.09.003 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 878BR UT WOS:000225622000004 PM 15576060 ER PT J AU Perlman, WR Webster, MJ Kleinman, JE Weickert, CS AF Perlman, WR Webster, MJ Kleinman, JE Weickert, CS TI Reduced glucocorticoid and estrogen receptor alpha messenger ribonucleic acid levels in the amygdala of patients with major mental illness SO BIOLOGICAL PSYCHIATRY LA English DT Article DE amygdala; postmortem; schizophrenia; depression; bipolar disorder; antidepressants ID CORTICOTROPIN-RELEASING HORMONE; DEXAMETHASONE-SUPPRESSION TEST; RAT-BRAIN; MINERALOCORTICOID RECEPTOR; PSYCHIATRIC-DISORDERS; HIPPOCAMPAL-FORMATION; GENDER-DIFFERENCES; GENE-EXPRESSION; MENSTRUAL-CYCLE; RNA LEVELS AB Background: The amygdala is a limbic structure involved in the stress response and the regulation of emotional behaviors, both of which are disrupted in patients with neuropsychiatric illnesses. Because glucocorticoids are mediators of the stress response, we hypothesized that glucocorticoid receptor (GR) messenger ribonucleic acid (mRIVA) levels might be altered in the amygdala. We also hypothesized that estrogen receptor alpha (ERalpha) mRNA expression might be altered in the amygdala, on the basis of observed gender differences in mental illness. Methods: Using quantitative film autoradiography after in situ hybridization with human GR and ERalpha probes, we measured mRNA levels on adjacent amygdala sections in four groups (n = 15 each of subjects with schizophrenia, major depressive disorder, and bipolar disorder, and unaffected control subjects) provided by the Stanley Consortium. Results: We detected main effects of diagnosis and exposure to antidepressant medication on the levels of both mRNAs but no main effect of gender. Compared with control subjects, GR mRNA expression was reduced in the basolateral/lateral nuclei in schizophrenia and bipolar disorder. Estrogen receptor a mRNA levels were reduced in the basomedial nucleus in major depressive disorder and bipolar disorder. Conclusions: Our results support and extend previous findings describing a pattern of steroid hormone mRIVA alterations that differs depending on which brain region is being examined in a given mental illness. C1 Uniformed Serv Univ Hlth Sci, Stanley Fdn Lab Brain Res, Dept Psychiat, Bethesda, MD 20814 USA. NIMH, Clin Brain Disorders Branch, Intramural Res Program, US Dept HHS, Bethesda, MD 20892 USA. RP Perlman, WR (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, US Dept HHS, 10 Ctr Dr,Room 4N313C, Bethesda, MD 20892 USA. EM perlmanw@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011 NR 80 TC 103 Z9 107 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2004 VL 56 IS 11 BP 844 EP 852 DI 10.1016/j.biopsych.2004.09.006 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 878BR UT WOS:000225622000005 PM 15576061 ER PT J AU Hibbeln, JR Bissette, G Umhau, JC George, DT AF Hibbeln, JR Bissette, G Umhau, JC George, DT TI Omega-3 status and cerebrospinal fluid corticotrophin releasing hormone in perpetrators of domestic violence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE corticotrophin releasing hormone; omega-3 acids; docosahexaenoic acid; violence; stress ID ESSENTIAL FATTY-ACIDS; DOUBLE-BLIND; DOCOSAHEXAENOIC ACID; ANXIETY DISORDERS; YOUNG-ADULTS; RAT-BRAIN; DEPRESSION; PROSTAGLANDIN; AGGRESSION; PATHOPHYSIOLOGY AB Background: Elevated levels of corticotropbin-releasing hormone in the cortical-bippocampal-amygdala pathway increase fear and anxiety. which are components of defensive and violent behaviors. Prostaglandins E-2 and F-2omega which increase corticotropbin-releasing hormone RNA axpression in this pathway, are reduced by dietary intakes of omega-3 fiats. Methods: Among 21 perpetrators of domestic violence, cerebrospinal fluid and plasma were assessed for corticotropbin-releasing hormone and fatty acid compositions, respectively. Results: Lower plasma docosabexaenoic acid (wt%fatty acids) alone predicted greater cerebrospinal fluid corticotropbin-releasing hormone (pg/mL), in exponential (r = -.67 p <.006) and linear regressions (r = -0.68, p <.003 excluding four subjects with the highest docosabexaenate levels). Conclusions: In this small observational study, low plasma docosahexenoic acid levels were correlated to higher cerebrospinal fluid corticotropbin-releasing hormone levels. Placebo controlled trials can determine if dietary omega-3.fatty acids can reduce excessive corticotropbin-releasing hormone levels in psycbiatric illnesses. C1 NIAAA, Lab Membrane Biophys & Biochem, DICBR, NIH, Rockville, MD 20852 USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. RP Hibbeln, JR (reprint author), NIAAA, Lab Membrane Biophys & Biochem, DICBR, NIH, 12420 Parklawn Dr,Room 1-14, Rockville, MD 20852 USA. EM jhibbeln@mail.nih.gov NR 32 TC 38 Z9 40 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2004 VL 56 IS 11 BP 895 EP 897 DI 10.1016/j.biopsych.2004.08.021 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 878BR UT WOS:000225622000012 PM 15576068 ER PT J AU Grandjean-Laquerriere, A Laquerriere, P Laurent-Maquin, D Guenounou, M Phillips, TM AF Grandjean-Laquerriere, A Laquerriere, P Laurent-Maquin, D Guenounou, M Phillips, TM TI The effect of the physical characteristics of hydroxyapatite particles on human monocytes IL-18 production in vitro SO BIOMATERIALS LA English DT Article DE IL-18; hydroyapatite particles; human monocytes; physical characteristics ID GAMMA-INDUCING FACTOR; INHIBITS OSTEOCLAST FORMATION; COLONY-STIMULATING FACTOR; BLOOD MONONUCLEAR-CELLS; INTERFERON-GAMMA; IFN-GAMMA; MESSENGER-RNA; SINTERING TEMPERATURE; DIFFERENT FORMS; SURFACE-AREA AB Hydroxyapatite (HA) is widely used to coat the metal parts of prosthetic implants in order to improve their biocompatibility and as a bone defect filling material. HA has been demonstrated to produce particles at the prosthetic interface that lead to an activation of phagocytic cells that induce a cascade reaction leading to bone resorption and aseptic loosening. Monocytes/macrophages are commonly observed in the interface tissue, and are among the first cells to colonize the inflammatory site where they play a key role in the immune response. IL-18 is a pro-inflammatory cytokine. Monocytes/macrophages were described as IL-18 producing cells. IL-18 works antagonistically to IL-6, which activates osteoclastogenesis. In the present study, we investigated the ability of HA particles to induce the production of active IL-18 by human monocytes according to particle characteristics (size, sintering temperature and shape). Our study demonstrates, for the first time, that HA particles are capable of stimulating the production of the proinflammatory cytokine IL-18 in human monocytes according to their particle characteristics. The expression and the production of IL-18 was modified by the parameter studied. The difference observed between the expression and the production could be explain by the production of ICE. The needle shaped particles induced the larger production of IL-18. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. INSERM, ERM 0203, IFR 53, F-51096 Reims, France. UFR Pharm, EA2070, Lab Immunol & Biotechnol, IFR 53, F-51096 Reims, France. RP Grandjean-Laquerriere, A (reprint author), INSERM, ERM 0203, IFR 53, 21 Rue Clement Ader, F-51685 Reims, France. EM alexia.grandjean@univ-reims.fr RI Laquerriere, Patrice/P-1025-2016 OI Laquerriere, Patrice/0000-0001-7637-9094 NR 49 TC 39 Z9 39 U1 2 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD DEC PY 2004 VL 25 IS 28 BP 5921 EP 5927 DI 10.1016/j.biomaterials.2004.02.003 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 845AQ UT WOS:000223208400002 PM 15183606 ER PT J AU Liu, AY Troendle, JF Yu, KF Yuan, VW AF Liu, AY Troendle, JF Yu, KF Yuan, VW TI Conditional maximum likelihood estimation following a group sequential test SO BIOMETRICAL JOURNAL LA English DT Article DE adaptive designs; bias adjustment; conditional bias; interim analysis; secondary endpoints ID CLINICAL-TRIALS; SAMPLE-SIZE; CONFIDENCE-INTERVALS; UNBIASED ESTIMATION; INFERENCE; DESIGN; BIAS AB We consider estimation after a group sequential test. An estimator that is unbiased or has small bias may have substantial conditional bias (Troendle and Yu, 1999, Coburger and Wassmer, 2001). In this paper we derive the conditional maximum likelihood estimators of both the primary parameter and a secondary parameter, and investigate their properties within a conditional inference framework. The method applies to both the usual and adaptive group sequential test designs. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol Therapeut Evaluat Branch, Rockville, MD 20852 USA. RP Liu, AY (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD 20852 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 NR 31 TC 7 Z9 7 U1 1 U2 4 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD DEC PY 2004 VL 46 IS 6 BP 760 EP 768 DI 10.1002/bimj.200410076 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 884KJ UT WOS:000226083300012 ER PT J AU Herring, AH Dunson, DB Dole, N AF Herring, AH Dunson, DB Dole, N TI Modeling the effects of a bidirectional latent predictor from multivariate questionnaire data SO BIOMETRICS LA English DT Article DE Bayes; categorical data; discrete choice model; joint modeling; MCMC algorithm; Poisson latent variables; random effects; stress ID PRETERM DELIVERY; MATERNAL STRESS; BIRTH; RESPONSES AB Researchers often measure stress using questionnaire data on the occurrence of potentially stress-inducing life events and the strength of reaction to these events, characterized as negative or positive and assigned an ordinal ranking. In studying the health effects of stress, one needs to obtain measures of an individual's negative and positive stress levels to be used as predictors. Motivated by data of this type, we propose a latent variable model, which is characterized by event-specific negative and positive reaction scores. If the positive reaction score dominates the negative reaction score for an event, then the individual's reported response to that event will be positive, with an ordinal ranking determined by the value of the score. Measures of overall positive and negative stress can be obtained by summing the reactivity scores across the events that occur for an individual. By incorporating these measures as predictors in a regression model and fitting the stress and outcome models jointly using Bayesian methods, inferences can be conducted without the need to assume known weights for the different events. We propose an MCMC algorithm for posterior computation and apply the approach to study the effects of stress on preterm delivery. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27599 USA. RP Herring, AH (reprint author), Univ N Carolina, Dept Biostat, Campus Box 7420, Chapel Hill, NC 27599 USA. EM aherring@bios.unc.edu OI Dole, Nancy/0000-0002-2113-7984 FU NCRR NIH HHS [RR00046]; NICHD NIH HHS [HD28684]; PHS HHS [S1099-19/21, S455-16/17, S0807-18/20] NR 17 TC 1 Z9 1 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2004 VL 60 IS 4 BP 926 EP 935 DI 10.1111/j.0006-341X.2004.00248.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 882LB UT WOS:000225939300010 PM 15606413 ER PT J AU Kim, HJ Fay, MP Yu, BB Barrett, MJ Feuer, EJ AF Kim, HJ Fay, MP Yu, BB Barrett, MJ Feuer, EJ TI Comparability of segmented line regression models SO BIOMETRICS LA English DT Article DE change point; comparability; joinpoint regression; permutation test; segmented regression; spline regression ID JOIN POINTS; CURVES; SPLINES; TESTS AB Segmented line regression models, which are composed of continuous linear phases, have been applied to describe changes in rate trend patterns. In this article, we propose a procedure to compare two segmented line regression functions, specifically to test (i) whether the two segmented line regression functions are identical or (ii) whether the two mean functions are parallel allowing different intercepts. A general form of the test statistic is described and then the permutation procedure is proposed to estimate the p-value of the test. The permutation test is compared to an approximate F-test in terms of the p-value estimation and the performance of the permutation test is studied via simulations. The tests are applied to compare female lung cancer mortality rates between two registry areas and also to compare female breast cancer mortality rates between two states. C1 Syracuse Univ, Dept Math, Syracuse, NY 13244 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD 20904 USA. RP Kim, HJ (reprint author), Syracuse Univ, Dept Math, Syracuse, NY 13244 USA. EM hjkim@syr.edu RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 19 TC 66 Z9 69 U1 1 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2004 VL 60 IS 4 BP 1005 EP 1014 DI 10.1111/j.0006-341X.2004.00256.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 882LB UT WOS:000225939300018 PM 15606421 ER PT J AU Bertram, R Sherman, A AF Bertram, R Sherman, A TI Filtering of calcium transients by the endoplasmic reticulum in pancreatic beta-cells SO BIOPHYSICAL JOURNAL LA English DT Article ID CA2+-INDUCED CA2+ RELEASE; ELECTRICAL-ACTIVITY; INSULIN-SECRETION; CYTOPLASMIC CA2+; B-CELLS; GLUCOSE; ISLETS; OSCILLATIONS; ACTIVATION; LANGERHANS AB Calcium handling in pancreatic beta-cells is important for intracellular signaling, the control of electrical activity, and insulin secretion. The endoplasmic reticulum (ER) is a key organelle involved in the storage and release of intracellular Ca2+. Using mathematical modeling, we analyze the filtering properties of the ER and clarify the dual role that it plays as both a Ca2+ source and a Ca2+ sink. We demonstrate that recent time-dependent data on the free Ca2+ concentration in pancreatic islets and beta-cell clusters can be explained with a model that uses a passive ER that takes up Ca2+ when the cell is depolarized and the cytosolic Ca2+ concentration is elevated, and releases Ca2+ when the cell is repolarized and the cytosolic Ca2+ is at a lower concentration. We find that Ca2+-induced Ca2+ release is not necessary to explain the data, and indeed the model is inconsistent with the data if Ca2+-induced Ca2+ release is a dominating factor. Finally, we show that a three-compartment model that includes a subspace compartment between the ER and the plasma membrane provides the best agreement with the experimental Ca2+ data. C1 Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. RP Bertram, R (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. EM bertram@math.fsu.edu NR 33 TC 18 Z9 18 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2004 VL 87 IS 6 BP 3775 EP 3785 DI 10.1529/biophysj.104.050955 PG 11 WC Biophysics SC Biophysics GA 875NH UT WOS:000225426700016 PM 15465863 ER PT J AU Boustany, NN Tsai, YC Pfister, B Joiner, WM Oyler, GA Thakor, NV AF Boustany, NN Tsai, YC Pfister, B Joiner, WM Oyler, GA Thakor, NV TI BCL-x(L)-dependent light scattering by apoptotic cells SO BIOPHYSICAL JOURNAL LA English DT Article ID CYTOCHROME-C RELEASE; BCL-X-L; MITOCHONDRIAL STRUCTURE; BAX; LINE; MASS AB We measured the intensity ratio of wide-to-narrow angle scatter, optical scatter image ratio (OSIR), in single cells during apoptosis and after overexpression of the mitochondria-bound antiapoptotic protein lBCL-x(L). OSIR is sensitive to particle size/shape for objects with wavelength-scale dimensions, and was used as a morphometric measure of cellular response. Three cell variants were treated with staurosporine (STS): nontransfected parental CSM14.1, CSM14.1 stably expressing yellow fluorescent protein (YFP) with diffuse YFP fluorescence, and apoptosis-resistant CSM14.1 stably expressing the fusion protein construct YFP-BCL-x(L) with YFP fluorescence localized on the mitochondria. After treatment with 1 or 2 muM STS, the measured OSIR decreased monotonically by similar to25% in the nontransfected and YFP variants, and reached a steady-state value 40 - 60 min after STS treatment. The decrease in OSIR at the onset of apoptosis preceded phosphatidyl serine exposure by 5 h. In the YFP-BCL- x(L) cell variant, the initial OSIR was already similar to24% lower than the initial OSIR in YFP and nontransfected cells, and only decreased by <10% after STS treatment. Alterations in light scattering by cells overexpressing BCL-x(L) even before apoptosis induction raise interesting questions as to the role of BCL-x(L) in conferring apoptosis resistance by preconditioning the cells and possibly altering mitochondrial morphology. C1 Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. Baltimore VA Med Ctr, Res Serv, Baltimore, MD USA. RP Boustany, NN (reprint author), Rutgers State Univ, Dept Biomed Engn, 617 Bowser Rd, Piscataway, NJ 08854 USA. EM nboustan@rci.rutgers.edu RI Thakor, Nitish/G-9110-2015; OI Thakor, Nitish/0000-0002-9981-9395; Tsai, Yien Che/0000-0001-9624-1092 FU NCRR NIH HHS [R21-RR15264] NR 23 TC 31 Z9 31 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2004 VL 87 IS 6 BP 4163 EP 4171 DI 10.1529/biophysj.104.048736 PG 9 WC Biophysics SC Biophysics GA 875NH UT WOS:000225426700051 PM 15377529 ER PT J AU Michael, DJ Geng, XH Cawley, NX Loh, YP Rhodes, CJ Drain, P Chow, RH AF Michael, DJ Geng, XH Cawley, NX Loh, YP Rhodes, CJ Drain, P Chow, RH TI Fluorescent cargo proteins in pancreatic beta-cells: Design determines secretion kinetics at exocytosis SO BIOPHYSICAL JOURNAL LA English DT Letter ID EVANESCENT-WAVE MICROSCOPY; RELEASE; GRANULES; VESICLES AB We compared secretion kinetics for four different fluorescent cargo proteins, each targeted to the lumen of insulin secretory vesicles. Upon stimulation, individual vesicles displayed one of four distinct patterns of fluorescence change: i), disappearance, ii), dimming, iii), transient brightening, or iv), persistent brightening. For each fusion protein, a different pattern of fluorescence change dominated. Furthermore, we demonstrated that the dominant pattern depends upon both i), the specific choice of fluorescent protein, and ii), the sequence of amino acids linking the cargo protein to the fluorescent protein. Thus, in beta-cells, experiments involving fluorescent cargo proteins for the study of exocytosis must be interpreted carefully, as design of a fluorescent cargo protein determines secretion kinetics at exocytosis. C1 Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Physiol & Biophys, Los Angeles, CA 90089 USA. Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. NICHHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Pacific NW Res Inst, Seattle, WA 98122 USA. RP Chow, RH (reprint author), Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Physiol & Biophys, Los Angeles, CA 90089 USA. EM rchow@usc.edu RI Chow, Robert/B-8155-2013 FU NIDDK NIH HHS [F32 DK010181, DK10181, DK47919, DK60623, R01 DK047919, R01 DK060623] NR 8 TC 28 Z9 29 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 DEC PY 2004 VL 87 IS 6 BP L3 EP L5 DI 10.1529/biophysj.104.052175 PG 3 WC Biophysics SC Biophysics GA 875NH UT WOS:000225426700001 PM 15516519 ER PT J AU Tsuchida, T Berlin, WK Sauer, B AF Tsuchida, T Berlin, WK Sauer, B TI Dual chromogenic reporter gene detection in mammalian cells with IacZ and arabinofuranosidase SO BIOTECHNIQUES LA English DT Article ID ALPHA-L-ARABINOFURANOSIDASE; IN-SITU; MICE C1 Natl Inst Diabet Digest & Kidney Dis, Bethesda, MD USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Sauer, B (reprint author), Stowers Inst Med Res, Kansas City, MO 64110 USA. EM BLS@stowers-institute.org NR 12 TC 0 Z9 0 U1 0 U2 0 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 2004 VL 37 IS 6 BP 896 EP 897 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 879DL UT WOS:000225696500004 PM 15597535 ER PT J AU Kogan, JN Otto, MW Bauer, MS Dennehy, EB Miklowitz, DJ Zhang, HW Ketter, T Rudorfer, MV Wisniewski, SR Thase, ME Calabrese, J Sachs, GS AF Kogan, JN Otto, MW Bauer, MS Dennehy, EB Miklowitz, DJ Zhang, HW Ketter, T Rudorfer, MV Wisniewski, SR Thase, ME Calabrese, J Sachs, GS CA STEP-BD Investigators TI Demographic and diagnostic characteristics of the first 1000 patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; effectiveness research; illness description; sample characteristics ID MEDICATION ALGORITHM PROJECT; PHASE-3 TMAP-3; RATIONALE; HISTORY; ILLNESS; LITHIUM; DESIGN AB Objectives: Bipolar disorder is a severe, recurrent, and often highly impairing psychiatric disorder. The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) is a large-scale multicenter study funded by the National Institute of Mental Health (NIMH) to examine the longitudinal course of the disorder and the effectiveness of current treatments. The current report provides a context for interpreting studies resulting from STEP-BD by summarizing the baseline demographic and diagnostic characteristics of the first 1000 enrolled. Methods: The majority of the sample met DSM-IV criteria for bipolar I disorder (71%). Mean age of patients was 40.6 (+/-12.7) years and mean duration of bipolar illness was 23.1 (+/-12.9) years. Among the first 1000 subjects enrolled, 58.6% are females and 92.6% Caucasian. This report compares the STEP-BD sample with other large cohorts of bipolar patients (treatment and community samples). Results: Compared with US population and community studies, the first 1000 STEP-BD patients were less racially diverse, more educated, had lower income, and a higher unemployment rate. Results are discussed in terms of the contributions of STEP-BD (and other large-scale treatment studies) in understanding the nature, treatments, and outcomes of bipolar disorder for patients seeking care at academic treatment centers. Conclusions: The current report provides a context for interpreting future studies resulting from STEP-BD. The comparison of demographic and clinical characteristics between the samples across clinic-based studies suggests broad similarities despite the substantial differences in geography, payer mix, and clinical entry point. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brown Univ, Providence Vet Affairs Med Ctr, Providence, RI 02912 USA. So Methodist Univ, Dallas, TX 75275 USA. Univ Colorado, Boulder, CO 80309 USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. NIMH, Bethesda, MD 20892 USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Kogan, JN (reprint author), Community Care Behav Hlth, 1 Chatham Ctr,Suite 700, Pittsburgh, PA 15219 USA. EM koganjn@ccbh.com OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 25 TC 68 Z9 69 U1 4 U2 6 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2004 VL 6 IS 6 BP 460 EP 469 DI 10.1111/j.1399-5618.2004.00158.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 870TL UT WOS:000225081000003 PM 15541061 ER PT J AU Longo, DL AF Longo, DL TI Hodgkin disease: the sword of Damocles resheathed SO BLOOD LA English DT Editorial Material C1 NIA, Bethesda, MD 20892 USA. RP Longo, DL (reprint author), NIA, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 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 DEC 1 PY 2004 VL 104 IS 12 BP 3418 EP 3418 DI 10.1182/blood-2004-09-3410 PG 1 WC Hematology SC Hematology GA 874LJ UT WOS:000225351600002 ER PT J AU Weller, S Braun, MC Tan, BK Rosenwald, A Cordier, C Conley, ME Plebani, A Kumararatne, DS Bonnet, D Tournilhac, O Tchernia, G Steiniger, B Staudt, LM Casanova, JL Reynaud, CA Weill, JC AF Weller, S Braun, MC Tan, BK Rosenwald, A Cordier, C Conley, ME Plebani, A Kumararatne, DS Bonnet, D Tournilhac, O Tchernia, G Steiniger, B Staudt, LM Casanova, JL Reynaud, CA Weill, JC TI Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire SO BLOOD LA English DT Article ID INDUCED CYTIDINE DEAMINASE; AUTOSOMAL RECESSIVE FORM; VARIABLE REGION GENES; HYPER-IGM; SOMATIC HYPERMUTATION; ACTIVATION; EXPRESSION; MUTATIONS; SPLEEN; IMMUNODEFICIENCY AB The human peripheral B-cell compartment displays a large population of immunoglobulin M-positive, immunoglobulin D-positive CD27(+) (IgM(+)IgD(+)CD27(+)) "memory" B cells carrying a mutated immunoglobulin receptor. By means of phenotypic analysis, complementarity-determining region 3 (CDR3) spectratyping during a T-independent response, and gene-expression profiling of the different blood and splenic B-cell subsets, we show here that blood IgM(+)IgD(+)CD27(+) cells correspond to circulating splenic marginal zone B cells. Furthermore, analysis of this peripheral subset in healthy children younger than 2 years shows that these B cells develop and mutate their immunoglobulin receptor during ontogeny, prior to their differentiation into T-independent antigen-responsive cells. It is therefore proposed that these IgM(+)IgD(+)CD27(+) B cells provide the splenic marginal zone with a diversified and protective preimmune repertoire in charge of the responses against encapsulated bacteria. (C) 2004 by The American Society of Hematology. C1 INSERM, U373, F-75730 Paris 15, France. INSERM, IFR 94, Serv Commun Tri Cellulaire, F-75654 Paris, France. Hop Necker Enfants Malad, Paris, France. Fac Med Necker Enfants Malad, INSERM, U550, Paris, France. Fac Med Necker Enfants Malad, Serv Cardiol Pediat, Paris, France. Fac Med Necker Enfants Malad, Unite Hematol & Immunol Pediat, Paris, France. NCI, Med Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Dept Immunol, St Jude Childrens Res Hosp, Coll Med, Memphis, TN USA. Univ Brescia, Dept Pediat, Brescia, Italy. Ist Med Mol Angelo Nocivelli, Brescia, Italy. Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England. Addenbrookes Hosp, Dept Clin Immunol, Cambridge, England. CHU Hotel Dieu, Federat Malad Infect, Clermont Ferrand, France. Assistance Publ Hop Paris, Hematol Lab, Hop Bicetre, Le Kremlin Bicetre, France. Univ Marburg, Inst Anat & Cell Biol, Marburg, Germany. RP Weill, JC (reprint author), INSERM, U373, 156 Rue Vaugirard, F-75730 Paris 15, France. EM weill@necker.fr RI Plebani, Alessandro/C-8593-2011 NR 35 TC 431 Z9 439 U1 2 U2 13 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 DEC 1 PY 2004 VL 104 IS 12 BP 3647 EP 3654 DI 10.1182/blood-2004-01-0346 PG 8 WC Hematology SC Hematology GA 874LJ UT WOS:000225351600043 PM 15191950 ER PT J AU Sloand, EM Mainwaring, L Keyvanfar, K Chen, JC Maciejewski, J Klein, HG Young, NS AF Sloand, EM Mainwaring, L Keyvanfar, K Chen, JC Maciejewski, J Klein, HG Young, NS TI Transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria SO BLOOD LA English DT Article ID DECAY-ACCELERATING FACTOR; RED-BLOOD-CELLS; MEMBRANE; SURFACE; CD59; PNH; PROTECTION; HEMOLYSIS; INVIVO; PLASMA AB In paroxysmal nocturnal hemoglobinuria (PNH), an acquired mutation of the PIGA gene results in the absence of glycosylphosphatidylinositol (GPI)-anchored cell surface membrane proteins in affected hematopoietic cells. Absence of GPI-anchored proteins on erythrocytes is responsible for their increased sensitivity to complement-mediated lysis, resulting in hemolytic anemia. Cell-to-cell transfer of CD55 and CD59, 2 GPI-anchored proteins, by red cell microvesicles has been demonstrated in vitro, with retention of their function. Because red cell units stored for transfusion contain many erythrocyte microvesicles, transfused blood could potentially serve as a source of CD55 and CD59. We examined whether GPI-anchored proteins could be transferred in vivo to deficient cells following transfusions given to 6 patients with PNH. All patients were group A, blood type. Each was given transfusions of 3 U of compatible, washed group O blood. Patient group A, cells were distinguished from the transfused group O cells by flow cytometry and staining with a labeled lectin, Dolichos biflorus, which specifically binds to group A(1) erythrocytes. Increased surface CD59 was measured on recipient red cells and granulocytes 1, 3, and 7 days following transfusion in all 6 patients. Our data suggest a potential therapeutic role for GPI-anchored protein transfer for severe PNH. C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Sloand, EM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg10,Rm 7C103, Bethesda, MD 20892 USA. EM sloande@nhibi.nih.gov NR 36 TC 26 Z9 27 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 DEC 1 PY 2004 VL 104 IS 12 BP 3782 EP 3788 DI 10.1182/blood-2004-02-0645 PG 7 WC Hematology SC Hematology GA 874LJ UT WOS:000225351600060 PM 15304386 ER PT J AU Taylor, PA Panoskaltsis-Mortari, A Swedin, JM Lucas, PJ Gress, RE Levine, BL June, CH Serody, JS Blazar, BR AF Taylor, PA Panoskaltsis-Mortari, A Swedin, JM Lucas, PJ Gress, RE Levine, BL June, CH Serody, JS Blazar, BR TI L-Selectin(hi) but not the L-selectin(lo) CD4(+)25(+) T-regulatory cells are potent inhibitors of GVHD and BM graft rejection SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; TGF-BETA; TOLERANCE; MICE; SUBPOPULATION; LEUKEMIA; RECEPTOR; VIVO AB Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after bone marrow transplantation (BMT). CD4(+)CD25(+) immune regulatory T cells (Tregs), long recognized for their critical role in induction and maintenance of self-tolerance and prevention of autoimmunity, are also important in the regulation of immune responses in allogeneic bone marrow (BM) and solid organ transplantation. Published data indicate that ex vivo activated and expanded donor Tregs result in significant inhibition of lethal nor- or host-type LSel(hi), but not LSeIlo, Tregs potently increased donor BM engraftment in sublethally irradiated mice, an event occurring independently of transforming growth factor beta signaling of host T cells. These data indicate that Treg cellular therapy warrants clinical consideration for the inhibition of GVHD and the promotion of alloengraftment. C1 Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Dept Pediat, Div BMT, Minneapolis, MN 55455 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Abramson Family Canc Res Inst, Ctr Canc, Philadelphia, PA 19104 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. RP Blazar, BR (reprint author), Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. EM blaza001@umn.edu RI Levine, Bruce/D-1688-2009; OI Serody, Jonathan/0000-0003-4568-1092 FU NCI NIH HHS [CA 102052-02]; NHLBI NIH HHS [2 R37 HL56067, HL55209, R01 HL63452, R01 HL66308]; NIAID NIH HHS [R01 AI 34495] NR 24 TC 230 Z9 241 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2004 VL 104 IS 12 BP 3804 EP 3812 DI 10.1182/blood-2004-05-1850 PG 9 WC Hematology SC Hematology GA 874LJ UT WOS:000225351600063 PM 15292057 ER PT J AU Dalakas, MC AF Dalakas, MC TI Inhibiting leukocyte recruitment to the brain by IVIg: is it relevant to the treatment of demyelinating CNS disorders? SO BRAIN LA English DT Editorial Material ID AUTOIMMUNE NEUROMUSCULAR DISEASES; INTRAVENOUS IMMUNOGLOBULIN; MULTIPLE-SCLEROSIS; IMMUNOLOGY; MIGRATION C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov NR 10 TC 4 Z9 5 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 DEC PY 2004 VL 127 BP 2569 EP 2571 DI 10.1093/brain/awh343 PN 12 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 874PE UT WOS:000225361500003 PM 15561895 ER PT J AU Shan, L Yu, MS Clark, BD Snyderwine, EG AF Shan, L Yu, MS Clark, BD Snyderwine, EG TI Possible role of Stat5a in rat mammary gland carcinogenesis SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast; carcinoma; heterocyclic amine; human; mammary gland; rat; Stat5a ID FOOD-DERIVED CARCINOGEN; SPRAGUE-DAWLEY RATS; SIGNAL TRANSDUCER; MOLECULAR TARGETS; CYCLIN D1; TUMORS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; TUMORIGENESIS; ACTIVATION; CANCER AB Signal transducer and activator of transcription (Stat) 5a is a transcription factor mediating the action of specific cytokines, growth factors and hormones on gene expression. In the mammary gland, Stat5a is well recognized for its function in prolactin signaling, lobuloalveolar development, and milk protein expression during pregnancy and lactation. Latent cytoplasmic Stat5a is activated by tyrosine phosphorylation and following dimerization undergoes nuclear import. In the current study, Stat5a expression was examined immunohistochemically in carcinomas induced by the chemical carcinogens 7,12-dimethylbenz[a]anthracene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A high percentage of carcinomas showed nuclear labeling of Stat5a [44 of 68 (65%)] with Stat5a nuclear labeling index ranging from 18 to 77%. In contrast, control normal mammary gland tissue displayed cytosolic expression. Carcinomas with different Stat5a staining patterns (cytoplasmic or nuclear) showed a statistical difference for the proliferating cell nuclear antigen (PCNA) labeling, tumor differentiation, nuclear grade, mitotic activity, and tumor size. High Stat5a nuclear expression was closely correlated with the higher-grade carcinomas. Stat5a nuclear expression was also detected in intraductal proliferations (10 of 21 lesions) and in ductal carcinomas in situ (13 of 15 lesions). Immunohistochemical analysis was further carried out in human breast cancers. Stat5a nuclear expression was detected in ductal and lobular carcinomas and DCIS at a frequency of 48% (15/31), 33% (2/6), and 40% (2/5), respectively. Nuclear expression of Stat5a in human breast cancers also correlated with the PCNA nuclear labeling index. The findings implicate activated Stat5a in mammary gland cancer development in the rat and human. C1 NCI, CCR, Expt Carcinogenesis Lab, Chem Carcinogenesis Sect, Bethesda, MD 20892 USA. NCI, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Snyderwine, EG (reprint author), NCI, CCR, Expt Carcinogenesis Lab, Chem Carcinogenesis Sect, Bldg 37,Room 4146,37 Convent Dr, Bethesda, MD 20892 USA. EM elizabeth_snyder-wine@nih.gov NR 27 TC 23 Z9 23 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 DEC PY 2004 VL 88 IS 3 BP 263 EP 272 DI 10.1007/s10549-004-0805-2 PG 10 WC Oncology SC Oncology GA 881BM UT WOS:000225838400009 PM 15609129 ER PT J AU Chan, CC Reed, GF Kim, Y Agron, E Buggage, RR AF Chan, CC Reed, GF Kim, Y Agron, E Buggage, RR TI A correlation of pregnancy term, disease activity, serum female hormones, and cytokines in uveitis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; SEX-HORMONES; POSTPARTUM; DELIVERY; PROFILE AB Background/aims: Pregnancy and the postpartum period are associated with the activity of autoimmune diseases including uveitis. Although the exact mechanism is unknown, hormones are reported to alter inflammatory cytokines and influence disease activity. The authors studied ocular inflammation, female hormones, and serum cytokine levels during and after pregnancy. Methods: A prospective, observational case study was conducted. Four pregnant women in their first trimester with chronic non-infectious uveitis were followed monthly until 6 months after delivery. Serum female hormones (oestrogen, progesterone, prolactin) and various cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma, and TGF-beta) were measured by ELISA. Results: The four patients had five full term pregnancies. Uveitis activity decreased after the first trimester but flared in the early postpartum period. Serum female hormones, highly elevated during pregnancy, drastically dropped post partum. Cytokine levels except TGF-beta were mostly undetectable. Conclusion: Female hormones and TGF-beta may contribute to the activity of uveitis during pregnancy and the postpartum period. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 25 TC 16 Z9 20 U1 1 U2 2 PU B M J PUBLISHING 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 DEC PY 2004 VL 88 IS 12 BP 1506 EP 1509 DI 10.1136/bjo.2004.048595 PG 4 WC Ophthalmology SC Ophthalmology GA 871VP UT WOS:000225165000009 PM 15548800 ER PT J AU de Coupade, C Gear, RW Dazin, PF Sroussi, HY Green, PG Levine, JD AF de Coupade, C Gear, RW Dazin, PF Sroussi, HY Green, PG Levine, JD TI beta(2)-adrenergic receptor regulation of human neutrophil function is sexually dimorphic SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE cell recruitment; chemotaxis; chemokinesis; beta-adrenergic receptor; inflammation; sex differences; chemokine; polymorphonuclear leucocytes ID BRONCHIAL EPITHELIAL-CELLS; WALL INDUCED POLYARTHRITIS; INFLAMMATORY RESPONSE; INTERLEUKIN-8 RELEASE; RHEUMATOID-ARTHRITIS; LEUKOCYTE ADHESION; DOWN-REGULATION; MESSENGER-RNA; EXPRESSION; SEX AB 1 While the mechanisms underlying the marked sexual dimorphism in inflammatory diseases are not well understood, the sexually dimorphic sympathoadrenal axis profoundly affects the inflammatory response. We tested whether adrenergic receptor-mediated activation of human neutrophil function is sexually dimorphic, since neutrophils provide the first line of defense in the inflammatory response. 2 There was a marked sexual dimorphism in beta(2)-adrenergic receptor binding, using the specific beta(2)-adrenergic receptor ligand, [H-3]-dihydroalprenolol, with almost three times more binding sites on neutrophils from females (20,878+/-2470) compared to males (7331+/-3179). 3 There was also a marked sexual dimorphism in the effects of isoprenaline, a beta-adrenergic receptor agonist, which increased nondirected locomotion (chemokinesis) in neutrophils obtained from females, while having no effect on neutrophils from males. 4 Isoprenaline stimulated the release of a chemotactic factor from neutrophils obtained from females, but not from males. This chemotactic factor acts on the G protein-coupled CXC chemokine receptor 2 (CXCR2) chemokine receptor, since an anti-CXCR2 antibody and the selective nonpeptide CXCR2 antagonist SB225002, inhibited chemotaxis produced by this factor. While interleukin-(IL-) 8 is a principal CXCR2 ligand, isoprenaline did not produce an increase in IL- 8 release from neutrophils. 5 IL-8-induced chemotaxis was inhibited in a sexually dimorphic manner by isoprenaline, which also stimulated release of a mediator from neutrophils that induced chemotaxis, that was inhibited by anti-CXCR2 antibodies. 6 These findings indicate an important role for adrenergic receptors in the modulation of neutrophil trafficking, which could contribute to sex-differences in the inflammatory response. C1 Univ Calif San Francisco, Dept Med, NIH, Pain Ctr, San Francisco, CA 94143 USA. NIH, Dept Oral & Maxillofacial Surg, Pain Ctr, San Francisco, CA USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, Dept Med, NIH, Pain Ctr, C522 Box 0440,521 Parnassus Ave, San Francisco, CA 94143 USA. EM levine@itsa.ucsf.edu RI Green, Paul/C-5943-2011 FU NIAMS NIH HHS [R01 AR032634, AR 32634] NR 52 TC 28 Z9 28 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD DEC PY 2004 VL 143 IS 8 BP 1033 EP 1041 DI 10.1038/sj.bjp.0705972 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 882VM UT WOS:000225967300015 PM 15477226 ER PT J AU Chen, JB Breslow, NE AF Chen, JB Breslow, NE TI Semiparametric efficient estimation for the auxiliary outcome problem with the conditional mean model SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE auxiliary outcome; conditional mean model; Horvitz-Thompson estimator; missing at random; semiparametric efficient estimation ID MISSING DATA; REGRESSION; LIKELIHOOD; PREVALENCE; PARAMETERS AB The authors consider semiparametric efficient estimation of parameters in the conditional mean model for a simple incomplete data structure in which the outcome of interest is observed only for a random subset of subjects but covariates and surrogate (auxiliary) outcomes are observed for all. They use optimal estimating function theory to derive the semiparametric efficient score in closed form. They show that when covariates and auxiliary outcomes are discrete, a Horvitz-Thompson type estimator with empirically estimated weights is semiparametric efficient. The authors give simulation studies validating the finite-sample behaviour of the semiparametric efficient estimator and its asymptotic variance; they demonstrate the efficiency of the estimator in realistic settings. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Chen, JB (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. EM chenjin@mail.nih.gov; norm@u.washington.edu NR 30 TC 11 Z9 11 U1 0 U2 1 PU CANADIAN JOURNAL STATISTICS PI OTTAWA PA 675 DENBURY AVENUE, OTTAWA, ON K2A 2P2, CANADA SN 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD DEC PY 2004 VL 32 IS 4 BP 359 EP 372 DI 10.2307/3316021 PG 14 WC Statistics & Probability SC Mathematics GA 890IG UT WOS:000226504300003 ER PT J AU Etzioni, DA Ponce, NA Babey, SH Spencer, BA Brown, ER Ko, CY Chawla, N Breen, N Klabunde, CN AF Etzioni, DA Ponce, NA Babey, SH Spencer, BA Brown, ER Ko, CY Chawla, N Breen, N Klabunde, CN TI A population-based study of colorectal cancer test use - Results from the 2001 California Health Interview Survey SO CANCER LA English DT Article DE colorectal neoplasms; prevention and control; mass screening; ethnic; groups; statistics and numeric data; endoscopy; utilization; occult blood; California ID PRIMARY-CARE; LOW-INCOME; UNITED-STATES; BARRIERS; ACCESS; WOMEN; ASSOCIATION; PREDICTORS; INSURANCE; PROGRESS AB BACKGROUND. Recent research has supported the use of colorectal cancer (CRC) tests to reduce disease incidence, morbidity, and mortality. A new health survey has provided an opportunity to examine the use of these tests in California's ethnically diverse population. The authors used the 2001 California Health Interview Survey (CHIS 2001) to evaluate 1) rates of CRC test use, 2) predictors of the receipt of tests, and 3) reasons for nonuse of CRC tests. METHODS. The CHIS 2001 is a random-digit dial telephone survey that was conducted in California. Responses were analyzed from 22,343 adults age greater than or equal to 50 years. CRC test use was defined as receipt of a fecal occult blood test in the past year and/or receipt of an endoscopic examination in the past 5 years. RESULTS. Nearly 54% of California adults reported receipt of a recent CRC test. Insurance coverage and having a usual source of care were the most important predictors of CRC testing. Latinos age < 65 years were less likely to be tested than whites (relative risk [RR], 0.84; 95% confidence interval [95% CI], 0.77-0.92). Men were more likely to be tested than women, an effect that was greater among individuals age 50-64 years (RR, 1.28; 95% CI, 1.23-1.32) than among individuals age 65 years (RR, 1.19; 95% CI, 1.15-1.23). Women were more likely than men to say that their physician did not inform them the test was needed and that CRC tests were painful or embarrassing. CONCLUSIONS. Results of the current study indicate a need for physicians to recommend CRC testing to their patients. Assuring that all individuals have both health insurance and a usual source of care would help address gaps in the receipt of CRC tests. (C) 2004 American Cancer Society. C1 Univ Calif Los Angeles, Ctr Hlth Policy Res, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Dept Med, Los Angeles, CA USA. RAND, Santa Monica, CA USA. NCI, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. RP Ponce, NA (reprint author), Univ Calif Los Angeles, Ctr Hlth Policy Res, Dept Hlth Serv, 10911 Weyburn Ave,Suite 300, Los Angeles, CA 90024 USA. EM nponce@ucla.edu OI Ponce, Ninez/0000-0001-5151-6718 FU NCI NIH HHS [N02PC95057] NR 31 TC 80 Z9 81 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2004 VL 101 IS 11 BP 2523 EP 2532 DI 10.1002/cncr.20692 PG 10 WC Oncology SC Oncology GA 873ZS UT WOS:000225321300005 PM 15505783 ER PT J AU Ng, SSW Figg, WD AF Ng, SSW Figg, WD TI Upregulation of endogenous angiogenesis inhibitors - A mechanism of action of metronomic chemotherapy SO CANCER BIOLOGY & THERAPY LA English DT Article DE angiogenesis; cancer; metronomic chemotherapy; endothelial cells; thrombospondin-1; cyclophosphamide ID TUMOR-GROWTH; CYCLOPHOSPHAMIDE; THROMBOSPONDIN-1; ENDOSTATIN; TUMSTATIN; CANCER AB Antiangiogenic or metronomic chemotherapy, the frequent administration of conventional cytotoxic agents at low doses, is believed to target activated tumor endothelial cells. The mechanisms of action of such regimen remain poorly understood. In the March 2004 issue of Cancer Research, Hamano et al. demonstrated that low-dose cyclophosphamide inhibits tumor growth by upregulating the endogenous angiogenesis inhibitor thrombospondin-1 in tumor and perivascular cells. Thrombospondin-1, in turn, promotes endothelial cell apoptosis. It was also proposed that thrombospondin-1 levels might be used as a surrogate marker to monitor response to low- dose cyclophosphamide therapy in the clinic. C1 NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, NIH, Bethesda, MD 20892 USA. Canc Res Ctr, Canc Therapeut Branch, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, NIH, Bldg 10,Rm 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 19 TC 10 Z9 12 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2004 VL 3 IS 12 BP 1212 EP 1213 PG 2 WC Oncology SC Oncology GA 918WJ UT WOS:000228578000015 PM 15662130 ER PT J AU Macpherson, GR Singh, AS Bennett, CL Venzon, DJ Liewehr, DJ Franks, ME Dahut, WL Kantoff, PW Price, DK Figg, WD AF Macpherson, GR Singh, AS Bennett, CL Venzon, DJ Liewehr, DJ Franks, ME Dahut, WL Kantoff, PW Price, DK Figg, WD TI Genotyping and functional analysis of the D104N variant of human endostatin SO CANCER BIOLOGY & THERAPY LA English DT Article DE endostatin; prostate cancer; angiogenesis; single nucleotide polymorphism ID RECOMBINANT HUMAN ENDOSTATIN; ANGIOGENESIS INHIBITOR ENDOSTATIN; ADVANCED SOLID TUMORS; PROSTATE-CANCER; IN-VITRO; PHASE-I; ANTIANGIOGENIC THERAPY; ANTITUMOR-ACTIVITY; ENDOTHELIAL-CELLS; HEPARAN-SULFATE AB Endostatin is an endogenous inhibitor of angiogenesis derived from the extracellular matrix protein collagen XVIII. It has been reported that a variation at the 104 position (D104N) of human endostatin is associated with an increased risk of prostate cancer, potentially indicating that this protein variant is less active as an anti-angiogenic agent. Herein we reported the results of genotyping 389 patients with androgen independent prostate cancer ( AIPC) and 352 normal control individuals for D104N endostatin. There was no significant association between the frequency of 104N endostatin and the incidence of AIPC in either Caucasian or African American patients compared to controls (15% Caucasian AIPC versus 13.7% in Caucasian controls, p=0.79; 7.4% African American AIPC versus 5.6% in African American controls, p=0.64). Actuarial analysis revealed no statistically significant association between incidence of the DN heterozygous genotype and survival (p=0.62 by logrank test). To study the functional significance of the D104N conversion, we have expressed and purified insoluble recombinant human 104D and 104N endostatin and compared their respective activities in human umbilical vein endothelial cell ( HUVEC) tube formation assays. The 104N variant of human endostatin inhibited HUVEC tube formation at least as well as the wild-type form. We concluded that the D104N variation in human endostatin is neither clinically relevant nor suitable as a pharmacogenomic endpoint to assess the risk for developing AIPC. C1 NCI, Med Oncol Clin Res Unit, Clin Pharmacol Res Core,Biostat & Data Management, NIH,Mol Pharmacol Lab, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, VA Chicago Healthcare Syst Lakeside, Chicago, IL 60611 USA. Natl Inst Hlth Res Scholar, Howard Hughes Med Inst, Bethesda, MD USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Figg, WD (reprint author), NCI, Med Oncol Clin Res Unit, Clin Pharmacol Res Core,Biostat & Data Management, NIH,Mol Pharmacol Lab, Bldg 10,Rm 5A01,MSC 1910,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Venzon, David/B-3078-2008; Bennett, Charles/C-2050-2008; Figg Sr, William/M-2411-2016 NR 37 TC 11 Z9 11 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2004 VL 3 IS 12 BP 1298 EP 1303 PG 6 WC Oncology SC Oncology GA 918WJ UT WOS:000228578000030 PM 15662127 ER PT J AU Stoyanova, R Clapper, ML Bellacosa, A Henske, EP Testa, JR Ross, EA Yeung, AT Nicolas, E Tsichlis, N Li, YS Linehan, WM Howard, S Campbell, KS Godwin, AK Boman, BM Crowell, JA Kopelovich, L Knudson, AG AF Stoyanova, R Clapper, ML Bellacosa, A Henske, EP Testa, JR Ross, EA Yeung, AT Nicolas, E Tsichlis, N Li, YS Linehan, WM Howard, S Campbell, KS Godwin, AK Boman, BM Crowell, JA Kopelovich, L Knudson, AG TI Altered gene expression in phenotypically normal renal cells from carriers of tumor suppressor gene mutations SO CANCER BIOLOGY & THERAPY LA English DT Article DE tuberous sclerosis; von Hippel-Lindau; renal cancer; microarrays; gene expression profiling ID HIPPEL-LINDAU-DISEASE; TUBEROUS SCLEROSIS COMPLEX; SINGULAR-VALUE DECOMPOSITION; SIGNALING PATHWAY; UP-REGULATION; TSC1 GENE; PRODUCT; IDENTIFICATION; CARCINOMA; CANCER AB Background: The inherently complex signaling networks of tumors result from genetic and epigenetic alterations that occur during cancer initiation and progression. Methods: In an attempt to identify early molecular changes associated with dominantly inherited predisposition to "two-hit" renal tumors, the expression profiles of primary cultures of phenotypically normal renal epithelial cells from individuals bearing a germline mutation in either the von Hippel-Lindau (VHL) or the tuberous sclerosis complex (TSC) gene were compared to that of renal epithelial cells from control nonmutation carriers by microarray analysis. Results: Reliability of the microarray data from pooled samples was confirmed by real-time RT-PCR. Principal Component Analysis revealed substantial differences in the gene expression profiles of the renal epithelial cells from VHL and TSC mutation carriers. In several instances, the microarray data confirm our present knowledge of the cellular pathways affected by biallelic VHL and TSC mutations. Conclusions: These findings demonstrate that heterozygosity for a mutant tumor suppressor gene may alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner. Detectable effects of "one-hit" represent early molecular changes in tumorigenesis that may serve as targets for chemopreventive intervention. C1 Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. NCI, Urol Oncol Branch, Div Canc Prevent, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Div Genet & Prevent Med, Philadelphia, PA 19107 USA. RP Clapper, ML (reprint author), Fox Chase Canc Ctr, Div Populat Sci, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM margie.clapper@facc.edu; alfonso.bellacosa@fcc.edu FU NCI NIH HHS [CA-06927, N01 CN-95037] NR 66 TC 21 Z9 22 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2004 VL 3 IS 12 BP 1313 EP 1321 PG 9 WC Oncology SC Oncology GA 918WJ UT WOS:000228578000032 PM 15662135 ER PT J AU Sturgeon, SR Schairer, C Grauman, D El ghormli, L Devesa, S AF Sturgeon, SR Schairer, C Grauman, D El ghormli, L Devesa, S TI Trends in breast cancer mortality rates by region of the United States, 1950-1999 SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; mortality; trends ID GEOGRAPHIC-VARIATION; DEATH CERTIFICATE; WHITE WOMEN; SURVIVAL; ACCURACY; COHORT AB Introduction: Limited information is available on trends in breast cancer mortality by region of the country. Methods: Rates for broad age groups were calculated from 1950 to 1999 for whites and 1970-1999 for blacks for four census regions and 508 state economic areas of the United States. Results: For white women ages 50-64 years, the mortality relative risk [RR] for the Northeast compared to the South was 1.48 in 1950-1959 and 1.15 in 1990-1999. Rates increased in all regions from the 1950s to 1960s but more substantially in the South, increased slightly in the 1970s in all regions, declined slightly in the Northeast, Midwest and West but not in the South in the 1980s, and declined more in the Northeast, Midwest and West than in the South in the 1990s. Among similarly aged black women, the RRs for the Northeast compared to the South were 1.13 and 1.0 in 1970-1979 and 1990-1999, respectively. Among these women, rates increased in all regions in the 1980s, in the 1990s rates declined in the Northeast, Midwest and West but continued to increase in the South. Conclusion: The historically lower breast cancer mortality rates in the South have been eroded because of relatively less favorable trends in the South. C1 Univ Massachusetts, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Amherst, MA 01003 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. RP Sturgeon, SR (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Amherst, MA 01003 USA. EM ssturgeon@schoolph.umass.edu NR 30 TC 17 Z9 18 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2004 VL 15 IS 10 BP 987 EP 995 DI 10.1007/s10552-004-1092-2 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 891LR UT WOS:000226583100002 PM 15801483 ER PT J AU Roth, MJ Abnet, CC Johnson, LL Mark, SD Dong, ZW Taylor, PR Dawsey, SM Qiao, YL AF Roth, MJ Abnet, CC Johnson, LL Mark, SD Dong, ZW Taylor, PR Dawsey, SM Qiao, YL TI Polymorphic variation of CYPIA1 is associated with the risk of gastric cardia cancer: a prospective case-cohort study of cytochrome P-450 1A1 and GST enzymes SO CANCER CAUSES & CONTROL LA English DT Article DE cytochrome P-450; esophagus; gastrointestinal cancer; glutathione S-transferase; phase-I enzyme; Phase-II enzyme; polycyclic aromatic hydrocarbons; stomach; xenobiotic ID GLUTATHIONE S-TRANSFERASES; POLYCYCLIC AROMATIC-HYDROCARBONS; NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; SQUAMOUS-CELL CARCINOMA; RAT DIGESTIVE-TRACT; ESOPHAGEAL CANCER; SUBSEQUENT RISK; 1-HYDROXYPYRENE GLUCURONIDE; METABOLIZING-ENZYMES AB Objective: To determine if genetic polymorphisms of CYP1A1, GSTM1, GSTP1, or GSTT1 are associated with an increased risk of developing esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), or either in a high-risk Asian population. Methods: We conducted a case-cohort analysis with 5 years of prospective follow-up. The analytical cohort contained 642 individuals who participated in either the Dysplasia Trial (DT) or the General Population (GPT) of the Nutrition Intervention Trials conducted in Linxian, China, and included 131 cases of ESCC and 90 cases of GCC. Genotyping analysis was performed on DNA extracted from red blood cells using a PureGene kit (Gentra Systems, Inc., Minneapolis, MN) and real-time PCR analysis amplification (Taq-Man). Relative risks and 95% confidence intervals were estimated using the case - cohort estimator for the Cox proportional hazards models. p-values from nested models with genotyping variables came from score tests. Results: The relative risks for developing ESCC, GCC, or either cancer were calculated in the entire analytic cohort for GSTM1, P1*B (A313G), and T1 and CYP1A1*2A (T3801C) and *2C (A2455G) genotypes, and no significant associations were identified. However, because of the difference in cancer risks between the DT (9.3 cases per 1000 person years) and the GPT (5.3 cases), the analytical cohort was stratified by trial; the DT participants who were heterozvaous or homozygous for the variant-allele at CYP1A1*2A had a reduced risk for developing GCC (adjusted RR (95% CI) 0.47 (0.23-1.00) p = 0.037). Conclusions: This study found an association for the CYP1A1*2A variant allele and a reduced risk of GCC in people at high risk for development of this disease. This finding is consistent with previous studies suggesting that substrates for the cytochrome P-450 1A1 metabolic pathway, such as polycyclic aromatic hydrocarbons, may be etiologically significant in this high-risk region. C1 Chinese Acad Med Sci, Inst Canc, Dept Epidemiol, Beijing 100021, Peoples R China. NCI, NIH, CCR, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. NCI, NIH, DCEG, Biostat Branch, Bethesda, MD 20892 USA. RP Roth, MJ (reprint author), Chinese Acad Med Sci, Inst Canc, Dept Epidemiol, POB 2252, Beijing 100021, Peoples R China. EM mr166i@nih.gov; qiaoy@public.bta.net.en RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 46 TC 42 Z9 45 U1 0 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2004 VL 15 IS 10 BP 1077 EP 1083 DI 10.1007/s10552-004-2233-3 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 891LR UT WOS:000226583100010 PM 15801491 ER PT J AU McDonald, JA Mandel, MG Marchbanks, PA Folger, SG Daling, JR Ursin, G Simon, MS Bernstein, L Strom, BL Norman, SA Malone, KE Weiss, LK Burkman, RT Weber, AL Spirtas, R AF McDonald, JA Mandel, MG Marchbanks, PA Folger, SG Daling, JR Ursin, G Simon, MS Bernstein, L Strom, BL Norman, SA Malone, KE Weiss, LK Burkman, RT Weber, AL Spirtas, R TI Alcohol exposure and breast cancer: Results of the women's contraceptive and reproductive experiences study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HORMONE REPLACEMENT THERAPY; ESTROGEN-PROGESTIN-REPLACEMENT; RECEPTOR STATUS; POSTMENOPAUSAL WOMEN; COLLABORATIVE REANALYSIS; BEVERAGE CONSUMPTION; INDIVIDUAL DATA; RISK-FACTORS; COHORT; HEALTH AB Objectives: To explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship. Methods: In a population-based study of 4,575 women ages 35 to 64 years diagnosed with invasive breast cancer between 1994 and 1998 and 4,682 controls, we collected details of lifetime alcohol use and factors that could confound or modify the alcohol-breast cancer relationship. We used conditional logistic regression to compute the odds of breast cancer among drinkers relative to nondrinkers at all ages and at ages 35 to 49 and 50 to 64 years separately. Results: Recent consumption (at reference age minus two) of greater than or equal to7 drinks per week was associated with increased risk [odds ratio (OR), 1.2; 95% CI, 1.01-1.3] and evidence of dose response was observed. Most of the excess was observed among women ages 50-64 years (OR 1.3; 95% CI, 1.1-1.6), although the test for age interaction was not statistically significant. Exposure later in life seemed more important than early exposure. Excess breast cancer associated with recent consumption was restricted to localized disease. When outcome was examined according to tumor hormone receptor status, highest risks were observed for estrogen receptor-positive/progesterone receptor-negative tumors (OR 1.6; 95% CI, 1.2-2.3). Conclusions: The effect of timing of alcohol exposure on breast cancer risk is complicated and will require additional study focused on this one issue. Further work is needed to explain how alcohol exposure, sex hormones, and tumor receptor status interact. C1 Natl Ctr Chron Dis Prevent & Hlth Promot, Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA 30341 USA. Univ Vermont, Coll Med, Burlington, VT USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ Oslo, Inst Nutr Res, Oslo, Norway. Wayne State Univ, Div Epidemiol, Karmanos Canc Inst, Detroit, MI USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Bay State Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA. NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, Bethesda, MD USA. RP McDonald, JA (reprint author), Natl Ctr Chron Dis Prevent & Hlth Promot, Ctr Dis Control & Prevent, Div Reprod Hlth, 4770 Buford Highway NE,MS-K22, Atlanta, GA 30341 USA. EM ezm5@cdc.gov NR 77 TC 21 Z9 21 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2004 VL 13 IS 12 BP 2106 EP 2116 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100019 PM 15598768 ER PT J AU Carmella, SG Chen, M Yagi, H Jerina, DM Hecht, SS AF Carmella, SG Chen, M Yagi, H Jerina, DM Hecht, SS TI Analysis of phenanthrols in human urine by gas chromatography-mass spectrometry: Potential use in carcinogen metabolite phenotyping SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; LUNG-CANCER RISK; MYELOPEROXIDASE (-463)G->A POLYMORPHISM; SOLID-PHASE MICROEXTRACTION; TOBACCO-SMOKE CARCINOGENS; EXPOSED WORKERS; ACTIVATION; DNA; 4-HYDROXYPHENANTHRENE; 1-HYDROXYPHENANTHRENE AB Phenanthrene is the simplest polycyclic aromatic hydrocarbon (PAH) containing a bay region, a feature closely associated with carcinogenicity. We have proposed that measurement of phenanthrene metabolites in human urine could be used to identify interindividual differences in metabolic activation and detoxification of PAH, and that these differences may be related to cancer susceptibility in smokers and other exposed individuals. Previously, we reported a method for quantitation of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT) in human urine. trans, anti-PheT is the ultimate product of the diol epoxide metabolic activation pathway of phenanthrene. In this study, we have extended our carcinogen metabolite phenotyping approach by developing a method for quantitation of phenanthrols in human urine. PAH phenols such as phenanthrols are considered as detoxification products. After treatment of the urine by beta-glucuronidase and arylsulfatase, a fraction enriched in phenanthrols was prepared by partitioning and solid phase extraction. The phenanthrols were silylated and analyzed by gas chromatography-positive ion chemical ionization-mass spectrometry with selected ion monitoring. [ring-C-13(6)]3-phenanthrol was used as an internal standard. Accurate and reproducible quantitation of four phenanthrols, 1-phenanthrol (1-HOPhe), 2-HOPhe, 3-HOPhe, and 4-HOPhe, was readily achieved. In smokers, mean levels of 1-HOPhe (0.96 +/- 1.2 pmol/mg creatinine) and 3-HOPhe (0.82 +/- 0.62 pmol/mg creatinine) were greater than those of 2-HOPhe (0.47 +/- 0.29 pmol/mg creatinine), and 4-HOPhe (0.11 +/- 0.07 pmol/mg creatinine). There were no significant differences between the levels of any of the phenanthrols in smokers and nonsmokers. Total levels of the quantified phenanthrols were highly correlated with those of 3-HOPhe. Ratios of phenanthrene metabolites representing activation and detoxification were calculated as trans, anti-PheT divided by 3-HOPhe. There was a 7.5-fold spread of ratios in smokers, and a 12.3-fold spread in nonsmokers, suggesting that this may be a useful parameter for distinguishing individual metabolic responses to PAH exposure. C1 Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. NIDDK, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP Hecht, SS (reprint author), Univ Minnesota, Ctr Canc, Mayo Mail Code 806,420 Delaware St SE, Minneapolis, MN 55455 USA. EM hecht002@umn.edu FU NCI NIH HHS [CA-77598, CA-92025] NR 43 TC 28 Z9 33 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2004 VL 13 IS 12 BP 2167 EP 2174 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100027 PM 15598776 ER PT J AU Peters, U Chatterjee, N Yeager, M Chanock, SJ Schoen, RE McGlynn, KA Church, TR Weissfeld, JL Schatzkin, A Hayes, RB AF Peters, U Chatterjee, N Yeager, M Chanock, SJ Schoen, RE McGlynn, KA Church, TR Weissfeld, JL Schatzkin, A Hayes, RB TI Association of genetic variants in the calcium-sensing receptor with risk of colorectal adenoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AUTOSOMAL-DOMINANT HYPOCALCEMIA; BONE-MINERAL DENSITY; EXTRACELLULAR CALCIUM; VITAMIN-D; COLON-CANCER; A986S POLYMORPHISM; PROTEIN-KINASE; HAPLOTYPE RECONSTRUCTION; CA2+-SENSING RECEPTOR; RECTAL-CANCER AB Objective: Evidence suggests that calcium prevents colorectal cancer, possibly mediated through the calcium-sensing receptor (CASK). We assessed the associations between CASK gene variants and risk for colorectal adenoma, a cancer precursor. We further investigated gene-diet interactions between the CASK variants and calcium intake on adenoma risk. Methods: Individuals with advanced distal adenomas (n = 716) and controls with a negative sigmoidoscopy exam (n = 729) were randomly selected from participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Three nonsynonymous variants in the intracellular signaling region of CASK (A986S, R990G, Q1011E) were analyzed by Taqman. Results: Compared with the most common diplotype (haplotype pair), the odds ratios for advanced adenoma were 0.80 [95% confidence interval (CI), 0.60-1.06], 0.79 (95% CI, 0.55-1.13), and 0.56 (95% CI, 0.36-0.88) for the other three common diplotypes (>5% frequency). Although calcium intake was inversely associated with adenoma risk, CASR diplotypes did not modify this association. However, the power to investigate interactions was limited. Conclusion: Variants in the CASR intracellular signaling region were significantly associated with the risk of advanced adenoma. C1 Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98109 USA. NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. NCI, Dept Hlth & Human Serv, Core Genotype Facil, NIH, Gaithersburg, MD USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Minnesota, Div Environm & Occupat Hlth, Minneapolis, MN USA. RP Peters, U (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM upeters@fhcrc.org RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Church, Timothy R./0000-0003-3292-5035 NR 57 TC 29 Z9 29 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2004 VL 13 IS 12 BP 2181 EP 2186 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100029 PM 15598778 ER PT J AU Savage, SA Abnet, CC Mark, SD Qiao, YL Dong, ZW Dawsey, SM Taylor, PR Chanock, SJ AF Savage, SA Abnet, CC Mark, SD Qiao, YL Dong, ZW Dawsey, SM Taylor, PR Chanock, SJ TI Variants of the IL8 and IL8RB genes and risk for gastric cardia adenocarcinoma and esophageal squamous cell carcinoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; CASE-COHORT; MOLECULAR EPIDEMIOLOGY; INCIDENT ESOPHAGEAL; HELICOBACTER-PYLORI; CANCER INCIDENCE; SHANXI-PROVINCE; CHINA; INTERLEUKIN-8 AB The population of Linxian in north central China is at high risk for gastric cardia adenocarcinoma (GCC) and esophageal squamous cell carcinoma (ESCC), and chronic inflammation may contribute to this risk. Interleukin-8 (IL8), a potent chemoattractant, has three well-characterized single nucleotide polymorphisms (SNP), one (-251) of which alters transcriptional activity. Four well-described SNPs in the two ILS receptors, IL8RA and IL8RB, have been associated with inflammation. We conducted a case-cohort study in the Nutrition Intervention Trials (Linxian, China) to assess the association between these SNPs and incident GCC (n = 90) and ESCC (n = 131). IL8, IL8RA, and IL8RB SNPs were analyzed using a multiplex assay system, haplotypes were constructed, and risks were estimated using Cox proportional hazards models. The homozygous variants of ILS -251 and +396 were associated with 2-fold increased relative risks for GCC, but the highest risk observed was for the AGT/AGC haplotype of ILS -251/+396/+781 (relative risk, 4.14; 95% confidence interval, 1.31-13.1). Variation within ILS was not associated with ESCC. Few subjects had variation at the IL8RA SNP and no significant associations were observed for IL8RB SNPs or haplotypes with either GCC or ESCC. We conclude that variation in ILS seems to increase the risk for GCC but not ESCC in this high-risk population. These variants could confer an altered ILS expression pattern or interact with environmental factors to increase the risk for inflammation and GCC. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RP Savage, SA (reprint author), NCI, Ctr Canc Res, Ctr Adv Technol, Pediat Oncol Branch,Sect Genom Variat, 8717 Grovemont Circle, Gaithersburg, MD 20892 USA. EM savagesh@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015; Savage, Sharon/B-9747-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843; Savage, Sharon/0000-0001-6006-0740 NR 43 TC 67 Z9 73 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2004 VL 13 IS 12 BP 2251 EP 2257 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100039 PM 15598788 ER PT J AU Lavigne, JA Wimbrow, HH Clevidence, BA Albert, PS Reichman, ME Campbell, WS Barrett, JC Hursting, SD Judd, JT Taylor, PR AF Lavigne, JA Wimbrow, HH Clevidence, BA Albert, PS Reichman, ME Campbell, WS Barrett, JC Hursting, SD Judd, JT Taylor, PR TI Effects of alcohol and menstrual cycle on insulin-like growth factor-I and insulin-like growth factor binding protein-3 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; FACTOR BINDING-PROTEIN-3; PREMENOPAUSAL WOMEN; COLORECTAL-CANCER; PLASMA-LEVELS; LUNG-CANCER; IGF-I; SERUM; HORMONE; PROLACTIN AB Alcohol ingestion and insulin-like growth factor-I (IGFI) have been associated with increased breast cancer risk, the latter primarily in premenopausal women. We investigated whether alcohol ingestion altered IGF-I or its major binding protein (BP), IGFBP-3, in a controlled feeding study in premenopausal women. We also determined whether IGF-I or IGFBP-3 was affected by menstrual cycle phase. Serum was collected from 31 individuals who were randomly assigned to consume either 0 or 30 g (two drinks) of alcohol daily for three menstrual cycles and who then crossed over to the other alcohol level for three cycles. All calories were provided and weight was maintained during the study. For both alcohol levels, serum was collected during the final cycle at early follicular, periovulatory, and luteal phases. Relative to the follicular phase, IGF-I levels increased by 3.3% and 7.6% in the periovulatory and luteal phases, respectively (P for trend = 0.004). Although alcohol ingestion did not affect this increase, it significantly reduced IGF-I concentrations at all phases (9.5%; P < 0.001), whereas IGFBP-3 was unaffected by either menstrual phase or alcohol. This is the first controlled diet study to show that alcohol decreases serum IGF-I in premenopausal women and that IGF-I significantly increases over the course of the menstrual cycle whether or not alcohol is present. C1 NCI, Lab Biosyst & Canc, Canc Res Ctr, Bethesda, MD 20892 USA. USDA ARS, Betsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. RP Lavigne, JA (reprint author), NCI, Lab Biosyst & Canc, Canc Res Ctr, 9000 Rockville Pike,Bldg 37,Room5046, Bethesda, MD 20892 USA. EM lavignej@mail.nih.gov NR 29 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2004 VL 13 IS 12 BP 2264 EP 2267 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100041 PM 15598790 ER PT J AU Tsuda, H Birrer, MJ Ito, YM Ohashi, Y Lin, M Lee, C Wong, WH Rao, PH Lau, CC Berkowitz, RS Wong, KK Mok, SC AF Tsuda, H Birrer, MJ Ito, YM Ohashi, Y Lin, M Lee, C Wong, WH Rao, PH Lau, CC Berkowitz, RS Wong, KK Mok, SC TI Identification of DNA copy number changes in microdissected serous ovarian cancer tissue using a cDNA microarray platform SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CYTOKERATIN 5/6; AMPLIFICATION; EXPRESSION; ADENOCARCINOMA; CARCINOMAS; TUMORS; MESOTHELIOMA; REVEALS; PLEURA AB We have established a method for using a cDNA array platform in combination with degenerate oligonucleotide primer polymerase chain reaction (DOP-PCR) and taramide signal amplification (TSA) to identify DNA copy number abnormalities (CNA) in cancer cell lines and cancer cells procured with laser-based microdissection. To determine the sensitivity and specificity for detecting single-copy gain and loss, receiver-operator curve analysis was performed on hybridization signal ratios generated from non-DOP and DOP amplified female and male DNA using a 10,816-element cDNA microarray. A cutoff value of 1.12 and 1.07 average signal ratio for X-chromosomal genes versus autosomal genes provided a sensitivity and specificity of 50 and 79%, respectively, for non-DOP amplified DNA and a sensitivity and specificity of 50 and 72%, respectively, for DOP amplified DNA. We used this approach to identify DNA copy number abnormalities in the ovarian cancer cell line OVCA633, which has previously been shown to have 12p amplification. Transcription profiling of OVCA633 was also performed. Two amplified and overexpressed genes located on 12p 11, KRAS2 and LRMP, were identified; these were validated with quantitative real-time PCR. Subsequently, the same approach was used to identify CNAs and gene expression alterations in 11 microdissected serous ovarian adenocarcinoma cases. Validated data revealed amplification and overexpression of ERBB3 and FOS and deletion and underexpression of KRT6 and APXL in more than 50% of the tissue samples. These results show the feasibility of using the cDNA array platform to identify changes in DNA and mRNA copy number simultaneously in microdissected tumor tissues. (C) 2004 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, Lab Mol Cytogenet, Houston, TX 77030 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Tokyo, Sch Hlth Sci & Nursing, Dept Biostat Epidemiol & Prevent Hlth Sci, Tokyo, Japan. NCI, Biomarkers & Prevent Res Branch, Rockville, MD USA. Osaka City Gen Hosp, Dept Obstet & Gynecol, Osaka, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Gynceol Oncol,Dept Obst, Brigham & Womens Hosp,Lab Gynecol Oncol, Boston, MA 02115 USA. RP Wong, KK (reprint author), Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, Lab Mol Cytogenet, Houston, TX 77030 USA. EM kkwong@txccc.org; scmok@rics.bwh.harvard.edu RI Ito, Yoichi/E-2042-2012; OI Wong, Kwong-Kwok/0000-0002-0375-6669 FU NCI NIH HHS [P50CA165009, R33 CA103595, U01 CA86381] NR 29 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD DEC PY 2004 VL 155 IS 2 BP 97 EP 107 DI 10.1016/j.cancergencyto.2004.03.002 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 880SY UT WOS:000225810700001 PM 15571795 ER PT J AU Nanda, A Buckhaults, P Seaman, S Agrawal, N Boutin, P Shankara, S Nacht, M Teicher, B Stampfl, J Singh, S Vogelstein, B Kinzler, KW Croix, BS AF Nanda, A Buckhaults, P Seaman, S Agrawal, N Boutin, P Shankara, S Nacht, M Teicher, B Stampfl, J Singh, S Vogelstein, B Kinzler, KW Croix, BS TI Identification of a binding partner for the endothelial cell surface proteins TEM7 and TEM7R SO CANCER RESEARCH LA English DT Article ID CORTACTIN AB Tumor endothelial marker 7 (TEM7) was recently identified as an mRNA transcript overexpressed in the blood vessels of human solid tumors. Here, we identify several new variants of TEM7, derived by alternative splicing, that are predicted to be intracellular (TEM7-I), secreted (TEM7-S), or on the cell surface membrane (TEM7-M) of tumor endothelium. Using new antibodies against the TEM7 protein, we confirmed the predicted expression of TEM7 on the cell surface and demonstrated that TEM7-M protein, like its mRNA, is overexpressed on the endothelium of various tumor types. We then used an affinity purification strategy to search for TEM7-binding proteins and identified cortactin as a protein capable of binding to the extracellular region of both TEM7 and its closest homologue, TEM7-related (TEM7R), which is also expressed in tumor endothelium. The binding domain of cortactin was mapped to a unique nine-amino acid region in its plexin-like domain. These studies establish the overexpression of TEM7 protein in tumor endothelium and provide new opportunities for the delivery of therapeutic and imaging agents to the vessels of solid tumors. C1 NCI, Mouse Canc Genet Program, Tumor Angiogenesis Sect, Frederick, MD 21701 USA. Johns Hopkins Med Inst, Howard Hughes Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Program Human Genet & Mol Biol, Baltimore, MD 21205 USA. Univ S Carolina, Sch Med, Dept Pathol, S Carolina Canc Ctr,Div Basic res, Columbia, SC 29208 USA. Genzyme Mol Oncol, Framingham, MA USA. Imgenex Corp, San Diego, CA USA. RP Croix, BS (reprint author), NCI, Mouse Canc Genet Program, Tumor Angiogenesis Sect, Frederick, MD 21701 USA. EM stcroix@ncifcrf.gov RI Seaman, Steven/A-2755-2013 OI Seaman, Steven/0000-0003-3349-3334 FU NCI NIH HHS [CA57345] NR 9 TC 26 Z9 32 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2004 VL 64 IS 23 BP 8507 EP 8511 DI 10.1158/0008-5472.CAN-04-2716 PG 5 WC Oncology SC Oncology GA 874QT UT WOS:000225365600005 PM 15574754 ER PT J AU Izzotti, A Cartiglia, C Longobardi, M Bagnasco, M Merello, A You, M Lubet, RA De Flora, S AF Izzotti, A Cartiglia, C Longobardi, M Bagnasco, M Merello, A You, M Lubet, RA De Flora, S TI Gene expression in the lung of p53 mutant mice exposed to cigarette smoke SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; TRANSFORMING GROWTH-FACTOR-BETA-1; CHEMOPREVENTIVE AGENTS; RESPIRATORY-TRACT; OXIDATIVE STRESS; TOBACCO-SMOKE; CELLS; APOPTOSIS; CANCER; GROWTH AB We showed previously that p53 mutations play a role in cigarette smoke-related carcinogenesis not only in humans but also in A/J mice. In fact, (UL53-3 x A/J)F-1 mice, carrying a dominant-negative germ-line p53 mutation, responded to exposure to environmental cigarette smoke more efficiently than their wild-type (wt) littermate controls in terms of molecular alterations, cytogenetic damage, and lung tumor yield. To clarify the mechanisms involved, we analyzed by cDNA array the expression of 1,185 cancer-related genes in the lung of the same mice. Neither environmental cigarette smoke nor the p53 status affected the expression of the p53 gene, but the p53 mutation strikingly increased the basal levels of p53 nuclear protein in the lung. Environmental cigarette smoke increased p53 protein levels in wt mice only. The p53 mutation enhanced the expression of positive cell cycle regulators in sham-exposed mice, which suggests a physiologic protective role of p53. In environmental cigarette smoke-exposed mice, the p53 mutation resulted in a lack of induction of proapoptotic genes and in overexpression of genes involved in cell proliferation, signal transduction, angiogenesis, inflammation, and immune response. Mutant mice and wt mice reacted to environmental cigarette smoke in a similar manner regarding genes involved in metabolism of xenobiotics, multidrug resistance, and protein repair. Irrespective of the p53 status, environmental cigarette smoke poorly affected the expression of oncogenes, tumor suppressor genes, and DNA repair genes. Taken together, these findings may explain the increased susceptibility of p53 mutant mice to smoke-related alterations of intermediate biomarkers and lung carcinogenesis. C1 Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. Washington Univ, Sch Med, St Louis, MO USA. NCI, Rockville, MD USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it OI izzotti, alberto/0000-0002-8588-0347 FU NCI NIH HHS [N01-CN-752008] NR 50 TC 29 Z9 31 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2004 VL 64 IS 23 BP 8566 EP 8572 DI 10.1158/0008-5472.CAN-04-1420 PG 7 WC Oncology SC Oncology GA 874QT UT WOS:000225365600014 PM 15574763 ER PT J AU Eckfeld, K Hesson, L Vos, MD Bieche, I Latif, F Clark, GI AF Eckfeld, K Hesson, L Vos, MD Bieche, I Latif, F Clark, GI TI RASSF4/AD037 is a potential ras effector/tumor suppressor of the RASSF family SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR; EPIGENETIC INACTIVATION; PROSTATE-CANCER; CELL; GENE; APOPTOSIS; IDENTIFICATION; 3P21.3; NORE1; LUNG AB Activated Ras proteins interact with a broad range of effector proteins to induce a diverse series of biological consequences. Although typically associated with enhanced growth and transformation, activated Ras may also induce growth antagonistic effects such as senescence or apoptosis. It is now apparent that some of the growth-inhibitory properties of Ras are mediated via the RASSF family of Ras effector/tumor suppressors. To date, four members of this family have been identified (Nore1, RASSF1, RASSF2, and RASSF3). We now identify a fifth member of this group, RASSF4 (AD037). RASSF4 shows approximately 25% identity with RASSF1A and 60% identity with RASSF2. RASSF4 binds directly to activated K-Ras in a GTP-dependent manner via the effector domain, thus exhibiting the basic properties of a Ras effector. Overexpression of RASSF4 induces Ras-dependent apoptosis in 293-T cells and inhibits the growth of human tumor cell lines. Although broadly expressed in normal tissue, RASSF4 is frequently down-regulated by promoter methylation in human tumor cells. Thus, RASSF4 appears to be a new member of the RASSF family of potential Ras effector/tumor suppressors. C1 NCI, Dept Cell & Canc Biol, Rockville, MD 20850 USA. Univ Birmingham, Div Reprod & Child Hlth, Sect Med & Mol Genet, Birmingham, W Midlands, England. Ctr Rene Huguenin, INSERM E0017, Lab Oncogenet, St Cloud, France. RP Clark, GI (reprint author), NCI, Dept Cell & Canc Biol, 9610 Med Ctr Dr, Rockville, MD 20850 USA. EM gclark@mail.nih.gov NR 34 TC 63 Z9 67 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2004 VL 64 IS 23 BP 8688 EP 8693 DI 10.1158/0008-5472.CAN-04-2065 PG 6 WC Oncology SC Oncology GA 874QT UT WOS:000225365600029 PM 15574778 ER PT J AU Baek, SJ Kim, JS Jackson, FR Eling, TE McEntee, MF Lee, SH AF Baek, SJ Kim, JS Jackson, FR Eling, TE McEntee, MF Lee, SH TI Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells SO CARCINOGENESIS LA English DT Article ID DRUG-ACTIVATED GENE; BETA SUPERFAMILY MEMBER; BONE MORPHOGENETIC PROTEIN; GREEN TEA CATECHINS; PROSTATE-CANCER; CARCINOMA CELLS; TUMOR-CELLS; DNA-DAMAGE; P53; CYCLOOXYGENASE AB There is persuasive epidemiological and experimental evidence that dietary polyphenolic plant-derived compounds have anticancer activity. Many laboratories, including ours, have reported such an effect in cancers of the gastrointestinal tract, lung, skin, prostate and breast. The catechins are a group of polyphenols found in green tea, which is one of the most commonly consumed beverages in the world. While the preponderance of the data strongly indicates significant antitumorigenic benefits from the green tea catechins, the potential molecular mechanisms involved remain obscure. We found that green tea components induce apoptosis via a TGF-beta superfamily protein, NAG-1 (Non-steroidal anti-inflammatory drug Activated Gene). In this report, we show that ECG is the strongest NAG-1 inducer among the tested catechins and that treatment of HCT-116 cells results in an increasing G(1) sub-population, and cleavage of poly (ADP-ribose) polymerase ( PARP), consistent with apoptosis. In contrast, other catechins do not significantly induce NAG-1 expression, PARP cleavage or morphological changes at up to a 50-muM concentration. Furthermore, we provide evidence that ECG induces the ATF3 transcription factor, followed by NAG-1 induction at the transcriptional level in a p53-independent manner. The data generated by this study will help elucidate mechanisms of action for components in green tea and this information may lead to the design of more effective anticancer agents and informed clinical trials. C1 Univ Tennessee, Coll Vet Med, Dept Pathobiol, Lab Environm Carcinogenesis, Knoxville, TN 37996 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Baek, SJ (reprint author), Univ Tennessee, Coll Vet Med, Dept Pathobiol, Lab Environm Carcinogenesis, 2407 River Dr, Knoxville, TN 37996 USA. EM sbaek2@utk.edu OI Baek, Seung/0000-0001-7866-7778; McEntee, Michael/0000-0002-1616-3715 FU NIEHS NIH HHS [K22ES011657] NR 55 TC 98 Z9 101 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2004 VL 25 IS 12 BP 2425 EP 2432 DI 10.1093/carcin/bgh255 PG 8 WC Oncology SC Oncology GA 876XK UT WOS:000225531900017 PM 15308587 ER PT J AU Goodman, JE Bowman, ED Chanock, SJ Alberg, AJ Harris, CC AF Goodman, JE Bowman, ED Chanock, SJ Alberg, AJ Harris, CC TI Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk SO CARCINOGENESIS LA English DT Article ID HUMAN 5-LIPOXYGENASE GENE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLORECTAL-CANCER; HAPLOTYPE RECONSTRUCTION; PROMOTER GENOTYPE; POPULATION; ASPIRIN; ACID; CARCINOGENESIS; LEUKOTRIENES AB In the human colon, arachidonic acid is metabolized primarily by cyclooxygenase (COX) and arachidonate lipoxygenase (ALOX) to bioactive lipids, which are implicated in colon cancer risk. Several polymorphisms in ALOX and COX genes have been identified, including G-1752A, G-1699A and Glu254Lys in ALOX5; Gln261Arg in ALOX12; Leu237Met and Val481Ile in COX1; and C-645T and Val511Ala in COX2. Because of the significant role of arachidonic acid metabolism in colon cancer, we hypothesized that these polymorphisms could influence susceptibility to colon cancer. We addressed this hypothesis in African-Americans and Caucasians using colon cancer cases (n = 293) and hospital- (n = 229) and population-based (n = 304) control groups. Polymorphisms did not differ between the control groups (P > 0.05); thus, they are combined for all analyses presented. ALOX5 Glu254Lys and COX2 C-645T and Val511Ala allele frequencies differed between Caucasians and African-American controls (P < 0.001). The ALOX5 -1752 and -1699 polymorphisms were in linkage disequilibrium (P < 0.001) and associated with a decreased risk in Caucasians in ALOX5 haplotype analyses (P = 0.03). Furthermore, an inverse association was observed between A alleles at positions -1752 and -1699 of ALOX5 and colon cancer risk in Caucasians, but not in African-Americans. Caucasians with A alleles at ALOX5 -1752 had a reduced odds of colon cancer versus those with G alleles [odds ratio (OR) (GA versus GG), 0.63; 95% confidence interval (CI), 0.39-1.01; OR (AA versus GG), 0.33; 95% CI, 0.07-1.65, P-trend = 0.02]. Similar results were observed for ALOX5 G-1699A [OR (GA versus GG), 0.59, 95% CI, 0.37-0.94; OR (AA versus GG), 0.27, 95% CI, 0.06-1.32, P-trend = 0.01]. Statistically significant associations with colon cancer were not observed for the other polymorphisms investigated. We have shown for the first time that a haplotype containing ALOX5 G-1752A and G-1699A in a negative regulatory region of the promoter may influence colon cancer risk in Caucasians. C1 NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Bldg 37, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov NR 32 TC 61 Z9 70 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2004 VL 25 IS 12 BP 2467 EP 2472 DI 10.1093/carcin/bgh260 PG 6 WC Oncology SC Oncology GA 876XK UT WOS:000225531900022 PM 15308583 ER PT J AU Mans, BJ Anantharaman, V Aravind, L Koonin, EV AF Mans, BJ Anantharaman, V Aravind, L Koonin, EV TI Comparative genomics, evolution and origins of the nuclear envelope and nuclear pore complex SO CELL CYCLE LA English DT Review DE nuclear pore; nuclear envelope; karyopherins; nucleoporins; eukaryotic; evolution; prekaryote; horizontal gene transfer; evolutionary parsimony ID MESSENGER-RNA EXPORT; SACCHAROMYCES-CEREVISIAE GENE; MULTIPLE SEQUENCE ALIGNMENT; YEAST IMPORTIN ALPHA; RAN GTPASE CYCLE; MEMBRANE-PROTEIN; BINDING-PROTEINS; CAENORHABDITIS-ELEGANS; ENDOPLASMIC-RETICULUM; NUCLEOCYTOPLASMIC TRANSPORT AB The presence of a distinct nucleus, the compartment for confining the genome, transcription and RNA maturation, is a central (and eponymous) feature that distinguishes eukaryotes from prokaryotes. Structural integrity of the nucleus is maintained by the nuclear envelope (NE). A crucial element of this structure is the nuclear pore complex (NPC), a macromolecular machine with over 90 protein components, which mediates nucleo-cytoplasmic communication. We investigated the provenance of the conserved domains found in these perinuclear proteins and reconstructed a parsimonious scenario for NE and NPC evolution by means of comparative-genomic analysis of their components from the available sequences of 28 sequenced eukaryotic genomes. We show that the NE and NPC proteins were tinkered together from diverse domains, which evolved from prokaryotic precursors at different points in eukaryotic evolution, divergence from pre-existing eukaryotic paralogs performing other functions, and de novo. It is shown that several central components of the NPC, in particular, the RanGDP import factor NTF2, the HEH domain of Src1p-Man1, and, probably, also the key domains of karyopherins and nucleoporins, the HEAT/ARM and WD40 repeats, have a bacterial, most likely, endosymbiotic origin. The specialized immunoglobulin (Ig) domain in the globular tail of the animal lamins, and the Ig domains in the nuclear membrane protein GP210 are shown to be related to distinct prokaryotic families of Ig domains. This suggests that independent, late horizontal gene transfer events from bacterial sources might have contributed to the evolution of perinuclear proteins in some of the major eukaryotic lineages. Snurportin 1, one of the highly conserved karyopherins, contains a cap-binding domain which is shown to be an inactive paralog of the guanylyl transferase domain of the mRNA-capping enzyme, exemplifying recruitment of paralogs of pre-exsiting proteins for perinuclear functions. It is shown that several NPC proteins containing super-structure-forming alpha-helical and beta-propeller modules are most closely related to corresponding proteins in the cytoplasmic vesicle biogenesis and coating complexes. From these observations, we infer an autogenous scenario of nuclear evolution in which the nucleus emerged in the primitive eukaryotic ancestor (the "prekaryote") as part of cell compartmentalization triggered by archaeo-bacterial symbiosis. A pivotal event in this process was the radiation of Ras-superfamily GTPases yielding Ran, the key regulator of nuclear transport. A primitive NPC with approximately 20 proteins and a Src1p-Man1-like membrane protein with a DNA-tethering HEH domain are inferred to have been integral perinuclear components in the las common ancestor of modern eukaryotes. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA. EM aravind@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov OI Anantharaman, Vivek/0000-0001-8395-0009; Mans, Ben/0000-0002-0177-0029 NR 252 TC 206 Z9 213 U1 3 U2 13 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC PY 2004 VL 3 IS 12 BP 1612 EP 1637 PG 26 WC Cell Biology SC Cell Biology GA 902SE UT WOS:000227376000025 PM 15611647 ER PT J AU Carvalho, ACP Sharpe, J Rosenstock, TR Teles, AFV Youle, RJ Smaili, SS AF Carvalho, ACP Sharpe, J Rosenstock, TR Teles, AFV Youle, RJ Smaili, SS TI Bax affects intracellular Ca2+ stores and induces Ca2+ wave propagation SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE Bax; calcium signaling; mitochondria; endoplasmic reticulum; calcium waves; wave propagation; apoptosis ID CYTOCHROME-C RELEASE; MITOCHONDRIAL PERMEABILITY TRANSITION; ENDOPLASMIC-RETICULUM; CELL-DEATH; CALCIUM OSCILLATIONS; APOPTOTIC PROTEINS; MEMBRANE; SIGNALS; MECHANISMS; RECEPTORS AB In the present study, we evaluated proapoptotic protein Bax on mitochondria and Ca2+ homeostasis in primary cultured astrocytes. We found that recombinant Bax (rBax, 10 and 100 ng/ml) induces a loss in mitochondrial membrane potential (DeltaPsi(m)). This effect might be related to the inhibition of respiratory rates and a partial release of cytochrome c, which may change mitochondrial morphology. The loss of DeltaPsi(m) and a selective permeabilization of mitochondrial membranes contribute to the release of Ca2+ from the mitochondria. This was inhibited by cyclosporin A (5 muM) and Ruthenium Red (1 mug/ml), indicating the involvement of mitochondrial Ca2+ transport mechanisms. Bax-induced mitochondrial Ca2+ release evokes Ca2+ waves and wave propagation between cells. Our results show that Bax induces mitochondrial alteration that affects Ca2+ homeostasis and signaling. These changes show that Ca2+ signals might be correlated with the proapoptotic activities of Bax. C1 Univ Fed Sao Paulo, UNIFESP, INFAR, Dept Pharmacol, BR-04044020 Sao Paulo, Brazil. NINDS, Biochem Sect, NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, Inst Quim, Dept Biochem, Sao Paulo, Brazil. RP Smaili, SS (reprint author), Univ Fed Sao Paulo, UNIFESP, INFAR, Dept Pharmacol, Rua Tres Maio 100, BR-04044020 Sao Paulo, Brazil. EM ssmaili@farm.epm.br RI Rosenstock, Tatiana/N-1949-2013 OI Rosenstock, Tatiana/0000-0003-1153-7412 NR 60 TC 31 Z9 32 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD DEC PY 2004 VL 11 IS 12 BP 1265 EP 1276 DI 10.1038/sj.cdd.4401508 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 871DP UT WOS:000225109800004 PM 15499375 ER PT J AU Wang, LH Zhang, XH Farrar, WL Yang, XY AF Wang, Lihua Zhang, Xiaohu Farrar, William L. Yang, Xiaoyi TI Transcriptional Crosstalk between Nuclear Receptors and Cytokine Signal Transduction Pathways in Immunity SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Review DE nuclear receptor; cytokine; signaling transduction; crosstalk; transcriptional factor; immunity AB The nuclear receptor superfamily and the transcriptional factors associated with cytokines are inherently different families of signaling molecules and activate gene transcription by binding to their respective responsive element. However, it has become increasingly clear from our works and others that nuclear receptors are important regulators of cytokine production and function through complex and varied interactions between these distinct transcriptional factors. This review provides a general overview of the mechanism of action of nuclear receptors and their transcriptional crosstalk with transcriptional factors associated with cytokine transduction pathways. One of the most important mechanistic aspects is protein to protein interaction through a direct or co-regulator-mediated indirect manner. Such crosstalk is crucially involved in physiological and therapeutic roles of nuclear receptors and their ligands in immunity, inflammation and cytokine-related tumors. C1 [Wang, Lihua; Zhang, Xiaohu; Yang, Xiaoyi] NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21701 USA. [Farrar, William L.; Yang, Xiaoyi] NCI, Div Basic Sci, Mol Immunoregulat Lab, Cytokine Mol Mech Sect, Frederick, MD 21701 USA. RP Yang, XY (reprint author), 1050 Bayles St, Frederick, MD 21702 USA. EM yangx@ncifcrf.gov FU NCI/NIH [NO1-CO-12400] FX This project has been funded in whole or in part with Federal Funds from the NCI/NIH under Contract NO1-CO-12400. NR 108 TC 13 Z9 14 U1 0 U2 1 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD DEC PY 2004 VL 1 IS 6 BP 416 EP 424 PG 9 WC Immunology SC Immunology GA V32AQ UT WOS:000208924500003 PM 16293210 ER PT J AU Xiao, WH AF Xiao, Weihua TI Advances in NF-kappa B Signaling Transduction and Transcription SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Review DE transcription factor; NF-kappa B; signaling pathway; immunology; transcriptional regulation AB The molecular mechanisms for NF-kappa B signaling transduction and transcription have been the most attractive subjects for both basic research and pharmaceutical industries due to its important roles in both physiological and pathogenesis, particularly the close association of dysregulated NF-kappa B with tumorgenesis and inflammation. Several novel intracellular molecular events that regulate NF-kappa B activity have been described recently, including the discovery of an alternative signaling pathway that appears inducing a specific subset genes involved in adoptive immune response. Multi-level and multi-dimensional regulation of NF-kappa B activity by phosphorylation and acetylation modifications have unveiled and became the hottest targets for potentially tissue specific molecular interventions. Another emerging mechanism for NF-kB-responsive gene's regulation where NF-kappa B participates the transcriptional regulation independent of its cognate regulatory binding site within the target gene's promoter but facilitating the transaction activity of other involved transcription factors, that implicated an novel transcriptional activities for NF-kappa B. Thus, the current review will focus on these recent progresses that have been made on NF-kappa B signaling transduction and transcription. C1 [Xiao, Weihua] Univ Sci & Technol China, Hefei 230027, Anhui, Peoples R China. [Xiao, Weihua] NCI, Immunogenet Mol Lab, Frederick, MD 21702 USA. RP Xiao, WH (reprint author), Univ Sci & Technol China, Sch Life Sci, Inst Immunol, 443 Huangshan Rd, Hefei 230027, Anhui, Peoples R China. EM xiaow@ustc.edu RI Xiao, Weihua/N-2775-2013 OI Xiao, Weihua/0000-0001-9102-6326 NR 132 TC 58 Z9 66 U1 1 U2 4 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD DEC PY 2004 VL 1 IS 6 BP 425 EP 435 PG 11 WC Immunology SC Immunology GA V32AQ UT WOS:000208924500004 PM 16293211 ER PT J AU Wang, YZ Schnetz-Boutaud, NC Kroth, H Yagi, H Sayer, JM Kumar, S Donald, JM Stone, MP AF Wang, YZ Schnetz-Boutaud, NC Kroth, H Yagi, H Sayer, JM Kumar, S Donald, JM Stone, MP TI Structures of the 1S and 1R trans-opened benzo[c]phenanthrene diol epoxide dG adducts in a frameshift-prone (CpG)3 repeat sequence from the Salmonella typhimurium his D3052 gene. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 Vanderbilt Univ, Dept Chem, Ctr Mol Toxicol, Nashville, TN 37235 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. SUNY Coll Buffalo, Great Lakes Lab, Buffalo, NY 14222 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 DEC PY 2004 VL 17 IS 12 MA 42 BP 1766 EP 1766 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 881XK UT WOS:000225902600068 ER PT J AU Srinivasan, A Citro, ML Davies, KM Espey, MG Keefer, LK Miranda, KM Ridnour, LA Saavedra, JE Thomas, L Thomas, DD Waterhouse, DJ Wink, DA AF Srinivasan, A Citro, ML Davies, KM Espey, MG Keefer, LK Miranda, KM Ridnour, LA Saavedra, JE Thomas, L Thomas, DD Waterhouse, DJ Wink, DA TI Chemistry of the diazeniumdiolates. RHN[N(O)NO](-) ions as progenitors of both nitroxyl and nitric oxide. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, BRP, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. EM srinin@aol.com RI Miranda, Katrina/B-7823-2009; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2004 VL 17 IS 12 MA 54 BP 1769 EP 1769 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 881XK UT WOS:000225902600080 ER PT J AU Taveira-DaSilva, AM Stylianou, MP Hedin, CJ Hathaway, A Moss, J AF Taveira-DaSilva, AM Stylianou, MP Hedin, CJ Hathaway, A Moss, J TI Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone SO CHEST LA English DT Article DE interstitial lung diseases; progesterone; respiratory function ID DEPOT-MEDROXYPROGESTERONE ACETATE; SMOOTH-MUSCLE-CELLS; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; TUBEROUS SCLEROSIS; STEROID-RECEPTORS; WOMEN; THERAPY; DISEASE; BIOAVAILABILITY; CONTRACEPTION AB Study objective: Lymphangioleiomyomatosis (LAM), a disease affecting women and causing cystic lung lesions, and, in some instances, leading to respiratory failure and death, appears to be exacerbated by estrogens. Hence, hormonal therapy with progesterone is frequently employed: however, efficacy has not been demonstrated. Our aim was to determine whether progesterone administration slowed the decline in lung function in LAM. Design: Retrospective study. Design: Retrospective study. Setting: National Institutes of Health, Bethesda, MD. Design and subjects: The study population comprised 348 patients with I-A-M participating in a longitudinal research protocol. Declines in diffusion capacity of the lung for carbon monoxide (DLCO) and FEV1 were measured in 275 patients observed for approximately 4 years. The declines in DLCO and FEV1 of patients treated with progesterone, po (n = 67) or IM (n =72) were compared with those of untreated patients (n = 136). Measurements and results: Overall yearly rates of decline in DLCO and FEV1 were 2.4 +/- 0.4% predicted (0.69 +/- 0.07 mL/min/mm Hg) and 1.7 +/- 0.4% predicted (75 +/- 9 mL), respectively (mean SEM). The most significant predictors of functional decline were initial lung function and age. After adjusting for initial FEV1, age, and duration of disease.. patients treated with LM progesterone tended to have lower rates of decline in FEV1 than patients treated po (1.9 +/- 0.6%, predicted vs 3.2 +/- 0.8% predicted, respectively, p = 0.081). However. there was no significant difference in rates of decline in FEV1 between patients treated with IM progesterone and untreated patients (1.9 +/- 0.6% predicted vs 0.8 +/- 0.5% predicted, respectively; p = 0.520): and patients treated with po progesterone and untreated patients (3.2 +/- 0.8%, predicted vs 0.8 +/- 0.5% predicted, respectively; p = 0.064). After a adjusting for initial DLCO. rates of decline in DLCO were significantly higher in patients treated with po progesterone (3.6 +/- 0.7% predicted. p = 0.002) and IM progesterone (2.8 +/- 0.5% predicted p = 0.022) than in untreated patients (1.6 +/- 0.6% predicted). Conclusions: Within the limitations of a retrospective study, our data suggest that progesterone therapy does not slow the decline in lung function in LAM. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 6D-05,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov NR 50 TC 102 Z9 109 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2004 VL 126 IS 6 BP 1867 EP 1874 DI 10.1378/chest.126.6.1867 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 879YI UT WOS:000225754900028 PM 15596686 ER PT J AU Stanyon, R Bigoni, F Slaby, T Muller, S Stone, G Bonvicino, CR Neusser, M Seuanez, HN AF Stanyon, R Bigoni, F Slaby, T Muller, S Stone, G Bonvicino, CR Neusser, M Seuanez, HN TI Multi-directional chromosome painting maps homologies between species belonging to three genera of New World monkeys and humans SO CHROMOSOMA LA English DT Article ID OWL MONKEY; BANDING-PATTERNS; SAGUINUS-OEDIPUS; GENUS AOTUS; CELL-LINE; PLATYRRHINI; PHYLOGENY; CEBIDAE; PRIMATES; CALLICEBUS AB We mapped chromosomal homologies in two species of Chiropotes (Pitheciini, Saki Monkeys) and one species of Aotus (Aotinae, Owl Monkey) by multi-directional chromosome painting. Human chromosome probes were hybridized to Chiropotes utahicki, C. israelita and Aotus nancymae metaphases. Wooly Monkey chromosome paints were also hybridized to Owl Monkey metaphases. We established Owl Monkey chromosome paint probes by flow sorting and reciprocally hybridized them to human chromosomes. The karyotypes of the Bearded Saki Monkeys studied here are close to the hypothesized ancestral platyrrhine karytoype, while that of the Owl Monkey appears to be highly derived. The A. nancymae karyotype is highly shuffled and only three human syntenic groups were found conserved coexisting with 17 derived human homologous associations. A minimum of 14 fissions and 13 fusions would be required to derive the A. nancymae karyotype from that of the ancestral New World primate karyotype. An inversion between homologs to segments of human 10 and 16 suggests a link between Callicebus and Chiropotes, while the syntenic association of 10/11 found in Aotus and Callicebus suggests a link between these two genera. Future molecular cytogenetic work will be needed to determine whether these rearrangements represent synapomorphic chromosomal traits. C1 NCI, Comparat Mol Cytogenet Core, BRL, Frederick, MD 21701 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Munich, Dept Biol 2, Inst Anthropol & Human Genet, Munich, Germany. Inst Nacl Canc, Div Genet, Rio De Janeiro, Brazil. Inst Oswaldo Cruz, Dept Trop Med, BR-20001 Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Dept Genet, Rio De Janeiro, Brazil. RP Stanyon, R (reprint author), NCI, Comparat Mol Cytogenet Core, BRL, Frederick, MD 21701 USA. EM stanyonr@ncifcrf.gov RI Bonvicino, Cibele /O-3390-2014; OI Stanyon, Roscoe/0000-0002-7229-1092 NR 40 TC 18 Z9 19 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD DEC PY 2004 VL 113 IS 6 BP 305 EP 315 DI 10.1007/s00412-004-0320-6 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 875IT UT WOS:000225414400005 PM 15616867 ER PT J AU Goldstein, DS Holmes, C Kaufmann, H Freeman, R AF Goldstein, DS Holmes, C Kaufmann, H Freeman, R TI Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE DOPS; norepinephrine; dihydroxyphenylglycol; autonomic failure; sympathetic nervous system ID NEUROGENIC ORTHOSTATIC HYPOTENSION; PARKINSONS-DISEASE; ORAL LEVODOPA; CATECHOLAMINES; DENERVATION; KINETICS AB Background Oral L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic catechol amino acid, increases standing blood pressure and improves standing ability in patients with neurogenic orthostatic hypotension, by conversion of L-DOPS to norepinephrine (NE) outside the brain. This study assessed the pharmacokinetics of L-DOPS, NE, and dihydroxyphenylglycol (DHPG), the main neuronal metabolite of NE, in patients with primary chronic autonomic failure from pure autonomic failure (PAF) or multiple system atrophy (MSA). Methods In 5 MSA and 4 PAF patients, antecubital venous blood was drawn during supine rest and plasma levels of catechols measured at various times for 48 hours after a single oral dose of 400 mg of L-DOPS. Results Plasma L-DOPS peaked at 1.9 mug/ml (9 mumol/L) about 3 hours after drug administration, followed by a monoexponential decline with a half-time of 2-3 hours in both patient groups. Plasma NE and DHPG also peaked at about 3 hours, but at much lower concentrations (4 and 42 nmol/L). Compared to the MSA group, the PAF group had a smaller calculated volume of distribution of L-DOPS and up to 10-fold lower plasma NE levels at all time points. Plasma NE was above baseline in MSA even at 48 hours after L-DOPS. Conclusions The relatively long half-time for disappearance of L-DOPS compared to that of NE explains their very different attained plasma concentrations. The similar NE and DHPG responses in PAF and MSA suggests production of NE from L-DOPS mainly in non-neuronal cells. Persistent elevation of plasma NE in MSA suggests residual release of NE from sympathetic nerves. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, New York, NY USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 10,Room 6N252,10 Ctr Dr,MSC 1620, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov OI Kaufmann, Horacio/0000-0002-1851-9981 NR 19 TC 29 Z9 30 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD DEC PY 2004 VL 14 IS 6 BP 363 EP 368 DI 10.1007/s10286-004-0221-z PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 884IZ UT WOS:000226079500009 PM 15666063 ER PT J AU Tykodi, SS Warren, EH Thompson, JA Riddell, SR Childs, RW Otterud, BE Leppert, MF Storb, R Sandmaier, BM AF Tykodi, SS Warren, EH Thompson, JA Riddell, SR Childs, RW Otterud, BE Leppert, MF Storb, R Sandmaier, BM TI Allogeneic hematopoietic cell transplantation for metastatic renal cell carcinoma after nonmyeloablative conditioning: Toxicity, clinical response, and immunological response to minor histocompatibility antigens SO CLINICAL CANCER RESEARCH LA English DT Article ID VERSUS-HOST-DISEASE; CYTOTOXIC T-LYMPHOCYTES; CLASS-II EXPRESSION; COMPLEX CLASS-I; H-Y-ANTIGEN; HLA-CLASS-I; REDUCED-INTENSITY; HEMATOLOGIC MALIGNANCIES; SOLID TUMORS; PREPARATIVE REGIMEN AB Purpose: This phase I trial assessed the safety, efficacy, and immunologic responses to minor histocompatibility antigens following nonmyeloablative allogeneic hematopoietic cell transplantation as treatment for metastatic renal cell carcinoma. Experimental Design: Eight patients received conditioning with fludarabine and low-dose total body irradiation followed by hematopoietic cell transplantation from an HLA-matched sibling donor. Cyclosporine and mycophenolate mofetil were administered as posttransplant immunosuppression. Patients were monitored for donor engraftment of myeloid and lymphoid cells, for clinical response by serial imaging, and for immunologic response by in vitro isolation of donor-derived CD8(+) CTLs recognizing recipient minor histocompatibility (H) antigens. Results: All patients achieved initial mixed hematopoietic chimerism with two patients rejecting their graft and recovering host hematopoiesis. Four patients developed acute, grade 2 to 3, graft-versus-host disease and four patients developed extensive chronic graft-versus-host disease. Five patients had progressive disease, two patients had stable disease, and one patient experienced a partial response after receiving donor lymphocyte infusions and IFN-alpha. CD8(+) CTL clones recognizing minor H antigens were isolated from five patients studied. Clones from three patients with a partial response or stable disease recognized antigens expressed on renal cell carcinoma tumor cells. Conclusions: Treatment of metastatic renal cell carcinoma with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning with fludarabine/total body irradiation is feasible and may induce tumor regression or stabilization in some patients. CD8(+) CTL-recognizing minor H antigens on tumor cells can be isolated posttransplant and could contribute to the graft-versus-tumor effect. Such antigens may represent therapeutic targets for posttransplant vaccination or adoptive T-cell therapy to augment the antitumor effects of allogeneic hematopoietic cell transplantation. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Seattle, WA 98195 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT USA. RP Sandmaier, BM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM bsandmai@fhcrc.org FU NCI NIH HHS [P01 CA078902, CA91553, CA15704, CA18029, CA78902] NR 65 TC 66 Z9 67 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2004 VL 10 IS 23 BP 7799 EP 7811 DI 10.1158/1078-0432.CCR-04-0072 PG 13 WC Oncology SC Oncology GA 878US UT WOS:000225673200003 PM 15585611 ER PT J AU Milenic, DE Garmestani, K Brady, ED Albert, PS Ma, DS Abdulla, A Brechbiel, MW AF Milenic, DE Garmestani, K Brady, ED Albert, PS Ma, DS Abdulla, A Brechbiel, MW TI Targeting of HER2 antigen for the treatment of disseminated peritoneal disease SO CLINICAL CANCER RESEARCH LA English DT Article ID ALPHA-PARTICLE-EMITTER; HUMANIZED MONOCLONAL-ANTIBODY; BREAST-CANCER XENOGRAFTS; SINGLE-CHAIN FV; OVARIAN-CANCER; RADIOLABELED ANTIBODIES; PROSTATE-CANCER; RADIOIMMUNOTHERAPY; THERAPY; PHARMACOKINETICS AB The studies reported herein demonstrate the efficacy of alpha-particle-targeted radiation therapy of peritoneal disease with Herceptin as the targeting vehicle. Using the CHX-A-DTPA linker, Herceptin was radiolabeled with indium-111 and bismuth-213 with high efficiency without compromising immunoreactivity. A pilot radioimmunotherapy study treating mice bearing 5-day LS-174T (i.p.) xenografts, a low but uniform HER2 expressing, human colon carcinoma, with a single dose of Bi-213-CHX-A"-Herceptin, proved disappointing. This defined the effect of tumor burden/size on tumor response to radioimmunotherapy with alpha-radiation. A more successful experiment with a lower tumor burden (3 days) in mice followed. A specific dose-response (P = 0.009) was observed, and although a maximum-tolerated dose was not determined, a dose of 500 to 750 muCi was selected as the operating dose for future experiments based on changes in animal weight. Median survival was increased from 20.5 days for the mock-treated mice to 43 and 59 days with 500 and 750 muCi, respectively. The therapeutic effectiveness of Bi-213-CHX-A"-Herceptin was also evaluated in a second animal model for peritoneal disease with a human pancreatic carcinoma (Shaw). The results of this study were not as dramatic as with the former model, and higher doses were required to obtain an increase in survival of the mice (P = 0.001). C1 NCI, Radioimmuno & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmuno & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,MSC-1002,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. NR 54 TC 51 Z9 52 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2004 VL 10 IS 23 BP 7834 EP 7841 DI 10.1158/1078-0432.CCR-04-1226 PG 8 WC Oncology SC Oncology GA 878US UT WOS:000225673200007 PM 15585615 ER PT J AU Bull, EEA Dote, H Brady, KJ Burgan, WE Carter, DJ Cerra, MA Oswald, KA Hollingshead, MG Camphausen, K Tofilon, PJ AF Bull, EEA Dote, H Brady, KJ Burgan, WE Carter, DJ Cerra, MA Oswald, KA Hollingshead, MG Camphausen, K Tofilon, PJ TI Enhanced tumor cell radiosensitivity and abrogation of G(2) and S phase arrest by the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA-DAMAGE; IONIZING IRRADIATION; SIGNAL-TRANSDUCTION; TISSUE DISTRIBUTION; CANCER-CELLS; IN-VITRO; RADIATION; CHECKPOINT; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; GELDANAMYCIN AB Purpose: Because of the potential for affecting multiple signaling pathways, inhibition of Hsp90 may provide a strategy for enhancing tumor cell radiosensitivity. Therefore, we have investigated the effects of the orally bioavailable Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) on the radiosensitivity of human tumor cells in vitro and grown as tumor xenografts. Experimental Design: The effect of 17-DMAG on the levels of three proteins (Raf-1, ErbB2, and Akt) previously implicated in the regulation of radiosensitivity was determined in three human solid tumor cell lines. A clonogenic assay was then used to evaluate cell survival after exposure to 17-DMAG followed by irradiation. For mechanistic insight, the G(2)- and S-phase checkpoints were evaluated in 17-DMAG-treated cells. Finally, the effect of in vivo administration of 17-DMAG in combination with radiation on the growth rate of xenograft tumors was determined. Results: 17-DMAG exposure reduced the levels of the three radiosensitivity-associated proteins in a cell line-specific manner with ErbB2 being the most susceptible. Corresponding concentrations of 17-DMAG enhanced the radiosensitivity of each of the tumor cell lines. This sensitization seemed to be the result of a 17-DMAG-mediated abrogation of the G(2)- and S-phase cell cycle checkpoints. The oral administration of 17-DMAG to mice bearing tumor xenografts followed by irradiation resulted in a greater than additive increase in tumor growth delay. Conclusions: These data indicate that 17-DMAG enhances the in vitro and in vivo radiosensitivity of human tumor cells. The mechanism responsible seems to involve the abrogation of radiation-induced G(2)- and S-phase arrest. C1 NCI, Mol Radiat Therapeut Branch, Radiat Res Program, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick, MD USA. RP Tofilon, PJ (reprint author), NCI, Mol Radiat Therapeut Branch, Radiat Res Program, EPN 6015A,6130 Execut Blvd,MSC 7440, Bethesda, MD 20892 USA. EM tofilonp@mail.nih.gov NR 31 TC 69 Z9 75 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2004 VL 10 IS 23 BP 8077 EP 8084 DI 10.1158/1078-0432.CCR-04-1212 PG 8 WC Oncology SC Oncology GA 878US UT WOS:000225673200035 PM 15585643 ER PT J AU Drake, SK Bowen, RAR Remaley, AT Hortin, GL AF Drake, SK Bowen, RAR Remaley, AT Hortin, GL TI Potential interferences from blood collection tubes in mass spectrometric analyses of serum polypeptides SO CLINICAL CHEMISTRY LA English DT Letter ID CANCER; DIAGNOSTICS; PROTEOMICS C1 NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov NR 15 TC 69 Z9 73 U1 0 U2 4 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 DEC PY 2004 VL 50 IS 12 BP 2398 EP 2401 DI 10.1373/clinchem.2004.040303 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 874NI UT WOS:000225356700030 PM 15563493 ER PT J AU Elphinstone, MS Gordon, RD So, A Jeske, YWA Stratakis, CA Stowasser, M AF Elphinstone, MS Gordon, RD So, A Jeske, YWA Stratakis, CA Stowasser, M TI Genomic structure of the human gene for protein kinase A regulatory subunit R1-beta (PRKAR1B) on 7p22: no evidence for mutations in familial hyperaldosteronism type II in a large affected kindred SO CLINICAL ENDOCRINOLOGY LA English DT Article ID PRIMARY ALDOSTERONISM; HYPERTENSIVE PATIENTS; CLONING; PREVALENCE; EXPRESSION; PRODUCT AB OBJECTIVE Familial hyperaldosteronism type II (FH-II) is characterized by inheritance of primary aldosteronism (PAL) but, unlike FH-I, is not glucocorticoid remediable and not associated with the hybrid CYP11B1/CYP11B2 gene mutation. Analysis of two pedigrees previously demonstrated linkage of FH-II with a locus at chromosome 7p22. We sought to determine whether mutations in the exons or intron/exon boundaries in PRKAR1B (encoding protein kinase A regulatory subunit R1-beta), which resides within the linked locus, are associated with FH-II. METHODS Primers enabling sequencing of all exons and intron/exon boundaries were designed by BLAT search using known mRNA sequence, and comparison with an orthologous mouse gene. Sequences from four affected and two unaffected subjects from an Australian family with FH-II demonstrating linkage at 7p22 were compared with published sequences. RESULTS A probable two-nucleotide GenBank sequence error, resulting in an amino acid change, was detected. Two of seven single nucleotide polymorphisms (SNPs) identified were in exons and five in introns. Neither exon-localized SNP resulted in an amino acid change. All intron-localized SNPs were at least 16 nucleotides from the closest intron/exon boundary and therefore unlikely to interfere with gene splicing. Importantly, none of the identified SNPs was exclusively associated with affectation status. CONCLUSIONS Mutations in the exons or intron/exon boundaries of PRKAR1B do not appear to be responsible for FH-II in this family, but a mutation in the promoter or remaining intronic or 5' or 3' untranslated regions could be. Alternatively, a mutation within another gene residing at the 7p22 locus may be responsible. C1 Univ Queensland, Dept Med, Princess Alexandra Hosp, Hypertens Unit, Brisbane, Qld 4102, Australia. Univ Queensland, Dept Med, Greenslopes Hosp, Hypertens Unit, Brisbane, Qld 4102, Australia. NICHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD USA. RP Stowasser, M (reprint author), Univ Queensland, Dept Med, Princess Alexandra Hosp, Hypertens Unit, Ipswich Rd, Brisbane, Qld 4102, Australia. EM m.stowasser@uq.edu.au RI Stowasser, Michael/F-4121-2010; Gordon, Richard/K-2555-2012 NR 34 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2004 VL 61 IS 6 BP 716 EP 723 DI 10.1111/j.1365-2265.2004.02155.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 881RJ UT WOS:000225886800009 PM 15579186 ER PT J AU Stratakis, CA Batista, D Sabnis, G Brodie, A AF Stratakis, CA Batista, D Sabnis, G Brodie, A TI Prepubertal gynaecomastia caused by medication or the aromatase excess syndrome SO CLINICAL ENDOCRINOLOGY LA English DT Letter ID GENE C1 NICHHD, Sect Endocrinol & Genet SEGEN, Dev Endocrinol Branch, NICHD, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet SEGEN, Dev Endocrinol Branch, NICHD, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 3 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2004 VL 61 IS 6 BP 779 EP 780 DI 10.1111/j.1365-2265.2004.02158.x PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 881RJ UT WOS:000225886800018 PM 15579195 ER PT J AU Shatunov, A Fridman, EA Pagan, FI Leib, J Singleton, A Hallett, M Goldfarb, LG AF Shatunov, A Fridman, EA Pagan, FI Leib, J Singleton, A Hallett, M Goldfarb, LG TI Small de novo duplication in the repeat region of the TATA-box-binding protein gene manifest with a phenotype similar to variant Creutzfeldt-Jakob disease SO CLINICAL GENETICS LA English DT Article DE DNA rearrangement; insertion/duplication; spinocerebellar ataxia; TATA-box binding protein; variant Creutzfeldt-Jakob disease ID OCULOPHARYNGEAL MUSCULAR-DYSTROPHY; SPINOCEREBELLAR ATAXIA TYPE-17; UNIQUE PABP2 MUTATIONS; TRINUCLEOTIDE REPEAT; REDUCED PENETRANCE; JAPANESE PATIENTS; SCA17; EXPANSION; FEATURES; TBP AB A 20-year-old North American patient developed rapidly progressive cognitive decline and pronounced ataxia, a phenotype compatible with prion disease. No structural changes were found in the PRNP gene, which excludes genetic prion disease, but the patient's PRNP codon 129 Met/Met genotype is known to predispose to variant Creutzfeldt-Jakob disease (vCJD). Further studies identified an expanded allele with 55 CAG/CAA repeats in the TBP gene. The increase of trinucleotide repeat number in the coding region of the TBP gene has previously been associated with spinocerebellar ataxia type 17 (SCA17). The patient's unaffected parents and siblings show normal-size TBP alleles with 37-38 repeats. Haplotype and nucleotide sequence analyses clearly indicate that the mutation has occurred de novo on a paternal chromosome by insertion/duplication of a (CAA)(CAG)(CAA)(CAG)(15) sequence. This report presents a second fully investigated sporadic case of SCA17 occurring as a result of a DNA rearrangement within the polymorphic TBP trinucleotide repeat region. Our findings suggest that patients suspected of vCJD should undergo testing for SCA17, Huntington's disease and other neurodegener-ative disorders having phenotypic similarities with vCJD. C1 NINDS, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Goldfarb, LG (reprint author), NINDS, NIH, 10 Ctr Dr,Bldg 10,Room 4B37, Bethesda, MD 20892 USA. EM goldfarbl@ninds.nih.gov RI Singleton, Andrew/C-3010-2009; Shatunov, Aleksey/E-6946-2011; OI Fridman, Esteban/0000-0001-7879-8874 NR 26 TC 12 Z9 12 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD DEC PY 2004 VL 66 IS 6 BP 496 EP 501 DI 10.1111/j.1399-0004.2004.00356.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 867QG UT WOS:000224856500003 PM 15521976 ER PT J AU Matthews, L Chapman, S Ramchandani, MS Lane, HC Davey, RT Sereti, I AF Matthews, L Chapman, S Ramchandani, MS Lane, HC Davey, RT Sereti, I TI BAY 50-4798, a novel, high-affinity receptor-specific recombinant interleukin-2 analog, induces dose-dependent increases in CD25 expression and proliferation among unstimulated, human peripheral blood mononuclear cells in vitro SO CLINICAL IMMUNOLOGY LA English DT Article DE interleukin-2; HIV; CD25; pro-inflammatory cytokines; T cells; cell proliferation ID HUMAN-IMMUNODEFICIENCY-VIRUS; PULMONARY VASCULAR LEAK; T-CELLS; SUBCUTANEOUS INTERLEUKIN-2; CONTROLLED-TRIAL; NK CELLS; IL-2; THERAPY; CD4(+); NAIVE AB Interleukin-2 administration induces CD4 T cell expansion in HIV-infected patients, however, toxicity can limit dosing. BAY 50-4798 is a recombinant IL-2 analog with >1000-fold specificity for the high-affinity IL-2 receptor. The effects of this compound on unstimulated human PBMC were evaluated. PBMC from HIV- and HIV+ donors were cultured in vitro with incremental doses of BAY 50-4798 or aldesleukin. CD25 expression and proliferation were evaluated with flow cytometry. Cytokine levels were measured by ELISA in culture supernatants. BAY 50-4798 induced dose-dependent increases in CD25 expression and proliferation of T cells, NK, and B cells and showed selectivity for CD4 T cells expressing CD25. Induction of pro-inflammatory cytokines was also dose-dependent and was observed at the concentrations of BAY 50-4798 with the highest biologic activity. These data suggest that BAY 50-4798 can induce proliferation of unstimulated T cells but loss of T cell selectivity and induction of pro-inflammatory cytokines occur at concentrations exerting the highest biologic activity. Published by Elsevier Inc. C1 NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Res Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Sereti, I (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11B04, Bethesda, MD 20892 USA. EM isereti@niaid.nih.gov NR 28 TC 6 Z9 6 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD DEC PY 2004 VL 113 IS 3 BP 248 EP 255 DI 10.1016/j.clim.2004.07.009 PG 8 WC Immunology SC Immunology GA 869ID UT WOS:000224975700006 PM 15507389 ER PT J AU Maertens, J Raad, I Petrikkos, G Boogaerts, M Selleslag, D Petersen, FB Sable, CA Kartsonis, NA Ngai, A Taylor, A Patterson, TF Denning, DW Walsh, TJ AF Maertens, J Raad, I Petrikkos, G Boogaerts, M Selleslag, D Petersen, FB Sable, CA Kartsonis, NA Ngai, A Taylor, A Patterson, TF Denning, DW Walsh, TJ CA Caspofungin Salvage Aspergillosis TI Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; OPPORTUNISTIC FUNGAL-INFECTIONS; CELL TRANSPLANT RECIPIENTS; DOUBLE-BLIND; IMMUNOCOMPROMISED PATIENTS; HEMATOLOGIC MALIGNANCIES; PULMONARY ASPERGILLOSIS; MK-0991 L-743,872; FILAMENTOUS FUNGI; ORAL ITRACONAZOLE AB Background. Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immuno-compromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo activity against Aspergillus species. Methods. We investigated the efficacy and safety of caspofungin in the treatment of IA. Ninety patients with IA who were refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B, or triazoles were enrolled to receive caspofungin. Results. Efficacy was assessed for 83 patients who had infection consistent with definitions of IA and who received greater than or equal to1 dose of study drug. Common underlying conditions included hematologic malignancy ( 48% of patients), allogeneic blood and marrow transplantation (25% of patients), and solid-organ transplantation (11% of patients). Seventy-one patients (86%) were refractory to and 12 patients (14%) were intolerant of previous therapy. A favorable response to caspofungin therapy was observed in 37 (45%) of 83 patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13 with disseminated aspergillosis. Two patients discontinued caspofungin therapy because of drug-related adverse events. Drug-related nephrotoxicity and hepatotoxicity occurred infrequently. Conclusion. Caspofungin demonstrated usefulness in the salvage treatment of IA. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Athens, Laiko Gen Hosp, GR-10679 Athens, Greece. AZ St Jan Brugge, Brugge, Belgium. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. Merck Res Labs, W Point, PA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Manchester, Manchester M13 9PL, Lancs, England. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N-240, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov OI Denning, David/0000-0001-5626-2251 NR 41 TC 398 Z9 435 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2004 VL 39 IS 11 BP 1563 EP 1571 DI 10.1086/423381 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JI UT WOS:000227492100001 PM 15578352 ER PT J AU Cherry, JD Chang, SJ Klein, D Lee, M Barenkamp, S Bernstein, D Edelman, R Decker, MD Greenberg, DP Keitel, W Treanor, J Ward, JI AF Cherry, JD Chang, SJ Klein, D Lee, M Barenkamp, S Bernstein, D Edelman, R Decker, MD Greenberg, DP Keitel, W Treanor, J Ward, JI TI Prevalence of antibody to Bordetella pertussis antigens in serum specimens obtained from 1793 adolescents and adults SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HOUSEHOLD EXPOSURE; VACCINE EFFICACY; COUGH ILLNESSES; INFECTIONS; SEARCH; PROTECTION AB Serum specimens were obtained from all subjects in the adolescent and adult acellular pertussis (aP) vaccine efficacy trial before and after immunization to study the prevalence of IgG and IgA antibody and geometric mean titers to 4 Bordetella pertussis antigens. Of 1793 adolescents and adult subjects who received aP vaccine, only 20%, 68%, 59%, and 39% had concentrations of IgG antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3, respectively, that were greater than or equal to the limit of quantitation of the enzyme-linked immunosorbent assay used in the analysis. There was minimal variation in antibody prevalence with respect to geographic area, age, sex, or race. C1 Univ Calif Los Angeles, David Geffen Sch Med, Harbor UCLA Med Ctr, UCLA Ctr Vaccine Res, Torrance, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Harbor UCLA Med Ctr, Res & Educ Inst, Torrance, CA USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Cincinnati Childrens Hosp, Med Ctr, Div Infect Dis, Cincinnati, OH USA. Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med Infect Dis, Nashville, TN 37212 USA. St Louis Univ, St Louis, MO 63103 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Rochester, New York, NY USA. RP Cherry, JD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, MDCC 22-442, Los Angeles, CA 90095 USA. EM jcherry@mednet.ucla.edu FU PHS HHS [1-A115124] NR 19 TC 15 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2004 VL 39 IS 11 BP 1715 EP 1718 DI 10.1086/425003 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JI UT WOS:000227492100027 PM 15578376 ER PT J AU Yuan, PX Gould, TD Gray, NA Bachmann, RF Schloesser, RJ Lan, MJK Du, J Moore, GJ Manji, HK AF Yuan, PX Gould, TD Gray, NA Bachmann, RF Schloesser, RJ Lan, MJK Du, J Moore, GJ Manji, HK TI Neurotrophic signaling cascades are major long-term targets for lithium: clinical implications SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE manic depressive illness; lithium; neuroprotection; Alzheimer's disease; stroke; Huntington's disease; brain; psychopharmacology; mood stabilizer ID GLYCOGEN-SYNTHASE KINASE-3-BETA; WHITE-MATTER HYPERINTENSITIES; CEREBELLAR GRANULE NEURONS; FAMILY TRANSCRIPTION FACTOR; CEREBRAL CORTICAL-NEURONS; MANIC-DEPRESSIVE ILLNESS; N-ACETYL-ASPARTATE; BIPOLAR DISORDER; INDUCED APOPTOSIS; OXIDATIVE STRESS AB Although mood disorders have traditionally been regarded as good prognosis diseases, a growing body of data suggests that the long-term outcome for many patients is often much less favorable than previously thought. Recent morphometric studies have been investigating potential structural brain changes in mood disorders, and there is now evidence from a variety of sources demonstrating significant reductions in regional CNS volume, as well as regional reductions in the numbers and/or sizes of glia and neurons. In this perspective paper, we discuss the preclinical and clinical evidence that lithium has neuroprotective and neurotrophic effects, and furthermore, show that these effects may have great relevance for the optimal treatment of severe mood disorders. Lithium has been noted to have neuroprotective effects in cell culture. and in animal models of neurodegeneration such as stroke, Huntington's disease and Alzheimer's disease. This may be due to the findings that lithium regulates the expression and/or activity of numerous molecules and enzymes involved in neuroplasticity, neuroprotection and mitochondrial function including bcl-2, GSK-3 and the ERK/MAP kinase pathway. Emerging clinical evidence additionally suggests that lithium may have similar effects in patients; these findings include an increase in N-acetyl aspartate (NAA) and gray matter in patients following long-term lithium treatment. Together, the data has implications not only for the optimal treatment of severe mood disorders, but potentially also for the treatment of other, more classical, neurodegenerative disorders. (C) 2004 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved. C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Dept Psychiat, Detroit, MI USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, 49 Convent Dr,Bldg 49,Room B1EE16, Bethesda, MD 20892 USA. EM manjih@intra.nimh.nih.gov RI Moore, Gregory/E-7184-2010 OI Moore, Gregory/0000-0001-8541-3194 NR 142 TC 9 Z9 9 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2004 VL 4 IS 3-4 BP 137 EP 153 DI 10.1016/j.cnr.2004.09.006 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 884YX UT WOS:000226123700003 ER PT J AU Chuang, DM AF Chuang, DM TI Lithium protection from glutamate excitotoxicity: therapeutic implications SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE (6-8); lithium; excitotoxiciy; neurodegeneration; brain neurons; neuroprotection; neurogenesis; Bcl-2; heat shock protein ID CEREBELLAR GRANULE CELLS; GLYCOGEN-SYNTHASE KINASE-3-BETA; CEREBRAL CORTICAL-NEURONS; CULTURED BRAIN NEURONS; HUNTINGTONS-DISEASE; RAT STRIATUM; MOOD DISORDERS; NERVOUS-SYSTEM; CALCIUM INFLUX; VALPROIC ACID AB Long-term treatment with lithium, the primary drug used to treat bipolar mood disorder, robustly protects against glutamate-induced, NMDA receptor-mediated excitotoxicity in primary cultures of rat brain neurons. The neuroprotective effects of lithium are accompanied by a reduction in NMDA receptor-mediated calcium influx, up-regulation of anti-apoptotic Bcl-2, down-regulation of pro-apoptotic p53 and Bax, and activation of the cell survival signaling pathway. In addition, lithium antagonizes glutamate-induced activation of c-Jun-N-terminal kinase (INK), p38 kinase and AP-1 binding, and suppresses glutamate-induced loss of phosphorylated CREB due to activation of protein phosphatase 1. Evidence has also been obtained that lithium induces BDNF and activates its receptor TrkB in cortical neurons and this BDNF/TrkB signaling activation is imperative for the neuroprotective effects of this drug. In a rat stroke model, post-insult treatments with therapeutic doses of lithium or valproic acid (VPA) markedly reduce ischemia-induced brain infarction and neurological deficits. These neuroprotective effects are associated with suppression of caspase-3 activation and induction of chaperone proteins. In a rat excitotoxicity model of Huntington's disease (HD) in which an excitotoxin was infused into the striatum, both long- and short-term pretreatment with lithium reduces excitotoxin-induced DNA damage, caspase-3 activation and striatal neuronal loss. This neuroprotection is associated with up-regulation of Bcl-2 in neurons. Lithium also induces cell proliferation near the injury site with a concomitant loss of proliferating cells in the subventricular zone. Some of these proliferating cells display neuronal or astroglial phenotypes. This finding corroborates our in vitro results showing that lithium stimulates the proliferation of neuroblasts in primary cultures of CNS neurons. (C) 2004 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved. C1 NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bldg 10,Rm 4C-206,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov NR 66 TC 10 Z9 12 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2004 VL 4 IS 3-4 BP 243 EP 252 DI 10.1016/j.cnr.2004.09.016 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 884YX UT WOS:000226123700012 ER PT J AU Riggs, MA Klebanoff, MA AF Riggs, MA Klebanoff, MA TI Treatment of vaginal infections to prevent preterm birth: A meta-analysis SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; BACTERIAL VAGINOSIS; PREGNANT-WOMEN; UREAPLASMA-UREALYTICUM; INTRAUTERINE INFECTION; ASYMPTOMATIC WOMEN; CLINICAL-TRIAL; DELIVERY; LABOR C1 NICHD, DESPR, NIH, Dept Hlth & Human Serv,Div Epidemiol Stat & Preve, Bethesda, MD 20892 USA. RP Klebanoff, MA (reprint author), NICHD, DESPR, NIH, Dept Hlth & Human Serv,Div Epidemiol Stat & Preve, 6100 Bldg,Room 7B05, Bethesda, MD 20892 USA. EM mk90h@nih.gov NR 63 TC 41 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD DEC PY 2004 VL 47 IS 4 BP 796 EP 807 DI 10.1097/01.grf.0000141450.61310.81 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 959PU UT WOS:000231531000006 PM 15596934 ER PT J AU Booth, NL Nikolic, D van Breemen, RB Geller, SE Banuvar, S Shulman, LP Farnsworth, NR AF Booth, NL Nikolic, D van Breemen, RB Geller, SE Banuvar, S Shulman, LP Farnsworth, NR TI Confusion regarding anticoagulant coumarins in dietary supplements SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID ANTIPLATELET AGGREGATION; CONSTITUENTS; PRINCIPLES; DISEASE C1 Univ Illinois, Dept Med Chem & Pharmacognosy, NIH, Ctr Bot Dietary Supplement Res Womens Hlth, Chicago, IL 60612 USA. Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Northwestern Univ, Dept Obstet & Gynecol, Evanston, IL USA. RP van Breemen, RB (reprint author), Univ Illinois, Dept Med Chem & Pharmacognosy, NIH, Ctr Bot Dietary Supplement Res Womens Hlth, 833 S Wood St,M-C 781, Chicago, IL 60612 USA. EM breemen@uic.edu FU NCCIH NIH HHS [F31 AT00804, P50 AT00155] NR 19 TC 14 Z9 16 U1 2 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2004 VL 76 IS 6 BP 511 EP 516 DI 10.1016/j.clpt.2004.08.023 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 881NE UT WOS:000225873400001 PM 15592321 ER PT J AU Leger, F Loos, WJ Bugat, R Mathijssen, RHJ Goffinet, M Verweij, J Sparreboom, A Chatelut, E AF Leger, F Loos, WJ Bugat, R Mathijssen, RHJ Goffinet, M Verweij, J Sparreboom, A Chatelut, E TI Mechanism-based models for topotecan-induced neutropenia SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ORAL TOPOTECAN; OVARIAN-CANCER; PHASE-I; PHARMACODYNAMICS; PHARMACOKINETICS; BIOAVAILABILITY; CISPLATIN; INHIBITOR; KINETICS AB Objective: A semiphysiologic pharmacokinetic-pharmacodynamic model was applied to describe topotecan-induced neutropenia, to quantify interindividual and intraindividual pharmacodynamic variability, and to study the effect of covariates on the model. Methods. Data were obtained from patients treated with topotecan given either orally (118 patients) or intravenously (71 patients), according to different schedules (5 to 21 consecutive days), with or without cisplatin. The model mimics the maturation chain of neutrophils. Topotecan concentration-time profiles affected the proliferation of neutrophil precursors (sensitive cells) through an inhibitory linear model (topotecan is assumed to induce cell loss by a function, E-drug, proportional to the topotecan concentration in the central compartment: E-drug = Slope (.) Concentration). The topotecan plasma concentration versus time profile was generated for each patient by modeling the data according to a 2-compartment pharmacokinetic model and first-order absorption for oral administration by use of NONMEM. Results. The model described the time course of neutrophil values well. Topotecan neutropenic effect exhibited a large interpatient variability (coefficient of variation of 82% for the slope values). The oral route was associated with a 43% lower value for slope, corresponding to a lower toxicity. The combination with cisplatin increased the neutropenic effect compared with topotecan alone by a factor 3.5. The intrapatient variability between cycle 1 and cycle 2 on slope was lower for the intravenous administration than for the oral administration. By application of the model to a new weekly schedule of topotecan, neutrophil values at the nadir were consistent with those observed during a phase I study of this regimen. Conclusion: This model can be used to describe both the duration and intensity of neutropenia; the area between the curve of neutrophil count versus time and a critical neutrophil count (such as 0.500 x 10(3)/mm(3)) would be a better toxic endpoint than the unique observed value of neutrophil at nadir. The model may be used to predict neutropenia corresponding to regimens of topotecan not yet explored. C1 Inst Claudius Regaud, F-31052 Toulouse, France. Erasmus Univ, Dr Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands. NCI, Bethesda, MD 20892 USA. RP Chatelut, E (reprint author), Inst Claudius Regaud, 20-24 Rue Pont St Pierre, F-31052 Toulouse, France. EM chatelut@icr.fnclcc.fr RI Sparreboom, Alex/B-3247-2008; Chatelut, Etienne/I-7916-2014 NR 16 TC 29 Z9 29 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2004 VL 76 IS 6 BP 567 EP 578 DI 10.1016/j.clpt.2004.08.008 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 881NE UT WOS:000225873400008 PM 15592328 ER PT J AU Vourlekis, JS AF Vourlekis, JS TI Acute interstitial pneumonia SO CLINICS IN CHEST MEDICINE LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS; RESPIRATORY-DISTRESS-SYNDROME; DIFFUSE ALVEOLAR DAMAGE; HAMMAN-RICH SYNDROME; ACUTE EOSINOPHILIC PNEUMONIA; NECROSIS-FACTOR-ALPHA; PATHOLOGICAL FINDINGS; RHEUMATOID-ARTHRITIS; LUNG TRANSPLANTATION; COMPUTED-TOMOGRAPHY AB The idiopathic interstitial pneumonias have unknown etiology and are characterized by diffuse parenchymal lung involvement and the potential to develop pulmonary fibrosis. Most portend a reduction in life expectancy due, in part, to the absence of effective therapies. The symptoms of idiopathic interstitial pneumonia develop insidiously. In contradistinction, acute interstitial pneumonia (AIP, also known as acute interstitial pneumonitis) is unique in that it has a very rapid to fulminant onset, leading to early hospitalization and a high initial case fatality ratio but, potentially, a more favorable long-term prognosis for survivors. Despite its contemporary description nearly 20 years ago, knowledge of this disease has increased little. This article focuses on AIP and its current place among the idiopathic interstitial pneumonias. C1 Natl Naval Med Res Inst, Sect Pulm Med, Bethesda, MD USA. RP Vourlekis, JS (reprint author), NCI, Dept Hlth & Human Serv, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent,NIH, 6130 Execut Blvd,Suite 2136, Bethesda, MD 20892 USA. EM vourlekj@mail.nih.gov NR 52 TC 14 Z9 21 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 2004 VL 25 IS 4 BP 739 EP + DI 10.1016/j.ccm.2004.07.001 PG 10 WC Respiratory System SC Respiratory System GA 883CQ UT WOS:000225988200010 PM 15564019 ER PT J AU Garruto, RM Little, MA Weitz, CA AF Garruto, RM Little, MA Weitz, CA TI Environmental stress and adaptational responses: Consequences for human health outcomes SO COLLEGIUM ANTROPOLOGICUM LA English DT Review DE hypoxic stress; altitude; HIF; prion diseases; kuru; co-evolution; reproduction ID CREUTZFELDT-JAKOB-DISEASE; CHRONIC WASTING DISEASE; BOVINE SPONGIFORM ENCEPHALOPATHY; NOMADIC TURKANA PASTORALISTS; POST-PARTUM AMENORRHEA; HIGH-ALTITUDE HYPOXIA; ROCKY-MOUNTAIN ELK; HAN CHINESE BORN; PLASMODIUM-FALCIPARUM; MORPHOLOGICAL GROWTH AB With the dramatic pace of modernization of the world's population, human adaptation as a theoretical construct and paradigm will likely become a focal scientific issue involving scientists from many disciplinary areas during the 21st Century. Macro and micro environments are in rapid flux and human populations are exposed to rapid change. The concept of adaptation, at least in the field of biological anthropology and human biology, will likely remain tied to evolutionary processes and concepts of selection and fitness. In this paper, we discuss the theoretical constructs of adaptation and adaptability and select three current examples from our ongoing research that involve studies of adaptation and evolutionary processes in modernizing populations in different locations worldwide. C1 SUNY Binghamton, Dept Anthropol, Binghamton, NY 13902 USA. NIH, Bethesda, MD 20892 USA. Temple Univ, Dept Anthropol, Philadelphia, PA 19122 USA. RP Garruto, RM (reprint author), SUNY Binghamton, Dept Anthropol, Sci 1,Room 113,POB 6000, Binghamton, NY 13902 USA. NR 170 TC 4 Z9 4 U1 1 U2 12 PU COLLEGIUM ANTROPOLOGICUM PI ZAGREB PA INST ANTHROPOLOGICAL RES, P O BOX 290, ULICA GRADA VUKOVARA 72/IV, 10000 ZAGREB, CROATIA SN 0350-6134 J9 COLLEGIUM ANTROPOL JI Coll. Anthropol. PD DEC PY 2004 VL 28 IS 2 BP 509 EP 540 PG 32 WC Anthropology SC Anthropology GA 886RU UT WOS:000226246900002 PM 15666583 ER PT J AU Sansone, SA Morrison, N Rocca-Serra, P Fostel, J AF Sansone, SA Morrison, N Rocca-Serra, P Fostel, J TI Standardization initiatives in the (eco)toxicogenomics domain: a review SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Article; Proceedings Paper CT 2nd Conference on Standards and Ontologies for Functional Genomics (SOFG) CY OCT 23-26, 2004 CL Univ Penn, Philadelphia, PA HO Univ Penn DE toxicogenomics; ecotoxicogenomics; toxicology; environment; functional genomics; standards; database ID GENE-EXPRESSION; SCIENTIFIC JOURNALS; MICROARRAY DATA; TOXICOGENOMICS; INFORMATION; REPOSITORY; DATABASE AB The purpose of this document is to provide readers with a resource of different ongoing standardization efforts within the 'omics' (genomic, proteomics, metabolomics) and related communities, with particular focus on toxicological and environmental applications. The review includes initiatives within the research community as well as in the regulatory arena. It addresses data management issues (format and reporting structures for the exchange of information) and database interoperability, highlighting key objectives, target audience and participants. A considerable amount of work still needs to be done and, ideally, collaboration should be optimized and duplication and incompatibility should be avoided where possible. The consequence of failing to deliver data standards is an escalation in the burden and cost of data management tasks. Copyright (c) 2005 John Wiley T Sons, Ltd. C1 EBI, EMBL, Cambridge GB10 1SD, England. Univ Manchester, Sch Comp Sci, Manchester M13 9PL, Lancs, England. Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. RP Sansone, SA (reprint author), EBI, EMBL, Wellcome Trust Campus, Cambridge GB10 1SD, England. EM sansone@ebi.ac.uk OI Sansone, Susanna-Assunta/0000-0001-5306-5690 NR 21 TC 8 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PD DEC PY 2004 VL 5 IS 8 BP 633 EP 641 DI 10.1002/cfg.447 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 908FE UT WOS:000227772000005 PM 18629184 ER PT J AU Fragoso, G de Coronado, S Haber, M Hartel, F Wright, L AF Fragoso, G de Coronado, S Haber, M Hartel, F Wright, L TI Overview and utilization of the NCI thesaurus SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Article; Proceedings Paper CT 2nd Conference on Standards and Ontologies for Functional Genomics (SOFG) CY OCT 23-26, 2004 CL Univ Penn, Philadelphia, PA HO Univ Penn DE biomedical terminology; ontology AB The NCI Thesaurus is a reference terminology covering areas of basic and clinical science, built with the goal of facilitating translational research in cancer. It contains nearly 110000 terms in approximately 36000 concepts, partitioned in 20 subdomains, which include diseases, drugs, anatomy, genes, gene products, techniques, and biological processes, among others, all with a cancer-centric focus in content, and originally designed to support coding activities across the National Cancer Institute. Each concept represents a unit of meaning and contains a number of annotations, such as synonyms and preferred name, as well as annotations such as textual definitions and optional references to external authorities. In addition, concepts are modelled with description logic (DL) and defined by their relationships to other concepts; there are currently approximately 90 types of named relations declared in the terminology. The NCI Thesaurus is produced by the Enterprise Vocabulary Services project, a collaborative effort between the NCI Center for Bioinformatics and the NCI Office of Communications, and is part of the caCORE infrastructure stack (http://ncicb.nci.nih.gov/NCICB/core). It can be accessed programmatically through the open caBIO API and browsed via the web (http://nciterms.nci.nih.gov). A history of editing changes is also accessible through the API. In addition, the Thesaurus is available for download in various file formats, including OWL, the web ontology language, to facilitate its utilization by others. Published in 2005 by John Wiley T Sons, Ltd. C1 NCI, Ctr Bioinformat, NIH, Bethesda, MD 20892 USA. NCI, Off Commun, NIH, Bethesda, MD 20892 USA. RP Fragoso, G (reprint author), NCI, Ctr Bioinformat, NIH, 6116 Execut Blvd,Ste 403, Bethesda, MD 20892 USA. EM fragosog@mail.nih.gov NR 8 TC 41 Z9 41 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PD DEC PY 2004 VL 5 IS 8 BP 648 EP 654 DI 10.1002/cfg.445 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 908FE UT WOS:000227772000007 PM 18629178 ER PT J AU Sato, A Klaunberg, B Tolwani, R AF Sato, A Klaunberg, B Tolwani, R TI In vivo bioluminescence imaging SO COMPARATIVE MEDICINE LA English DT Article ID GENE-EXPRESSION; TRANSGENIC MOUSE; LIVING MICE; INFECTION; REPORTER; CANCER; THERAPY; MODEL AB In vivo bioluminescent imaging (BLI) is a versatile and sensitive tool that is based on detection of light emission from cells or tissues. Bioluminescence, the biochemical generation of light by a living organism. is a naturally occurring phenomenon. Luciferase enzymes, such as that from the North American firefly (Photinus pyralis), catalyze the oxidation of a substrate (luciferin), and photons of light are a product of the reaction. Optical imaging by bioluminescence allows a low-cost, noninvasive, and real-time analysis of disease processes at the molecular level in living organisms. Bioluminescence has been used to track tumor cells, bacterial and viral infections. gene expression. and treatment response. Biolumineseence in vivo imaging allows longitudinal monitoring of a disease course in the same animal, a desirable alternative to analyzing a number of animals at many time points during the course of the disease. We provide a brief introduction to BLI technology, specific examples of in vivo BLI studies investigating bacterial/viral pathogenesis and tumor growth in animal models, and highlight some future perspectives of BLI as a molecular imaging tool. C1 Stanford Univ, Sch Med, Dept Comparat Med, Stanford, CA 94305 USA. NIH, Mouse Imaging Facil, Bethesda, MD 20892 USA. RP Tolwani, R (reprint author), Stanford Univ, Sch Med, Dept Comparat Med, Stanford, CA 94305 USA. NR 26 TC 70 Z9 74 U1 2 U2 9 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD DEC PY 2004 VL 54 IS 6 BP 631 EP 634 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 888JF UT WOS:000226369500005 PM 15679260 ER PT J AU Hassan, M Klaunberg, BA AF Hassan, M Klaunberg, BA TI Biomedical applications of fluorescence imaging in vivo SO COMPARATIVE MEDICINE LA English DT Article ID INFRARED-LABELED ENDOSTATIN; QUANTUM DOTS; PROTEIN EXPRESSION; BREAST-CANCER; GENE-EXPRESSION; CONTRAST AGENTS; VIRUS INFECTION; FLOW-CYTOMETRY; HUMAN-TUMORS; BLOOD-FLOW AB Optical imaging can advance knowledge of cellular biology and disease at the molecular level in vitro and.. more recently, in vivo. In vivo optical imaging has enabled real-time study to track cell movement. cell growth. and even some cell functions. Thus, it can be used in intact animals for disease detection, screening, diagnosis. drug development, and treatment evaluation. This review includes a brief introduction to fluorescence imaging, fluorescent probes, imaging devices, and in vivo applications in animal models. It also describes a quantitative fluorescence detection method with a reconstruction algorithm for determining the location of fluorophores in tissue and addresses future applications of in vivo fluorescence imaging. C1 NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Klaunberg, BA (reprint author), NINDS, Mouse Imaging Facil, NIH, 10 Ctr Dr,B1D-69, Bethesda, MD 20892 USA. NR 78 TC 20 Z9 20 U1 0 U2 4 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD DEC PY 2004 VL 54 IS 6 BP 635 EP 644 PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 888JF UT WOS:000226369500006 PM 15679261 ER PT J AU Smith, L Wilbur, WJ AF Smith, L Wilbur, WJ TI Retrieving definitional content for ontology development SO COMPUTATIONAL BIOLOGY AND CHEMISTRY LA English DT Article DE ontology development; definitional content; expert writing AB Ontology construction requires an understanding of the meaning and usage of its encoded concepts. While definitions found in dictionaries or glossaries may be adequate for many concepts, the actual usage in expert writing could be a better source of information for many others. The goal of this paper is to describe an automated procedure for finding definitional content in expert writing. The approach uses machine learning on phrasal features to learn when sentences in a book contain definitional content, as determined by their similarity to glossary definitions provided in the same book. The end result is not a concise definition of a given concept, but for each sentence, a predicted probability that it contains information relevant to a definition. The approach is evaluated automatically for terms with explicit definitions, and manually for terms with no available definition. (C) 2004, Elsevier Ltd. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Smith, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM lsmith@ncbi.nlm.nih.gov; wilbur@ncbi.nlm.nih.gov NR 17 TC 4 Z9 5 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1476-9271 J9 COMPUT BIOL CHEM JI Comput. Biol. Chem. PD DEC PY 2004 VL 28 IS 5-6 BP 387 EP 391 DI 10.1016/j.compbiolchem.2004.09.007 PG 5 WC Biology; Computer Science, Interdisciplinary Applications SC Life Sciences & Biomedicine - Other Topics; Computer Science GA 888OA UT WOS:000226382900007 PM 15556479 ER PT J AU Durairaj, DC Krishna, MC Murugesan, R AF Durairaj, DC Krishna, MC Murugesan, R TI Integration of color and boundary information for improved region of interest identification in electron magnetic resonance images SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE electron magnetic resonance images; color image segmentation; clustering technique; border detection; feature identification ID PARAMAGNETIC-RESONANCE; SEGMENTATION; TUMOR; SPECTROMETER; EPR; ALGORITHMS AB A Windows-based, object-oriented application system for segmentation and analysis of electron magnetic resonance (EMR) images is described. The integrated system is developed for better recognition of regions of interest (ROI) in murine EMR images. The system combines the clustering method of color segmentation with boundary detection, for efficient segmentation of regions of interest in EMR images. Initially, the red/green/blue (RGB) color space is converted into spherical coordinates transform (SCT) space. Color quantization is then achieved by center split algorithm applied on the color dimensions of the SCT space. Subsequently, Laplacian boundary detection operator is used to extract the contours of the ROI from the variegated coloring information. The system is implemented in Visual C++ and tested on temporal EMR color images of mouse. The system performs well giving perceptually reasonable segmentation of tumor, kidney and bladder of the mouse image. Experimental results with extensive set of EMR color images demonstrate the efficacy of the system developed. (C) 2004 Published by Elsevier Ltd. C1 Madurai Kamaraj Univ, Dept Chem Phys, Madurai 625021, Tamil Nadu, India. VHNSN Coll, Dept Comp Sci, Virudunagar 626001, India. NCI, Radiat Biol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Murugesan, R (reprint author), Madurai Kamaraj Univ, Dept Chem Phys, Madurai 625021, Tamil Nadu, India. EM rammku@eth.net NR 42 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD DEC PY 2004 VL 28 IS 8 BP 445 EP 452 DI 10.1016/j.compmedimag.2004.07.006 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 874SA UT WOS:000225368900002 PM 15541951 ER PT J AU Domanski, M Antman, EM McKinlay, S Varshavsky, S Platonov, P Assmann, SF Norman, J AF Domanski, M Antman, EM McKinlay, S Varshavsky, S Platonov, P Assmann, SF Norman, J TI Geographic variability in patient characteristics, treatment and outcome in an International Trial of Magnesium in acute myocardial infarction SO CONTROLLED CLINICAL TRIALS LA English DT Article DE myocardial infarction; coronary disease; magnesium; ST elevation myocardial infarction ID UNITED-STATES; HEART-DISEASE; GUSTO TRIAL; MORTALITY; MANAGEMENT; RESOURCES; COUNTRIES; DECLINE; CANADA AB Background: The interpretation of clinical trials and efforts directed at reducing the worldwide burden of coronary, disease must take regional differences into account. This study examined the regional differences in baseline characteristics, treatment, and outcome in patients presenting with ST elevation myocardial infarction (STEM) who were entered into the Magnesium in Coronaries (MAGIC) trial. Methods and results: MAGIC randomized 6213 patients to standard care with either placebo infusion or infusion of intravenous magnesium sulphate. There was no difference in mortality between these groups. For this analysis. three geographic regions were identified (Region 1=United States and Canada: Region 2=Bulgaria. Greorgia and Russia; Region 3=Austria, Belgium, Chile, Hungary, Israel, the Netherlands. New Zealand, and Venezuela) and compared with respect to baseline characteristics, treatment,. and 30-day mortality. Patients in Region 2 had the highest prevalence of adverse risk factors at entry, including history of prior myocardial infarction, heart failure, stroke, and hypertension: anterior location of index acute. myocardial infarction; and presence of pulmonary congestion at presentation. Furthermore. Region 2 patients, infrequently received reperfusion therapy compared with those in Region 1. Region 3 was intermediate in this regard. Morality was highest in Region 2, least in Region 1, and intermediate in Region 3. Conclusion: Geographic location, particularly, parts of Eastern Europe, is strongly and independently associated with mortality following STEMI. This geographic variation in mortality confirms prior reports, although adequate explanations continue to be elusive and are beyond the scope of this large simple trial. Future international trials must recognize this variation in design, analysis, and interpretation. (C) 2004 Elsevier Inc. All rights reserved. C1 NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. New England Res Inst inc, Watertown, MA USA. EVIDENCE Clin & Pharmaceut Res, Los Altos, CA USA. RP Domanski, M (reprint author), NHLBI, Clin Trials Grp, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. EM domanskm@nhlbi.nih.gov NR 17 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 2004 VL 25 IS 6 BP 553 EP 562 DI 10.1016/j.cct.2004.08.005 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 881ZI UT WOS:000225907700002 PM 15588742 ER PT J AU Berger, VW AF Berger, VW TI On the generation and ownership of alpha in medical studies SO CONTROLLED CLINICAL TRIALS LA English DT Editorial Material DE alpha; medical studies; researchers ID I ERROR RATE; CLINICAL-TRIALS; SELECTION BIAS AB Much is known about how to split alpha between or among several comparisons. or how to preserve the nominal alpha level with an exact analysis, but the issue of how alpha is generated. or where it comes from. has not received a commensurate degree of attention. It would seem that there is little point in working out methods to allocate or conserve alpha if it is unlimited in supply. Moreover. there seems to be a logical inconsistency in requiring that a given amount of alpha, generally 0.05, be split among the primary comparisons performed by a given set of researchers, yet allowing other researchers to analyze the same data with a new 0.05 to work with. We will address these inconsistencies, and ask more generally where alpha comes from. how it can be generated. and under what conditions it should be one-tailed or two-tailed. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Maryland Baltimore Cty, Natl Canc Inst, Biometry Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), Univ Maryland Baltimore Cty, Natl Canc Inst, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 16 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 2004 VL 25 IS 6 BP 613 EP 619 DI 10.1016/j.cct.2004.07.006 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 881ZI UT WOS:000225907700007 PM 15588747 ER PT J AU Deans, KJ Minneci, PC Banks, SM Natanson, C Eichacker, PQ AF Deans, KJ Minneci, PC Banks, SM Natanson, C Eichacker, PQ TI Substantiating the concerns about recombinant human activated protein C use in sepsis SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE activated protein C; drotrecogin alfa; PROWESS; mortality; recombinant human activated protein C; corticosteroids; clinical practice C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Deans, KJ (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 8 TC 14 Z9 14 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 DEC PY 2004 VL 32 IS 12 BP 2542 EP 2543 DI 10.1097/01.CCM.0000148090.94378.6A PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 881NG UT WOS:000225873600027 PM 15599164 ER PT J AU Baid, S Nieman, LK AF Baid, S Nieman, LK TI Glucocorticoid excess and hypertension SO CURRENT HYPERTENSION REPORTS LA English DT Article ID ECTOPIC ADRENOCORTICOTROPIN SYNDROME; ATRIAL-NATRIURETIC-PEPTIDE; RENIN-ANGIOTENSIN SYSTEM; CUSHINGS-SYNDROME; BLOOD-PRESSURE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; NITRIC-OXIDE; CARDIOVASCULAR RISK; ENDOTHELIN RECEPTOR; CORTISOL AB Cushing syndrome is a rare disorder characterized by chronic, excess glucocorticoid exposure. Hypertension is one of the most discriminating features of the disease, as it is present in 80% of patients. Patients with Cushing's syndrome have a morality rate four times that of the general population, most likely secondary to an increased number of cardiovascular risk factors, including hypertension. In this article, we review several pathogenetic mechanisms of glucocorticoid-induced hypertension, including the role of sodium/water and mineralocorticoid excess, as well as involvement of the vasculature and kidney. Although treatment of hypertension with available antihypertensive medications is only moderately successful, after cure of Cushing's syndrome, approximately 30% of patients have persistent hypertension. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Baid, S (reprint author), NICHHD, NIH, Bldg 10,Room 9D42 MSC 1583,10 Ctr Dr, Bethesda, MD 20892 USA. EM NiemanL@nih.gov NR 53 TC 27 Z9 28 U1 0 U2 2 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1522-6417 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD DEC PY 2004 VL 6 IS 6 BP 493 EP 499 DI 10.1007/s11906-004-0046-0 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 991HL UT WOS:000233803000015 PM 15527696 ER PT J AU Dharmawardana, PG Giubellino, A Bottaro, DP AF Dharmawardana, PG Giubellino, A Bottaro, DP TI Hereditary papillary renal carcinoma type I SO CURRENT MOLECULAR MEDICINE LA English DT Review DE c-Met; HGF/SF; HPRC; missense mutations; renal carcinoma ID HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; FACTOR SCATTER FACTOR; HEPARIN-BINDING SITE; CELL LUNG-CANCER; C-MET; INVASIVE GROWTH; ONCOGENIC ACTIVATION; COLORECTAL-CANCER; SOMATIC MUTATIONS AB Germline missense mutations in the tyrosine kinase domain of the hepatocyte growth factor/scatter factor (HGF/SF) receptor, c-Met, are thought to be responsible for hereditary papillary renal carcinoma (HPRC) type 1, a form of human kidney cancer. In addition to extensive linkage analysis of HPRC families localizing the HPRC type 1 gene within chromosome 7, the demonstration that individual c-Met mutations reconstituted in cultured cells display enhanced and dysregulated kinase activity, and confer cell transformation and tumorigenicity in mice, solidifies this conclusion. Our prior knowledge of HGF/SF biology and c-Met signaling enabled rapid progress in unraveling the molecular pathogenesis of HPRC type 1, and in laying the framework for the development of novel therapeutics for the treatment of this cancer. At the same time, the study of HPRC type 1 has refined our appreciation of the oncogenic potential of c-Met signaling, and challenges our current understanding of HGF/SF and c-Met function in health and disease. C1 NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Bottaro, DP (reprint author), NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bldg 10,Rm 2B47,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dbottaro@helix.nih.gov RI Bottaro, Donald/F-8550-2010; OI Bottaro, Donald/0000-0002-5057-5334; Giubellino, Alessio/0000-0002-5352-0662 NR 109 TC 43 Z9 46 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD DEC PY 2004 VL 4 IS 8 BP 855 EP 868 DI 10.2174/1566524043359674 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 875JJ UT WOS:000225416100009 PM 15579033 ER PT J AU Schmidt, LS AF Schmidt, LS TI Birt-Hogg-Dubllb syndrome, a genodermatosis that increases risk for renal carcinoma SO CURRENT MOLECULAR MEDICINE LA English DT Review DE BHD; Birt-Hogg-Dube syndrome; renal oncocytic hybrid tumor; chromophobe RCC; tumor suppressor; fibrofolliculoma ID TUMOR-SUPPRESSOR GENE; GERMAN-SHEPHERD DOG; NIHON RAT MODEL; DUBE BHD GENE; CELL CARCINOMA; SPONTANEOUS PNEUMOTHORAX; NODULAR DERMATOFIBROSIS; PERIFOLLICULAR FIBROMAS; INTESTINAL POLYPOSIS; HOMONUCLEOTIDE TRACTS AB Over the past decade cancer-causing genes have been identified for the most common histologic types of renal cancer, specifically clear cell, papillary type 1 and papillary type 2. Genes predisposing to the more rare chromophobe renal carcinoma and renal oncocytoma were unknown until the recent discovery of a novel gene, BHD, on chromosome 17p that was found to be mutated in the germline of affected family members with the Birt-Hogg-Dube (BHD) syndrome. These patients develop the hallmark BHD skin lesions (fibrofolliculomas), lung cysts and spontaneous pneumothorax. Importantly, BHD patients have an increased risk for developing a variety of renal neoplasia, most commonly chromophobe and oncocytic hybrid tumors. This review will describe the phenotypic manifestations of BHD including the histologic features of BHD-associated renal tumors, the identification of this novel renal cancer-predisposing gene, the BHD mutation spectrum found in BHD patients, and will discuss the potential role of BHD as a tumor suppressor gene. C1 SAIC Frederick Inc, Basic Res Program, Immunobiol Lab, NCI, Frederick, MD 21702 USA. RP Schmidt, LS (reprint author), SAIC Frederick Inc, Basic Res Program, Immunobiol Lab, NCI, Bldg 560,Rm 12-69, Frederick, MD 21702 USA. EM schmidtl@ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 44 TC 15 Z9 15 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD DEC PY 2004 VL 4 IS 8 BP 877 EP 885 DI 10.2174/1566524043359773 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 875JJ UT WOS:000225416100011 PM 15579035 ER EF