FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Engel, E Santarelli, F Vasold, R Maisch, T Howard, P Ulrich, H Konig, B Landthaler, M Baumler, W AF Engel, E. Santarelli, F. Vasold, R. Maisch, T. Howard, P. Ulrich, H. Koenig, B. Landthaler, M. Baeumler, W. TI Quantitative extraction of tattoo pigments from skin to determine the concentration of pigments in tattooed skin SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung CY MAR 08, 2004-MAR 10, 2007 CL Freiburg, GERMANY SP Arbeitsgermeinsch Dermatolog Forschung C1 Univ Regensburg, Inst Organ Chem, D-8400 Regensburg, Germany. Univ Regensburg, Dept Dermatol, D-8400 Regensburg, Germany. US FDA, Jefferson, AR USA. Natl Ctr Toxicol Res, Natl Toxicol ProgramCtr Phototoxicol, Jefferson, AR USA. RI Koenig, Burkhard/A-1362-2009 OI Koenig, Burkhard/0000-0002-6131-4850 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2007 VL 16 IS 3 BP 283 EP 284 PG 2 WC Dermatology SC Dermatology GA 134BC UT WOS:000244056600286 ER PT J AU Beger, RD AF Beger, Richard D. TI Cambridge Healthtech Institute's 7th Annual, Identifying and Validating Metabolic Markers for Drug Development and Clinical Studies - 4-6 December, 2006, Orlando, FL, USA SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material ID METABONOMICS C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM richard.beger@fda.hhs.gov NR 6 TC 1 Z9 1 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAR PY 2007 VL 7 IS 2 BP 113 EP 115 DI 10.1586/14737159.7.2.113 PG 3 WC Pathology SC Pathology GA 150GK UT WOS:000245203500002 PM 17331060 ER PT J AU Santiago, C Ballesteros, A Tami, C Martinez-Munoz, L Kaplan, GG Casasnovas, JM AF Santiago, Cesar Ballesteros, Angela Tami, Cecilia Martinez-Munoz, Laura Kaplan, Gerardo G. Casasnovas, Jose M. TI Structures of T cell immunoglobulin mucin receptors 1 and 2 reveal mechanisms for regulation of immune responses by the TIM receptor family SO IMMUNITY LA English DT Article ID HEPATITIS-A-VIRUS; MONOCLONAL-ANTIBODY 190/4; MONKEY KIDNEY-CELLS; CRYSTAL-STRUCTURE; ADHESION MOLECULE; SOLUBLE FORM; GENE FAMILY; ACTIVATION; DOMAIN; IDENTIFICATION AB The T cell immunoglobulin mucin (TIM) receptors are involved in the regulation of immune responses, autoimmunity, and allergy. Structures of the N-terminal ligand binding domain of the murine mTIM-1 and mTIM-2 receptors revealed an immunoglobulin (Ig) fold, with four Cys residues bridging a distinctive CC' loop to the GFC beta-sheet. The structures showed two ligand-recognition modes in the TIM family. The mTIM-1 structure identified a homophilic TIM-TIM adhesion interaction, whereas the mTIM-2 domain formed a dimer that prevented homophilic binding. Biochemical, mutational, and cell adhesion analyses confirmed the divergent ligand-binding modes revealed by the structures. Structural features characteristic of mTIM-1 appear conserved in human TIM-1, which also mediated homophilic interactions. The extracellular mucin domain enhanced binding through the Ig domain, modulating TIM receptor functions. These results explain the divergent immune functions described for the murine receptors and the role of TIM-1 as a cell adhesion receptor in renal regeneration and cancer. C1 CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Casasnovas, JM (reprint author), CSIC, Ctr Nacl Biotecnol, Campus Univ Autonoma, E-28049 Madrid, Spain. EM jcasasnovas@cnb.uam.es RI Casasnovas, Jose/L-6299-2014; Santiago, Cesar/K-4240-2014 OI Casasnovas, Jose/0000-0002-2873-6410; Santiago, Cesar/0000-0002-5149-1722 FU NIAID NIH HHS [P01 AI54456] NR 32 TC 64 Z9 70 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2007 VL 26 IS 3 BP 299 EP 310 DI 10.1016/j.immuni.2007.01.014 PG 12 WC Immunology SC Immunology GA 150PG UT WOS:000245228100007 PM 17363299 ER PT J AU Yadava, A Sattabongkot, J Washington, MA Ware, LA Majam, V Zheng, H Kumar, S Ockenhouse, CF AF Yadava, Anjali Sattabongkot, Jetsumon Washington, Michael A. Ware, Lisa A. Majam, Victoria Zheng, Hong Kumar, Sanjai Ockenhouse, Christian F. TI A novel chimeric Plasmodium vivax circumsporozoite protein induces biologically functional antibodies that recognize both VK210 and VK247 sporozoites SO INFECTION AND IMMUNITY LA English DT Article ID B-CELL EPITOPES; MALARIA VACCINE; FALCIPARUM SPOROZOITES; IMMUNODOMINANT EPITOPE; MONOCLONAL-ANTIBODIES; PROTECTIVE IMMUNITY; SURFACE PROTEIN; AOTUS MONKEYS; REGION-II; ANTIGEN AB A successful vaccine against Plasmodium vivax malaria would significantly improve the health and quality of the lives of more than I billion people around the world. A subunit vaccine is the only option in the absence of long-term culture of P. vivax parasites. The circumsporozoite protein that covers the surface of Plasmodium sporozoites is one of the best-studied malarial antigens and the most promising vaccine in clinical trials. We report here the development of a novel "immunologically optimal" recombinant vaccine expressed in Escherichia coli that encodes a chimeric CS protein encompassing repeats from the two major alleles, VK210 and VK247. This molecule is widely recognized by sera from patients naturally exposed to P. vivax infection and induces a highly potent immune response in genetically disparate strains of mice. Antibodies from immunized animals recognize both VK210 and VK247 sporozoites. Furthermore, these antibodies appear to be protective in nature since they cause the agglutination of live sporozoites, an in vitro surrogate of sporozoite infectivity. These results strongly suggest that recombinant CS is biologically active and highly immunogenic across major histocompatibility complex strains and raises the prospect that in humans this vaccine may induce protective immune responses. C1 Walter Reed Army Inst Res, Div Malaria Vaccine Dev, Silver Spring, MD 20910 USA. Armed Forces Res Inst Med Sci, Dept Entomol, US Army Med Component, Bangkok 10400, Thailand. Ctr Biol Evaluat & Res, Food & Drug Adm, Kensington, MD 20895 USA. RP Yadava, A (reprint author), Walter Reed Army Inst Res, Div Malaria Vaccine Dev, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM anjali.yadava@us.army.mil NR 54 TC 37 Z9 38 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2007 VL 75 IS 3 BP 1177 EP 1185 DI 10.1128/IAI.01667-06 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 143PD UT WOS:000244733900011 PM 17158893 ER PT J AU Whittaker, P Day, JB Curtis, SK Fry, FS AF Whittaker, Paul Day, James B. Curtis, Sherill K. Fry, Frederick S. TI Evaluating the use of fatty acid profiles to identify Francisella tularensis SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TULAREMIA AB Rapid capillary gas chromatography (GC) with flame-ionization detection was used to determine the cellular fatty acid profiles of Francisella tularensis. Two subspecies of F. tularensis, the live vaccine strain (LVS) derived from holarctica and a novicida strain Utah 112 (U112), were used to compare the extracted fatty acid methyl esters (FAMES). A data set for the 2 subspecies was prepared using fatty acid profiles of bacteria grown on 2 types of media, Mueller-Hinton and cysteine heart agar supplemented with 5% rabbit blood (CHAB), and harvested at various time intervals (Day 1 through Day 4) with replicates prepared on different days. A total of 204 samples were analyzed. The results showed that these fatty acid quantitative profiles were unique for each of the subspecies and could be used as a fingerprint for the organism. It was determined by this rapid method that approximately 88% of the fatty acids in both the LVS and U112 strains included 6 saturated fatty acids: 10:0, 12:0, 14:0, 16:0, 18:0, and 20:0; and 4 hydroxy fatty acids 10:0 20H, 16:0 30H, 17:0 30H, and 18:0 30H. Data analysis and determination of clustering were performed by principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA). Both PCA and SIMCA showed clear separation of the LVS and U112 strain and would be useful for prediction of unknowns. It was determined that the incubation time can be reduced from 48 to 24 h, and results are highly predictive for the identification of F. tularensis. In summary, analysis of FAMEs from F. tularensis subspecies LVS and U112 grown on CHAB or Mueller-Hinton media, and using a rapid GC method can provide a sensitive procedure for identification of these organisms. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov NR 14 TC 12 Z9 16 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2007 VL 90 IS 2 BP 465 EP 469 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 158BO UT WOS:000245766100016 PM 17474518 ER PT J AU McClure, FD Lee, JK AF McClure, Foster D. Lee, Jung K. TI On using an approximate noncentral t-distribution in determining a one-side upper limit for future sample relative reproducibility standard deviations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB For future sample relative reproducibility standard deviations (RSDR), collaboratively obtained under a completely randomized model (CRM), a new formula for determining a one-tailed 100p% upper limit (kappa(p)) for such RSDR values was developed based on an approximate noncentral t-distribution with degrees of freedom obtained using Satterthwaite's adjustment. The accuracy of kappa(p) was assessed by comparing kappa(p) and its probability levels with similar values associated with a Monte Carlo simulation and with those obtained using another formula (gamma(p)) that was developed for the same purpose but based on a normal approximation. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Analysis & Support, Div Math, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Analysis & Support, Div Math, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM foster.mcclure@fda.hhs.gov NR 14 TC 4 Z9 4 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2007 VL 90 IS 2 BP 575 EP 581 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 158BO UT WOS:000245766100025 PM 17474527 ER PT J AU Zhan, CL Kaczmarek, R Loyo-Berrios, N Sangl, J Bright, RA AF Zhan, Chunliu Kaczmarek, Ronald Loyo-Berrios, Nilsa Sangl, Judith Bright, Roselie A. TI Incidence and short-term outcomes of primary and revision hip replacement in the United States SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ELECTIVE TOTAL HIP; VENOUS THROMBOEMBOLISM; KNEE ARTHROPLASTY; POSTOPERATIVE COMPLICATIONS; DEEP SEPSIS; MORTALITY; VOLUME; RATES; SURGERY; COMORBIDITY AB Background: The purpose of this study was to use 2003 nationwide United States data to determine the incidences of primary total hip replacement, partial hip replacement, and revision hip replacement and to assess the short-term patient outcomes and factors associated with the outcomes. Methods: We screened more than eight million hospital discharge abstracts from the 2003 Healthcare Cost and Utilization Project Nationwide Inpatient Sample and approximately nine million discharge abstracts from five state inpatient databases. Patients who had undergone total, partial, or revision hip replacement were identified with use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes. In-hospital mortality, perioperative complications, readmissions, and the association between these outcomes and certain patient and hospital variables were analyzed. Results: Approximately 200,000 total hip replacements, 100,000 partial hip replacements, and 36,000 revision hip replacements were performed in the United States in 2003. Approximately 60% of the patients were sixty-five years of age or older and at least 75% had one or more comorbid diseases. The in-hospital mortality rates associated with these three procedures were 0.33%, 3.04%, and 0.84%, respectively. The perioperative complication rates associated with the three procedures were 0.68%, 1.36%, and 1.08%, respectively, for deep vein thrombosis or pulmonary embolism; 0.28%, 1.88%, and 1.27% for decubitus ulcer; and 0.05%, 0.06%, and 0.25% for postoperative infection. The rates of readmission, for any cause, within thirty days were 4.91%, 12.15%, and 8.48%, respectively, and the rates of readmissions, within thirty days, that resulted in a surgical procedure on the affected hip were 0.79%, 0.91%, and 1.53%. The rates of readmission, for any cause, within ninety days were 8.94%, 21.14%, and 15.72%, and the rates of readmissions, within ninety days, that resulted in a surgical procedure on the affected hip were 2.15%, 1.61%, and 3.99%. Advanced age and comorbid diseases were associated with worse outcomes, while private insurance coverage and planned admissions were associated with better outcomes. No consistent association between outcomes and hospital characteristics, such as hip procedure volume, was identified. Conclusions: Total hip replacement, partial hip replacement, and revision hip replacement are associated with different rates of postoperative complications and readmissions. Advanced age, comorbidities, and nonelective admissions are associated with inferior outcomes. Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence. C1 Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD 20850 USA. Agcy Healthcare Res & Qual, Ctr Qual Improvement & Patient Safety, Rockville, MD 20850 USA. US FDA, Epidemiol Branch, Div Postmarket Surveillance, Off Surveillance & Biomet,Ctr Devices & Radiol Hl, Rockville, MD 20850 USA. RP Zhan, CL (reprint author), Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, 540 Gaither Rd, Rockville, MD 20850 USA. EM chunliu.zhan@ahrq.hhs.gov; rxk@cdrh.fda.gov; nlb@cdrh.fda.gov; judith.sangl@ahrq.hhs.gov; rxb@cdrh.fda.gov RI Bright, Roselie/D-2240-2016 NR 40 TC 116 Z9 118 U1 0 U2 12 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 2007 VL 89A IS 3 BP 526 EP 533 DI 10.2106/JBJS.F.00952 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 143OG UT WOS:000244731400009 PM 17332101 ER PT J AU Kunwar, S Prados, MD Chang, SM Berger, MS Lang, FF Piepmeier, JM Sampson, JH Ram, Z Gutin, PH Gibbons, RD Aldape, KD Croteau, DJ Sherman, JW Puri, RK AF Kunwar, Sandeep Prados, Michael D. Chang, Susan M. Berger, Mitchel S. Lang, Frederick F. Piepmeier, Joseph M. Sampson, John H. Ram, Zvi Gutin, Philip H. Gibbons, Robert D. Aldape, Kenneth D. Croteau, David J. Sherman, Jeffrey W. Puri, Raj K. TI Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: A report by the Cintredekin Besudotox Intraparenchymal Study Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONVECTION-ENHANCED DELIVERY; INTERLEUKIN-13 RECEPTOR; PHASE-II; GLIOBLASTOMA-MULTIFORME; 1ST RELAPSE; TEMOZOLOMIDE; INFUSION; THERAPY; PROTEIN; BRAIN AB Purpose Glioblastoma multiforme (GBM) is a devastating brain tumor with a median survival of 6 months after recurrence. Cintredekin besudotox (CB) is a recombinant protein consisting of interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin (PE38QQR). Convection-enhanced delivery (CED) is a locoregional-administration method leading to high-tissue concentrations with large volume of distributions. We assessed the use of intracerebral CED to deliver CB in patients with recurrent malignant glioma (MG). Patients and Methods Three phase I clinical studies evaluated intracerebral CED of CB along with tumor resection. The main objectives were to assess the tolerability of various concentrations and infusion durations; tissue distribution; and methods for optimizing delivery. All patients underwent tumor resection followed by a single intraparenchymal infusion (in addition to the intraparenchymal one following resection), with a portion of patients who had a preresection intratumoral infusion. Results A total of 51 patients with MG were treated including 46 patients with GBM. The maximum tolerated intraparenchymal concentration was 0.5 mu g/mL and tumor necrosis was observed at this concentration. Infusion durations of up to 6 days were well tolerated. Postoperative catheter placement appears to be important for optimal drug distribution. CB- and procedure-related adverse events were primarily limited to the CNS. Overall median survival for GBM patients is 42.7 weeks and 55.6 weeks for patients with optimally positioned catheters with patient follow-up extending beyond 5 years. Conclusion CB appears to have a favorable risk-benefit profile. CED is a complex delivery method requiring catheter placement via a second procedure to achieve accurate catheter positioning, better drug distribution, and better outcome. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Yale Univ, New Haven, CT USA. Duke Univ, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Illinois, Chicago, IL USA. NeoPharm Inc, Waukegan, IL USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RP Kunwar, S (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus Ave,A808, San Francisco, CA 94143 USA. EM KunwarS@neurosurg.ucsf.edu RI leng, xianwei/F-9073-2011 NR 31 TC 179 Z9 181 U1 2 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2007 VL 25 IS 7 BP 837 EP 844 DI 10.1200/JCO.2006.08.1117 PG 8 WC Oncology SC Oncology GA 145SK UT WOS:000244884600016 PM 17327604 ER PT J AU Jhoo, JW Ang, CYW Heinze, TM Deck, J Schnackenberg, LK Beger, RD Dragull, K Tang, CS AF Jhoo, J. -W. Ang, C. Y. W. Heinze, T. M. Deck, J. Schnackenberg, L. K. Beger, R. D. Dragull, K. Tang, C. -S. TI Identification of C-glycoside flavonoids as potential mutagenic compounds in kava SO JOURNAL OF FOOD SCIENCE LA English DT Article DE flavonoid; kava; kavalactones; mutagenicity; Piper methysticum ID ANXIETY DISORDERS; TOXICITY; HEPATOTOXICITY; KAVALACTONES AB Kava (Piper methysticum) extract products have been implicated in a number of severe hepatotoxicity cases. However, systematic toxicological studies regarding kava consumption have not been reported. In this study, 6 major kavalactones and different solvent fractions of kava roots, leaves, and stem peelings were evaluated for their mutagenic potential. None of the kavalactones was found to be positive in the experimental concentration ranges tested by the umu test (a sensitive test for point mutations). However, among the different solvent fractions, the n-butanol fraction of kava leaves was positive. Further investigations using bioassay-directed isolation and analysis indicated that 2 C-glycoside flavonoid compounds accounted for the positive mutagenic results. Two isolated compounds were identified as 2"-O-rhamnosylvitexin and schaftoside by NMR and MS techniques. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Kangwon Natl Univ, Dept Food Sci & Technol Anim Resources, Kangwon Do 200701, South Korea. Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA. RP Jhoo, JW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jjhoo@kangwon.ac.kr NR 25 TC 5 Z9 5 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD MAR PY 2007 VL 72 IS 2 BP C120 EP C125 DI 10.1111/j.1750-3841.2007.00278.x PG 6 WC Food Science & Technology SC Food Science & Technology GA 148MS UT WOS:000245079900010 PM 17995826 ER PT J AU Adjei, MD Deck, J Heinze, TM Freeman, JP Williams, AJ Sutherland, JB AF Adjei, M. D. Deck, J. Heinze, T. M. Freeman, J. P. Williams, A. J. Sutherland, J. B. TI Identification of metabolites produced from N-phenylpiperazine by Mycobacterium spp SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE biotransformation; fluoroquinolones; Mycobacterium; N-phenylpiperazine; piperazine ID FUNGUS GLOEOPHYLLUM-STRIATUM; IN-SITU H-1-NMR; ANTIBACTERIAL AGENT; MUCOR-RAMANNIANUS; DEGRADATION; CIPROFLOXACIN; NORFLOXACIN; ACETYLTRANSFERASES; BIODEGRADATION; TRANSFORMATION AB Mycobacterium sp. 7E1B1W and seven other mycobacterial strains known to degrade hydrocarbons were investigated to determine their ability to metabolize the piperazine ring, a substructure found in many drugs. Cultures were grown at 30 degrees C in tryptic soy broth and dosed with 3.1 mM N-phenylpiperazine hydrochloride; samples were removed at intervals and extracted with ethyl acetate. Two metabolites were purified from each of the extracts by high-performance liquid chromatography; they were identified by mass spectrometry and H-1 nuclear magnetic resonance spectroscopy as N-(2-anilinoethyl)acetamide and N-acetyl-N'-phenylpiperazine. The results show that mycobacteria have the ability to acetylate piperazine rings and cleave carbon-nitrogen bonds. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov NR 33 TC 3 Z9 3 U1 2 U2 9 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD MAR PY 2007 VL 34 IS 3 BP 219 EP 224 DI 10.1007/s10295-006-0189-x PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 134ER UT WOS:000244066500006 PM 17186210 ER PT J AU Liu, AY Wua, CQ Yu, KF Yuan, WS AF Liu, Aiyi Wua, Chengqing Yu, Kai F. Yuan, Weishi TI Completeness and unbiased estimation of mean vector in the multivariate group sequential case SO JOURNAL OF MULTIVARIATE ANALYSIS LA English DT Article DE bias; interim analysis; mean squared error; medical trials; minimum variance; multiple endpoints; restricted completeness; truncation-adaptation ID MULTIPLE END-POINTS; CLINICAL-TRIALS; F-TESTS; DESIGN AB We consider estimation after a group sequential test about a multivariate normal mean, such as a chi(2) test or a sequential version of the Bonferroni procedure. We derive the density function of the sufficient statistics and show that the sample mean remains to be the maximum likelihood estimator but is no longer unbiased. We propose an alternative Rao-Blackwell type unbiased estimator. We show that the family of distributions of the sufficient statistic is not complete, and there exist infinitely many unbiased estimators of the mean vector and none has uniformly minimum variance. However, when restricted to truncation-adaptable statistics, completeness holds and the Rao-Blackwell estimator has uniformly minimum variance. Published by Elsevier Inc. C1 NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, Rockville, MD 20852 USA. US FDA, Rockville, MD 20857 USA. Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China. RP Liu, AY (reprint author), NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD 20852 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 NR 28 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0047-259X J9 J MULTIVARIATE ANAL JI J. Multivar. Anal. PD MAR PY 2007 VL 98 IS 3 BP 505 EP 516 DI 10.1016/j.jmva.2006.01.001 PG 12 WC Statistics & Probability SC Mathematics GA 118AF UT WOS:000242913700005 ER PT J AU Cohen, ED AF Cohen, Ethan D. TI Safety and effectiveness considerations for clinical studies of visual prosthetic devices SO JOURNAL OF NEURAL ENGINEERING LA English DT Article; Proceedings Paper CT Eye and the Chip World Congress on Artificial Vision CY JUN 15-17, 2006 CL Detroit Inst Ophthalmol, Detroit, MI HO Detroit Inst Ophthalmol ID ELECTRICAL-STIMULATION; VISION; BLIND; NERVE AB With the advent of new designs of visual prostheses for the blind, FDA is faced with developing guidance for evaluating their engineering, safety and patient performance. Visual prostheses are considered significant risk medical devices, and their use in human clinical trials must be approved by FDA under an investigation device exemption (IDE). This paper contains a series of test topics and design issues that sponsors should consider in order to assess the safety and efficacy of their device. The IDE application includes a series of pre-clinical and clinical data sections. The pre-clinical section documents laboratory, animal and bench top performance tests of visual prostheses safety and reliability to support a human clinical trial. The materials used in constructing the implant should be biocompatible, sterile, corrosion resistant, and able to withstand any forces exerted on it during normal patient use. The clinical data section is composed of items related to patient-related evaluation of device performance. This section documents the implantation procedure, trial design, statistical analysis and how visual performance is assessed. Similar to cochlear implants, a visual prosthesis is expected to last in the body for many years, and good pre-clinical and clinical testing will help ensure its safety, durability and effectiveness. C1 Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, Rockville, MD 20852 USA. RP Cohen, ED (reprint author), Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, HFZ130,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM ethan.cohen@fda.hhs.gov OI COHEN, ETHAN/0000-0001-6365-2266 NR 15 TC 14 Z9 14 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD MAR PY 2007 VL 4 IS 1 SI SI BP S124 EP S129 DI 10.1088/1741-2560/4/1/S14 PG 6 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 155XT UT WOS:000245612700015 PM 17325410 ER PT J AU Pal, G Dutta, A Mitra, K Grace, MS Amat, A Romanczyk, TB Wu, XJ Chakrabarti, K Anders, J Gorman, E Waynant, RW Tata, DB AF Pal, Gopalendu Dutta, Ashim Mitra, Kunal Grace, Michael S. Amat, Albert Romanczyk, Tara B. Wu, Xingjia Chakrabarti, Kristi Anders, Juanita Gorman, Erik Waynant, Ronald W. Tata, Darrell B. TI Effect of low intensity laser interaction with human skin fibroblast cells using fiber-optic nano-probes SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE cell proliferation; fluorescence life-time imaging; low level light therapy (LLLT); low power laser irradiation; nano-probes; reactive oxygen species ID HE-NE-LASER; WOUND-HEALING MODEL; CALCIUM-TRANSPORT; IN-VITRO; CONFOCAL MICROSCOPY; HUMAN-LYMPHOCYTES; MURINE SKIN; IRRADIATION; NM; LEVEL AB Over the past forty years, many efforts have been devoted to study low power laser light interactions with biological systems. Some of the investigations were performed in-vitro, on bulk cell populations. Our present work was undertaken to apply specially engineered fiber-optic based nano-probes for the precise delivery of laser light on to a single cell and to observe production of low power laser light induced reactive oxygen species (ROS). A normal human skin fibroblast (NHF) cell line was utilized in this investigation and the cells were irradiated under two different schemes of exposure: (1) an entire NHF cell population within a Petri dish using a fan beam methodology, and (2) through the precise delivery of laser energy on to a single NHF cell using fiber-optic nano-probe. Photobiostimulative studies were conducted through variation of laser intensity, exposure time, and the energy dose of exposure. Laser irradiation induced enhancement in the rate of cell proliferation was observed to be dependent on laser exposure parameters and the method of laser delivery. The total energy dose (fluence) had a greater influence on the enhancement in the rate of cellular proliferation than compared to laser intensity. The enhancement in the growth rate was observed to have a finite life-time of several days after the initial laser exposure. Fluorescent life-time imaging of ROS was performed during the nano-based single cell exposure method. The kinetics of ROS generation was found to depend strongly on the laser fluence and not on the laser intensity. (c) 2006 Elsevier B.V. All rights reserved. C1 Florida Inst Technol, Dept Mech & Aerosp Engn, Melbourne, FL 32901 USA. Florida Inst Technol, Dept Biol Sci, Melbourne, FL 32901 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. US FDA, Rockville, MD 20857 USA. RP Mitra, K (reprint author), Florida Inst Technol, Dept Mech & Aerosp Engn, 150 W Univ Blvd, Melbourne, FL 32901 USA. EM kmitra@fit.edu RI Mitra, Kunal/C-6560-2016 OI Mitra, Kunal/0000-0002-7277-4908 NR 43 TC 29 Z9 32 U1 1 U2 8 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD MAR 1 PY 2007 VL 86 IS 3 BP 252 EP 261 DI 10.1016/j.jphotobiol.2006.12.001 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 144YW UT WOS:000244833500009 PM 17224276 ER PT J AU Whiting, SJ Green, TJ Calvo, MS AF Whiting, Susan J. Green, Timothy J. Calvo, Mona S. TI Vitamin D intakes in North America and Asia-Pacific countries are not sufficient to prevent vitamin D insufficiency SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 13th Workshop on Vitamin D CY APR 07-12, 2006 CL Victoria, CANADA SP Novacea Inc, Solvay Pharmaceut BV, Teijin Ltd DE vitamin D intake; fortification; supplementation ID WOMEN; HEALTH; SUPPLEMENTATION; CHOLECALCIFEROL; PERSPECTIVE; BARRIERS; CALCIUM; TRIAL AB Worldwide, vitamin D status is suboptimal relative to circulating levels of 25-hydroxyvitamin D (25OHD) needed to prevent a variety of chronic conditions, however, it has long been assumed that dietary intake is sufficient to meet needs when sun exposure is limited. In the USA, mean vitamin D intake from foods is close to 5 mu g, the Dietary Reference Intake (DRI) recommendation for persons up to 50 years; however, the amount of vitamin D needed to maintain a sufficient 25OHD level during winter is > 12.5 mu g, and that needed for darkly pigmented, veiled, or sun protected persons is > 50 mu g. In the USA, most vitamin D intake from foods is provided by fortification. Canada and New Zealand have fewer fortified choices, and intakes are correspondingly lower. Supplement use can increase mean intake to > 12.5 mu g but does not always reach those who need it most. Serum 25OHD levels in New Zealand reveal much more insufficiency than expected, especially for Pacific people and Maori; low serum 25OHD concentrations are seen throughout the Asia-Pacific region. Fortification and supplementation may be effective to achieve intakes of 12.5 mu g vitamin D in some of the population, but for many achieving the amount needed in the absence of skin synthesis requires intakes above the current upper level for vitamin D of 50 mu g. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. Univ Otago, Dept Human Nutr, Dunedin, New Zealand. USDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Whiting, SJ (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, 110 Sci Pl, Saskatoon, SK S7N 5C9, Canada. EM susan.whiting@usask.ca RI Green, Tim/E-5043-2010; OI Green, Timothy/0000-0002-0667-4300 NR 30 TC 33 Z9 33 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD MAR PY 2007 VL 103 IS 3-5 SI SI BP 626 EP 630 DI 10.1016/j.jsbmb.2006.12.067 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 158WU UT WOS:000245826800080 PM 17218094 ER PT J AU Maruvada, S Harris, GR Herman, BA King, RL AF Maruvada, Subha Harris, Gerald R. Herman, Bruce A. King, Randy L. TI Acoustic power calibration of high-intensity focused ultrasound transducers using a radiation force technique SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID EXPOSIMETRY AB To address the challenges associated with measuring the ultrasonic power from high-intensity focused ultrasound transducers via radiation force, a technique based on pulsed measurements was developed and analyzed. Two focused ultrasound transducers were characterized in terms of an effective duty factor, which was then used to calculate the power during the pulse at high applied power levels. Two absorbing target designs were used, and both gave comparable results and displayed no damage and minimal temperature rise if placed near the transducer and away from the focus. The method yielded reproducible results up to the maximum pulse power generated of approximately 230 W, thus allowing the radiated power to be calibrated in terms of the peak-to-peak voltage applied to the transducer. (c) 2007 Acoustical Society of America. C1 US FDA, Ctr Dev & Radiol Hlth, Rockville, MD 20850 USA. King Acoust Technol LLC, Washington, DC 20007 USA. RP Maruvada, S (reprint author), US FDA, Ctr Dev & Radiol Hlth, Rockville, MD 20850 USA. NR 23 TC 35 Z9 36 U1 2 U2 8 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAR PY 2007 VL 121 IS 3 BP 1434 EP 1439 DI 10.1121/1.2431332 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 147VT UT WOS:000245031600019 PM 17407880 ER PT J AU Jensen, PS Youngstrom, EA Steiner, H Findling, RL Meyer, RE Malone, RP Carlson, GA Coccaro, EF Aman, MG Blair, J Dougherty, D Ferris, C Flynn, L Green, E Hoagwood, K Hutchinson, J Laughren, T Leve, LD Novins, DK Vitiello, B AF Jensen, Peter S. Youngstrom, Eric A. Steiner, Hans Findling, Robert L. Meyer, Roger E. Malone, Richard P. Carlson, Gabrielle A. Coccaro, Emil F. Aman, Michael G. Blair, James Dougherty, Donald Ferris, Craig Flynn, Laurie Green, Evelyn Hoagwood, Kimberly Hutchinson, Janice Laughren, Tom Leve, Leslie D. Novins, Douglas K. Vitiello, Benedetto TI Consensus report on impulsive aggression as a symptom across diagnostic categories in child psychiatry: Implications for medication studies SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE impulsivity; aggression; clinical trials; assessment ethics ID INTERMITTENT EXPLOSIVE DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; RANDOMIZED CLINICAL-TRIAL; ANTISOCIAL-BEHAVIOR; AUTISTIC-CHILDREN; CONDUCT DISORDER; TREATMENT RECOMMENDATIONS; PROACTIVE AGGRESSION; JUVENILE-OFFENDERS; SOCIAL-CONTEXT AB Objective: To determine whether impulsive aggression (IA) is a meaningful clinical construct and to ascertain whether it is sufficiently similar across diagnostic categories, such that parallel studies across disorders might constitute appropriate evidence for pursuing indications. If so, how should IA be assessed, pharmacological studies designed, and ethical issues addressed? Method: Experts from key stakeholder communities, including academic clinicians, researchers, practicing clinicians, U.S. Food and Drug Administration, National Institute of Mental Health, industry sponsors, and patient and family advocates, met for a 2-day consensus conference on November 4 and 5, 2004. After evaluating summary presentations on current research evidence, participants were assigned to three workgroups, examined core issues, and generated consensus guidelines in their areas. Workgroup recommendations were discussed by the whole group to reach consensus, and then further iterated and condensed into this report postconference by the authors. Results: Conference participants agreed that IA is a substantial public health and clinical concern, constitutes a key therapeutic target across multiple disorders, and can be measured with sufficient precision that pharmacological studies are warranted. Additional areas of consensus concerned types of measures, optimal study designs, and ethical imperatives. Conclusion: Derived from scientific evidence and clinical experience, these consensus-driven recommendations can guide the design of future studies. C1 Columbia Univ, Ctr Advancement Childrens Menatl Hlth, NYSPI, Unit 78, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Best Practice Project Management Inc, Bethesda, MD USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Chicago, Sch Med, Chicago, IL 60637 USA. Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. NIMH, NIH, Bethesda, MD 20892 USA. Wake Forest Hlth Sci, Wake Forest, NC USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Attent Deficit Disorders Assoc, Chicago, IL USA. Howard Univ Hosp, Washington, DC USA. US FDA, Rockville, MD 20857 USA. Oregon Social Learning Ctr, Eugene, OR 97401 USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. RP Jensen, PS (reprint author), Columbia Univ, Ctr Advancement Childrens Menatl Hlth, NYSPI, Unit 78, 1051 Riverside Dr, New York, NY 10032 USA. EM pj131@columbia.edu OI Jensen, Peter/0000-0003-2387-0650; Leve, Leslie/0000-0003-3061-4524 NR 63 TC 68 Z9 69 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2007 VL 46 IS 3 BP 309 EP 322 DI 10.1097/CHI.0b013e31802f1454 PG 14 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 139JT UT WOS:000244428800006 PM 17314717 ER PT J AU Blanck, HM Serdula, MK Gillespie, C Galuska, DA Sharpe, PA Conway, JM Kettel, L Ainsworth, BE AF Blanck, Heidi Michels Serdula, Mary K. Gillespie, Cathleen Galuska, Deborah A. Sharpe, Patricia A. Conway, Joan M. Kettel, Laura Ainsworth, Barbara E. TI Use of nonprescription dietary supplements for weight loss is common among Americans SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID SYNEPHRINE ALKALOIDS; CITRUS-AURANTIUM; EPHEDRA; REDUCTION; PRODUCTS; CONTAIN AB Objective Dietary supplements are not, recommended as part of a weight-loss program due to concerns about efficacy and safety. This study sought to assess prevalence and duration of nonprescription weight-loss supplement use, associated weight-control behaviors, discussion of use with a health care professional, and specific ingredient use. Participants and design Adults aged >= 18 years (n=9,403) completed a cross-sectional population-based telephone survey of health behaviors from September 2002 through December 2002. Statistical analyses performed Both chi(2) and t tests were conducted for categorical and mean comparisons and Multiple variable logistic regression was used to determine significant predictors. Results An estimated 15.2% of adults (women 20.6%, men 9.7%) had ever used a weight-loss supplement and 8.7% had past year use (women 11.3%, men 6.0%); highest use was among women aged 18 to 34 years (16.7%). In regression models, use was equally prevalent among race/ethnic groups and education levels. One in 10 (10.2%) of users reported >= 12 month use, with less frequent long-term use in women (7.7%) than men (15.0%), P=0.01. Almost one third (30.2%) of users discussed use during the past year; 73.8% used a supplement containing a stimulant including ephedra, caffeine, and/or bitter orange. Conclusions Use of supplements for losing weight seems to be common among many segments of the US adult population. Many adults are long-term users and most do not discuss this practice with their physician. Most of the weight-loss supplements taken contain stimulants. Qualified professionals should inquire about use of supplements for weight loss to facilitate discussion about the lack of efficacy data, possible adverse effects, as well as to dispel misinformation that may interfere with sound weight-management practices. C1 Ctr Dis Control & Prevent, Div Nutr & Phys Act, Atlanta, GA 30341 USA. Univ S Carolina, Arnold Sch Publ Hlth, Prevent Res Ctr, Columbia, SC 29208 USA. US FDA, Rockville, MD 20857 USA. Arizona State Univ, Dept Exercise & Wellness, Mesa, AZ USA. RP Blanck, HM (reprint author), Ctr Dis Control & Prevent, Div Nutr & Phys Act, 4770 Buford Hwy NE,Mailstop K26, Atlanta, GA 30341 USA. EM nblanck@cdc.gov OI Gillespie, Cathleen/0000-0003-1878-1055 FU PHS HHS [U48/CCU409664] NR 33 TC 72 Z9 75 U1 0 U2 6 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2007 VL 107 IS 3 BP 441 EP 447 DI 10.1016/j.jada.2006.12.009 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 141BK UT WOS:000244551100019 PM 17324663 ER PT J AU Shankavaram, UT Reinhold, WC Nishizuka, S Major, S Morita, D Chary, KK Reimers, MA Scherf, U Kahn, A Dolginow, D Cossman, J Kaldjian, EP Scudiero, DA Petricoin, E Liotta, L Lee, JK Weinstein, JN AF Shankavaram, Uma T. Reinhold, William C. Nishizuka, Satoshi Major, Sylvia Morita, Daisaku Chary, Krishna K. Reimers, Mark A. Scherf, Uwe Kahn, Ari Dolginow, Douglas Cossman, Jeffrey Kaldjian, Eric P. Scudiero, Dominic A. Petricoin, Emanuel Liotta, Lance Lee, Jae K. Weinstein, John N. TI Transcript and protein expression profiles of the NCI-60 cancer cell panel: an integromic microarray study SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ANTICANCER DRUG SCREEN; GENE-EXPRESSION; MOLECULAR PHARMACOLOGY; MESSENGER-RNA; LINES; DISCOVERY; CHEMOSENSITIVITY; DIFFERENTIATION; INFORMATION; RESISTANCE AB To evaluate the utility of transcript profiling for prediction of protein expression levels, we compared profiles across the NCl-60 cancer cell panel, which represents nine tissues of origin. For that analysis, we present here two new NCl-60 transcript profile data sets (A based on Affymetrix HG-U95 and HG-U133A chips; Affymetrix, Santa Clara, CA) and one new protein profile data set (based on reverse-phase protein lysate arrays). The data sets are available online at http://discover.nci.nih.gov in the CelllMiner program package. Using the new transcript data in combination with our previously published cDNA array and Affymetrix HU6800 data sets, we first developed a "consensus set" of transcript profiles based on the four different microarray platforms. Using that set, we found that 65% of the genes showed statistically significant transcript-protein correlation, and the correlations were generally higher than those reported previously for panels of mammalian cells. Using the predictive analysis of microarray nearest shrunken centroid algorithm for functional prediction of tissue of origin, we then found that (a) the consensus mRNA set did better than did data from any of the individual mRNA platforms and (b) the protein data seemed to do somewhat better (P = 0.027) on a gene-for-gene basis in this particular study than did the consensus mRNA data, but both did well. Analysis based on the Gene Ontology showed protein levels of structure-related genes to be well predicted by mRNA levels (mean r = 0.71). Because the transcript-based technologies are more mature and are currently able to assess larger numbers of genes at one time, they continue to be useful, even when the ultimate aim is information about proteins. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Off Informat Technol, Rockville, MD 20857 USA. Gene Log Inc, Gaithersburg, MD USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21701 USA. George Mason Univ, Manassas, VA USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM weinstein@dtpax2.ncifcrf.gov FU Intramural NIH HHS NR 41 TC 198 Z9 202 U1 4 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2007 VL 6 IS 3 BP 820 EP 832 DI 10.1158/1535-7163.MCT-06-0650 PG 13 WC Oncology SC Oncology GA 148NO UT WOS:000245082100004 PM 17339364 ER PT J AU Chekhun, VF Lukyanova, NY Kovalchuk, O Tryndyak, VP Pogribny, IP AF Chekhun, Vasyl' F. Lukyanova, Nataliya Yu. Kovalchuk, Olga Tryndyak, Volodymyr P. Pogribny, Igor P. TI Epigenetic profiling of multidrug-resistant human MCF-7 breast adenocarcinorna cells reveals novel hyper- and hypomethylated targets SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ACQUIRED DOXORUBICIN RESISTANCE; CPG ISLAND METHYLATION; CANCER-CELLS; DNA METHYLATION; CHROMATIN-STRUCTURE; CHEMOTHERAPY RESISTANCE; HISTONE MODIFICATIONS; BURKITTS-LYMPHOMA; DRUG-RESISTANCE; MOLECULAR-BASIS AB The successful treatment of cancer requires a clear understanding of multiple interacting factors involved in the development of drug resistance. Presently, two hypotheses, genetic and epigenetic, have been proposed to explain mechanisms of acquired cancer drug resistance. In the present study, we examined the alterations in epigenetic mechanisms in the drug-resistant MCF-7 human breast cancer cells induced by doxorubicin (DOX) and cisplatin (cisDDP), two chemotherapeutic drugs with different modes of action. Despite this difference, both of the drug-resistant cell lines displayed similar pronounced changes in the global epigenetic landscape showing loss of global DNA methylation, loss of histone H4 lysine 20 trimethylation, increased phosporylation of histone H3 serine 10, and diminished expression of Suv4-20h2 histone methyltransferase compared with parental MCF-7 cells. In addition to global epigenetic changes, the MCF-7/ DOX and MCF-7/cisDDP drug-resistant cells are characterized by extensive alterations in region-specific DNA methylation, as indicated by the appearance of the number of differentially methylated DNA genes. A detailed analysis of hypo- and hypermethylated DNA sequences revealed that the acquisition of drug-resistant phenotype of MCF-7 cells to DOX and cisDDP, in addition to specific alterations induced by a particular drug only, was characterized by three major common mechanisms: dysfunction of genes involved in estrogen metabolism (sulfatase 2 and estrogen receptor alpha), apoptosis (p73, alpha-tubulin, BCL2-antagonist of cell death, tissue transglutaminase 2 and forkhead box protein K1), and cell-cell contact (leptin, stromal cell-derived factor receptor 1, activin A receptor E-cadherin) and showed that two opposing hypo- and hypermethylation processes may enhance and complement each other in the disruption of these pathways. These results provided evidence that epigenetic changes are an important feature of cancer cells with acquired drug-resistant phenotype and may be a crucial contributing factor to its development. Finally, deregulation of similar pathways may explain the existence and provide mechanism of cross-resistance of cancer cells to different types of chemotherapeutic agents. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. RE Kavetsky Inst Expt Pathol Oncol & Radiobiol, Dept Mech Anticanc Therapy, Kiev, Ukraine. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 58 TC 63 Z9 71 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2007 VL 6 IS 3 BP 1089 EP 1098 DI 10.1158/1535-7163.MCT-06-0663 PG 10 WC Oncology SC Oncology GA 148NO UT WOS:000245082100032 PM 17363502 ER PT J AU Tryndyak, VP Kovalchuk, O Muskhelishvili, L Montgomery, B Rodriguez-Juarez, R Melnyk, S Ross, SA Beland, FA Pogribny, IP AF Tryndyak, Volodymyr P. Kovalchuk, Olga Muskhelishvili, Levan Montgomery, Beverly Rodriguez-Juarez, Rocio Melnyk, Stepan Ross, Sharon A. Beland, Frederick A. Pogribny, Igor P. TI Epigenetic reprogramming of liver cells in tamoxifen-induced rat hepatocarcinogenesis SO MOLECULAR CARCINOGENESIS LA English DT Article DE tamoxifen; rat; hepatocarcinogenesis; DNA hypomethylation; cell proliferation ID DNA-POLYMERASE-BETA; HISTONE METHYLTRANSFERASES; HEPATOCELLULAR-CARCINOMA; HIGH-FREQUENCY; BREAST-CANCER; AURORA-A; METHYLATION; PROLIFERATION; DEFICIENCY; EXPRESSION AB Tamoxifen, a nonsteroidal anti-estrogen, is a potent genotoxic hepatocarcinogen in rats; with both tumor initiating and promoting properties. Recently it has been demonstrated that genotoxic carcinogens, in addition to exerting genotoxic effects, often cause epigenetic alterations and these induced epigenetic changes may play important mechanistic role in carcinogenesis. In the present study, we investigated the role of tamoxifen-induced epigenetic changes in hepatocarcinogenic process. The results of the study showed that exposure of female F344 rats to tamoxifen resulted in progressive loss of CpG methylation in regulatory sequences of long interspersed nucleotide elements (LINE-1) and prominent increase in expression of LINE-1 elements and c-myc proto-oncogene. The accumulation of tamoxifen-induced DNA lesions was accompanied by the decreased level of Rad51, Ku70, and DNA polymerase beta (Pol beta) proteins that play a crucial role in maintenance of genomic stability. Furthermore, feeding rats with tamoxifen-containing diet led to increased regenerative cell proliferation, as indicated by the increased level of Ki67 and proliferating cell nuclear antigen (PCNA) proteins. These data indicate that exposure of animals to genotoxic hepatocarcinogen tamoxifen led to early phenotypical alterations in livers characterized by emergence of epigenetically reprogrammed cells with a specific cancer-related epigenetic phenotype prior to tumor formation. (c) 2007 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 56 TC 29 Z9 32 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 2007 VL 46 IS 3 BP 187 EP 197 DI 10.1002/mc.20263 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 141RX UT WOS:000244597500003 PM 17219426 ER PT J AU Elespuru, RK Sankaranarayanan, K AF Elespuru, R. K. Sankaranarayanan, K. TI New approaches to assessing the effects of mutagenic agents on the integrity of the human genome SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE germ cell mutagenesis; heritable alterations; human genetic disease; integrity of the genome; environmental mutagenesis; molecular epidemiology ID RADIATION-INDUCED MUTATIONS; MAMMALIAN GERM-CELL; IONIZING-RADIATION; APOLIPOPROTEIN-E; GENETIC RISKS; ALZHEIMER-DISEASE; TYPE-4 ALLELE; CANCER; DNA; SPECIFICITY AB Heritable genetic alterations, although individually rare, have a substantial collective health impact. Approximately 20% of these are new mutations of unknown cause. Assessment of the effect of exposures to DNA damaging agents, i.e. mutagenic chemicals and radiations, on the integrity of the human genome and on the occurrence of genetic disease remains a daunting challenge. Recent insights may explain why previous examination of human exposures to ionizing radiation, as in Hiroshima and Nagasaki, failed to reveal heritable genetic effects. New opportunities to assess the heritable genetic damaging effects of environmental mutagens are afforded by: (1) integration of knowledge on the molecular nature of genetic disorders and the molecular effects of mutagens; (2) the development of more practical assays for germline mutagenesis; (3) the likely use of population-based genetic screening in personalized medicine. (c) 2006 Published by Elsevier B.V. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol, Silver Spring, MD 20993 USA. Leiden Univ, Ctr Med, Dept Toxicogenet, NL-2300 RC Leiden, Netherlands. RP Elespuru, RK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol, Silver Spring, MD 20993 USA. EM Rosalie.Elespuru@fda.hhs.gov NR 76 TC 7 Z9 10 U1 0 U2 1 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 MAR 1 PY 2007 VL 616 IS 1-2 BP 83 EP 89 DI 10.1016/j.mrfmmm.2006.11.015 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 143YC UT WOS:000244761300010 PM 17174354 ER PT J AU Desai, VG Fuscoe, JC AF Desai, Varsha G. Fuscoe, James C. TI Transcriptional profiling for understanding the basis of mitochondrial involvement in disease and toxicity using the mitochondria-specific MitoChip SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE mitochondrial dysfunction; mouse MitoChip; microarray ID OXIDATIVE-PHOSPHORYLATION; DYSFUNCTION; DRUGS; MICE AB It is well documented that mitochondrial dysfunction significantly contributes to a number of degenerative diseases, metabolic disorders, and drug- and chemical-induced toxicities. Thus far, information gained by several molecular and biochemical techniques used to delineate the mechanism of impaired mitochondrial activity underlying different diseases and various toxicities is still limited due to their low throughput potential. Here, we describe the development of mitochondria-specific mouse oligonucleotide, microarray and its potential to define mechanisms of disease progression and drug toxicities associated with mitochondfial dysfunction at both nuclear and mitochondrial genome level. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Funct Genom, Jefferson, AR 72079 USA. RP Desai, VG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Funct Genom, 3900 NCTR Rd HFT-130, Jefferson, AR 72079 USA. EM varsha.desai@fda.hhs.gov NR 18 TC 5 Z9 5 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 MAR 1 PY 2007 VL 616 IS 1-2 BP 210 EP 212 DI 10.1016/j.mrfmmm.2006.11.011 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 143YC UT WOS:000244761300024 PM 17174985 ER PT J AU Ferguson, SA Berry, KJ AF Ferguson, Sherry A. Berry, Kimberly J. TI Oral Accutane (R) (1.3-cis-retinoic acid) has no effects on spatial learning and memory in male and female Sprague-Dawley rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE accutane; isotretinoin; learning; memory; water maze; radial maze ID TRANS-RETINOIC ACID; MORRIS WATER MAZE; STEADY-STATE PHARMACOKINETICS; VITAMIN-A-DEFICIENCY; 13-CIS-RETINOIC ACID; SEX-DIFFERENCES; ISOTRETINOIN; HIPPOCAMPAL; MICE; PERFORMANCE AB Descriptions of psychiatric effects with Accutan (R) (13-cis-retinoic acid (13-cis-RA)) use prompted a series of studies in a rodent model to ascertain its cognitive effects. Previously, we reported no effects on measures of anhedonia and depression in rats treated with 7.5, 22.5, or 30 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459 [16]; S.A. Ferguson, F.J., Cisneros, J.P. Hanig, K.J. Berry, Chronic oral treatment with Accutane (13-cis-retinoic acid) does not increase measures of anhedonia, or depression in male and female Sprague-Dawley rats, (in preparation) [19]]. Here, we assessed spatial learning and memory in male and female Sprague-Dawley rats gavaged daily beginning on postnatal day (PND) 59 with vehicle control (soybean oil), 7.5 or 30 mg/kg of 13-cis-RA. We have reported that 7.5 mg/kg produces serum levels of 13-civ-RA comparable to those of humans prescribed Accutane (R) [S.A. Ferguson, P.H. Siitonen, F.J. Cisneros, B. Gough, J.F. Young, Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats, Basic Clin. Pharmacol. Toxicol. 98 (2006) 582-587 [18]]. Three behavioral tasks assessed spatial learning and memory after chronic 13-cis-RA treatment: the escape-reinforced Morris water maze (PNDs 111-115), the food-reinforced 8-arm radial maze (PNDs 132-136), and the water-reinforced NCTR complex maze (PNDs 153-157). Behaviors were measured after a minimum of 52 and maximum of 94 days of 13-cis-RA treatment. 13-cis-RA treatment had no effects on performance of the 8-arm radial maze or the NCTR complex maze. Treatment effects on Morris water maze performance were negligible and neither dose-related nor consistent. Performances of the control group were quite similar to those previously described in this laboratory. These results indicate that chronic 13-cis-RA treatment in male and female rats has few effects on measures of spatial learning and memory. (c) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov NR 39 TC 14 Z9 14 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 2007 VL 29 IS 2 BP 219 EP 227 DI 10.1016/j.ntt.2006.10.008 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 157IQ UT WOS:000245712600005 PM 17161936 ER PT J AU Fang, H Fan, XH Guo, L Shi, LM Perkins, R Ge, WG Dragan, YP Tong, WD AF Fang, Hong Fan, Xiaohui Guo, Lei Shi, Leming Perkins, Roger Ge, Weigong Dragan, Yvonne P. Tong, Weida TI Hybridization as an alternative experiment design to dye swap for two-color microarrays SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID GENE-EXPRESSION MEASUREMENTS; CDNA MICROARRAY; CLASSIFICATION; BIAS; PREDICTION; CANCER AB Dye-specific bias effects, commonly observed in the two-color microarray platform, are normally corrected using the dye swap design. This design, however, is relatively expensive and labor-intensive. We propose a self-self hybridization design as an alternative to the dye swap design. In this design, the treated and control samples are labeled with Cy5 and Cy3 (or Cy3 and Cy5), respectively, without dye swap, along with a set of self-self hybridizations on the control sample. We compare this design with the dye swap design through investigation of mouse primary hepatocytes treated with three peroxisome proliferator-activated receptor-alpha (PPAR alpha) agonists at three dose levels. Using Agilent's Whole Mouse Genome microarray, differentially expressed genes (DEG) were determined for both the self-self hybridization and dye swap designs. The DEG concordance between the two designs was over 80% across each dose treatment and chemical. Furthermore, 90% of DEG-associated biological pathways were in common between the designs, indicating that biological interpretations would be consistent. The reduced labor and expense for the self-self hybridization design make it an efficient substitute for the dye swap design. For example, in larger toxico-genomic studies, only about half the chips are required for the self-self hybridization design compared to that needed in the dye swap design. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Toxicoinformat, Jefferson, AR 72079 USA. ZTech Corp, Div Bioinformat, Jefferson, AR USA. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Toxicoinformat, HFT-020,3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov RI Guo, Lei/E-9232-2011 NR 28 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD MAR PY 2007 VL 11 IS 1 BP 14 EP 24 DI 10.1089/omi.2006.0002 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 157SC UT WOS:000245740000002 PM 17411393 ER PT J AU D'Angio, CT Boohene, PA Mowrer, A Audet, S Menegus, MA Schmid, DS Beeler, JA AF D'Angio, Carl T. Boohene, Paulina A. Mowrer, Anne Audet, Susette Menegus, Marilyn A. Schmid, D. Scott Beeler, Judy A. TI Measles-mumps-rubella and varicella vaccine responses in extremely preterm infants SO PEDIATRICS LA English DT Article DE vaccines; premature infant; measles-mumps-rubella vaccine; varicella vaccine; very low birth weight infant; immunology; humoral immunity; immunization ID INFLUENZAE TYPE-B; EXTREMELY PREMATURE-INFANTS; BIRTH-WEIGHT INFANTS; HAEMOPHILUS-INFLUENZAE; CONJUGATE VACCINE; HEPATITIS-B; IMMUNE-RESPONSES; HEALTHY-CHILDREN; UNITED-STATES; TERM INFANTS AB OBJECTIVE. Extremely preterm infants mount lower antibody responses than term infants to several vaccines. The objective of this study was to measure the immunogenicity of measles- mumps- rubella and varicella vaccines in preterm and term children. METHODS. Immune status before immunization and immune response after immunization with measles- mumps- rubella and varicella vaccines at 15 months of age were compared in 32 infants, 16 of whom were preterm ( < 29 weeks' gestation) and 16 of whom were term ( >= 37 weeks' gestation) at birth. Blood was drawn before vaccination and 3 to 6 weeks thereafter. Measles antibody was measured by plaque reduction neutralization assay. Mumps and rubella immunoglobulin G were measured in available sera by enzyme- linked fluorescent immunoassay. Varicella immunoglobulin G was measured in available sera by glycoprotein enzyme- linked immunosorbent assay. Values that were above or below the assay limits were assigned values double or half those limits, respectively. The primary outcome was the geometric mean antibody titer. RESULTS. Preterm children had lower mumps and rubella geometric mean titers than did term children before vaccine, and nearly all children were seronegative for each of the 4 vaccine antigens before immunization. Measles, mumps, rubella, and varicella geometric mean titers were similar between groups after vaccine. All children were seropositive for measles after vaccine, whereas 13 of 14 preterm and 11 of 13 term children were seropositive for mumps, 13 of 14 preterm and 13 of 13 term children were seropositive for rubella, and 11 of 16 preterm and 9 of 15 term children were seropositive for varicella. CONCLUSIONS. Preterm children mounted antibody responses that were similar to those of term children after measles- mumps- rubella and varicella vaccines at 15 months of age. C1 Univ Rochester, Dept Pediat, Rochester, NY 14642 USA. Univ Rochester, Dept Med, Rochester, NY USA. Univ Rochester, Dept Microbiol & Immunol, Rochester, NY USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Ctr Dis Control & Prevent, Natl VZU Lab, Atlanta, GA USA. RP D'Angio, CT (reprint author), Univ Rochester, Dept Pediat, 601 Elmwood Ave,Box 651, Rochester, NY 14642 USA. EM carl_dangio@urmc.rochester.edu FU NCRR NIH HHS [5 M01 RR00044]; PHS HHS [N01-A1-25460] NR 41 TC 8 Z9 10 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2007 VL 119 IS 3 BP E574 EP E579 DI 10.1542/peds.2006-2241 PG 6 WC Pediatrics SC Pediatrics GA 141LK UT WOS:000244579800051 PM 17332177 ER PT J AU Devadas, K Boykins, RA Hewlett, IK Wood, OL Clouse, KA Yamada, KM Dhawan, S AF Devadas, Krishnakumar Boykins, Robert A. Hewlett, Indira K. Wood, Owen L. Clouse, Kathleen A. Yamada, Kenneth M. Dhawan, Subhash TI Antibodies against a multiple-peptide conjugate comprising chemically modified human immunodeficiency virus type-1 functional Tat peptides inhibit infection SO PEPTIDES LA English DT Article DE HIV-Tat; peptides; AIDS; vaccination ID NF-KAPPA-B; RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES; T-CELLS; PROTEIN; HIV-1; MONOCYTES; ACTIVATION; IDENTIFICATION AB We demonstrated recently that selective side-chain modification of functional cysteine-rich (Tat(21-40)) and arginine-rich (Tat(53-68)) domains of the HIV-1 Tat protein blocks pathogenic activities of these peptides while retaining their immunological characteristics. In the present study, we have synthesized a multiple-peptide conjugate system comprising modified Tat(21-40) and Tat(53-68) peptides (HIV-1-Tat-MPC). Immunization of mice with this highly homogeneous 10.7 kDa HIV-1-Tat-MPC synthetic construct induced an effective immune response in mice. The antibodies generated against HIV-1-Tat-MPC efficiently suppressed Tat-induced viral replication and significantly reduced HIV-associated cytopathic effects in human monocytes. These results indicate that epitope-specific antibodies directed against functional sites of Tat protein using non-pathogenic peptides inhibit HIV pathogenesis. The HIV-1-Tat-MPC, therefore, has potential for the development of a safe, effective, and economical therapeutic vaccine to reduce the progression of HIV infection. (c) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Immunopathogenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA. Cell Biol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Dhawan, S (reprint author), US FDA, Immunopathogenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, 140 Rockville Pike,HFM 315, Rockville, MD 20852 USA. EM subhash.dhawan@fda.hhs.gov OI Yamada, Kenneth/0000-0003-1512-6805 NR 42 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAR PY 2007 VL 28 IS 3 BP 496 EP 504 DI 10.1016/j.peptides.2006.11.007 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 141XG UT WOS:000244611700002 PM 17188401 ER PT J AU Uhl, K Trontell, A Kennedy, D AF Uhl, Kathleen Trontell, Anne Kennedy, Dianne TI Risk minimization practices for pregnancy prevention: understanding risk, selecting tools SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Review DE pregnancy; drugs/medications; teratogens; birth defects; risk management; risk minimization; prevention; pregnancy prevention ID CONGENITAL-MALFORMATIONS; DISEASE MANAGEMENT; TUBERCULOSIS; CISAPRIDE; PROGRAM; TRENDS; DRUGS AB According to the March of Dimes, approximately 4% (1/28) of babies are born in the US each year with a birth defect. For the majority of birth defects the etiology is unknown, although chemicals, including drug exposures, probably account for less than 1% of all birth defects. The identification of potential human teratogenicity during drug development is important because drug-induced adverse fetal effects are potentially preventable with the application of risk assessment strategies and risk minimization tools and programs to minimize risk of pregnancy exposure while preserving access to drug benefits; risk assessment and risk minimization together comprise risk management. It is important that risk minimization programs intended to limit fetal exposure use a consistent approach and are tailored to the product-specific risk concerns in order to optimize the benefit-fisk balance for a particular drug. This paper highlights general considerations in developing specific risk minimization programs to prevent fetal drug exposure including the relative advantages and disadvantages of each strategy. Published in 2006 by John Wiley and Sons Ltd. C1 US FDA, Off Womens Hlth, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20857 USA. Ctr Outcomes & Evidence, Agcy Healthcare Res & Qual, Rockville, MD USA. RP Uhl, K (reprint author), US FDA, Off Womens Hlth, 5600 Fishers Lane,PKLN 16-65,HF-8, Rockville, MD 20857 USA. EM kathleen.uhl@fda.hhs.gov NR 24 TC 4 Z9 7 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAR PY 2007 VL 16 IS 3 BP 337 EP 348 DI 10.1002/pds.1312 PG 12 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 146EV UT WOS:000244918200010 PM 16953517 ER PT J AU Schech, S Graham, D Staffa, J Andrade, SE La Grenade, L Burgess, M Blough, D Stergachis, A Chan, KA Platt, R Shatin, D AF Schech, Stephanie Graham, David Staffa, Judy Andrade, Susan E. La Grenade, Lois Burgess, Margaret Blough, David Stergachis, Andy Chan, K. Arnold Platt, Richard Shatin, Deborah TI Risk factors for statin-associated rhabdomyolysis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE rhabdomyolysis; automated data; lipid-lowering medications; risk factors ID THERAPY; CERIVASTATIN; MYOPATHY AB Purpose To identify and characterize risk factors for rhabdomyolysis in patients prescribed statin monotherapy or statin plus fibrate therapy. Methods A nested case-control study was conducted within a cohort of 252460 new users of lipid-lowering medications across I I geographically dispersed U.S. health plans. Twenty-one cases of rhabdomyolysis confirmed by medical record review were compared to 200 individually matched controls without rhabdomyolysis. A conditional logistic regression model was applied to evaluate the effects of age, gender, comorbidities, concurrent medication use, dosage, and duration of statin use on the development of rhabdomyolysis. Results Statin users 65 years of age and older have four times the risk of hospitalization for rhabdomyolysis than those under age 65 (odds ratio (OR) = 4.36, 95% confidence interval (Cl): 1.5,14, 1). We also observed a joint effect of high statin dosage and renal disease (p = 0.022). When these two variables were added to the model with age, we obtained an OR of 5.73 for dosage (95%CI: 0.63, 52.6) and 6.26 for renal disease (95%CI: 0.46, 63.38). Although not statistically significant, we did observe a greater than twofold increase in risk for rhabdomyolysis among females (OR= 2.53, 95%CI: 0.91, 7.32). Conclusions Findings of this study indicate that older age is a risk factor for rhabdomyolysis among statin users. Although the evidence is not as strong, high statin dosage, renal disease, and female gender may be additional risk factors. Patients at higher risk of developing rhabdomyolysis should be closely monitored for signs and symptoms of the disease. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN 55344 USA. US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Silver Spring, MD USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Fallon Fdn, Meyers Primary Care Inst, Worcester, MA USA. Univ Washington, Dept Pharm, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Harvard Pilgrim Hlth Care, Sch Med, Channing Lab, Boston, MA USA. Harvard Univ, Harvard Pilgrim Hlth Care, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RP Schech, S (reprint author), Ctr Hlth Care Policy & Evaluat, 12125 Technol Dr,MN002-0258, Eden Prairie, MN 55344 USA. EM stephanie_d_schech@uhc.com OI Chan, Kinwei/0000-0001-8161-1986 FU FDA HHS [FD-U-001641, FD-U-001643, FD-U-002067-02, FD-U-002067-03] NR 19 TC 47 Z9 52 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAR PY 2007 VL 16 IS 3 BP 352 EP 358 DI 10.1002/pds.1287 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 146EV UT WOS:000244918200012 PM 16892458 ER PT J AU Fu, PP Xia, QS Yin, JJ Cherng, SH Yan, J Mei, N Chen, T Boudreau, MD Howard, PC Wamer, WG AF Fu, Peter P. Xia, Qingsu Yin, Jun Jie Cherng, Shu-Hui Yan, Jian Mei, Nan Chen, Tao Boudreau, Mary D. Howard, Paul C. Wamer, Wayne G. TI Photodecomposition of vitamin a and photobiological implications for the skin SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article; Proceedings Paper CT 12th International Conference on Retinal Proteins CY JUN 04-08, 2006 CL Awaji Isl, JAPAN ID ALL-TRANS-RETINOL; OXYGEN PARTIAL-PRESSURE; MOUSE LYMPHOMA-CELLS; RAT SERTOLI-CELLS; SINGLET OXYGEN; HUMAN KERATINOCYTES; LIPID-PEROXIDATION; PULSE-RADIOLYSIS; OXIDATIVE STRESS; ALPHA-TOCOPHEROL AB Vitamin A (retinol), an essential human nutrient, plays an important role in cellular differentiation, regulation of epidermal cell growth and normal cell maintenance. In addition to these physiological roles, vitamin A has a rich photochemistry. Photoisomerization of vitamin A, involved in signal transduction for vision, has been extensively investigated. The biological effects of light-induced degradation of vitamin A and formation of reactive species are less understood and may be important for light-exposed tissues, such as the skin. Photochemical studies have demonstrated that excitation of retinol or its esters with UV light generates a number of reactive species including singlet oxygen and superoxide radical anion. These reactive oxygen species have been shown to damage a number of cellular targets, including lipids and DNA. Consistent with the potential for damaging DNA, retinyl palmitate has been shown to be photomutagenic in an in vitro test system. The results of mechanistic studies were consistent with mutagenesis through oxidative damage. Vitamin A in the skin resides in a complex environment that in many ways is very different from the chemical environment in solution and in in vitro test systems. Relevant clinical studies or studies in animal models are therefore needed to establish whether the pro-oxidant activity of photoexcited vitamin A is observed in vivo, and to assess the related risks. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov RI mei, nan/E-8915-2011; Yin, Jun Jie /E-5619-2014 OI mei, nan/0000-0002-3501-9014; NR 96 TC 28 Z9 28 U1 1 U2 7 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR-APR PY 2007 VL 83 IS 2 BP 409 EP 424 DI 10.1562/2006-10-23-IR-1065 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 156OE UT WOS:000245658000029 PM 17576350 ER PT J AU Matthews, EJ Kruhlak, NL Benz, RD Contrera, JF AF Matthews, Edwin J. Kruhlak, Naomi L. Benz, R. Daniel Contrera, Joseph F. TI A comprehensive model for reproductive and developmental toxicity hazard identification: I. Development of a weight of evidence QSAR database SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE developmental toxicity; dysmorphogenesis; quantitative structure-activity relationships; QSAR; reproductive toxicity; reprotox; teratogenicity; weight of evidence ID CARCINOGENICITY DATA; GENETIC TOXICITY; METHODOLOGY; TESTS AB A weight of evidence (WOE) reproductive and developmental toxicology (reprotox) database was constructed that is suitable for quantitative structure-activity relationship (QSAR) modeling and human hazard identification of untested chemicals. The database was derived from multiple publicly available reprotox databases and consists of more than 10,000 individual rat, mouse, or rabbit reprotox tests linked to 2134 different organic chemical structures. The reprotox data were classified into seven general classes (male reproductive toxicity, female reproductive toxicity, fetal dysmorphogenesis, functional toxicity, mortality, growth, and newborn behavioral toxicity), and 90 specific categories as defined in the source reprotox databases. Each specific category contained over 500 chemicals, but the percentage of active chemicals was low, generally only 0.1-10%. The mathematical WOE model placed greater significance on confirmatory observations from repeat experiments, chemicals with multiple findings within a category, and the categorical relatedness of the findings. Using the weighted activity scores, statistical analyses were performed for specific data sets to identify clusters of categories that were correlated, containing similar profiles of active and inactive chemicals. The analysis revealed clusters of specific categories that contained chemicals that were active in two or more mammalian species (trans-species). Such chemicals are considered to have the highest potential risk to humans. In contrast, some specific categories exhibited only single species-specific activities. Results also showed that the rat and mouse were more susceptible to dysmorphogenesis than rabbits (6.1- and 3.6-fold, respectively). Published by Elsevier Inc. C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, ICSAS, Silver Spring, MD 20993 USA. RP Matthews, EJ (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, ICSAS, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM edwin.matthews@fda.hhs.gov NR 27 TC 22 Z9 22 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD MAR PY 2007 VL 47 IS 2 BP 115 EP 135 DI 10.1016/j.yrtph.2006.11.002 PG 21 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 143ZZ UT WOS:000244766200001 PM 17207562 ER PT J AU Matthews, EJ Kruhlak, NL Benz, RD Ivanov, J Klopman, G Contrera, JF AF Matthews, Edwin J. Kruhlak, Naomi L. Benz, R. Daniel Ivanov, Julian Klopman, Gilles Contrera, Joseph F. TI A comprehensive model for reproductive and developmental toxicity hazard identification: II. Construction of QSAR models to predict activities of untested chemicals SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE MC4PC; computational toxicology; developmental toxicity; dysmorphogenesis; predictive modeling; quantitative structure activity relationships (QSAR); reproductive toxicity; reprotox; teratogenicity; weight of evidence ID ESTROGEN-RECEPTOR BINDING; PRODUCTION VOLUME CHEMICALS; MULTICASE EXPERT-SYSTEM; DECISION TREE MODELS; STRUCTURAL DETERMINANTS; CARCINOGENICITY DATA; LIGAND FLEXIBILITY; GENETIC TOXICITY; SAR MODELS; AFFINITY AB This report describes the construction, optimization and validation of a battery of quantitative structure-activity relationship (QSAR) models to predict reproductive and developmental (reprotox) hazards of untested chemicals. These models run with MC4PC software to predict seven general reprotox classes: mate and female reproductive toxicity, fetal dysmorphogenesis, functional toxicity, mortality, growth, and newborn behavioral toxicity. The reprotox QSARs incorporate a weight of evidence paradigm using rats, mice, and rabbit reprotox study data and are designed to identify trans-species reprotoxicants. The majority of the reprotox QSARs exhibit good predictive performance properties: high specificity (> 80%), low false positives (< 20%), significant receiver operating characteristic (ROC) values (> 2.00), and high coverage (> 80%) in 10% leave-many-out validation experiments. The QSARs are based on 627-2023 chemicals and exhibited a wide applicability domain for FDA regulated organic chemicals for which they were designed. Experiments were also performed using the MC4PC multiple module prediction technology, and ROC statistics, and adjustments to the ratio of active to inactive (A/I ratio) chemicals in training data sets were made to optimize the predictive performance of QSAR models. Results revealed that an A/I ratio of similar to 40% was optimal for MC4PC. We discuss specific recommendations for the application of the reprotox QSAR battery. Published by Elsevier Inc. C1 US FDA, Silver Spring, MD 20993 USA. Multicase Inc, Beachwood, OH 44122 USA. RP Matthews, EJ (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM edwin.matthews@fda.hhs.gov NR 51 TC 34 Z9 35 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD MAR PY 2007 VL 47 IS 2 BP 136 EP 155 DI 10.1016/j.yrtph.2006.10.001 PG 20 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 143ZZ UT WOS:000244766200002 PM 17175082 ER PT J AU Maldjian, C Patel, TY Klein, RM Smith, RC AF Maldjian, C. Patel, T. Y. Klein, R. M. Smith, R. C. TI Efficacy of MRI in classifying proximal focal femoral deficiency SO SKELETAL RADIOLOGY LA English DT Article DE femur; deficiency; congenital; hip; MRI AB Objective To evaluate the efficacy of MRI in classifying PFFD and to compare MRI to radiographic classification of PFFD. Design Radiographic and MRI classification of the cases was performed utilizing the Amstutz classification system. Patients Retrospective evaluation of radiographs and MRI exams in nine hips of eight patients with proximal focal femoral deficiency was performed by two radiologists. Results The cases were classified by radiographs as Amstutz 1: n=3, Amstutz 3: n=3, Amstutz 4: n=1 and Amstutz 5: n=2. The classifications based on MRI were Amstutz 1: n=6, Amstutz 2: n=1, Amstutz 3: n=0, Amstutz 4: n=2 and Amstutz 5: n=0. Three hips demonstrated complete agreement. There were six discordant hips. In two of the discordant cases, follow-up radiographs of 6 months or greater intervals were available and helped to confirm MRI findings. Errors in radiographic evaluation consisted of overestimating the degree of deficiency. Conclusion MRI is more accurate than radiographic evaluation for the classification of PFFD, particularly early on, prior to the ossification of cartilaginous components in the femurs. Since radiographic evaluation tends to overestimate the degree of deficiency, MRI is a more definitive modality for evaluation of PFFD. C1 New York Med Coll, Valhalla, NY 10595 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Patel, TY (reprint author), New York Med Coll, 95 Grasslands Rd, Valhalla, NY 10595 USA. EM patelt@wcmc.com NR 7 TC 9 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAR PY 2007 VL 36 IS 3 BP 215 EP 220 DI 10.1007/s00256-006-0218-x PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 134PL UT WOS:000244095200007 PM 17051388 ER PT J AU Jacobson-Kram, D Contrera, JF AF Jacobson-Kram, David Contrera, Joseph F. TI Genetic toxicity assessment: Employing the best science for human safety evaluation Part I: Early screening for potential human mutagens SO TOXICOLOGICAL SCIENCES LA English DT Article DE mutagenesis; clastogenesis; structure activity; bacterial mutation ID DEVELOPMENTAL TOXICITY; CARCINOGENICITY DATA; GENOTOXICITY; ASSAY; IDENTIFICATION; SENSITIVITY; CHEMICALS AB Results of genetic toxicology tests are used by FDA's Center for Drug Evaluation and Research as a surrogate for carcinogenicity data during the drug development process. Mammalian in vitro assays have a high frequency of positive results which can impede or derail the drug development process. To reduce the risk of such delays, most pharmaceutical companies conduct early non-GLP (good laboratory practices) studies to eliminate drug candidate with mutagenic or clastogenic activity. Early screens include in silico structure activity assessments and various iterations of the ultimate regulatory mandated GLP studies. C1 US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Jacobson-Kram, D (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM david.jacobsonkram@fda.hhs.gov NR 24 TC 23 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2007 VL 96 IS 1 BP 16 EP 20 DI 10.1093/toxsci/kfl191 PG 5 WC Toxicology SC Toxicology GA 136ZP UT WOS:000244262900003 PM 17194803 ER PT J AU Kim, CS Ross, IA Sprando, RL Johnson, WD Sahu, SC Flynn, T Wiesenfeld, PL Collins, TFX O'Neilll, RK Sapienza, P AF Kim, C. S. Ross, I. A. Sprando, R. L. Johnson, W. D. Sahu, S. C. Flynn, T. J. Wiesenfeld, P. L. Collins, T. F. X. O'Neilll, R. K. Sapienza, P. TI Distribution of androstenedione and its effects on total free fatty acids in pregnant rats SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE androstenedione; free fatty acids; Oxidative stress; brain; liver; pregnant rats ID NONPREGNANT FEMALE RATS; ORAL ANDROSTENEDIONE; STEROID-METABOLISM; OXIDATIVE STRESS; REACTIVE OXYGEN; BRAIN; LIVER; SERUM; APOPTOSIS; DISEASES AB Androstenedione, an anabolic steroid used to enhance athletic performance, was administered in corn oil by gastric intubation once daily in the morning to nonpregnant female rats at a dose of 5 or 60 mg/kg/day, beginning two weeks before mating and continuing through gestation day (GD) 19. On GD 20, the distribution of androstenedione and other steroid metabolites was investigated in the maternal plasma and target organs,. including brain and liver. The concentration of estradiol in plasma approached a statistically significant increase after treatment as compared with the controls, whereas the levels of androstenedione, testosterone and progesterone were not significantly different from the controls. In the liver, the concentrations of androstenedione and estradiol only were increased in a dose-related manner. None of these steroids was detectable in the brain. Androstenedione treatment also produced changes in the level of selected free fatty acids (FFAs) in the maternal blood, brain, liver and fetal brain. The concentrations of palmitic acid (16:0) and stearic acid (18:0) in the plasma were not significantly different between the controls and treated rats. However, oleic acid (18: 1), linoleic acid (18:2) and docosahexaenoic acid (DHA, 22:6) were 17.94 +/- 2.06 mu g/ml, 24.23 +/- 2.42 [mu g/ml and 4.08 +/- 0.53 mu g/ml, respectively, in the controls, and none of these fatty acids was detectable in the treated plasma. On the other hand, palmitic, stearic, oleic, linoleic and DHA were present in both control and treated livers. Among the FFAs in liver, linoleic and DHA were increased 87% and 169%, respectively, over controls. Palmitic, stearic and oleic acids were not significantly affected by the 60 mg/kg treatment. These were present in both control maternal and fetal brains, whereas linoleic acid was found only in fetal brain control. DHA was present only in the control maternal brain (0.02 +/- 0.02 mu g/mg protein) and fetal brain (0.24 +/- 0.15 mu g/mg protein). The results indicated that androstenedione exhibits significantly different effects on the FFA composition among target organs during pregnancy. C1 [Kim, C. S.; Ross, I. A.; Sprando, R. L.; Johnson, W. D.; Sahu, S. C.; Flynn, T. J.; Wiesenfeld, P. L.; Collins, T. F. X.; Sapienza, P.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. [O'Neilll, R. K.] US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Laurel, MD 20708 USA. RP Kim, CS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. EM chung.kim@fda.hhs.gov OI Flynn, Thomas/0000-0002-7248-0643 NR 38 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD MAR PY 2007 VL 23 IS 2 BP 65 EP 74 DI 10.1177/0748233707076774 PG 10 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 243OS UT WOS:000251807800001 PM 18203558 ER PT J AU Tang, SX Ablan, S Dueck, M Ayala-Lopez, W Soto, B Caplan, M Nagashima, K Hewlett, IK Freed, EO Levin, JG AF Tang, Shixing Ablan, Sherimay Dueck, Megan Ayala-Lopez, Wilfredo Soto, Brenda Caplan, Margaret Nagashima, Kunio Hewlett, Indira K. Freed, Eric O. Levin, Judith G. TI A second-site suppressor significantly improves the defective phenotype impolsed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein SO VIROLOGY LA English DT Article DE HIV-1 capsid protein; second-site suppressors; HIV-1 viral cores; dominant-negative inhibition; HIV-1 assembly; structural models; reverse transcriptase; transmission electron microscopy ID HUMAN-IMMUNODEFICIENCY-VIRUS; ROUS-SARCOMA-VIRUS; FUSION INHIBITOR T-20; WILD-TYPE VIRUS; IN-VITRO; GAG PROTEINS; TYPE-1 GAG; 3-DIMENSIONAL STRUCTURE; REVERSE-TRANSCRIPTASE; VIRION MORPHOGENESIS AB The HIV-1 capsid (CA) protein plays an important role in virus assembly and infectivity. Previously, we showed that Ala substitutions in the N-terminal residues Trp23 and Phe40 cause a severely defective phenotype. In searching for mutations at these positions that result in a non-lethal phenotype, we identified one candidate, W23F. Mutant virions contained aberrant cores, but unlike W23A, also displayed some infectivity in a single-round replication assay and delayed replication kinetics in MT-4 cells. Following long-term passage in MT-4 cells, two second-site mutations were isolated. In particular, the W23F/V261 mutation partially restored the wild-type phenotype, including production of particles with conical cores and wild-type replication kinetics in MT-4 cells. A structural model is proposed to explain the suppressor phenotype. These findings describe a novel occurrence, namely suppression of a mutation in a hydrophobic residue that is critical for maintaining the structural integrity of CA and proper core assembly. Published by Elsevier Inc. C1 NICHHD, Mol Genet Lab, Viral Gene Regulat Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Image Anal Lab, Frederick, MD 21702 USA. RP Levin, JG (reprint author), NICHHD, Mol Genet Lab, Viral Gene Regulat Sect, NIH, Bldg 6B,Room 216, Bethesda, MD 20892 USA. EM levinju@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NICHD NIH HHS [Z01 HD000069-33] NR 68 TC 3 Z9 3 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 0042-6822 J9 VIROLOGY JI Virology PD MAR 1 PY 2007 VL 359 IS 1 BP 105 EP 115 DI 10.1016/j.virol.2006.09.027 PG 11 WC Virology SC Virology GA 143PT UT WOS:000244735700012 PM 17055023 ER PT J AU Doerge, DR Twaddle, NC Boettcher, MI McDaniel, LP Angerer, J AF Doerge, Daniel R. Twaddle, Nathan C. Boettcher, Melanie I. McDaniel, L. Patrice Angerer, Juergen TI Urinary excretion of acrylamide and metabolites in Fischer 344 rats and B6C3F(1) mice administered a single dose of acrylamide SO TOXICOLOGY LETTERS LA English DT Article DE acrylamide; glycidamide; urine; mass spectrometry; biomarkers ID MERCAPTURIC ACIDS; HEMOGLOBIN ADDUCTS; DIETARY EXPOSURE; DRINKING-WATER; GLYCIDAMIDE; TOXICOKINETICS; BIOMARKERS; GENOTOXICITY; HUMANS; DNA AB Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in mice and rats. AA is also formed during cooking in many commonly consumed starchy foods. Our previous toxicokinetic investigations of AA and its genotoxic metabolite, glycidamide (GA), in rodents showed that AA is highly bioavailable from oral routes of administration, is widely distributed to tissues, and that the dietary route, in particular, favors metabolism to GA. Formation and accumulation of mutagenic GA-DNA adducts in many tissues support the hypothesis that AA is carcinogenic in rodent bioassays through metabolism to GA. The current investigation describes the quantification of 24h urinary metabolites, including free AA and GA and their mercapturic acid conjugates (AAMA and GAMA, respectively), using LC/MS/MS in F344 rats and 136C3F(I) mice following a dose of 0.1 mg/kg bw given by intravenous, gavage, and dietary routes of administration. Similar groups of rodents were used previously for serum/tissue toxicokinetic and adduct determinations (DNA and hemoglobin). The goal was to investigate relationships between urinary and circulating biomarkers of exposure, toxicokinetic parameters for AA and GA, and tissue GA-DNA adducts in rodents from single doses of AA. Significant linear correlations were observed between urinary levels of AA with AAMA and GA with GAMA in the current data sets for rats and mice. Concentrations of AA and AAMA correlated significantly with average AUC values determined previously for AA in groups of rats and mice similarly dosed with AA. Urinary GA and GAMA concentrations showed significant correlations with average AUC values for GA and liver GA-DNA adducts determined previously in rats and mice similarly dosed with AA. Despite statistical significance, considerable inter-animal variability was observed in all urinary measurements, which limited the degree of correlation with either average toxicokinetic or biomarker data collected from different groups of animals. These results suggest that urinary measurements of AA and its metabolites may be useful for prediction of internal exposures to AA and GA. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Erlangen Nurnberg, Inst & Outpatient Clin Occupat Social & Environm, D-91054 Erlangen, Germany. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov NR 38 TC 15 Z9 16 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD FEB 28 PY 2007 VL 169 IS 1 BP 34 EP 42 DI 10.1016/j.toxlet.2006.12.002 PG 9 WC Toxicology SC Toxicology GA 144CE UT WOS:000244772000005 PM 17224249 ER PT J AU Wong, JW Hennessy, MK Hayward, DG Krynitsky, AJ Cassias, I Schenck, FJ AF Wong, Jon W. Hennessy, Michael K. Hayward, Douglas G. Krynitsky, Alexander J. Cassias, Irene Schenck, Frank J. TI Analysis of organophosphorus pesticides in dried ground ginseng root by capillary gas chromatography-mass spectrometry and -flame photometric detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Panax quinquefolius (American ginseng); Panax ginseng(Asian ginseng); ginseng root; capillary gas chromatography; mass spectrometry (GC-MS); gas chromatography-flame photometric detection (GC-FPD); organophosphorus pesticides (OPs); solid-phase dispersive cleanup ID ORGANOCHLORINE PESTICIDES; MEDICINAL-PLANTS; RESIDUES; METALS; ENHANCEMENT; FOOD AB A method was developed to determine organophosphorus pesticides (OPs) in dried ground ginseng root. Pesticides were extracted from the sample using acetonitrile/water saturated with salts, followed by solid-phase dispersive cleanup, and analyzed by capillary gas chromatography with electron ionization mass spectrometry in selective ion monitoring mode (GC-MS/SIM) and flame photometric detection (GC-FPD) in phosphorus mode. The detection limits for most of the pesticides were 0.025-0.05 mu g/g using GC-FPD but were analyte-dependent for GC-MS/SIM, ranging from 0.005 to 0.50 mu g/g. Quantitation was determined from 0.050 to 5.0 mu g/g with r(2) > 0.99 for a majority of the pesticides using both detectors. Recovery studies were performed by fortifying the dried ground ginseng root samples to concentrations of 0.025, 0.1, and 1.0 mu g/g, resulting in recoveries of > 90% for most pesticides by GC-FPD. Lower (< 70%) and higher (> 120%) recoveries were most likely from complications of pesticide lability or volatility, matrix interference, or inefficient desorption from the solid-phase sorbents. There was difficulty in analyzing the ginseng samples for the OPs using GC-MS at the lower fortification levels for some of the OPs due to lack of confirmation. GC-FPD and GC-MS/SIM complement each other in detecting the OPs in dried ground ginseng root samples. This procedure was shown to be effective and was applied to the analysis of OPs in ginseng root samples. One particular sample, a ground and dried American ginseng (Panax quinquefolius) root sample, was found to contain diazinon quantified at approximately 25 mu g/kg by external calibration using matrix-matched standards or standard addition using both detectors. The advantage of using both detectors is that confirmation can be achieved using GC-MS, whereas the use of a megabore column in GC-FPD can be used to quantitate some of the nonpolar OPs without the use of matrix-matched standards or standard addition. C1 USDA, Off Plant & Dairy Foods, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. USDA, Off Regulatroy Affairs, Pacific Reg Lab SW, Irvine, CA 92612 USA. USDA, SE Reg Lab, Atlanta, GA 30309 USA. RP Wong, JW (reprint author), USDA, Off Plant & Dairy Foods, Ctr Food Safety & Appl Nutr, HFS-336,5100 Paint Branch Parkway, College Pk, MD 20740 USA. EM jon.wong@fda.hhs.gov FU NIH HHS [Y1 OD 6412-01] NR 24 TC 54 Z9 56 U1 5 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD FEB 21 PY 2007 VL 55 IS 4 BP 1117 EP 1128 DI 10.1021/jf062774q PG 12 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 136EZ UT WOS:000244206700009 PM 17249685 ER PT J AU McMullan, LK Grakoui, A Evans, MJ Mihalik, K Puig, M Branch, AD Feinstone, SM Rice, CM AF McMullan, Laura K. Grakoui, Arash Evans, Matthew J. Mihalik, Kathleen Puig, Montserrat Branch, Andrea D. Feinstone, Stephen M. Rice, Charles M. TI Evidence for a functional RNA element in the hepatitis C virus core gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE alternative reading frame; RNA replication; RNA structure ID READING FRAME; CELL-CULTURE; SECONDARY STRUCTURES; IMMUNE-RESPONSES; CODING REGION; VIRAL GENOME; IN-VITRO; REPLICATION; PROTEIN; INFECTION AB In the core protein-coding region of hepatitis C virus (HCV), evidence exists for both phylogenetically conserved RNA structures and a + 1 alternative reading frame (ARF). To investigate its role in HCV infection, we introduced four stop codons into the ARF of a genotype 1aH77 molecular clone. The changes did not alter the core protein sequence, but were predicted to disrupt RNA secondary structures. An attenuated infection was established after inoculation of the mutant HCV RNA into an HCV naive chimpanzee. The acute infection was atypical with low peak viremia, minimal alanine aminotransferase elevation, and early virus control by a diverse adaptive immune response. Sequencing circulating virus revealed progressive reversions at the third and then fourth stop codon. In cell culture, RNA replication of a genome with four stop codons was severely impaired. In contrast, the revertant genome exhibited only a 5-fold reduction in replication. Genomes harboring only the first two stop codons replicated to WT levels. Similarly, reversions at stop codons 3 and 4, which improved replication, were selected with recombinant, infectious HCV in cell culture. We conclude that ARF-encoded proteins initiating at the polyprotein AUG are not essential for HCV replication in cell culture or in vivo. Rather, our results provide evidence for a functionally important RNA element in the ARF region. C1 Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10021 USA. US FDA, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Med, Div Liver Dis, New York, NY 10029 USA. RP Rice, CM (reprint author), Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10021 USA. EM ricec@rockefeller.edu OI Evans, Matthew/0000-0002-4991-3877 FU NCI NIH HHS [CA 85883, R01 CA057973, R01 CA085883, CA 57973]; NIAID NIH HHS [AI 40034, N01AI40034]; NIDA NIH HHS [DA 016156]; NIDDK NIH HHS [DK 066936] NR 43 TC 79 Z9 81 U1 1 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 FEB 20 PY 2007 VL 104 IS 8 BP 2879 EP 2884 DI 10.1073/pnas.0611267104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 140NC UT WOS:000244511200057 PM 17299041 ER PT J AU Yue, HF Jansen, SA Strauss, KI Borenstein, MR Barbe, MF Rossi, LJ Murphy, E AF Yue, Hongfei Jansen, Susan A. Strauss, Kenneth I. Borenstein, Michael R. Barbe, Mary F. Rossi, Luella J. Murphy, Elise TI A liquid chromatography/mass spectrometric method for simultaneous analysis of arachidonic acid and its endogenous eicosanoid metabolites prostaglandins, dihydroxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids in rat brain tissue SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE LC/MS; brain tissue; arachidonic acid; prostaglandins (PGs); hydroxyeicosatetraenoic acids (HETEs); dihydroxyeicosatrienoic acids (DiHETrEs); epoxyeicosatrienoic acids (EETs) ID TANDEM MASS-SPECTROMETRY; ELECTROSPRAY-IONIZATION; SIMULTANEOUS QUANTIFICATION; FLUORESCENCE DETECTION; BIOANALYTICAL METHODS; P-450 METABOLITES; METHOD VALIDATION; INJURY; INFLAMMATION; CYCLOOXYGENASE-2 AB A sensitive, specific, and robust liquid chromatography/mass spectrometric (LC/MS) method was developed and validated that allows simultaneous analysis of arachidonic acid (AA) and its cyclooxygenase, cytochrome P450, and lipoxygenase pathway metabolites prostaglandins (PGs), dihydroxyeicosatrienoic acids (DiHETrEs), hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs), including PGF(2 alpha), PGE(2), PGD(2), PGJ(2),14,15-DiHETrE, 11, 12-DiHETrE, 8,9-DiHETrE, 5,6-DiHETrE, 20-HETE, 15-HETE, 12-HETE, 9-HETE, 8-HETE, 5-HETE, 14,15-EET, 11, 12-EET, 8,9-EET, and 5,6-EET in rat brain tissues. Deuterium labeled PGF(2 alpha)-d(4), PGD(2)-d(4), 15(S)-HETE-d(8), 14,15-EET-d(8), 11,12-EET-d(8), 8,9-EET-d(8), and AA-d(8) were used as intemal standards. Solid phase extraction was used for sample preparation. A gradient LUMS method using a C18 column and electrospray ionization source under negative ion mode was optimized for the best sensitivity and separation within 35 min. The method validation, including LUMS instrument qualification, specificity, calibration model, accuracy, precision (without brain matrix and with brain matrix), and extraction efficiency were performed. The linear ranges of the calibration curves were 2-1000 pg for PGs, DiHETrEs, HETEs, and EETs, 10-2400 pg for PGE(2) and PGD(2), and 20-2000 ng for AA, respectively. (c) 2006 Published by Elsevier B.V. C1 Temple Univ, Dept Chem, Philadelphia, PA 19122 USA. Univ Cincinnati, Coll Med, Dept Neurosurg, Cincinnati, OH 45267 USA. US FDA, Philadelphia, PA 19106 USA. Temple Univ, Sch Pharm, Philadelphia, PA 19140 USA. Temple Univ, Dept Phys Therapy, Philadelphia, PA 19140 USA. RP Jansen, SA (reprint author), Temple Univ, Dept Chem, 1901 N 13th St, Philadelphia, PA 19122 USA. EM suebee@temple.edu FU NINDS NIH HHS [R01 NS038654, R01 NS038654-04] NR 59 TC 63 Z9 63 U1 1 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD FEB 19 PY 2007 VL 43 IS 3 BP 1122 EP 1134 DI 10.1016/j.jpba.2006.10.009 PG 13 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 142BG UT WOS:000244623000045 PM 17125954 ER PT J AU Osorio, M Bray, MD Walker, RI AF Osorio, Manuel Bray, Mechelle D. Walker, Richard I. TI Vaccine potential for inactivated shigellae SO VACCINE LA English DT Article DE inactivated bacteria; enteric vaccines; dendritic cells ID ENTEROTOXIGENIC ESCHERICHIA-COLI; HUMAN DENDRITIC CELLS; IMMUNE-RESPONSES; FLEXNERI 2A; PROTECTIVE EFFICACY; CROSS-PROTECTION; CHOLERA VACCINE; HELICOBACTER-PYLORI; ORAL IMMUNIZATION; FIELD TRIAL AB We used human monocyte-derived dendritic cells (DC) and Balb/c mice as models to establish the immunogenic and protective potential of formalin-inactivated Shigella spp. Incubation of DC with inactivated or live bacteria induced DC maturation and cytokine release. Mice immunized orally or intranasally with killed S. flexneri, S. sonnei, or S. dysenteriae developed IgG and fecal IgA titers to the homologous LIPS. Following respiratory challenge with the live homologous organisms, 80-100% survival was seen in all vaccinated groups compared to negligible survival in mice given PBS. Oral or intranasal immunization with an inactivated S. flexneri 2a strain (CVD 1203) expressing the CFA/I and CS3 antigens of enterotoxigenic Escherichia coli induced IgG responses to both heterologous antigens. These in vivo and in vitro data indicate that inactivated shigellae retain the ability to interact effectively with key antigen presenting cells and induce protective immune responses in mice. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Walker, RI (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM Richard.Walker@fda.hhs.gov NR 41 TC 17 Z9 18 U1 0 U2 0 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 FEB 19 PY 2007 VL 25 IS 9 BP 1581 EP 1592 DI 10.1016/j.vaccine.2006.11.012 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 135MX UT WOS:000244158800003 PM 17178431 ER PT J AU Burkhart, BA Kennett, SB Archer, TK AF Burkhart, Barbara A. Kennett, Sarah B. Archer, Trevor K. TI Osmotic stress-dependent repression is mediated by histone H3 phosphorylation and chromatin structure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TRANSFORMED MOUSE FIBROBLASTS; B-INDUCED PHOSPHORYLATION; GLUCOCORTICOID-RECEPTOR; CHROMOSOME CONDENSATION; MITOTIC PHOSPHORYLATION; SER-10 PHOSPHORYLATION; BETAINE TRANSPORTER; KIDNEY-CELLS; IN-VIVO AB Histone H3 phosphorylation has been linked to various environmental stress responses and specific chromatin structure. The role of H3 phosphorylation in the osmotic stress response was investigated on the mouse mammary tumor virus (MMTV) promoter in different chromatin configurations. Hormone-dependent transcription from the MMTV promoter is repressed by osmotic stress when the promoter is integrated and has a normal chromatin structure. However, when the MMTV promoter is transiently transfected, the chromatin structure is less organized, and hormone induction is not affected by osmotic stress. On the integrated MMTV promoter, phosphorylation of histone H3 serine 10 and 28 increases in response to osmotic stress, but the transient promoter shows no change. Hormone-dependent glucocorticoid receptor binding is reduced on the repressed promoter, and elevated H3 phosphorylation is temporally correlated with maximal MMTV repression Additionally, the protein kinase C inhibitor rottlerin, but not other kinase inhibitors, blocks both histone H3 phosphorylation and osmotic repression of MMTV transcription. Glucocorticoid receptor binding is inversely correlated with H3 phosphorylation, suggesting that displacement of the glucocorticoid receptor from the promoter is due to H3 phosphorylation and is the mechanism for the osmotic repression of hormone-dependent transcription. C1 Interagcy Oncol Task Force Food & Drug Adm, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIEHS, Lab Mol Carcinogenesis, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), Interagcy Oncol Task Force Food & Drug Adm, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA. EM archer1@niehs.nih.gov FU Intramural NIH HHS NR 44 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 16 PY 2007 VL 282 IS 7 BP 4400 EP 4407 DI 10.1074/jbc.M609041200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 140CX UT WOS:000244482000020 PM 17158874 ER PT J AU Jia, YP Buehler, PW Boykins, RA Venable, RM Alayash, AI AF Jia, Yiping Buehler, Paul W. Boykins, Robert A. Venable, Richard M. Alayash, Abdu I. TI Structural basis of peroxide-mediated changes in human hemoglobin - A novel oxidative pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOMBINANT HUMAN ALPHA-1-ANTITRYPSIN; CROSS-LINKED HEMOGLOBIN; HEME PROSTHETIC GROUP; HYDROGEN-PEROXIDE; METHIONINE OXIDATION; CIRCULAR-DICHROISM; FREE-RADICALS; IN-VITRO; PROTEIN; MYOGLOBIN AB Hydrogen peroxide (H2O2) triggers a redox cycle between ferric and ferryl hemoglobin (Hb) leading to the formation of a transient protein radical and a covalent hemeprotein cross-link. Addition of H2O2 to highly purified human hemoglobin (HbA(0)) induced structural changes that primarily resided within beta subunits followed by the internalization of the heme moiety within a subunits. These modifications were observed when an equal molar concentration of H2O2 was added to HbA(0) yet became more abundant with greater concentrations of H2O2. Mass spectrometric and amino acid analysis revealed for the first time that beta Cys-93 and beta Cys-112 were oxidized extensively and irreversibly to cysteic acid when HbA(0) was treated with H2O2. Oxidation of further amino acids in HbA(0) exclusive to the beta-globin chain included modification of beta Trp-15 to oxyindolyl and kynureninyl products as well as beta Met-55 to methionine sulfoxide. These findings may therefore explain the premature collapse of the beta subunits as a result of the H2O2 attack. Analysis of a tryptic digest of the main reversed phase-high pressure liquid chromatography fraction revealed two a-peptide fragments (alpha 128 - alpha 139) and a heme moiety with the loss of iron, cross-linked between alpha Ser-138 and the porphyrin ring. The novel oxidative pathway of HbA(0) modification detailed here may explain the diverse oxidative, toxic, and potentially immunogenic effects associated with the release of hemoglobin from red blood cells during hemolytic diseases and/or when cell-free Hb is used as a blood substitute. C1 Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA. Food & Drug Adm, Ctr Biol Evaluat & Res, Biophys Lab, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. NHLBI, Membrane Biophys Sect, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov NR 47 TC 58 Z9 58 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 FEB 16 PY 2007 VL 282 IS 7 BP 4894 EP 4907 DI 10.1074/jbc.M609955200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 140CX UT WOS:000244482000072 PM 17178725 ER PT J AU Voetsch, AC Angulo, FJ Jones, TF Moore, MR Nadon, C McCarthy, P Shiferaw, B Megginson, MB Hurd, S Anderson, BJ Cronquist, A Vugia, DJ Medus, C Segler, S Graves, LM Hoekstra, RM Griffin, PM AF Voetsch, Andrew C. Angulo, Frederick J. Jones, Timothy F. Moore, Matthew R. Nadon, Celine McCarthy, Patrick Shiferaw, Beletshachew Megginson, Melanie B. Hurd, Sharon Anderson, Bridget J. Cronquist, Alicia Vugia, Duc J. Medus, Carlota Segler, Suzanne Graves, Lewis M. Hoekstra, Robert M. Griffin, Patricia M. CA Ctr Dis Control Prevention Emergin TI Reduction in the incidence of invasive listeriosis in Foodborne Diseases Active Surveillance Network sites, 1996-2003 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MEXICAN-STYLE CHEESE; RAW-MILK CHEESE; UNITED-STATES; MONOCYTOGENES INFECTION; SPORADIC LISTERIOSIS; MULTISTATE OUTBREAK; MYCOBACTERIUM-BOVIS; DIARRHEAL ILLNESS; HUMAN BRUCELLOSIS; FOODNET AB Background. Listeriosis is a leading cause of death among patients with foodborne diseases in the United States. Monitoring disease incidence is an important element of listeriosis surveillance and control. Method. We conducted population-based surveillance for Listeria monocytogenes isolates obtained from normally sterile sites at all clinical diagnostic laboratories in the Foodborne Diseases Active Surveillance Network from 1996 through 2003. Results. The incidence of laboratory-confirmed invasive listeriosis decreased by 24% from 1996 through 2003; pregnancy-associated disease decreased by 37%, compared with a decrease of 23% for patients >= 50 years old. The highest incidence was reported among Hispanic persons from 1997 through 2001. Differences in incidence by age group and ethnicity may be explained by dietary preferences. Conclusion. The marked decrease in the incidence of listeriosis may be related to the decrease in the prevalence of L. monocytogenes contamination of ready-to-eat foods since 1996. The crude incidence in 2003 of 3.1 cases per 1 million population approaches the government's Healthy People objective of 2.5 cases per 1 million population by 2005. Further decreases in listeriosis incidence will require continued efforts of industry and government to reduce contamination of food and continued efforts to educate consumers and clinicians. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Resp Dis Branch, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Biostat & Informat Management Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Georgia Emerging Infect Program, Atlanta, GA USA. Tennessee Dept Hlth, Nashville, TN USA. USDA, Food Safety & Inspect Serv, Washington, DC 20250 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20250 USA. Oregon Dept Human Serv, Portland, OR USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. Connecticut Emerging Infect Program, New Haven, CT USA. New York State Dept Hlth, Albany, NY 12201 USA. Colorado Dept Publ Hlth & Environm, Denver, CO USA. Minnesota Dept Hlth, St Paul, MN USA. Calif Dept Hlth Serv, Richmond, CA USA. RP Voetsch, AC (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, 1600 Clifton Rd,Mailstop E 46, Atlanta, GA 30333 USA. EM AVoetsch@cdc.gov NR 39 TC 53 Z9 56 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 FEB 15 PY 2007 VL 44 IS 4 BP 513 EP 520 DI 10.1086/511006 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 127PB UT WOS:000243597700009 PM 17243053 ER PT J AU Varma, JK Samuel, MC Marcus, R Hoekstra, RM Medus, C Segler, S Anderson, BJ Jones, TF Shiferaw, B Haubert, N Megginson, M McCarthy, PV Graves, L Van Gilder, T Angulo, FJ AF Varma, Jay K. Samuel, Michael C. Marcus, Ruthanne Hoekstra, Robert M. Medus, Carlota Segler, Suzanne Anderson, Bridget J. Jones, Timothy F. Shiferaw, Beletshachew Haubert, Nicole Megginson, Melanie McCarthy, Patrick V. Graves, Lewis Van Gilder, Thomas Angulo, Frederick J. TI Listeria monocytogenes infection from foods prepared in a commercial establishment: A case-control study of potential sources of sporadic illness in the United States SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RISK-FACTORS; FOODBORNE LISTERIOSIS; EPIDEMIC LISTERIOSIS; OUTBREAK; ASSOCIATION; PERSPECTIVE; MEAT AB Background. Listeria monocytogenes has been estimated to cause 12500 illnesses and 500 deaths annually in the United States. Efforts to reduce foodborne listeriosis have focused on foods frequently implicated in outbreaks. Potential sources for L. monocytogenes infection not associated with outbreaks remain poorly understood. Methods. The Foodborne Diseases Active Surveillance Network conducts surveillance for culture-confirmed listeriosis at clinical laboratories in 9 states. After excluding outbreak-associated cases, we attempted to enroll eligible case patients with L. monocytogenes infection in a case-control study from 2000 through 2003. Control subjects were recruited through health care providers and were matched to case patients by state, age, and immunosuppression status. Data were collected about exposures occurring in the 4 weeks before specimen collection from the case patients. Results. Of the 249 case patients with L. monocytogenes infection, only 12 (5%) had cases that were associated with outbreaks; 6 other patients were ineligible for other reasons. Of 231 eligible case patients, 169 (73%) were enrolled in the study. We classified 28 case patients as having pregnancy-associated cases. We enrolled 376 control subjects. In multivariable analysis, L. monocytogenes infection was associated with eating melons at a commercial establishment ( odds ratio, 2.6; 95% confidence interval, 1.4-5.0)and eating hummus prepared in a commercial establishment ( odds ratio, 5.7; 95% confidence interval, 1.7-19.1). Conclusions. Most cases of L. monocytogenes infection were not associated with outbreaks. Reducing the burden of foodborne listeriosis may require interventions directed at retail environments and at foods, such as melons and hummus, that are not commonly recognized as high risk. Because of the severity of listeriosis, pregnant women and other persons at risk may wish to avoid eating these newly implicated foods. C1 Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Biostat & Informat Management, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Georgia Emerging Infect Program, Atlanta, GA USA. Calif Emerging Infect Program, Oakland, CA USA. Connecticut Emerging Infect Program, New Haven, CT USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. Tennesse Dept Hlth, Nashville, TN USA. New York Dept Hlth, Albany, NY USA. Oregon Dept Human Serv, Portland, OR USA. Colorado Dept Publ Hlth & Environm, Denver, CO USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD USA. US FDA, College Pk, MD USA. RP Angulo, FJ (reprint author), Ctr Dis Control & Prevent, Epidem Intelligence Serv, Mailstop D63,1600 Clifton Rd, Atlanta, GA 30333 USA. EM fangulo@cdc.gov NR 48 TC 67 Z9 72 U1 1 U2 11 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 FEB 15 PY 2007 VL 44 IS 4 BP 521 EP 528 DI 10.1086/509920 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 127PB UT WOS:000243597700010 PM 17243054 ER PT J AU Cieslak, J Kauffman, JS Kolodziejski, MJ Lloyd, JR Beaucage, SL AF Cieslak, Jacek Kauffman, Jon S. Kolodziejski, Michelle J. Lloyd, John R. Beaucage, Serge L. TI Assessment of 4-nitrogenated benzyloxymethyl groups for 2 '-hydroxyl protection in solid-phase RNA synthesis SO ORGANIC LETTERS LA English DT Article ID CHEMICAL-SYNTHESIS; 2'-O-PROTECTING FUNCTIONS; OLIGORIBONUCLEOTIDES; INTERFERENCE; NUCLEOTIDES; ACETALS AB The search for a 2'-OH protecting group that would impart ribonucleoside phosphoramidites with coupling kinetics and coupling efficiencies comparable to those of deoxyribonucleoside phosphoramidites led to an assessment of 2'-O-(4-nitrogenated benzyloxy)methyl groups through solid-phase RNA synthesis using phosphoramidites 2a-d, 12a, and 14a. These phosphoramidites exhibited rapid and efficient coupling properties. Particularly noteworthy is the cleavage of the 2'-O-[4-(N-methylamino)benzyloxy]methyl groups in 0.1 M AcOH, which led to U(19)dT within 15 min at 90 degrees C. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Lancaster Labs, Lancaster, PA 17605 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Cieslak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM serge.beaucage@fda.hhs.gov NR 25 TC 16 Z9 16 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD FEB 15 PY 2007 VL 9 IS 4 BP 671 EP 674 DI 10.1021/ol0629824 PG 4 WC Chemistry, Organic SC Chemistry GA 133UQ UT WOS:000244039800032 PM 17256869 ER PT J AU Chilakapati, J Korrapati, MC Shankar, K Hill, RA Warbritton, A Latendresse, JR Mehendale, HM AF Chilakapati, Jaya Korrapati, Midhun C. Shankar, Kartik Hill, Ronald A. Warbritton, Alan Latendresse, John R. Mehendale, Harihara M. TI Role of CYP2E1 and saturation kinetics in the bloactivation of thioacetamide: Effects of diet restriction and phenobarbital SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE cyp2e1 knockouts; diet restriction; phenobarbital; liver injury; thioacetamide ID LIVER-TISSUE REPAIR; DOSE-DEPENDENT METABOLISM; INDUCED HEPATIC-NECROSIS; CALORIC RESTRICTION; RAT-LIVER; FISCHER-344 RAT; VINYL-CHLORIDE; DIABETIC-RATS; S-OXIDE; TOXICITY AB Thioacetamide (TA) undergoes saturation toxicokinetics in ad libitum (AL) fed rats. Diet restriction (DR) protects rats from lethal dose of TA despite increased bioactivation-mediated liver injury via CYP2E1 induction. While a low dose (50 mg TA/kg) produces 6-fold higher initial injury, a 12-fold higher dose produces delayed and mere 2.5-fold higher injury. The primary objective was to determine if this less-than-expected increase in injury is due to saturation toxicokinetics. Rats on AL and DR for 21 days received either 50 or 600 mg TA/kg i.p. T-1/2 and AUCs for TA and TA-S-oxide were consistent with saturable kinetics. Covalent binding of C-14-TA-derived-radiolabel to liver macromolecules after low dose was 2-fold higher in DR than AL rats. However, following lethal dose, no differences were found between AL and DR. This lack of dose-dependent response appears to be due to saturation of bioactivation at the higher dose. The second objective was to investigate the effect of phenobarbital pretreatment (PB) on TA-initiated injury following a sub-lethal dose (500 mg/kg). PB induced CYP2B1/2 similar to 350-fold, but did not increase covalent binding of C-14-TA, TA-induced liver injury and mortality, suggesting that CYP2B1/2 has no major role in TA bioactivation. The third objective was to investigate the role of CYP2E1 using cyp2e1 knockout mice (KO). Injury was assessed over time (0-48 h) in wild type (WT) and KO mice after LD100 dose (500 mg/kg) in WT. While WT mice exhibited robust injury which progressed to death, KO mice exhibited neither initiation nor progression of injury. These findings confirm that CYP2E1 is responsible for TA bioactivation. (c) 2006 Elsevier Inc. All rights reserved. C1 NE Louisiana Univ, Dept Toxicol, Coll Pharm, Monroe, LA 71209 USA. NE Louisiana Univ, Div Basic Pharmaceut Sci RAH, Coll Pharm, Monroe, LA 71209 USA. Arkansas Childrens Nutr Ctr, Little Rock, AR USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Dept Toxicol, Coll Pharm, 700 Univ Ave,Sugar Hall 306, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 FU NIEHS NIH HHS [ES-09870] NR 50 TC 16 Z9 16 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB 15 PY 2007 VL 219 IS 1 BP 72 EP 84 DI 10.1016/j.taap.2006.11.036 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 140IQ UT WOS:000244498600009 PM 17234228 ER PT J AU Chilakapati, J Korrapati, MC Hill, RA Warbritton, A Latendresse, JR Mehendale, HM AF Chilakapati, Jaya Korrapati, Midhun C. Hill, Ronald A. Warbritton, Alan Latendresse, John R. Mehendale, Harihara M. TI Toxicokinetics and toxicity of thioacetamide sulfoxide: a metabolite of thioacetamide SO TOXICOLOGY LA English DT Article DE thioacetamide; thioacetamide sulfoxide; liver injury; bioactivation; saturation ID INDUCED HEPATIC-NECROSIS; DIET-RESTRICTED RATS; LIVER-TISSUE REPAIR; MEDIATES PROGRESSION; DIABETIC-RATS; S-OXIDE; HEPATOTOXICITY; INJURY; MICE; SURVIVAL AB Thioacetamide (TA) is bioactivated by CYP2E1 to TA sulfoxide (TASO), and to the highly reactive sulfdioxide (TASO(2)), which initiates hepatic necrosis by covalent binding. Previously, we have established that TA exhibits saturation toxicokinetics over a 12-fold dose range, which explains the lack of dose-response for bioactivation-based liver injury. In vivo and in vitro studies indicated that the second step (TASO -> TASO(2)) of TA bioactivation is less efficient than the first one (TA -> TASO). The objective of the present study was to specifically test the saturation of the second step of TA bioactivation by directly administering TASO, which obviates the contribution from first step, i.e. TA -> TASO. Male SD rats were injected with low (50 mg/kg, ip), medium (100 mg/kg) and high (LD70, 200 mg/kg) doses of TASO. Bioactivation-mediated liver injury that occurs in the initial time points (6 and 12 h), estimated by plasma ALT, AST and liver histopathology over a time course, was not dose-proportional. Escalation of liver injury thereafter was dose dependent: low dose injury subsided; medium dose injury escalated upto 36 h before declining; high dose injury escalated from 24 h leading to 70% mortality. TASO was quantified in plasma by HPLC at various time points after administration of the three doses. With increasing dose (i.e., from 50 to 200 mg/kg), area under the curve (AUC) and C-max increased more than dose proportionately, indicating that TASO bioactivation exhibits saturable kinetics. Toxicokinetics and initiation of liver injury of TASO are similar to that of TA, although TASO-initiated injury occurs at lower doses. These findings indicate that bioactivation of TASO to its reactive metabolite is saturable in the rat as suggested by previous studies with TA. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Univ Louisiana Monroe, Coll Pharm, Dept Basic Pharmaceut Sci, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 FU NIEHS NIH HHS [ES-09870] NR 32 TC 37 Z9 37 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD FEB 12 PY 2007 VL 230 IS 2-3 BP 105 EP 116 DI 10.1016/j.tox.2006.11.050 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 138QI UT WOS:000244376900001 PM 17187915 ER PT J AU Ahmad, SR AF Ahmad, Syed Rizwanuddin TI Safety of recommended doses of paracetamol SO LANCET LA English DT Letter ID OVERDOSES C1 US FDA, Ctr Drug Evaluat & Res, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Ahmad, SR (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, HFD-430,MS 3411,WO22 Rm 3464,10903 New Hampshire, Silver Spring, MD 20993 USA. EM syed.ahmad@fda.hhs.gov NR 4 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD FEB 10 PY 2007 VL 369 IS 9560 BP 462 EP 463 DI 10.1016/S0140-6736(07)60229-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 135XX UT WOS:000244188300024 PM 17292760 ER PT J AU Kim, W Ahn, H Moon, H AF Kim, Wonkuk Ahn, Hongshik Moon, Hojin TI A dose-response test via closed-form solutions for constrained MLEs in survival/sacrifice experiments SO STATISTICS IN MEDICINE LA English DT Article DE animal carcinogenicity experiments; competing risks; dose response; survival function; tumour onset ID SURVIVAL SACRIFICE EXPERIMENTS; MAXIMUM-LIKELIHOOD ESTIMATORS; OF-DEATH INFORMATION; POLY-K TEST; ANIMAL CARCINOGENICITY; TUMOR-INCIDENCE; BODY-WEIGHT; TREND; ONSET; TIME AB In most survival-sacrifice experiments in animal carcinogenicity studies, the onset of the tumour of interest is not clinically observable. Due to the complexity of constraints for a biological justification, recently developed methods for estimating the tumour onset function and tumour-specific survival function employ computer-intensive numerical solutions. In this paper, closed-form solutions for nonparametric maximum likelihood estimators are derived under explicit and implicit inequality constraints obtained from the monotonicity of the survival functions. Our methods do not require cause-of-death information. The proposed methods can be used to estimate the tumour onset function and the survival function of the tumour of interest. We use the proposed estimators for the development of our new dose-response trend test. A modification of the Poly-k test is made by replacing the time-at-risk weight to a function of the tumour onset survival function. The weighted least square regression method is applied to the estimated survival functions in order to construct a dose-response trend test. A simulation study is conducted to evaluate the performance of the proposed test and compare it with existing trend tests. A real example is used to illustrate the methods. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ahn, H (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. EM hahn@ams.stonybrook.edu NR 36 TC 1 Z9 2 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 10 PY 2007 VL 26 IS 3 BP 694 EP 708 DI 10.1002/sim.2549 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 126KI UT WOS:000243511400016 PM 16596576 ER PT J AU Li, JS Eisenstein, EL Grabowski, HG Reid, ED Mangum, B Schulman, KA Goldsmith, JV Murphy, MD Califf, RM Benjamin, DK AF Li, Jennifer S. Eisenstein, Eric L. Grabowski, Henry G. Reid, Elizabeth D. Mangum, Barry Schulman, Kevin A. Goldsmith, John V. Murphy, M. Dianne Califf, Robert M. Benjamin, Daniel K., Jr. TI Economic return of clinical trials performed under the pediatric exclusivity program SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TREATING DEPRESSION; CHILDREN; ANTIDEPRESSANTS; PATENTS; RISK AB Context In 1997, Congress authorized the US Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children and has been criticized as a "windfall" to the innovator drug industry. This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007. Objective To quantify the economic return to industry for completing pediatric exclusivity trials. Design and Setting A cohort study of programs conducted for pediatric exclusivity. Nine drugs that were granted pediatric exclusivity were selected. From the final study reports submitted to the FDA (2002-2004), key elements of the clinical trial design and study operations were obtained, and the cost of performing each study was estimated and converted into estimates of after-tax cash outflows. Three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return ( cash inflows minus outflows) and net return-to-costs ratio ( net economic return divided by cash outflows) for each product were then calculated. Main Outcome Measures Net economic return and net return-to-cost ratio. Results The indications studied reflect a broad representation of the program: asthma, tumors, attention-deficit/hyperactivity disorder, hypertension, depression/ generalized anxiety disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of exclusivity varied substantially among products ( net economic return ranged from -$ 8.9 million to $507.9 million and net return-to-cost ratio ranged from - 0.68 to 73.63). Conclusions The economic return for pediatric exclusivity is variable. As an incentive to complete much-needed clinical trials in children, pediatric exclusivity can generate lucrative returns or produce more modest returns on investment. C1 Duke Univ, Duke Clin Res Inst, Dept Pediat, Durham, NC 27705 USA. Duke Univ, Dept Econ, Durham, NC 27705 USA. US FDA, Off Policy & Planning, Rockville, MD 20857 USA. US FDA, Off Pediat Therapeut, Rockville, MD 20857 USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Li, JS (reprint author), Duke Univ, Duke Clin Res Inst, Dept Pediat, POB 17969, Durham, NC 27705 USA. EM jennifer.li@duke.edu FU NCRR NIH HHS [UL1 RR024128, 1UL 1RR024128-01, UL1 RR024128-01]; NICHD NIH HHS [1U10-HD45962-02, HD-044799-02, K23 HD044799, K23 HD044799-02, U10 HD045962, U10 HD045962-02] NR 18 TC 79 Z9 81 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 7 PY 2007 VL 297 IS 5 BP 480 EP 488 DI 10.1001/jama.297.5.480 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 133FP UT WOS:000243999100025 PM 17284698 ER PT J AU Kirkland, DJ Hayashi, M Jacobson-Kram, D Kasper, P MacGregor, JT Muller, L Uno, Y AF Kirkland, D. J. Hayashi, M. Jacobson-Kram, D. Kasper, P. MacGregor, J. T. Muller, L. Uno, Y. TI The International Workshops on Genotoxicity Testing (IWGT): History and achievements SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Editorial Material DE genotoxicity testing; IWGT workshops; history ID GENE MUTATION ASSAY; MICRONUCLEUS ASSAY; WORKGROUP REPORT; WORKING GROUP; IN-VITRO C1 Covance Labs Ltd, Harrogate HG3 1PY, England. Natl Inst Hlth Sci, Setagaya Ku, Tokyo 1588501, Japan. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD USA. BfArM, D-53175 Bonn, Germany. Toxicol Consulting Serv, Arnold, MD 21012 USA. PRBNT, Safety & Tech Sci, CH-4070 Basel, Switzerland. Mitsubishi Pharma Co, Toxicol Lab, Chiba 2920818, Japan. RP Kirkland, DJ (reprint author), Covance Labs Ltd, Otley Rd, Harrogate HG3 1PY, England. EM david.kirkland@covance.com NR 18 TC 5 Z9 6 U1 0 U2 2 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 FEB 3 PY 2007 VL 627 IS 1 SI SI BP 1 EP 4 DI 10.1016/j.mrgentox.2006.08.012 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 134KG UT WOS:000244081300001 PM 17127092 ER PT J AU Kirkland, DJ Hayashi, M Jacobson-Kram, D Kasper, P MacGregor, JT Muller, L Uno, Y AF Kirkland, D. J. Hayashi, M. Jacobson-Kram, D. Kasper, P. MacGregor, J. T. Muller, L. Uno, Y. TI Summary of major conclusions from the 4th IWGT, San Francisco, 9-10 September, 2005 SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Editorial Material DE genotoxicity; IWGT workshop; conclusions ID GENOTOXICITY TEST PROCEDURES; GENE MUTATION ASSAY; INTERNATIONAL WORKSHOP; WORKGROUP REPORT; PHARMACEUTICALS C1 Covance Labs Ltd, Harrogate HG3 1PY, England. Natl Inst Hlth Sci, Setagaya Ku, Tokyo 1588501, Japan. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD USA. BfArM, D-53175 Bonn, Germany. Toxicol Consulting Serv, Arnold, MD 21012 USA. PRBNT, Safety & Tech Sci, CH-4070 Basel, Switzerland. Mitsubishi Pharma Co, Toxicol Lab, Chiba 2920818, Japan. RP Kirkland, DJ (reprint author), Covance Labs Ltd, Otley Rd, Harrogate HG3 1PY, England. EM david.kirkland@covance.com NR 15 TC 27 Z9 29 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 FEB 3 PY 2007 VL 627 IS 1 SI SI BP 5 EP 9 DI 10.1016/j.mrgentox.2006.08.009 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 134KG UT WOS:000244081300002 PM 17137830 ER PT J AU Moore, MM Honma, M Clements, J Bolcsfoldi, G Burlinson, B Cifone, M Clarke, J Clay, P Doppalapudi, R Fellows, M Gollapudi, B Hou, S Jenkinson, P Muster, W Pant, K Kidd, DA Lorge, E Lloyd, M Myhr, B O'Donovan, M Riach, C Stankowski, LF Thakur, AK Van Goethem, F AF Moore, Martha M. Honma, Masamitsu Clements, Julie Bolcsfoldi, George Burlinson, Brian Cifone, Maria Clarke, Jane Clay, Philip Doppalapudi, Rupa Fellows, Michael Gollapudi, Bhaskar Hou, Saimei Jenkinson, Peter Muster, Wolfgang Pant, Kamala Kidd, Darren A. Lorge, Elisabeth Lloyd, Melvyn Myhr, Brian O'Donovan, Michael Riach, Colin Stankowski, Leon F., Jr. Thakur, Ajit K. Van Goethem, Freddy TI Mouse lymphoma thymidine kinase gene mutation assay: Meeting of the International Workshop on Genotoxicity Testing, San Francisco, 2005, recommendations for 24-h treatment SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE mouse lymphoma assay; in vitro mutation; thymidine kinase ID WORKGROUP REPORT AB The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Testing (IWGT), comprised of experts from Japan, Europe and the United States, met on September 9,2005, in San Francisco, CA, USA. This meeting of the MLA Workgroup was devoted to reaching a consensus on issues involved with 24-h treatment. Recommendations were made concerning the acceptable values for the negative/solvent control (mutant frequency, cloning efficiency and suspension growth) and the criteria to define an acceptable positive control response. Consensus was also reached concerning the use of the global evaluation factor (GEF) and appropriate statistical trend analysis to define positive and negative responses for the 24-h treatment. The Workgroup agreed to continue their support of the International Committee on Harmonization (ICH) recommendation that the MLA assay should include a 24-h treatment (without S-9) in those situations where the short treatment (3-4 h) gives negative results. (c) 2006 Elsevier B.V. All rights reserved. C1 Food & Drug Adm, DGRT, NCTR, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. Covance Labs Ltd, Harrogate, N Yorkshire, England. AstraZeneca R&D, Safety Assessment, Sodertalje, Sweden. Huntingdon Life Sci, Huntingdon, England. Covance Labs Inc, Vienna, VA USA. BioReliance Invitrogen Bioserv, Rockville, MD USA. Drug Safety Assessment, Servier Grp, F-45403 Orleans, France. SRI Int, Menlo Pk, CA USA. AstraZeneca R&D, Safety Assessment, Macclesfield, Cheshire, England. Dow Chem Co USA, TERC, Midland, MI 48674 USA. Safepharm Labs Ltd, Shardlow, Derby, England. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. Syngenta CTL, Macclesfield SK10 4TJ, Cheshire, England. Genotox Consulting, Bethesda, MD USA. Charles River Labs, Edinburgh, Midlothian, Scotland. Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. RP Moore, MM (reprint author), Food & Drug Adm, DGRT, NCTR, Natl Ctr Toxicol Res, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Martha.Moore@fda.hhs.gov NR 6 TC 28 Z9 32 U1 1 U2 7 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 FEB 3 PY 2007 VL 627 IS 1 SI SI BP 36 EP 40 DI 10.1016/j.mrgentox.2006.08.013 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 134KG UT WOS:000244081300005 PM 17157054 ER PT J AU Thybaud, V Aardema, M Clements, J Dearfield, K Galloway, S Hayashi, M Jacobson-Kram, D Kirkland, D MacGregor, JT Marzin, D Ohyama, W Schuler, M Suzuki, H Zeiger, E AF Thybaud, V. Aardema, M. Clements, J. Dearfield, K. Galloway, S. Hayashi, M. Jacobson-Kram, D. Kirkland, D. MacGregor, J. T. Marzin, D. Ohyama, W. Schuler, M. Suzuki, H. Zeiger, E. TI Strategy for genotoxicity testing: Hazard identification and risk assessment in relation to in vitro testing SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE genotoxicity; hazard identification; risk assessment; testing strategy ID BIOLOGICAL RELEVANCE; GENETIC TOXICITY; CHEMICALS; PHARMACEUTICALS; MUTAGENICITY; GUIDELINES AB This report summarizes the proceedings of the September 9-10, 2005 meeting of the Expert Working Group on Hazard Identification and Risk Assessment in Relation to In Vitro Testing, part of an initiative on genetic toxicology. The objective of the Working Group was to develop recommendations for interpretation of results from tests commonly included in regulatory genetic toxicology test batteries, and to propose an appropriate strategy for follow-up testing when positive in vitro results were obtained in these assays. The Group noted the high frequency of positive in vitro findings in the genotoxicity test batteries with agents found not to be carcinogenic and thought not to pose a carcinogenic health hazard to humans. The Group agreed that a set of consensus principles for appropriate interpretation and follow-up testing when initial in vitro tests are positive was needed. Current differences in emphasis and policy among different regulatory agencies were recognized as a basis of this need. Using a consensus process among a balanced, up of recognized international authorities from industry, government, and academia, it was agreed that a strategy based on these principles should include guidance on: (1) interpretation of initial results in the "core" test battery; (2) criteria for determining when follow-up testing is needed; (3) criteria for selecting appropriate follow-up tests; (4) definition of when the evidence is sufficient to define the mode of action and the relevance to human exposure; and (5) definition of approaches to evaluate the degree of health risk under conditions of exposure of the species of concern (generally the human). A framework for addressing these issues was discussed, and a general "decision tree" was developed that included criteria for assessing the need for further testing, selecting appropriate follow-up tests, and determining a sufficient weight of evidence to attribute a level of risk and stop testing. The discussion included case studies based on actual test results that illustrated common situations encountered, and consensus opinions were developed based on group analysis of these cases. The Working Group defined circumstances in which the pattern and magnitude of positive results was such that there was very low or no concern (e.g., nonreproducible or marginal responses), and no further testing would be needed. This included a discussion of the importance of the use of historical control data. The criteria for determining when follow-up testing is needed included factors, such as evidence of reproducibility, level of cytotoxicity at which an increased DNA damage or mutation frequency is observed, relationship of results to the historical control range of values, and total weight of evidence across assays. When the initial battery is negative, further testing might be required based on information from the published literature, structure activity considerations, or the potential for significant human metabolites not generated in the test systems. Additional testing might also be needed retrospectively when increase in tumors or evidence of pre-neoplastic change is seen. When follow-up testing is needed, it should be based on knowledge about the mode of action, based on reports in the literature or learned from the nature of the responses observed in the initial tests. The initial findings, and available information about the biochemical and pharmacological nature of the agent, are generally sufficient to conclude that the responses observed are consistent with certain molecular mechanisms and inconsistent with others. Follow-up tests should be sensitive to the types of genetic damage known to be capable of inducing the response observed initially. It was recognized that genotoxic events might arise from processes other than direct reactivity with DNA, that these mechanisms may have a non-linear, or threshold, dose-response relationship, and that in such cases it may be possible to determine an exposure level below which there is negligible concern about an effect due to human exposures. When a test result is clearly positive, consideration of relevance to human health includes whether other assays for the same endpoint support the results observed, whether the mode or mechanism of action is relevant to the human, and most importantly - whether the effect observed is likely to occur in vivo at concentrations expected as a result of human exposure. Although general principles were agreed upon, time did not permit the development of recommendations for the selection of specific tests beyond those commonly employed in initial test batteries. (c) 2006 Elsevier B.V. All rights reserved. C1 Drug Safety Evaluat, F-94400 Vitry Sur Seine, France. Procter & Gamble Co, Cincinnati, OH 45253 USA. USDA, Off Publ Hlth Sci, Food Safety & Inspect Serv, Washington, DC 20250 USA. Merck Res Labs, West Point, PA 19486 USA. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. Toxicol Consulting Serv, Arnold, MD 21012 USA. Inst Pasteur, F-59019 Lille, France. Yakult Cent Inst Microbiol Res, Tokyo 1868650, Japan. Pfizer Inc, Global Res & Dev, Groton, CT 06340 USA. Ina Res Inc, Nagano 3994501, Japan. Errol Zeiger Consulting, Chapel Hill, NC 27514 USA. RP Thybaud, V (reprint author), Drug Safety Evaluat, F-94400 Vitry Sur Seine, France. EM Veronique.Thybaud@sanofi-aventis.com NR 43 TC 69 Z9 71 U1 2 U2 7 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 FEB 3 PY 2007 VL 627 IS 1 SI SI BP 41 EP 58 DI 10.1016/j.mrgentox.2006.10.003 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 134KG UT WOS:000244081300006 PM 17126066 ER PT J AU Ku, WW Bigger, A Brambilla, G Glatt, H Gocke, E Guzzie, PJ Hakura, A Honma, M Martus, HJ Obach, RS Roberts, S AF Ku, Warren W. Bigger, Anita Brambilla, Giovanni Glatt, Hansruedi Gocke, Elmar Guzzie, Peggy J. Hakura, Atsushi Honma, Masamitsu Martus, Hans-Joerg Obach, R. Scott Roberts, Stanley TI Strategy for genotoxicity testing - Metabolic considerations SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE genotoxicity; metabolism; testing; strategy ID SALMONELLA-MICROSOME TEST; HUMAN LIVER-MICROSOMES; RAT-LIVER; CARCINOGENIC ACTIVITY; ORGANIC-SOLVENTS; B6C3F1 MICE; AMES TEST; IN-VITRO; ACTIVATION; SULFOTRANSFERASE AB The report from the 2002 International Workshop on Genotoxicity Tests (IWGT) Strategy Expert Group emphasized metabolic considerations as an important area to address in developing a common strategy for genotoxicity testing. A working group convened at the 2005 4th IWGT to discuss this area further and propose practical strategy recommendations. To propose a strategy, the working group reviewed: (1) the current status and deficiencies, including examples of carcinogens "missed" in genotoxicity testing, established shortcomings of the standard in vitro induced S9 activation system and drug metabolite case examples; (2) the current status of possible remedies, including alternative S9 sources, other external metabolism systems or genetically engineered test systems; (3) any existing positions or guidance. The working group established consensus principles to guide strategy development. Thus, a human metabolite of interest should be represented in genotoxicity and carcinogenicity testing, including evaluation of alternative genotoxicity in vitro metabolic activation or test systems, and the selection of a carcinogenicity test species showing appropriate biotransformation. Appropriate action triggers need to be defined based on the extent of human exposure, considering any structural knowledge of the metabolite, and when genotoxicity is observed upon in vitro testing in the presence of metabolic activation. These triggers also need to be considered in defining the timing of human pharmaceutical ADME assessments. The working group proposed two strategies to consider; a more proactive approach, which emphasizes early metabolism predictions to drive appropriate hazard assessment;, and a retroactive approach to manage safety risks of a unique or "major" metabolite once identified and quantitated from human clinical ADME studies. In both strategies, the assessment of the genotoxic potential of a metabolite could include the use of an alternative or optimized in vitro metabolic activation system, or direct testing of an isolated or synthesized metabolite. The working group also identified specific areas where more data or experiences need to be gained to reach consensus. These included defining a discrete exposure action trigger for safety assessment and when direct testing of a metabolite of interest is warranted versus the use of an alternative in vitro activation system, a universal recommendation for the timing of human ADME studies for drug candidates and the positioning of metabolite structural knowledge (through in silico systems, literature, expert analysis) in supporting metabolite safety qualification. Lastly, the working group outlined future considerations for refining the initially proposed strategies. These included the need for further evaluation of the current in vitro genotoxicity testing protocols that can potentially perturb or reduce the level of metabolic activity (potential alterations in metabolism associated with both the use of some solvents to solubilize test chemicals and testing to the guidance limit dose), and proposing broader evaluations of alternative metabolic activation sources or engineered test systems to further challenge the suitability of (or replace) the current induced liver S9 activation source. (c) 2006 Elsevier B.V. All rights reserved. C1 Pfizer Inc, Global Res & Dev, Drug Safety Res & Dev, Groton, CT 06340 USA. US FDA, CDER, Div Antiviral Prod, Silver Spring, MD 20993 USA. Univ Genoa, Div Clin Pharmacol & Toxicol, Dept Internal Med, I-16132 Genoa, Italy. German Inst Human Nutr Potsdam Rehbrucke, D-14558 Nuthetal, Germany. F Hoffmann La Roche & Co Ltd, Preclin Safety, CH-4070 Basel, Switzerland. Eisai & Co Ltd, Drug Safety Res Labs, Gifu 5016195, Japan. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 1588501, Japan. Novartis Pharma AG, Exploratory Dev, Genet Toxicol & Safety Pharmacol, CH-4002 Basel, Switzerland. Pfizer Inc, Global Res & Dev, Pharmacokinet Dynam & Metab, Groton, CT 06340 USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Ku, WW (reprint author), Pfizer Inc, Global Res & Dev, Drug Safety Res & Dev, Groton, CT 06340 USA. EM warren.w.ku@pfizer.com OI Glatt, Hansruedi/0000-0001-6053-0562 NR 73 TC 55 Z9 58 U1 0 U2 13 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 FEB 3 PY 2007 VL 627 IS 1 SI SI BP 59 EP 77 DI 10.1016/j.mrgentox.2006.10.004 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 134KG UT WOS:000244081300007 PM 17141553 ER PT J AU Tweats, DJ Blakey, D Heflich, RH Jacobs, A Jacobsen, SD Morita, T Nohmi, T O'Donovan, MR Sasaki, YF Sofuni, T Tice, R AF Tweats, D. J. Blakey, D. Heflich, R. H. Jacobs, A. Jacobsen, S. D. Morita, T. Nohmi, T. O'Donovan, M. R. Sasaki, Y. F. Sofuni, T. Tice, R. TI Report of the IWGT working group on strategies and interpretation of regulatory in vivo tests - I. Increases in micronucleated bone marrow cells in rodents that do not indicate genotoxic hazards SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE IWGT; genotoxicity tests; in vivo; rodent bone marrow; micronucleus; specificity; false positive; changes in physiology; hypothermia; hyperthermia; spindle disruption; erythropoiesis; bone marrow cell toxicity; pharmacologically related changes; regulatory implications ID HAMSTER OVARY CELLS; HYDRAZINE DERIVATIVES; ANILINE HYDROCHLORIDE; ERYTHROPOIETIN; HYPERTHERMIA; HYPOTHERMIA; INDUCTION; ASSAY; RATS; MICE AB In vivo genotoxicity tests play a pivotal role in genotoxicity testing batteries. They are used both to determine if potential genotoxicity observed in vitro is realised in vivo and to detect any genotoxic carcinogens that are poorly detected in vitro. It is recognised that individual in vivo genotoxicity tests have limited sensitivity but good specificity. Thus, a positive result from the established in vivo assays is taken as strong evidence for genotoxic carcinogenicity of the compound tested. However, there is a growing body of evidence that compound-related disturbances in the physiology of the rodents used in these assays can result in increases in micronucleated cells in the bone marrow that are not related to the intrinsic genotoxicity of the compound under test. For rodent bone marrow or peripheral blood micronucleus tests, these disturbances include changes in core body temperature (hypothermia and hyperthermia) and increases in erythropoiesis following prior toxicity to erythroblasts or by direct stimulation of cell division in these cells. This paper reviews relevant data from the literature and also previously unpublished data obtained from a questionnaire devised by the IWGT working group. Regulatory implications of these findings are discussed and flow diagrams have been provided to aid in interpretation and decision-making when such changes in physiology are suspected. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Coll Swansea, Ctr Mol Genet & Toxicol, Swansea, W Glam, Wales. Hlth Canada, Safe Environm Programme, Ottawa, ON K1A 0L2, Canada. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20852 USA. Novo Nordisk AS, Malov, Denmark. Natl Inst Hlth Sci, Div Safety Informat Drug Food & Chem, Tokyo 158, Japan. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 158, Japan. Safety Assessment UK, Macclesfield, Cheshire, England. Hachinohe Inst Technol, Hachinohe, Aomori, Japan. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 158, Japan. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Tweats, DJ (reprint author), Univ Coll Swansea, Ctr Mol Genet & Toxicol, Swansea, W Glam, Wales. EM djtweats@fish.co.uk NR 45 TC 56 Z9 57 U1 0 U2 2 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 FEB 3 PY 2007 VL 627 IS 1 SI SI BP 78 EP 91 DI 10.1016/j.mrgentox.2006.10.005 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 134KG UT WOS:000244081300008 PM 17116417 ER PT J AU Tweats, DJ Blakey, D Heflich, RH Jacobs, A Jacobsen, SD Morita, T Nohmi, T O'Donovan, MR Sasaki, YF Sofuni, T Tice, R AF Tweats, D. J. Blakey, D. Heflich, R. H. Jacobs, A. Jacobsen, S. D. Morita, T. Nohmi, T. O'Donovan, M. R. Sasaki, Y. F. Sofuni, T. Tice, R. TI Report of the IWGT working group on strategy/interpretation for regulatory in vivo tests - II. Identification of in vivo-only positive compounds in the bone marrow micronucleus test SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE IWGT; genotoxicity tests; in vivo; rodent bone marrow; micronucleus test; in vivo-only positive compounds; ADME; in vitro versus in vivo metabolism; sex-specific metabolism; influence of gut flora; pharmacological mechanisms; kinase inhibitors; regulatory implication; pharmaceuticals; cosmetics; food additives; in vitro-only genotoxicity test batteries ID ETHYL CARBAMATE URETHANE; CHROMOSOMAL DAMAGE; HUMAN-LYMPHOCYTES; TRANSGENIC MICE; GENOTOXICITY; SALICYLAZOSULFAPYRIDINE; MUTAGENICITY; METABOLISM; INDUCTION; CELLS AB A survey conducted as part of an International Workshop on Genotoxicity Testing (IWGT) has identified a number of compounds that appear to be more readily detected in vivo than in vitro. The reasons for this property varies from compound to compound and includes metabolic differences; the influence of gut flora; higher exposures in vivo compared to in vitro; effects on pharmacology, in particular folate depletion or receptor kinase inhibition. It is possible that at least some of these compounds are detectable in vitro if a specific in vitro test is chosen as part of the test battery, but the 'correct' choice of test may not always be obvious when testing a compound of unknown genotoxicity. It is noted that many of the compounds identified in this study interfere with cell cycle kinetics and this can result in either aneugenicity or chromosome breakage. A decision tree is outlined as a guide for the evaluation of compounds that appear to be genotoxic agents in vivo but not in vitro. The regulatory implications of these findings are discussed. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Coll Swansea, Ctr Mol Genet & Toxicol, Swansea, W Glam, Wales. Hlth Canada, Safe Environm Programme, Ottawa, ON K1A 0L2, Canada. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20852 USA. Novo Nordisk AS, Malov, Denmark. Natl Inst Hlth Sci, Div Safety Informat Drug Food & Chem, Setagaya Ku, Tokyo, Japan. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 158, Japan. Safety Assessment UK, Macclesfield, Cheshire, England. Hachinohe Inst Technol, Hachinohe, Aomori, Japan. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 158, Japan. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Tweats, DJ (reprint author), Univ Coll Swansea, Ctr Mol Genet & Toxicol, Swansea, W Glam, Wales. EM djtweats@fish.co.uk FU Intramural NIH HHS [Z99 ES999999] NR 40 TC 29 Z9 32 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 FEB 3 PY 2007 VL 627 IS 1 SI SI BP 92 EP 105 DI 10.1016/j.mrgentox.2006.10.006 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 134KG UT WOS:000244081300009 PM 17113817 ER PT J AU Kasper, P Uno, Y Mauthe, R Asano, N Douglas, G Matthews, E Moore, M Mueller, L Nakajima, M Singer, T Speit, G AF Kasper, Peter Uno, Yoshifumi Mauthe, Robert Asano, Norihide Douglas, George Matthews, Edwin Moore, Martha Mueller, Lutz Nakajima, Madoka Singer, Tim Speit, Guenter TI Follow-up testing of rodent carcinogens not positive in the standard genotoxicity testing battery: IWGT workgroup report SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE IWGT; genetic toxicology testing; organ-specificity; mode of action; carcinogenicity testing; transgenic mutation assay; comet assay; DNA adducts ID DRUG CYPROTERONE-ACETATE; EXOGENOUS SEX STEROIDS; DNA-REPAIR SYNTHESIS; NO-EFFECT LEVEL; IN-VIVO; RAT-LIVER; GENETIC TOXICOLOGY; CHEMICAL-STRUCTURE; MUTAGENIC-ACTIVITY; MUTATION ASSAYS AB At the Plymouth Third International Workshop on Genotoxicity Testing in June 2002, a new expert group started a working process to provide guidance on a common strategy for genotoxicity testing beyond the current standard battery. The group identified amongst others "Follow-up testing of tumorigenic agents not positive in the standard genotoxicity test battery" as one subject for further consideration [L. Muller, D. Blakey, K.L. Dearfield, S. Galloway, P. Guzzie, M. Hayashi, P. Kasper, D. Kirkland, IT. MacGregor, J.M. Parry, L. Schechtman, A. Smith, N. Tanaka, D. Tweats, H. Yamasaki, Strategy for genotoxicity testing and stratification of genotoxicity test results-report on initial activities of the IWGT Expert Group, Mutat. Res. 540 (2003) 177-181]. A workgroup devoted to this topic was formed and met on September 9-10, 2005, in San Francisco. This workgroup was devoted to the discussion of when it would be appropriate to conduct additional genetic toxicology studies, as well as what type of studies, if the initial standard battery of tests was negative, but tumor formation was observed in the rodent carcinogenicity assessment. The important role of the standard genetic toxicology testing to determine the mode of action (MOA) for carcinogenesis (genotoxic versus non-genotoxic) was discussed, but the limitations of the standard testing were also reviewed. The workgroup also acknowledged that the entire toxicological profile (e.g. structure-activity relationships, the nature of the tumor finding and metabolic profiles) of a compound needed to be taken into consideration before the conduct of any additional testing. As part of the meeting, case studies were discussed to understand the practical application of additional testing as well as to form a decision tree. Finally, suitable additional genetic toxicology assays to help determine the carcinogenic MOA or establish a weight of evidence (WOE) argument were discussed and formulated into a decision tree. (c) 2006 Elsevier B.V. All rights reserved. C1 Fed Inst Drugs & Med Devices, BfArM, D-53175 Bonn, Germany. Mitsubishi Pharma Co, Toxicol Lab, Chiba, Japan. Pfizer Global Res & Dev, Ann Arbor, MI USA. Nitto Denko Corp, Toxicol Res Ctr, Osaka, Japan. Hlth Canada, Mutagenesis Sect, Ottawa, ON K1A 0L2, Canada. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Hoffmann La Roche Ag, Safety & Tech Sci, CH-4002 Basel, Switzerland. Biosafety Res Ctr, Shizuoka, Japan. Univ Ulm, Ulm, Germany. RP Kasper, P (reprint author), Fed Inst Drugs & Med Devices, BfArM, Kurt Georg Kiesinger Allee 3, D-53175 Bonn, Germany. EM p.kasper@bfarm.de NR 49 TC 10 Z9 11 U1 0 U2 2 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 FEB 3 PY 2007 VL 627 IS 1 SI SI BP 106 EP 116 DI 10.1016/j.mrgentox.2006.10.007 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 134KG UT WOS:000244081300010 PM 17123861 ER PT J AU Beach, D Gonen, R Bogin, Y Reischl, IG Yablonski, D AF Beach, Dvora Gonen, Ronnie Bogin, Yaron Reischl, Ilona G. Yablonski, Deborah TI Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE PHOSPHORYLATION; PLASMA-MEMBRANE; ANTIGEN RECEPTOR; DIFFERENTIAL ROLE; PROTEIN NETWORKS; LIPID RAFTS; LAT LINKER; C-GAMMA; PLC-GAMMA-1; DOMAIN AB Phospholipase C-gamma 1 (PLC-gamma 1) activation depends on a heterotrimeric complex of adaptor proteins composed of LAT, Gads, and SLP-76. Upon T cell receptor stimulation, a portion of PLC-gamma 1 is recruited to a detergent-resistant membrane fraction known as the glycosphingolipid-enriched membrane microdomains (GEMs), or lipid rafts, to which LAT is constitutively localized. In addition to LAT, PLC-gamma 1 GEM recruitment depended on SLP-76, and, in particular, required the Gads-binding domain of SLP-76. The N-terminal tyrosine phosphorylation sites and P-I region of SLP-76 were not required for PLC-gamma 1 GEM recruitment, but were required for PLC-gamma 1 phosphorylation at Tyr(783). Thus, GEM recruitment can be insufficient for full activation of PLC-gamma 1 in the absence of a second SLP-76-mediated event. Indeed, a GEM-targeted derivative of PLC-gamma 1 depended on SLP-76 for T cell receptor-induced phosphorylation at Tyr(783) and subsequent NFAT activation. On a biochemical level, SLP-76 inducibly associated with both Vav and catalytically active ITK, which efficiently phosphorylated a PLC-gamma 1 fragment at Tyr(783) in vitro. Both associations were disrupted upon mutation of the N-terminal tyrosine phosphorylation sites of SLP-76. The P-I region deletion disrupted Vav association and reduced SLP-76-associated kinase activity. A smaller deletion within the P-I region, which does not impair PLC-gamma 1 activation, did not impair the association with Vav, but reduced SLP-76-associated kinase activity. These results provide new insight into the multiple roles of SLP-76 and the functional importance of its interactions with other signaling proteins. C1 Technion Israel Inst Technol, Rappaport Fac Med, Rappaport Family Inst Res Med Sci, IL-31096 Haifa, Israel. US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Yablonski, D (reprint author), Technion Israel Inst Technol, Rappaport Fac Med, Rappaport Family Inst Res Med Sci, POB 9649 Bat Galim, IL-31096 Haifa, Israel. EM debya@tx.technion.ac.il NR 57 TC 29 Z9 31 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 2 PY 2007 VL 282 IS 5 BP 2937 EP 2946 DI 10.1074/jbc.M606697200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130IS UT WOS:000243793900020 PM 17148460 ER PT J AU Baron, S Hernandez, J Bekisz, J Poast, J Goldman, N Clouse, K Fields, K Bacot, S Wang, J Zoon, K AF Baron, Samuel Hernandez, Jessica Bekisz, Joseph Poast, Joyce Goldman, Neil Clouse, Kathleen Fields, Karen Bacot, Sylvia Wang, Jiun Zoon, Kathryn TI Clinical model: Interferons activate human monocytes to an eradicative tumor cell level in vitro SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID CENTRIFUGAL ELUTRIATION CCE; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; ADOPTIVE IMMUNOTHERAPY; MACROPHAGE ACTIVATION; EFFECTOR-CELLS; PERITONEAL-MACROPHAGES; ENRICHED FRACTIONS; MONONUCLEAR-CELLS; DENDRITIC CELLS AB Eradicative levels of antitumor activity by cytokines and leukocytes have not yet been reached experimentally and are needed clinically. Only a limited number of human cancers respond to therapy with interferon (IFN), other cytokines, or mononuclear leukocytes despite significant antitumor activity in vitro. We studied the IFN and monocytic cell conditions that would lead to an eradicative effect using human cells in vitro. Targets of the IFN-activated monocytic cells were either four human tumor cell lines (human osteosarcoma [HOS], LOX melanoma, A549 lung tumor, and SNB-19 glioblastoma) or two diploid cell lines (W138 and MRC5). An average of 30-90 colony-forming tumor target cells were cultured overnight in 96-well tissue culture plates prior to treatment with serially diluted IFN with or without activated elutriation-purified monocytes or lymphocytes. The target cell colonies were treated for 3 days. The colonies were then stained with crystal violet to determine the levels of antitumor activity. IFN-activated human monocytes reached an eradicative level (95%-100%) against three of four tumor cell lines. The eradicative level (1) was induced best in human monocytes activated by combined type I and II IFNs, (2) was effective against tumor cells that were growing for 24 h, (3) was specific for human tumors, as diploid human cells were not inhibited, and (4) required contact between the macrophage and the tumor cells. Also, for the first time, the minimal effective concentration (MEC) of IFNs to activate monocytes can approach those needed for antiviral activity. To our knowledge, this is the first report of near total eradication of many tumor cells, but not diploid cells, by IFN-activated monocytes. Because of its potency and specificity, the IFN-activated monocyte arm of the innate immune system may be a candidate for therapy of established tumors. C1 Univ Texas, Med Branch, Galveston, TX 77555 USA. NCI, NIH, Bethesda, MD 20892 USA. Food & Drug Adm, Bethesda, MD 20892 USA. RP Baron, S (reprint author), Univ Texas, Med Branch, Galveston, TX 77555 USA. EM sabaron@utmb.edu NR 65 TC 7 Z9 9 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD FEB 2 PY 2007 VL 27 IS 2 BP 157 EP 163 DI 10.1089/jir.2006.0083 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 140SG UT WOS:000244526400010 PM 17316143 ER PT J AU Grajkowski, A Ausin, C Kauffman, JS Snyder, J Hess, S Lloyd, JR Beaucage, SL AF Grajkowski, Andrzej Ausin, Cristina Kauffman, Jon S. Snyder, John Hess, Sonja Lloyd, John R. Beaucage, Serge L. TI Solid-phase synthesis of thermolytic DNA oligonucleotides functionalized with a single 4-hydroxy-1-butyl or 4-phosphato-/thiophosphato-1-butyl thiophosphate protecting group SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SULFUR-TRANSFER REAGENT; OLIGODEOXYRIBONUCLEOSIDE PHOSPHOROTHIOATES; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; 2'-TETRAHYDROFURANYL PROTECTION; 3-(PIVALOYLOXY)PROPYL GROUPS; PROOLIGONUCLEOTIDE APPROACH; PHOSPHORAMIDITE APPROACH; EFFICIENT REAGENT; PRODRUGS; PHOSPHODIESTER AB Several thermolytic CpG-containing DNA oligonucleotides analogous to 1 have been synthesized to serve as potential immunotherapeutic oligonucleotide prodrug formulations for the treatment of infectious diseases in animal models. Specifically, the CpG motif (GACGTT) of each DNA oligonucleotide has been functionalized with either the thermolabile 4-hydroxy-1-butyl or the 4-phosphato-/thiophosphato-1-butyl thiophosphate protecting group. This functionalization was achieved through incorporation of activated deoxyribonucleoside phosphoramidite 8b into the oligonucleotide chain during solid-phase synthesis and, optionally, through subsequent phosphorylation effected by phosphoramidite 9. Complete conversion of CpG ODNs hbu1555, psb1555, and pob1555 to CpG ODN 1555 (homologous to 2) occurred under elevated temperature conditions, thereby validating the function of these diastereomeric oligonucleotides as prodrugs in vitro. Noteworthy is the significant increase in solubility of CpG ODN psb1555 and CpG pob1555 in water when compared to that of neutral CpG ODN fma1555 (homologous to 1). C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Lancaster Labs, Lancaster, PA 17605 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM Serge.Beaucage@fda.hhs.gov RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 NR 44 TC 11 Z9 11 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD FEB 2 PY 2007 VL 72 IS 3 BP 805 EP 815 DI 10.1021/jo062087y PG 11 WC Chemistry, Organic SC Chemistry GA 129NF UT WOS:000243735500017 PM 17253799 ER PT J AU Kan, VL Manischewitz, J King, LR Golding, H AF Kan, Virginia L. Manischewitz, Jody King, Lisa R. Golding, Hana TI Durable neutralizing antibodies after remote smallpox vaccination among adults with and without HIV infection SO AIDS LA English DT Article ID PLASMA-CELLS; ANTIVIRAL IMMUNITY; MEASLES; PERSISTENCE; POPULATION; MEMORY; VIRUS AB The only US licensed vaccine with established efficacy against smallpox, Dryvax, is contraindicated for HIV patients. Detectable smallpox-neutralizing antibodies are still present among US adults. This study compared vaccinia-neutralizing antibody titers between 20 HIV-infected and 20 uninfected veterans matched for age and military entry. Vaccinia-neutralizing antibodies were detected in 95% HIV-infected and 100% uninfected veterans; 40% HIV-infected and 70% uninfected adults had protective titers. Therefore, after robust vaccination, neutralizing antibodies are maintained for prolonged times despite CD4 cell depletion. C1 Vet Affairs Med Ctr, Infect Dis Sect, Washington, DC 20422 USA. FDA, CBER, Div Viral Prod, Bethesda, MD USA. RP Kan, VL (reprint author), Vet Affairs Med Ctr, Infect Dis Sect, 50 Irving St NW, Washington, DC 20422 USA. NR 17 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD FEB 1 PY 2007 VL 21 IS 4 BP 521 EP 524 DI 10.1097/QAD.0b013e32802f7d7c PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 146BR UT WOS:000244910000017 PM 17301573 ER PT J AU Osmanov, S Ackland, J Allen, S Barth-Jones, D Birx, D Chomba, E Churchyard, G Duerr, A Jin, SG Johnston, M Fast, PE Fix, A Foulkes, M Follmann, D Hutubessy, R Malone, S Gray, R Indrayan, A Levin, J Mathieson, BJ Mastro, TD McNeil, J Pitisuttithum, P Peters, B Karita, E Robertson, MN Ramakrishnan, R Rees, H Rida, W Ruan, YH Sandstrom, E Schmidt, C Smith, P Self, S Thiry, G Wasserheit, J Priddy, F Thior, I Warren, M Cooper, D Kaleebu, P Macklin, R Tangwa, G AF Osmanov, Saladin Ackland, Jim Allen, Susan Barth-Jones, Daniel Birx, Deborah Chomba, Elwyn Churchyard, Gavin Duerr, Ann Jin, Shiugao Johnston, Margaret Fast, Patricia E. Fix, Alan Foulkes, Mary Follmann, Dean Hutubessy, Raymond Malone, Siobhan Gray, Ronald Indrayan, Abhay Levin, Jonathan Mathieson, Bonnie J. Mastro, Timothy D. McNeil, John Pitisuttithum, Punnee Peters, Barry Karita, Etienne Robertson, Michael N. Ramakrishnan, R. Rees, Helen Rida, Wasima Ruan, Yuhua Sandstrom, Eric Schmidt, Claudia Smith, Peter Self, Steven Thiry, Georges Wasserheit, Judith Priddy, Frances Thior, Ibou Warren, Mitchell Cooper, David Kaleebu, Pontiano Macklin, Ruth Tangwa, Godfrey CA WHO UNAIDS IAVI Intl Expert Grp TI Executive summary and recommendations from the WHO/UNAIDS/IAVI expert group consultation on 'Phase IIB-TOC trials as a novel strategy for evaluation of preventive HIV vaccines', 31 January-2 February 2006, IAVI, New York, USA SO AIDS LA English DT Article DE clinical trial design; HIV vaccines; phase IIB trials; proof of concept trials; test of concept trials; vaccine efficacy ID RANDOMIZED CONTROLLED-TRIAL; HUMAN-PAPILLOMAVIRUS TYPE-16; PARTICLE VACCINE; YOUNG-WOMEN; EFFICACY; INFECTION; WORKSHOP AB This report summarizes the discussions and recommendations from a consultation held in New York City, USA (31 January-2 February 2006) organized by the joint World Health Organization-United Nations Programme on HIV/AIDS HIV Vaccine Initiative and the International AIDS Vaccine Initiative. The consultation discussed issues related to the design and implementation of phase IIB 'test of concept' trials (phase IIB-TOC), also referred to as 'proof of concept' trials, in evaluating candidate HIV vaccines and their implications for future approval and licensure. The results of a single phase IIB-TOC trial would not be expected to provide sufficient evidence of safety or efficacy required for licensure. In many instances, phase IIB-TOC trials may be undertaken relatively early in development, before manufacturing processes and capacity are developed sufficiently to distribute the vaccine on a large scale. However, experts at this meeting considered the pressure that could arise, particularly in regions hardest hit by AIDS, if a phase IIB-TOC trial showed high levels of efficacy. The group largely agreed that full-scale phase III trials would still be necessary to demonstrate that the vaccine candidate was safe and effective, but emphasized that governments and organizations conducting trials should consider these issues in advance. The recommendations from this meeting should be helpful for all organizations involved in HIV vaccine trials, in particular for the national regulatory authorities in assessing the utility of phase IIB-TOC trials in the overall HIV vaccine research and development process. (c) 2007 Lippincott Williams & Wilkins. C1 Global BioSolut, Craigieburn, Vic, Australia. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Wayne State Univ, Sch Med, Pediat Prevent Res Ctr, Detroit, MI 48202 USA. Ctr Dis Control & Prevent, GAP, Global AIDS Program, Atlanta, GA USA. Zambia Emory HIV Res Project, Lusaka, Zambia. Ernest Oppenheimer Hosp, Welkom, South Africa. HIV Vaccine Trials Network, Sci Support Unit, Seattle, WA USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. NIAID, Vaccine & Prevent Res Program, Seattle, WA USA. Int AIDS Vaccine Initiat, New York, NY USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. WHO, UNAIDS HIV Vaccine Initiat, CH-1211 Geneva, Switzerland. Bill & Melinda Gates Fdn, Global Hlth Program, Seattle, WA USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Coll Med Sci, Div Biostat & Med Informat, New Delhi, India. Med Res Council S Africa, Pretoria, South Africa. OAR HIV AIDS Vaccine Coordinating Comm, Bethesda, MD USA. Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Mahidol Univ, Fac Trop Med, Dept Clin Trop Med, Bangkok 10700, Thailand. St Thomas Hosp, London, England. Projet San Francisco IAVI, Kigali, Rwanda. Natl Inst Epidemiol, Madras, Tamil Nadu, India. Univ Witwatersrand, Reprod Hlth Res Unit, Dept Obstet & Gynecol, Johannesburg, South Africa. Stat Collaborat, Washington, DC USA. Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. IAVI, New York, NY USA. Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA. HIV Vaccine Trials Network, Seattle, WA USA. Emory Vaccine Ctr, Hope Clin, Decatur, GA USA. Princess Marina Hosp, Botswana Harvard Partnership, Gaborone, Botswana. AIDS Vaccine Advocacy Coalit, New York, NY USA. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Uganda Virus Res Inst, Entebbe, Uganda. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. Univ Yaounde, Yaounde, Cameroon. RP Osmanov, S (reprint author), WHO, UNAIDS HIV Vaccine Initiat, 20 Ave Appia, CH-1211 Geneva, Switzerland. EM osmanovs@who.int NR 9 TC 11 Z9 12 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 FEB 1 PY 2007 VL 21 IS 4 BP 539 EP 546 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 146BR UT WOS:000244910000026 ER PT J AU Myint, MS Johnson, YJ Paige, JC Bautista, DA AF Myint, Maung S. Johnson, Yvette J. Paige, Joseph C. Bautista, Daniel A. TI A cross-sectional study of bacterial contamination in plant-protein feed from feed stores in Northern Virginia and Maryland SO ANIMAL FEED SCIENCE AND TECHNOLOGY LA English DT Article DE animal feed; enteric bacteria; Campylobacter; Salmonella; E. coli; Enterococcus ID SALMONELLA CONTAMINATION; ESCHERICHIA-COLI; POULTRY FEEDS; ANIMAL FEED; ENTEROCOCCI; EPIDEMIOLOGY; ENVIRONMENT; ENTERICA; HUMANS AB The objectives of this study were to estimate the prevalence of the enteric microbes: Escherichia coli, Salmonella, Campylobacter and Entemcoccus spp., in plant-protein-based animal feed products and milk replacer and to identify risk factors associated with contamination by these bacteria. A cross-sectional survey of 158 plant-derived feed and milk replacer samples was conducted using eight animal feed stores in Northern Virginia and Maryland from January 2002 to September 2002. Overall all samples were negative for Campylobacter; one sample (0.6%) was positive for Salmonella; nine samples (5.7%) were positive for E. coli and 80 samples (50.6%) were positive for Enterococcus. Positive samples included: whole maize, cracked peanut, cotton seed, mixed grain horse feed, and milk replacer. Samples collected during the month of January (winter) had a lower prevalence of contamination with enteric bacteria than samples collected in August and September (summer/autumn). Samples collected in January 2002 were negative for both E. coli and Salmonella. Samples collected in August and September 2002 included one Salmonella positive, and nine E. coli positive. Animal feed purchased during August and September had a 38-fold increase (95% Cl: 15.60-95.16) in the risk of contamination by Enterococcus than those samples purchased during January and February of that same year (P < 0.001). Enterococcus positive samples were eight times more likely to also be E. coli positive than Enterococcus negative samples (95% Cl: 1.04-70.12). Non-pelleted feed was 13 times more likely to be contaminated with Enterococcus than pelleted feed (95% Cl: 3.02-59.84). (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Illinois, Coll Vet Med, Dept Vet Clin Med, Urbana, IL 61802 USA. Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Maryland Dept Agr, Diagnost Lab, Salisbury, MD 21801 USA. RP Johnson, YJ (reprint author), Univ Illinois, Coll Vet Med, Dept Vet Clin Med, LAC-227,1008 W Hazelwood Dr, Urbana, IL 61802 USA. EM yjjohn38@uiuc.edu NR 43 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0377-8401 J9 ANIM FEED SCI TECH JI Anim. Feed Sci. Technol. PD FEB 1 PY 2007 VL 133 IS 1-2 BP 137 EP 148 DI 10.1016/j.anifeedsci.2006.08.007 PG 12 WC Agriculture, Dairy & Animal Science SC Agriculture GA 129MU UT WOS:000243734400007 ER PT J AU Chen, S Cui, SH McDermott, PF Zhao, SH White, DG Paulsen, I Meng, JH AF Chen, Sheng Cui, Shenghui McDermott, Patrick F. Zhao, Shaohua White, David G. Paulsen, Ian Meng, Jianghong TI Contribution of target gene mutations and efflux to decreased susceptibility of Salmonella enterica serovar Typhimurium to fluoroquinolones and other antimicrobials SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MULTIPLE-ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI; MULTIDRUG-RESISTANCE; UNITED-STATES; QUINOLONE RESISTANCE; PARC MUTATIONS; IN-VITRO; ACRB; PUMPS; GYRA AB The mechanisms involved in fluoroquinolone resistance in Salmonella enterica include target alterations and overexpression of efflux pumps. The present study evaluated the role of known and putative multidrug resistance efflux pumps and mutations in topoisomerase genes among laboratory-selected and naturally occurring fluoroquinolone-resistant Salmonella enterica serovar Typhimurium strains. Strains with ciprofloxacin MICs of 0.25, 4, 32, and 256 mu g/ml were derived in vitro using serovar Typhimurium S21. These mutants also showed decreased susceptibility or resistance to many nonfluoroquinolone antimicrobials, including tetracycline, chloramphenicol, and several beta-lactams. The expression of efflux pump genes acrA, acrB, acrE, acrF, emrB, emrD, and mdlB were substantially increased (>= 2-fold) among the fluoroquinolone-resistant mutants. Increased expression was also observed, but to a lesser extent, with three other putative efflux pumps: mdtB (yegN), mdtC (yegO), and emrA among mutants with ciprofloxacin MICs of >= 32 mu g/ml. Deletion of acrAB or tolC in S21 and its fluoroquinolone-resistant mutants resulted in increased susceptibility to fluoroquinolones and other tested antimicrobials. In naturally occurring fluoroquinolone-resistant serovar Typhimurium strains, deletion of acrAB or tolC increased fluoroquinolone susceptibility 4-fold, whereas replacement of gyrA double mutations (S83F D87N) with wild-type gyrA increased susceptibility > 500-fold. These results indicate that a combination of topoisomerase gene mutations, as well as enhanced antimicrobial efflux, plays a critical role in the development of fluoroquinolone resistance in both laboratory-derived and naturally occurring quinolone-resistant serovar Typhimurium strains. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. Inst Genom Res, Rockville, MD 20860 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu RI Paulsen, Ian/K-3832-2012; OI Paulsen, Ian/0000-0001-9015-9418; Chen, Sheng/0000-0003-3526-7808 NR 51 TC 65 Z9 75 U1 4 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 FEB PY 2007 VL 51 IS 2 BP 535 EP 542 DI 10.1128/AAC.00600-06 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 131WB UT WOS:000243900600019 PM 17043131 ER PT J AU Harris, NB Payeur, J Bravo, D Osorio, R Stuber, T Farrell, D Paulson, D Treviso, S Mikolon, A Rodriguez-Lainz, A Cernek-Hoskins, S Rast, R Ginsberg, M Kinde, H AF Harris, N. Beth Payeur, Janet Bravo, Doris Osorio, Ruben Stuber, Tod Farrell, David Paulson, Debra Treviso, Scarlett Mikolon, Andrea Rodriguez-Lainz, Alfonso Cernek-Hoskins, Shannon Rast, Robert Ginsberg, Michele Kinde, Hailu TI Recovery of Mycobacterium bovis from soft fresh cheese originating in Mexico SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID LENGTH-POLYMORPHISM ANALYSIS; SAN-DIEGO; IDENTIFICATION; TUBERCULOSIS; EPIDEMIOLOGY; CALIFORNIA; CHILDREN; CATTLE; MILK AB Recent outbreaks of human tuberculosis in the United States caused by Mycobacterium bovis have implicated cheese originating in Mexico as a source of these infections. A total of 203 samples of cheese originating in Mexico were cultured, and M. bovis was recovered from one specimen. Therefore, M. bovis can be recovered from cheese and may be a source of human infections. C1 USDA, APHIS, NVSL, Ames, IA 50010 USA. Calif Anim Hlth & Food Safety Lab Syst, San Bernardino, CA 92408 USA. Calif Dept Food & Agr, Anim Hlth & Food Safety Serv, Sacramento, CA 95814 USA. Calif Dept Hlth Serv, Calif Off Binatl Border Hlth, San Diego, CA 92110 USA. US FDA, Off Regulatory Affairs, San Diego, CA 92154 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Cty San Diego HHSA, Community Epidemiol Branch, Publ Hlth Serv, San Diego, CA 92101 USA. RP Harris, NB (reprint author), USDA, APHIS, NVSL, 1800 Dayton Ave, Ames, IA 50010 USA. EM Beth.N.Harris@aphis.usda.gov NR 24 TC 28 Z9 29 U1 0 U2 5 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 FEB PY 2007 VL 73 IS 3 BP 1025 EP 1028 DI 10.1128/AEM.01956-06 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 136ZY UT WOS:000244263800047 PM 17142354 ER PT J AU Curtis, SK Kothary, MH Blodgett, RJ Raybourne, RB Ziobro, GC Tall, BD AF Curtis, S. K. Kothary, M. H. Blodgett, R. J. Raybourne, R. B. Ziobro, G. C. Tall, B. D. TI Rugosity in Grimontia hollisae SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; O1 EL-TOR; VPS BIOSYNTHESIS GENES; VIBRIO-HOLLISAE; BIOFILM FORMATION; EXOPOLYSACCHARIDE PRODUCTION; SEVERE GASTROENTERITIS; SURVIVAL FORM; CHOLERAE; IDENTIFICATION AB Grimontia hollisae, formerly Vibrio hollisae, produces both smooth and rugose colonial variants. The rugose colony phenotype is characterized by wrinkled colonies producing copious amounts of exopolysaccharide. Cells from a rugose colony grown at 30 degrees C form rugose colonies, while the same cells grown at 37 degrees C form smooth colonies, which are characterized by a nonwrinkled, uncrannied appearance. Stress response studies revealed that after exposure to bleach for 30 min, rugose survivors outnumbered smooth survivors. Light scatter information obtained by flow cytometry indicated that rugose cells clumped into clusters of three or more cells (average, five cells) and formed two major clusters, while smooth cells formed only one cluster of single cells or doublets. Fluorescent lectin-binding How cytometry studies revealed that the percentages of rugose cells that bound either wheat germ agglutinin (WGA) or Galanthus nivalis lectin (GNL) were greater than the percentages of smooth cells that bound the same lectins (WGA, 35% versus 3.5%; GNL, 67% versus 0.21%). These results indicate that the rugose exopolysaccharide consists partially of N-acetylglucosamine and mannose. Rugose colonies produced significantly more biofilm material than did smooth colonies, and rugose colonies grown at 30 degrees C produced more biofilm material than rugose colonies grown at 37 degrees C. Ultrastructurally, rugose colonies show regional cellular differentiation, with apical and lateral colonial regions containing cells embedded in a matrix stained by Alcian Blue. The cells touching the agar surface are packed tightly together in a palisade-like manner. The central region of the colony contains irregularly arranged, fluid-filled spaces and loosely packed chains or arrays of coccoid and vibrioid cells. Smooth colonies, in contrast, are flattened, composed of vibrioid cells, and lack distinct regional cellular differences. Results from suckling mouse studies showed that both orally fed rugose and smooth variants elicited significant, but similar, amounts of fluid accumulated in the stomach and intestines. These observations comprise the first report of expression and characterization of rugosity by G. hollisae and raise the possibility that expression of rugose exopolysaccharide in this organism is regulated at least in part by growth temperature. C1 US FDA, Virulence Mech Branch, Div Virulence Assessment, OARSA,Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, College Pk, MD 20740 USA. RP Tall, BD (reprint author), US FDA, Virulence Mech Branch, Div Virulence Assessment, OARSA,Ctr Food Safety & Appl Nutr, HFS 025,Lab 3607,MOD 1 Facil,8301 MuirKirk Rd, Laurel, MD 20708 USA. EM ben.tall@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 NR 39 TC 7 Z9 9 U1 1 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 FEB PY 2007 VL 73 IS 4 BP 1215 EP 1224 DI 10.1128/AEM.02553-06 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 139PG UT WOS:000244443700022 PM 17189437 ER PT J AU Rafii, F Park, M AF Rafii, Fatemeh Park, Miseon TI Substitutions of amino acids in alpha-helix-4 of gyrase A confer fluoroquinolone resistance on Clostridium perfringens SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE fluoroquinolones; gyrase A; mutations; Clostridium; resistance ID URINARY-TRACT-INFECTIONS; QUINOLONE RESISTANCE; ESCHERICHIA-COLI; BACTEROIDES-FRAGILIS; DNA GYRASE; TOPOISOMERASE-IV; ANAEROBIC-BACTERIA; MUTATIONS; CIPROFLOXACIN; DIFFICILE AB DNA gyrase, an essential enzyme that regulates DNA topology in bacteria, is the target of fluoroquinolones. Three fluoroquinolone-resistant mutants derived from one strain of Clostridium perfringens had amino acid substitutions of glycine 81 to cysteine, aspartic acid 87 to tyrosine, or both, in alpha-helix-4 of gyrase A. The gyrase mutations affected the growth kinetics of mutants differently when the mutants were exposed to increasing concentrations of gatifloxacin and ciprofloxacin. Fluoroquinolone concentration-dependent effects observed during growth in the exponential and stationary phases depended on the presence of particular gyrA mutations. Introduction of a wild-type gyrA gene into the mutants enhanced their susceptibility to fluoroquinolones and decreased their growth rates proportional to increases in fluoroquinolone concentrations. Amino acid substitutions in alpha-helix-4 of gyrase A protected C. perfringens from fluoroquinolones, and a strain with two substitutions was the most resistant. C1 Natl Ctr Toxicol Res, Div Microbiol, FDA, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), Natl Ctr Toxicol Res, Div Microbiol, FDA, Jefferson, AR 72079 USA. EM Fatemeh.rafii@fda.hhs.gov NR 32 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD FEB PY 2007 VL 187 IS 2 BP 137 EP 144 DI 10.1007/s00203-006-0180-y PG 8 WC Microbiology SC Microbiology GA 131WV UT WOS:000243903700005 PM 17051403 ER PT J AU Pennello, GA AF Pennello, Gene A. TI Duncan's k-ratio Bayes rule approach to multiple comparisons: An overview SO BIOMETRICAL JOURNAL LA English DT Article; Proceedings Paper CT 4th International Conference on Multiple Comparison Procedures (MCP2005) CY AUG 17-19, 2005 CL Shanghai, PEOPLES R CHINA SP Int Chinese Stat Assoc, Sch Public Hlth, Fudan Univ DE additive losses; comparisonwise; decision theory; empirical Bayes; exchangeability ID T-TESTS; INTERVALS AB An alternative to frequentist approaches to multiple comparisons is Duncan's k-ratio Bayes rule approach. The purpose of this paper is to compile key results on k-ratio Bayes rules for a number of multiple comparison problems that heretofore, have only been available in separate papers or doctoral dissertations. Among other problems, multiple comparisons for means in one-way, two-way, and treatments-vs.-control structures will be reviewed. In the k-ratio approach, the optimal joint rule for a multiple comparisons problem is derived under the assumptions of additive losses and prior exchangeability for the component comparisons. In the component loss function for a comparison, a balance is achieved between the decision losses due to Type I and Type II errors by assuming that their ratio is k. The component loss is also linear in the magnitude of the error. Under the assumption of additive losses, the joint Bayes rule for the component comparisons applies to each comparison the Bayes test for that comparison considered alone. That is, a comparisonwise approach is optimal. However, under prior exchangeability of the comparisons, the component test critical regions adapt to omnibus patterns in the data. For example, for a balanced one-way array of normally distributed means, the Bayes critical t value for a difference between means is inversely related to the F ratio measuring heterogeneity among the means, resembling a continuous version of Fisher's F-protected least significant difference rule. For more complicated treatment structures, the Bayes critical t value for a difference depends intuitively on multiple F ratios and marginal difference(s) (if applicable), such that the critical t value warranted for the difference can range from being as conservative as that given by a familywise rule to actually being anti-conservative relative to that given by the unadjusted 5%-level Student's t test. C1 Food & Drug Adm, Div Biostat, Rockville, MD 20850 USA. RP Pennello, GA (reprint author), Food & Drug Adm, Div Biostat, 1350 Piccard Dr, Rockville, MD 20850 USA. EM gene.pennello@fda.hhs.gov NR 32 TC 0 Z9 0 U1 0 U2 2 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD FEB PY 2007 VL 49 IS 1 BP 78 EP 93 DI 10.1002/bimj.200610292 PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 139FB UT WOS:000244416600008 PM 17342951 ER PT J AU Ng, D Toure, O Wei, MH Arthur, DC Abbasi, F Fontaine, L Marti, GE Fraumeni, JF Goldin, LR Caporaso, N Toro, JR AF Ng, David Toure, Ousmane Wei, Ming-Hui Arthur, Diane C. Abbasi, Fatima Fontaine, Laura Marti, Gerald E. Fraumeni, Joseph F., Jr. Goldin, Lynn R. Caporaso, Neil Toro, Jorge R. TI Identification of a novel chromosome region, 13q21.33-q22.2, for susceptibility genes in familial chronic lymphocytic leukemia SO BLOOD LA English DT Article ID TUMOR-SUPPRESSOR LOCUS; BREAST-CANCER; FLOW-CYTOMETRY; TRANSCRIPTION FACTOR; UNIPARENTAL DISOMY; BAND 13Q14; DELETIONS; CLL; PREDISPOSITION; ABNORMALITIES AB Chronic lymphocytic leukemia (CLL) is the most prevalent form of leukemia in adults in western countries. A genome scan of CLL-prone families revealed a lod score of one in band 13q22.1. To investigate this finding, we selected 6 CLL families consisting of 63 individuals (CLL affected, n = 19; unaffected, n = 44) for fine mapping of a 23-megabase region in 13q14.2-q22.2. Interphase fluorescence in situ hybridization (FISH) revealed 13q14 deletion in 85% (11/13) of CLL patients. Four CLL families shared a 3.68-Mb minimal region in 13q21.33-q22.2. Two asymptomatic siblings who shared the 13q2l.33q22.2 at-risk haplotype exhibited CD5+ monoclonal B-cell lymphocytosis (MBL) on flow cytometry. One of these individuals also had a 13q14 deletion by FISH. These 2 individuals with MBL shared the at-risk haplotype with their CLL-affected relatives, providing further evidence of the relationship between CLL and MBL, as well as of the biologic significance of this novel region. Using direct DNA sequencing analysis, we screened 13 genes for mutations, but no frameshift or nonsense mutations were detected. Our studies revealed that 11 of the 13 genes in the candidate region were expressed in immune tissues, supporting their functional relevance in investigations of familial CLL. In conclusion, we identified a novel candidate region that may predispose to familial CLL. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Program Div Canc Epidemiol & Genet, Frederick, MD USA. NCI, Pathol Lab, Canc Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. US FDA, Flow & Image Cytometry Lab, Cellular Therapy & Tissues Branch, Div Gene & Cell Therapy,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. WESTAT Corp, Rockville, MD 20850 USA. NCI, Off Director, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA. RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S,Rm 7012, Bethesda, MD 20892 USA. EM toroj@mail.nih.gov FU Intramural NIH HHS NR 49 TC 35 Z9 37 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2007 VL 109 IS 3 BP 916 EP 925 DI 10.1182/blood-2006-03-011825 PG 10 WC Hematology SC Hematology GA 135CX UT WOS:000244132800020 PM 17047154 ER PT J AU Rohrmann, S Platz, EA Kavanaugh, CJ Thuita, L Hoffman, SC Helzlsouer, KJ AF Rohrmann, Sabine Platz, Elizabeth A. Kavanaugh, Claudine J. Thuita, Lucy Hoffman, Sandra C. Helzlsouer, Kathy J. TI Meat and dairy consumption and subsequent risk of prostate cancer in a US cohort study SO CANCER CAUSES & CONTROL LA English DT Article DE prostate cancer; meat; dairy; cohort study ID GROWTH-FACTOR-I; ANIMAL PRODUCTS; CALCIUM; DIET; MEN AB Objective: To evaluate the association of meat and dairy food consumption with subsequent risk of prostate cancer. Methods: In 1989, 3,892 men 35+ years old, who participated in the CLUE II study of Washington County, MD, completed an abbreviated Block food frequency questionnaire. Intake of meat and dairy foods was calculated using consumption frequency and portion size. Incident prostate cancer cases (n = 199) were ascertained through October 2004. Cox proportional hazards regression was used to calculate hazard ratios (HR) of total and advanced (SEER stages three and four; n = 54) prostate cancer and 95% confidence intervals (CI) adjusted for age, BMI at age 21, and intake of energy, saturated fat, and tomato products. Intakes of total meat (HR = 0.90, 95% CI 0.60-1.33, comparing highest to lowest tertile) and red meat (HR = 0.87, 95% CI 0.59-1.32) were not statistically significantly associated with prostate cancer. However, processed meat consumption was associated with a non-statistically significant higher risk of total (5+ vs. <= 1 servings/week: HR = 1.53, 95% CI 0.98-2.39) and advanced (HR = 2.24; 95% CI 0.90-5.59) prostate cancer. There was no association across tertiles of dairy or calcium with total prostate cancer, although compared to <= 1 serving/week consumption of 5+ servings/week of dairy foods was associated with an increased risk of prostate cancer (HR = 1.65, 95% CI 1.02-2.66). Conclusion: Overall, consumption of processed meat, but not total meat or red meat, was associated with a possible increased risk of total prostate cancer in this prospective study. Higher intake of dairy foods but not calcium was positively associated with prostate cancer. Further investigation into the mechanisms by which processed meat and dairy consumption might increase the risk of prostate cancer is suggested. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. US FDA, Ctr Food Safety & Nutr, College Pk, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, George W comstock Ctr Publ Hlth Res & Prevent, Baltimore, MD 21205 USA. Mercy Med Ctr, Baltimore, MD USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Rm E 6138, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu RI Rohrmann, Sabine/D-2113-2012 FU NCI NIH HHS [CA08030]; NIA NIH HHS [AG18033] NR 27 TC 65 Z9 68 U1 4 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2007 VL 18 IS 1 BP 41 EP 50 DI 10.1007/s10552-006-0082-y PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119RW UT WOS:000243031800004 PM 17315319 ER PT J AU da Costa, GG Pereira, PC Churchwell, MI Beland, FA Marques, MM AF da Costa, Goncalo Gamboa Pereira, Pedro C. Churchwell, Mona I. Beland, Frederick A. Marques, M. Matilde TI DNA adduct formation in the livers of female Sprague-Dawley rats treated with toremifene or alpha-hydroxytoremifene SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID BREAST-CANCER PATIENTS; K-RAS MUTATION; ENDOMETRIAL CANCER; POSTMENOPAUSAL PATIENTS; PHASE-III; ANTIESTROGEN TOREMIFENE; N-DESMETHYLTAMOXIFEN; ADJUVANT TAMOXIFEN; HORMONE-RECEPTORS; MASS-SPECTROMETRY AB Toremifene, an analogue of tamoxifen in which the ethyl side chain has been replaced with a 2-chloroethyl substituent, is used as a chemotherapeutic agent in postmenopausal women with advanced breast cancer. Toremifene is metabolized in a manner similar to that of tamoxifen, with alpha-hydroxytoremifene being a predominant metabolite in incubations in vitro. DNA adducts have been detected previously in liver DNA upon the administration of toremifene to rats; however, the identity of these adducts is unknown. In the present study, we have characterized the DNA adducts produced by alpha-hydroxytoremifene and have compared the extent of hepatic DNA adduct formation in rats administered toremifene, alpha-hydroxytoremifene, or tamoxifen. alpha-Hydroxytoremifene was synthesized, further activated by sulfation, and then reacted with salmon testis DNA. After enzymatic hydrolysis to deoxynucleosides, HPLC analysis indicated the formation of two major DNA adducts, which were characterized as (E)- and (Z)-alpha-(deoxyguanosin-N-2-yl)toremifene on the basis of H-1 NMR and mass spectral analyses. To assess the formation of toremifene DNA adducts in vivo, female Sprague-Dawley rats were treated intraperitoneally with toremifene, alpha-hydroxytoremifene, or tamoxifen. P-32-Postlabeling analyses of hepatic DNA from the tamoxifen-treated rats indicated three DNA adducts at a total level of 2,200 +/- 270 adducts/10(8) nucleotides. DNA adducts were not detected (< 5 adducts/10(8) nucleotides) in the livers of rats treated with toremifene. Two DNA adducts, of which the major one coeluted with the 3',5'-bis-phosphate of (E)-alpha-(deoxyguanosin-N-2-yl)toremifene, were present at a level of 57 +/- 12 adducts/10(8) nucleotides in hepatic DNA from rats administered alpha-hydroxytoremifene. The low level of hepatic DNA adduct formation observed with both toremifene and alpha-hydroxytoremifene, as compared to that with tamoxifen, may be due to the limited esterification of alpha-hydroxytoremifene and/or the poor reactivity of alpha-sulfoxytoremifene. C1 Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Marques, MM (reprint author), Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, Complexo 1,Av Rovisco Pais, P-1049001 Lisbon, Portugal. EM matilde.marques@ist.utl.pt RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014 OI Marques, M. Matilde/0000-0002-7526-4962; NR 85 TC 5 Z9 5 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD FEB PY 2007 VL 20 IS 2 BP 300 EP 310 DI 10.1021/tx600275d PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 136UA UT WOS:000244248400016 ER PT J AU Williams, AJ Deck, J Freeman, JP Chiarelli, MP Adjei, MD Heinze, TM Sutherland, JB AF Williams, Anna J. Deck, Joanna Freeman, James P. Chiarelli, M. Paul Adjei, Michael D. Heinze, Thomas M. Sutherland, John B. TI Transformation of flumequine by the fungus Cunninghamella elegans SO CHEMOSPHERE LA English DT Article DE fluoroquinolones; fungi; hydroxylation; oxidation; transformation ID PERFORMANCE LIQUID-CHROMATOGRAPHY; METABOLISM; 7-HYDROXYFLUMEQUINE; PHARMACOKINETICS; ENVIRONMENT; AQUACULTURE; TISSUES; PLASMA AB The metabolism of the antibacterial fluoroquinolone drug flumequine by Cunninghamella elegans was investigated using cultures grown in Sabouraud dextrose broth with 308 mu M flumequine. The cultures were extracted with ethyl acetate; metabolites were separated by high-performance liquid chromatography and identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. Flumequine was transformed to two diastereomers of 7-hydroxyflumequine (23 and 43% of the total chromatographic peak area at 280 nm) and 7-oxoflumequine (11% of the total peak area). This is the first time that the two 7-hydroxy diastereomers have been characterized structurally; the hydroxyflumequines are known to have less antimicrobial activity than flumequine. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Loyola Univ, Dept Chem, Chicago, IL 60626 USA. Norfolk Dept Publ Hlth, Norfolk, VA 23510 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov NR 20 TC 18 Z9 20 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD FEB PY 2007 VL 67 IS 2 BP 240 EP 243 DI 10.1016/j.chemosphere.2006.10.016 PG 4 WC Environmental Sciences SC Environmental Sciences & Ecology GA 142DO UT WOS:000244629600004 PM 17123578 ER PT J AU Buckman, S Huang, SM Murphy, S AF Buckman, S. Huang, S-M Murphy, S. TI Medical product development and regulatory science for the 21st century: The critical path vision and its impact on health care SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 Off Translat Sci, Food & Drug Adm, Silver Spring, MD USA. Off Clin Pharmacol, Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. RP Huang, SM (reprint author), Off Translat Sci, Food & Drug Adm, Silver Spring, MD USA. EM shiewmei.huang@fda.hhs.gov NR 16 TC 18 Z9 20 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2007 VL 81 IS 2 BP 141 EP 144 DI 10.1038/sj.clpt.2007.6100085 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 132TR UT WOS:000243965600001 PM 17259935 ER PT J AU Woodcock, J AF Woodcock, J. TI The prospects for "personalized medicine" in drug development and drug therapy SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB There has been much recent discussion about the advent of "personalized medicine," but controversy exists over its exact definition; how, when, and whether it will be brought about, and what means could be used to measure its attainment. In fact, the concept of "personalized medicine" is a sort of shorthand used to represent the logical next steps in progression of medical science toward greater mechanistic understanding of health, disease, and treatment. This shorthand is attractive to the public because of its intuitive appeal, and irritating to the biomedical community because it glosses over the very real scientific and implementation challenges. This paper evaluates the trajectory and promise of these next steps for the currently problematic states of both drug development and therapy. C1 Food & Drug Adm, Rockville, MD USA. RP Woodcock, J (reprint author), Food & Drug Adm, Rockville, MD USA. EM janet.woodcock@fda.hhs.gov NR 6 TC 108 Z9 111 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2007 VL 81 IS 2 BP 164 EP 169 DI 10.1038/sj.clpt.6100063 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 132TR UT WOS:000243965600006 PM 17259943 ER PT J AU Lesko, LJ AF Lesko, L. J. TI Paving the critical path: How can clinical pharmacology help achieve the vision? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID REGULATORY DECISION-MAKING; DRUG DEVELOPMENT AB It has been almost 3 years since the launch of the FDA critical path initiative following the publication of the paper "Innovation or Stagnation: Challenges and Opportunities on the Critical Path of New Medical Product Development." The initiative was intended to create an urgency with the drug development enterprise to address the so-called "productivity problem" in modern drug development. Clinical pharmacologists are strategically aligned with solutions designed to reduce late phase clinical trial failures to show adequate efficacy and/or safety. This article reviews some of the ways that clinical pharmacologists can lead and implement change in the drug development process. It includes a discussion of model-based, semi-mechanistic drug development, drug/disease models that facilitate informed clinical trial designs and optimal dosing, the qualification process and criteria for new biomarkers and surrogate endpoints, approaches to streamlining clinical trials and new types of interaction between industry and FDA such as the end-of-phase 2A and voluntary genomic data submission meetings respectively. C1 Food & Drug Adm, Off Clin Pharmacol & Biopharmaceut, Rockville, MD USA. RP Lesko, LJ (reprint author), Food & Drug Adm, Off Clin Pharmacol & Biopharmaceut, Rockville Pike, Rockville, MD USA. EM lawrence.lesko@fda.hhs.gov NR 17 TC 54 Z9 58 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2007 VL 81 IS 2 BP 170 EP 177 DI 10.1038/sj.clpt.6100045 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 132TR UT WOS:000243965600007 PM 17259944 ER PT J AU Bhattaram, VA Bonapace, C Chilukuri, DM Duan, JZ Garnett, C Gobburu, JVS Jang, SH Kenna, L Lesko, LJ Madabushi, R Men, Y Powell, JR Qiu, W Ramchandani, RP Tornoe, CW Wang, Y Zheng, JJ AF Bhattaram, V. A. Bonapace, C. Chilukuri, D. M. Duan, J. Z. Garnett, C. Gobburu, J. V. S. Jang, S. H. Kenna, L. Lesko, L. J. Madabushi, R. Men, Y. Powell, J. R. Qiu, W. Ramchandani, R. P. Tornoe, C. W. Wang, Y. Zheng, J. J. TI Impact of pharmacometric reviews on new drug approval and labeling decisions - a survey of 31 new drug applications submitted between 2005 and 2006 SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID EXPERIENCE AB Exploratory analyses of data pertaining to pharmacokinetic, pharmacodynamic, and disease progression are often referred to as the pharmacometrics (PM) analyses. The objective of the current report is to assess the role of PM, at the Food and Drug Administration (FDA), in drug approval and labeling decisions. We surveyed the impact of PM analyses on New Drug Applications (NDAs) reviewed over 15 months in 2005-2006. The survey focused on both the approval and labeling decisions through four perspectives: clinical pharmacology primary reviewer, their team leader, the clinical team member, and the PM reviewer. A total of 31 NDAs included a PM review component. Review of NDAs involved independent quantitative evaluation by FDA pharmacometricians. PM analyses were ranked as important in regulatory decision making in over 85% of the 31 NDAs. Case studies are presented to demonstrate the applications of PM analysis. C1 Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. RP Gobburu, JVS (reprint author), Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. EM jogarao.gobburu@fda.hhs.gov NR 7 TC 70 Z9 80 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2007 VL 81 IS 2 BP 213 EP 221 DI 10.1038/sj.clpt.6100051 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 132TR UT WOS:000243965600012 PM 17259946 ER PT J AU Orr, MS Goodsaid, F Amur, S Rudman, A Frueh, FW AF Orr, M. S. Goodsaid, F. Amur, S. Rudman, A. Frueh, F. W. TI The experience with voluntary genomic data submissions at the FDA and a vision for the future of the Voluntary Data Submission Program SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB Drug developers have been using genomic information in drug development strategies for a number of years, but it was unclear how this information would be reviewed by the Food and Drug Administration (FDA). In order to evaluate the regulatory impact of genomic data in current drug development, a workshop was held in May 2002 to discuss aspects surrounding genomic data submission to the FDA (Figure 1). C1 Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. RP Orr, MS (reprint author), Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. EM michael.orr@fda.hhs.gov NR 3 TC 21 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2007 VL 81 IS 2 BP 294 EP 297 DI 10.1038/sj.clpt.6100053 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 132TR UT WOS:000243965600023 PM 17259954 ER PT J AU Huang, SM Temple, R Throckmorton, DC Lesko, LJ AF Huang, S-M Temple, R. Throckmorton, D. C. Lesko, L. J. TI Drug interaction studies: Study design, data analysis, and implications for dosing and labeling SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB One of the most effective ways in which regulatory agencies communicate with sponsors and guide drug development is through the issuance of guidances or guidelines. These can be issued domestically in a given region such as the United States by the Food and Drug Administration (FDA) or internationally through the International Conference on Harmonization. Currently, there are over 400 final or draft guidances that can be found through the FDA website. The development of guidances proceeds through a process known as Good Guidance Practices, which is intended to assure that there is an appropriate level of meaningful public participation in the development of guidance. In the past 10 years, clinical pharmacology guidances covering important areas have been issued, including pharmacokinetic data in patients with renal and hepatic impairment, dose-response studies, and drug-drug interactions. C1 Off Clin Pharmacol, Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. Off Med Policy, Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. Off Ctr Director, Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. RP Huang, SM (reprint author), Off Clin Pharmacol, Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. EM shiewmei.Huang@Fda.hhs.gov NR 7 TC 169 Z9 179 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2007 VL 81 IS 2 BP 298 EP 304 DI 10.1038/sj.clpt.6100054 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 132TR UT WOS:000243965600024 PM 17259955 ER PT J AU Su, ZQ Hong, HX Perkins, R Shao, XG Cai, WS Tong, WD AF Su, Zhenqiang Hong, Huixiao Perkins, Roger Shao, Xueguang Cai, Wensheng Tong, Weida TI Consensus analysis of multiple classifiers using non-repetitive variables: Diagnostic application to microarray gene expression data SO COMPUTATIONAL BIOLOGY AND CHEMISTRY LA English DT Article DE consensus approach; microarray gene expression; diagnostics; prognostics ID PENALIZED LOGISTIC-REGRESSION; PARTIAL LEAST-SQUARES; PROSTATE-CANCER; TUMOR CLASSIFICATION; CLASS PREDICTION; DISCOVERY; ASSOCIATION; ALGORITHM; SAMPLES; MODEL AB Class prediction based on DNA microarray data has been emerged as one of the most important application of bioinformatics for diagnostics/prognostics. Robust classifiers are needed that use most biologically relevant genes embedded in the data. A consensus approach that combines multiple classifiers has attributes that mitigate this difficulty compared to a single classifier. A new classification method named as consensus analysis of multiple classifiers using non-repetitive variables (CAMCUN) was proposed for the analysis of hyper-dimensional gene expression data. The CAMCUN method combined multiple classifiers, each of which was built from distinct, non-repeated genes that were selected for effectiveness in class differentiation. Thus, the CAMCUN utilized most biologically relevant genes in the final classifier. The CAMCUN algorithm was demonstrated to give consistently more accurate predictions for two well-known datasets for prostate cancer and leukemia. Importantly, the CAMCUN algorithm employed an integrated 10-fold cross-validation and randomization test to assess the degree of confidence of the predictions for unknown samples. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Sci & Technol China, Dept Chem, Hefei 230026, Anhui, Peoples R China. Natl Ctr Toxicol Res, Div Bioinformat, Z Tech FDA, Jefferson, AR 72079 USA. Nankai Univ, Dept Chem, Tianjin 300071, Peoples R China. US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. RP Cai, WS (reprint author), Univ Sci & Technol China, Dept Chem, Hefei 230026, Anhui, Peoples R China. EM wscai@ustc.edu.cn; weida.tong@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012 NR 41 TC 13 Z9 14 U1 0 U2 3 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 FEB PY 2007 VL 31 IS 1 BP 48 EP 56 DI 10.1016/j.compbiolchem.2007.01.001 PG 9 WC Biology; Computer Science, Interdisciplinary Applications SC Life Sciences & Biomedicine - Other Topics; Computer Science GA 147JJ UT WOS:000244998900005 PM 17303535 ER PT J AU Cotter, PA Stibitz, S AF Cotter, Peggy A. Stibitz, Scott TI c-di-GMP-mediated regulation of virulence and biofilm formation SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID CYCLIC DIGUANYLIC ACID; TOXIN-COREGULATED PILI; VIBRIO-CHOLERAE; PSEUDOMONAS-AERUGINOSA; BORDETELLA-PERTUSSIS; XANTHOMONAS-CAMPESTRIS; ACETOBACTER-XYLINUM; GENE-EXPRESSION; DOMAIN PROTEIN; RESPIRATORY-INFECTION AB It is now apparent that the signaling molecule 3',5-cyclic diguanylic acid (c-di-GMP) is a central regulator of the prokaryote biofilm lifestyle and recent evidence also links this molecule to virulence. Environmentally responsive signal transduction systems that control expression and/or activity of the enzymes (GGDEF and EAL domain containing proteins) that are responsible for synthesis and degradation of c-di-GMP have recently been identified. Members of the phosphorelay family feature prominently amongst these systems, which include several with hybrid polydomain sensors and one that is similar to well-characterized chemotaxis-controlling pathways. These findings support the hypothesis that c-di-GMP levels are tightly controlled in response to a broad range, in terms of both diversity and intensity, of extracellular signals. Insight into how c-di-GMP affects changes in gene expression and/or protein activity has come from the demonstration that proteins containing the PilZ domain can bind c-di-GMP and control phenotypes involved in biofilm formation and virulence. These recent developments should pave the way for researchers to answer the important question of how a vast array of extracellular signals that are sensed by multiple sensory transduction pathways which all lead to the production or destruction of c-di-GMP are coordinated such that the appropriate phenotypic response is produced. C1 Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Cotter, PA (reprint author), Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. EM cotter@lifesci.ucsb.edu FU NIAID NIH HHS [AI065359, AI43876] NR 52 TC 188 Z9 195 U1 1 U2 49 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD FEB PY 2007 VL 10 IS 1 BP 17 EP 23 DI 10.1016/j.mib.2006.12.006 PG 7 WC Microbiology SC Microbiology GA 144QB UT WOS:000244809900004 PM 17208514 ER PT J AU Fraunfelder, FW AF Fraunfelder, Frederick W. TI Drug-induced ocular inflammatory diseases SO DRUGS OF TODAY LA English DT Article ID PAMIDRONATE DISODIUM; BETA-BLOCKERS; UVEITIS; BISPHOSPHONATES; RIFABUTIN AB Ocular inflammation can arise in the form of conjunctivitis, uveitis, episcleritis and scleritis. The uveiticles can be subdivided by anatomical location into anterior and posterior uveitis or categorized by location of inflammation, e.g., iritis, pars planitis or iridocyclitis. Multiple drugs have been associated with ocular inflammation and much has been written on the subject. Discussed here is a sampling of drugs representing classes of medication associated with ocular inflammation. However, this is not a comprehensive list and interested readers are encouraged to access the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, Oregon, www.eyedrugregistry.com) or the textbook Drug-Induced Ocular Side Effects for further information (1). The agents discussed may be administered systemically, topically or intracamerally (inside the eye). The mechanism behind ocular inflammation is frequently unknown. Prevention and treatment are based upon physician recognition and withdrawal of the drug in some instances. Consultation with an ophthalmologist is recommended, as many types of ocular inflammation can threaten vision. (c) 2007 Prous Science. All rights reserved. C1 Oregon Hlth & Sci Univ, Casey Eye Inst, Natl Registry Drug Induced Ocular Side Effects, Portland, OR 97239 USA. World Hlth Org, Collaborating Ctr Int Drug Monitoring, Uppsala, Sweden. US FDA, Silver Spring, MD USA. RP Fraunfelder, FW (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, Natl Registry Drug Induced Ocular Side Effects, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM eyedrug@ohsu.edu NR 17 TC 9 Z9 9 U1 0 U2 1 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 1699-3993 J9 DRUGS TODAY JI Drugs Today PD FEB PY 2007 VL 43 IS 2 BP 117 EP 123 DI 10.1358/dot.2007.43.2.1050789 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 170AA UT WOS:000246632000005 PM 17353948 ER PT J AU Benz, RD AF Benz, R. Daniel TI Toxicological and clinical computational analysis and the USFDA/CDER SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE computational toxicology; QSAR; quantitative structure-activity relationship; predictive modeling ID E-STATE INDEXES; DEVELOPMENTAL TOXICITY; CARCINOGENICITY DATA; GENETIC TOXICITY; PHARMACEUTICALS; IDENTIFICATION; PREDICTION; MOLECULES; SOFTWARE; MCASE AB In this article the author attempts to introduce those not familiar with computational toxicology to some of the terminology and basic principles of the field. The author then reports on the progress that the FDA, Center for Drug Evaluation and Research has made in compiling databases of toxicological and clinical data from which successful predictive toxicology models have been made, many of which are now commercially available through FDA software developer collaborators. This report is concluded with the author's personal speculations on the future of computational toxicology in general, and at US FDA in particular. C1 US FDA, Informat & Computat Safety Anal Staff, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Benz, RD (reprint author), US FDA, Informat & Computat Safety Anal Staff, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM R.Daniel.Benz@fda.hhs.gov NR 16 TC 24 Z9 24 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD FEB PY 2007 VL 3 IS 1 BP 109 EP 124 DI 10.1517/17425255.3.1.109 PG 16 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 167VI UT WOS:000246480200009 PM 17269898 ER PT J AU Matthews, EJ Contrera, JF AF Matthews, Edwin J. Contrera, Joseph F. TI In silico approaches to explore toxicity end points: issues and concerns for estimating human health effects SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE computational toxicology; human health effect; predictive modeling; quantitative structure-activity relationships; weight of evidence ID E-STATE INDEXES; DEVELOPMENTAL TOXICITY; CARCINOGENICITY DATA; GENETIC TOXICITY; PHARMACEUTICALS; RECOMMENDATIONS; IDENTIFICATION; SOFTWARE AB The European Chemicals Bureau and the Organisation for Economic Cooperation and Development are currently compiling a sanctioned list of quantitative structure-activity relationship (QSAR) risk assessment models and data sets to predict the physiological properties, environmental fate, ecological effects and human health effects of new and existing chemicals in commerce in the European Union. This action implements the technical requirements of the European Commission's Registration, Evaluation and Authorisation of Chemicals legislation. The goal is to identify a battery of QSARs that can furnish rapid, reliable and cost-effective decision support information for regulatory decisions that can substitute for results from animal studies. This report discusses issues and concerns that need to be addressed when selecting QSARs to predict human health effect end points. C1 US FDA, Silver Spring, MD 20993 USA. RP Matthews, EJ (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Edwin.Matthews@fda.hhs.gov NR 27 TC 24 Z9 24 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD FEB PY 2007 VL 3 IS 1 BP 125 EP 134 DI 10.1517/17425255.3.1.125 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 167VI UT WOS:000246480200010 PM 17269899 ER PT J AU Hirsch, DS Wu, WJ AF Hirsch, Dianne S. Wu, Wen Jin TI Cdc42: an effector and regulator of ErbB1 as a strategic target in breast cancer therapy SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE breast cancer; c-Cbl; Cdc42; ErbB1; ErbB1 degradation; monoclonal antibody; targeted therapy ID GROWTH-FACTOR RECEPTOR; GUANINE-NUCLEOTIDE-EXCHANGE; RHO-GTPASES; TYROSINE KINASES; RAS TRANSFORMATION; GENE-EXPRESSION; C-CBL; FARNESYLTRANSFERASE INHIBITORS; CELLULAR-TRANSFORMATION; MONOCLONAL-ANTIBODIES AB ErbB1 and ErbB2 are often overexpressed in breast cancer. Overexpression of these receptors is correlated with poor prognosis. ErbB receptor-targeted therapies have been developed for the treatment of human breast cancer. While ErbB2 overexpression is usually caused by gene amplification, the mechanism for ErbB1 overexpression remains elusive. An important mechanism for the downregulation of ErbB1 is via Cbl-mediated receptor ubiquitination and degradation. Increasing evidence suggests that loss of Cbl-regulated ErbB1 degradation contributes to ErbB1 overexpression in cancer cells. Cdc42 is overexpressed in some breast cancers and evidence is accumulating that activated Cdc42 contributes to the accumulation of ErbB1 in cells through the regulation of c-Cbl function. Different therapeutic strategies targeting ErbB receptors and Cdc42 will be reviewed and discussed. C1 US FDA, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, HFD 123,Bldg 29B,Room 3NN-15,29 Lincoln Dr, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov NR 98 TC 10 Z9 10 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD FEB PY 2007 VL 7 IS 2 BP 147 EP 157 DI 10.1586/14737140.7.2.147 PG 11 WC Oncology SC Oncology GA 141VA UT WOS:000244605700012 PM 17288526 ER PT J AU Yu, HN Shen, SR Yin, JJ AF Yu, Hai-Ning Shen, Sheng-Rong Yin, Jun-Jie TI Effects of interactions of EGCG and Cd2+ on the growth of PC-3 cells and their mechanisms SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE EGCG; Cd2+; Zn2+; prostate cancer ID PROSTATE-CANCER CELLS; EPIGALLOCATECHIN GALLATE; GREEN TEA; DU145 CELLS; CADMIUM; ZINC; INDUCTION; APOPTOSIS; CATECHINS; INHIBITION AB The preventive and therapeutic effects of a major component of catechins of green tea, epigallocatechin-3-gallate (EGCG), on prostate cancer have been demonstrated in many studies. It is well known that metal ions are necessary for human health, but an imbalance in metal ions metabolism can lead to many diseases including prostate cancer. Understanding the interactions of EGCG with metal ions might elucidate its mechanism in preventing and curing prostate cancer. The present study focused on the effects of Cd2+ and EGCG on the growth of androgen-insensitive prostate cancer cell PC-3 investigated by MTT assay, the effects of EGCG and Cd2+ on absorption of Cd2+ and Zn2+ by PC-3 cells were detected by atomic absorption spectroscopy (AAS), and the interactions of EGCG with Cd2+ were determined by distribution coefficient and UV-Vis spectroscopy detection. The results showed that Cd2+ suppressed viability of PC-3 cells in concentration- and time-dependent manner, and EGCG enhanced the effect of Cd2+ on PC-3 cells. EGCG was shown to decrease the absorption Cd2+ and increase the absorption of Zn2+ by PC-3 cells, while the effects of Cd2+ on the absorption of Cd2+ and Zn2+ were opposite to that of EGCG. In the presence of both EGCG and Cd2+, absorption of Cd2+ and Zn2+ by PC-3 cells was dependent on concentrations of EGCG, Cd2+ and its order of addition. Results from the distribution coefficient determination and UV-Vis spectroscopy analysis indicated that Cd2+ might affect conformation of EGCG, while no complex of EGCG with Cd2+ was observed in the system. (c) 2006 Elsevier Ltd. All rights reserved. C1 Zhejiang Univ Technol, Coll Agr & Biotechnol, Dept Tea Sci, Hangzhou 310029, Peoples R China. Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310032, Peoples R China. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Shen, SR (reprint author), Zhejiang Univ Technol, Coll Agr & Biotechnol, Dept Tea Sci, Hangzhou 310029, Peoples R China. EM shrshen@zju.edu.cn RI Yin, Jun Jie /E-5619-2014 NR 31 TC 19 Z9 24 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD FEB PY 2007 VL 45 IS 2 BP 244 EP 249 DI 10.1016/j.fct.2006.08.015 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 135LU UT WOS:000244155900008 PM 17046135 ER PT J AU Villareal, TA Hanson, S Qualia, S Jester, ELE Granade, HR Dickey, RW AF Villareal, T. A. Hanson, S. Qualia, Steve Jester, E. L. E. Granade, H. R. Dickey, R. W. TI Petroleum production platforms as sites for the expansion of ciguatera in the northwestern Gulf of Mexico SO HARMFUL ALGAE LA English DT Article DE artificial reefs; barracuda; ciguatera; Gambierdiscus; global change; Gulf of Mexico ID SEA; TEMPERATURE; COMMUNITY; VECTOR; TOXINS AB Ciguatera is a common human disease of tropical, coral reef ecosystems acquired by consuming finfish-containing ciguatoxins (CTX). There are few records of this disease in the northwestern Gulf of Mexico, a region characterized by soft muddy bottoms that are considered poor habitat for the CTX source dinoflagellate Gambierdiscus toxicus. However, the approximately 4000 petroleum production platforms and hundreds of state-sponsored artificial reefs located in the Gulf of Mexico provide hard substrate and often support coral and other components of the tropical benthos. In addition to their role in their resource extraction, these oil production platforms are also popular sites for recreational fishing and sport diving. We examined these platforms as potential substrate for G. toxicus and report a first record of this species in the NW Gulf of Mexico. All the platforms (n = 6) examined harbored the dinoflagellate as an epiphyte on the fouling community, with three finds of G. toxicus associated with the pelagic macroalga, Sargassum. Only minor toxicity (< 0.15 ppb) was noted in two of 20 great barracuda (Sphyraena barracuda) examined. Tagging data suggest trans-Gulf migrations by barracuda are common; thus, we cannot determine if the toxicity was acquired locally or transported in migrating fish. These platforms are a clear example of how human activity has altered the environment in a way that allows expansion of a HA-B population. The rapid increase in production platforms since 1942 has provided novel substrate in a sandy/muddy bottom environment generally considered to be poor habitat for these benthic dinoflagellates. These platforms create a unique habitat in the upper euphotic zone and serve as intersection points for fishermen and potentially toxic fish. Many Gulf of Mexico states have active programs to turn non-producing platforms into artificial reefs. Our results suggest that the use of these platforms as fisheries enhancement structures could have unintended consequences for human health, particularly if projected rising sea-surface temperatures over the next century alter benthic distributions and fish migration patterns. These concerns also extend to mariculture operations around oil production rigs or offshore wind farms, both of which would also add substrate for epibenthic microalgae. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Texas, Inst Marine Sci, Port Aransas, TX 78373 USA. Univ Texas, Dept Marine Sci, Port Aransas, TX 78373 USA. Fishtrackers Inc, Corpus Christi, TX 78469 USA. US FDA, Gulf Coast Seafood Lab, Chem Hazards Res Unit, Dauphin Isl, AL 36528 USA. RP Villareal, TA (reprint author), Univ Texas, Inst Marine Sci, 750 Channel View Dr, Port Aransas, TX 78373 USA. EM tracy@utmsi.utexas.edu RI Villareal, Tracy/I-9462-2012 NR 38 TC 34 Z9 37 U1 2 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 J9 HARMFUL ALGAE JI Harmful Algae PD FEB PY 2007 VL 6 IS 2 BP 253 EP 259 DI 10.1016/j.hal.2006.08.008 PG 7 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 138WS UT WOS:000244394600008 ER PT J AU Donthamsetty, S Bhave, VS Mitra, MS Latendresse, JR Mehendale, HM AF Donthamsetty, Shashikiran Bhave, Vishakha S. Mitra, Mayurranjan S. Latendresse, John R. Mehendale, Harihara M. TI Nonalcoholic fatty liver sensitizes rats to carbon tetrachloride hepatotoxicity SO HEPATOLOGY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis ID FORKHEAD BOX M1B; ANTIMITOTIC AGENT COLCHICINE; TRANSCRIPTION FACTOR; CCL4 HEPATOTOXICITY; DIABETIC-RATS; UP-REGULATION; TRANSFORMING GROWTH-FACTOR-BETA-1; UNCOUPLING PROTEIN-2; MEDIATES PROGRESSION; PARTIAL-HEPATECTOMY AB This study tested whether hepatic steatosis sensitizes liver to toxicant-induced injury and investigated the potential mechanisms of hepatotoxic sensitivity. Male Sprague-Dawley rats were fed a methionine- and choline-deficient diet for 31 days to induce steatosis. On the 32nd day, administration of a nonlethal dose of CCl4 (2 mL/kg, intraperitoneally) yielded 70% mortality in steatotic rats 12-72 hours after CCl4 administration, whereas all nonsteatotic rats survived. Neither CYP2E1 levels nor covalent binding of [C-14] CCl4-derived radio-label differed between the groups, suggesting that increased bioactivation is not the mechanism for this amplified toxicity. Cell division and tissue repair, assessed by [H-3]thymidine incorporation and proliferative cell nuclear antigen assay, were inhibited in the steatotic livers after CCl4 administration and led to progressive expansion of liver injury culminating in mortality. The hypothesis that fatty hepatocytes undergo cell cycle arrest due to (1) an inability to replenish ATP due to overexpressed uncoupling protein-2 (UCP-2) or (2) induction of growth inhibitor p21 leading to G(1)/S phase arrest was tested. Steatotic livers showed 10-fold lower ATP levels due to upregulated UCP-2 throughout the time course after CCl4 administration, leading to sustained inhibition of cell division. Western blot analysis revealed an up-regulation of p21 due to overexpression of TGF beta 1 and p53 and down-regulation of transcription factor Foxm 1b in steatotic livers leading to lower phosphorylated retinoblastoma protein. Thus, fatty hepatocytes fail to undergo compensatory cell division, rendering the liver susceptible to progression of liver injury. Conclusion: Impaired tissue repair sensitizes the steatotic livers to hepatotoxicity. C1 Univ Louisiana, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306B, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009; OI Bhave, Vishakha/0000-0003-0149-579X NR 59 TC 31 Z9 32 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2007 VL 45 IS 2 BP 391 EP 403 DI 10.1002/hep.21530 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 132NI UT WOS:000243949100018 PM 17256749 ER PT J AU Derrick, SC Evering, TH Sambandamurthy, VK Jalapathy, KV Hsu, TD Chen, B Chen, M Russell, RG Junqueira-Kipnis, AP Orme, IM Porcelli, SA Jacobs, WR Morris, SL AF Derrick, Steven C. Evering, Teresa H. Sambandamurthy, Vasan K. Jalapathy, Kripa V. Hsu, Tsungda Chen, Bing Chen, Mei Russell, Robert G. Junqueira-Kipnis, Ana Paula Orme, Ian M. Porcelli, Steven A. Jacobs, William R., Jr. Morris, Sheldon L. TI Characterization of the protective T-cell response generated in CD4-deficient mice by a live attenuated Mycobacterium tuberculosis vaccine SO IMMUNOLOGY LA English DT Article DE cytokines; T cells; tuberculosis; vaccine ID INTRACELLULARE COMPLEX INFECTION; PANTOTHENATE AUXOTROPH; PULMONARY TUBERCULOSIS; ANTIGEN PRESENTATION; CD8-T-CELL MEMORY; CD4-T-CELL HELP; CALMETTE-GUERIN; BOVIS BCG; CD4; LYMPHOCYTES AB The global epidemic of tuberculosis, fuelled by acquired immune-deficiency syndrome, necessitates the development of a safe and effective vaccine. We have constructed a Delta RD1 Delta panCD mutant of Mycobacterium tuberculosis (mc(2)6030) that undergoes limited replication and is severely attenuated in immunocompromised mice, yet induces significant protection against tuberculosis in wild-type mice and even in mice that completely lack CD4(+) T cells as a result of targeted disruption of their CD4 genes (CD4(-/-) mice). Ex vivo studies of T cells from mc(2)6030-immunized mice showed that these immune cells responded to protein antigens of M. tuberculosis in a major histocompatibility complex (MHC) class II-restricted manner. Antibody depletion experiments showed that antituberculosis protective responses in the lung were not diminished by removal of CD8(+), T-cell receptor gamma delta (TCR-gamma delta(+)) and NK1.1(+) T cells from vaccinated CD4(-/-) mice before challenge, implying that the observed recall and immune effector functions resulting from vaccination of CD4(-/-) mice with mc(2)6030 were attributable to a population of CD4(-) CD8(-) (double-negative) TCR-alpha beta(+), TCR-gamma delta(-), NK1.1(-) T cells. Transfer of highly enriched double-negative TCR-alpha beta(+) T cells from mc(2)6030-immunized CD4(-/-) mice into naive CD4(-/-) mice resulted in significant protection against an aerosol tuberculosis challenge. Enriched pulmonary double-negative T cells transcribed significantly more interferon-gamma and interleukin-2 mRNA than double-negative T cells from naive mice after a tuberculous challenge. These results confirmed previous findings on the potential for a subset of MHC class II-restricted T cells to develop and function without expression of CD4 and suggest novel vaccination strategies to assist in the control of tuberculosis in human immunodeficiency virus-infected humans who have chronic depletion of their CD4(+) T cells. C1 NINCDS, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Georgetown Univ, Lombardi Canc Ctr, Dept Pathol, Washington, DC 20007 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. RP Derrick, SC (reprint author), NINCDS, Ctr Biol Evaluat & Res, Bldg 10, Bethesda, MD 20892 USA. EM steven.derrick@fda.hhs.gov; Jacobsw@hhmi.org NR 48 TC 21 Z9 22 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD FEB PY 2007 VL 120 IS 2 BP 192 EP 206 DI 10.1111/j.1365-2567.2006.02491.x PG 15 WC Immunology SC Immunology GA 122PP UT WOS:000243239200006 PM 17076705 ER PT J AU Tanaka, T Porter, CM Horvath-Arcidiacono, JA Bloom, ET AF Tanaka, Toru Porter, Cynthia M. Horvath-Arcidiacono, Judith A. Bloom, Eda T. TI Lipophilic statins suppress cytotoxicity by freshly isolated natural killer cells through modulation of granule exocytosis SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD107a; granzyme B; human; NK cells; statins ID COA REDUCTASE INHIBITORS; NK CELLS; LYMPHOCYTE FUNCTION; MEDIATED CYTOTOXICITY; HEART-TRANSPLANTATION; FUNCTION ANTIGEN-1; CANCER-RISK; FAS LIGAND; REJECTION; ADHESION AB NK cells, a component of the innate immune system, provide a first line of defense against viral infections and malignancies, interact with the adaptive immune system and have a role in rejection of allogeneic bone marrow transplants and solid allo- and xenotransplants. Immunoregulatory activity by the anti-hypercholesterolemia agents, 3-hydroxy-3-methyl-glutaryl Coenzyme A (HMG-CoA) reductase inhibitors, known as statins, has recently been reported. We analyzed the effects of three statins on human NK cell cytotoxicity. Two lipophilic statins (simvastatin and fluvastatin) suppressed the cytotoxic activity of fresh and IL-2-stimulated NK cells, while pravastatin, a hydrophilic statin, did not. Suppression was not associated with changes in intracellular perforin, granzyme A or granzyme B levels, or with changes in expression of leukocyte function-associated antigen-1, an integrin known to regulate NK activity and reported to be altered by statin treatment. Decreased cytotoxicity was associated with decreased CD107a surface expression, indicating that the exocytosis pathway was compromised by simvastatin and fluvastatin but not by pravastatin. Mevalonate, the immediate downstream product of HMG-CoA reductase, partially reversed the effect of lipophilic statins on cytotoxicity and CD107a expression. Lipophilic statins also suppressed the release of the granule component, granzyme B, by IL-2-activated NK cells following stimulation with K562. That lipophilic statins suppress NK cell activity through inhibition of the exocytosis pathway suggest an additional potential role for statins in inhibition of transplantation responses. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies HFM725, Gene Transfer & Immunogen Branch, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies HFM725, Gene Transfer & Immunogen Branch, 800 Rockville Pike, Bethesda, MD 20892 USA. EM eda.bloom@fda.hhs.gov NR 59 TC 19 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD FEB PY 2007 VL 19 IS 2 BP 163 EP 173 DI 10.1093/intimm/dxl133 PG 11 WC Immunology SC Immunology GA 130NI UT WOS:000243805900006 PM 17182966 ER PT J AU Gavigan, CS Shen, M Machado, SG Bell, A AF Gavigan, C. S. Shen, M. Machado, S. G. Bell, A. TI Influence of the Plasmodium falciparum P-glycoprotein homologue 1 (pfmdr1 gene product) on the antimalarial action of cyclosporin SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE malaria; cyclosporin A; Pgh1 ID P-GLYCOPROTEIN HOMOLOG; MEFLOQUINE RESISTANCE; DIGESTIVE VACUOLE; SENSITIVITY; MECHANISMS; CYCLOPHILIN; QUININE; CALCINEURIN; CHLOROQUINE; INHIBITORS AB Background and objectives: The immunosuppressant cyclosporin A and a number of other cyclosporins have potent and selective antimalarial activity. Their exact mechanism of antimalarial action is unknown but the structure-activity relationships for malarial parasite inhibition and immunosuppression differ markedly. The T-keto derivative of cyclosporin D (valspodar) is particularly potent against the human malarial parasite Plasmodium falciparum in culture but causes negligible immunosuppression. Multidrug resistance in mammalian cancer cells, the result of overproduction of the P-glycoprotein, can be reversed by certain cyclosporins, particularly valspodar. We therefore investigated the possibility that the antimalarial target of cyclosporin might be a P-glycoprotein homologue. P. falciparum P-glycoprotein homologue 1 (Pgh1; the pfmdr1 gene product) is located in the digestive vacuole (DV) membrane of the parasite. Its function is unknown but it modulates the susceptibility of parasites to quinolines and related antimalarial drugs, including quinine, mefloquine, halofantrine and chloroquine, and to artemisinin. Methods and results: Here we demonstrate that (i) sequence polymorphisms in pfmdr1 altered the susceptibility of parasites to cyclosporin A and (ii) pfmdr1-overexpressing strains were slightly less susceptible to the drug. Furthermore, we found synergistic antimalarial interactions between cyclosporin A and quinine, mefloquine or halofantrine and antagonism between cyclosporin A and chloroquine. However, we were unable to detect a direct interaction between cyclosporin and Pgh1. Conclusions: The amino acid sequence and copy number of Pgh1 may influence cyclosporin susceptibility as a result of a direct interaction between the drug and the protein, or via indirect effects on the physiology of the DV. C1 Univ Dublin Trinity Coll, Moyne Inst Prevent Med, Dept Microbiol, Dublin 2, Ireland. US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Bell, A (reprint author), Univ Dublin Trinity Coll, Moyne Inst Prevent Med, Dept Microbiol, Dublin 2, Ireland. EM abell@tcd.ie OI Bell, Angus/0000-0002-0578-8656 NR 38 TC 9 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD FEB PY 2007 VL 59 IS 2 BP 197 EP 203 DI 10.1093/jac/dkl461 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 147OH UT WOS:000245011800005 PM 17105736 ER PT J AU Moore, MM Feist, MD AF Moore, M. M. Feist, M. D. TI Real-time PCR method for Salmonella spp. targeting the stn gene SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE enterotoxin; real-time PCR; Salmonella; Salmonella bongori; stn ID POLYMERASE-CHAIN-REACTION; COMPLETE GENOME SEQUENCE; MOLECULAR CHARACTERIZATION; RAPID DETECTION; REACTION ASSAY; ENTERICA; TYPHIMURIUM; ENTEROTOXIN; BONGORI; FOOD AB To develop a real-time PCR assay for Salmonella spp. targeting the stn gene. The presence of stn in the Salmonella bongori genome was found by a BLAST with Salmonella enterica stn sequence. Manual alignment of stn sequences showed that Salm. bongori had 88% sequence identity with Salm. enterica. Two primers (stnL-433 and stnR-561) and a probe (stnP-452) were designed to target conserved regions in stn and meet the requirements of a 5'-nuclease assay. The primers and probe were evaluated against 353 isolates, including 255 Salm. enterica representing 158 serotypes, 14 Salm. bongori representing 12 serotypes and 84 non-Salmonella representing 56 species from 31 genera. All isolates were correctly identified, with the exception of three isolates of Citrobacter amalonaticus, which gave false positives. The limit of detection with cultured Salmonella was 3 CFU per reaction. The stn real-time PCR method had 100% inclusivity, 96.4% exclusivity and a level of detection of 3 CFU per reaction for cultured Salmonella spp. The study showed that stn is present in Salm. bongori and is a valid target for both species of Salmonella. The Salmonella s tn real-time PCR is a useful method for identifying Salmonella spp. C1 US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Moore, MM (reprint author), US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM michelle.moore@fda.hhs.gov NR 42 TC 28 Z9 30 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD FEB PY 2007 VL 102 IS 2 BP 516 EP 530 DI 10.1111/j.1365-2672.2006.03079.x PG 15 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 126IT UT WOS:000243507300025 PM 17241358 ER PT J AU Shames, D Gassman, A Handelsman, H AF Shames, Daniel Gassman, Audrey Handelsman, Harry TI Commentary: Guideline for male testosterone therapy: A regulatory perspective SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Div Reprod & Urol Prod, Silver Spring, MD 20993 USA. RP Shames, D (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Reprod & Urol Prod, 10903 New Hampshire Ave,White Oak Bldg 22, Silver Spring, MD 20993 USA. EM daniel.shames@fda.hhs.gov NR 8 TC 10 Z9 10 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2007 VL 92 IS 2 BP 414 EP 415 DI 10.1210/jc.2006-2642 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 134ED UT WOS:000244064900006 PM 17284641 ER PT J AU Duan, JZ AF Duan, J. Z. TI Applications of population pharmacokinetics in current drug labelling SO JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS LA English DT Article DE drug-drug interaction; labelling; physician desk reference; population pharmacokinetics ID ROUTINE CLINICAL-DATA; VOLUNTEERS; CLEARANCE; MODELS; SEX; AGE AB Background and Objective: The application of population pharmacokinetics (PopPK) appears increasingly in drug labelling. The current study was to examine the use of PopPK in dose recommendation in drug-product labels. Method: PopPK information was identified in the data sheets included in the physician desk reference (PDR). Electronic key word searches were conducted in the electronic library of PDR. The use of PopPK in the prescribing information, including the determination of dosing regimen, dosing in special populations and dose-adjustments was summarized and evaluated. The reliability and criteria for integrating the information derived from PopPK studies into the product labelling were discussed. Results and Discussion: Among more than 2500 items listed in the PDR, 88 listings were found to have PopPK information in the labelling. The information included general data (Gen) on pharmacokinetics (PK) and the effects of gender (sex), age, race, drug-drug interactions (DDI), smoking (Smk), alcohol consumption (Alc), disease state (Dis), renal impairment (Ren) and metabolic status (Met) on the PK parameters (Table). Whether there was an effect (+) or not (-) is also shown. Appendix 1 lists the products included in each category. [GRAPHICS] Searches conducted at different times suggest an increase in both quantity and quality of PopPK data in drug development. PopPK is widely used in paediatric studies and the sample sizes in these studies are sometimes too small. The application of PopPK to protein drugs is increasing rapidly (Appendix 2). Several precautions should be exercised when PopPK is applied to protein drugs. When considering gender effects, different normalization methods for body weight have been used. The number of subjects included in the PopPK analysis should be given and the influence of the imbalance in any covariate should be investigated. PopPK-DDI results are particularly difficult to evaluate unless details about potentially influential factors such as dosing and sampling information for both drug and interacting drugs are given. Conclusions: The use of PopPK to aid optimal dosing is increasing. Several noticeable problems raised usually avoid the acceptability of PopPK studies. More investigations are needed to inform the development of consensuses on these issues. There is an accelerating shift from PopPK to PopPK/PD. The limitations of such modelling should be recognized. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. RP Duan, JZ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. EM john.duan@fda.hhs.gov NR 36 TC 17 Z9 19 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-4727 J9 J CLIN PHARM THER JI J. Clin. Pharm. Ther. PD FEB PY 2007 VL 32 IS 1 BP 57 EP 79 DI 10.1111/j.1365-2710.2007.00799.x PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 132WO UT WOS:000243973800007 PM 17286790 ER PT J AU Cavanaugh, KJ Abel, DB AF Cavanaugh, K. J., Jr. Abel, D. B. TI Differences in optimizing patient selection and evaluating treatment options SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Meeting Abstract CT 20th International Congress on Endovascular Interventions CY FEB 11-15, 2007 CL Arizona Heart Inst Fdn, Scottsdale, AZ SP Int Soc Endovasc Specialists HO Arizona Heart Inst Fdn C1 US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD FEB PY 2007 VL 14 SU 1 BP I7 EP I7 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 143FQ UT WOS:000244705800011 ER PT J AU Blackstone, GM Nordstrom, JL Bowen, MD Meyer, RF Imbro, P DePaola, A AF Blackstone, George M. Nordstrom, Jessica L. Bowen, Michael D. Meyer, Richard F. Imbro, Paula DePaola, Angelo TI Use of a real time PCR assay for detection of the ctxA gene of vibrio cholerae in an environmental survey of Mobile Bay SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE vibrio cholerae; real time PCR; cholerae toxin ID STATES GULF-COAST; VIBRIO-CHOLERAE-O1; PARAHAEMOLYTICUS; TRANSMISSION; BANGLADESH; OYSTERS; SHRIMP; STRAIN; O139 AB Toxigenic Vibrio cholerae, the etiological agent of cholera, is a natural inhabitant of the marine environment and causes severe diarrheal disease affecting thousands of people each year in developing countries. It is the subject of extensive testing of shrimp produced and exported from these countries. We report the development of a real time PCR (qPCR) assay to detect the gene encoding cholera toxin, ctxA, found in toxigenic V cholerae strains. This assay was tested against DNA isolated from soil samples collected from diverse locations in the US, a panel of eukaryotic DNA from various sources, and prokaryotic DNA from closely related and unrelated bacterial sources. Only Fibrio strains known to contain ctxA generated a fluorescent signal with the 5' nuclease probe targeting the ctxA gene, thus confirming the specificity of the assay. In addition, the assay was quantitative in pure culture across a six-log dynamic range down to < 10 CFU per reaction. To test the robustness of this assay, oysters, aquatic sediments, and seawaters from Mobile Bay, AL, were analyzed by qPCR and traditional culture methods. The assay was applied to overnight alkaline peptone water enrichments of these matrices after boiling the enrichments for 10 min. Toxigenic V. cholerae strains were not detected by either qPCR or conventional methods in the 16 environmental samples examined. A novel exogenous internal amplification control developed by us to prevent false negatives identified the samples that were inhibitory to the PCR. This assay, with the incorporated internal control, provides a highly specific, sensitive, and rapid detection method for the detection of toxigenic strains of V cholerae. Published by Elsevier B.V. C1 US FDA, GCSL, Dauphin Isl, AL 36528 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Homeland Secur Inst, Arlington, VA 22206 USA. RP Blackstone, GM (reprint author), US FDA, GCSL, 1 Iberville Dr,POB 158, Dauphin Isl, AL 36528 USA. EM George.Blackstone@fda.hhs.gov NR 24 TC 65 Z9 69 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD FEB PY 2007 VL 68 IS 2 BP 254 EP 259 DI 10.1016/j.mimet.2006.08.006 PG 6 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 138SK UT WOS:000244382400008 PM 17034889 ER PT J AU Vickery, MCL Nilsson, WB Strom, MS Nordstrom, JL DePaola, A AF Vickery, Michael C. L. Nilsson, William B. Strom, Mark S. Nordstrom, Jessica L. DePaola, Angelo TI A real-time PCR assay for the rapid determination of 16S rRNA genotype in Vibrio vulnificus SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE vibrio vulnificus; real-time PCR; 16S rRNA ID FIELD GEL-ELECTROPHORESIS; POLYMORPHIC DNA ANALYSIS; FRAGMENT-LENGTH-POLYMORPHISM; ESCHERICHIA-COLI; AP-PCR; GENES; IDENTIFICATION; EPIDEMIOLOGY; POLYMERASE; SEQUENCES AB In a terminal restriction fragment polymorphism (T-RFLP) study, we recently reported a significant association between the type B 16S rRNA gene and clinical strains of Vibrio vulnificus associated with the consumption of raw oysters. In the present study we describe a real-time PCR assay for the rapid determination of the 16S rRNA type of V vulnificus isolates. This assay was used to reexamine the 16S rRNA gene type in the strains studied previously by T-RFLP and additional isolates from selected sources. Analyses revealed that 15 of the strains (10 environmental and 5 clinical) previously found to be 16S rRNA type A actually appear to possess both the type A and B genes. The presence of both alleles was confirmed by cloning and sequencing both gene types from one strain. To our knowledge, this is the first report of 16S rRNA sequence heterogeneity within individual strains of V vulnificus. The findings confirm the T-RFLP data that 16S rRNA type may be a useful marker for determining the clinical significance of V. vulnificus in disease in humans and cultured eels. The real-time PCR assay is much more rapid and less resource-intensive than T-RFLP, and should facilitate further study of the occurrence and distribution of the 16S rRNA genotypes of V vulnificus. These studies should provide more definitive estimates of the risks associated with this organism and may lead to a better understanding of its virulence mechanism(s). (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Fishery Res Branch, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. US Dept Commerce, Natl Ocean Atmospher Adm, Natl Marine Fisheries Serv, NW Fisheries Sci Ctr, Seattle, WA 98112 USA. RP Nordstrom, JL (reprint author), US FDA, Fishery Res Branch, Gulf Coast Seafood Lab, POB 158,1 Iberville, Dauphin Isl, AL 36528 USA. EM michael.vickery@cepheid.com; jessica.nordstrom@fda.hhs.gov NR 43 TC 51 Z9 51 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD FEB PY 2007 VL 68 IS 2 BP 376 EP 384 DI 10.1016/j.mimet.2006.02.018 PG 9 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 138SK UT WOS:000244382400025 PM 17070612 ER PT J AU Schneeman, B AF Schneeman, Barbara TI FDA's review of scientific evidence for health claims SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Evidence-Based Public Nutrition - An Evolving Concept CY APR 04, 2006 CL San Francisco, CA AB Under the Federal Food, Drug, and Cosmetic Act health claims on foods or dietary supplements must be authorized by the FDA. Health claims describe the relationship between a food, food component, or dietary supplement and reducing the risk of a disease or health-related condition. Under interim guidance and enforcement discretion, certain qualified health claims have been provided for on foods and dietary supplements; these claims contain language to qualify the quality and strength of scientific evidence to support the claim because they are not based on significant scientific agreement, which is the standard for health claims authorized by the Federal Food, Drug, and Cosmetic Act. In order to meet its statutory responsibility for evaluation of health claims, the agency has developed guidelines for review of scientific evidence in support of a health claim. C1 US FDA, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Schneeman, B (reprint author), US FDA, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM barbara.schneeman@fda.hhs.gov FU NIMHD NIH HHS [1P20MD001765-01] NR 0 TC 14 Z9 14 U1 1 U2 4 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2007 VL 137 IS 2 BP 493 EP 494 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 130DM UT WOS:000243779600035 PM 17237334 ER PT J AU Mackey, AC Green, L Liang, LC Dinndorf, P Avigan, M AF Corken Mackey, Ann Green, Lanh Liang, Li-ching Dinndorf, Patricia Avigan, Mark TI Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE tumor necrosis factor alpha; immunosuppressive agents; hepatosplenic T cell lymphoma; inflammatory bowel disease AB Hepatosplenic T cell lymphoma (HSTCL) are rare cancers (Pz 100 published cases worldwide) and comprise 5% of peripheral T cell lymphomas. As of October 5, 2006, the FDA's Adverse Event Reporting System has received 8 cases of HSTCL in young patients using infliximab, a tumor necrosis factor-alpha blocking agent, to treat inflammatory bowel disease (6 of the 8 cases had a fatal outcome). All 8 patients were receiving concomitant immunosuppressant therapy (eg, azathioprine, prednisone). It has not been established that infliximab had an exclusive or primary role in the pathogenesis of these HSTCL cases; however, it appears that patients using this product may be at greater risk for developing this rare lymphoma. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Mackey, AC (reprint author), Bldg 22,Room 3472,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ann.mackey@fda.hhs.gov NR 6 TC 277 Z9 284 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 2007 VL 44 IS 2 BP 265 EP 267 DI 10.1097/MPG.0b013e31802f6424 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 131EU UT WOS:000243851900019 PM 17255842 ER PT J AU Zhang, ZW Rockette, HE AF Zhang, Zhiwei Rockette, Howard E. TI An EM algorithm for regression analysis with incomplete covariate information SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION LA English DT Article ID MODELS AB Regression analysis is often challenged by the fact that some covariates are not completely observed. Among other approaches is a newly developed semiparametric maximum likelihood (SML) method that requires no parametric specification of the selection mechanism or the covariate distribution and that yields efficient inference, at least in some specific models. In this paper, we propose an EM algorithm for finding the SML estimate and for variance estimation. Simulation results suggest that the SML method performs reasonably well in moderate-sized samples. In contrast, the analogous parametric maximum likelihood method is subject to severe bias under model mis-specification, even in large samples. C1 Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. US FDA, Div Biostat, OSB, CDRH, Rockville, MD 20850 USA. RP Rockette, HE (reprint author), Univ Pittsburgh, Dept Biostat, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM herbst@pitt.edu NR 6 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0094-9655 J9 J STAT COMPUT SIM JI J. Stat. Comput. Simul. PD FEB PY 2007 VL 77 IS 2 BP 163 EP 173 DI 10.1080/10629360600565202 PG 11 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 108BY UT WOS:000242216500006 ER PT J AU Gogichaeva, NV Williams, T Alterman, MA AF Gogichaeva, Natalia V. Williams, Todd Alterman, Michail A. TI MALDI TOF/TOF tandem mass spectrometry as a new tool for amino acid analysis SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID ELECTROSPRAY-IONIZATION; QUANTITATIVE-ANALYSIS; FRAGMENTATION; PERFORMANCE; MOLECULES; SPECTRA; QUANTIFICATION; IDENTIFICATION; METABOLISM; DISORDERS AB This is the first report of an application of collisionally induced fragmentation of amino acids (AA) and their derivatives by MALDI TOF/TOF tandem mass spectrometry (MS). In this work, we collected the data on high-energy fragmentation reactions of a large group of protonated amino acids and their derivatives with the goal of determining which product ions are analyte specific and if yields of these fragment could be used for quantitative analysis. From 34 different amino acids (20 alpha-amino acids, beta-amino acids, homocysteine, GABA, and modified AA Met sulfone and sulfoxide, hydroxyproline, etc.) we observed that high yields of the target specific immonium ions and fragmentation patterns are most similar to EI or FAB CID on sector instruments. The major exceptions were two highly basic amino acids, Arg and Orn. It is noted that neither beta-, gamma-, nor delta-amino acids produce immonium ions. As might be predicted from high-energy CID work on peptides from the sectors and TOF/TOF, the presence of specific indicator ions in MALDI tandem MS allows distinguishing isomeric and isobaric amino acids. These indicator ions, in combination with careful control of data acquisition, ensure quantitative analysis of amino acids. We believe our data provide strong basis for the application of MALDI TOF/TOF MS/MS in qualitative and quantitative analysis of amino and organic acids, including application in clinical medicine. C1 US FDA, Tumor Vaccines & Biotechnol Branch, CBER, NIH, Bethesda, MD 20892 USA. Univ Kansas, Analyt Proteom Lab, Lawrence, KS 66045 USA. RP Alterman, MA (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, CBER, NIH, Bldg 29A,Room 2D12,HFM 735,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Michail.Alterman@fda.hhs.gov NR 26 TC 31 Z9 35 U1 3 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD FEB PY 2007 VL 18 IS 2 BP 279 EP 284 DI 10.1016/j.jasms.2006.09.013 PG 6 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 134UJ UT WOS:000244109300014 PM 17074506 ER PT J AU Margolis, TP Imai, Y Yang, L Vallas, V Krause, PR AF Margolis, Todd P. Imai, Yumi Yang, Li Vallas, Vicky Krause, Philip R. TI Herpes simplex virus type 2 (HSV-2) establishes latent infection in a different population of ganglionic neurons than HSV-1: Role of latency-associated transcripts SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY SENSORY NEURONS; RABBIT EYE MODEL; IN-VIVO; IMMUNOHISTOCHEMICAL ANALYSIS; SPONTANEOUS REACTIVATION; TRIGEMINAL GANGLIA; GENE-EXPRESSION; GENITAL HERPES; MUTANT; CELLS AB Herpes simplex virus type 1 (HSV-1) and HSV-2 cause very similar acute infections but differ in their abilities to reactivate from trigeminal and dorsal root ganglia. To investigate differences in patterns of viral infection, we colabeled murine sensory ganglia for evidence of HSV infection and for the sensory neuron marker A5 or KH10. During acute infection, 7 to 10% of HSV-1 or HSV-2 antigen-positive neurons were A5 positive and 13 to 16% were KH10 positive, suggesting that both viruses reach each type of neuron in a manner proportional to their representation in uninfected ganglia. In murine trigeminal ganglia harvested during HSV latency, 25% of HSV-1 latency-associated transcript (LAT)- and 4% of HSV-2 IAT-expressing neurons were A5 positive, while 12% of HSV-1 LAT- and 42% of HSV-2 LAT-expressing neurons were KH10 positive. A similar difference was observed in murine dorsal root ganglia. These differences could not be attributed to differences in LAT expression levels in A5- versus KH10-positive neurons. Thus, HSV-1 demonstrated a preference for the establishment of latency in A5-positive neurons, while HSV-2 demonstrated a preference for the establishment of latency in KH10-positive neurons. A chimeric HSV-2 mutant that expresses the HSV-1 LAT exhibited an HSV-1 phenotype, preferentially establishing latency in A5-positive neurons. These data imply that the HSV-1 and HSV-2 LAT regions influence the ability of virus to establish latency in different neuronal subtypes. That the same chimeric virus has a characteristic HSV-1 reactivation phenotype further suggests that LAT-influenced establishment of latency in specific neuronal subtypes could be an important part of the mechanism by which LAT influences viral reactivation phenotypes. C1 Univ Calif San Francisco, FI Proctor Fdn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Margolis, TP (reprint author), Univ Calif San Francisco, FI Proctor Fdn, Med Sci Bldg,S-310,513 Parnassus Ave,Box 0412,95, San Francisco, CA 94143 USA. EM todd.margolis@ucsf.edu OI Krause, Philip/0000-0002-1045-7536; Vallas, Vicky/0000-0002-3919-3773 FU NEI NIH HHS [EY02162, EY10008, P30 EY002162, R01 EY010008] NR 35 TC 49 Z9 50 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2007 VL 81 IS 4 BP 1872 EP 1878 DI 10.1128/JVI.02110-06 PG 7 WC Virology SC Virology GA 136RI UT WOS:000244241400031 PM 17151134 ER PT J AU Liang, HY Badano, A AF Liang, Hongye Badano, Aldo TI Temporal response of medical liquid crystal displays SO MEDICAL PHYSICS LA English DT Article DE liquid crystal display; gray level resolution; temporal blur; temporal response; motion artifact ID AAPM/RSNA TUTORIAL; PACS EQUIPMENT; SELECTION AB Displays based on liquid crystal technology suffer from slow temporal response due to the dynamics of the molecular rearrangement in response to a pixel voltage change. A slow display can affect the visualization by the human observer of subtle contrast in dynamic presentation of volumetric image datasets or real-time image sequences. In this paper, we describe a measurement method for the characterization of the temporal response of medical liquid crystal displays (LCDs). The ratio of luminance difference to noise at the gray levels of concern determines the reliability of measurements. Coefficients of variations are used to represent the measurement reliability. We optimized the repeatability of most response time measurements to less than 10%. However, poor repeatability is encountered for the response of adjacent gray levels. 256 x 255 inter-gray-level transition time matrices were measured for four medical displays and one high-definition TV LCD display. Response times range from below 20 ms to above 150 ms. For each display, response times are not uniformly distributed, with a faster response for large gray-level transitions. Transition times are smaller when the starting gray level is between 10 and 20 for a target between 25 and 150. The difference could be over 100 ms for different transitions within a display. For transitions with poor temporal response, the luminance after 1, 3, and 5 frames reaches only 12, 45, and 75% of the target value, respectively. We also found that LCD response time depends on temperature, with I h warm-up reducing the response time by a factor of 2. C1 NIBIB Lab Assesment Med Imaging Syst, CDRH, US FDA, Rockville, MD 20857 USA. RP Liang, HY (reprint author), NIBIB Lab Assesment Med Imaging Syst, CDRH, US FDA, 12720 Twinbrook Pkwy,HFZ 142, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 14 TC 17 Z9 17 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 2007 VL 34 IS 2 BP 639 EP 646 DI 10.1118/1.2428403 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 139HZ UT WOS:000244424200029 PM 17388181 ER PT J AU DeBell, K Graham, L Reischl, I Serrano, C Bonvini, E Rellahan, B AF DeBell, Karen Graham, Laurie Reischl, Ilona Serrano, Carmen Bonvini, Ezio Rellahan, Barbara TI Intramolecular regulation of phospholipase C-gamma 1 by its C-terminal Src homology 2 domain SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; PLECKSTRIN HOMOLOGY DOMAIN; PLC-GAMMA-L; SH2 DOMAIN; TYROSINE PHOSPHORYLATION; PH DOMAIN; CELL-LINE; C-GAMMA-1; RECEPTOR; ACTIVATION AB Phosphoinositide-specific phospholipase C-gamma 1 (PLC-gamma 1) is a key enzyme that governs cellular functions such as gene transcription, secretion, proliferation, motility, and development. Here, we show that PLC-gamma 1 is regulated via a novel autoinhibitory mechanism involving its carboxy-terminal Src homology (SH2C) domain. Mutation of the SH2C domain tyrosine binding site led to constitutive PLC-gamma 1 activation. The amino-terminal split pleckstrin homology (sPHN) domain was found to regulate the accessibility of the SH2C domain. PLC-gamma 1 constructs with mutations in tyrosine 509 and phenylalanine 510 in the sPHN domain no longer required an intact amino-terminal Src homology (SH2N) domain or phosphorylation of tyrosine 775 or 783 for activation. These data are consistent with a model in which the SH2C domain is blocked by an intramolecular interaction(s) that is released upon cellular activation by occupancy of the SH2N domain. C1 FDA, DMA OPS, CDER, Lab Immunobiol, Bethesda, MD 20892 USA. MacroGenetics Inc, Rockville, MD USA. RP Rellahan, B (reprint author), FDA, DMA OPS, CDER, Lab Immunobiol, NIH Bldg 29B,3NN06,29 Lincoln Dr, Bethesda, MD 20892 USA. EM barbara.rellahan@fda.hhs.gov NR 42 TC 21 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2007 VL 27 IS 3 BP 854 EP 863 DI 10.1128/MCB.01400-06 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 132MD UT WOS:000243946000006 PM 17116690 ER PT J AU Do, TV Symowicz, JC Berman, DM Liotta, LA Petricoin, EF Stack, MS Fishman, DA AF Do, Thuy-Vy Symowicz, Jay C. Berman, David M. Liotta, Lance A. Petricoin, Emanuel F., III Stack, M. Sharon Fishman, David A. TI Lysophosphatidic acid down-regulates stress fibers and up-regulates pro-matrix metalloproteinase-2 activation in ovarian cancer cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID GELATINASE-A ACTIVATION; BINDING PROTEIN RHO; EPITHELIAL-CELLS; FOCAL ADHESIONS; EXTRACELLULAR-MATRIX; ACTIN CYTOSKELETON; COLLAGEN LATTICES; HUMAN-FIBROBLASTS; PHOSPHOLIPASE-D; GROWTH-FACTOR AB Epithelial ovarian cancer (EOC) is asymptomatic at early stages and is often diagnosed late when tumor cells are highly metastatic. Lysophosphatidic acid (LPA) has been implicated in ovarian oncogenesis as levels of this lipid are elevated in patient ascites and plasma. Because the underlying mechanism governing LPA regulation of matrix metalloproteinase-2 (MMP-2) activation remains undefined, we investigated the relationship between LPA-induced changes in actin microfilament organization and MMP-2 enzymatic activity. We report that when cells were cultured at a high density, LPA mediated stress fiber and focal adhesion disassembly and significantly repressed RhoA activity in EOC cells. Inhibition of Rho-kinase/ROCK enhanced both LPA-stimulated loss of stress fibers and pro-MMP-2 activation. In contrast, expression of the constitutively active RhoA(G14V) mutant diminished LPA-induced pro-MMP-2 activation. LPA had no effects on membrane type 1-MMP or tissue inhibitor of metalloproteinase-2 expression, but up-regulated MMP-2 levels, contributing to the induction of MMP-2 activation. Interestingly, when cells were cultured at a low density, stress fibers were present after LPA stimulation, and ROCK activity was required for EOC cell migration. Collectively, these results were consistent with a model in which LPA stimulates the metastatic dissemination of EOC cells by initiating loss of adhesion and metalloproteinase activation. C1 Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, New York, NY 10016 USA. Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, New York, NY 10016 USA. NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Off Director, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Dept Obsted & Gynecol Gynecol Oncol, New York, NY USA. RP Fishman, DA (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, 550 1st Ave, New York, NY 10016 USA. EM director-gynonc@med.nyu.edu FU NCI NIH HHS [R01 CA82562, R01 CA01015, U01 CA85133, P50 CA83639, R01 CA89503] NR 53 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD FEB PY 2007 VL 5 IS 2 BP 121 EP 131 DI 10.1158/1541-7786.MCR-06-0319 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 140WT UT WOS:000244538200002 PM 17314270 ER PT J AU Klaschik, S Gursel, I Klinman, DA AF Klaschik, Sven Gursel, Ihsan Klinman, Dennis A. TI CpG-mediated changes in gene expression in murine spleen cells identified by microarray analysis SO MOLECULAR IMMUNOLOGY LA English DT Article DE gene regulation; CpG oligodeoxynucleotides; inflammation; molecular biology ID TOLL-LIKE RECEPTORS; BACTERIAL-DNA; DENDRITIC CELLS; IMMUNE-RESPONSE; CUTTING EDGE; IN-VIVO; ACTIVATION; MACROPHAGES; OLIGODEOXYNUCLEOTIDES; MOTIFS AB Unmethylated CpG motifs interact with Toll-like receptor 9 (TLR9), triggering an innate immune response characterized by the production of cytokines, chemokines and immunoglobulins. Microarray analysis of cDNA from murine spleen cells stimulated with CpG oligodeoxynucleotides (ODN) identified reproducible changes in gene expression over time. Eight genes are significantly up-regulated 2 h post CpG ODN stimulation, most of which contribute to the induction of innate or adaptive immune responses. Network analysis indicates that TNF and NFKB1 are key regulators of gene expression at this early time point. At 4h, ILIB in addition to TNF and NFKB1 play dominant roles in the up-regulation of immune gene expression, whereas by 8 h this function is mediated by TNF, IFNG, and MYC. Genes responsible for down-regulating CpG-induced responses were also identified, dampening what would otherwise be a continuous positive feedback loop. This work provides novel insights into the regulatory process embedded in the gene expression profile induced by CpG ODN, identifies novel genes associated with CpG-induced immune stimulation, and clarifies the breadth of the immune response elicited via TLR9. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bethesda, MD 20892 USA. RP Klinman, DA (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bldg 29A,Room 3D10, Bethesda, MD 20892 USA. EM dennis.klinman@fda.hhs.gov OI Gursel, Ihsan/0000-0003-3761-1166 NR 45 TC 26 Z9 30 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD FEB PY 2007 VL 44 IS 6 BP 1095 EP 1104 DI 10.1016/j.molimm.2006.07.083 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 118NT UT WOS:000242949700005 PM 16930709 ER PT J AU Shen, SR Yu, HN Chen, P Yin, JJ Xiong, YK AF Shen, Sheng-rong Yu, Hai-ning Chen, Ping Yin, Jun-jie Xiong, Yao-kang TI Fatty acids in tea shoots (Camellia sinensis (L.) O. Kuntze) and their effects on the growth of retinal RF/6A endothelial cell lines SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE ESR; long chain fatty acids; RF/6A cells; retinal; tea ID ALPHA-LINOLENIC ACID; DOCOSAHEXAENOIC ACID; EXPRESSION; INFLAMMATION; CATECHINS; INFANTS; DISEASE; MARKERS; STRESS; BLACK AB Chemo-protective effects of tea on ocular diseases were recorded in Chinese pharmacopoeia about 2000 years ago by eating tea. In the present study, contents of fatty acids (FAs) in tea shoots were determined by capillary GC; and the growth of RF/6A cells was also investigated by exposure to various representative FAs existing in tea shoots with pathologically relevant concentrations (40500 mu M) by ameliorated MTT assay and flow cytometry. Electron spin resonance (ESR) was used to measure oxygen consumption and investigate the free radical scavenging ability of linoleic acid (LA). Results showed that the most abundant long chain FAs were palmitic, linoleic, and a-linolenic acid in tea shoots; some RF/6A cells became suspended in culture medium treated by a high dose of both saturated and unsaturated FAs, but no apoptosis was observed. Moreover, it seemed that those FAs with different structure had various effects on the cell proliferation at their relatively low concentrations, LA expressed antioxidant activity in this study, which might be an important mechanism on the protection of eyes. C1 Zhejiang Univ, Dept Tea Sci, Hangzhou 310029, Peoples R China. Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310027, Peoples R China. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Zhejiang Univ, Coll Pharmaacol, Hangzhou 310027, Peoples R China. RP Shen, SR (reprint author), Zhejiang Univ, Dept Tea Sci, Hangzhou 310029, Peoples R China. EM shrshen@zju.edu.cn RI Yin, Jun Jie /E-5619-2014 NR 25 TC 9 Z9 11 U1 2 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD FEB PY 2007 VL 51 IS 2 BP 221 EP 228 DI 10.1002/mnfr.200600147 PG 8 WC Food Science & Technology SC Food Science & Technology GA 148TY UT WOS:000245098700008 PM 17262883 ER PT J AU Sampson, JH Brady, ML Petry, NA Croteau, D Friedman, AH Friedman, HS Wong, T Bigner, DD Pastan, I Puri, RK Pedain, C AF Sampson, John H. Brady, Martin L. Petry, Neil A. Croteau, David Friedman, Allan H. Friedman, Henry S. Wong, Terence Bigner, Darell D. Pastan, Ira Puri, Raj K. Pedain, Christoph TI Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: Descriptive effects of target anatomy and catheter positioning SO NEUROSURGERY LA English DT Article DE brain neoplasms; convection; drug delivery systems; glioblastoma; single-photon emission-computed tomography ID IL4-PSEUDOMONAS EXOTOXIN NBI-3001; BRAIN-TUMORS; PSEUDOMONAS EXOTOXIN; NEUROTROPHIC FACTOR; GLIAL NEOPLASMS; COMPUTED-TOMOGRAPHY; FUSION PROTEINS; DRUG-DELIVERY; INFUSION; MICROINFUSION AB OBJECTIVE: Convection-enhanced delivery (CED) holds tremendous potential for drug delivery to the brain. However, little is known about the volume of distribution achieved within human brain tissue or how target anatomy and catheter positioning influence drug distribution. The primary objective of this study was to quantitatively describe the distribution of a high molecular weight agent by CED relative to target anatomy and catheter position in patients with malignant gliomas. METHODS: Seven adult patients with recurrent malignant gliomas underwent intracerebral infusion of the tumor-targeted cytotoxin, cintredekin besudotox, concurrently with I-123-labeled human serum albumin. High-resolution single-photon emission computed tomographic images were obtained at 24 and 48 hours and were coregistered with magnetic resonance imaging scans. The distribution of I-123-labeled human serum albumin relative to target anatomy and catheter position was analyzed. RESULTS: Intracerebral CED infusions were well-tolerated and some resulted in a broad distribution of I-123-labeled human serum albumin, but target anatomy and catheter positioning had a significant influence on infusate distribution even within non-contrast-enhancing areas of brain. Intratumoral infusions were anisotropic and resulted in limited coverage of the enhancing tumor area and adjacent peritumoral regions. CONCLUSIONS: CED has the potential to deliver high molecular weight agents into tumor-infiltrated brain parenchyma with volumes of distribution that are clinically relevant. Target tissue anatomy and catheter position are critical parameters in optimizing drug delivery. C1 Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Therataxis LLC, Baltimore, MD USA. NeoPharm Inc, Lake Forest, IL USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. BrainLAB AG, Heimstetten, Germany. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Box 3050,Room 220,Sands Bldg, Durham, NC 27710 USA. EM john.sampson@duke.edu NR 56 TC 51 Z9 52 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 2007 VL 60 IS 2 SU S BP 89 EP 98 DI 10.1227/01.NEU.0000249256.09289.5F PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 136NE UT WOS:000244230600025 ER PT J AU Trumbo, PR Ellwood, KC AF Trumbo, Paula R. Ellwood, Kathleen C. TI Supplemental calcium and risk reduction of hypertension, pregnancy-induced hypertension, and preeclampsia: An evidence-based review by the US food and drug administration SO NUTRITION REVIEWS LA English DT Review DE calcium; hypertension; pre-eclampsia; pregnancy ID AMBULATORY BLOOD-PRESSURE; RANDOMIZED CONTROLLED-TRIAL; ORAL CALCIUM; DIETARY CALCIUM; DOUBLE-BLIND; MILD HYPERTENSION; NONPHARMACOLOGIC INTERVENTIONS; GESTATIONAL HYPERTENSION; NORMOTENSIVE SUBJECTS; NULLIPAROUS WOMEN AB The labeling of health claims that meet the significant scientific agreement (SSA) standard (authorized health claims) and qualified health claims on conventional foods and dietary supplements requires premarket approval by the US Food and Drug Administration (FDA). FDA conducts an evidence-based review to determine whether there is sufficient evidence to support an authorized or qualified health claim. An evidence-based review was conducted on the human intervention and observational studies evaluating the role of supplemental calcium in reducing the risk of hypertension, pregnancy-induced hypertension, and preeclampsia. This review provides FDA's evaluation of the current scientific evidence on the role of supplemental calcium in reducing the risk of these three end points. Based on this evidence-based review, the agency concluded that the relationship between calcium and risk of hypertension is inconsistent and inconclusive, and the relationship between calcium and risk of pregnancy-induced hypertension and preeclampsia is highly unlikely. C1 US FDA, Div Nutr Programs & Labeling, College Pk, MD 20740 USA. RP Trumbo, PR (reprint author), US FDA, Div Nutr Programs & Labeling, HFS-830,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Paula.Trumbo@FDA.HHS.gov NR 86 TC 31 Z9 37 U1 2 U2 8 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD FEB PY 2007 VL 65 IS 2 BP 78 EP 87 DI 10.1301/nr.2007.feb.78-87 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 136NI UT WOS:000244231000003 PM 17345960 ER PT J AU Tavris, DR Gallauresi, BA Dey, S Brindis, R Mitchel, K AF Tavris, Dale R. Gallauresi, Beverly Albrecht Dey, Syamal Brindis, Ralph Mitchel, Kristi TI Risk of local adverse events by gender following cardiac catheterization SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE hemostasis device; cardiac catheterization; adverse event ID COMPLICATIONS; CLOSURE; DEVICES AB Purpose To assess the reason for the relative high risk of local complications for women following cardiac catheterization by evaluating the associations between gender, sheath size, and local adverse outcomes following cardiac catheterization. Methods The data used in this study were obtained from a portion of the American College of Cardiology-National Cardiovascular Data Registry(TM) (ACC-NCDRTM), which included 13 878 patients who underwent cardiac catheterization at one of 59 participating cardiac catheterization institutions throughout the United States during late 2003. Rates of serious local vascular adverse events were calculated by gender following cardiac catheterization, by type of vascular hemostasis used, stratified by arterial sheath size. Results Serious local vascular events were reported in 3.54% of patients, most commonly hematoma (2.00%). The relative risk for women of any vascular complication was 1.40 [95%CI = 1.17,1.67, p = 0.0002]. A statistically significant relative risk for woman was evident when collagen plug devices or manual compression alone were used as the first method for hemostasis. The rate of vascular complications increased progressively with increasing sheath size, more so in women than in men. Conclusions High relative risk for women of local vascular complications following cardiac catheterization was demonstrated with use of manual compression, as well as with collagen plug devices to control femoral artery bleeding. Large sheath size is associated with both a relatively high absolute risk and a high relative risk for women. Knowledge of this information should be considered by interventional cardiologists in making decisions on how to achieve hemostasis following cardiac catheterization. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 US FDA, CDRH, Epidemiol Branch, Rockville, MD 20857 USA. San Francisco Kaiser Hosp, ACC, NCDR, San Francisco, CA USA. RP Tavris, DR (reprint author), US FDA, CDRH, Epidemiol Branch, Rockville, MD 20857 USA. EM drt@cdrh.fda.gov NR 13 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD FEB PY 2007 VL 16 IS 2 BP 125 EP 131 DI 10.1002/pds.1307 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 139MC UT WOS:000244434900001 PM 16981230 ER PT J AU Miller, SA Coelho, SC Zmudzka, BZ Beer, JZ AF Miller, Sharon A. Coelho, Sergio C. Zmudzka, Barbara Z. Beer, Janusz Z. TI Criticism of FDA pilot study unfounded (response to R. M. Sayre and J. C. Dowdy) SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Letter ID BED C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 8 TC 2 Z9 2 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD FEB PY 2007 VL 23 IS 1 BP 59 EP 60 DI 10.1111/j.1600-0781.2007.00272.x PG 2 WC Dermatology SC Dermatology GA 129US UT WOS:000243756200015 ER PT J AU Miyamura, Y Coelho, SG Wolber, R Miller, SA Wakamatsu, K Zmudzka, BZ Ito, S Smuda, C Passeron, T Choi, W Batzer, J Yamaguchi, Y Beer, JZ Hearing, VJ AF Miyamura, Yoshinori Coelho, Sergio G. Wolber, Rainer Miller, Sharon A. Wakamatsu, Kazumasa Zmudzka, Barbara Z. Ito, Shosuke Smuda, Christoph Passeron, Thierry Choi, Wonseon Batzer, Jan Yamaguchi, Yuji Beer, Janusz Z. Hearing, Vincent J. TI Regulation of human skin pigmentation and responses to ultraviolet radiation SO PIGMENT CELL RESEARCH LA English DT Review DE skin; pigmentation; ultraviolet; photoprotection; DNA damage; repeated irradiation ID INDUCED DNA-DAMAGE; CUTANEOUS MALIGNANT-MELANOMA; CULTURED HUMAN MELANOCYTES; PHOTOPROTECTED HUMAN SKIN; MELANOCORTIN-1 RECEPTOR; HUMAN-EPIDERMIS; ANIMAL-MODELS; UV-RADIATION; DISTRIBUTION PATTERNS; ORGANELLE TRANSPORT AB Pigmentation of human skin is closely involved in protection against environmental stresses, in particular exposure to ultraviolet (UV) radiation. It is well known that darker skin is significantly more resistant to the damaging effects of UV, such as photocarcinogenesis and photoaging, than is lighter skin. Constitutive skin pigmentation depends on the amount of melanin and its distribution in that tissue. Melanin is significantly photoprotective and epidermal cells in darker skin incur less DNA damage than do those in lighter skin. This review summarizes current understanding of the regulation of constitutive human skin pigmentation and responses to UV radiation, with emphasis on physiological factors that influence those processes. Further research is needed to characterize the role of skin pigmentation to reduce photocarcinogenesis and to develop effective strategies to minimize such risks. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Beiersdorf AG, Dept Skin Res, Hamburg, Germany. Ctr Devices & Radiol Hlth Food & Drug Adm, Rockville, MD USA. Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Toyoake, Aichi 47011, Japan. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008; OI Wakamatsu, Kazumasa/0000-0003-1748-9001; Ito, Shosuke/0000-0001-9182-5144; Passeron, Thierry/0000-0002-0797-6570 FU Intramural NIH HHS NR 107 TC 83 Z9 84 U1 2 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD FEB PY 2007 VL 20 IS 1 BP 2 EP 13 DI 10.1111/j.1600-0749.2006.00358.x PG 12 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 125AL UT WOS:000243413800002 PM 17250543 ER PT J AU Martins, C Oliveira, NG Pingarilho, M da Costa, GG Martins, V Marques, MM Beland, FA Churchwell, MI Doerge, DR Rueff, J Gaspar, JF AF Martins, Celia Oliveira, Nuno G. Pingarilho, Marta da Costa, Goncalo Gamboa Martins, Vanda Marques, M. Matilde Beland, Frederick A. Churchwell, Mona I. Doerge, Daniel R. Rueff, Jose Gaspar, Jorge Francisco TI Cytogenetic damage induced by acrylamide and glycidamide in mammalian cells: Correlation with specific glycidamide-DNA adducts SO TOXICOLOGICAL SCIENCES LA English DT Article DE acrylamide; glycidamide; DNA adducts; chromosomal aberrations; sister chromatid exchanges ID METABOLITE GLYCIDAMIDE; HEMOGLOBIN ADDUCTS; B6C3F(1) MICE; GENOTOXICITY; RAT; TOXICOKINETICS; PRODUCTS; BREAKS; RISK; V79 AB Acrylamide (AA) is a suspected human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is thought to be the active metabolite playing a central role in AA genotoxicity. In this work we investigated DNA damage induced by AA and GA in mammalian cells, using V79 Chinese hamster cells. For this purpose, we evaluated two cytogenetic end points, chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs), as well as the levels of specific GA-DNA adducts, namely, N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl)adenine (N3-GA-Ade) using high-performance liquid chromatography coupled with tandem mass spectrometry. GA was more cytotoxic and clastogenic than AA. Both AA and GA induced CAs (breaks and gaps) and decreased the mitotic index. GA induced SCEs in a dose-responsive manner; with AA, SCEs were increased at only the highest dose tested (2mM). A linear dose-response relationship was observed between the GA concentration and the levels of N7-GA-Gua. This adduct was detected for concentrations as low as 1 mu M GA. N3-GA-Ade was also detected, but only at very high GA concentrations (>= 250 mu M). There was a very strong correlation between the levels of N7-GA-Gua in the GA- and AA-treated cells and the extent of SCE induction. Such correlation was not apparent for CAs. These data suggest that the induction of SCEs by AA is associated with the metabolism of AA to GA and subsequent formation of depurinating DNA adducts; however, other mechanisms must be involved in the induction of CAs. C1 Univ Nova Lisboa, Dept Genet, Fac Med Sci, P-1349008 Lisbon, Portugal. Univ Lisbon, Fac Pharm, P-1649019 Lisbon, Portugal. Inst Canc Res, Sect Mol Carcinogenesis, Sutton SM2 5NG, Surrey, England. Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Gaspar, JF (reprint author), Univ Nova Lisboa, Dept Genet, Fac Med Sci, Rua Junqueira 96, P-1349008 Lisbon, Portugal. EM jgaspar.gene@fcm.unl.pt RI Rueff, Jose/E-6426-2013; Gaspar, Jorge/M-9078-2013; Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; iMed.ULisboa, iMed.ULisboa/C-6292-2014; Oliveira, Nuno/A-7407-2014; iMed.ULisboa, CBT /B-4215-2014; Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013; OI Gaspar, Jorge/0000-0002-2102-4920; Marques, M. Matilde/0000-0002-7526-4962; Oliveira, Nuno/0000-0001-6114-6829; Martins, Celia/0000-0002-8488-5103; Rueff, Jose/0000-0002-0969-610X; Rueff, Jose/0000-0002-8456-7295 NR 37 TC 36 Z9 42 U1 0 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2007 VL 95 IS 2 BP 383 EP 390 DI 10.1093/toxsci/kfl155 PG 8 WC Toxicology SC Toxicology GA 130GL UT WOS:000243787800011 PM 17088317 ER PT J AU Stantchev, TS Markovic, I Telford, WG Clouse, KA Broder, CC AF Stantchev, Tzanko S. Markovic, Ingrid Telford, William G. Clouse, Kathleen A. Broder, Christopher C. TI The tyrosine kinase inhibitor genistein blocks HIV-1 infection in primary human macrophages SO VIRUS RESEARCH LA English DT Review DE HIV; macrophage tyrosine kinase; genistem; entry; fusion; receptor; CD4; CCR5; CXCR4; envelope glycoprotem; gp120; infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMARY T-LYMPHOCYTES; JUN NH2-TERMINAL KINASE; CHEMOKINE RECEPTOR 5; ENVELOPE GLYCOPROTEIN; SIGNAL-TRANSDUCTION; MONONUCLEAR PHAGOCYTES; MEMBRANE MICRODOMAINS; ACTIN POLYMERIZATION; NEUROBLASTOMA-CELLS AB Binding of HIV-1 envelope glycoprotein (Env) to its cellular receptors elicits a variety of signaling events, including the activation of select tyrosine kinases. To evaluate the potential role of such signaling, we examined the effects of the tyrosine kinase inhibitor, genistein, on HIV-1 entry and infection of human macrophages using a variety of assays. Without altering cell viability, cell surface expression of CD4 and CCR5 or their abilities to interact with Env, genistein inhibited infection of macrophages by reporter gene-encoding, P-lactamase containing, or wild type virions, as well as Env-mediated cell-fusion. The observation that genistein blocked virus infection if applied before, during or immediately after the infection period, but not 24 h later: coupled with a more pronounced inhibition of infection in the reporter gene assays as compared to both P-lactamase and p24 particle entry assays, imply that genistein exerts its inhibitory effects on both entry and early post-entry steps. These findings suggest that other exploitable targets, or steps, of the HIV-1 infection process may exist and could serve as additional opportunities for the development of new therapeutics. Published by Elsevier B.V. C1 Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Broder, CC (reprint author), Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM cbroder@usuhs.mil FU NIAID NIH HHS [R01 AI043885, R21 AI043885, AI43885] NR 108 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD FEB PY 2007 VL 123 IS 2 BP 178 EP 189 DI 10.1016/j.virusres.2006.09.004 PG 12 WC Virology SC Virology GA 133MP UT WOS:000244017300009 PM 17030448 ER PT J AU Fricke, M Zeller, M Cullen, W Witkowski, M Creed, J AF Fricke, Michael Zeller, Matthias Cullen, William Witkowski, Mark Creed, John TI Dimethylthioarsinic anhydride: A standard for arsenic speciation SO ANALYTICA CHIMICA ACTA LA English DT Article DE inductively coupled plasma-mass spectrometry; electrospray ionization-mass spectrometry; dimethylarsinic acid; dimethylarsinothioic acid; hydrogen sulfide; speciation ID DIMETHYLARSINIC ACID; HUMAN URINE; TOXICITY; METABOLITES; ARSENOSUGAR; INGESTION; COMPOUND; WATER AB Dimethylthioarsinic acid (DMTA(V)) has recently been identified in biological, dietary and environmental matrices. The relevance of this compound to the toxicity of arsenic in humans is unknown and further exposure assessment and metabolic studies are difficult to conduct because of the unavailability of a well characterized standard. The synthesis of DMTA(V) was accomplished by the reaction of dimethylarsinic acid (DMA(V)) with hydrogen sulfide. The initial reaction product produced is DMTA(V) but multiple products over the course of the reaction are also observed. Therefore, a chromatographic separation was developed to monitor the reaction progress via LC-ICP-MS. In this synthesis, conversion of DMA(V) to DMTA(V) was not taken to completion to avoid the production of side products. The product was isolated from the starting material by standard organic techniques. Single crystal diffraction demonstrated that solid DMTA(V) is present in the form of the oxygen-bridged dimethylthioarsinic anhydride. Dissolution of the anhydride in water produces the acid form of DMTA(V) and the aqueous phase DMTA(V) provided a characteristic molecular ion of m/z 155 by LC-ESI-MS. The synthesis and isolation of dimethylthioarsinic anhydride provides a stable crystalline standard suitable for identification, toxicological study and exposure assessment of dimethylthioarsinic acid. (c) 2006 Published by Elsevier B.V. C1 US EPA, Natl Exposure Res Lab, Microbiol & Chem Exposure Assessment Res Div, Cincinnati, OH 45268 USA. Youngstown State Univ, Dept Chem, STaRBURST Cyberdiffract Consortium, Youngstown, OH 44555 USA. Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. US FDA, Forens Chem Ctr, Vibrat Spect Lab, Cincinnati, OH 45237 USA. RP Creed, J (reprint author), US EPA, Natl Exposure Res Lab, Microbiol & Chem Exposure Assessment Res Div, 26 W Martin Luther King Dr, Cincinnati, OH 45268 USA. EM creed.jack@epa.gov RI Creed, John/A-9187-2009; Zeller, Matthias/C-2255-2009 OI Zeller, Matthias/0000-0002-3305-852X NR 20 TC 22 Z9 23 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD JAN 30 PY 2007 VL 583 IS 1 BP 78 EP 83 DI 10.1016/j.aca.2006.09.048 PG 6 WC Chemistry, Analytical SC Chemistry GA 129CH UT WOS:000243705500011 PM 17386529 ER PT J AU Tesfamariam, B AF Tesfamariam, Belay TI Local vascular toxicokinetics of stent-based drug delivery SO TOXICOLOGY LETTERS LA English DT Review DE stents; drug delivery; release kinetics; vascular toxicity; restenosis ID SIROLIMUS-ELUTING STENTS; PORCINE CORONARY MODEL; NEOINTIMAL FORMATION; CELLULAR PROLIFERATION; BALLOON ANGIOPLASTY; ARTERIAL INJURY; RESTENOSIS; PACLITAXEL; HUMANS; THROMBOSIS AB One of the major limitations of balloon angioplasty is early restenosis as a result of elastic recoil leading to vessel occlusion. The constrictive (negative) remodeling of the blood vessel is overcome by implanting a balloon expandible, metal stent to dilate the artery and thereby prevent elastic recoil. However, bare metal stent implants cause mechanical injury to the intima and release of inflammatory mediators which then initiates formation of neointimal layer leading to restenosis. In-stent restenosis is histologically distinct from restenosis following balloon angioplasty, in which in-stent restenosis is accompanied by increased smooth muscle proliferation, migration, extracellular matrix and collagen synthesis leading to neointimal hyperplasia. To overcome neointimal hyperplasia, stents have been coated with pharmacological agents that inhibit smooth muscle cell proliferation and migration. The drug and polymer combination coated onto stent device is an efficient form of drug delivery system which can provide high concentrations of drug in the tissues over an extended period of time to achieve antiproliferative therapeutic effect. The permanent stent implants pose the risk of a continuous interaction between the non-biodegradable polymer coating and intimal surface leading to physical irritation, endothelial dysfunction, hypersensitivity reactions, delayed healing and excess risk of late stent thrombosis. This review highlights the relationship between local drug delivery using the stent platform, release kinetics and local vascular toxicity. Published by Elsevier Ireland Ltd. C1 US FDA, Div Cardiovasc & Renal, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Tesfamariam, B (reprint author), US FDA, Div Cardiovasc & Renal, Ctr Drug Evaluat & Res, Bldg 22,Rm 4176,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM belay.tesfamariam@fda.hhs.gov NR 47 TC 23 Z9 25 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JAN 30 PY 2007 VL 168 IS 2 BP 93 EP 102 DI 10.1016/j.toxlet.2006.11.013 PG 10 WC Toxicology SC Toxicology GA 134CD UT WOS:000244059300001 PM 17169513 ER PT J AU Xia, Q Yin, JJ Fu, PP Boudreau, MD AF Xia, Qingsu Yin, Jun Jie Fu, Peter P. Boudreau, Mary D. TI Photo-irradiation of Aloe vera by UVA - Formation of free radicals, singlet oxygen, superoxide, and induction of lipid peroxidation SO TOXICOLOGY LETTERS LA English DT Article DE Aloe vera; UVA; photo-irradiation; lipid peroxidation; reactive oxygen species; ESR ID LIVER-INJURY; SOYBEAN LIPOXYGENASE; ANTIOXIDANT ACTIVITY; RETINYL PALMITATE; BARBALOIN CONTENT; LIGHT; EMODIN; DAMAGE; DNA; IDENTIFICATION AB Aloe vera whole leaf extracts are incorporated into a wide variety of topically applied commercial products. Aloe vera whole leaf extracts may contain anthraquinones, which have been shown to generate reactive oxygen species in the presence of ultraviolet A (UVA) light. Exposure to UVA light alone can also generate reactive oxygen species and is associated with photo-damaged and photo-aged skin in humans. This paper examines the photochemical properties of two Aloe vera whole leaf extracts that differed in their anthraquinone content. In the presence of methyl linoleate, the UVA irradiation of Aloe vera leaf extracts induced lipid peroxidation. The amounts of lipid peroxides formed were higher in the Aloe vera leaf extract that contained lower amounts of anthraquinones. Superoxide dismutase and sodium azide inhibited and deuterium oxide enhanced the formation of lipid peroxides, suggesting that singlet oxygen and superoxide were involved in the mechanism. Spin trapping electron spin resonance (ESR) spectroscopy was used to investigate the generation of free radicals by the UVA photo-irradiated Aloe vera plant extracts. ESR measurements indicated that the UVA photo-irradiation of Aloe vera plant extracts produced carbon-centered free radicals. These results suggest that humans exposed to products that contain Aloe vera whole leaf extracts may have enhanced sensitivity to ultraviolet light. Published by Elsevier Ireland Ltd. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Boudreau, MD (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Mboudreau@nctr.fda.gov RI Yin, Jun Jie /E-5619-2014 NR 48 TC 28 Z9 28 U1 3 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JAN 30 PY 2007 VL 168 IS 2 BP 165 EP 175 DI 10.1016/j.toxlet.2006.11.015 PG 11 WC Toxicology SC Toxicology GA 134CD UT WOS:000244059300009 PM 17197137 ER PT J AU Kimchi-Sarfaty, C Oh, JM Kim, IW Sauna, ZE Calcagno, AM Ambudkar, SV Gottesman, MM AF Kimchi-Sarfaty, Chava Oh, Jung Mi Kim, In-Wha Sauna, Zuben E. Calcagno, Anna Maria Ambudkar, Suresh V. Gottesman, Michael M. TI A "silent" polymorphism in the MDR1 gene changes substrate specificity SO SCIENCE LA English DT Article ID SYNONYMOUS CODON USAGE; SINGLE-NUCLEOTIDE POLYMORPHISMS; MULTIDRUG-RESISTANCE GENE; VIRUS EXPRESSION SYSTEM; HUMAN P-GLYCOPROTEIN; MESSENGER-RNA; IN-VITRO; FUNCTIONAL-CHARACTERIZATION; PROTEIN-STRUCTURE; VIVO C1 NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), US FDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr,Room 316, Bethesda, MD 20892 USA. EM kimchi@cber.fda.gov; jmoh@snu.ac.kr; mgottesman@nih.gov RI Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753; Oh, JungMi/0000-0002-1836-1707 FU Intramural NIH HHS NR 29 TC 1332 Z9 1398 U1 11 U2 82 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 JAN 26 PY 2007 VL 315 IS 5811 BP 525 EP 528 DI 10.1126/science.1135308 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129JU UT WOS:000243726600050 PM 17185560 ER PT J AU Noonan, GO Begley, TH Diachenko, GW AF Noonan, G. O. Begley, T. H. Diachenko, G. W. TI Rapid quantitative and qualitative confirmatory method for the determination of monofluoroacetic acid in foods by liquid chromatography-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE fluoroacetic acid; food adulteration ID SODIUM MONOFLUOROACETATE; GAS-CHROMATOGRAPHY; FLUOROACETIC ACID; CARBOXYLIC-ACIDS; AQUEOUS SAMPLES; 2-NITROPHENYLHYDRAZIDES; COMPOUND-1080; PENTAFLUOROBENZYLATION; BEVERAGES; HPLC AB A rapid quantitative method and a qualitative confirmatory method for the determination of monolluoroacefic acid (MFA) in complex food matrices are presented. The quantitative method utilizes a water extraction, solid phase extraction clean-up and liquid chromatography-mass spectrometry (LC-MS) for determination of MFA. This method showed a high degree of specificity, detecting MFA in all of the spiked samples, while none of the unfortified samples tested positive for MFA. Spike recoveries were high in all matrices analyzed, varying from 85 to 110%, and comparable at low (2 mg/L) and high (20 mg/L) spiking levels. Repeatability tests at the low spiking levels yielded RSDs of less than 5% for all matrices analyzed. The qualitative confirmatory method developed is conceptually different from the quantitative method, ensuring that both methods would not be subject to the same interferences. The method uses the formation of the hydrazide of MFA through derivatization with 2-nitrophenylhydrazine. This derivatization is well established for the determination of carboxylic acids, but this is the first application to the determination of MFA. The derivatization yield was matrix dependent, however the limit of detection (LOD) (0.8 mu g/L) was sufficient to confirm the presence of MFA in all spiked matrices. Repeatability tests at the low spiking levels yielded RSDs of approximately 7% for all matrices analyzed. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Noonan, GO (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Gregory.noonan@fda.hhs.gov NR 26 TC 11 Z9 11 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JAN 19 PY 2007 VL 1139 IS 2 BP 271 EP 278 DI 10.1016/j.chroma.2006.11.034 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 127HA UT WOS:000243574900016 PM 17141253 ER PT J AU Granasy, L Pusztai, T Saylor, D Warren, JA AF Granasy, Laszlo Pusztai, Tamas Saylor, David Warren, James A. TI Phase field theory of heterogeneous crystal nucleation SO PHYSICAL REVIEW LETTERS LA English DT Article ID SOLID-LIQUID INTERFACE; MOLECULAR-DYNAMICS; LINE-TENSION; SOLIDIFICATION; SIMULATION; LAYERS; MODEL AB The phase field approach is used to model heterogeneous crystal nucleation in an undercooled pure liquid in contact with a foreign wall. We discuss various choices for the boundary condition at the wall and determine the properties of critical nuclei, including their free energy of formation and the contact angle as a function of undercooling. For particular choices of boundary conditions, we may realize either an analog of the classical spherical cap model or decidedly nonclassical behavior, where the contact angle decreases from its value taken at the melting point towards complete wetting at a critical undercooling, an analogue of the surface spinodal of liquid-wall interfaces. C1 Res Inst Solid State Phys & Opt, H-1525 Budapest, Hungary. US FDA, Rockville, MD 20852 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RP Granasy, L (reprint author), Res Inst Solid State Phys & Opt, POB 49, H-1525 Budapest, Hungary. RI Pusztai, Tamas/A-5718-2012; Granasy, Laszlo/A-6221-2012; Warren, James/B-1698-2008 OI Pusztai, Tamas/0000-0002-1281-2933; Warren, James/0000-0001-6887-1206 NR 35 TC 78 Z9 78 U1 2 U2 57 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD JAN 19 PY 2007 VL 98 IS 3 AR 035703 DI 10.1103/PhysRevLett.98.035703 PG 4 WC Physics, Multidisciplinary SC Physics GA 127LJ UT WOS:000243587200034 PM 17358695 ER PT J AU Puccioni-Sohler, M Yamano, Y Rios, M Carvalho, SMF Vasconcelos, CCF Papais-Alvarenga, R Jacobson, S AF Puccioni-Sohler, M. Yamano, Y. Rios, M. Carvalho, S. M. F. Vasconcelos, C. C. F. Papais-Alvarenga, R. Jacobson, S. TI Differentiation of HAM/TSP from patients with multiple sclerosis infected with HTLV-I SO NEUROLOGY LA English DT Article ID VIRUS TYPE-I; PROVIRAL LOAD; INTRATHECAL SYNTHESIS; DIAGNOSTIC-CRITERIA; CEREBROSPINAL-FLUID; PREDICT CONVERSION; MRI CRITERIA; MYELOPATHY; ANTIBODY; IGG AB Objective: To better differentiate patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) from patients with multiple sclerosis (MS) who are HTLV-I seropositive, we compared the HTLV-I antibodies and HTLV-I proviral DNA loads in CSF and peripheral blood mononuclear cells (PBMC). Methods: Intrathecal synthesis of HTLV-I antibodies and HTLV-I proviral DNA loads in CSF and PBMC were measured and compared in 39 Brazilian patients: 17 HAM/TSP and 22 HTLV-I-seropositive non-HAM/ TSP (7 with other neurologic diseases, 11 asymptomatic carriers, and 4 HTLV-I-seropositive patients with an MS-like phenotype). In addition, we followed immunologic and virologic markers in comparison to the clinical course ( by Kurtzke Expanded Disability Status Scale) of seven patients (five with HAM/TSP and two with an MS-like phenotype) for a mean period of 16 (SD +/- 5) months. Results: The proviral load in CSF and PBMC was higher in HAM/TSP than in non-HAM/TSP patients, except in the two HTLV-I-seropositive patients with an MS-like phenotype that also fulfilled the criteria for HAM/TSP. Higher HTLV-I proviral DNA load in CSF was associated with the higher proviral DNA load in PBMC and lower intrathecal synthesis of HTLV-I antibodies. These laboratory findings remained stable during follow-up. Conclusion: The high proviral load in peripheral blood mononuclear cells or in CSF or both may be a good marker of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and can differentiate patients with HAM/TSP from patients with multiple sclerosis infected with HTLV-I. C1 Univ Fed Rio de Janeiro, Gaffree Guinle Univ Hosp, Serv Neurol, BR-21941 Rio De Janeiro, Brazil. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD USA. Univ Fed Fluminense, Antonio Pedro Hosp, Neurol Serv, Rio De Janeiro, Brazil. Inst Estadual Hematol Arthur De S Cavalcanti, Neuolife Cerebrosinal Fluid Lab, Rio De Janeiro, Brazil. RP Puccioni-Sohler, M (reprint author), Rua Dezenove De Fevereiro 185-705, BR-22280030 Rio De Janeiro, Brazil. EM mpuccioni@hucff.ufrj.br NR 26 TC 21 Z9 22 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 16 PY 2007 VL 68 IS 3 BP 206 EP 213 DI 10.1212/01.wnl.0000251300.24540.c4 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 126CB UT WOS:000243488700010 PM 17224575 ER PT J AU Naeger, LK Struble, KA AF Naeger, Lisa K. Struble, Kimberly A. TI Food and drug administration analysis of tipranavir clinical resistance in HIV-1-infected treatment-experienced patients SO AIDS LA English DT Article DE HIV protease inhibitor; virologic response; resistance; tipranavir enfurvirtide ID PROTEASE INHIBITOR; SUSCEPTIBILITY; PNU-140690 AB Objective: To assess the resistance profile of tipranavir. Methods: Resistance analyses were performed on Boehringer Ingelheim-sponsored studies examining the safety and efficacy of tipranavir in highly treatment-experienced individuals at 24 weeks. Virologic response rates based on the presence of baseline primary protease inhibitor mutations and based on baseline tipranavir susceptibility were evaluated, and the development of protease mutations during treatment with tipranavir was analyzed. Results: Virologic response rates in tipranavir-treated individuals were reduced when isolates with substitutions at amino acid positions 113, V32, M36,147, Q58, D60 V82 or 184 were present at baseline. In addition, virologic response rates to tipranavir decreased when the number of baseline protease inhibitor (PI) mutations was five or more. Individuals who received tipranavir without concomitant enfurvitide and had five or more baseline PI mutations group began to lose antiviral response between weeks 4 and 8. However, individuals taking enfuvirtide with tipranavir were able to achieve greater than 1.5 log(10) reductions in viral load from baseline out to 24 weeks even if they had five or more baseline PI mutations. Virologic response rates to tipranavir decreased when the baseline phenotype for tipranavir had a greater than three-fold shift in the 50% effective concentration (EC50) from reference. The most common protease mutations that developed in tipranavir-treated individuals who experienced virologic failure were L10I/V/S, I13V, L33V/I/F, M36V/I/L V82T, V82L, and 184V. The resistance profile in treatment-naive individuals was not characterized. Conclusions: Baseline genotypic and phenotypic data provide valuable information on the likelihood of a virologic response to tipranavir. (c) 2007 Lippincott Williams & Wilkins. C1 US FDA, Div Antiviral Prod, Ctr New Drug Evaluat, Silver Spring, MD 20993 USA. RP Naeger, LK (reprint author), US FDA, Div Antiviral Prod, Ctr New Drug Evaluat, 10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM lisa.naeger@fda.hhs.gov NR 11 TC 27 Z9 28 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 JAN 11 PY 2007 VL 21 IS 2 BP 179 EP 185 DI 10.1097/QAD.0b013e3280119213 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 127FQ UT WOS:000243571100007 PM 17197808 ER PT J AU Basak, AK Raw, AS Yu, LX AF Basak, Arup K. Raw, Andre S. Yu, Lawrence X. TI Pharmaceutical impurities: Analytical, toxicological and regulatory perspectives - Preface SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. RP Basak, AK (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, 7500 Standish Pl, Rockville, MD 20855 USA. EM arup.basak@fda.hhs.gov; andre.raw@fda.hhs.gov; lawrence.yu@fda.hhs.gov NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD JAN 10 PY 2007 VL 59 IS 1 BP 1 EP 2 DI 10.1016/j.addr.2006.10.004 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144NN UT WOS:000244803200001 PM 17196297 ER PT J AU Jacobson-Kram, D McGovern, T AF Jacobson-Kram, David McGovern, Timothy TI Toxicological overview of impurities in pharmaceutical products SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE toxicology; pharmaceutical impurities; European medicines agency (EMEA); genotoxic impurities AB While the use of pharmaceuticals is always a balance of risks and benefits, the same is not true for impurities in pharmaceuticals; impurities convey only risk. A number of international guidelines and regional guidances instruct drug developers and regulatory agencies on how to evaluate and control impurities in drug substances and drug products. While impurities should always be reduced to the lowest levels that are reasonably practical, it is acknowledged that impurities cannot be reduced to zero and specifications for impurities need to be established. This chapter discusses practical and theoretical methods for qualification of different classes of impurities. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Pulm & Allergy Prod, Silver Spring, MD 20993 USA. RP Jacobson-Kram, D (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Pulm & Allergy Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM david.jacobsonkram@fda.hhs.gov NR 7 TC 49 Z9 49 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD JAN 10 PY 2007 VL 59 IS 1 BP 38 EP 42 DI 10.1016/j.addr.2006.10.007 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144NN UT WOS:000244803200005 PM 17188779 ER PT J AU Kruhlak, NL Contrera, JF Benz, RD Matthews, EJ AF Kruhlak, Naomi L. Contrera, Joseph F. Benz, R. Daniel Matthews, Edwin J. TI Progress in QSAR toxicity screening of pharmaceutical impurities and other FDA regulated products SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE genotoxicity; carcinogenicity; in silico screening; predictive toxicology; drug development; OECD principles ID E-STATE INDEXES; DEVELOPMENTAL TOXICITY; CARCINOGENICITY DATA; GENETIC TOXICITY; DRUG DISCOVERY; END-POINTS; IDENTIFICATION; CHEMICALS; MUTAGENICITY; SIMILARITY AB Active ingredients in pharmaceutical products undergo extensive testing to ensure their safety before being made available to the American public. A consideration during the regulatory review process is the safety of pharmaceutical contaminants and degradents which may be present in the drug product at low levels. Several published guidances are available that outline the criteria for further testing of these impurities to assess their toxic potential, where further testing is in the form of a battery of toxicology assays and the identification of known structural alerts. However, recent advances in the development of computational methods have made available additional resources for safety assessment such as structure similarity searching and quantitative structure-activity relationship (QSAR) models. These methods offer a rapid and cost-effective first-pass screening capability to assess toxicity when conventional toxicology data are limited or lacking, with the potential to identify compounds that would be appropriate for further testing. This article discusses some of the considerations when using computational toxicology methods for regulatory decision support and gives examples of how the technology is currently being applied at the US Food and Drug Administration. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, Silver Spring, MD 20993 USA. RP Contrera, JF (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM joseph.contrera@fda.hhs.gov NR 39 TC 48 Z9 52 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD JAN 10 PY 2007 VL 59 IS 1 BP 43 EP 55 DI 10.1016/j.addr.2006.10.008 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144NN UT WOS:000244803200006 PM 17229485 ER PT J AU Basak, AK Raw, AS Al Hakim, AH Furness, S Samaan, NI Gill, DS Patel, HB Powers, RF Yu, L AF Basak, Arup K. Raw, Andre S. Al Hakim, Ali H. Furness, Scott Samaan, Nashed I. Gill, Devinder S. Patel, Hasmukh B. Powers, Roslyn F. Yu, Lawrence TI Pharmaceutical impurities: Regulatory perspective for Abbreviated New Drug Applications SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE impurity; drug substance; drug product; abbreviated new drug applications (ANDAs) AB Impurities in drug substances and drug products have been important regulatory issues in the Office of Generic Drugs by having significant impact on the approvability of Abbreviated New Drug Application (ANDAs). This review begins with a discussion of ANDAs and its similarity/ differences with NDAs, highlighting the importance of control of pharmaceutical impurities in generic drug product development and regulatory assessment. An overview of the FDA draft guidance documents "ANDAs: Impurities in Drug Substances" and "ANDAs: Impurities in Drug Products" are provided. This introduces the identification and qualification procedures for ANDAs and approaches to the establishment of acceptance criteria for both drug substance and drug product. Case studies included in this review illustrate the proposed pathway for determination of impurities and their acceptance criteria, based upon the general principles of these guidances. Published by Elsevier B.V. C1 US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. US FDA, Off New Drug Qual Assessment, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Basak, AK (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, 7500 Standish Pl, Rockville, MD 20855 USA. EM arup.basak@fda.hhs.gov NR 7 TC 30 Z9 32 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD JAN 10 PY 2007 VL 59 IS 1 BP 64 EP 72 DI 10.1016/j.addr.2006.10.010 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144NN UT WOS:000244803200008 PM 17196703 ER PT J AU Wang, JY Heflich, RH Moore, MM AF Wang, Jianyong Heflich, Robert H. Moore, Martha M. TI A method to distinguish between the de novo induction of thymidine kinase mutants and the selection of pre-existing thymidine kinase mutants in the mouse lymphoma assay SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE mouse lymphoma assay; thymidine analogue; mutant selection; mutant frequency ID 4-NITROQUINOLINE 1-OXIDE; MUTAGENESIS; INFECTIONS; ZIDOVUDINE; STAVUDINE; CANCER; CELLS; GENE; TFT; TK AB The mouse lymphoma assay (MLA) is the most widely used in vitro mammalian gene mutation assay. It detects various mutation events involving the thymidine kinase (Tk) gene in L5178Y/Tk(+/-) -3.7.2C mouse lymphoma cells. Mutants are detected using a thymidine analogue that arrests the growth of cells containing a functional Tk gene. However, there are a number of potential test chemicals that are thymidine analogues, and there is a problem when using the MLA to evaluate the mutagenicity of these chemicals. Thymidine analogues are activated by Tk before eliciting their toxicity. Therefore, any pre-existing Tk(-)/(-) mutants may avoid the toxicity of the test chemical and obtain a growth advantage over the Tk(+/-) cells, increasing the Tk mutant frequency (MF) in the culture via a selection mechanism. This potential mutant selection effect needs to be distinguished from de novo mutant induction in order to properly evaluate the mutagenicity of these chemicals. Here we describe a simple MLA study design that can differentiate between the selection of pre-existing mutants and de novo mutant induction. Trifluorothymidine (TFT), a thymidine analogue and the selection agent normally used in the MLA, and 4-nitroquinoline-1-oxide (4-NQO), a potent mutagen, were used to treat cells from two different Tk(+/-) mouse lymphoma cell cultures with different background MEs (approximately 112 and 305 x 10(-6)). Both agents significantly increased the Tk MFs in both the normal and high background cultures (p < 0.01). In 4-NQO-treated cultures, the induced MFs (MF of treated culture - MF of control) for the cultures with different background MFs were about the same (p > 0.1), while in TFT-treated cultures, they were significantly different (p < 0.01). In TFT-treated cultures, the fold-increases of MF (MF of treated culture/MF of control) for the cultures with different background MFs were about the same (p > 0.1), while in 4-NQO-treated cultures, they were significantly different (p < 0.01). This study confirms that, when de novo mutations are induced, the induced MF is the same for cultures with normal and artificially high background MEs. In situations where the increase in MF is due solely to selection of pre-existing mutants, the "induced" MF will be a multiple of the background MF and the magnitude of the increase of the induced MF will depend upon the magnitude of the background ME Our results demonstrate that it is possible, using this experimental design, to distinguish between chemicals acting primarily via the selection of pre-existing Tk mutants and those inducing de novo mutants in the MLA. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Wang, JY (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jianyong.wang@fda.hhs.gov NR 26 TC 1 Z9 1 U1 1 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 JAN 10 PY 2007 VL 626 IS 1-2 BP 185 EP 190 DI 10.1016/j.mrgentox.2006.09.002 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 128FR UT WOS:000243644100023 PM 17055776 ER PT J AU Embury, JE Charron, CE Martynyuk, A Zori, AG Liu, B Ali, SF Rowland, NE Laipis, PJ AF Embury, Jennifer E. Charron, Catherine E. Martynyuk, Anatoly Zori, Andreas G. Liu, Bin Ali, Syed F. Rowland, Neil E. Laipis, Philip J. TI PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pah(enu2) mice SO BRAIN RESEARCH LA English DT Article DE phenylketonuria; oxidative stress; monoamines; gene therapy; adeno-associated virus ID EARLY-TREATED PHENYLKETONURIA; NITRIC-OXIDE; OXIDATIVE STRESS; PLASMA PHENYLALANINE; ANTIOXIDANT STATUS; ADULT PATIENTS; MOUSE MODEL; RAT-BRAIN; PEROXYNITRITE; DEGENERATION AB Phenylketonuria (PKU) is a common genetic disorder in humans that arises from deficient activity of phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine. There is a resultant hyperphenylalanemia with subsequent impairment in cognitive abilities, executive functions and motor coordination. The neuropathogenesis of the disease has not been completely elucidated, however, oxidative stress is considered to be a key feature of the disease process. Hyperphenylalanemia also adversely affects monoaminergic metabolism in the brain. For this reason we chose to evaluate the nigrostriatum of Pub(enu2) mice, to determine if alterations of monoamine metabolism resulted in morphologic nigrostriatal pathology. Furthermore, we believe that recent developments in adeno-associated virus (AAV)-based vectors have greatly increased the potential for long-term gene therapy and may be a viable alternative to dietary treatment for this metabolic disorder. In this study we identified neurodegenerative changes with regenerative responses in the nigrostriatum of pah(enu2) mice that are consistent with oxidative injury and occurred as early as 4 weeks of age. These neuropathologic changes were reversed following portal vein delivery of a recombinant adeno-associated virus-mouse phenylalanine hydroxylase-woodchuck hepatitis virus post-transcriptional response element (rAAV-mPAH-WPRE) vector to pah(enu2) mice and corresponded to rapid reduction of serum Phe levels. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Anesthesiol, Gainesville, FL 32610 USA. Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USA. Univ Florida, Coll Liberal Arts & Sci, Dept Psychol, Gainesville, FL 32610 USA. Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. RP Embury, JE (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, POB 100245, Gainesville, FL 32610 USA. EM jembury@ufl.edu FU NCRR NIH HHS [K01 RR019979, K01 RR019979-03]; NIDDK NIH HHS [DK58327, P01 DK058327] NR 43 TC 17 Z9 17 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 5 PY 2007 VL 1127 IS 1 BP 136 EP 150 DI 10.1016/j.brainres.2006.09.101 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 130VP UT WOS:000243827400017 PM 17112485 ER PT J AU Wang, C Sadovova, N Ali, HK Duhart, HM Fu, X Zou, X Patterson, TA Binienda, ZK Virmani, A Paule, MG Slikker, W Ali, SF AF Wang, C. Sadovova, N. Ali, H. K. Duhart, H. M. Fu, X. Zou, X. Patterson, T. A. Binienda, Z. K. Virmani, A. Paule, M. G. Slikker, W., Jr. Ali, S. F. TI L-carnitine protects neurons from 1-methyl-4-phenylpyridinium-induced neuronal apoptosis in rat forebrain culture SO NEUROSCIENCE LA English DT Article DE L-carnitine; neuronal rescue; 1-methyl-4-phenylpyridinium ion; MPP+; neurodegeneration; apoptosis ID ACETYL-L-CARNITINE; ORNITHINE TRANSCARBAMYLASE DEFICIENCY; FACTOR-KAPPA-B; PARKINSONS-DISEASE; PC12 CELLS; SELECTIVE ALTERATIONS; INDUCED NEUROTOXICITY; MITOCHONDRIAL DECAY; OXIDATIVE STRESS; CYTOCHROME-C AB 1-Methyl-4-phenylpyridinium ion (MPP+), an inhibitor of mitochondrial complex 1, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with an elevation of intracellular reactive oxygen species (ROS) and apOptOSiS. (L)-Carnitine plays an integral role in attenuating the brain injury associated with mitochondrial neurodegenerative disorders. The present study investigates the effects of (L)-carnitine against the toxicity of MPP+ in rat forebrain primary cultures. Cells in culture were treated for 24 h with 100, 250, 500 and 1000 mu M MPP+ alone or co-incubated with (L)-carnitine. MPP+ produced a dose-related increase in DNA fragmentation as measured by cell death ELISA (enzyme-linked immunosorbent assay), an increase in the number of TUNEL (terminal dUTP nick-end labeling)-positive cells and a reduction in the mitochondrial metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). No significant effect was observed with the release of lactate dehydrogenase (LDH), indicating that cell death presumably occurred via apoptotic mechanisms. Co-incubation of MPP+ with (L)-carnitine significantly reduced MPP+-induced apoptosis. Western blot analyses showed that neurotoxic concentrations of MPP+ decreased the ratio of BCL-X-L to Bax and decreased the protein levels of polysialic acid neural cell adhesion molecules (PSA-NCAM), a neuron specific marker. (L)-Carnitine blocked these effects of MPP+ suggesting its potential therapeutic utility in degenerative disorders such as Parkinson's disease, Alzheimer's disease, ornithine transcarbamylase deficiency and other mitochondrial diseases. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132, Jefferson, AR 72079 USA. Toxicol Pathol Assoc, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Sigma Tau HealthSci SpA, Res & Dev, I-00040 Monte Porzio Catone, Italy. RP Wang, C (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132, Jefferson, AR 72079 USA. EM cheng.wang@fda.hhs.gov; syed.ali@fda.hhs.gov NR 48 TC 33 Z9 36 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN 5 PY 2007 VL 144 IS 1 BP 46 EP 55 DI 10.1016/j.neuroscience.2006.08.083 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 117GD UT WOS:000242860100006 PM 17084538 ER PT J AU Bowyer, JF Pogge, AR Delongchamp, RR O'Callaghan, JP Patel, KM Vrana, KE Freeman, WM AF Bowyer, J. F. Pogge, A. R. Delongchamp, R. R. O'Callaghan, J. P. Patel, K. M. Vrana, K. E. Freeman, W. M. TI A threshold neurotoxic amphetamine exposure inhibits parietal cortex expression of synaptic plasticity-related genes SO NEUROSCIENCE LA English DT Article DE activity-related cytoskeletal protein; amphetamine; nerve growth-factor inducible proteins; neurotoxicity; gene expression; challenge ID IMMEDIATE-EARLY GENES; MESSENGER-RNA EXPRESSION; METHAMPHETAMINE-DEPENDENT SUBJECTS; NMDA RECEPTOR ACTIVATION; CDNA ARRAY DATA; RAT FOREBRAIN; C-FOS; SUBSTITUTED AMPHETAMINES; DIFFERENTIAL EXPRESSION; RECOGNITION MEMORY AB Compulsive drug abuse has been conceptualized as a behavioral state where behavioral stimuli override normal decision making. Clinical studies of methamphetamine users have detailed decision making changes and imaging studies have found altered metabolism and activation in the parietal cortex. To examine the molecular effects of amphetamine (AMPH) on the parietal cortex, gene expression responses to amphetamine challenge (7.5 mg/kg) were examined in the parietal cortex of rats pretreated for nine days with either saline, non-neurotoxic amphetamine, or neurotoxic AMPH dosing regimens. The neurotoxic AMPH exposure [three doses of 7.5 mg/kg/day AMPH (6 h between doses), for nine days] produced histological signs of neurotoxicity in the parietal cortex while a non-neurotoxic dosing regimen (2.0 mg/kg/dayx3) did not. Neurotoxic AMPH pretreatment resulted in significantly diminished AMPH challenge-induced mRNA increases of activity-regulated cytoskeletal protein (ARC), nerve growth-factor inducible protein A (NGFI-A), and nerve growth-factor inducible protein B (NGFI-B) in the park etal cortex while neither saline pretreatment nor non-neurotoxic AMPH pretreatment did. This effect was specific to these genes as tissue plasminogen activator (t-PA), neuropeptide Y (NPY) and c-jun expression in response to AMPH challenge was unaltered or enhanced by amphetamine pretreatments. In the striatum, there were no differences between saline, neurotoxic AMPH, and non-neurotoxic AMPH pretreatments on ARC, NGFI-A or NGFI-B expression elicited by the AMPH challenge. These data indicate that the responsiveness of synaptic plasticity-related genes is sensitive to disruption specifically in the parietal cortex by threshold neurotoxic AMPH exposures. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NIOSH, CDC, Toxicol & Mol Biol Branch, Morgantown, WV 26505 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132, Jefferson, AR 72079 USA. EM john.bowyer@fda.hhs.gov RI O'Callaghan, James/O-2958-2013; OI Vrana, Kent/0000-0003-4902-7733; Freeman, Willard/0000-0001-7027-999X FU NIDA NIH HHS [R01 DA013770, R01 DA013770-08, R01DA013770] NR 62 TC 21 Z9 21 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN 5 PY 2007 VL 144 IS 1 BP 66 EP 76 DI 10.1016/j.neuroscience.2006.08.076 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 117GD UT WOS:000242860100008 PM 17049170 ER PT J AU Kauffman, JF Dellibovi, M Cunningham, CR AF Kauffman, John F. Dellibovi, Marybeth Cunningham, Charles R. TI Raman spectroscopy of coated pharmaceutical tablets and physical models for multivariate calibration to tablet coating thickness SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE tablet coating analysis; Raman spectroscopy; multivariate calibration; chemometrics; target factor analysis ID NET ANALYTE SIGNAL; SPECTROMETRY AB Raman spectra of a set of coated pharmaceutical tablets were analyzed for the purpose of calibrating the spectra to tablet coating thickness. Acetaminophen tablets were coated with a hydroxypropylmethylcellulose/polyethylene glycol film coating whose thickness was varied from 0 to 6% weight gain. Coatings were also prepared with two concentrations of TiO2 at several film thicknesses. The resulting spectral data set was analyzed using several different multivariate calibration procedures. The procedures examined in this study included spectral correction followed by target factor analysis, spectral correction with baseline subtraction followed by principal component regression, and first derivative computation followed by principal component regression. The results demonstrate that target factor analysis is a viable method for calibration of Raman spectra to tablet coating thickness. Calibration based on derivative spectra resulted in linear correlation that was equal to that of the results of target factor analysis for coatings without TiO2. However, target factor analysis was found to be superior to other methods when TiO2 was present in the tablet coatings. The effect of sample fluorescence on each of these chemometric methods was also examined. It was found that when photobleaching of fluorescent impurities due to exposure to the Raman excitation source was controlled, the tablet coating thickness could be calibrated to the intensity of the fluorescence signal. The results also demonstrate that for the samples examined here, calibration by target factor analysis is insensitive to variation in fluorescent intensity when the tablet coating emission spectrum is included in the matrix of target vectors. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. Colorcon, Pharmaceut Tech Serv, West Point, PA 19486 USA. RP Kauffman, JF (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM John.Kauffman@fda.hhs.gov NR 15 TC 33 Z9 35 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JAN 4 PY 2007 VL 43 IS 1 BP 39 EP 48 DI 10.1016/j.jpba.2006.06.017 PG 10 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 126ZS UT WOS:000243554900005 PM 16860508 ER PT J AU Seymour, SM Chowdhury, BA AF Seymour, Sally M. Chowdhury, Badrul A. TI Immunotherapy with a ragweed vaccine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Silver Spring, MD 20993 USA. RP Seymour, SM (reprint author), US FDA, Silver Spring, MD 20993 USA. EM sally.seymour@fda.hhs.gov NR 2 TC 1 Z9 1 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 JAN 4 PY 2007 VL 356 IS 1 BP 86 EP 86 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 122EX UT WOS:000243209600015 PM 17202461 ER PT J AU Kessler, LG Ramsey, SD AF Kessler, Larry G. Ramsey, Scott D. TI The forest and the trees: the human costs of cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CARE C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Rockville, MD 20850 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Kessler, LG (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 9200 Corp Blvd,HFZ-100, Rockville, MD 20850 USA. EM lgk@cdrh.fda.gov NR 6 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 3 PY 2007 VL 99 IS 1 BP 2 EP 3 DI 10.1093/jnci/djk013 PG 2 WC Oncology SC Oncology GA 126GF UT WOS:000243499900001 PM 17202102 ER PT J AU Temple, R Stockbridge, NL AF Temple, Robert Stockbridge, Norman L. TI BiDil for heart failure in black patients: The U.S. Food and Drug Administration perspective SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ISOSORBIDE DINITRATE; MORTALITY; HYDRALAZINE; ENALAPRIL; SURVIVAL; TRIALS; RACE AB Critics of the U. S. Food and Drug Administration (FDA) approval of the fixed combination of hydralazine hydrochloride, 37.5 mg, and isosorbide dinitrate, 20 mg, for treating heart failure in black patients have suggested that data were insufficient to distinguish treatment effects in black and white people; that distinctions based on race, rather than pathophysiology, were scientifically unreasonable; and that a "race-based" approval could be a commercial ploy to avoid a more expensive and prolonged full evaluation of a drug. The criticisms acknowledge that data supporting the approval came from a well-designed clinical trial in which self-identified black patients with heart failure who took hydralazine hydrochloride-isosorbide dinitrate with standard therapy experienced a statistically significant 43% (95% CI, 11% to 63%) reduction in mortality compared with those who took only the standard therapy. The criticisms do not always recognize that the decision to conduct the trial in only black patients reflected careful analyses of 2 previous trials in racially mixed patient populations that compared hydralazine hydrochloride-isosorbide dinitrate with placebo or with enalapril. Both trials showed little or no overall effect of hydralazine hydrochloride-isosorbide dinitrate in the mostly white patient population but hinted at a substantial effect in subsets of black patients. Perhaps most critically, the criticisms do not appreciate the urgency of strong scientific evidence of a substantial survival benefit in black patients. A serious attempt to avoid race-based approval by mandating study of a mixed population to identify a possible white patient-responder subset, particularly without a plausible hypothesis as to what that subset might be, would have required years of work, many thousands of patients, and wholly unreasonable delay in approval of a treatment whose effectiveness had been well-documented in the group for which it was intended. C1 US FDA, Silver Spring, MD 20993 USA. RP Temple, R (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM robert.temple@fda.hhs.gov NR 26 TC 56 Z9 56 U1 0 U2 6 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 JAN 2 PY 2007 VL 146 IS 1 BP 57 EP W9 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 188BK UT WOS:000247893300008 PM 17200223 ER PT S AU Samuelson, FW Petrick, N Paquerault, S AF Samuelson, Frank W. Petrick, Nicholas Paquerault, Sophie GP IEEE TI Advantages and examples of resampling for CAD evaluation SO 2007 4TH IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING : MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 4th IEEE International Symposium on Biomedical Imaging CY APR 12-15, 2007 CL Arlington, VA SP IEEE DE evaluation; FROG; resampling; bootstrap; permutation; computer-aided diagnosis ID FROC CURVES; MODEL; LOCALIZATION; MAMMOGRAPHY; OBSERVER AB Comparison of performance accuracy between different computer-aided diagnosis (CAD) devices is a challenging task. Anatomical structure of the patient and imaging geometry introduce many possible correlations among scores produced by a CAD. Numerous analysis methods have been designed to account for the correlations among CAD scores or the variable number of CAD marks, but usually not both. However, methods that resample by case incorporate both of these sources of variability while accounting for in-case correlations. In this paper we present some examples of the use of resampling on CAD score data. C1 [Samuelson, Frank W.; Petrick, Nicholas; Paquerault, Sophie] US FDA, Ctr Devices & Radiol Hlth, CDRH NIBIB Lab Assessment Med Imaging Syst, Rockville, MD USA. RP Samuelson, FW (reprint author), US FDA, Ctr Devices & Radiol Hlth, CDRH NIBIB Lab Assessment Med Imaging Syst, HFZ 140,12720 Twinbrook Pkwy, Rockville, MD USA. NR 14 TC 16 Z9 16 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-0671-5 J9 I S BIOMED IMAGING PY 2007 BP 492 EP 495 DI 10.1109/ISBI.2007.356896 PG 4 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Imaging Science & Photographic Technology SC Computer Science; Engineering; Imaging Science & Photographic Technology GA BHG38 UT WOS:000252957300124 ER PT S AU Hsu, ER Gallas, BD Jeronimo, J AF Hsu, Elizabeth R. Gallas, Brandon D. Jeronimo, Jose GP IEEE TI Methods for MRMC ROC analysis and components-of-variance modeling using colposcopy images SO 2007 4TH IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING : MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 4th IEEE International Symposium on Biomedical Imaging CY APR 12-15, 2007 CL Arlington, VA SP IEEE AB In cervical cancer screening, colposcopically-directed biopsies determine disease severity and management. Multi-reader multi-case receiver operating characteristic (MRMC ROC) analysis can be used to evaluate the diagnostic performance and reader variability of colposcopy. We describe the constrained one-shot variance estimate of the empirical area under the ROC curve and analyze a dataset of colposcopists reading images of the cervix. We demonstrate how to extrapolate the variance estimate to larger studies and how to estimate essential components of variance: reader, case, and an interaction component. These methods allow us to investigate the variance reduction of strategies for adding more cases. For our data (21 readers, 16 normal and 4 diseased cases), variance decreases the fastest by adding more diseased cases (short-term) or a ratio of diseased and normal cases (long-term). C1 [Hsu, Elizabeth R.; Gallas, Brandon D.] US FDA, Ctr Devices & Radiol Hlth,NIBI CDRH, Off Sci Engn Lab,Div Imaging & Appl Math, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. [Hsu, Elizabeth R.] Natl Inst Hlth, Natl Canc Inst, Canc Prevent Fellowship & Inter Agcy oncol Task F, Bethesda, MD USA. [Jeronimo, Jose] Natl Inst Hlth, Natl Canc Inst, Div Canc Edidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD USA. RP Hsu, ER (reprint author), US FDA, Ctr Devices & Radiol Hlth,NIBI CDRH, Off Sci Engn Lab,Div Imaging & Appl Math, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. OI Gallas, Brandon/0000-0001-7332-1620 NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-0671-5 J9 I S BIOMED IMAGING PY 2007 BP 1264 EP + DI 10.1109/ISBI.2007.357089 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Imaging Science & Photographic Technology SC Computer Science; Engineering; Imaging Science & Photographic Technology GA BHG38 UT WOS:000252957300317 ER PT S AU Sloane, EB Carey, CC AF Sloane, Elliot B. Carey, Carole C. GP IEEE TI Using standards to automate electronic health records (EHRs) and to create integrated healthcare enterprises SO 2007 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-16 SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 29th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 22-26, 2007 CL Lyon, FRANCE SP IEEE Engn Med & Biol Soc AB President Bush's 2004 Executive Order mandated the creation within the Secretary of Health and Human Services' staff of a new Office of the National Coordinator for Healthcare Information Technology (ONCHIT) that was tasked with creating the United States National Healthcare Information Network (NHIN). The Health Insurance Portability and Accountability Act of 1996 (HIPAA) and the 2004 and a subsequent 2006 Executive Orders have finally set the stage to design, and require, the use of standardized, electronic data interchange-enabled information systems as quickly as possible. C1 [Sloane, Elliot B.] Villanova Univ, Villanova, PA 19085 USA. [Carey, Carole C.] FDA, Silver Spring, MD 20903 USA. RP Sloane, EB (reprint author), Villanova Univ, Villanova, PA 19085 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 978-1-4244-0787-3 J9 P ANN INT IEEE EMBS PY 2007 BP 6178 EP + PG 2 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BHI92 UT WOS:000253467005073 ER PT B AU Kim, DH Kang, JU Waynant, RW Ilev, IK AF Kim, Do-Hyun Kang, Jin U. Waynant, Ronald W. Ilev, Ilko K. GP IEEE TI Upconversion Fiber-Optic Confocal Microscopy using a Near-Infrared Light Source SO 2007 CONFERENCE ON LASERS & ELECTRO-OPTICS/QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (CLEO/QELS 2007), VOLS 1-5 LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics/Quantum Electronics and Laser Science Conference CY MAY 06-11, 2007 CL Baltimore, MD AB An upconversion confocal microscope was developed and studied using rare-earth-doped glass sample powder. The process was highly efficient with upconversion fluorescence efficiency in excess of 2% with the pumping wavelength at 1550 nm and ensured high lateral resolution. C1 [Kim, Do-Hyun; Waynant, Ronald W.; Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, HFZ 130,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. [Kang, Jin U.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ 130,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. RI Kang, Jin/A-3228-2010 NR 4 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3590-6 PY 2007 BP 512 EP + PG 2 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BKO20 UT WOS:000268751000258 ER PT B AU Wang, Q Agrawal, A Matchette, S Wang, N Pfefer, J AF Wang, Q. Agrawal, A. Matchette, S. Wang, N. Pfefer, J. GP IEEE TI Evaluation of a Multi-wavelength Reflectance System for Determination of Tissue Optical Properties in the UVA-VIS SO 2007 CONFERENCE ON LASERS & ELECTRO-OPTICS/QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (CLEO/QELS 2007), VOLS 1-5 LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics/Quantum Electronics and Laser Science Conference CY MAY 06-11, 2007 CL Baltimore, MD AB Tissue optical properties at ultraviolet-A and visible wavelengths are needed to elucidate diagnostic device performance. We have developed a multi-wavelength fiberoptic reflectance system for optical property measurement and evaluated its performance using hemoglobin-based tissue phantoms. (C) 2007 Optical Society of America C1 [Wang, Q.; Agrawal, A.; Matchette, S.; Pfefer, J.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. [Wang, Q.; Wang, N.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20740 USA. RP Wang, Q (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM quanzeng_wang@yahoo.com NR 3 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3590-6 PY 2007 BP 1551 EP + PG 2 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BKO20 UT WOS:000268751001217 ER PT B AU Ilev, I Faaland, R Calogero, D AF Ilev, Ilko Faaland, Robert Calogero, Don GP IEEE TI A Novel Confocal Fiber-Optic Laser Method for Exact Intraocular Lens Dioptric Power Measurement SO 2007 CONFERENCE ON LASERS & ELECTRO-OPTICS/QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (CLEO/QELS 2007), VOLS 1-5 LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics/Quantum Electronics and Laser Science Conference CY MAY 06-11, 2007 CL Baltimore, MD AB Based on a fiber-optic confocal design, we have developed a simple, accurate, objective and quick method for exact focal length measurement of both positive and negative intraocular lenses providing a spatial resolution exceeding 1 mu m. (C)2007 Optical Society of America C1 [Ilev, Ilko; Faaland, Robert] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, HFZ 130, Rockville, MD 20857 USA. [Calogero, Don] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Ilev, I (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, HFZ 130, Rockville, MD 20857 USA. EM ilko.ilev@eob.cdrh.fda.gov; robert.faaland@fda.hhs.gov; don.calogero@fda.hhs.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3590-6 PY 2007 BP 1876 EP + PG 2 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BKO20 UT WOS:000268751001381 ER PT B AU Kim, DH Waynant, RW Ilev, IK Kang, JU AF Kim, Do-Hyun Waynant, Ronald W. Ilev, Ilko K. Kang, Jin U. GP IEEE TI An All-Fiber-Optic Confocal Interference Microscope Using Low-Coherence Near-Infrared Light Source SO 2007 CONFERENCE ON LASERS & ELECTRO-OPTICS/QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (CLEO/QELS 2007), VOLS 1-5 LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics/Quantum Electronics and Laser Science Conference CY MAY 06-11, 2007 CL Baltimore, MD AB An all-fiber-optic confocal interference microscope using a broadband near-infrared light source is demonstrated. Detection of interference fringes increases sensitivity and usage of a broadband source reduces undesirable interference between optical components. C1 [Kim, Do-Hyun; Waynant, Ronald W.; Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, HFZ 130,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. [Kang, Jin U.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ 130,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. RI Kang, Jin/A-3228-2010 NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3590-6 PY 2007 BP 1882 EP + PG 2 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BKO20 UT WOS:000268751001384 ER PT B AU Bassen, H Seidman, S Rogul, J Desta, A Wolfgang, S AF Bassen, H. Seidman, S. Rogul, J. Desta, A. Wolfgang, S. GP IEEE TI An exposure system for evaluating possible effects of RFID on various formulations of drug products SO 2007 IEEE INTERNATIONAL CONFERENCE ON RFID LA English DT Proceedings Paper CT 1st IEEE International Conference on RFID CY MAR 26-28, 2007 CL Grapevine, TX SP IEEE, IEEE New Technol Direct Comm, IEEE Reg AB We developed hardware and software to perform exposure studies of the effects of certain radio frequency (RF) electromagnetic fields on solid and liquid pharmaceuticals and biologics. The RE fields generated by our systems are similar to those emitted by radio frequency identification (RFID) readers operating in the USA licensed high frequency (HF) and ultra high frequency (UHF) bands (13.56 and 915 MHz respectively). Our systems can expose drug samples (pharmaceuticals and biologics) to uniform electric (E) and/or magnetic (H) fields at levels that are much higher than those experienced by drugs near "worst-case" readers at a distance of 20 cm. Worst-case readers are defined as those that emit the highest allowable field strengths. Maximum field strengths near these readers were identified by measurements and computations of fields from commercial readers, and are extrapolated to the maximum allowable effective isotropic radiated power or field strength dictated by the U.S. Federal Communications Commission (FCC). The UHF system we developed included a commercially available circularly polarized antenna, a microwave generator with pulse modulation, a high power amplifier, a plastic foam enclosure, and fiber optic temperature monitoring probes placed in the drugs and the surrounding air. The HF system we developed included a specially designed Helmholtz coil pair, an HF signal generator with pulse modulation, an HF amplifier, an RF impedance matching device, and the same enclosure, and thermometry system as in the UHF system. Exposures can be performed for each drug in both its retail primary package (the smallest container produced with an RFID tag on it, e.g. bottle) and in 54 mm diameter culture dishes. The containers are suitable for exposing a wide variety of formulations of drugs (tablets, liquids, powers, capsules, creams, etc.). Exposures of drugs in culture dishes assure uniform induced electric fields and currents. In contrasts exposures in the primary containers (e.g. vials) allow studies that account for the interactions of RF fields with the packaging materials and container geometry. In our UHF system we can expose drugs to over 20 Watts Effective Isotropic Radiated Power over 5 times the FCC limits. We evaluated H fields emitted by commercially available RFID readers. In our HF system we can expose drugs to at least 5 times the H field they produce at 20 cm from the reader. We can expose samples to 5 A/m in primary packaging or in special organ culture dishes with an outer concentric ring. The ring has inner and outer diameters of 32 mm and 55 mm respectively. Computer monitoring of power, drug temperature, and air temperature can be performed continuously during exposure. Surrounding air temperature is monitored at all times while in our lab (storage and exposure) and while shipped to drug laboratories for analysis. C1 [Bassen, H.; Seidman, S.; Rogul, J.; Desta, A.] US FDA, Silver Spring, MD 20993 USA. RP Bassen, H (reprint author), US FDA, Silver Spring, MD 20993 USA. EM howard.bassen@fda.hhs.gov; jonathan.rogul@gmail.com NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1012-5 PY 2007 BP 201 EP + PG 2 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA BGP10 UT WOS:000249265000028 ER PT S AU Brown, DG Gallas, BD AF Brown, David G. Gallas, Brandon D. GP IEEE TI Performance studies for validation of CAD systems SO 2007 IEEE INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS, VOLS 1-6 SE IEEE International Joint Conference on Neural Networks (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks CY AUG 12-17, 2007 CL Orlando, FL SP IEEE ID OPERATING CHARACTERISTIC ANALYSIS; DORFMAN-BERBAUM-METZ; MRMC METHOD; PROBABILISTIC MODEL; MULTIREADER; VARIANCE; READERS; SAMPLE AB Evaluation of computational intelligence (CI) systems designed to improve the performance of a human operator is complicated by the necessity of including the effect of human variability. In this paper we examine the methodology available for addressing this variability within the context of medical imaging computer-assisted diagnosis (CAD) systems. We present a review of currently available techniques and give an example using computer simulation. It is shown how advanced statistical techniques lead to more efficient measures of CAD performance. C1 [Brown, David G.; Gallas, Brandon D.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Brown, DG (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1098-7576 BN 978-1-4244-1379-9 J9 IEEE IJCNN PY 2007 BP 2856 EP 2861 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Software Engineering SC Computer Science GA BHM64 UT WOS:000254291102133 ER PT S AU Kim, DH Ilev, IK Kang, JU AF Kim, Do-Hyun Ilev, Ilko K. Kang, Jin U. GP IEEE TI Using mid-infrared glucose absorption peak changes for high-precision glucose detection SO 2007 IEEE LEOS ANNUAL MEETING CONFERENCE PROCEEDINGS, VOLS 1 AND 2 SE IEEE Lasers and Electro-Optics Society (LEOS) Annual Meeting LA English DT Proceedings Paper CT 20th Annual Meeting of the IEEE-Lasers-and-Electro-Optics-Society CY OCT 21-25, 2007 CL Lake Buena Vista, FL AB We experimentally observed mid-infrared glucose absorption peak changes using Fourier-transform infrared spectroscopy. While all the transmission peaks at different wavelength increased as the glucose concentration was increased, their rate of increase were all different. Comparison of rates can be used for determination of blood glucose level. C1 [Kim, Do-Hyun; Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. [Kang, Jin U.] Johns Hopkins Univ, Elect & Comp Engn Dept, Baltimore, MD 21218 USA. RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. RI Kang, Jin/A-3228-2010 NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1092-8081 BN 978-1-4244-0924-2 J9 IEEE LEOS ANN MTG PY 2007 BP 226 EP + PG 2 WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Optics SC Engineering; Science & Technology - Other Topics; Optics GA BIG51 UT WOS:000259345200110 ER PT S AU Wear, KA AF Wear, Keith A. GP IEEE TI Improved accuracy of broadband ultrasound attenuation measurement using phase insensitve detection: Results in 73 women SO 2007 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1-6 SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY OCT 28-31, 2007 CL New York, NY SP IEEE DE bone; attenuation ID TOMOGRAPHY AB Broadband Ultrasonic Attenuation (BUA) Is a clinically-accepted measurement for diagnosis of osteoporosts. Typical clinical BUA measurements are performed with phase sensitive receivers and therefore can be affected by phase cancellation. In order to separate the effects of conventional attenuation (absorption plus scattering) from phase cancellation, BUA was measured on phantoms with acrylic wedge phase aberrators and on 73 women using both phase sensitive (PS) and phase insensitive (PI) reception. A clinical bone sonometer (GE Lunar Achilles Insight (R)) with a two dimensional receiver array was used. PI BUA measurements on phantoms with acrylic wedge phase aberrators were found to be far more resistant to phase cancellation than PS BUA measurements. In data from 73 women, means and standard deviations for BUA measurements were 81.4 +/- 21.4 dB/MHz (PS) and 67.2 +/- 9.7 dB/MHz (PI). C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 8 TC 0 Z9 0 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-1383-6 J9 ULTRASON PY 2007 BP 1113 EP 1115 DI 10.1109/ULTSYM.2007.281 PG 3 WC Acoustics; Biophysics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology SC Acoustics; Biophysics; Engineering; Physics; Imaging Science & Photographic Technology GA BHM55 UT WOS:000254281801029 ER PT S AU Harris, GR Liu, Y Maruvada, S Gammell, PM AF Harris, G. R. Liu, Y. Maruvada, S. Gammell, P. M. GP IEEE TI Finite amplitude method for measurement of nonlinearity parameter B/A using plane-wave tone bursts SO 2007 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1-6 SE Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY OCT 28-31, 2007 CL New York, NY SP IEEE DE nonlinear parameter B/A; nonlinear acoustics ID BIOLOGICAL MEDIA AB Several finite amplitude approaches have been used to determine the nonlinearity parameter B/A of different materials. However, diffraction corrections or measurements far from the transmitting transducer are necessary to comply with the plane wave assumption inherent in the classical method. Alternatively, broadband, absolute pressure measurements in combination with theoretical nonlinear field calculations must be performed. In this study a measurement technique is proposed that eliminates the need for any of these steps. The technique is a variation of the finite amplitude insert substitution (FAIS) method. An 8 cm diameter, 2.25 MHz transmitting transducer was used to generate sinusoidal tone burst pulses, and the second harmonic amplitude was measured with and without the unknown sample in the beam per the FAIS method. Measurements were made near the transmitting transducer face where the field is reasonably plane until the diffracted wave from the transducer edge arrives, so a diffraction correction was not necessary. Results for two materials, glycerol and corn oil, were within 10% of published values for B/A. C1 [Harris, G. R.; Liu, Y.; Maruvada, S.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Maruvada, S.; Gammell, P. M.] LLC, Gammell Applied Technol, Exmore, VIRGINIA. RP Harris, GR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. FU Defense Advanced Research Projects Agency (DARPA) through IAG [224-05- 6016] FX This work was supported by the Defense Advanced Research Projects Agency (DARPA) through IAG # 224-05- 6016. NR 14 TC 4 Z9 4 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-1383-6 J9 ULTRASON PY 2007 BP 2072 EP + DI 10.1109/ULTSYM.2007.521 PG 2 WC Acoustics; Biophysics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology SC Acoustics; Biophysics; Engineering; Physics; Imaging Science & Photographic Technology GA BHM55 UT WOS:000254281802018 ER PT S AU Wear, KA AF Wear, Keith A. GP IEEE TI A method for improved standardization of in vivo calcaneal time-domain speed-of-sound measurements SO 2007 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1-6 SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY OCT 28-31, 2007 CL New York, NY SP IEEE DE bone; speed of sound AB Clinical SOS measurements exhibit a high degree of inter-system variability. Calcaneal SOS is usually computed from time-of-flight measurements of broadband ultrasound pulses that propagate through the foot. In order to minimize the effects of multi-path interference, many investigators measure time-of-flight from markers near the leading edge of the pulse. The calcaneus Is a highly attenuating, highly inhomogeneous bone that distorts propagating ultrasound pulses via frequency-dependent attenuation, reverberation, dispersion, multiple scattering, and refraction. This pulse distortion can produce errors In leading-edge transit-time marker based SOS measurements. In this paper, an equation to predict dependence of time-domain SOS measurements on system parameters (center frequency and bandwidth), transit-time marker location, and bone properties (attenuation coefficient and thickness) Is validated with through-transmission measurements in a bone-mimicking phantom and in 73 women in vivo, using a clinical bone sonometer. In order to test the utility of the formula for suppressing system dependence of SOS measurements, a wideband laboratory data acquisition system was used to make a second set of through-transmission measurements on the phantom. The compensation formula reduced system-dependent leading-edge transit-time marker based SOS measurements in the phantom from 41 m/s to 5 m/s and reduced transit-time marker related SOS variability in 73 women from 40 m/s to 10 m/s. The compensation formula can be used to improve standardization In bone sonometry. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-1383-6 J9 ULTRASON PY 2007 BP 2159 EP 2162 DI 10.1109/ULTSYM.2007.543 PG 4 WC Acoustics; Biophysics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology SC Acoustics; Biophysics; Engineering; Physics; Imaging Science & Photographic Technology GA BHM55 UT WOS:000254281802040 ER PT B AU Spees, W AF Spees, William TI Considering Cardinality in a Medical Device PnP System SO 2007 JOINT WORKSHOP ON HIGH CONFIDENCE MEDICAL DEVICES, SOFTWARE AND SYSTEMS AND MEDICAL DEVICE PLUG-AND PLAY INTEROPERABILITY LA English DT Proceedings Paper CT Joint Workshop on High Confidence Medical Devices, Software, and Systems/Medical Device Plug-and-Play Interoperability CY JUN 25-27, 2007 CL Cambridge, MA SP NSF, AHRO, TATRC, CIMIT, Massachusetts Gen Hosp, Partners AB In designing systems of hardware and software, we get more leverage from decisions about cardinality than almost any other choices. When we study an existing system, the fundamental insight we gain is an understanding of the cardinalities of the system. From the cardinalities we can choose (or infer) the basic operation and prioritization of the system, without being distracted by details. This paper will briefly explore some of the cardinality-sensitive attributes of Medical Device Plug and Play systems. C1 US FDA, Rockville, MD 20857 USA. RP Spees, W (reprint author), US FDA, Rockville, MD 20857 USA. EM william.spees@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3081-9 PY 2007 BP 144 EP 145 DI 10.1109/HCMDSS-MDPnP.2007.21 PG 2 WC Computer Science, Information Systems; Computer Science, Software Engineering; Engineering, Biomedical SC Computer Science; Engineering GA BJD66 UT WOS:000265022300018 ER PT S AU Liang, HY Park, S Gallas, BD Badano, A Myers, KJ AF Liang, Hongye Park, Subok Gallas, Brandon D. Badano, Aldo Myers, Kyle J. GP SID TI Assessment of temporal blur-reduction methods using a computational observer that predicts human performance SO 2007 SID INTERNATIONAL SYMPOSIUM, DIGEST OF TECHNICAL PAPERS, VOL XXXVIII, BOOKS I AND II SE SID INTERNATIONAL SYMPOSIUM DIGEST OF TECHNICAL PAPERS LA English DT Proceedings Paper CT International Symposium of the Society-for-Information-Display (SID 2007) CY MAY 20-25, 2007 CL Long Beach, CA SP Soc Informat Display AB We report on a method to assess the impact of temporal blur reduction techniques based on measured or modeled device temporal characteristics with a contrast-sensitive computational observer that predicts human performance. We applied the method to the comparison of different devices and temporal blur reduction approaches. C1 [Liang, Hongye; Park, Subok; Gallas, Brandon D.; Badano, Aldo; Myers, Kyle J.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Liang, HY (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU SOC INFORMATION DISPLAY PI PLAYA DEL REY PA 8055 W MANCHESTER AVE SUITE 615, PLAYA DEL REY, CA 90293 USA SN 0097-966X J9 SID INT SYMP DIG TEC PY 2007 VL 38 BP 967 EP 970 DI 10.1889/1.2785466 PN 1-2 PG 4 WC Computer Science, Cybernetics; Instruments & Instrumentation; Imaging Science & Photographic Technology SC Computer Science; Instruments & Instrumentation; Imaging Science & Photographic Technology GA BIF19 UT WOS:000259075300253 ER PT S AU King, RL Herman, BA Maruvada, S Wear, KA Harris, GR AF King, Randy L. Herman, Bruce. A. Maruvada, Subha Wear, Keith A. Harris, Gerald R. BE Coussios, CC TerHaar, G TI Development of a HIFU phantom SO 6TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 6th International Symposium on Therapeutic Ultrasound CY AUG 30-SEP 02, 2006 CL Oxford, ENGLAND SP Int Soc Therapeut Ultrasound, China Med Technologies, HAIFU, Phillips Med Syst, EDAP, Mianyang Son Elect Ltd, Imasonic, Ultra Shape Ltd, British Med Ultrasound Soc, ImRx Therapeut, Liposonix SA, Theraclion, SRA Dev Ltd, UKHIFU DE high intensity focused ultrasound; phantoms ID ULTRASONIC BACKSCATTER; IN-VIVO; MHZ AB The field of high intensity focused ultrasound (HIFU) is developing rapidly. For basic research, quality control, and regulatory assessment a reusable phantom that has both thermal and acoustic properties close to that of soft tissue is critical. A hydrogel-based tissue mimicking material (TMM) has been developed that shows promise for such a phantom. The acoustic attenuation, speed of sound, B/A, thermal diffusivity and conductivity, as well as the cavitation threshold, were measured and found to mimic published values for soft tissue. The attenuation of 0.53f(1.04) from 1 MHz to 8 MHz, as well as the sound speed of 1565 m/s and the tissue-like image quality, indicate the usefulness of the TMM for ultrasound imaging applications. These properties along with the thermal conductivity of 0.58 W/m- degrees C, diffusivity of 0.15 (mm(2))/s, and the ability to withstand temperatures above 95 degrees C make this material appropriate for HIFU applications. The TMM also allows for the embedding of thermocouples and the formation of wall-less vessels that do not deteriorate as a result of continuous flow of blood mimicking fluids through the material. Tissue characteristics are strongly dependent on the fabrication technique, and care must be taken to achieve reproducible results. Note: This research was supported by the Defense Advanced Research Projects Agency (DARPA). C1 [King, Randy L.; Herman, Bruce. A.; Maruvada, Subha; Wear, Keith A.; Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,Mail Stop HFZ-170, Rockville, MD 20850 USA. RP King, RL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,Mail Stop HFZ-170, Rockville, MD 20850 USA. FU Defense Advanced Research Projects Agency (DARPA) FX This research was supported by the Defense Advanced Research Projects Agency (DARPA). The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the U.S. Department of Health and Human Services. NR 11 TC 6 Z9 6 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0419-9 J9 AIP CONF PROC PY 2007 VL 911 BP 351 EP + PG 2 WC Acoustics; Physics, Multidisciplinary; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BGI56 UT WOS:000247342200054 ER PT J AU Chaurasia, CS Muller, M Bashaw, ED Benfeldt, E Bolinder, J Bullock, R Bungay, PM DeLange, ECM Derendorf, H Elmquist, WF Hammarlund-Udenaes, M Joukhadar, C Kellogg, DL Lunte, CE Nordstrom, CH Rollema, H Sawchuk, RJ Cheung, BWY Shah, VP Stahle, L Ungerstedt, U Welty, DF Yeo, H AF Chaurasia, Chandra S. Mueller, Markus Bashaw, Edward D. Benfeldt, Eva Bolinder, Jan Bullock, Ross Bungay, Peter M. DeLange, Elizabeth C. M. Derendorf, Hartmut Elmquist, William F. Hammarlund-Udenaes, Margareta Joukhadar, Christian Kellogg, Dean L., Jr. Lunte, Craig E. Nordstrom, Carl Henrik Rollema, Hans Sawchuk, Ronald J. Cheung, Belinda W. Y. Shah, Vinod P. Stahle, Lars Ungerstedt, Urban Welty, Devin F. Yeo, Helen TI AAPS-FDA workshop white paper: Microdialysis principles, application, and regulatory perspectives report from the joint AAPS-FDA workshop, November 4-5, 2005, Nashville, TN SO AAPS JOURNAL LA English DT Article ID IN-VIVO MICRODIALYSIS; BLOOD-BRAIN-BARRIER; ZERO-NET-FLUX; CONCENTRATION PROFILES; CEREBROSPINAL-FLUID; DIABETIC-PATIENTS; SKELETAL-MUSCLE; DRUG-DELIVERY; PHARMACOKINETICS; TISSUE C1 US FDA, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria. US FDA, Off Clin Pharmacol, Div Clin Pharmacol 3, Silver Spring, MD USA. Univ Copenhagen, Dept Dermatol, Copenhagen NV, Denmark. Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, Stockholm, Sweden. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. NIH, Off Res Serv, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. LACDR, Leiden, Netherlands. Univ Florida, Dept Pharmaceut, Gainesville, FL 32611 USA. Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. Uppsala Univ, Dept Pharmaceut, Uppsala, Sweden. Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. Univ Lund Hosp, Dept Neurosurg, S-22185 Lund, Sweden. Pfizer Global Res, Dept Neurosci, Groton, CT USA. Astra Zeneca, Sodertalje, Sweden. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. Allergan Pharmaceut Inc, Pharmacokinet & Drug Metab, Irvine, CA 92715 USA. Roche, Dept Drug Metab & Pharmacokinet, Palo Alto, CA USA. RP Chaurasia, CS (reprint author), US FDA, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. EM chandra.chaurasia@fda.hhs.gov RI Derendorf, Hartmut/B-4628-2012 OI Derendorf, Hartmut/0000-0003-4016-1370 NR 61 TC 6 Z9 6 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PY 2007 VL 9 IS 1 BP E48 EP E59 AR 6 DI 10.1208/aapsj0901006 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 160LT UT WOS:000245943200006 ER PT J AU Goodsaid, F Frueh, F AF Goodsaid, Federico Frueh, Felix TI Biomarker qualification pilot process at the US food and drug administration SO AAPS JOURNAL LA English DT Article DE biomarker; validation; FDA AB New biomarkers of safety and efficacy are becoming powerful tools in drug development. Their application can be accelerated if a consensus can be reached about their qualification for regulatory applications. This consensus requires a review structure within the US Food and Drug Administration (FDA) that can evaluate qualification data for these biomarkers and determine whether these biomarkers can be qualified. A pilot process and corresponding Biomarker Qualification Review Team have been developed to test how the FDA can work on biomarker qualification. C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol,Genom Grp, Silver Spring, MD 20903 USA. RP Goodsaid, F (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol,Genom Grp, 10903 New Hampshire Ave,Bldg 21,Room 3663, Silver Spring, MD 20903 USA. EM Federico.goodsaid@fda.hhs.gov NR 5 TC 76 Z9 79 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PY 2007 VL 9 IS 1 BP E105 EP E108 AR 10 DI 10.1208/aapsj0901010 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 160LT UT WOS:000245943200010 PM 17408233 ER PT J AU Martinez, MN Bonate, P Chapman, RL De Groot, A D'Souza, S Ghilazi, N Gray, V Gupta, VK Huynh-Ba, K Iyer, S Jayatilaka, A Joshi, A Karnes, HT Khan, M Liu, P Lunte, C McCurdy, CR Morris, ME Norris, KJ Ramsey, P Sehgal, S Zahn, M AF Martinez, Marilyn N. Bonate, Peter Chapman, Robert L. De Groot, Anne D ' Souza, Susan Ghilazi, Naushad Gray, Vivian Gupta, Vishal K. Huynh-Ba, Kim Iyer, Sunil Jayatilaka, Arya Joshi, Amita Karnes, H. Thomas Khan, Mansoor Liu, Patrick Lunte, Craig McCurdy, Christopher R. Morris, Marilyn E. Norris, Kenneth J. Ramsey, Phillip Sehgal, Sanjay Zahn, Manuel TI 2007 highlights of advances in the pharmaceutical sciences: An American association of pharmaceutical scientists (AAPS) perspective SO AAPS JOURNAL LA English DT Editorial Material DE dose predictions; product design; product quality control; population kinetics; dose individualization; regulatory sciences; pharmacostatistics; process analytical technology; medical imagining; quantitative pharmacology; dissolution; biotechnology ID PEMETREXED THERAPY; MODEL AB The American Association of Pharmaceutical Scientists (AAPS) covers the full range of areas of expertise associated with the resolution of concerns pertaining to drugs and drug products. This editorial highlights the initiatives, issues, and challenges that are the forefront of the pharmaceutical sciences in 2007. It also provides an overview of how these difficult questions are being addressed through the programs and events associated with the AAPS 2007 Annual Meeting that will be held at the San Diego, California, Convention Center from November 11 to 15, 2007. C1 US FDA, Rockville, MD 20855 USA. Genzyme Corp, San Antonio, TX USA. Midwestern Univ, Chicago Coll Pharm, Dept Pharmaceut Sci, Providence, RI USA. Schering Plough Res Inst, Scotch Plains, NJ USA. Lake Erie Coll Osteopath Med, Dept Pharmaceut Sci, Erie, PA USA. VA Gray Consulting, Hockessin, DE USA. Pharmaceut R&D, St Louis, MO USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. Pfizer Inc, Kalamazoo, MI USA. Genentech Inc, San Francisco, CA 94080 USA. Tanox Biosyst Inc, Houston, TX USA. Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. Pfizer Inc, Groton, CT USA. SAIC Frederick, Frederick, MD USA. Wyeth Ayerst Res, Global Regulatory Affairs, Collegeville, PA USA. Astra Zeneca, Plankstadt, Germany. RP Martinez, MN (reprint author), US FDA, 7500 Standish Pl,HFV-130, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 8 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PY 2007 VL 9 IS 2 BP E219 EP E226 AR 24 DI 10.1208/aapsj0902024 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 200DQ UT WOS:000248744500013 ER PT J AU Viswanathan, CT Bansal, S Booth, B DeStefano, AJ Rose, MJ Sailstad, J Shah, VP Skelly, JP Swann, PG Weiner, R AF Viswanathan, C. T. Bansal, Surendra Booth, Brian DeStefano, Anthony J. Rose, Mark J. Sailstad, Jeffrey Shah, Vinod P. Skelly, Jerome P. Swann, Patrick G. Weiner, Russell TI Workshop/conference report - Quantitative bioanalytical methods validation and implementation: Best practices for chromatographic and ligand binding assays SO AAPS JOURNAL LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Procter & Gamble Pharmaceut, Mason, OH 45040 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Sailstad & Associates, Durham, NC 27707 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Bristol Myers Squibb Inc, Pennington, NJ 08534 USA. RP Skelly, JP (reprint author), 9321 Coral Lane, Alexandria, VA 22309 USA. EM Jeromepskelly@msn.com NR 5 TC 331 Z9 333 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PY 2007 VL 9 IS 1 BP E30 EP E42 AR 4 DI 10.1208/aapsj0901004 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 160LT UT WOS:000245943200004 ER PT J AU Adams, WP Christopher, D Lee, DS Morgan, B Pan, ZP Singh, GJP Tsong, Y Lyapustina, S AF Adams, Wallace P. Christopher, David Lee, Douglas S. Morgan, Beth Pan, Ziqing Singh, Gur Jai Pal Tsong, Yi Lyapustina, Svetlana TI Product Quality Research Institute evaluation of cascade impactor profiles of pharmaceutical aerosols, part 1: Background for a statistical method SO AAPS PHARMSCITECH LA English DT Article DE chi-square ratio; bioequivalence; cascade impactor; particle size distribution AB The purpose of this article is 2- fold: ( 1) to document in the public domain the considerations that led to the development of a regulatory statistical test for comparison of aerodynamic particle size distribution ( APSD) of aerosolized drug formulations, which was proposed in a US Food and Drug Administration ( FDA) draft guidance for industry; and ( 2) to explain the background and process for evaluation of that test through a working group involving scientists from the FDA, industry, academia, and the US Pharmacopeia, under the umbrella of the Product Quality Research Institute ( PQRI). The article and the referenced additional statistical information posted on the PQRI Web site explain the reasoning and methods used in the development of the APSD test, which is one of the key tests required for demonstrating in vitro equivalence of orally inhaled and nasal aerosol drug products. The article also describes the process by which stakeholders with different perspectives have worked collaboratively to evaluate properties of the test by drawing on statistical models, historical and practical information, and scientific reasoning. Overall, this article provides background information to accompany the companion article's discussion of the study's methods and results. C1 Drinker Biddle & Reath LLP, Pharmaceut Practice Grp, Washington, DC 20005 USA. US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20857 USA. Schering Plough Res Inst, Kenilworth, NJ USA. Pfizer Global R&D, Nonclin Stat, Groton, CT USA. GlaxoSmithKline Inc, Mfg & Supply, Zebulon, NC USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Lyapustina, S (reprint author), Drinker Biddle & Reath LLP, Pharmaceut Practice Grp, 1301 K St NW,Suite 900 E Tower, Washington, DC 20005 USA. EM svetlana.lyapustina@dbr.com NR 19 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201-3042 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2007 VL 8 IS 1 AR 4 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 160LS UT WOS:000245943100004 PM 17408227 ER PT J AU Christopher, D Adams, W Amann, A Bertha, C Byron, PR Doub, W Dunbar, C Hauck, W Lyapustina, S Mitchell, J Morgan, B Nichols, S Pan, Z Pal Singh, GJ Tougas, T Tsong, Y Wolff, R Wyka, B AF Christopher, David Adams, Wallace Amann, Anthony Bertha, Craig Byron, Peter R. Doub, William Dunbar, Craig Hauck, Walter Lyapustina, Svetlana Mitchell, Jolyon Morgan, Beth Nichols, Steve Pan, Ziqing Pal Singh, Gur Jai Tougas, Terrence Tsong, Yi Wolff, Ron Wyka, Bruce TI Product Quality Research Institute evaluation of cascade impactor profiles of pharmaceutical aerosols, Part 3: Final report on a statistical procedure for determining equivalence SO AAPS PHARMSCITECH LA English DT Review DE chi-square; population bioequivalence; particle size distribution; inhaler ID MILD ASTHMATICS; SIZE AB The purpose of this article is to report final results of the evaluation of a chi-square ratio test proposed by the US Food and Drug Administration (FDA) for demonstrating equivalence of aerodynamic particle size distribution (APSD) profiles of nasal and orally inhaled drug products. A working group of the Product Quality Research Institute previously published results demonstrating some limitations of the proposed test. In an effort to overcome the test's limited discrimination, the group proposed a supplemental test, a population bioequivalence (PBE) test for impactor-sized mass (ISM). In this final report the group compares the chi-square ratio test to the ISM-PBE test and to the combination of both tests. The basis for comparison is a set of 55 realistic scenarios of cascade impactor data, which were evaluated for equivalence by the statistical tests and independently by the group members. In many instances, the combined application of these 2 tests appeared to increase the discriminating ability of the statistical procedure compared with the chi-square ratio test alone. In certain situations the chi-square ratio test alone was sufficient to determine equivalence of APSD profiles, while in other situations neither of the tests alone nor their combination was adequate. This report describes all of these scenarios and results. In the end, the group did not recommend a statistical test for APSD profile equivalence. The group did not investigate other in vitro tests, in vivo issues, or other statistical tests for APSD profile comparisons. The studied tests are not intended for routine quality control of APSD. C1 Drinker Biddle & Reath LLP, Washington, DC 20005 USA. Schering Plough Res Inst, Kenilworth, NJ USA. US FDA, Ctr Drug Evaluat & Res, Off Gen Drug, Rockville, MD USA. ACN Pharma, LLC, Naperville, IL USA. US FDA, Ctr Drug Evaluat & Res, Off New Drug Assessment, Silver Spring, MD USA. Virginia Commonwealth Univ, Richmond, VA USA. US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, St Louis, MO USA. Alkermes, Cambridge, MA USA. US Pharmacopeia, Rockville, MD USA. Trudell Med Int, London, ON, Canada. GlaxoSmithKline Inc, Zebulon, NC USA. Ind Dev Sanofi Aventis, Holmes Chapel, Cheshire, England. Watson Lab, Ridgefield, CT USA. US FDA, Ctr Drug Evaluat & Res, Off Biometr, Rockville, MD USA. Nektar Therapeut, San Carlos, CA USA. RP Lyapustina, S (reprint author), Drinker Biddle & Reath LLP, 1500 K St N W,Ste 1100, Washington, DC 20005 USA. EM Svetlana.Lyapustina@dbr.com RI Doub, Bill/B-7106-2015 OI Doub, Bill/0000-0003-3750-9049 NR 24 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2007 VL 8 IS 4 AR 90 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 239RR UT WOS:000251535900010 ER PT J AU Christopher, D Adams, WP Lee, DS Morgan, B Pan, ZQ Singh, GJP Tsong, Y Lyapustina, S AF Christopher, David Adams, Wallace P. Lee, Douglas S. Morgan, Beth Pan, Ziqing Singh, Gur Jai Pal Tsong, Yi Lyapustina, Svetlana TI Product Quality Research Institute evaluation of cascade impactor profiles of pharmaceutical aerosols: Part 2 - Evaluation of a method for determining equivalence SO AAPS PHARMSCITECH LA English DT Article DE chi-square ratio; bioequivalence; cascade impactor; particle size distribution ID FAILURE INVESTIGATION TREE AB The purpose of this article is to present the thought process, methods, and interim results of a PQRI Working Group, which was charged with evaluating the chi-square ratio test as a potential method for determining in vitro equivalence of aerodynamic particle size distribution ( APSD) profiles obtained from cascade impactor measurements. Because this test was designed with the intention of being used as a tool in regulatory review of drug applications, the capability of the test to detect differences in APSD profiles correctly and consistently was evaluated in a systematic way across a designed space of possible profiles. To establish a " base line," properties of the test in the simplest case of pairs of identical profiles were studied. Next, the test's performance was studied with pairs of profiles, where some difference was simulated in a systematic way on a single deposition site using realistic product profiles. The results obtained in these studies, which are presented in detail here, suggest that the chi-square ratio test in itself is not sufficient to determine equivalence of particle size distributions. This article, therefore, introduces the proposal to combine the chi- square ratio test with a test for impactor- sized mass based on Population Bioequivalence and describes methods for evaluating discrimination capabilities of the combined test. The approaches and results described in this article elucidate some of the capabilities and limitations of the original chi- square ratio test and provide rationale for development of additional tests capable of comparing APSD profiles of pharmaceutical aerosols. C1 Drinker Biddle & Reath LLP, Washington, DC 20005 USA. Schering Plough Res Inst, Kenilworth, NJ USA. US FDA, CDER, Off Gener Drugs, Rockville, MD 20857 USA. Pfizer Global R&D, Nonclin Stat, Groton, CT USA. GlaxoSmithKline Inc, Mfg & Supply, Zebulon, NC USA. Schering Plough Res Inst, Stat, Kenilworth, NJ USA. US FDA, CDER, Rockville, MD 20857 USA. RP Lyapustina, S (reprint author), Drinker Biddle & Reath LLP, 1301 K St NW,Suite 900,E Tower, Washington, DC 20005 USA. EM svetlana.lyapustina@dbr.com NR 17 TC 11 Z9 11 U1 1 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201-3042 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2007 VL 8 IS 1 AR 5 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 160LS UT WOS:000245943100005 PM 17408228 ER PT J AU Gao, Z Moore, T Smith, AP Doub, W Westenberger, B Buhse, L AF Gao, Zongming Moore, Terry Smith, Anjanette P. Doub, William Westenberger, Benjamin Buhse, Lucinda TI Gauge repeatability and reproducibility for accessing variability during dissolution testing: A technical note SO AAPS PHARMSCITECH LA English DT Article DE dissolution test; gauge R&R; variability ID USP; APPARATUS-2; TABLETS C1 US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Gao, Z (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St, Room 1002, St Louis, MO 63101 USA. EM Zongming.Gao@fda.hhs.gov NR 21 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2007 VL 8 IS 4 AR 82 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 239RR UT WOS:000251535900003 ER PT J AU Prodduturi, S Urman, KL Otaigbe, JU Repka, MA AF Prodduturi, Suneela Urman, Kevin L. Otaigbe, Joshua U. Repka, Michael A. TI Stabilization of hot-melt extrusion formulations containing solid solutions using polymer blends SO AAPS PHARMSCITECH LA English DT Article DE solid solution; physical stability; hot-melt; extrusion; polymers; physicochemical characterization ID DIFFERENTIAL SCANNING CALORIMETRY; RELEASE CHARACTERISTICS; POLY(ETHYLENE OXIDE); FILMS; STABILITY; DRUGS; STATE AB This study was aimed at enhancing the physical stability of the drug clotrimazole (CT) and the polymer contained within hot-melt extrusion (HME) films using polymer blends of hydroxypropyl cellulose (HPC) and poly(ethylene oxide) (PEO). The HME films were investigated for solid-state characteristics, moisture sorption, bioadhesivity, mechanical properties, glass transition temperature, release characteristics, and physical and chemical stability of the drug and the polymer within the HME films. The solid-state characterization of the drug and the polymer was performed using differential scanning calorimetry, x-ray diffractometry, and dynamic mechanical analysis. A texture analyzer was used to study the bioadhesive and mechanical properties of the HME films. The physical and chemical stability of the films, stored at 25 degrees C/60% relative humidity or in a desiccator, was studied for up to 12 months. CT was found to be in solid solution within all of the formulations extruded. The physical stability of the drug and PEO in the HME films increased with increasing HPC concentration, but the bioadhesivity and flexibility of the PEO films decreased with increasing HPC concentration. Films containing HPC:PEO:CT in the ratio of 55:35:10 demonstrated optimum physical-mechanical, bioadhesive, and release properties. In conclusion, polymer blends of HPC and PEO were used successfully to tailor the drug release, mechanical and bioadhesive properties, and stability of the HME films. C1 Univ Mississippi, Sch Pharm, Dept Pharmaceut, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA. US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. Univ So Mississippi, Sch Polymers & High Performance Mat, Hattiesburg, MS 39406 USA. RP Repka, MA (reprint author), Univ Mississippi, Sch Pharm, Dept Pharmaceut, Faser 104A, University, MS 38677 USA. EM marepka@olemiss.edu NR 25 TC 11 Z9 11 U1 1 U2 7 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201-3042 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2007 VL 8 IS 2 AR 50 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 200DS UT WOS:000248744700021 ER PT S AU Agrawal, A Parker, C Qazi, T Agrawal, K Pfefer, J AF Agrawal, Anant Parker, Camisha Qazi, Tariq Agrawal, Krishan Pfefer, Joshua BE VoDinh, T Grundfest, WS Benaron, DA Cohn, GE Raghavachari, R TI Sensitivity and robustness of methods for analyzing time-resolved fluorescence measurements of layered biological tissue - art. no. 643022 SO Advanced Biomedical and Clinical Diagnostic Systems V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Advanced Biomedical and Clinical Diagnostic Systems V CY JAN 21-23, 2007 CL San Jose, CA SP SPIE DE time-resolved fluorescence; data analysis; curve fitting; Laguerre functions ID AUTOFLUORESCENCE; SPECTROSCOPY AB Time-resolved fluorescence (TRF) measurements from layered biological tissue provide chemical and structural information which may be useful for imaging or single-point tissue diagnostics. While several techniques for analyzing TRF data have been proposed in the literature, a rigorous theoretical evaluation of these approaches has not been performed. In this study we have evaluated the sensitivity and robustness of four methods for analyzing TRF signals: biexponential deconvolution, single exponential deconvolution, Laguerre deconvolution, and direct peak width computation. Each of these analyses was performed on a large dataset of synthetic fluorescence decay curves. Each decay curve was generated by numerically convolving a pre-recorded nitrogen laser pulse with a biexponential decay based on fluorescence lifetimes of colonic mucosa. The relative contribution of each mucosal layer to the total TRF signal as well as the superficial layer's inherent lifetime were varied so as to investigate sensitivity to morphological and biochemical changes representative of a neoplastic disease process. To evaluate robustness, pre-set levels of Gaussian-distributed noise were added to the convolved curves to achieve variations in the signal-to-noise ratio. The relative merits and pitfalls of each analytical method are discussed. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Agrawal, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6543-6 J9 P SOC PHOTO-OPT INS PY 2007 VL 6430 BP 43022 EP 43022 AR 643022 DI 10.1117/12.717654 PG 8 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BGB90 UT WOS:000245947500044 ER PT B AU Lachenbruch, PA Wittes, J AF Lachenbruch, Peter A. Wittes, Janet BE Auget, JL Balakrishnan, N Mesbah, M Molenberghs, G TI Sentinel event methods for monitoring unanticipated adverse events SO ADVANCES IN STATISTICAL METHODS FOR THE HEALTH SCIENCES: APPLICATIONS TO CANCER AND AIDS STUDIES, GENOME SEQUENCE ANALYSIS, AND SURVIVAL ANALYSIS SE Statistics for Industry and Technology LA English DT Proceedings Paper CT International Conference on Statistics in Health Science CY JUN 23-25, 2004 CL Univ Nantes, Nantes, FRANCE HO Univ Nantes DE safety; data monitoring; sentinel events; group sequential plans; time to event analyses; progressive censoring AB We propose an approach to monitoring unanticipated adverse events in a clinical trial. For a specific type of event, the methods allow the first occurrence, the first few occurrences, or an elevated rate to trigger a formal monitoring plan to identify whether that event occurs more frequently in the treated than in the control arm. The methods can apply either to rare events or to common events not expected to occur at an elevated rate in the treated group. We offer some simple models, emphasizing that, by the very nature of its rarity, a rare event is quite difficult to monitor. C1 [Lachenbruch, Peter A.] US FDA, Rockville, MD 20857 USA. Stat Collaborat, Washington, DC USA. RP Lachenbruch, PA (reprint author), US FDA, Rockville, MD 20857 USA. EM lachenbruch@cber.fda.gov; janet@statcollab.com NR 7 TC 2 Z9 3 U1 0 U2 1 PU BIRKHAUSER BOSTON PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139-2333 USA BN 978-0-8176-4368-3 J9 STAT IND TECHNOL PY 2007 BP 61 EP + DI 10.1007/978-0-8176-4542-7_4 PG 2 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Public, Environmental & Occupational Health; Mathematics GA BFP98 UT WOS:000243687100004 ER PT B AU Foulkes, MA AF Foulkes, Mary A. BE Auget, JL Balakrishnan, N Mesbah, M Molenberghs, G TI Safety assessment versus efficacy assessment SO Advances in Statistical Methods for the Health Sciences: Applications to Cancer and Aids Studies, Genome Sequence Analysis, and Survival Analysis SE STATISTICS FOR INDUSTRY AND TECHNOLOGY LA English DT Proceedings Paper CT International Conference on Statistics in Health Science CY JUN 23-25, 2004 CL Univ Nantes, Nantes, FRANCE HO Univ Nantes DE patient safety; clinical evaluations ID CLINICAL-TRIALS; LONGITUDINAL DATA; MISSING DATA; METAANALYSIS; DROPOUTS; MODEL AB Many statistical methods have been developed that focus primarily on efficacy. Safety evaluation frequently involves many additional considerations. Randomized controlled trials, especially later phase 3 trials, are infrequently designed based on safety outcomes. Most of these trials are designed based on efficacy outcomes, and therefore have limited power to detect important differences in safety outcomes. Recently, there have been calls to design trials with sufficient power to address known safety concerns. When prevention trials introduce an experimental preventive intervention (e.g., a vaccine) to an otherwise healthy (although at-risk) population, safety considerations can substantially affect the benefit:risk ratio and thus the utility and acceptability of the intervention. Observation of safety outcomes is often less controlled than for efficacy outcomes, particularly for safety concerns that emerge during the course of the trial. When either safety or efficacy outcomes are missing, specific assumptions are required for analysis (e.g., missing completely at random, MCAR), but often these assumptions may not apply. The statistical methods that rely on these assumptions have largely been developed with a focus on efficacy outcomes. Illustrative examples, including meta-analyses, will be presented and the underdeveloped areas highlighted. C1 FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Foulkes, MA (reprint author), FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. NR 25 TC 0 Z9 1 U1 2 U2 2 PU BIRKHAUSER BOSTON PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139-2333 USA BN 978-0-8176-4368-3 J9 STAT IND TECHNOL PY 2007 BP 323 EP 334 DI 10.1007/978-0-8176-4542-7_21 PG 12 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Public, Environmental & Occupational Health; Mathematics GA BFP98 UT WOS:000243687100021 ER PT J AU Woo, JJY AF Woo, Jason J. Y. TI Adverse event monitoring and multivitamin-multimineral dietary supplements SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Conference on Multiviitamin/Mineral Supplements and Chronic Disease Prevention CY MAY 15-17, 2006 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth DE adverse events; dietary supplements; multivitamins; minerals AB study commissioned by the Food and Drug Administration (FDA) estimated that the FDA is notified of < 1% of all adverse events associated with dietary supplements. Among the factors that may contribute to underreporting are that many consumers presume supplements to be safe, use these products without the supervision of a health care professional, and may be unaware that the FDA regulates them. In 2001 an Office of the Inspector General report identified many of the difficulties in evaluating adverse events in a voluntary system and the barriers to effective analysis of these reports to generate possible signals of concern. These include factors such as limited medical information, limited product information, limited manufacturer information, limited information on dietary supplement consumers, and limited ability to analyze trends. In addition, for dietary supplements, vital premarket information (which is available for drug products) is often missing so that possible public health concerns generated by the adverse event reporting system, such as limited clinical information, product identification, and information on consumer use, cannot be adequately assessed. Thus, the FDA is inherently limited in its ability to investigate signals of public health problems generated by the system. However, the FDA can use adverse event reports to identify areas of concern warranting further investigation. The FDA then initiates collaboration with federal partners to identify knowledge gaps in the safety of individual dietary ingredients and products and works with these partners to fill these information gaps to support appropriate regulatory action. C1 US FDA, Div Dietary Supplement Programs, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Woo, JJY (reprint author), US FDA, Div Dietary Supplement Programs, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-810, College Pk, MD 20740 USA. EM jason.woo@fda.hhs.gov NR 5 TC 31 Z9 33 U1 1 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2007 VL 85 IS 1 BP 323S EP 324S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 125CP UT WOS:000243419400054 PM 17209219 ER PT J AU Gonzalez-Escalona, N Jaykus, LA DePaola, A AF Gonzalez-Escalona, Narjol Jaykus, Lee-Ann DePaola, Angelo TI Accurate identification of desired clones from 16S-23S rDNA spacer libraries using single PCR SO ANALYTICAL BIOCHEMISTRY LA English DT Editorial Material ID VIBRIO-PARAHAEMOLYTICUS; BACTERIA; REGIONS C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. RP Gonzalez-Escalona, N (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. EM narjol@gmail.com RI Gonzalez-Escalona, Narjol/A-7598-2009; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 NR 9 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 2007 VL 360 IS 1 BP 146 EP 147 DI 10.1016/j.ab.2006.10.026 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 123IS UT WOS:000243290200020 PM 17113024 ER PT J AU Kingsley, DH Hollinian, DR Calci, KR Chen, HQ Flick, GJ AF Kingsley, David H. Hollinian, Daniel R. Calci, Kevin R. Chen, Haiqiang Flick, George J. TI Inactivation of a norovirus by high-pressure processing SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HEPATITIS-A VIRUS; HIGH HYDROSTATIC-PRESSURE; NORWALK-LIKE VIRUS; VIRAL GASTROENTERITIS; FELINE CALICIVIRUS; OYSTERS; TEMPERATURE; FOOD; PICORNAVIRUSES; SURROGATE AB Murine norovirus (strain MNV-1), a propagable norovirus, was evaluated for susceptibility to high-pressure processing. Experiments with virus stocks in Dulbecco's modified Eagle medium demonstrated that at room temperature (20 degrees C) the virus was inactivated over a pressure range of 350 to 450 MPa, with a 5-min, 450-MPa treatment being sufficient to inactivate 6.85 log(10) PFU of MNV-1. The inactivation of MNV-1 was enhanced when pressure was applied at an initial temperature of 5 degrees C; a 5-min pressure treatment of 350 MPa at 30 degrees C inactivated 1.15 log(10) PFU of virus, while the same treatment at 5 degrees C resulted in a reduction of 5.56 log(10) PFU. Evaluation of virus inactivation as a function of treatment times ranging from 0 to 150 s and 0 to 900 s at 5 degrees C and 20 degrees C, respectively, indicated that a decreasing rate of inactivation with time was consistent with Weibull or log-logistic inactivation kinetics. The inactivation of MNV-1 directly within oyster tissues was demonstrated; a 5-min, 400-MPa treatment at 5 degrees C was sufficient to inactivate 4.05 log(10) PFU. This work is the first demonstration that norovirus can be inactivated by high pressure and suggests good prospects for inactivation of nonpropagable human norovirus strains in foods. C1 Delaware State Univ, James WW Baker Ctr, Microbial Food Safety Res Unit, USDA ARS, Dover, DE 19901 USA. Virginia Polytech Inst & State Univ, Dept Food Sci & Technol, Blacksburg, VA 24061 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ Delaware, Dept Anim & Food Sci, Newark, DE 19716 USA. RP Kingsley, DH (reprint author), Delaware State Univ, James WW Baker Ctr, Microbial Food Safety Res Unit, USDA ARS, Dover, DE 19901 USA. EM dkingsle@desu.edu NR 39 TC 112 Z9 116 U1 0 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 JAN PY 2007 VL 73 IS 2 BP 581 EP 585 DI 10.1128/AEM.02117-06 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 136BK UT WOS:000244197400025 PM 17142353 ER PT J AU Joner, M Farb, A Cheng, Q Finn, AV Acampado, E Burke, AP Skorija, K Creighton, W Kolodgie, FD Gold, HK Virmani, R AF Joner, Michael Farb, Andrew Cheng, Qi Finn, Aloke V. Acampado, Eduardo Burke, Allen P. Skorija, Kristi Creighton, Wendy Kolodgie, Frank D. Gold, Herman K. Virmani, Renu TI Pioglitazone inhibits in-stent restenosis in atherosclerotic rabbits by targeting transforming growth factor-beta and MCP-1 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE inflammation; pioglitazone; rabbit; restenosis; stent ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; ACTIVATED-RECEPTOR-GAMMA; MUSCLE-CELL-PROLIFERATION; NECROSIS-FACTOR-ALPHA; PPAR-GAMMA; GENE-EXPRESSION; INSULIN-RESISTANCE; TYROSINE KINASES; ARTERY INJURY; LIGANDS AB Objective-Although emerging data from preclinical and clinical studies suggests a reduction of in-stent restenosis with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, the reduction of neointimal growth via anti-inflammatory mechanisms has not been explored. Methods and Results-Hypercholesterolemic New Zealand White rabbits (n=45) received bilateral balloon-expandable stents implanted into atherosclerotic iliac arteries. Animals were randomized to oral pioglitazone 3 ( low dose) or 10 mg/kg per day (high dose) started on the day of stent implantation; control rabbits received placebo. Tissue harvest was performed 28 days after stenting, and stented segments underwent histology, morphometry, immunostaining for macrophages, and scanning electron microscopy. In selected animals, stented arterial segments were placed in organoid culture for 48 hours, and the conditioned media was assayed for 23 different cytokines. There was a 21% reduction in neointimal area for high-dose pioglitazone treated versus placebo rabbits (P < 0.005), which was associated with a significant reduction of neointimal macrophages. Analysis of conditioned media revealed an 82% and 74% reduction in the release of monocyte chemoattractant protein-1 (MCP-1) (P < 0.007) and transforming growth factor (TGF)-beta 1 (P < 0.01), respectively, in stented segments from animals treated with 10 mg/kg per day pioglitazone versus placebo. Conclusions-Oral pioglitazone suppresses in-stent neointimal growth by limiting local inflammatory pathways and may be useful as an adjunctive therapy in patients undergoing percutaneous interventions. C1 CVPath Inst Inc, Int Registry Pathol, Gaithersburg, MD 20878 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Virmani, R (reprint author), CVPath Inst Inc, Int Registry Pathol, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 40 TC 58 Z9 64 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2007 VL 27 IS 1 BP 182 EP 189 DI 10.1161/01.ATV.0000251021.28725.e8 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 127FZ UT WOS:000243572000029 PM 17068283 ER PT J AU Almond, CSD Chen, EA Berman, MR Less, JR Baldwin, JT Linde-Feucht, SR Hoke, TR Pearson, GD Jenkins, K Duncan, BW Zuckerman, BD AF Almond, Christopher S. D. Chen, Eric A. Berman, Michael R. Less, Joanne R. Baldwin, J. Timothy Linde-Feucht, Sarah R. Hoke, Tracey R. Pearson, Gail D. Jenkins, Kathy Duncan, Brian W. Zuckerman, Bram D. TI High-risk medical devices, children and the FDA: Regulatory challenges facing pediatric mechanical circulatory support devices SO ASAIO JOURNAL LA English DT Article; Proceedings Paper CT 2nd International Conference on Pediatric Mechanical Circulatory Support Systems/Pediatric Cardiopulmonary Perfusion CY MAY 18-20, 2006 CL Toronto, CANADA ID EXTRACORPOREAL MEMBRANE-OXYGENATION; CARDIAC TRANSPLANTATION; ASSIST DEVICES; LIFE-SUPPORT; INFANTS; BRIDGE; HEART; ECMO AB Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted. C1 Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Cardiol, Boston, MA 02115 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NHLBI, NIH, Bethesda, MD 20892 USA. US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. Cleveland Clin Fdn, Childrens Hosp, Dept Cardiac Surg, Cleveland, OH 44195 USA. RP Almond, CSD (reprint author), Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. NR 21 TC 14 Z9 14 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD JAN-FEB PY 2007 VL 53 IS 1 BP 4 EP 7 DI 10.1097/01.mat.0000247958.84788.3a PG 4 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 128XE UT WOS:000243692200002 PM 17237642 ER PT S AU Marutyan, KR Anderson, CC Wear, KA Holland, MR Miller, JG Bretthorst, GL AF Marutyan, Karen R. Anderson, Christian C. Wear, Keith A. Holland, Mark R. Miller, James G. Bretthorst, G. Larry BE Knuth, KH Caticha, A Giffin, A Rodriguez, CC Center, JL TI Parameter estimation in ultrasonic measurements on trabecular bone SO BAYESIAN INFERENCE AND MAXIMUM ENTROPY METHODS IN SCIENCE AND ENGINEERING SE AIP Conference Proceedings LA English DT Proceedings Paper CT 27th International Workshop on Bayesian Inference and Maximum Entropy Methods in Science and Engineering CY JUL 08-13, 2007 CL Saratoga Springs, NY SP Boise State Univ, Edwin T Jaynes Int Ctr Bayesian Methods & Maximum Entropy, Univ Albany, MaxEnt Workshops Inc DE Bayesian probability theory; tissue characterization; bone; ultrasound; osteoporosis ID CANCELLOUS BONE; DISPERSION; WAVES AB Ultrasonic tissue characterization has shown promise for clinical diagnosis of diseased bone (e.g., osteoporosis) by establishing correlations between bone ultrasonic characteristics and the state of disease. Porous (trabecular) bone supports propagation of two compressional modes, a fast wave and a slow wave, each of which is characterized by an approximately linear-withfrequency attenuation coefficient and monotonically increasing with frequency phase velocity. Only a single wave, however, is generally apparent in the received signals. The ultrasonic parameters that govern propagation of this single wave appear to be causally inconsistent [1]. Specifically, the attenuation coefficient rises approximately linearly with frequency, but the phase velocity exhibits a decrease with frequency. These inconsistent results are obtained when the data are analyzed under the assumption that the received signal is composed of one wave. The inconsistency disappears if the data are analyzed under the assumption that the signal is composed of superposed fast and slow waves. In the current investigation, Bayesian probability theory is applied to estimate the ultrasonic characteristics underlying the propagation of the fast and slow wave from computer simulations. Our motivation is the assumption that identifying the intrinsic material properties of bone will provide more reliable estimates of bone quality and fracture risk than the apparent properties derived by analyzing the data using a one-mode model. C1 [Marutyan, Karen R.; Bretthorst, G. Larry] Washington Univ, Mallinckrodt Inst Radiol, Biomed Magnet Resonance Lab, St Louis, MO 63110 USA. [Anderson, Christian C.; Holland, Mark R.; Miller, James G.] Washington Univ, Dept Phys, Lab Ultrason, St Louis, MO 63130 USA. [Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Marutyan, KR (reprint author), Washington Univ, Mallinckrodt Inst Radiol, Biomed Magnet Resonance Lab, St Louis, MO 63110 USA. NR 7 TC 2 Z9 2 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 978-0-7354-0468-7 J9 AIP CONF PROC PY 2007 VL 954 BP 329 EP + PG 2 WC Mathematics, Applied; Physics, Applied SC Mathematics; Physics GA BGY63 UT WOS:000251381000036 ER PT S AU Anderson, CC Marutyan, KR Wear, KA Holland, MR Miller, JG Bretthorst, GL AF Anderson, Christian C. Marutyan, Karen R. Wear, Keith A. Holland, Mark R. Miller, James G. Bretthorst, G. Larry BE Knuth, KH Caticha, A Giffin, A Rodriguez, CC Center, JL TI Model selection in ultrasonic measurements on trabecular bone SO BAYESIAN INFERENCE AND MAXIMUM ENTROPY METHODS IN SCIENCE AND ENGINEERING SE AIP Conference Proceedings LA English DT Proceedings Paper CT 27th International Workshop on Bayesian Inference and Maximum Entropy Methods in Science and Engineering CY JUL 08-13, 2007 CL Saratoga Springs, NY SP Boise State Univ, Edwin T Jaynes Int Ctr Bayesian Methods & Maximum Entropy, Univ Albany, MaxEnt Workshops Inc DE Bayesian probability theory; model selection; tissue characterization; bone; ultrasound; osteoporosis ID CANCELLOUS BONE; PROPAGATION; DISPERSION; VELOCITY AB Previous work from our laboratory showed that the widely reported decrease in phase velocity with frequency (negative dispersion) for ultrasonic waves propagating through trabecular bone can arise from the interference of two compressional waves, each of which exhibits a positive dispersion. Previous simulations suggest that Bayesian probability theory can be employed to recover the material properties linked to these two interfering waves, even when the waves overlap sufficiently that visual inspection cannot distinguish two modes. In the present study, Bayesian probability theory is applied first to simulated data and then to representative experimental bone data to determine whether one or two compressional wave modes are present. Model selection is implemented by evaluating the posterior probability for each model. The calculation is implemented by defining a model indicator and then using Markov chain Monte Carlo with simulated annealing to draw samples from the joint posterior probability for the ultrasonic parameters and the model indicator. Monte Carlo integration is used to evaluate the marginal posterior probability for each parameter given the model indicator. C1 Washington Univ, Dept Phys, Lab Ultrason, St Louis, MO 63130 USA. [Marutyan, Karen R.; Bretthorst, G. Larry] Washington Univ, Biomed Magnet Resonance Lab, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Wear, Keith A.] US FDA, Ctr Devices & Radiol Hth, Silver Spring, MD 20993 USA. RP Anderson, CC (reprint author), Washington Univ, Dept Phys, Lab Ultrason, St Louis, MO 63130 USA. NR 8 TC 2 Z9 2 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 978-0-7354-0468-7 J9 AIP CONF PROC PY 2007 VL 954 BP 337 EP + PG 3 WC Mathematics, Applied; Physics, Applied SC Mathematics; Physics GA BGY63 UT WOS:000251381000037 ER PT J AU Yoon, DM Hawkins, EC Francke-Carroll, S Fisher, JP AF Yoon, Diana M. Hawkins, Emily C. Francke-Carroll, Sabine Fisher, John P. TI Effect of construct properties on encapsulated chondrocyte expression of insulin-like growth factor-1 SO BIOMATERIALS LA English DT Article DE alginate; cell signaling; chondrocyte; insulin-like growth factor-1 ID ARTICULAR-CARTILAGE; STIMULATION; SCAFFOLDS; CULTURE; SERUM AB Hydrogels are a promising type of biomaterial for articular cartilage constructs since they have been shown to enable encapsulated chondrocytes to express their predominant phenotypic marker, type II collagen. Endogenously expressed signaling molecules, such as insulin-like growth factor-1 (IGF-1), are also known to facilitate the retention of this chondrocytic phenotype. Recent investigations have attempted to enhance the ability of encapsulated chondrocytes to regenerate cartilage through delivery of exogenous signaling molecules. However, we hypothesize that by altering construct properties, such as cell density and polymer concentration, we can augment the expression of endogenous IGF-1 in chondrocytes. To this end, bovine articular chondrocytes were encapsulated within alginate hydrogels at two different cell densities (25,000 and 100,000 cells/bead) and various alginate concentrations (0.8%, 1.2%, and 2.0% w/v). These parameters were chosen to simultaneously investigate cell-to-cell distance on paracrine signaling and water content on IGF-1 diffusion by chondrocytes. At 1, 4, and 8 d, chondrocytes were analyzed for protein and mRNA expression of IGF-1 as well as type II collagen. Results suggest that cell density and alginate concentration at high cell density can significantly affect the endogenous IGF-1 expression by chondrocytes. Therefore, these results indicate that construct properties can impact chondrocyte gene expression and should be considered in order to create a proper engineered articular cartilage construct. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. US FDA, Pathol Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Fisher, JP (reprint author), Univ Maryland, Fischell Dept Bioengn, 3238 Jeong H Kim Engn Bldg, College Pk, MD 20742 USA. EM jpfisher@umd.edu RI Fisher, John/F-8078-2012 NR 23 TC 30 Z9 32 U1 0 U2 7 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 JAN PY 2007 VL 28 IS 2 BP 299 EP 306 DI 10.1016/j.biomaterials.2006.08.039 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 109LV UT WOS:000242310500017 PM 16982090 ER PT J AU Nijdam, AJ Cheng, MMC Geho, DH Fedele, R Herrmann, P Killian, K Espina, V Petricoin, EF Liotta, LA Ferrari, M AF Nijdam, A. Jasper Cheng, Mark Ming- Cheng Geho, David H. Fedele, Roberta Herrmann, Paul Killian, Keith Espina, Virginia Petricoin, Emanuel F., III Liotta, Lance A. Ferrari, Mauro TI Physicochemically modified silicon as a substrate for protein microarrays SO BIOMATERIALS LA English DT Article DE protein adsorption; silicon; surface modification; surface treatment ID POLY(ETHYLENE GLYCOL) FILMS; POROUS SILICON; SEMICONDUCTOR NANOCRYSTALS; ENZYME IMMOBILIZATION; QUANTUM DOTS; HUMAN PLASMA; SURFACES; CANCER; MICRODEVICES; BIOMOLECULES AB Reverse phase protein microarrays (RPMA) enable high throughput screening of posttranslational modifications of important signaling proteins within diseased cells. One limitation of protein-based molecular profiling is the lack of a PCR-like intrinsic amplification system for proteins. Enhancement of protein microarray sensitivities is an important goal, especially because many molecular targets within patient tissues are of low abundance. The ideal array substrate will have a high protein-binding affinity and low intrinsic signal. To date, nitrocellulose-coated glass has provided an effective substrate for protein binding in the microarray format when using chromogenic detection systems. As fluorescent systems, such as quantum dots, are explored as potential reporter agents, the intrinsic fluorescent properties of nitrocellulose-coated glass slides limit the ability to image microarrays for extended periods of time where increases in net sensitivity can be attained. Silicon, with low intrinsic autofluorescence, is being explored as a potential microarray surface. Native silicon has low binding potential. Through titrated reactive ion etching (RIE), varying surface areas have been created on silicon in order to enhance protein binding. Further, via chemical modification, reactive groups have been added to the surfaces for comparison of relative protein binding. Using this combinatorial method of surface roughening and surface coating, 3-aminopropyltriethoxysilane (APTES) and mercaptopropyltrimethoxysilane (MPTMS) treatments were shown to transform native silicon into a protein-binding substrate comparable to nitrocellulose. (c) 2006 Elsevier Ltd. All rights reserved. C1 Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat, Rockville, MD 20857 USA. Univ Texas, Hlth Sci Ctr, Houston, TX 77030 USA. RP Ferrari, M (reprint author), Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. EM Mauro.Ferrari@uth.tmc.edu OI Espina, Virginia/0000-0001-5080-5972 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 54 TC 46 Z9 47 U1 1 U2 15 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 JAN PY 2007 VL 28 IS 3 BP 550 EP 558 DI 10.1016/j.biomaterials.2006.08.051 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 118SB UT WOS:000242960900020 PM 16987550 ER PT J AU Zhukovsky, MA Markovic, I Bailey, AL AF Zhukovsky, Mikhail A. Markovic, Ingrid Bailey, Austin L. TI Influence of calcium on membrane fusion mediated by influenza hemagglutinin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc ID SITES C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. Cephalon Inc, Med Sci Liaison, Hoboken, NJ USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 243A EP 243A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401345 ER PT J AU Guo, L Mei, N Dial, S Fuscoe, J Chen, T AF Guo, Lei Mei, Nan Dial, Stacey Fuscoe, James Chen, Tao TI Comparison of gene expression profiles altered by comfrey and riddelliine in rat liver SO BMC BIOINFORMATICS LA English DT Article ID PYRROLIZIDINE ALKALOID RIDDELLIINE; DNA MICROARRAY TECHNOLOGY; BIG BLUE RATS; SYMPHYTUM-OFFICINALE; GLUTATHIONE CONJUGATE; VENOOCCLUSIVE DISEASE; METABOLIC-ACTIVATION; ADDUCT FORMATION; HUMAN CANCER; IN-VIVO AB Background: Comfrey (Symphytum officinale) is a perennial plant and has been consumed by humans as a vegetable, a tea and an herbal medicine for more than 2000 years. It, however, is hepatotoxic and carcinogenic in experimental animals and hepatotoxic in humans. Pyrrolizidine alkaloids (PAs) exist in many plants and many of them cause liver toxicity and/or cancer in humans and experimental animals. In our previous study, we found that the mutagenicity of comfrey was associated with the PAs contained in the plant. Therefore, we suggest that carcinogenicity of comfrey result from those PAs. To confirm our hypothesis, we compared the expression of genes and processes of biological functions that were altered by comfrey (mixture of the plant with PAs) and riddelliine (a prototype of carcinogenic PA) in rat liver for carcinogenesis in this study. Results: Groups of 6 Big Blue Fisher 344 rats were treated with riddelliine at 1 mg/kg body weight by gavage five times a week for 12 weeks or fed a diet containing 8% comfrey root for 12 weeks. Animals were sacrificed one day after the last treatment and the livers were isolated for gene expression analysis. The gene expressions were investigated using Applied Biosystems Rat Whole Genome Survey Microarrays and the biological functions were analyzed with Ingenuity Analysis Pathway software. Although there were large differences between the significant genes and between the biological processes that were altered by comfrey and riddelliine, there were a number of common genes and function processes that were related to carcinogenesis. There was a strong correlation between the two treatments for fold-change alterations in expression of drug metabolizing and cancer-related genes. Conclusion: Our results suggest that the carcinogenesis-related gene expression patterns resulting from the treatments of comfrey and riddelliine are very similar, and PAs contained in comfrey are the main active components responsible for carcinogenicity of the plant. C1 [Guo, Lei; Dial, Stacey; Fuscoe, James] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Mei, Nan; Chen, Tao] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov; nan.mei@fda.hhs.gov; stacey.dial@fda.hhs.gov; jame.fuscoe@fda.hhs.gov; tao.chen@fda.hhs.gov OI MEI, NAN/0000-0002-3501-9014 NR 44 TC 16 Z9 16 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2007 VL 8 SU 7 AR S22 DI 10.1186/1471-2105-8-S7-S22 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA V23BB UT WOS:000208317200022 PM 18047722 ER PT J AU Mei, N Guo, L Liu, RQ Fuscoe, JC Chen, T AF Mei, Nan Guo, Lei Liu, Ruqing Fuscoe, James C. Chen, Tao TI Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats SO BMC BIOINFORMATICS LA English DT Article AB Background: Pyrrolizidine alkaloids (PAs) are probably the most common plant constituents that poison livestock, wildlife, and humans worldwide. Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study. Previously we observed that the mutant frequency in the liver of rats gavaged with riddelliine was 3-fold higher than that in the control group. Molecular analysis of the mutants indicated that there was a statistically significant difference between the mutational spectra from riddelliine-treated and control rats. Results: Riddelliine-induced gene expression profiles in livers of Big Blue transgenic rats were determined. The female rats were gavaged with riddelliine at a dose of 1 mg/kg body weight 5 days a week for 12 weeks. Rat whole genome microarray was used to perform genome-wide gene expression studies. When a cutoff value of a two-fold change and a P-value less than 0.01 were used as gene selection criteria, 919 genes were identified as differentially expressed in riddelliine-treated rats compared to the control animals. By analysis with the Ingenuity Pathway Analysis Network, we found that these significantly changed genes were mainly involved in cancer, cell death, tissue development, cellular movement, tissue morphology, cell-to-cell signaling and interaction, and cellular growth and proliferation. We further analyzed the genes involved in metabolism, injury of endothelial cells, liver abnormalities, and cancer development in detail. Conclusion: The alterations in gene expression were directly related to the pathological outcomes reported previously. These results provided further insight into the mechanisms involved in toxicity and carcinogenesis after exposure to riddelliine, and permitted us to investigate the interaction of gene products inside the signaling networks. C1 [Mei, Nan; Chen, Tao] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Guo, Lei; Fuscoe, James C.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Liu, Ruqing] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Liu, Ruqing] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510089, Guangdong, Peoples R China. RP Mei, N (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM nan.mei@fda.hhs.gov; lei.guo@fda.hhs.gov; liuruqing@hotmail.com; james.fuscoe@fda.hhs.gov; tao.chen@fda.hhs.gov OI MEI, NAN/0000-0002-3501-9014 NR 41 TC 15 Z9 16 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2007 VL 8 SU 7 AR S4 DI 10.1186/1471-2105-8-S7-S4 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA V23BB UT WOS:000208317200004 PM 18047727 ER PT J AU Schnackenberg, LK Sun, JC Espandiari, P Holland, RD Hanig, J Beger, RD AF Schnackenberg, Laura K. Sun, Jinchun Espandiari, Parvaneh Holland, Ricky D. Hanig, Joseph Beger, Richard D. TI Metabonomics evaluations of age-related changes in the urinary compositions of male Sprague Dawley rats and effects of data normalization methods on statistical and quantitative analysis SO BMC BIOINFORMATICS LA English DT Article AB Background: Urine from male Sprague-Dawley rats 25, 40, and 80 days old was analyzed by NMR and UPLC/MS. The effects of data normalization procedures on principal component analysis (PCA) and quantitative analysis of NMR-based metabonomics data were investigated. Additionally, the effects of age on the metabolic profiles were examined by both NMR and UPLC/MS analyses. Results: The data normalization factor was shown to have a great impact on the statistical and quantitative results indicating the need to carefully consider how to best normalize the data within a particular study and when comparing different studies. PCA applied to the data obtained from both NMR and UPLC/MS platforms reveals similar age-related differences. NMR indicated many metabolites associated with the Krebs cycle decrease while citrate and 2-oxoglutarate, also associated with the Krebs cycle, increase in older rats. Conclusion: This study compared four different normalization methods for the NMR-based metabonomics spectra from an age-related study. It was shown that each method of normalization has a great effect on both the statistical and quantitative analyses. Each normalization method resulted in altered relative positions of significant PCA loadings for each sample spectra but it did not alter which chemical shifts had the highest loadings. The greater the normalization factor was related to age, the greater the separation between age groups was observed in subsequent PCA analyses. The normalization factor that showed the least age dependence was total NMR intensity, which was consistent with UPLC/MS data. Normalization by total intensity attempts to make corrections due to dietary and water intake of the individual animal, which is especially useful in metabonomics evaluations of urine. Additionally, metabonomics evaluations of age-related effects showed decreased concentrations of many Krebs cycle intermediates along with increased levels of oxidized antioxidants in urine of older rats, which is consistent with current theories on aging and its association with diminishing mitochondrial function and increasing levels of reactive oxygen species. Analysis of urine by both NMR and UPLC/MS provides a comprehensive and complementary means of examining metabolic events in aging rats. C1 [Schnackenberg, Laura K.; Holland, Ricky D.; Beger, Richard D.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Sun, Jinchun] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Espandiari, Parvaneh; Hanig, Joseph] Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Beger, RD (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM laura.schnackenberg@fda.hhs.gov; jsun@uams.edu; parvaneh.espandiari@fda.hhs.gov; ricky.holland@fda.hhs.gov; joseph.hanig@fda.hhs.gov; richard.beger@fda.hhs.gov NR 37 TC 30 Z9 31 U1 1 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2007 VL 8 SU 7 AR S3 DI 10.1186/1471-2105-8-S7-S3 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA V23BB UT WOS:000208317200003 PM 18047726 ER PT J AU Kiess, AS Kenney, PB Nayak, RR AF Kiess, A. S. Kenney, P. B. Nayak, R. R. TI Campylobacter detection in commercial turkeys SO BRITISH POULTRY SCIENCE LA English DT Article ID BROILER-CHICKENS; JEJUNI; COLONIZATION; EGGS AB Frequency of Campylobacter detection was monitored in three flocks of turkeys. The effect of week of production was evaluated for hens in flocks 1 and 2, and the effect of week, gender and litter ( fresh or used) was assessed for flock 3. 2. Gastrointestinal tracts, poult box liners, drinkers and faecal droppings were sampled. Conventional microbiological procedures were used to isolate and identify the presence of Campylobacter. Campylobacter latex agglutination tests were used for confirmation. 3. Peak colonisation occurred at approximately 3 weeks of production. Frequency of Campylobacter isolation from bird sources paralleled isolation from waterers. Frequency of detection from birds placed on used litter was lower than detection from birds placed on fresh litter ( 2% vs 58%). Gender did not affect frequency of detection. 4. Minimising peak colonisation at 3 weeks and managing litter are opportunities to reduce the occurrence of this organism in turkeys. C1 W Virginia Univ, Div Anim & Vet Sci, Morgantown, WV 26506 USA. Purdue Univ, Dept Anim Sci, W Lafayette, IN 47907 USA. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Kenney, PB (reprint author), W Virginia Univ, Div Anim & Vet Sci, Morgantown, WV 26506 USA. EM bkenney@wvu.edu NR 16 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0007-1668 J9 BRIT POULTRY SCI JI Br. Poult. Sci. PY 2007 VL 48 IS 5 BP 567 EP 572 DI 10.1080/00071660701573094 PG 6 WC Agriculture, Dairy & Animal Science SC Agriculture GA 222TB UT WOS:000250319000006 PM 17952728 ER PT J AU Adjei, MD Heinze, TM Deck, J Freeman, JP Williams, AJ Sutherland, JB AF Adjei, Michael D. Heinze, Thomas M. Deck, Joanna Freeman, James P. Williams, Anna J. Sutherland, John B. TI Acetylation and nitrosation of ciprofloxacin by environmental strains of mycobacteria SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE acetylation; ciprofloxacin; fluoroquinolones; Mycobacterium; nitrosation ID ARYLAMINE N-ACETYLTRANSFERASES; FUNGUS MUCOR-RAMANNIANUS; NITROSAMINE FORMATION; ESCHERICHIA-COLI; SECONDARY-AMINES; MICROORGANISMS; RESISTANCE; CATALYSIS; ENZYME; BIOTRANSFORMATION AB To determine the ability of environmental bacteria to metabolize the frequently prescribed fluoroquinolone drug ciprofloxacin, eight Mycobacterium spp. cultures were grown for 4 days in a medium containing sorbitol and yeast extract with 100 mg. L-1 ciprofloxacin. After the cultures had been centrifuged and the supernatants extracted with ethyl acetate, two metabolites were purified by using high-performance liquid chromatography. They were identified with liquid chromatography/electro spray ionization mass spectrometry and proton nuclear magnetic resonance spectroscopy. Ciprofloxacin was transformed to both N-acetylciprofloxacin (2.5%-5.5% of the total peak area at 280 nm) and N-nitrosociprofloxacin (6.0%-8.0% of the peak area) by Mycobacterium gilvum PYR-GCK and Mycobacterium sp. PYR100 but it was transformed only to N-acetylciprofloxacin by Mycobacterium frederiksbergense FAn9, M. gilvum ATCC 43909, M. gilvum BB 1, Mycobacterium smegmatis me 2 155, Mycobacterium sp. 7E1B1W, and Mycobacterium sp. RJGII-135. The results suggest that biotransformation may serve as a ciprofloxacin resistance mechanism for these bacteria. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov NR 32 TC 11 Z9 11 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD JAN PY 2007 VL 53 IS 1 BP 144 EP 147 DI 10.1139/W06-101 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 153XE UT WOS:000245470600019 PM 17496960 ER PT J AU Hasinoff, BB Herman, EH AF Hasinoff, Brian B. Herman, Eugene H. TI Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? SO CARDIOVASCULAR TOXICOLOGY LA English DT Article; Proceedings Paper CT International Workshop on Anthracycline Cardiotoxicity - Molecular Mechanisms and Clinical Correlate CY OCT 20-21, 2006 CL Scen Environm Villa Olmo, Como, PORTUGAL SP Dept Drug Sci & Ctr Excellence on Aging, G Annunzio Univ Sch Med, Menarini Fdn HO Scen Environm Villa Olmo DE dexrazoxane; cardioprotective; cardiotoxicity; chemoprotective; topoisomerase II ID HAMSTER OVARY CELLS; TOPOISOMERASE-II; ICRF-187 DEXRAZOXANE; CYTOTOXICITY; METABOLISM; INHIBITOR; CANCER; AGENT; CARDIOPROTECTANT; DAUNORUBICIN AB Dexrazoxane is highly effective in reducing anthracycline-induced cardiotoxicity and extravasation injury and is used clinically for these indications. Dexrazoxane has two biological activities: it is a prodrug that is hydrolyzed to an iron chelating EDTA-type structure and it is also a strong inhibitor of topoisomerase II. Doxorubicin is able to be reductively activated to produce damaging reactive oxygen species. Iron-dependent cellular damage is thought to be responsible for its cardiotoxicity. The available experimental evidence supports the conclusion that dexrazoxane reduces doxorubicin cardiotoxicity by binding free iron and preventing site-specific oxidative stress on cardiac tissue. However, it cannot be ruled out that dexrazoxane may also be protective through its ability to inhibit topoisomerase II. C1 Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. Ctr Drug Evaluat & Res Food & Drug Adm, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. RP Hasinoff, BB (reprint author), Univ Manitoba, Fac Pharm, 50 Sifton Rd, Winnipeg, MB R3T 2N2, Canada. EM B_Hasinoff@UManitoba.ca NR 23 TC 53 Z9 53 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1530-7905 J9 CARDIOVASC TOXICOL JI Cardiovasc. Toxicol. PY 2007 VL 7 IS 2 BP 140 EP 144 DI 10.1007/s12012-007-0023-3 PG 5 WC Cardiac & Cardiovascular Systems; Toxicology SC Cardiovascular System & Cardiology; Toxicology GA 202YT UT WOS:000248941700017 PM 17652819 ER PT J AU Wu, HQ Khan, MA Hussain, AS AF Wu, Huiquan Khan, Mansoor A. Hussain, Ajaz S. TI Process control perspective for process analytical technology: Integration of chemical engineering practice into semiconductor and pharmaceutical industries SO CHEMICAL ENGINEERING COMMUNICATIONS LA English DT Article DE chemical engineering principles; on-line process control; Process Analytical Technology (PAT); quality-by-design; Taguchi robust engineering design ID SCALE-UP; SENSOR; HYDRODYNAMICS; VARIABILITY; LIQUID AB FDA's Process Analytical Technology ( PAT) initiative provides an unprecedented opportunity for chemical engineers to play significant roles in the pharmaceutical industry. In this article, the authors provide their perspectives on ( 1) the need for chemical engineering principles in pharmaceutical development for a thorough process understanding; ( 2) applications of chemical engineering principles to meet the challenges from the semiconductor and pharmaceutical industries; and ( 3) the integration of chemical engineering practice into the semiconductor and pharmaceutical industries to achieve process understanding and the desired state of quality-by-design. A real-world case study from the semiconductor industry is presented to demonstrate how a classic chemical engineering concept, mixing homogeneity, can be implemented by inducing forced flow to ensure an excellent copper electrochemical plating process performance and to improve product quality substantially. Further, a case study of brake system design is discussed with the concept of Dr. Taguchi's robust engineering design to illustrate how quality-by-design can be achieved through appropriate experimental design, in conjunction with the discussion on the concept of quality-by-design in pharmaceuticals. Third, a case study of freeze-dried sodium ethacrynate is presented to demonstrate the vital importance of controlling the processing factors to achieve the desired product stability. Finally, the problems of the current pharmaceutical manufacturing mode, the opportunities and engineering challenges during implementation of PAT in the pharmaceutical industry, and the role of chemical engineering in implementation of PAT is discussed in detail. C1 US FDA, Div Prod Qual Res, HFD 940, OTR,OPS,CDER, Silver Spring, MD 20993 USA. RP Wu, HQ (reprint author), US FDA, Div Prod Qual Res, HFD 940, OTR,OPS,CDER, White Oak Campus LIfe Sci Bldg 64,Room 1080,10903, Silver Spring, MD 20993 USA. EM huiquan.wu@fda.hhs.gov NR 42 TC 22 Z9 23 U1 1 U2 14 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0098-6445 J9 CHEM ENG COMMUN JI Chem. Eng. Commun. PY 2007 VL 194 IS 6 BP 760 EP 779 DI 10.1080/00986440601098755 PG 20 WC Engineering, Chemical SC Engineering GA 156JD UT WOS:000245643000004 ER PT J AU Twaroski, ML Batarseh, LI Bailey, AB AF Twaroski, M. L. Batarseh, L. I. Bailey, A. B. BE Barnes, KA Sinclair, CR Watson, DH TI Regulation of food contact materials in the USA SO CHEMICAL MIGRATION AND FOOD CONTACT MATERIALS LA English DT Article; Book Chapter C1 [Twaroski, M. L.; Batarseh, L. I.; Bailey, A. B.] US FDA, Off Food Addit Safety HFS 275, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Twaroski, ML (reprint author), US FDA, Off Food Addit Safety HFS 275, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM michelle.twaroski@fda.hhs.gov; layla.batarshe@fda.hhs.gov; Allan.Bailey@fda.hhs.gov NR 11 TC 5 Z9 5 U1 1 U2 1 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND BN 978-1-84569-029-8 PY 2007 BP 17 EP 42 D2 10.1201/9781439824474 PG 26 WC Food Science & Technology SC Food Science & Technology GA BNC38 UT WOS:000274154800002 ER PT B AU Arvidson, KB Cheeseman, MA McDougal, AJ AF Arvidson, K. B. Cheeseman, M. A. McDougal, A. J. BE Barnes, KA Sinclair, CR Watson, DH TI Toxicology and risk assessment of chemical migrants from food contact materials SO CHEMICAL MIGRATION AND FOOD CONTACT MATERIALS LA English DT Article; Book Chapter ID SUBSTANCES PRESENT; CARCINOGENICITY; THRESHOLDS; MUTAGENICITY; INFORMATION; DESIGN; HAZARD; DIET; EPA C1 [Arvidson, K. B.; Cheeseman, M. A.; McDougal, A. J.] US FDA, Off Food Addit Safety HFS 275, College Pk, MD 20740 USA. RP Arvidson, KB (reprint author), US FDA, Off Food Addit Safety HFS 275, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM kirk.arvidson@fda.hhs.gov; mitchell.cheeseman@fda.hhs.gov; andrew.mcdougal@fda.hhs.gov NR 41 TC 1 Z9 1 U1 0 U2 0 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND BN 978-1-84569-029-8 PY 2007 BP 158 EP 179 D2 10.1201/9781439824474 PG 22 WC Food Science & Technology SC Food Science & Technology GA BNC38 UT WOS:000274154800007 ER PT J AU Rafii, F Shahverdi, AR AF Rafii, Fatemeh Shahverdi, Ahmad R. TI Comparison of essential oils from three plants for enhancement of antimicrobial activity of nitrofurantoin against enterobacteria SO CHEMOTHERAPY LA English DT Article DE nitrofurantoin; enterobacteria; monoterpenes; carvone; piperitone; essential oils ID URINARY-TRACT-INFECTIONS; FLUOROQUINOLONE; CATHETERIZATION; ANTIBACTERIAL; LEVOFLOXACIN; RESISTANCE AB Background: Piperitone from plant essential oils enhances bactericidal activities of nitrofurantoin and furazolidone against bacteria from the family Enterobacteriaceae. In this study, the essential oils of spearmint ( Mentha spicata L.), dill ( Anethum graveolens L.) and peppermint ( Mentha piperita L.) were screened for augmentation of nitrofurantoin activity and the most active components were determined. Method: The effects of essential oils and their components on the bactericidal activity of nitrofurantoin against Enterobacter cloacae were studied using disk-diffusion and agar-dilution methods. The composition of essential oils was studied using gas chromatography-mass spectrometry. Results: M. spicata and A. graveolens oils exhibited the highest effects. Gas chromatography-mass spectrometry analysis showed that the oils of these two plants contained 40.12 and 20.32% carvone, respectively. Pure carvone and piperitone equally increased the bactericidal activity of nitrofurantoin. Other ingredients of essential oils, including camphor, limonene and menthone, were less effective. Copyright (c) 2007 S. Karger AG, Basel C1 Univ Tehran Med Sci, Fac Pharm, Dept Pharmaceut Biotechnol, Tehran 14174, Iran. US FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Shahverdi, AR (reprint author), Univ Tehran Med Sci, Fac Pharm, Dept Pharmaceut Biotechnol, Tehran 14174, Iran. EM shahverd@sina.tums.ac.ir NR 20 TC 35 Z9 37 U1 2 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0009-3157 J9 CHEMOTHERAPY JI Chemotherapy PY 2007 VL 53 IS 1 BP 21 EP 25 DI 10.1159/000098246 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 127DE UT WOS:000243564700004 PM 17192709 ER PT J AU Ko, HS AF Ko, Hon-Sum TI Infusion reactions from human plasma-derived products SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 Food & Drug Adm, Div Hematol, Potomac, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S79 EP S80 DI 10.1016/j.clim.2007.03.406 PG 2 WC Immunology SC Immunology GA 177EU UT WOS:000247137200207 ER PT J AU Peng, L Sun, S AF Peng, Liang Sun, Shan TI Comparisons between local linear estimator and kernel smooth estimator for a smooth distribution based on MSE under right censoring SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE censored data; distribution function; local linear estimation; MSE; product-limit estimator ID NONPARAMETRIC-ESTIMATION; BANDWIDTH SELECTION; QUANTILES AB We propose a local linear estimator for a smooth distribution function based on censored data. This new estimator applies local linear techniques to observations from a regression model where the value of the product limit estimator equals the value of the true distribution plus an error term. We show that the advantage of using the local linear estimator over the smooth kernel estimator is that, for most commonly used kernel functions, local linear estimator has a smaller mean squared error than the kernel smooth estimator studied by Ghorai and Susarla (1990). C1 Georgia Inst Technol, Sch Math, Atlanta, GA 30332 USA. Texas Tech Univ, Lubbock, TX 79409 USA. US FDA, Ctr Drug Evaluat & Res, Lubbock, TX USA. RP Peng, L (reprint author), Georgia Inst Technol, Sch Math, Atlanta, GA 30332 USA. EM peng@math.gatech.edu NR 16 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2007 VL 36 IS 1-4 BP 297 EP 312 DI 10.1080/03610920600974351 PG 16 WC Statistics & Probability SC Mathematics GA 153BV UT WOS:000245407600026 ER PT J AU Blodgett, RJ AF Blodgett, Robert J. TI The path of the minimum l(P)-norm estimator for p between 1 and infinity SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE Descartes's rule of signs; equal sums of like powers; exponential sums; linear combinations of exponentials; norms; Prohet-Tarry-Escott problem AB The minimum l(P)-norm estimator is the point that minimizes the sum of the distance from each data point in the l(p)-norm. The path of this location estimate for an l(P)-norm is found as p goes from 1 to infinity. This path indicates how critical the selection of an exponent is. An alternative proof of Descartes's rule of signs, applied to exponential sums, limits the number of repeated exponents for the same minimum point with usual data sets. Several bounds on this path include that it stays among the averages of pairs of data points. C1 [Blodgett, Robert J.] Ctr Food Safety & Appl Nutr, US FDA, College Pk, MD 20740 USA. RP Blodgett, RJ (reprint author), Ctr Food Safety & Appl Nutr, US FDA, 5100 Paint Branch Pkway, College Pk, MD 20740 USA. EM robert.blodgett@fda.hhs.gov NR 7 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 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2007 VL 36 IS 13-16 BP 2829 EP 2839 DI 10.1080/03610920701386950 PG 11 WC Statistics & Probability SC Mathematics GA 244OY UT WOS:000251876400036 ER PT S AU Katz, LM AF Katz, Linda M. BE Morgan, SE Havelka, KO Lochhead, RY TI Nanotechnology and Applications in Cosmetics: General Overview SO COSMETIC NANOTECHNOLOGY: POLYMERS AND COLLOIDS IN COSMETICS SE ACS Symposium Series LA English DT Article; Book Chapter ID SOLID LIPID NANOPARTICLES C1 US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Katz, LM (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-100, College Pk, MD 20740 USA. NR 11 TC 4 Z9 4 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3996-8 J9 ACS SYM SER JI ACS Symp. Ser. PY 2007 VL 961 BP 193 EP 200 D2 10.1021/bk-2007-0961 PG 8 WC Chemistry, Applied; Nanoscience & Nanotechnology; Polymer Science SC Chemistry; Science & Technology - Other Topics; Polymer Science GA BOD43 UT WOS:000276307300011 ER PT J AU Yu, HN Shen, SR Yin, JJ AF Yu, Hai-Ning Shen, Sheng-Rong Yin, Jun-Jie TI Effects of metal ions, catechins, and their interactions on prostate cancer SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review DE green tea; prostate cancer; metal ions ID GREEN TEA POLYPHENOLS; NOBLE NBL/CR RAT; NF-KAPPA-B; CELL-CYCLE; GENE-EXPRESSION; CARCINOMA-CELLS; EPIGALLOCATECHIN GALLATE; PROTEASOME INHIBITORS; PROLIFERATIVE LESIONS; MEDIATED APOPTOSIS AB Prostate cancer is threatening human health heavily,for its causes are related to diet, genetic factors, and lifestyle. Metal ions, which are necessary to our health, are important factors inducing many diseases including prostate cancer in the condition of absence or excess. Epidemiological and laboratory studies provide convincing evidence that green tea prevents and cures prostate cancer. Practically, interactions of catechins, which are the main bioactive components in green tea or GTP, with metal ions have a new aspect to investigate their mechanism in preventing and curing prostate cancer. In the present paper, we summarize some research about the effects of catechins with metal ions related to prostate cancer and their interactions on prostate cancer. C1 Zhejiang Univ, Sch Biosyst Engn & Food Sci, Hangzhou 310029, Peoples R China. Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310032, Peoples R China. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Shen, SR (reprint author), Zhejiang Univ, Sch Biosyst Engn & Food Sci, Hangzhou 310029, Peoples R China. EM shrshen@zju.edu.cn RI Yin, Jun Jie /E-5619-2014 NR 77 TC 10 Z9 11 U1 2 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2007 VL 47 IS 8 BP 711 EP 719 DI 10.1080/10408390600948873 PG 9 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 235DR UT WOS:000251214200002 PM 17987445 ER PT J AU Rhomberg, LR Baetcke, K Blancato, J Bus, J Cohen, S Conolly, R Dixit, R Doe, J Ekelman, K Fenner-Crisp, P Harvey, P Hattis, D Jacobs, A Jacobson-Kram, D Lewandowski, T Liteplo, R Pelkonen, O Rice, J Somers, D Turturro, A West, W Olin, S AF Rhomberg, Lorenz R. Baetcke, Karl Blancato, Jerry Bus, James Cohen, Samuel Conolly, Rory Dixit, Rakesh Doe, John Ekelman, Karen Fenner-Crisp, Penny Harvey, Paul Hattis, Dale Jacobs, Abigail Jacobson-Kram, David Lewandowski, Tom Liteplo, Robert Pelkonen, Olavi Rice, Jerry Somers, Diana Turturro, Angelo West, Webster Olin, Stephen TI Issues in the design and interpretation of chronic toxicity and carcinogenicity studies in rodents: Approaches to dose selection SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review ID HEART-RATE-VARIABILITY; PROTEIN CROSS-LINKS; ELEVATED LUTEINIZING-HORMONE; QUANTITATIVE RISK ASSESSMENT; SPRAGUE-DAWLEY RATS; GENE-EXPRESSION; CELL-PROLIFERATION; TRANSGENIC MOUSE; F344 RATS; INHALED FORMALDEHYDE AB For more than three decades chronic studies in rodents have been the benchmark for assessing the potential long- term toxicity, and particularly the carcinogenicity, of chemicals. With doses typically administered for about 2 years (18 months to lifetime), the rodent bioassay has been an integral component of testing protocols for food additives, pesticides, pharmaceuticals, industrial chemicals, and all manner of byproducts and environmental contaminants. Over time, the data from these studies have been used to address an increasing diversity of questions related to the assessment of human health risks, adding complexity to study design and interpretation. An earlier ILSI RSI working group developed a set of principles for the selection of doses for chronic rodent studies ( ILSI, 1997). The present report builds on that work, examining some of the issues that arise and offering new perspectives and approaches for putting the principles into practice. Dose selection is considered both from the prospective viewpoint of the choosing of dose levels for a study and from the retrospective interpretation of study results in light of the doses used. A main theme of this report is that the purposes and objectives of chronic rodent studies vary and should be clearly defined in advance. Dose placement, then, should be optimized to achieve study objectives. For practical reasons, most chronic studies today must be designed to address multiple objectives, often requiring trade-offs and innovative approaches in study design. A systematic approach to dose selection should begin with recognition that the design of chronic studies occurs in the context of a careful assessment of the accumulated scientific information on the test substance, the relevant risk management questions, priorities and mandates, and the practical limitations and constraints on available resources. A stepwise process is described. The aim is to increase insofar as possible the utility of an expensive and time-consuming experiment. The kinds of data that are most commonly needed for dose selection and for understanding the dose-related results of chronic rodent studies, particularly carcinogenicity studies, are discussed as " design/ interpretation factors." They comprise both the inherent characteristics of the test substance and indicators of biological damage, perturbation or stress among the experimental animals. They may be primary toxicity endpoints, predictors or indicators of appropriate dose selection, or indicators of conditions to be avoided in dose selection. The application and interpretation of design/ interpretation factors is conditioned by the study objectives-what is considered desirable will depend on the strategy for choice of doses that is being followed. The challenge is to select doses that accommodate all of the issues raised by the relevant design/ interpretation factors. Three case studies are presented here that illustrate the interplay between study objectives and the design and selection of doses for chronic rodent studies. These examples also highlight issues associated with multiple plausible modes of action, multiple pathways for biotransformation of the chemical, extraneous high-dose effects, the use of modeling in dose selection, and the implications of human exposure levels. Finally, looking to the future, the report explores seven potential paradigm shifts for risk assessment that will significantly impact the design and interpretation of toxicity and carcinogenicity studies. C1 ILSI Res Fdn, Washington, DC 20005 USA. Gradient Corp, Cambridge, MA 02138 USA. US EPA, OPP, HED, Washington, DC 20460 USA. US EPA, ORD, NERL, Res Triangle Pk, NC 27711 USA. Dow Chem Co USA, Midland, MI 48674 USA. Univ Nebraska Med Ctr, Omaha, NE USA. US EPA, ORD, NCCT, Res Triangle Pk, NC 27711 USA. Medimmune Inc, Gaithersburg, MD 20878 USA. Syngenta CTL, Macclesfield, Cheshire, England. US FDA, CVM, Rockville, MD 20857 USA. ILSI RF, RSI, Washington, DC USA. NICNAS, Sydney, NSW, Australia. Clark Univ, Worcester, MA 01610 USA. US FDA, CDER, Silver Spring, MD USA. RP Olin, S (reprint author), ILSI Res Fdn, 1 Thomas Circle,NW,Suite 900, Washington, DC 20005 USA. EM solin@ilsi.org RI Doe, Jane/B-8500-2015; OI Blancato, Jerry/0000-0002-7023-5767 NR 301 TC 29 Z9 30 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PY 2007 VL 37 IS 9 BP 729 EP 837 DI 10.1080/10408440701524949 PG 109 WC Toxicology SC Toxicology GA 226QM UT WOS:000250603600001 PM 17957539 ER PT J AU Sharma, HS Sjoquist, PO Ali, SF AF Sharma, Hari Shanker Sjoquist, Per-Ove Ali, Syed F. TI Drugs of abuse-induced hyperthermia, blood-brain barrier dysfunction and neurotoxicity: Neuroprotective effects of a new antioxidant compound H-290/51 SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE morphine; methamphetamine; drugs of abuse; dependence; withdrawal symptoms; antioxidants; H-290/51; free radical formation; lipid peroxidation; neuroprotection; blood-brain barrier; hyperthermia ID CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; RAT SPINAL-CORD; NORMOTENSIVE YOUNG-RATS; INDUCED DOPAMINERGIC NEUROTOXICITY; 72 KD RESPONSE; AMPHETAMINE-REGULATED TRANSCRIPT; ACIDIC PROTEIN IMMUNOREACTIVITY; MORPHINE-INDUCED HYPERTHERMIA; VENTRAL TEGMENTAL AREA AB The psychostimulants, morphine and methamphetamine are well known drugs of abuse that induce brain pathology and/or neurodegeneration resulting in a huge burden on our society. The possible mechanisms of psychostimulants induced neuropathology and neurodegeneration are still not well known. The drugs of abuse results in profound hyperthermia and widespread alterations in neurochemical metabolism in the central nervous system (CNS). It appears that psychostimulants induced hyperthermia and/or release of neurochemicals influence the blood-brain barrier (BBB) dysfunction leading to brain pathology. The drugs of abuse also induce oxidative stress resulting in generation of free radicals and lipid peroxidation. Thus, further research is needed to understand the basic function of BBB disruption and temperature regulation by psychostimulants and to modify them pharmacologically to attenuate brain dysfunction and neuropathology. This review is focused on the problems of morphine and methamphetamine induced hyperthermia and their effects on breakdown of the BBB function leading to brain damage. Works done in our laboratory suggest that hyperthermia caused by these drugs is responsible for BBB disruption and neurodegeneration. This hypothesis is further supported by our observation that pretreatment with a portent antioxidant compound H-290/51 attenuates the BBB disruption and induces marked neuroprotection following morphine induced withdrawal and methamphetamine induced neurotoxicity. The possible mechanisms and functional significance of these findings are discussed. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Uppsala Univ, Univ Hosp, Dept Surg Sci Anesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. Astra Zeneca Molndal, Dept Integrat Pharmacol, Molndal, Sweden. RP Sharma, HS (reprint author), Frodingsgatan 12-28, SE-75421 Uppsala, Sweden. EM Sharma@surgsci.uu.se RI Sharma, Hari/G-4508-2016 NR 174 TC 51 Z9 52 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 18 BP 1903 EP 1923 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 183FF UT WOS:000247557400006 PM 17584116 ER PT J AU Kraeling, MEK Bronaugh, RL Jung, CT AF Kraeling, Margaret E. K. Bronaugh, Robert L. Jung, Connie T. TI Absorption of lawsone through human skin SO CUTANEOUS AND OCULAR TOXICOLOGY LA English DT Article DE human skin; lawsone; percutaneous absorption ID INVITRO PERCUTANEOUS-ABSORPTION; PENETRATION; METABOLISM; INGREDIENT AB Lawsone (2-hydroxy-1,4-naphthoquinone) is the principal color ingredient in henna, a color additive approved with limitations for coloring hair by the Food and Drug Administration (FDA) under 21 CFR 73.2190. In 2002, the scientific committee on cosmetics and non-food products (SCCNFP), now known as the scientific committee for consumer products (SCCP), evaluated the safety of lawsone as a coloring agent in hair dye products of the European Union (EU). The SCCNFP concluded that lawsone was mutagenic and not suitable for use as a hair coloring agent. As a result, studies were conducted to measure the extent of lawsone absorption through human skin. Lawsone skin absorption was determined from two hair coloring products and two shampoo products, all containing henna. [C-14]- Lawsone (sp. act. 22.9 mCilmmol) was added to each commercial product and the products were applied to dermatomed, nonviable human skin mounted in flow-through diffusion cells perfused with a physiological buffer (HEPES-buffered Hanks' balanced salt solution, pH 7.4). Products remained on the skin for 5 minutes (shampoos) and I hour (hair color paste). For the henna hair paste products, 0.3 and 1.3% of the applied dose)Vas absorbed into the receptor fluid in 24 hours while 2.2 and 4.0% remained in the skin. For both henna shampoo products, 0.3% of the applied dose was absorbed into the receptor fluid at 24 hours while 3.6 and 6.8% remained in the skin. For all products, most of the lawsone applied was washed from the surface of the skin (83-102%) at the end of the exposure period. Extended absorption studies were conducted for 72 hours to determine if skin levels of lawsone in the 24 hour studies might eventually be percutaneously absorbed. These studies determined that the majority of the lawsone remained in the skin with only a small but significant increase (for three out of four products) in receptor fluid values. Therefore, it appears that receptor fluid values would give a good estimate of lawsone absorption for an exposure estimate and that skin levels of lawsone need not be included. C1 US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. US FDA, Off Policy, Off Commissioner, Rockville, MD 20857 USA. RP Kraeling, MEK (reprint author), US FDA, Off Cosmet & Colors, Harvey W Wiley Bldg,Room 4E021,5100 Paint Branch, College Pk, MD 20740 USA. EM margaret.kraeling@fda.hhs.gov NR 17 TC 6 Z9 6 U1 2 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1556-9527 J9 CUTAN OCUL TOXICOL JI Cutan. Ocul. Toxicol. PY 2007 VL 26 IS 1 BP 45 EP 56 DI 10.1080/15569520601183856 PG 12 WC Ophthalmology; Toxicology SC Ophthalmology; Toxicology GA 162JM UT WOS:000246083100005 PM 17464748 ER PT J AU Lindsey, WB Lowdell, MW Marti, GE Abbasi, F Zenger, V King, KM Lamb, LS AF Lindsey, W. B. Lowdell, M. W. Marti, G. E. Abbasi, F. Zenger, V. King, K. M. Lamb, L. S., Jr. TI CD69 expression as an index of T-cell function: assay standardization, validation and use in monitoring immune recovery SO CYTOTHERAPY LA English DT Article DE immune function; immune recovery; immunophenotyping; quantitative flow cytometry ID BONE-MARROW-TRANSPLANTATION; HIV-INFECTED INDIVIDUALS; LYMPHOCYTE-ACTIVATION; FLOW-CYTOMETRY; RAPID METHOD; ANTIGEN; RECONSTITUTION; REGENERATION; STIMULATION; POPULATIONS AB Background CD69 is a surrogate marker of T-cell responsiveness to mitogen and Ag stimulus and can be used as a measure of T-lymphcyte activation. Quantitative flow cytometric determination of CD69 expression on T lymphocytes has several advantages over traditional lymphocyte proliferation assays, but this method has not yet been standardized for clinical applications. Methods We qualified a commercially available assay using the manufacturers procedures for measurement of T-cell response to a mitogen (PHA), superantigen (Staphylococcus endotoxin B; SEB) and Ca(2+) ionophore (phorbyl myrisiate acetate; PMA) with peripheral blood from healthy volunteers. Following this, we tested the usefulness of the assay in determining T-cell responses to PHA and SEB for six immunocompromised patients. Results Healthy volunteers showed 17-fold increases in T-cell CD69 Ab bound per cell (ABC) with PHA stimulation compared with the baseline. SEB was also an effective T-cell activating agent, increasing CD69 ABC by 5-fold, comparable with results obtained with PMA stimulation. PHA- andSEB-stimulated T-cell CD69 ABC for patients 100 days post-BM transplant were generally below 1 SD of that from healthy volunteers. SEB-stimulated T-cell CD69 expression was significantly depressed for CD8(+) T cells while CD4(+) T-cell responses to SEB were generally within I SD of the mean for healthy volunteers. Discussion These results suggest that quantitative measurement of CD69 surface expression by flow cytometry is a useful diagnostic tool for detailed assessment of T-lymphocyte and subset activation. C1 Univ Alabama, BM Transplantat Program, Div Hematol & Oncol, Dept Med, Birmingham, AL 35294 USA. S Carolina Canc Ctr, Columbia, SC USA. UCL, Royal Free & Univ Coll Med Sch, London, England. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Lamb, LS (reprint author), Univ Alabama, BM Transplantat Program, Div Hematol & Oncol, Dept Med, Tinsley Harrison Tower,Suite 541,1530 3rd Ave S, Birmingham, AL 35294 USA. EM Lawrence.Lamb@ccc.uab.edu RI Lowdell, Mark/G-4359-2011 NR 27 TC 24 Z9 26 U1 1 U2 15 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2007 VL 9 IS 2 BP 123 EP 132 DI 10.1080/14653240601182838 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 164BX UT WOS:000246208700003 PM 17453964 ER PT J AU Radoja, N Guerrini, L Lo Iacono, N Merlo, GR Costanzo, A Weinberg, WC La Mantia, G Calabro, V Morasso, MI AF Radoja, Nadezda Guerrini, Luisa Lo Iacono, Nadia Merlo, Giorgio R. Costanzo, Antonio Weinberg, Wendy C. La Mantia, Girolama Calabro, Viola Morasso, Maria I. TI Homeobox gene Dlx3 is regulated by p63 during ectoderm development: relevance in the pathogenesis of ectodermal dysplasias SO DEVELOPMENT LA English DT Article DE Dlx3; p63; transcription; ectodermal dysplasias; mouse development ID P53 HOMOLOG; MICE LACKING; DIFFERENTIATION; LIMB; IDENTIFICATION; KERATINOCYTES; ORGANOGENESIS; MORPHOGENESIS; EXPRESSION; ISOFORMS AB Ectodermal dysplasias (EDs) are a group of human pathological conditions characterized by anomalies in organs derived from epithelial-mesenchymal interactions during development. Dlx3 and p63 act as part of the transcriptional regulatory pathways relevant in ectoderm derivatives, and autosomal mutations in either of these genes are associated with human EDs. However, the functional relationship between both proteins is unknown. Here, we demonstrate that Dlx3 is a downstream target of p63. Moreover, we show that transcription of Dlx3 is abrogated by mutations in the sterile alpha-motif (SAM) domain of p63 that are associated with ankyloblepharon-ectodermal dysplasia-clefting (AEC) dysplasias, but not by mutations found in ectrodactylyectodermal dysplasia-cleft lip/palate ( EEC), Limb-mammary syndrome (LMS) and split hand-foot malformation (SHFM) dysplasias. Our results unravel aspects of the transcriptional cascade of events that contribute to ectoderm development and pathogenesis associated with p63 mutations. C1 NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. Univ Milan, Dept Biomol & Biotechnol Sci, I-20133 Milan, Italy. CNR, Inst Tecnol Biomed, Dulbecci Telethon Inst, I-20100 Milan, Italy. Univ Roma Tor Vergata, Dept Dermatol, I-00133 Rome, Italy. FDA, Div Monoclonal Antibodies, CDER, Bethesda, MD 20892 USA. Univ Naples, Dept Struct & Funct Biol, I-80126 Naples, Italy. RP Morasso, MI (reprint author), NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. EM morassom@mail.nih.gov RI Weinberg, Wendy/A-8920-2009; Costanzo, Antonio/D-3896-2012; OI Costanzo, Antonio/0000-0001-9697-2557 FU Intramural NIH HHS; Telethon [GGP030326] NR 32 TC 35 Z9 36 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN 1 PY 2007 VL 134 IS 1 BP 13 EP 18 DI 10.1242/dev.02703 PG 6 WC Developmental Biology SC Developmental Biology GA 119KK UT WOS:000243011000003 PM 17164413 ER PT J AU Zhen, BGA AF Zhen, Boguang Andy TI Consideration of operational alpha level with different approval strategies SO DRUG INFORMATION JOURNAL LA English DT Article DE clinical trials; "two-trial rule"; operational alpha level; approval strategies AB It has been the position of the Food and Drug Administration to require at least two adeqate and well-controlled studies, each convincing on its own, to establish effectiveness. Under some specific circumstances, a sponsor may propose to conduct a single trial first and then may be willing or may be asked to start the second trial only if the positive results from the first trial are not striking. If using different strategies regarding how to launch clinical trials for approval in a drug development program, the operation alpha level (maximum chance of approving an ineffective drug) may not be controlled at the same level. This article presents a method to calculate the operational alpha level for different strategies and shows that the alpha level under certain strategies may be inflated compared to the one based on "the two-trial rule." This method also permits examination of the effect on the operation alpha level if different strategies of testing are invoked. It is suggested that consideration of the operational alpha level should be taken into account when selecting different approval strategies. C1 US FDA, BTSS, OB, OPaSS,CDER, Silver Spring, MD 20993 USA. RP Zhen, BGA (reprint author), US FDA, BTSS, OB, OPaSS,CDER, 10903 New Hampshire Ave,Room 1210,Bldg 22, Silver Spring, MD 20993 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU DRUG INFORMATION ASSOCIATION PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 1 BP 23 EP 29 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 126MN UT WOS:000243517100004 ER PT J AU Webber, K Spindler, P AF Webber, Keith Spindler, Per TI Environmental assessment of human pharmaceuticals in the United States of America SO DRUG INFORMATION JOURNAL LA English DT Article; Proceedings Paper CT Joint DIA/HESI/SAPS Conference o Environmental Assessment of Human Medicines CY MAY 22-23, 2006 CL Stockholm, SWEDEN SP DIA, HESI, SAPS DE human pharmaceuticals; human medicines; environmental protection; environmental assessment; guideline; United States; FDA AB This article provides an overview of a presentation of the environmental assessment process for drugs in the United States from the joint DIA/HESI/SAPS conference on Environmental Assessment of Human Medicines held in Stockholm, Sweden, May 22-23, 2006. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. Univ Copenhagen, Copenhagen, Denmark. RP Webber, K (reprint author), US FDA, Ctr Drug Evaluat & Res, 5630 Fishers Lane, Rockville, MD 20852 USA. EM keith.webber@fda.hhs.gov NR 1 TC 1 Z9 1 U1 0 U2 4 PU DRUG INFORMATION ASSOCIATION PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 2 BP 155 EP 157 PG 3 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 146CV UT WOS:000244913000005 ER PT J AU Claycamp, HG AF Claycamp, H. Gregg TI Perspective on quality risk management of pharmaceutical quality SO DRUG INFORMATION JOURNAL LA English DT Article DE quality risk management; risk assessment; uncertainty; FMEA; CGMP; variability ID UNCERTAINTY; VARIABILITY; ASSESSMENTS; INTEGRATION AB Quality risk management for the pharmaceutical industry was recently defined in internationally harmonized guidance as a systematic process for the assessment, control, communication, and review of risks to the quality of the drug product across the product life cycle. Two overarching principles for quality risk management are that evaluations of risk should be scientifically based and ultimately linked to risk to the patient, and the level of effort and documentation of quality risk management processes should be commensurate with the level of risk. Numerous tools for risk management come from other applied sciences and manufacturing having a longer history of risk management. The degree of quantitative sophistication among tools varies from generalized and qualitative, "high-level" tools to computationally rigorous, "low-level, "quantitative tools. Risk is described in recent guidance as a combination of the probability of occurrence of harm and the severity of that harm. Risk management always comes with uncertainty, given that it calls for projections of the likelihood of adverse events forgiven severities. As a relatively new application of risk management, quality risk management can benefit from adapting existing theory and practice to pharmaceutical manufacturing. C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. RP Claycamp, HG (reprint author), US FDA, CDER, Off Compliance, HFD-300,11919 Rockville Pike, Rockville, MD 20852 USA. EM gregg.claycamp@fda.hhs.gov NR 56 TC 4 Z9 4 U1 1 U2 10 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 3 BP 353 EP 367 PG 15 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 163MY UT WOS:000246165200009 ER PT J AU Chen, L Tsong, Y AF Chen, Ling Tsong, Yi TI Design and analysis for drug abuse potential studies: Issues and strategies for implementing a crossover design SO DRUG INFORMATION JOURNAL LA English DT Article DE crossover design; drug abuse potential studies; mixed carryover effect; orthogonal Latin squares; Williams design ID MODEL AB It is important to conduct a drug abuse potential study for a new drug that may have potential to be abused. The acute dose-effect comparisons of the test, positive control, and placebo treatments are often performed on healthy volunteers with histories of drug abuse in drug abuse clinical trials. Because of large between-subject variability in the endpoint measurements based on self-evaluated responses and the difficulty in recruiting appropriate study subjects; the designs for such studies are typically crossover, with self-control. In this article, design issues and statistical analysis issues are presented. The advantages and disadvantages of currently used study designs are discussed. Some new ideas for improving existing designs are proposed. C1 US FDA, Off Biostat Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Chen, L (reprint author), US FDA, Off Biostat Off Translat Sci, Ctr Drug Evaluat & Res, Bldg 22,Room 5241,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ling.chen@fda.hhs.gov NR 10 TC 10 Z9 10 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 4 BP 481 EP 489 PG 9 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 185MD UT WOS:000247714200006 ER PT J AU Lin, SC AF Lin, Stan C. TI Statistical considerations for some studies of over-the-counter drugs SO DRUG INFORMATION JOURNAL LA English DT Article DE over-the-counter drugs; label comprehension and actual use studies; confidence intervals; sample size; variance estimate AB In this article, the label comprehension and actual use studies that may be required for an over-the-counter new drug regulatory submission are introduced. Design for these studies and statistical issues are described. Because confidence interval is a tool that plays a central role in these studies, information needed and appropriate sample size estimation approaches are discussed. Carefully designed and analyzed studies would enhance their success rate and provide more useful information from the studies. C1 US FDA, Div Biometr 4, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Lin, SC (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM stan.lin@hhs.fda.gov NR 4 TC 1 Z9 1 U1 1 U2 1 PU DRUG INFORMATION ASSOCIATION PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 4 BP 511 EP 516 PG 6 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 185MD UT WOS:000247714200009 ER PT J AU Lesko, LJ AF Lesko, Lawrence J. TI A regulatory perspective on validation of surrogate endpoints SO DRUG INFORMATION JOURNAL LA English DT Article DE biomarkers; surrogate endpoints; drug development; FDA AB The use of biomarkers as surrogate endpoints has had a dramatic and powerful impact on health care and the development and accessibility of drugs. For example, cholesterol is a biomarker used in many clinical trials of cardiovascular drugs such as "statins" where cholesterol reduction is used as a surrogate endpoint for reduced mortality. Although much progress had already been made over the past 20 years-especially in terms of the very real benefits surrogate endpoints: have made to efficient medical product development and patient care-the industry faces a host of future challenges as the use of biomarkers and surrogate endpoints play a more integral role in the advancement Of new medicines along the critical path of drug development. During the 41 st DIA Annual Meeting in Washington, DC, Dr Lawrence Lesko from the Office of Clinical Pharmacology at the Food and Drug Administration presented a discussion on the challenges associated with the validation of surrogate endpoints, highlighting progress to date as well as future objectives. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. RP Lesko, LJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. EM Lawrence.Lesko@fda.hhs.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 5 BP 587 EP 594 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 207YP UT WOS:000249287300005 ER PT J AU Chen, L AF Chen, Ling TI A statistician's viewpoint of responders in the treatment of neuropathic pain SO DRUG INFORMATION JOURNAL LA English DT Article DE diabetic peripheral neuropathy; neuropathy pain : responder mean; responder rate AB In many clinical studies, the efficacy of a new drug is measured by the mean difference in primary endpoint between the new drug and an active control drug or between the new drug and the placebo. Clinicians sometimes do not believe that the mean difference in primary end point between two treatments is clinically meaningful for some drug indications, such as a drug for neuropathic pain associated with diabetic peripheral neuropathy. They prefer to investigate the difference between responder rates. The responder for a treatment for neuropathic pain is defined as a patient who experiences a specific level, often at least 50% in pain reduction from baseline. In this article, the disadvantages of using such a definition are discussed. Some new ideas of defining a responder are proposed. This is illustrated with a real data example. C1 US FDA, Ctr Drug Evaluat & Res, Div Biometr 6, Off Biostat,Off Translat Sci, Silver Spring, MD 20993 USA. RP Chen, L (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Biometr 6, Off Biostat,Off Translat Sci, 10903 New Hampshire Ave,Bldg 22,Room 5241, Silver Spring, MD 20993 USA. EM ling.chen@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 5 BP 685 EP 689 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 207YP UT WOS:000249287300015 ER PT J AU Permutt, T AF Permutt, Thomas TI A note on stratification in clinical trials SO DRUG INFORMATION JOURNAL LA English DT Article DE stratification; interaction; analysis of covariance; imbalance; adjustment AB Stratification is sometimes proposed to deal with problems of influential covariates in clinical trials. The word stratification, however, may refer to any of four different methods of design and analysis. The methods are capable of addressing three different problems. Which problem and which method are being discussed is Often misunderstood. Consequently, the method adopted may not solve the problem that provoked its consideration. C1 US FDA, Div Biometr 2, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Permutt, T (reprint author), US FDA, Div Biometr 2, Ctr Drug Evaluat & Res, 10901 New Hampshire Ave,Bldg 22,Room 3105, Silver Spring, MD 20993 USA. EM thomas.permutt@fda.hhs.gov NR 3 TC 6 Z9 6 U1 0 U2 2 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 6 BP 719 EP 722 PG 4 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 227MM UT WOS:000250660800004 ER PT J AU Honein, MA Lindstrom, JA Kweder, SL AF Honein, Margaret A. Lindstrom, Jill A. Kweder, Sandra L. TI Can we ensure the safe use of known human teratogens? The iPLEDGE (TM) test case SO DRUG SAFETY LA English DT Article ID RETINOIC ACID; BIRTH-DEFECTS; ISOTRETINOIN; PREGNANCIES AB Minimising the public health burden of isotretinoin-induced teratogenicity has been a challenge for 24 years, the duration of availability of isotretinoin in the US for the treatment of severe, recalcitrant nodular acne. Although the teratogenicity of this drug is well known and risk-management programmes had been implemented, preventable fetal exposures continued to occur, largely as a result of the lack of sufficient controls within the programmes themselves. The manufacturers of isotretinoin implemented a new risk-management programme, iPLEDGE (TM), in March 2006. iPLEDGE (TM) is a comprehensive distribution system that includes mandatory registration of patients, healthcare providers, pharmacies, and wholesalers. It allows real-time linkage of pregnancy-test results for verification prior to the dispensing of isotretinoin. Although the challenges of implementing a closed distribution system for a very widely used medication have been extensive, the potential public health benefits from preventing fetal exposure to isotretinoin are substantial. C1 Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Honein, MA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd,Mailstop E-86, Atlanta, GA 30333 USA. NR 24 TC 18 Z9 18 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2007 VL 30 IS 1 BP 5 EP 15 DI 10.2165/00002018-200730010-00002 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 129OX UT WOS:000243739900002 PM 17194167 ER PT J AU Kelly, WN Arellano, FM Barnes, J Bergman, U Edwards, RI Fernandez, AM Freedman, SB Goldsmith, DI Huang, KA Jones, JK McLeay, R Moore, N Stather, RH Trenque, T Troutman, WG van Puijenbroek, E Williams, F Wise, RP AF Kelly, William N. Arellano, Felix M. Barnes, Joanne Bergman, Ulf Edwards, Ralph I. Fernandez, Alina M. Freedman, Stephen B. Goldsmith, David I. Huang, Kui A. Jones, Judith K. McLeay, Rachel Moore, Nicholas Stather, Rosie H. Trenque, Thierry Troutman, William G. van Puijenbroek, Eugene Williams, Frank Wise, Robert P. TI Guidelines for submitting adverse event reports for publication SO DRUG SAFETY LA English DT Article ID DRUG-REACTIONS; PHARMACOVIGILANCE; ANECDOTES; STANDARDS; CRITERIA; QUALITY AB Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines, and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports, and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic, and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' websites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation, and reporting of suspected drug or other medical product adverse events. C1 William N Kelly Consulting Inc, Oldsmar, FL 34677 USA. Risk Management Resources, Bridgewater, NJ USA. Risk Management Resources, Zaragoza, Spain. Univ Auckland, Auckland 1, New Zealand. Karolinska Inst, Stockholm, Sweden. Uppsala Monitoring Ctr, Uppsala, Sweden. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Goldsmiht Pharmacovigilance & Syst, New York, NY USA. Pfizer Pharmaceut Inc, New York, NY USA. Degge Grp Ltd, Arlington, VA USA. Wolters Kluwer Hlth, Auckland, New Zealand. Univ Victor Segalen, Bordeaux, France. Ctr Hosp Univ Reims, Reims, France. Univ New Mexico, Albuquerque, NM 87131 USA. Netherlands Pharmacovigilance Ctr, Shertogenbosch, Netherlands. USN, Bethesda, MD 20084 USA. US FDA, Rockville, MD 20857 USA. RP Kelly, WN (reprint author), William N Kelly Consulting Inc, 2147 Warwick Dr, Oldsmar, FL 34677 USA. EM wnkelly@earthlink.net RI Moore, nicholas/B-2368-2013 NR 20 TC 58 Z9 61 U1 1 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2007 VL 30 IS 5 BP 367 EP 373 DI 10.2165/00002018-200730050-00001 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 172TR UT WOS:000246827800001 PM 17472416 ER PT J AU Wysowski, DK AF Wysowski, Diane K. TI Surveillance of prescription drug-related mortality using death certificate data SO DRUG SAFETY LA English DT Article ID CLOSTRIDIUM-DIFFICILE; UNITED-STATES; RHABDOMYOLYSIS; ABUSE; AGRANULOCYTOSIS; METHADONE; FENTANYL AB Background: The prescription drugs or drug classes that are most frequently associated with death in the US might be identifiable from death certificate data. Objective: To identify the drugs/drug classes associated with the greatest numbers of deaths in the US that might be considered as possible targets for prevention. Study design: US vital statistics data were accessed in order to identify International Classification of Diseases (10th Revision) [ICD-10] codes indicating that prescription drugs had caused or contributed to death and diseases with significant drug-related mortality. Main outcome measure: ICD-10 codes for primarily prescription drugs that were listed as the underlying cause or as 'total mentions' on death certificates and were implicated in >= 1000 deaths in any one year were selected. The annual number of deaths by ICD-10 code was obtained from the Division of Vital Statistics, National Center for Health Statistics. Codes for diseases with significant drug-related aetiologies and involvement in >= 1000 deaths in any one year were also identified and analysed separately. Results: For the selected ICD-10 codes, a total of 25 031 deaths were listed as having a prescription drug as the underlying cause in 2003, compared with 16 135 in 1999, a 55% increase. Total mentions of these codes increased from 46 523 in 1999 to 72 080 in 2003, also a 55% increase. Most codes involved 'poisonings' (overdose or the wrong substance given or taken in error that is accidental, intentional or with undetermined intent). Drugs associated with poisoning deaths had central nervous system effects. Among the codes associated with specified drug classes, poisonings and accidental poisonings involving narcotics, hallucinogens,psychoactive substances and opioids (other than opium and heroin) were associated with the largest numbers of deaths. Drug-related codes associated with the largest percentage increases in deaths between 1999 and 2003 included poisoning due to methadone (275%); poisoning by other and unspecified antidepressants (primarily selective serotonin reuptake inhibitors) [130%]; and poisoning by psychostimulants with potential for abuse (amfetamines and drugs for attention deficit hyperactivity disorder) [117%]. Anticoagulants were associated with the largest numbers of deaths with codes involving '' adverse effects in therapeutic use ''. Among diseases with significant drug-related aetiologies, Clostridium difficile enterocolitis (associated primarily with antibacterials) had the largest percentage increase in total mentions, with a 203% rise between 1999 and 2003. Conclusions: Deaths due to overdoses are the most prominent cause of drug-related mortality in death certificate data. Certain drugs and drug classes, especially the opioids (e.g. narcotics, methadone), psychoactive drugs (e.g. antidepressants, amfetamines), anticoagulants and antibacterials (which cause or contribute to C. difficile enterocolitis) are associated with large and increasing numbers of deaths and preventive strategies should be considered. C1 Food & Drug Adm, Div Drug Risk Evaluat, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), Food & Drug Adm, Div Drug Risk Evaluat, HFD-430,Bldg 22,Room 3424,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 30 TC 46 Z9 46 U1 1 U2 5 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2007 VL 30 IS 6 BP 533 EP 540 DI 10.2165/00002018-200730060-00007 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 181PB UT WOS:000247447500007 PM 17536879 ER PT J AU Brinker, A Schech, SD Burgess, M Avigan, M AF Brinker, Allen Schech, Stephanie D. Burgess, Margaret Avigan, Mark TI An observational study of cholecystectomy in patients receiving tegaserod SO DRUG SAFETY LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; SYMPTOMS; PAIN AB Background: Registrational studies of patients treated with tegaserod for irritable bowel syndrome (IBS) suggest an increased risk for cholecystectomy versus treatment with placebo. Objective: To study cholecystectomy rates in association with tegaserod within a large administrative medical claims database. Methods: Patients were drawn from a large population within the US with commercial medical insurance. The primary analysis consisted of a comparison of the observed incidence rate for cholecystectomy claims among a large cohort of new-to-therapy tegaserod users with an incidence rate published for tegaserod-naive patients classified with IBS within the same insured population. Results: An inception cohort of 7475 individuals with up to 103 weeks of claims history following initiation of therapy with tegaserod was identified. After a follow-up of 3 months (and thus similar to the longest registrational trials), the observed cholecystectomy incidence rate was 340 per 10 000 person-years (95% CI 258, 442). The rate of cholecystectomy was highest in the earliest months of observation following initiation of tegaserod. The observed cholecystecomy incidence rate is 2.9 times higher than an IBS-specific rate of 119 per 10 000 person-years as published for patients so classified within the same insured population. Conclusion: Based on a large, inception cohort, we report a strong temporal association between the initiation of tegaserod therapy and an increased rate for cholecystectomy. The effect size at 3 months was similar to the relative risk for cholecystectomy reported in registrational studies comparing tegaserod with placebo. As misclassification of initial diagnosis for patients presenting with biliary colic-like symptoms may occur, precise measurements of tegaerod-related risk for cholecystectomy from observational studies are problematic and will require prospective studies. C1 US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemol, Silver Spring, MD 20993 USA. Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN USA. RP Brinker, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemol, White oak Campus,Room 3412,Bldg 22,10903 New Hamp, Silver Spring, MD 20993 USA. EM allen.brinker@fda.hhs.gov FU FDA HHS [FD-U-002067-02, FD-U-002067-03] NR 16 TC 1 Z9 1 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2007 VL 30 IS 7 BP 581 EP 588 DI 10.2165/00002018-200730070-00003 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 194YF UT WOS:000248379000003 PM 17604409 ER PT J AU Hayward, D Wong, J Krynitsky, AJ AF Hayward, Douglas Wong, Jon Krynitsky, Alexander J. TI Polybrominated diphenyl ethers and polychlorinated biphenyls in commercially wild caught and farm-raised fish fillets in the United States SO ENVIRONMENTAL RESEARCH LA English DT Article DE polybrominated diphenyl ethers (PBDES); polychlorinated biphenyls (PCBs); polychlorodibenzo-p-dioxins/dibenzofurans (PCDD/Fs); wild fish; farmed fish; bluefish; striped bass; salmon; correlation ID PERSISTENT ORGANIC POLLUTANTS; RESOLUTION MASS-SPECTROMETRY; HUMAN ADIPOSE-TISSUE; DIBENZO-P-DIOXINS; FLAME RETARDANTS; HUMAN EXPOSURE; HUMAN SERUM; MILK; PBDES; PCBS AB Wild caught and farm-raised fish fillets collected in fish markets and large-chain super markets located in the Maryland, Washington, DC, and North Carolina were measured for their polybrominated diphenyl ether (PBDE), polychlorinated biphenyl (PCB), and polychlorodibenzo-p-dioxins/dibenzofurans (PCDD/Fs) levels. PCB and PBDE concentrations were the highest in a wild bluefish fillet (800 and 38 ng/g wet weight, respectively) and the lowest in wild Coho salmon fillet (0.35 and 0.04 ng/g, respectively). Levels for both PCBs and PBDEs in ng/g wet weight decreased from bluefish with medians of 200 and 6.2, to rockfish 66 and 4.7, followed by farmed-raised salmon with 9.0 and 1.1, with the lowest in wild salmon, 4.0 and 0.3 ng/g for PCBs and PBDEs, respectively (PCBs are the sum of 25 congeners). The chlorinated biphenyl (CB)-153 and brominated diphenyl ether (BDE)-47 levels correlated in the 22 fish fillets with a Pearson correlation coefficient of 0.94. Bluefish, rockfish (striped bass), wild caught and farm-raised salmons all showed different linear regression slopes between CB-153 and BDE-47 of 7.5, 2.7, 0.97, and 1.5, respectively. A Wilcoxon rank sum test showed no significant difference in the CB-153/BDE-47 ratios between farmed raised and all species of wild salmon combined, but was significant between bluefish and rockfish, farmed raised salmon or wild salmon. Published by Elsevier Inc. C1 US FDA, College Pk, MD 20740 USA. RP Hayward, D (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM douglas.hayward@fda.hhs.gov NR 37 TC 44 Z9 44 U1 2 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JAN PY 2007 VL 103 IS 1 BP 46 EP 54 DI 10.1016/j.envres.2006.05.002 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 128YX UT WOS:000243696700006 PM 16769049 ER PT J AU Axume, J Smith, SS Pogribny, IP Moriarty, DJ Caudill, MA AF Axume, Juan Smith, Steven S. Pogribny, Igor P. Moriarty, David J. Caudill, Marie A. TI Global leukocyte DNA methylation is similar in African American and Caucasian women under conditions of controlled folate intake SO EPIGENETICS LA English DT Article DE folate; DNA methylation; ethnicity; epigenetics; women; race ID YOUNG-WOMEN; CANCER; MORTALITY; DISEASE; WHITES AB DNA methylation is an epigenetic feature that may modify disease risk, and can be influenced by folate status as well as by methylenetetrahydrofolate reductase (MTHFR) C677T genotype. The aim of this study was to investigate the influence of ethnicity/race on global leukocyte DNA methylation under conditions of controlled folate intake. Caucasian (n = 14) and African American (n = 14) women (18-45y) possessing the MTHFR 677CC genotype consumed a folate restricted diet (135 mu g/d as dietary folate equivalents, DFE) for 7 week followed by folate treatment with 400 or 800 mu g DFE/d for 7 week. Global leukocyte DNA methylation was assessed via the cytosine extension assay at baseline (wk 0), after folate restriction (wk 7) and after folate treatment (wk 14). Ethnicity/race was not a determinant of global leukocyte DNA methylation. No differences (p > 0.05) were detected in DNA methylation between African American and Caucasian women at baseline or any other study time point. In addition, folate intake did not modify global leukocyte DNA methylation. These data suggest that global leukocyte DNA methylation does not differ between Caucasian and African American women and that short-term folate restriction is not sufficient to modify methylation content in young women with the MTHFR 677CC genotype. C1 [Axume, Juan; Caudill, Marie A.] Dept Food Sci & Human Nutr, Pomona, CA 91768 USA. [Moriarty, David J.] Calif State Polytech Univ Pomona, Dept Biol Sci, Pomona, CA 91768 USA. [Smith, Steven S.] City Hope Natl Med Ctr, Beckman Res Inst, Kaplan Clin Res Lab, Duarte, CA 91010 USA. [Pogribny, Igor P.] NCTR, Div Biochem Toxicol, Jefferson, AR USA. RP Caudill, MA (reprint author), Dept Food Sci & Human Nutr, 3801 W Temple Ave, Pomona, CA 91768 USA. EM macaudill@csupomona.edu FU NCI NIH HHS [CA102521-01, R01 CA102521]; NIGMS NIH HHS [S06 GM053933-050010, S06 GM053933-060010, S06 GM053933, S06 GM053933-070010, S06GM53933, S06 GM053933-040010] NR 16 TC 15 Z9 15 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1559-2294 J9 EPIGENETICS JI Epigenetics PD JAN-MAR PY 2007 VL 2 IS 1 BP 66 EP 68 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 306BW UT WOS:000256223000012 PM 17965592 ER PT J AU Bough, KJ Rho, JM AF Bough, Kristopher J. Rho, Jong M. TI Anticonvulsant mechanisms of the ketogenic diet SO EPILEPSIA LA English DT Review DE ketogenic diet; epilepsy; metabolism; polyunsaturated fatty acids ID POLYUNSATURATED FATTY-ACIDS; TEMPORAL-LOBE EPILEPSY; MITOCHONDRIAL UNCOUPLING PROTEINS; HIPPOCAMPAL SLICE CULTURES; GAMMA-AMINOBUTYRIC-ACID; ANIMAL SEIZURE MODELS; K-ATP CHANNELS; KETONE-BODIES; INTRACTABLE EPILEPSY; EPILEPTIFORM ACTIVITY AB The ketogenic diet (KD) is a broadly effective treatment for medically refractory epilepsy. Despite nearly a century of use, the mechanisms underlying its clinical efficacy remain unknown. In this review, we present one intersecting view of how the KD may exert its anticonvulsant activity against the backdrop of several seemingly disparate mechanistic theories. We summarize key insights gleaned from experimental and clinical studies of the KD, and focus particular attention on the role that ketone bodies, fatty acids, and limited glucose may play in seizure control. Chronic ketosis is anticipated to modify the tricarboxcylic acid cycle to increase GABA synthesis in brain, limit reactive oxygen species (ROS) generation, and boost energy production in brain tissue. Among several direct neuro-inhibitory actions, polyunsaturated fatty acids increased after KD induce the expression of neuronal uncoupling proteins (UCPs), a collective up-regulation of numerous energy metabolism genes, and mitochondrial biogenesis. These effects further limit ROS generation and increase energy production. As a result of limited glucose and enhanced oxidative phosphorylation, reduced glycolytic flux is hypothesized to activate metabolic K(ATP) channels and hyperpolarize neurons and/or glia. Although it is unlikely that a single mechanism, however well substantiated, will explain all of the diet's clinical benefits, these diverse, coordinated changes seem poised to stabilize synaptic function and increase the resistance to seizures throughout the brain. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. RP Bough, KJ (reprint author), US FDA, Ctr Drug Evaluat & Res, MPN 1 Room 1345,7520 Standish Pl, Rockville, MD 20855 USA. EM Kristopher.Bough@fda.hhs.gov NR 153 TC 173 Z9 186 U1 6 U2 35 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JAN PY 2007 VL 48 IS 1 BP 43 EP 58 DI 10.1111/j.1528-1167.2007.00915.x PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA 125WB UT WOS:000243473100005 PM 17241207 ER PT J AU Benazza-Benyahia, A Pesquet, JC Hattay, J Masmoudi, H AF Benazza-Benyahia, Amel Pesquet, Jean-Christophe Hattay, Jamel Masmoudi, Hela TI Block-Based Adaptive Vector Lifting Schemes for Multichannel Image Coding SO EURASIP JOURNAL ON IMAGE AND VIDEO PROCESSING LA English DT Article ID SUBBAND DECOMPOSITION; MULTISPECTRAL IMAGES; WAVELET TRANSFORMS; COMPRESSION; RECONSTRUCTION; PREDICTION; FILTERS AB We are interested in lossless and progressive coding of multispectral images. To this respect, nonseparable vector lifting schemes are used in order to exploit simultaneously the spatial and the interchannel similarities. The involved operators are adapted to the image contents thanks to block-based procedures grounded on an entropy optimization criterion. A vector encoding technique derived from EZW allows us to further improve the efficiency of the proposed approach. Simulation tests performed on remote sensing images show that a significant gain in terms of bit rate is achieved by the resulting adaptive coding method with respect to the non-adaptive one. Copyright (C) 2007 Amel Benazza-Benyahia et al. C1 [Benazza-Benyahia, Amel; Hattay, Jamel] Ecole Super Commun SUPCOM, URISA, Tunis 2083, Tunisia. [Pesquet, Jean-Christophe] Univ Marne La Vallee, Inst Gaspard Monge, F-77454 Marne La Vallee 2, France. [Pesquet, Jean-Christophe] Univ Marne La Vallee, CNRS, UMR 8049, F-77454 Marne La Vallee 2, France. [Masmoudi, Hela] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA. [Masmoudi, Hela] US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, Rockville, MD 20852 USA. RP Benazza-Benyahia, A (reprint author), Ecole Super Commun SUPCOM, URISA, Tunis 2083, Tunisia. NR 34 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1687-5281 J9 EURASIP J IMAGE VIDE JI EURASIP J. Image Video Process. PY 2007 AR 13421 DI 10.1155/2007/13421 PG 10 WC Engineering, Electrical & Electronic; Imaging Science & Photographic Technology SC Engineering; Imaging Science & Photographic Technology GA V14TC UT WOS:000207755700001 ER PT S AU Cavanaugh, KJ Holt, VM Goode, JL Anderson, E AF Cavanaugh, Kenneth J., Jr. Holt, Vivianne M. Goode, Jennifer L. Anderson, Evan BA Mitchell, MR BF Mitchell, MR BE Jerina, KL TI FDA recommendations for nitinol stent and endovascular graft fatigue characterization and fracture reporting SO Fatigue and Fracture of Medical Metallic Materials and Devices SE AMERICAN SOCIETY FOR TESTING AND MATERIALS SPECIAL TECHNICAL PUBLICATION LA English DT Proceedings Paper CT Symposium on Fatigue and Fracture of Medical Metallic Materials and Devices CY NOV 07-11, 2005 CL Dallas, TX SP ASTM Comm E08 & F04 DE medical device; stent; stent-graft AB Intravascular stents and endovascular stent-grafts provide a minimally invasive option for treating vascular disease and injury. Medical device manufacturers typically conduct radial pulsatile fatigue testing of intravascular stents and endovascular grafts to demonstrate that these devices will maintain their durability for ten years of implant life. While they are useful indicators of device performance, these test regimens do not always predict device durability in the clinical setting with perfect accuracy. In this paper, we address some of the common issues that should be considered in the design of fatigue tests, including appropriate sample sizes for fatigue testing, sample selection, loading conditions, and test setup issues. We also discuss finite element analysis of long-term cyclic fatigue. In addition, we describe appropriate methods for reporting the incidence of stent fractures after implantation. Our goals are to assist manufacturers and test laboratories in refining their in vitro fatigue testing methods to allow more accurate prediction of clinical device fractures, and to maximize the amount of useful data contained in clinical fracture reports. C1 US FDA, Div Cardiovasc Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Cavanaugh, KJ (reprint author), US FDA, Div Cardiovasc Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 12 TC 0 Z9 0 U1 1 U2 2 PU AMERICAN SOCIETY TESTING AND MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DRIVE, W CONSHOHOCKEN, PA 19428-2959 USA SN 1040-1695 BN 978-0-8031-4511-5 J9 AM SOC TEST MATER PY 2007 VL 1481 BP 110 EP 116 DI 10.1520/STP45244S PG 7 WC Engineering, Biomedical; Metallurgy & Metallurgical Engineering SC Engineering; Metallurgy & Metallurgical Engineering GA BGW07 UT WOS:000250865700011 ER PT J AU Cassidy, K Elyashiv-Barad, S AF Cassidy, K. Elyashiv-Barad, S. TI USFDA's revised consumption factor for polystyrene used in food-contact applications SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE polystyrene; consumption factor; food-contact polymers; exposure ID ARTICLES; STYRENE AB US FDA's continual effort to evaluate the safety of food-contact materials includes periodically re-examining our established packaging factors, such as consumption and food-type distribution factors. The use of polystyrene in food-contact and disposable food-packaging applications has expanded and is expected to continue to increase in the future. Therefore, it is important to revise the polystyrene consumption factor to account for increases in consumer exposure to substances migrating from styrenic food packaging. The currently used consumption factor for polystyrene is 0.1, which is based on market data collected around 1980. US FDA has revised the polystyrene consumption factor utilizing three different sources of market data. Using consumption and population data, US FDA calculated a new consumption factor of 0.14 for polystyrene. This consumption factor has been further subdivided to allow for the refinement of exposure estimates for uses limited to specific subcategories of polystyrene packaging. C1 US FDA, Div Food Contact Notificat, College Pk, MD 20740 USA. RP Elyashiv-Barad, S (reprint author), US FDA, Div Food Contact Notificat, 5100 Paint Brach Parkway,HFS 275, College Pk, MD 20740 USA. EM sharon.elyashiv-barad@fda.hhs.gov NR 8 TC 1 Z9 1 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PY 2007 VL 24 IS 9 BP 1026 EP 1031 DI 10.1080/02652030701313797 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 205QM UT WOS:000249129700014 PM 17691017 ER PT J AU Von Escrenbach, AC AF von Escrenbach, Andrew C. TI State of the FDA SO FOOD AND DRUG LAW JOURNAL LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Von Escrenbach, AC (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2007 VL 62 IS 2 BP 423 EP 427 PG 5 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 225CR UT WOS:000250495200008 PM 17632970 ER PT J AU Bradshaw, ST AF Bradshaw, Sheldon T. TI New FDA guidance documents SO FOOD AND DRUG LAW JOURNAL LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Bradshaw, ST (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2007 VL 62 IS 2 BP 429 EP 431 PG 3 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 225CR UT WOS:000250495200009 PM 17632971 ER PT J AU Goldman, SA AF Goldman, Stephen A. TI U.S. postmarketing pharmacovigilance compliance in the midst of regulatory uncertainty SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, MedWatch, Rockville, MD 20857 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2007 VL 62 IS 3 BP 513 EP 528 PG 16 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 225CS UT WOS:000250495300005 PM 17915393 ER PT J AU Jacobson, JD Feigal, D AF Jacobson, Jill D. Feigal, David TI Red sky in the morning: Modifying prescription drug labels as a result of postmarket surveillance SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 Bowman & Brooke LLP, Richmond, VA USA. NDA Partners, Falls Church, VA USA. US FDA, Rockville, MD 20857 USA. RP Jacobson, JD (reprint author), Bowman & Brooke LLP, Richmond, VA USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2007 VL 62 IS 3 BP 529 EP 545 PG 17 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 225CS UT WOS:000250495300006 PM 17915395 ER PT J AU Schultz, D AF Schultz, Daniel TI Medical device safety: FDAs postmarket transformation initiative SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Schultz, D (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2007 VL 62 IS 3 BP 593 EP 595 PG 3 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 225CS UT WOS:000250495300011 PM 17915401 ER PT J AU Marinac-Dabic, D Bonhomme, M Loyo-Berrios, N Gross, T Ciperson, R Gardner, S Marcarelli, M AF Marinac-Dabic, Danica Bonhomme, Michele Loyo-Berrios, Nilsa Gross, Thomas Ciperson, Robert Gardner, Susan Marcarelli, Michael TI Medical devices Post-Approval Studies Program: Vision, strategies, challenges and opportunities SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Epidemiol Branch, Div Postmarket Surveillance, Off Surveillance & Biometr,Ctr Devices & Radiol H, Rockville, MD 20857 USA. US FDA, Off Compliance, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Marinac-Dabic, D (reprint author), US FDA, Epidemiol Branch, Div Postmarket Surveillance, Off Surveillance & Biometr,Ctr Devices & Radiol H, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2007 VL 62 IS 3 BP 597 EP 604 PG 8 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 225CS UT WOS:000250495300012 PM 17915402 ER PT J AU Bright, RA AF Bright, Roselie A. TI Strategy for surveillance of adverse drug events. SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID RISK-FACTORS C1 US FDA, Surveillance & Data Anal Branch, Div Compliance Risk Management & Surveillance, Off Compliance,Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Bright, RA (reprint author), US FDA, Surveillance & Data Anal Branch, Div Compliance Risk Management & Surveillance, Off Compliance,Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RI Bright, Roselie/D-2240-2016 NR 34 TC 3 Z9 3 U1 1 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2007 VL 62 IS 3 BP 605 EP 615 PG 11 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 225CS UT WOS:000250495300013 PM 17915403 ER PT J AU Su, L Yin, JJ Charles, D Zhou, KQ Moore, J Yu, LL AF Su, Lan Yin, Jun-Jie Charles, Denys Zhou, Kequan Moore, Jeffrey Yu, Liangli (Lucy) TI Total phenolic contents, chelating capacities, and radical-scavenging properties of black peppercorn, nutmeg, rosehip, cinnamon and oregano leaf SO FOOD CHEMISTRY LA English DT Article DE antioxidant; free radicals; black peppercorn; nutmeg; rosehip; cinnamon; oregano leaf ID ANTIOXIDANT PROPERTIES; WHEAT BRAN; IN-VITRO; EXTRACTS; SPICES; OILS; ASSAY AB Black peppercorn, nutmeg, rosehip, cinnamon and oregano leaf were extracted with 50% acetone and 80% methanol, and evaluated for their radical-scavenging activities against cation (ABTS(.+)), DPPH., peroxyl (ORAC) and hydroxyl (HO.) radicals. For each extract, total phenolic content (TPC) and chelating activity were also determined. The extracts of all botanical samples showed significant radical-scavenging capacities, TPC and chelating abilities. The 50% acetone extract of cinnamon had the highest ABTS(.+)-scavenging capacity of 1243 mu mol TE/g and the greatest ORAC value of 1256 mu mol TE/g on a per weight basis. The 50% acetone extracts of black peppercorn and cinnamon showed higher ABTS(+)-scavenging, ORAC, Fe+2 chelating ability and TPC value, but lower DPPH. value than the corresponding 80% methanol extracts. The 80% methanol extract of nutmeg had greater ABTS(+), ORAC and TPC values than the 50% acetone extract. Electronic spin resonance (ESR) measurements demonstrated that cinnamon had the strongest HO.-scavenging activities among all the tested botanical materials. These data indicate that black peppercorn, nutmeg, rosehip, cinnamon and oregano leaf may serve as potential dietary sources of natural antioxidants for improving human nutrition and health. The extracting solvent may alter the antioxidant activity measurement for selected botanicals, including spices and herbs. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yu, LL (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM lyu5@umd.edu RI Yin, Jun Jie /E-5619-2014 NR 26 TC 93 Z9 102 U1 2 U2 40 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PY 2007 VL 100 IS 3 BP 990 EP 997 DI 10.1016/j.foodchem.2005.10.058 PG 8 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 089GY UT WOS:000240869800017 ER PT J AU Pierson, MD Zink, DL Smoot, LM AF Pierson, Merle D. Zink, Don L. Smoot, L. Michele BE Doyle, MP Beuchat, LR TI Indicator Microorganisms and Microbiological Criteria SO FOOD MICROBIOLOGY: FUNDAMENTALS AND FRONTIERS, THIRD EDITION LA English DT Article; Book Chapter ID FOOD SAFETY OBJECTIVES; INTERNATIONAL-TRADE; RISK-ASSESSMENT; SPECIFICATIONS; ESTABLISHMENT; PRODUCE C1 [Pierson, Merle D.] Virginia Polytech Inst & State Univ, Dept Food Sci & Technol, Blacksburg, VA 24061 USA. [Zink, Don L.] US FDA, College Pk, MD 20740 USA. [Smoot, L. Michele] Silliker Inc, Columbus, OH 43204 USA. RP Pierson, MD (reprint author), Virginia Polytech Inst & State Univ, Dept Food Sci & Technol, Blacksburg, VA 24061 USA. NR 55 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-407-6 PY 2007 BP 69 EP 85 PG 17 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPJ57 UT WOS:000279003400005 ER PT J AU Meng, JH Doyle, MP Zhao, T Zhao, SH AF Meng, Jianghong Doyle, Michael P. Zhao, Tong Zhao, Shaohua BE Doyle, MP Beuchat, LR TI Enterohemorrhagic Escherichia coli SO FOOD MICROBIOLOGY: FUNDAMENTALS AND FRONTIERS, THIRD EDITION LA English DT Article; Book Chapter ID HEMOLYTIC-UREMIC SYNDROME; SHIGA-TOXIN; ACID RESISTANCE; UNITED-STATES; ANTIMICROBIAL RESISTANCE; HEMORRHAGIC COLITIS; GROUND-BEEF; O157-H7; VARIANT; CATTLE C1 [Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Doyle, Michael P.; Zhao, Tong] Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. [Zhao, Shaohua] US FDA, Div Anim & Food Microbiol, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NR 62 TC 39 Z9 41 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-407-6 PY 2007 BP 249 EP 269 PG 21 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPJ57 UT WOS:000279003400013 ER PT J AU Lampel, KA Maurelli, AT AF Lampel, Keith A. Maurelli, Anthony T. BE Doyle, MP Beuchat, LR TI Shigella Species SO FOOD MICROBIOLOGY: FUNDAMENTALS AND FRONTIERS, THIRD EDITION LA English DT Article; Book Chapter ID III SECRETION APPARATUS; ENTEROINVASIVE ESCHERICHIA-COLI; INVASION PLASMID ANTIGENS; HEMOLYTIC-UREMIC SYNDROME; TEMPERATURE-REGULATED EXPRESSION; LARGE VIRULENCE PLASMID; FLEXNERI IPA INVASINS; SHIGA-LIKE TOXINS; EPITHELIAL-CELLS; UNIPOLAR LOCALIZATION C1 [Lampel, Keith A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Maurelli, Anthony T.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. RP Lampel, KA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 146 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-407-6 PY 2007 BP 323 EP 341 PG 19 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPJ57 UT WOS:000279003400016 ER PT J AU Feng, P AF Feng, Peter BE Doyle, MP Beuchat, LR TI Rapid Methods for the Detection of Foodborne Pathogens: Current and Next-Generation Technologies SO FOOD MICROBIOLOGY: FUNDAMENTALS AND FRONTIERS, THIRD EDITION LA English DT Article; Book Chapter ID ESCHERICHIA-COLI O157-H7; SURFACE-PLASMON RESONANCE; REAL-TIME PCR; LISTERIA-MONOCYTOGENES CELLS; IMMUNOMAGNETIC SEPARATION; DNA MICROARRAYS; MULTIPLEX PCR; HUMAN STOOLS; TOXIN GENES; FOOD SAFETY C1 US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. RP Feng, P (reprint author), US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. NR 72 TC 25 Z9 26 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-407-6 PY 2007 BP 911 EP 934 PG 24 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPJ57 UT WOS:000279003400044 ER PT J AU Whiting, RC Buchanan, RL AF Whiting, R. C. Buchanan, R. L. BE Doyle, MP Beuchat, LR TI Progress in Microbiological Modeling and Risk Assessment SO FOOD MICROBIOLOGY: FUNDAMENTALS AND FRONTIERS, THIRD EDITION LA English DT Article; Book Chapter ID COLD-SMOKED SALMON; MICROBIAL SURVIVAL CURVES; FOOD SAFETY OBJECTIVES; DOSE-RESPONSE MODELS; LISTERIA-MONOCYTOGENES; ESCHERICHIA-COLI; THERMAL INACTIVATION; LAG-PHASE; PREDICTIVE MICROBIOLOGY; CROSS-CONTAMINATION C1 [Whiting, R. C.; Buchanan, R. L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Whiting, RC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 127 TC 6 Z9 6 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-407-6 PY 2007 BP 953 EP 969 PG 17 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPJ57 UT WOS:000279003400046 ER PT J AU Elkins, KL Cowley, SC Bosio, CM AF Elkins, Karen L. Cowley, Siobhan C. Bosio, Catharine M. TI Innate and adaptive immunity to Francisella SO FRANCISELLA TULARENSIS: BIOLOGY, PATHOGENICITY, EPIDEMIOLOGY, AND BIODEFENSE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE Francisella; T lymphocyte; B lymphocyte; macrophage; dendritic cell; natural killer cell; cytokine; chemokine; protective immunity ID LIVE VACCINE STRAIN; VIRULENT TYPE-A; CELL-MEDIATED-IMMUNITY; NECROSIS-FACTOR-ALPHA; LABORATORY-ACQUIRED TULAREMIA; LIPOPOLYSACCHARIDE O-ANTIGEN; INTRANASAL INTERLEUKIN-12 TREATMENT; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; FORMERLY YERSINIA-PHILOMIRAGIA; CHRONIC GRANULOMATOUS-DISEASE AB Studies of immune responses to Francisella have been conducted for well over 50 years. Here, the basic parameters of innate and adaptive immune responses to Francisella are reviewed, with an emphasis on those that may contribute directly to protection against infection. Although older literature provides a wealth of information on human immune responses to infection and vaccination, most recent information has been derived largely from studies in animals and using animal cells, particularly mice. In experimental animals, activation of macrophages, a major and probably preferred host cell for Francisella, appears central to control of infection. Thus, in animal models and in vitro studies using mouse macrophages, cytokines such as IFN-gamma and TNF-alpha, derived first from both nonspecific cells such as natural killer cells and later from Francisella-specific T cells, collaborate to effect intracellular killing. In mice, these intracellular killing mechanisms include reactive nitrogen and oxygen species, but killing mechanisms remain to be identified in humans. Ultimately both CD4(+) and CD8(+) T cells develop into Francisella-specific memory cells and are important for control of primary Francisella infection or vaccination-induced protection. The effector mechanisms invoked by either CD4+ or CD8+ T cells, beyond production of IFN-gamma and TNF-alpha, are the subject of ongoing studies. Both specific antibodies and B cells may contribute to control of primary infection or vaccination-induced protection in some circumstances, particularly against lower virulence Francisella strains. Thus a number of known proinflammatory and Th-1 T cell related components of the immune system combat this virulent bacterium; no doubt others remain to be discovered. C1 LMDCI, Bethesda, MD 20892 USA. US FDA, Div Bacterial Parasit & Allergen Prod, Lab Mycobacteriol Dis & Cellular Immunol, Bethesda, MD 20014 USA. NIAID, NIH, Lab Intracellular Parasites, Hamilton, MT USA. RP Elkins, KL (reprint author), LMDCI, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM karen.elkins@fda.hhs.gov RI Bosio, Catharine/D-7456-2015 NR 161 TC 108 Z9 108 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1105 BP 284 EP 324 DI 10.1196/annals.1409.014 PG 41 WC Medicine, Research & Experimental; Multidisciplinary Sciences SC Research & Experimental Medicine; Science & Technology - Other Topics GA BGM15 UT WOS:000248298500013 PM 17468235 ER PT J AU Rao, VA Klein, S Zielonka, J Kalvanaraman, B Shacter, E AF Rao, V. Ashutosh Klein, Sarah Zielonka, Jacek Kalvanaraman, B. Shacter, Emily TI The mitochondrially-targeted redox agent mitoquinone enhances doxorubicin-induced toxicity to breast cancer cells while protecting cardiac myocytes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Rao, V. Ashutosh] NCI, Natl Canc Inst, FDA, IOFF Program, Bethesda, MD 20892 USA. [Klein, Sarah; Shacter, Emily] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Zielonka, Jacek; Kalvanaraman, B.] Med Coll Wisconsin, Milwaukee, WI USA. RI Zielonka, Jacek/N-9546-2014 OI Zielonka, Jacek/0000-0002-2524-0145 NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S59 EP S59 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900156 ER PT J AU Wamer, W Yin, JJ AF Wamer, Wayne Yin, Jun Jie TI Determination of phototoxicity, crystalline form and light-induced free radical formation for tattoo inks containing TiO2 SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Wamer, Wayne; Yin, Jun Jie] US FDA, Rockville, MD 20857 USA. RI Yin, Jun Jie /E-5619-2014 NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S127 EP S127 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900342 ER PT J AU Zdanov, S Shacter, E AF Zdanov, Stephanie Shacter, Emily TI Role of cofilin-1 in taurine chloramine-induced premature senescence of human lung fibroblasts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Zdanov, Stephanie; Shacter, Emily] Ctr Drug Evaluat & Res, FDA, Bethesda, MD USA. RI Zdanov, Stephanie/G-2524-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S62 EP S63 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900168 ER PT J AU Dickensheets, H Vazquez, N Sheikh, F Gingras, S Murray, PJ Ryan, JJ Donnelly, RP AF Dickensheets, H. Vazquez, N. Sheikh, F. Gingras, S. Murray, P. J. Ryan, J. J. Donnelly, R. P. TI Suppressor of cytokine signaling-1 is an IL-4-inducible gene in macrophages and feedback inhibits IL-4 signaling SO GENES AND IMMUNITY LA English DT Article DE SOCS; STAT6; macrophages; interleukin-4 ID INTERFERON-GAMMA; IFN-GAMMA; ALTERNATIVE ACTIVATION; TARGETED DISRUPTION; HUMAN MONOCYTES; CUTTING EDGE; EXPRESSION; STAT6; CELLS; INTERLEUKIN-4 AB Interferon-gamma and interleukin-4 (IL-4) induce distinct gene expression profiles in macrophages by differentially activating signal transducers and activators of transcription ( STAT) 1 and STAT6, respectively. The role of suppressor of cytokine signaling (SOCS)-1 as a negative regulator of IFN-gamma signaling is well established. However, its potential role as a negative regulator of IL-4 signaling has not been explored. We found that IL-4, like IFN-gamma, induces rapid de novo expression of SOCS-1 in primary macrophages. Induction of SOCS-1 gene expression by IL-4 is STAT6- dependent, whereas induction of SOCS-1 by IFN-gamma is STAT1-dependent. Unlike their common ability to induce expression of SOCS-1, IL-4 also induced expression of SOCS-2 but not SOCS-3 in macrophages, whereas IFN-gamma induced expression of SOCS-3 but not SOCS-2. Forced expression of SOCS-1 or SOCS-3, but not SOCS-2, inhibited activation of STAT6 by IL-4. Moreover, SOCS-1 appears to serve as an endogenous regulator of IL-4 signaling in macrophages because the magnitude and duration of STAT6 activation as well as IL-4-mediated gene expression were much greater in SOCS-1-deficient (SOCS-1(-/-)) macrophages than in wild-type macrophages. Our findings demonstrate that, like IFN-gamma, IL-4 also induces expression of SOCS-1 in macrophages, and SOCS-1 feedback inhibits expression of STAT6- responsive genes. C1 US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA. RP Donnelly, RP (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, HFD-122,1401 Rockville Pike, Rockville, MD 20852 USA. EM Raymond.Donnelly@fda.hhs.gov FU NIAID NIH HHS [AI059638, AI062921] NR 34 TC 43 Z9 45 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JAN PY 2007 VL 8 IS 1 BP 21 EP 27 DI 10.1038/sj.gene.6364352 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 130EX UT WOS:000243783500003 PM 17093501 ER PT S AU Rollema, H Chaurasia, CS AF Rollema, Hans Chaurasia, Chandra S. BE Westerink, BHC Cremers, TIFH TI Use of microdialysis in drug discovery and development: industry and regulatory perspectives SO HANDBOOK OF MICRODIALYSIS: METHODS, APPLICATIONS AND PERSPECTIVES SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter ID RECEPTOR PARTIAL AGONIST; BLOOD-BRAIN-BARRIER; SUSTAINED-RELEASE BUPROPION; RANDOMIZED CONTROLLED-TRIAL; SMOKING-CESSATION; VARENICLINE; DOPAMINE; PERMEABILITY; TRANSPORTERS; PENETRATION AB This chapter discusses the role of microdialysis in the discovery and development of drugs that act on the central nervous system (CNS). The focus is on strategies that will help to select high-quality compounds for development and that contribute to reducing the current high attrition rate in the pharmaceutical industry. Pharmacodynamic and pharmacokinetic microdialysis applications are discussed to illustrate how and when microdialysis can be used in the different stages of the discovery and development process. Since microdialysis data are likely to become an important part of new drug submissions, and thus may potentially contribute to the FDA Critical Path Initiative to facilitate innovation in drug development, some regulatory aspects will be discussed as well. C1 [Rollema, Hans] Pfizer Global Res & Dev, Dept Neurosci, Groton Labs, Groton, CT 06340 USA. [Chaurasia, Chandra S.] US FDA, Div Bioequivalence, Rockville, MD 20855 USA. RP Rollema, H (reprint author), Pfizer Global Res & Dev, Dept Neurosci, Groton Labs, MS 8220-4159,Eastern Point Rd, Groton, CT 06340 USA. EM hans.rollema@pfizer.com NR 40 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-7339 BN 978-0-08-046966-9 J9 HBK BEHAV NEUROSCI PY 2007 VL 16 BP 513 EP 526 DI 10.1016/S1569-7339(06)16027-0 PG 14 WC Medicine, Research & Experimental; Neurosciences SC Research & Experimental Medicine; Neurosciences & Neurology GA BCQ67 UT WOS:000311036100028 ER PT B AU Husain, SR Puri, RK AF Husain, Syed Rafat Puri, Raj K. BE Barnett, GH TI Immunotoxins for Glioma Therapy SO HIGH-GRADE GLIOMAS: DIAGNOSIS AND TREATMENT SE Current Clinical Oncology Series LA English DT Article; Book Chapter DE Glioma; immunotoxin; IL13-PE; chimeric fusion protein; xenograft; clinical trial ID RECEPTOR-ALPHA CHAIN; PLASMINOGEN-ACTIVATOR RECEPTOR; RECURRENT MALIGNANT GLIOMA; HAIRY-CELL LEUKEMIA; COMMON GAMMA-CHAIN; PHASE-I TRIAL; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; FUSION-PROTEIN; IL-13 RECEPTOR AB Targeting cancer cells with an immunotoxin represents a novel therapeutic approach. Several immunotoxins composed of a ligand or antibody and truncated bacterial toxins are in clinical development to treat various cancers including glioblastoma multiforme (GBM). GBM is an infiltrative tumor that defies a "complete surgical resection" invariably recurring most often at the site of resection. A number of local therapies are being explored. One approach is to identify unique or over-expressed cell surface receptors on GBM cells and targeting them with a receptor-specific immunotoxin. We have identified over-expression of a receptor for an immune regulatory cytokine, interleukin-13 (IL-13) on human malignant glioma cell lines, primary brain tumor cell cultures, and tumor tissues. The targeting of IL-13 receptors (IL-13R) with a recombinant fusion protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL13-PE38QQR or IL-13-PE38, referred to here as IL13-PE) demonstrated a potent and specific cell-killing of GBM cells in vitro. Normal brain cells, immune cells, and endothelial cells devoid of the unique IL-13R chain were not susceptible to immunotoxin cell killing activity. Direct injection of IL13-PE into subcutaneous (sc) or intracranial human GBM tumors in nude mice resulted in complete and durable regression of tumors. IL13-PE delivered through intravenous (iv) and intraperitoneal (ip) routes of administration also reduced sc tumor burden with fewer complete responses (CR). High doses of systemic (up to 50 mu g/kg) or intracerebral (up to 100 mu g/mL) IL-13-PE were well tolerated in mice and rats, respectively without evidence of gross or microscopic necrosis. Based on these encouraging preclinical results, four phase I and II clinical trials were initiated to investigate the safety, toxicity, and optimal convection-enhanced delivery (CED) of IL13-PE to patients with recurrent malignant gliomas; patients had already undergone standard therapy including surgery, radiation, and chemotherapy. CED uses a positive pressure to generate a pressure gradient that optimizes distribution of the macromolecule within tumor and peritumoral regions. A total of 97 patients were treated with IL13-PE in these studies. CED of IL13-PE into sol id tumor component as well as the surrounding brain tissues felt to be at risk for residual infiltrating tumor before and after tumor resection, respectively was fairly well tolerated in terms of safety profile. Histological antitumor effects have been observed at drug concentrations of 0.5, 1.0 and 2.0 mu g/mL without apparent increased antitumor activity at higher concentrations. Duration of infusions up to 7 d was fairly well tolerated. A randomized worldwide phase III clinical trial (PRECISE, phase III Randomized Evaluation of Convection Enhanced Delivery of IL13-PE38QQR with Survival Endpoint) is currently recruiting patients with recurrent supratentorial GBM at first recurrence to evaluate overall survival duration, safety, and quality-of-life of patients treated by tumor resection followed by peritumoral IL13-PE infusion vs Gliadel (R) Wafer placement. C1 [Husain, Syed Rafat; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Husain, SR (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 95 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-511-8 J9 CURR CLIN ONCOL PY 2007 BP 315 EP 335 DI 10.1007/978-1-59745-185-7_19 D2 10.1007/978-1-59745-185-7 PG 21 WC Oncology; Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJZ79 UT WOS:000267545000020 ER PT J AU Whichard, JM Gay, K White, DG Chiller, TM AF Whichard, Jean M. Gay, Kathryn White, David G. Chiller, Tom M. BA Mikanatha, NM Lynfield, R VanBeneden, CA DeValk, H BF Mikanatha, NM Lynfield, R VanBeneden, CA DeValk, H TI Surveillance for antimicrobial resistance among foodborne bacteria: the US approach SO INFECTIOUS DISEASE SURVEILLANCE, 1ST EDITION LA English DT Article; Book Chapter ID UNITED-STATES; VETERINARY-MEDICINE; ESCHERICHIA-COLI; FOOD ANIMALS; SALMONELLA; INFECTIONS; SUSCEPTIBILITY; CAMPYLOBACTER; HUMANS C1 [Whichard, Jean M.; Gay, Kathryn; Chiller, Tom M.] Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, Atlanta, GA 30333 USA. [White, David G.] US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD USA. RP Whichard, JM (reprint author), Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, Atlanta, GA 30333 USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69209-7 PY 2007 BP 79 EP 92 DI 10.1002/9780470692097.ch7 D2 10.1002/9780470692097.ch1 PG 14 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA BCJ61 UT WOS:000310294400009 ER PT J AU Xu, LX Frucht, DA AF Xu, Lixin Frucht, David A. TI Bacillus anthracis: A multi-faceted role for anthrax lethal toxin in thwarting host immune defenses SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Bacillus anthracis; lethal toxin; pathogenesis ID CRYSTAL-STRUCTURE; RECEPTOR; ANTIGEN; RELEASE; CELLS AB Lethal factor (LF), along with its receptor-binding partner protective antigen (PA), forms lethal toxin (LT), a critical virulence factor for Bacillus anthracis. LF is a Zn2+ protease that cleaves specific mitogen activated protein kinase kinases (MAPKKs), inactivating signal transduction intermediates required for normal immune function. Initial research emphasized the role of LT in attenuating pro-inflammatory responses by macrophages, the primary targets of infection. More recent studies have revealed that LT affects a broad range of immune cells. In addition to direct effects on macrophages and neutrophils, LT suppresses the costimulatory functions of dendritic cells, thereby impeding essential cross-talk between innate and adaptive immune responses. Moreover, LT acts directly on T and B lymphocytes, blocking antigen receptor-dependent proliferation, cytokine production and Ig production. In this manner, LT mounts a broad-based attack on host immunity, thus providing B. anthracis with multiple mechanisms for avoiding protective host responses. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Frucht, DA (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bldg 29B,Room 3NN22, Bethesda, MD 20892 USA. EM david.frucht@fda.hhs.gov NR 20 TC 20 Z9 24 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2007 VL 39 IS 1 BP 20 EP 24 DI 10.1016/j.biocel.2006.08.010 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 104MR UT WOS:000241963000004 PM 17008119 ER PT J AU Zhang, QY Chen, YB Wang, BD He, P Su, YA AF Zhang, Qiuyang Chen, Yuanbin Wang, Bi-Dar He, Ping Su, Yan A. TI Differences in apoptosis and cell cycle distribution between human melanoma cell lines UACC903 and UACC903(+6), before and after UV irradiation SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE melanoma; UV irradiation; apoptosis; cell cycle arrest ID MALIGNANT-MELANOMA; DNA FRAGMENTATION; IN-SITU; TUMORIGENICITY; IDENTIFICATION; METASTASIS; PHOSPHATIDYLSERINE; CHROMOSOME-6; EXPRESSION; EXPOSURE AB Introduction of human chromosome 6 into malignant melanoma cell line UACC903 resulted in generation of the chromosome mediated suppressed cell subline UACC903(+6) that displays attenuated growth rate, anchorage-dependency, and reduced tumorigenicity. We have showed that overexpression of a chromosome 6-encoded tumor suppressor gene led to partial suppression to UACC903 cell growth. We now describe the differences in apoptosis and cell cycle between UACC903 and UACC903(+6) before and after UV irradiation. MTT assay revealed 86.92 +/- 8.24% of UACC903 cells viable, significantly (p < 0.01) higher than 48.76 +/- 5.31% of UACC903(+6), at 24 hr after 254-nm UV irradiation (40 J/M-2). Before UV treatment, flow cytometry analysis revealed 6.06 +/- 0.20% apoptosis in UACC903, significantly (p = 0.01) lower than 6.67 +/- 0.15% in UACC903(+6). The G0/G1, S and G2/M phase cells of UACC903 were, respectively, 54.10 +/- 0.59%, 22.31 +/- 0.50% and 16.85 +/- 0.25%, all significantly (p < 0.01) different from the corresponding percentages (58.82 +/- 0.35%, 20.48 +/- 0.05%, and 13.17 +/- 0.45%) of UACC903(+6). After the UV treatment, UACC903 cells in apoptosis, G0/G1, S, and G2/M became 12.59 +/- 0.17%, 38.90 +/- 0.67%, 19.74 +/- 0.70%, and 27.01 +/- 0.66%, respectively, while UACC903(+6) cells were 24.16 +/- 0.48%, 37.97 +/- 0.62%, 19.20 +/- 0.52%, and 15.69 +/- 0.14%. TUNEL assay revealed 2.31 +/- 0.62% apoptosis in UACC903, significantly (p < 0.01) lower than 9.60 +/- 1.14% of UACC903(+6), and a linear and exponential increase of apoptosis, respectively, in response to the UV treatment. These results indicate that UACC903(+6) cells have a greater tendency to undergo apoptosis and are thus much more sensitive to UV irradiation. Our findings further suggest a novel mechanism for chromosome 6-mediated suppression of tumorigenesis and metastasis, i. e., through increased cell death. C1 [Zhang, Qiuyang; Wang, Bi-Dar; Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Chen, Yuanbin] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [He, Ping] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Su, YA (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Ross Hall,Rm 555,2300 EYE St NW, Washington, DC 20037 USA. EM bcmyas@gwumc.edu FU PHS HHS [NIH-NIDDK-06-925] NR 21 TC 6 Z9 6 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2007 VL 3 IS 6 BP 342 EP 348 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 268VG UT WOS:000253607300001 PM 17657283 ER PT J AU Shames, D Monroe, SE Davis, D Soule, L AF Shames, D. Monroe, S. E. Davis, D. Soule, L. TI Regulatory perspective on clinical trials and end points for female sexual dysfunction, in particular, hypoactive sexual desire disorder: formulating recommendations in an environment of evolving clinical science SO INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH LA English DT Review DE female sexual dysfunction (FSD); hypoactive sexual desire disorder (HSDD); testosterone therapy in women AB This article examines the history, current status, and potential future challenges in the development of drugs for female sexual dysfunction (FSD) from the perspective of the United States Food and Drug Administration. In particular, the article focuses on testosterone therapy for hypoactive sexual desire disorder (a component of FSD), and the role of the Division of Reproductive and Urologic Products in facilitating the development of safe and effective therapies for this indication. C1 US FDA, Div Reprod & Urol Prod, Silver Spring, MD 20993 USA. RP Shames, D (reprint author), US FDA, Div Reprod & Urol Prod, 10903 New Hampshire Ave,WO BLDG 22, Silver Spring, MD 20993 USA. EM daniel.shames@fda.hhs.gov NR 7 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0955-9930 J9 INT J IMPOT RES JI Int. J. Impot. Res. PD JAN-FEB PY 2007 VL 19 IS 1 BP 30 EP 36 DI 10.1038/sj.ijir.3901481 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 128UW UT WOS:000243685500004 PM 16728969 ER PT J AU Bonaventura, C Henkens, R Alayash, AI Crumbliss, AL AF Bonaventura, Celia Henkens, Robert Alayash, Abdu I. Crumbliss, Alvin L. TI Allosteric effects on oxidative and nitrosative reactions of cell-free hemoglobins SO IUBMB LIFE LA English DT Review DE hemoglobin; redox chemistry; blood substitutes; HBOCs; allostery; nitric oxide; nitrite ID CROSS-LINKED HEMOGLOBIN; ELECTRON-PARAMAGNETIC-RESONANCE; RED-BLOOD-CELLS; NITRIC-OXIDE; OXYGEN CARRIERS; HYPOXIC VASODILATION; S-NITROSOHEMOGLOBIN; HEME DEGRADATION; BINDING; SUBSTITUTES AB A review of the oxidative and nitrosative reactions of cell- free hemoglobin- based oxygen carriers (HBOCs) shows that these reactions are intimately linked and are subject to allosteric control. Cross- linking reactions used to produce HBOCs introduce conformational constraints and result in Hbs with reduced responses to heterotropic and homotropic allosteric e. ectors. The Nernst plots of heme oxidation of cross- linked HBOCs are shifted to higher potentials relative to unmodifi. ed Hb in the absence of allosteric effectors, in accord with their T- state stabilization and right- shifted Hill plots of O-2 binding. They exhibit enhanced rates of autoxidation and nitrite- induced oxidation, features that appear due to their having more solvent- accessible heme pockets. The stability of their NO- Hb derivatives varies as a result of allosteric effects on the extent of formation of pentacoordinate NO- heme geometry by a chains and subsequent oxidation of partner beta chains. The physiological implications of these. findings on the safety, efficacy and design of second generation HBOCs are discussed in the framework of a reaction scheme showing linkages between Hb-mediated redox reactions. These redox reactions can drive formation of SNO- Hb and other reactive species and are of significance for the use of cell- free Hbs in vivo. C1 Duke Univ, Marine Lab, Nicholas Sch Environm & Earth Sci, Beaufort, NC 28516 USA. US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD USA. Duke Univ, Dept Chem, Durham, NC 27706 USA. RP Bonaventura, C (reprint author), Duke Univ, Marine Lab, Nicholas Sch Environm & Earth Sci, Beaufort, NC 28516 USA. EM bona@duke.edu FU NHLBI NIH HHS [5P01-HL-071064-04] NR 47 TC 13 Z9 13 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PY 2007 VL 59 IS 8-9 BP 498 EP 505 DI 10.1080/15216540601188546 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 199UT UT WOS:000248721400004 PM 17701544 ER PT J AU Chowdhury, BA AF Chowdhury, Badrul A. TI Antibiotics and asthma treatment SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 US FDA, Div Pulm & Allergy Prod, Silver Spring, MD USA. RP Chowdhury, BA (reprint author), US FDA, Div Pulm & Allergy Prod, Silver Spring, MD USA. EM badrul.chowdhury@fda.hhs.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 BP 251 EP 251 DI 10.1016/j.jaci.2006.07.048 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 127YL UT WOS:000243622200037 PM 17137863 ER PT J AU Devore, NC Slater, JE AF deVore, N. C. Slater, J. E. TI Development of a microarray assay to determine the potency of allergenic extracts using recombinant antibodies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [deVore, N. C.; Slater, J. E.] Food & Drug Administrat, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 1043 BP S267 EP S267 DI 10.1016/j.jaci.2006.12.413 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401426 ER PT J AU Kadegowda, AKG Teter, BB Sampugna, J Delmonte, P Piperova, LS Erdman, RA AF Kadegowda, A. K. G. Teter, B. B. Sampugna, J. Delmonte, P. Piperova, L. S. Erdman, R. A. TI Trans-7-octadecenoic acid decreased milk fat and altered CLA composition in milk of lactating mice SO JOURNAL OF ANIMAL SCIENCE LA English DT Meeting Abstract DE trans fatty acids; CLA; milk fat C1 [Kadegowda, A. K. G.; Teter, B. B.; Sampugna, J.; Piperova, L. S.; Erdman, R. A.] Univ Maryland, College Pk, MD 20742 USA. [Delmonte, P.] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PY 2007 VL 85 SU 1 BP 179 EP 180 PG 2 WC Agriculture, Dairy & Animal Science SC Agriculture GA 213UN UT WOS:000249692700555 ER PT J AU Rodriguez, CP Patazca, E Schlesser, JE AF Rodriguez, C. P. Patazca, E. Schlesser, J. E. TI Effects of High Pressure Processing on the reduction of Listeria monocytogenes in the manufacture of soft cheeses SO JOURNAL OF ANIMAL SCIENCE LA English DT Meeting Abstract DE Listeria monocytogenes; soft cheese; high pressure processing C1 [Rodriguez, C. P.; Patazca, E.] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. [Schlesser, J. E.] Natl Ctr Food Safety & Technol, FDA, Summit Argo, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PY 2007 VL 85 SU 1 BP 270 EP 270 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA 213UN UT WOS:000249692700840 ER PT J AU Billal, DS Fedorko, DP Yan, SS Hotomi, M Fujihara, K Nelson, N Yamanaka, N AF Billal, Dewan S. Fedorko, Daniel P. Yan, S. Steve Hotomi, Muneki Fujihara, Keiji Nelson, Nancy Yamanaka, Noboru TI In vitro induction and selection of fluoroquinolone-resistant mutants of Streptococcus pyogenes strains with multiple emm types SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE S pyogenes; resistance; laboratory induction and selection; point mutations ID REDUCED SUSCEPTIBILITY; STAPHYLOCOCCUS-AUREUS; TOPOISOMERASE-IV; CLONAL SPREAD; DNA GYRASE; PNEUMONIAE; MUTATIONS; PARC; QUINOLONES; ISOLATE AB Objectives: To perform a systematic analysis of point mutations in the quinolone resistance determining regions (QRDRs) of the DNA gyrase and topoisomerase genes of emm type 6 and other emm types of Streptococcus pyogenes strains after in vitro exposure to stepwise increasing concentrations of levofloxacin. Methods: Twelve parent strains of S. pyogenes, each with a different emm type, were chosen for stepwise exposure to increasing levels of levofloxacin followed by selection of resistant mutants. The QRDRs of gyrA, gyrB, parC and parE correlating to mutants with increased MICs were analysed for point mutations. Results: Multiple mutants with significantly increased MICs were generated from each strain. The amino acid substitutions identified were consistent regardless of emm type and were similar to the mechanisms of resistance reported in clinical isolates of S. pyogenes. The number of induction/selection cycles required for the emergence of key point mutations in gyrA and parC was variable among strains. For each parent-mutant set, when MIC increased, serine-81 of gyrA and serine-79 of parC were the primary targets for amino acid substitutions. No point mutations were found in the QRDRs of gyrB and parE in any of the resistant mutants sequenced. Conclusions: Despite its intrinsic polymorphism in the QRDR of parC, emm type 6 is not more likely to develop high-level resistance to fluoroquinolones when compared with other emm types. All emm types seem equally inducible to high-level fluoroquinolone resistance. C1 Wakayama Med Univ, Dept Otolaryngol Head & Neck Surg, Wakayama 6418510, Japan. NIH, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. US FDA, Dept Hlth & Human Serv, Rockville, MD 20855 USA. RP Yamanaka, N (reprint author), Wakayama Med Univ, Dept Otolaryngol Head & Neck Surg, 811-1 Kimiidera, Wakayama 6418510, Japan. EM ynobi@wakayama-med.ac.jp NR 22 TC 13 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JAN PY 2007 VL 59 IS 1 BP 28 EP 34 DI 10.1093/jac/dkl428 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 120FJ UT WOS:000243069600004 PM 17065188 ER PT J AU Poli, MA Rivera, VR Neal, DD Baden, DG Messer, SA Plakas, SM Dickey, RW El Said, K Flewelling, L Green, D White, J AF Poli, Mark A. Rivera, Victor R. Neal, Dwayne D. Baden, Daniel G. Messer, Shawn A. Plakas, Steven M. Dickey, Robert W. El Said, Kathleen Flewelling, Leanne Green, David White, Jill TI An electrochemiluminescence-based competitive displacement immunoassay for the type-2 brevetoxins in oyster extracts SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CRASSOSTREA-VIRGINICA; SHELLFISH; METABOLITES; TOXINS AB A new competitive electrochemiluminescence-based immunoassay for the type-2 brevetoxins in oyster extracts was developed. The assay was verified by spiking known amounts of PbTx-3 into 80% methanol extracts of Gulf Coast oysters. We also provide preliminary data demonstrating that 100% acetone extracts, aqueous homogenates, and the clinical matrixes urine and serum can also be analyzed without significant matrix interferences. The assay offers the advantages of speed (2 h analysis time); simplicity (only 2 additions, one incubation period, and no wash steps before analysis); low limit of quantitation (conservatively, 50 pg/mL = 1 ng/g tissue equivalents); and a stable, nonradioactive label. Due to the variety of brevetoxin metabolites present and the lack of certified reference standards for liquid chromatography-mass spectrometry confirmation, a true validation of brevetoxins in shellfish extracts is not possible at this time. However, our assay correlated well with another brevetoxin immunoassay currently in use in the United States. We believe this assay could be useful as a regulatory screening tool and could support pharmacokinetic studies in animals and clinical evaluation of neurotoxic shellfish poisoning victims. C1 USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Univ N Carolina, Ctr Marine Sci, Wilmington, NC USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Florida Fish & Wildlife Conservat Commiss, Fish & Wildlife Res Inst, St Petersburg, FL 33701 USA. Mesoscale Diagnost LLC, Gaithersburg, MD 20877 USA. BioVeris Corp, Gaithersburg, MD 20877 USA. RP Poli, MA (reprint author), USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. EM mark.poli@det.amedd.army.mil FU NIEHS NIH HHS [P01 ES010594-08, P01 ES010594] NR 12 TC 18 Z9 20 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2007 VL 90 IS 1 BP 173 EP 178 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 135BN UT WOS:000244128900021 PM 17373449 ER PT J AU Guan, D Joerger, RD Kniel, KE Calci, KR Hicks, DT Pivarnik, LF Hoover, DG AF Guan, D. Joerger, R. D. Kniel, K. E. Calci, K. R. Hicks, D. T. Pivarnik, L. F. Hoover, D. G. TI Effect of high hydrostatic pressure on four genotypes of F-specific RNA bacteriophages SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE bacteriophage; high pressure; inactivation ID HEPATITIS-A VIRUS; INACTIVATION; CALICIVIRUS; COLIPHAGES; PROTEIN; FOOD AB Aims: The pressure responses of four genotypes of F-specific RNA bacterio-phages, f2, GA, Q beta and SP, were evaluated with respect to pressure magnitude, treatment temperature and suspending medium. Method and Results: The pressure responses were studied with respect to pressure magnitude (350 to 600 MPa), treatment temperature (-10 to 50 degrees C) and suspending media. Phages f2 and GA had much higher pressure resistances than Q beta and SP. Pressure resistances of Q beta and SP were enhanced with increase in salt concentrations in the range of 350 to 600 MPa from -10 to 50 degrees C in PBS. Q beta and SP had greater pressure resistances when suspended in phosphate-buffered saline (PBS) with added glucose (5%, w/w), UHT whole milk and Dulbecco's Modified Eagle's Medium plus 10% fetal bovine sera than they did in PBS. Two surfactants, sucrose laurate and monolaurin, and one chelating agent, ethylenediamine tetraacetic acid (EDTA), increased the pressure resistance of Q beta and SP, but had modest effect on either f2 or GA. Conclusions: Four representative F-specific RNA bacteriophages, f2 (serotype I), GA (serotype II), Q beta (serotype III) and SP (serotype IV) showed different resistances to hydrostatic pressure in the range of 350-600 MPa. Significance and Impact of the Study: This study screened for practical surrogates of HAV for validation of commercial high hydrostatic pressure processing. C1 Univ Delaware, Dept Anim & Food Sci, Newark, DE 19716 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. Univ Delaware, Sea Grant Coll Program, Lewes, DE 19958 USA. Univ Rhode Isl, Dept Nutr & Food Sci, Kingston, RI 02881 USA. RP Hoover, DG (reprint author), Univ Delaware, Dept Anim & Food Sci, Newark, DE 19716 USA. EM dgh@udel.edu NR 28 TC 6 Z9 6 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD JAN PY 2007 VL 102 IS 1 BP 51 EP 56 DI 10.1111/j.1365-2672.2006.03064.x PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 116VY UT WOS:000242832900006 PM 17184319 ER PT J AU Kim, SJ Kweon, O Jones, RC Freeman, JP Edmondson, RD Cerniglia, CE AF Kim, Seong-Jae Kweon, Ohgew Jones, Richard C. Freeman, James P. Edmondson, Ricky D. Cerniglia, Carl E. TI Complete and integrated pyrene degradation pathway in Mycobacterium vanbaalenii PYR-1 based on systems biology SO JOURNAL OF BACTERIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; SP STRAIN PYR-1; CATABOLIC GENE-CLUSTER; MOLECULAR CHARACTERIZATION; DEGRADING MYCOBACTERIUM; MICROBIAL-METABOLISM; GEL ELECTROPHORESIS; PROTOCATECHUIC ACID; PSEUDOMONAS-PUTIDA; BETA-KETOADIPATE AB Mycobacterium vanbaalenii PYR-1 was the first bacterium isolated by virtue of its ability to metabolize the high-molecular-weight polycyclic aromatic hydrocarbon (PAH) pyrene. We used metabolic, genomic, and proteomic approaches in this investigation to construct a complete and integrated pyrene degradation pathway for M. vanbaalenii PYR-1. Genome sequence analyses identified genes involved in the pyrene degradation pathway that we have proposed for this bacterium. To identify proteins involved in the degradation, we conducted a proteome analysis of cells exposed to pyrene using one-dimensional gel electrophoresis in combination with liquid chromatography-tandem mass spectrometry. Database searching performed with the M. vanbaalenii PYR-1 genome resulted in identification of 1,028 proteins with a protein false discovery rate of < 1%. Based on both genomic and proteomic data, we identified 27 enzymes necessary for constructing a complete pathway for pyrene degradation. Our analyses indicate that this bacterium degrades pyrene to central intermediates through o-phthalate and the P-ketoadipate pathway. Proteomic analysis also revealed that 18 enzymes in the pathway were upregulated more than twofold, as indicated by peptide counting when the organism was grown with pyrene; three copies of the terminal subunits of ring-hydroxylating oxygenase (NidAB2, MvanDraft_0817/0818, and PhtAaAb), dihydrodiol dehydrogenase (MvanDraft_0815), and ring cleavage dioxygenase (MvanDraft_3242) were detected only in pyrene-grown cells. The results presented here provide a comprehensive picture of pyrene metabolism in M. vanbaalenii PYR-1 and a useful framework for understanding cellular processes involved in PAH degradation. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Carl.Cerniglia@fda.hhs.gov NR 62 TC 112 Z9 122 U1 4 U2 52 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2007 VL 189 IS 2 BP 464 EP 472 DI 10.1128/JB.01310-06 PG 9 WC Microbiology SC Microbiology GA 125OY UT WOS:000243452800022 PM 17085566 ER PT J AU Lee, SY Regnault, WF Antonucci, JM Skrtic, D AF Lee, Soo-Young Regnault, W. F. Antonucci, J. M. Skrtic, D. TI Effect of particle size of an amorphous calcium phosphate filler on the mechanical strength and ion release of polymeric composites SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE bioactive material; calcium phosphate(s); composite/hard tissue; ion release; particle size distribution ID DENTAL COMPOSITES; WATER SORPTION; HYBRID AB The random clustering of amorphous calcium phosphate (ACP) particles within resin matrices is thought to diminish the strength of their polymerized composites. The objective of this study was to elucidate the effect of ball-milling on the particle size distribution (PSD) of ACP fillers and assess if improved dispersion of milled ACP in methacrylate resin sufficiently enhanced filler/matrix interactions to result in improved biaxial flexure strength (BFS), without compromising the remineralizing potential of the composites. Unmilled and wet-milled zirconia-hybridized ACP (Zr-ACP) fillers were characterized by PSD analysis, X-ray diffraction, thermogravimetric and chemical analysis, infrared spectroscopy, and scanning electron microscopy. Composite specimens made from a photoactivated, ternary methacrylate resin admixed with a mass fraction of 40% of un-milled or milled Zr-ACP were evaluated for the BFS (dry and wet) and for the release of calcium and phosphate ions into saline solutions. While having no apparent effect on the structure, composition, and morphology/topology of the fillers, milling significantly reduced the average size of Zr-ACP particulates (median diameter, d(m)=0.9 +/- 0.2 mu m) and the spread of their PSD. Better dispersion of milled Zr-ACP in the resins resulted in the improved BFS of the composites, even after aqueous soaking, and also gave a satisfactory ion release profile. The demonstrated improvement in the mechanical stability of anti-demineralizing/remineralizing ACP composites based on milled Zr-ACP filler may be beneficial in potentially extending their dental utility. (c) 2006 Wiley Periodicals, Inc.* J Biomed Mater Res Part B: Appl Biomater 80B: 11-17, 2007 C1 Amer Dent Assoc Fdn, Paffenbarger Res Ctr, Gaithersburg, MD USA. Phil Dent Clin, Seoul, South Korea. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. RP Skrtic, D (reprint author), Amer Dent Assoc Fdn, Paffenbarger Res Ctr, Gaithersburg, MD USA. EM drago.skrtic@nist.gov FU NIDCR NIH HHS [R01 DE013169-07, R01 DE13169-07, R01 DE013169] NR 20 TC 24 Z9 24 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4973 EI 1552-4981 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD JAN PY 2007 VL 80B IS 1 BP 11 EP 17 DI 10.1002/jbm.b.30561 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 119NE UT WOS:000243018200002 PM 16649181 ER PT J AU Yue, LQ AF Yue, Lilly Q. TI Statistical and regulatory issues with the application of propensity score analysis to nonrandomized medical device clinical studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE medical devices; nonrandomized studies; propensity score analysis ID BIAS AB Propensity score analysis is a versatile statistical method used mainly in observational studies for improving treatment comparison by adjusting for up to a relatively large number of potentially confounding covariates. Recently, there has been an increased interest in applying this method to nonrandomized medical device clinical studies. In the application of the methodology, some statistical and regulatory issues arise in both study design and analysis of study results, such as the need for pre-specifying clinically relevant covariates to be measured, appropriate patient populations, and the essential elements of statistical analysis, planning sample size in the context of propensity score methodology, handling missing covariates in generating propensity scores, and assessing the success of the propensity score method by evaluating treatment group overlap in terms of the distributions of propensity scores. In this paper, the advantages and limitations of this methodology will be revisited, and the above issues will be discussed and illustrated with examples from a regulatory perspective. C1 US FDA, CDRH, Rockville, MD 20850 USA. RP Yue, LQ (reprint author), US FDA, CDRH, 1350 Piccard Dr, Rockville, MD 20850 USA. EM lilly.yue@fda.hhs.gov NR 9 TC 25 Z9 27 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN-FEB PY 2007 VL 17 IS 1 BP 1 EP 13 DI 10.1080/10543400601044691 PG 13 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 117IJ UT WOS:000242866300001 PM 17219753 ER PT J AU Yue, LQ AF Yue, Lilly Q. TI Rejoinder SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 US FDA, CDRH, Rockville, MD 20850 USA. RP Yue, LQ (reprint author), US FDA, CDRH, 1350 Piccard Dr, Rockville, MD 20850 USA. EM lilly.yue@fda.hhs.gov NR 1 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 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN-FEB PY 2007 VL 17 IS 1 BP 43 EP 43 DI 10.1080/10543400601051654 PG 1 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 117IJ UT WOS:000242866300008 ER PT J AU Tsong, Y Shen, MY AF Tsong, Yi Shen, Meiyu TI Parametric two-stage sequential quality assurance test of dose content uniformity SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE dose content uniformity; double one-sided test; tolerance interval; two-stage group sequential; US Pharmacopeia AB The United States Pharmacopeia (USP) content uniformity sampling acceptance plan consisting of a two-stage sampling plan with criteria on sample mean and number of out-of-range tablets is the standard for compendium. It is, however, often used mistakenly for lot quality assurance. In comparison to the Japan Phamacopeia ( JP) procedure, USP procedure is less discriminative between lots with on-target mean and small variance and lots with off-target mean and large variance. The new European Pharmacopeia (EP) and USP harmonized test adopted a tolerance interval approach. But the "no-difference zone" criteria modi. cation for off-target products make the approaches biased in favor of off-target products. We propose a parametric tolerance interval procedure to test a two-sided specification that is equivalent to the test of two one-sided hypotheses. Testing against a lower specification is to assure that the drug product is not under-dosed for the sake of efficacy. On the other hand, testing against an upper specification is to assure that the drug product is not over-dosed for the sake of safety. The operating curves of the proposed procedure are compared with those of the USP test to illustrate the difference in acceptance probability against the mean and variance of the lot. C1 US FDA, CDER, Off Biostat, Div Biometr 6, Silver Spring, MD 20903 USA. RP Tsong, Y (reprint author), US FDA, CDER, Off Biostat, Div Biometr 6, Room 5232,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM tsong@cder.fda.gov NR 8 TC 9 Z9 9 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN-FEB PY 2007 VL 17 IS 1 BP 143 EP 157 DI 10.1080/10543400601001527 PG 15 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 117IJ UT WOS:000242866300014 PM 17219760 ER PT J AU Tsong, Y AF Tsong, Yi TI Special issue on active controlled clinical trials - Guest editor's note SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 US FDA, Div Biometr 6, Off Biostat Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM yi.tsong@fda.hhs.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 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 197 EP 199 DI 10.1080/10543400601177269 PG 3 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300001 PM 17365217 ER PT J AU Hung, HMJ Wang, SJ O'Neill, R AF Hung, H. M. James Wang, Sue-Jane O'Neill, Robert TI Issues with statistical risks for testing methods in noninferiority trial without a placebo arm SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE across-trial or unconditional type I error rate; active-controlled; fixed margin method; noninferiority margin; placebo-controlled; within-trial or conditional type I error rate; synthesis method ID NON-INFERIORITY TRIALS; ACTIVE-CONTROL TRIALS; CLINICAL-TRIALS; EQUIVALENCE TRIALS; PRACTICAL ISSUES; DESIGN; CRITERION; EFFICACY; MARGIN; CHOICE AB Noninferiority trials without a placebo arm often require an indirect statistical inference for assessing the effect of a test treatment relative to the placebo effect or relative to the effect of the selected active control treatment. The indirect inference involves the direct comparison of the test treatment with the active control from the noninferiority trial and the assessment, via some type of meta-analyses, of the effect of the active control relative to a placebo from historical studies. The traditional within-noninferiority-trial Type I error rate cannot ascertain the statistical risks associated with the indirect inference, though this error rate is of the primary consideration under the frequentist statistical framework. Another kind of Type I error rate, known as across-trial Type I error rate, needs to be considered in order that the statistical risks associated with the indirect inference can be controlled at a small level. Consideration of the two kinds of Type I error rates is also important for de. ning a noninferiority margin. For the indirect statistical inference, the practical utility of any method that controls only the across-trial Type I error rate at a fixed small level is limited. C1 US FDA, Div Biometr 1, OB OTS CDER, Off Biostat, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr 1, OB OTS CDER, Off Biostat, 10903 New Hampshire Ave,Bldg 22,Rm 4238,HFD-710,M, Silver Spring, MD 20993 USA. EM hsienming.hung@fda.hhs.gov NR 44 TC 17 Z9 18 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 201 EP 213 DI 10.1080/10543400601177343 PG 13 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300002 PM 17365218 ER PT J AU Koti, KM AF Koti, Kallappa M. TI Use of the Fieller-Hinkley distribution of the ratio of random variables in testing for noninferiority SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE bivariate normal integral; bootstrap percentile interval; rejection region ID BIOEQUIVALENCE TRIALS; CONFIDENCE-INTERVALS; NON-INFERIORITY; EQUIVALENCE AB We address the noninferiority assessment problem defined in terms of the ratio of population means in a parallel group design analysis of variance setting. The sample ratio as a point estimate of the corresponding population ratio has been considered. It has been shown that the Fieller-Hinkley distribution of the ratio of two correlated normally distributed random variables readily provide a technique for constructing confidence intervals comparable to the bootstrap percentile and Fieller's confidence intervals. A finite parameter space based level alpha test of an inferiority hypothesis formulated in terms of a fixed margin has been derived. We illustrate our approach using the forced vital capacity (FVC) data. We claim that it is easy to construct and straight forward to interpret our bootstrap equivalent confidence intervals that are used to assess noninferiority. We discuss appropriate methods for calculation of sample sizes. C1 US FDA, Div Biometr, Silver Spring, MD 20993 USA. RP Koti, KM (reprint author), US FDA, Div Biometr, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kallappa.koti@fda.hhs.gov NR 19 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 215 EP 228 DI 10.1080/10543400601177335 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300003 PM 17365219 ER PT J AU Koti, KM AF Koti, Kallappa M. TI New tests for null hypothesis of non unity ratio of proportions SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE active control; binary data; clinical trials; risk ratio; stratified analysis ID CLINICAL-TRIALS; NON-INFERIORITY; MCNEMARS TEST; SAMPLE-SIZE; EQUIVALENCE; DESIGN AB Testing for noninferiority and equivalence between an experimental therapy and a standard therapy in terms of the ratio of binomial proportions is considered. New tests based on the Fieller-Hinkley distribution of the ratio of random variables are proposed. Restricted maximum likelihood estimates of the null variances are used to derive the tests. Sample size determination is discussed. The proposed test procedure is extended to multiple tables. The tests are applied to numerical examples. C1 US FDA, Silver Spring, MD 20993 USA. RP Koti, KM (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kallappa.koti@fda.hhs.gov NR 23 TC 0 Z9 0 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 229 EP 245 DI 10.1080/10543400601177426 PG 17 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300004 PM 17365220 ER PT J AU Tsong, Y Zhang, J AF Tsong, Yi Zhang, Joanne TI Simultaneous test for superiority and noninferiority hypotheses in active-controlled clinical trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE assay sensitivity; noninferiority test; simultaneous test; superiority test ID NON-INFERIORITY; STATISTICAL-METHODS; PLACEBO; RATIO AB Two stage switching between testing for superiority (SUP) and noninferiority (NI) has been an important statistical issue in the design and analysis of the active-controlled clinical trials. Tsong and Zhang (2005) has shown that the Type I error rates do not change when switching between SUP and NI with the traditional generalized historical control (GHC) approach, however, they may change when switching with the cross-trial comparison (X-trial) approach. Tsong and Zhang (2005) further proposed a simultaneous test for both hypotheses to avoid the problem. The procedure was based on Fieller's confidence interval proposed by Hauschke et al. (1999). Since with the X-trial approach, using the simultaneous test, superiority is tested using all four treatment arms (current test and active control arms, active control and placebo arms in historical trials), the Type I error rate and power are expected to be somewhat different from the conventional superiority test (using the current test and active control arms only). Through a simulation study, we demonstrate that the Type I error rate and power between simultaneous test and the conventional superiority test are compatible. We also examine the impact of the assumption of equal variances of the current trial and the historical trial. C1 US FDA, Div Biometr 6, Off Biostat Off Translat Sci, CDER, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat Off Translat Sci, CDER, Room 5244,Bldtg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tong@cder.hhs.gov NR 16 TC 5 Z9 5 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 247 EP 257 DI 10.1080/10543400601177434 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300005 PM 17365221 ER PT J AU Ng, TH AF Ng, Tie-Hua TI Simultaneous testing of noninferiority and superiority increases the false discovery rate SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE active control; Bayesian; false discovery rate; multiplicity adjustment; noninferiority; simultaneous testing ID CLINICAL-TRIALS AB It is well recognized that multiplicity adjustment is not necessary in simultaneous testing for noninferiority and superiority. However, Ng (2003) argued that there will be more experimental treatments that are expected to have the same effect as the active control tested for superiority in simultaneous testing than would occur if only one null hypothesis is tested, thereby increasing erroneous claims of superiority. This leads to an increase in the false discovery rate for superiority. C1 US FDA, Rockville, MD 20852 USA. RP Ng, TH (reprint author), US FDA, 1401 Rockville Pike,200S,HFM-219, Rockville, MD 20852 USA. EM tiehua.ng@fda.hhs.gov NR 9 TC 5 Z9 5 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 259 EP 264 DI 10.1080/10543400601177459 PG 6 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300006 PM 17365222 ER PT J AU Tsong, Y Zhang, J Levenson, M AF Tsong, Yi Zhang, Joanne Levenson, Mark TI Choice of delta noninferiority margin and dependency of the noninferiority trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE dependency of two noninferiority tests; generalized historical control approach; non-inferiority margin AB For a two-arm active control clinical trial designed to test for noninferiority of the test treatment to the active control standard treatment, data of historical studies were often used. For example, with a cross-trial comparison approach (also called synthetic approach or lambda-margin approach), the trial is conducted to test the hypothesis that the mean difference or the ratio between the current test product and the active control is no larger than a certain portion of the mean difference or no smaller that a certain portion of the ratio of the active control and placebo obtained in the historical data when the positive response indicates treatment effective. For a generalized historical control approach (also known as confidence interval approach or delta-margin approach), the historical data is often used to determine a fixed value noninferiority margin delta for all trials involving the active control treatment. The regulatory agency usually requires that the clinical trials of two different test treatments need to be independent and in most regular cases, it also requires to have two independent positive trials of the same test treatment in order to provide confirmatory evidence of the efficacy of the test product. Because of the nature of information (historical data) shared in active-controlled trials, the independency assumption of the trials is not satisfied in general. The correlation between two noninferiority tests has been examined which showed that it is an increasing function of (1-lambda) when the response variable is normally distributed. In this article, we examine the relationship between the correlation of the two test statistics and the choice of the noninferiority margin, delta as well as the sample sizes and variances under the normality assumption. We showed that when delta is determined by the lower limit of the confidence interval of the adjusted effect size of the active control treatment (mu(C) - mu(P)) using data from historical studies, dependency of the two noninferiority tests can be very high. In order to control the correlation under 15%, the overall sample C1 US FDA, Div Biometr 6, Off Biostat, CDER,Off Translat Sci, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Div Biometr & Biomatr 6, Off Biostat Off Translat Sci, CDER, Room 5244,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@fda.hhs.gov NR 5 TC 10 Z9 10 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 279 EP 288 DI 10.1080/10543400601177384 PG 10 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300008 PM 17365224 ER PT J AU Tsong, Y Chen, WJ AF Tsong, Yi Chen, Wen-Jen TI Noninferiority testing beyond simple two-sample comparison SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article; Proceedings Paper CT Conference on Therapeutic Equivalence - Clinical Issues and Statistical Methodology in Noninferiority Trials CY DEC 12-13, 2003 CL Dusseldorf, GERMANY DE cross-trial comparison; generalized historical control; noninferiority test ID ACTIVE-CONTROL TRIALS; CONTROLLED CLINICAL-TRIALS; NON-INFERIORITY HYPOTHESES; STANDARD DEVIATIONS; STATISTICAL-METHODS; ARITHMETIC MEANS; EQUIVALENCE; PLACEBO; ISSUES; DESIGN AB In order to fulfill the requirement of a new drug application, a sponsor often need to conduct multiple clinical trials. Often these trials are of designs more complicated than a randomized two-sample single-factor study. For example, these trials could be designed with multiple centers, multiple factors, covariates, group sequential and/or adaptive scheme, etc. When an active standard treatment used as the control treatment in a two-arm clinical trial, the efficacy of the test treatment is often established by performing a noninferiority test through comparison of the test treatment and the active standard treatment. Typically, the noninferiority trials are designed with either a generalized historical control approach (i.e., noninferiority margin approach or delta-margin approach) or a cross-trial comparison approach (i.e., synthesis approach or lambda-margin approach). Many of the statistical properties of the approaches discussed in the literature were focused on testing in a simple two sample comparison form. We studied the limitations of the two approaches for the consideration of switching between superiority and noninferiority testing, feasibility to be applied with group sequential design, constancy assumption requirements, test dependency in multiple trials, analysis of homogeneity of efficacy among centers in a multi-center trial, data transformation and changing analysis method from the historical studies. Our evaluation shows that the cross-trial comparison approach is more restricted to simple two sample comparison with normal approximation test because of its poor properties with more complicated design and analysis. On the other hand, the generalized historical control comparison approach may have more flexible properties when the variability of the margin delta is indeed negligibly small. C1 US FDA, Div Biometr 6, Off Biostat Off Translat Sci, CDER, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat Off Translat Sci, CDER, Room 5244,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tong@fda.hhs.gov NR 43 TC 3 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 289 EP 308 DI 10.1080/10543400601177368 PG 20 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300009 PM 17365225 ER PT J AU Tsong, Y Shen, MY AF Tsong, Yi Shen, Meiyu TI An alternative approach to assess exchangeability of a test treatment and the standard treatment with normally distributed response SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE coverage percentage; equivalence test; exchangeability AB In order to assess the equivalence of two treatments, clinical trials are designed to test against the null hypothesis that the difference ( or ratio) of two means ( proportions) is either smaller than a pre-specified lower equivalence limit or larger than a pre-specified upper equivalence limit. For example, in generic drug evaluation, such approach is defined as average bioequivalence. However, average equivalence type test is often criticized as lack of the ability to assess the exchangeability of the two treatments. In this article, we restate the statistical hypotheses in the form of stochastic inequalities. The stochastic statement can then be generalized to de. ne the probability of exchangeability (i.e., coverage percentage) of the two treatments. The approach will be illustrated with a numeric example. C1 US FDA, Div Biometr 6, Off Biostat Off Translat Sci, CDER, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat Off Translat Sci, CDER, Room 5244,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@fda.hhs.gov NR 7 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 329 EP 338 DI 10.1080/10543400601177301 PG 10 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300011 PM 17365227 ER PT J AU Tsou, HH Hsiao, CF Chow, SC Yue, L Xu, YL Lee, SJ AF Tsou, Hsiao-Hui Hsiao, Chin-Fu Chow, Shein-Chung Yue, Lilly Xu, Yunling Lee, Shiowjen TI Mixed noninferiority margin and statistical tests in active controlled trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE active control trials; constancy condition; noninferiority margin; superiority margin ID ISSUES AB In an active controlled noninferiority trial without a placebo arm, one of the major considerations is the selection of the noninferiority margin. Although the ICH E10 guideline provides general principles for the selection of appropriate noninferiority margins, there are no established rules or gold standards for the selection of noninferiority margins in active control trials. Hung et al. (2003) proposed a margin selection based on relative risk. However, with relative risk, it is difficult to adjust for covariates. On the other hand, Chow and Shao (2006) proposed a method for selecting noninferiority margins based on treatment difference. The determination of noninferiority margin based on either a test for treatment difference or a test for relative risk would be critical. In this paper, we propose a method for noninferiority testing with the use of a mixed null hypothesis. The mixed null hypothesis consists of a margin based on treatment difference and a margin based on relative risk. Both noninferiority margins will simultaneously satisfy the principles as described in the ICH E10 guideline. Statistical tests for mixed noninferiority margin are also derived. An example concerning the efficacy of a test therapy to an active control on a clinical adverse event in the target patient population with cardiovascular disease is presented to illustrate the proposed method. Simulation studies were also conducted to assess the type I error rate and the power. C1 Natl Hlth Res Inst, Div Biostat & Bioinformat, Zhunan 350, Miaoli, Taiwan. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Natl Cheng Kung Univ, Dept Stat, Tainan 70101, Taiwan. US FDA, CDRH, Rockville, MD 20857 USA. RP Hsiao, CF (reprint author), Natl Hlth Res Inst, Div Biostat & Bioinformat, 35 Keyan Rd, Zhunan 350, Miaoli, Taiwan. EM chinfu@nhri.org.tw RI Tsou, Hsiao-Hui /E-3837-2010; Hsiao, Chin-Fu/E-3993-2010 OI Tsou, Hsiao-Hui /0000-0001-6773-4111; NR 6 TC 6 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 2 BP 339 EP 357 DI 10.1080/10543400601183861 PG 19 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 146NW UT WOS:000244942300012 PM 17365228 ER PT J AU Tsai, CA Chen, DT Chen, JJ Balch, CM Thompson, JF Soong, SJ AF Tsai, Chen-An Chen, Dung-Tsa Chen, James J. Balch, Charles M. Thompson, John F. Soong, Seng-Jaw TI An integrated tree-based classification approach to prognostic grouping with application to localized melanoma patients SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE cross-validation; disease staging system; integrated tree-based classification; modified log-rank test ID AMERICAN JOINT COMMITTEE; STRUCTURED SURVIVAL ANALYSIS; CANCER STAGING SYSTEM; CUTANEOUS MELANOMA; REGRESSION TREES; STRATIFICATION; CARCINOMA; THICKNESS; FEATURES; MODELS AB We propose an integrated tree-based approach for prognostic grouping of localized melanoma patients. This approach incorporates the survival tree model with the agglomerative hierarchical clustering to group terminal subgroups with similar prognoses together. The Brier score is used to evaluate the goodness of fit and the k-fold cross-validation test is used to evaluate the reproducibility of the scheme for prediction. The proposed approach is applied to an American Joint Committee on Cancer (AJCC) localized melanoma data set and compared with the current AJCC staging system. This approach performs more efficiently than the standard tree methods and has made improvement over the current AJCC melanoma staging system. C1 Univ Alabama, Biostat & Bioinformat Unit, Birmingham, AL 35294 USA. Royal Prince Alfred Hosp, Sydney Canc Ctr, Sydney Melanoma Unit, Camperdown, NSW 2050, Australia. Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21205 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Div Biostat, Tampa, FL USA. Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan. RP Soong, SJ (reprint author), Univ Alabama, Biostat & Bioinformat Unit, NP 2540,1802 6th Ave S, Birmingham, AL 35294 USA. EM sjsoong@uab.edu OI Tsai, Chen-An/0000-0002-7490-4331 FU NCI NIH HHS [5P30 CA13148, P50 CA83591, 1P50 CA89019]; NIAID NIH HHS [5P30 AI27767] NR 27 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 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 3 BP 445 EP 460 DI 10.1080/10543400701199585 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 171GX UT WOS:000246725000007 PM 17479393 ER PT J AU Zaslavsky, BG AF Zaslavsky, Boris G. TI Calculation of tolerance limits and sample size determination for clinical trials with dichotomous outcomes SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE binomial distribution; clinical trial; confidence probability; dichotomous outcome; negative-binomial distribution; tolerance limit ID ASSESSING INDIVIDUAL BIOEQUIVALENCE; INTERVALS; DISTRIBUTIONS AB This research provides an algorithm for calculating uniformly most accurate tolerance intervals in clinical trials with dichotomous outcomes. The link between confidence intervals for proportions and tolerance intervals for numbers of outcomes is established. Tolerance intervals and sample size estimates for clinical trials may be calculated using StatXact. C1 US FDA, Rockville, MD 20852 USA. RP Zaslavsky, BG (reprint author), US FDA, 1401 Rockville Pike HFM-219, Rockville, MD 20852 USA. EM Boris.Zaslavsky@FDA.HHS.gov NR 21 TC 9 Z9 9 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 3 BP 481 EP 491 DI 10.1080/10543400701199601 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 171GX UT WOS:000246725000009 PM 17479395 ER PT J AU Li, L Hui, S Pennello, G Desta, Z Todd, S Nguyen, A Flockhart, D AF Li, Lang Hui, Sin Pennello, Gene Desta, Zeruesenay Todd, Skaar Nguyen, Anne Flockhart, David TI Estimating a positive false discovery rate for variable selection in pharmacogenetic studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE cross-validation; false discovery rate; multiple-comparisons; pharmacogenetics; variable selection ID MULTIPLE COMPARISONS; MODEL SELECTION; TAMOXIFEN; IDENTIFICATION; REPLACEMENT; CHOLESTEROL; METABOLISM; THERAPY; ENZYMES; DENSITY AB Selecting predictors to optimize the outcome prediction is an important statistical method. However, it usually ignores the false positives in the selected predictors. In this paper, we develop a positive false discovery rate (pFDR) estimate for a conventional step-wise forward variable selection procedure. We propose two views of a variable selection process, an overall and an individual test. An interesting feature of the overall test is that its power of selecting non-null predictors increases with the proportion of non-null predictors among all candidate predictors. Data analysis is illustrated with a pharmacogenetics example. C1 Indiana Univ, Dept Med, Div Biostat, Indianapolis, IN 46202 USA. US FDA, CDRH, Div Biostat, Rockville, MD 20857 USA. RP Li, L (reprint author), Indiana Univ, Dept Med, Div Biostat, Indianapolis, IN 46202 USA. EM lali@iupui.edu FU NIGMS NIH HHS [U-01 GM61373, R01- GM56898, R01 GM74217] NR 22 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 5 BP 883 EP 902 DI 10.1080/10543400701514056 PG 20 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 211BN UT WOS:000249499400008 PM 17885872 ER PT J AU Chen, DT Chen, JJ Cheng, G Lin, SH Soong, SJ AF Chen, Dung-Tsa Chen, James J. Cheng, Gary Lin, Sue-Hwa Soong, Seng-Jaw TI A two-stage binomial test approach of gene identification in oligonlicleotide arrays SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE gene selection; positive predictivity; sensitivity; two-stage binomial test; weighted probe rank ID OLIGONUCLEOTIDE ARRAYS; MICROARRAY ANALYSIS; ENDOTHELIAL-CELLS; EXPRESSION; PROLACTIN; PROSTATE; CANCER AB Most statistical approaches summarize the probe-level expression data into gene-level measures, which then are used for downstream statistical analyses. However, there are some limitations in using the gene level data for analysis, such as nonhomogeneous probe effects and the interaction effect (e.g., alternative splicing). In this paper, we consider a two-stage binomial test with a weighted probe rank approach to determine differentially expressed genes. Using a series of benchmark gene array datasets, we show the two-stage binomial test approach yielded a higher positive predictivity and a higher sensitivity than the conventional RMA, GCRMA, Dchip, and ANOVA approaches. In data application, the two-stage binomial test identified a subset of genes strongly related to cell proliferation in the prolactin study, and a subset of genes associated with lymph node metastasis in the breast cancer dataset. In addition, by exploring the proportion of probes with expression changes and the probe expression plot, the two-stage binomial test helped detect an alternative splicing form of the prolactin gene in the prolactin study. In the breast cancer dataset, the approach also identified one potential alternative splicing gene. C1 Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Div Biostat, Tampa, FL USA. US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. China Med Univ, Ctr Biostat, Taichung, Taiwan. Univ Alabama, Dept Mech Engn, Birmingham, AL USA. Univ Texas, Dept Mol Pathol, Houston, TX USA. Univ Alabama, Ctr Comprehens Canc, Biostat & Bioinformat Unit, Birmingham, AL 35294 USA. RP Chen, DT (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Div Biostat, Magnolia Dr, Tampa, FL USA. EM Dung-Tsa.Chen@moffitt.org FU NCI NIH HHS [5P30 CA-13148, 2P30 CA076292-09, 1U54 CA100949, 1P50 CA89019]; NIAID NIH HHS [P30 AI 27767]; NIDCD NIH HHS [N01-DC-5-0008] NR 27 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 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 5 BP 903 EP 918 DI 10.1080/10543400701514064 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 211BN UT WOS:000249499400009 PM 17885873 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI Discussion of the "white paper of the phrma working group on adaptive dose-ranging designs" SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material ID CLINICAL-TRIALS C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. EM suejane.wang@fda.hhs.gov NR 8 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 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 6 BP 1015 EP 1020 DI 10.1080/10543400701643897 PG 6 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 238AX UT WOS:000251420800007 PM 18027212 ER PT J AU Hung, HMJ Wang, SJ O'Neill, R AF Hung, H. M. James Wang, Sue-Jane O'Neill, Robert TI Statistical considerations for testing multiple endpoints in group sequential or adaptive clinical trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE adaptive design; closed testing; flexible design; group sequential; primary endpoint; secondary endpoint ID DESIGN AB Many clinical trials are designed with a fixed sample size or total number of events to detect a postulated size of treatment effect on a primary efficacy endpoint. When the trial is completed and the primary efficacy endpoint achieves statistical significance, formal statistical testing of other clinically important secondary endpoints often follows in order for the statistically and clinically significant results of these endpoints to be included in the label of the test pharmaceutical product. In conventional fixed designs without any interim analysis or trial extension, these endpoints are often tested in a pre-specified hierarchical order, following the closed testing principle. This testing strategy ensures a strong control of the overall type I error. However, when trials are conducted using a group-sequential design with interim analyses or can be extended using an adaptive design with an increase of sample size or total number of events, this conventional hierarchical testing strategy may violate the closure principle and the overall type I error rate may not be controlled in the strong sense. C1 FDA, OB OTS CDER, Div Biometr 1, Silver Spring, MD 20993 USA. FDA, OTS CDER, Off Biostat, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), FDA, OB OTS CDER, Div Biometr 1, 10903 New Hampshire Ave,Bldg 22,Room 4238,HFD-710, Silver Spring, MD 20993 USA. EM hsienming.hung@fda.hhs.gov NR 11 TC 23 Z9 23 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2007 VL 17 IS 6 BP 1201 EP 1210 DI 10.1080/10543400701645405 PG 10 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 238AX UT WOS:000251420800021 PM 18027226 ER PT J AU Ling, AE Bash, MC Lynn, F Lister, NA Zhu, P Garland, SM Fairley, CK Tabrizi, SN AF Ling, A. E. Bash, M. C. Lynn, F. Lister, N. A. Zhu, P. Garland, S. M. Fairley, C. K. Tabrizi, S. N. TI Evaluation of PorB variable region typing of Neisseria gonorrhoeae using PCR-ELISA in samples collected from men who have sex with men SO JOURNAL OF CLINICAL LABORATORY ANALYSIS LA English DT Article DE porB; PCR; ELISA; MSM; N. gonorrhoeae; typing ID REAL-TIME PCR; CHLAMYDIA-TRACHOMATIS; OPA GENE; INFECTION; IDENTIFICATION; EPIDEMIOLOGY; VERIFICATION; RESISTANCE; DIVERSITY; SPECIMENS AB A polymerase chain reaction (PCR)-based enzyme-linked immunosorbent assay (ELISA) methodology was developed to characterize Neisseria gonorrhoeae porB gene variable regions (VR); the methodology was evaluated in comparison to porB VR typing by checkerboard hybridization. Clinical noncultured samples from 35 men who have sex with men (MSM), positive by nucleic amplification assays for N. gonorrhoeae, were typed using a panel of 40 oligonucleotide probes to porB VRs and compared to checkerboard hybridization. Complete concordance was observed between the two methods at PIB VRs 1, 3, and 7. At the more degenerate VRs 5 and 6, PCR ELISA resulted in obtaining more typeable VRs than checkerboard hybridization due to single nucleotide mismatches. By PCR ELISA, two predominant PIB porB types were identified in 58% of the samples and the remaining 16 samples had one of six other porB types. Both PCR ELISA and checkerboard hybridization methods of porB VR typing allowed characterization of N. gonorrhoeae from noncultured clinical samples including throat and rectal swabs and discriminated N. gonorrhoeae from N. meningitides present in some of the samples. PCR ELISA is a rapid, relatively inexpensive and alternative molecular typing method for N. gonorrhoeae, suitable for use in conjunction with molecular diagnostic tests. (c) 2007 Wiley-Liss, Inc. C1 Royal Womens Hosp, Dept Microbiol & Infect Dis, Melbourne, Vic, Australia. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Melbourne Sexual Hlth Ctr, Melbourne, Vic, Australia. Creatv MicroTech Inc, Potomac, MD USA. Univ Melbourne, Dept Obstet & Gynaecol, Melbourne, Vic, Australia. Univ Melbourne, Sch Populat Hlth, Melbourne, Vic, Australia. RP Tabrizi, SN (reprint author), Royal Womens Hosp, 132 Grattan St, Carlton, Vic 3053, Australia. EM sepehr.Tabrizi@rch.org.au OI Christopher, Fairley/0000-0001-9081-1664 NR 33 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-8013 J9 J CLIN LAB ANAL JI J. Clin. Lab. Anal. PY 2007 VL 21 IS 4 BP 237 EP 243 DI 10.1002/jcla.20173 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 194QV UT WOS:000248359800006 PM 17621363 ER PT J AU Hinderling, PH Karara, AH Tao, B Pawula, M Wilding, I Lu, M AF Hinderling, Peter H. Karara, Adel H. Tao, Ben Pawula, Maria Wilding, Ian Lu, Ming TI Systemic availability of the active metabolite hydroxy-fasudil after administration of fasudil to different sites of the human gastrointestinal tract SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE fasudil; hydroxyl fasudil; antianginal drug; gastrointestinal tract; Rho kinase; site of drug absorption; remote-controlled capsule ID HUMAN SMALL-INTESTINE; DRUG ABSORPTION; KINASE; TRANSPORTERS; EXPRESSION; INHIBITOR; DELIVERY; COLON AB This study evaluated the gastrointestinal absorption of fasudil, a novel Rho kinase inhibitor for the treatment of stable angina, at different sites using remote-controlled capsules and assessed the feasibility of developing an extended-release formulation. Ten healthy male volunteers were enrolled, and 8 subjects completed this single-dose, open-label, randomized, 5-way crossover study. Forty milligrams of fasudil HCl was administered as solution to the distal ileum and ascending colon, as powder to the ascending colon, and orally as an immediate-release tablet and solution. All treatments were well-tolerated and no serious adverse events were observed. The mean systemic availabilities of M3 relative to the oral solution were 1.04 (distal ileum, solution), 1.14 (ascending colon, solution), 1.27 (ascending colon, powder) and 1.04 (oral tablet), indicating similar systemic availability of M3 after administration of fasudil HCl to different gastrointestinal sites. The results suggest that development of a once-a-day extended-release formulation for fasudil HCl should be readily achievable. C1 Berlex Pharmaceut, Clin Pharmacol Dept, Montville, NJ 07045 USA. US FDA, Ctr Drug Evaluat, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. Sankyo Pharma Dev, Edison, NJ USA. Huntingdon Life Sci, Huntingdon, England. RP Lu, M (reprint author), Berlex Pharmaceut, Clin Pharmacol Dept, POB 1000, Montville, NJ 07045 USA. NR 18 TC 12 Z9 13 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2007 VL 47 IS 1 BP 19 EP 25 DI 10.1177/0091270006293767 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 122LC UT WOS:000243227500003 PM 17192498 ER PT J AU Ramchandani, RP Wang, YN Booth, BP Ibrahim, A Johnson, JR Rahman, A Mehta, M Innocenti, F Ratain, MJ Gobburu, JVS AF Ramchandani, Roshni P. Wang, Yaning Booth, Brian P. Ibrahim, Amna Johnson, John R. Rahman, Atiqur Mehta, Mehul Innocenti, Federico Ratain, Mark J. Gobburu, Jogarao V. S. TI The role of SN-38 exposure, UGT1A1*28 polymorphism, and baseline bilirubin level in predicting severe irinotecan toxicity SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE irinotecan; SN-38; neutropenia; UDP-glucuronosyltransferase; genetic polymorphisms ID UDP-GLUCURONOSYLTRANSFERASE; COLORECTAL-CANCER; ACTIVE METABOLITE; GENETIC-VARIANTS; UGT1A1; GLUCURONIDATION; PHARMACOKINETICS; CPT-11; 1A1; GENOTYPE AB Irinotecan, an anticancer drug, is associated with severe and potentially fatal diarrhea and neutropenia. The objective of this analysis was to evaluate the role of SN-38 exposure, the active metabolite of irinotecan, UGT1A1 genotypes, and baseline bilirubin on the maximum decrease (nadir) in absolute neutrophil counts following irinotecan. This analysis extended the work of a previous study that examined the effect of UGT1A1 genotypes on the incidence of severe neutropenia in 86 advanced cancer patients following irinotecan treatment. Regression analysis showed that the absolute neutrophil count nadir depended on SN-38 exposure (AUG) and UGT1A1*28 homozygous 7/7 genotype. An increased SN-38 AUG and the 7/7 genotype were significantly associated with a lower absolute neutrophil count nadir (R-2 = .49). An alternate model suggested that higher baseline bilirubin and the 7/7 genotype were also significantly associated with a lower absolute neutrophil count nadir, although with a lower coefficient of determination (R-2 = .31). Based on these findings and other reports, the irinotecan label was modified to indicate the role of UGT1A1*28 polymorphism in the metabolism of irinotecan and the associated increased risk of severe neutropenia. The label modifications also included recommendations for lower starting doses of irinotecan in patients homozygous for the UGT1A1*28 (7/7) polymorphism. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. Univ Chicago, Dept Med, Comm Clin Pharmacol & Pharmacogenom, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. RP Ramchandani, RP (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, WO21,Rm 3667,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM roshni.ramchandani@fda.hhs.gov NR 20 TC 42 Z9 46 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2007 VL 47 IS 1 BP 78 EP 86 DI 10.1177/0091270006295060 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 122LC UT WOS:000243227500010 PM 17192505 ER PT J AU Booth, BP Rahman, A Dagher, R Griebel, D Lennon, S Fuller, D Sahajwalla, C Mehta, M Gobburu, JVS AF Booth, Brian P. Rahman, Atiqur Dagher, Ramzi Griebel, Donna Lennon, Shari Fuller, David Sahajwalla, Chandra Mehta, Mehul Gobburu, Jogarao V. S. TI Population pharmacokinetic-based dosing of intravenous busulfan in pediatric patients SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE busulfan; pharmacokinetics; dosing; modeling; pediatrics ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HIGH-DOSE BUSULFAN; HEMATOLOGIC MALIGNANCIES; ORAL BUSULFAN; CHILDREN; ADJUSTMENT; RECIPIENTS; LEUKEMIA; DISEASE AB The objective of this study was to characterize the pharmacokinetics (PK) of intravenous busulfan in pediatric patients and provide dosing recommendations. Twenty-four pediatric patients were treated with intravenous busulfan, 1.0 or 0.8 mg/kg for ages <= 4 years or > 4 years, respectively, 4 times a day for 4 days. Dense PK sampling was performed. Body weight, age, gender, and body surface area were explored for effects on PK, and Monte Carlo simulations were performed to assess different dosing regimens. The PK of intravenous busulfan was described by a 1-compartment model with clearance of 4.04 L/h/20 kg and volume of distribution of 12.8 L/20 kg. Simulations indicated that the mg/kg and mg/m(2) regimens were similar and achieved the desired target exposure in approximately 60% of patients. This model suggests that patients <= 12 kg should be dosed at 1.1 mg/kg and those > 12 kg dosed at 0.8 mg/kg. Therapeutic drug monitoring and dose adjustment will further improve therapeutic targeting. C1 US FDA, Off Clin Pharmacol, Div Clin Pharmacol, Silver Spring, MD USA. US FDA, Off Clin Pharmacol, Div Clin Pharmacol, Silver Spring, MD USA. US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Div Drug Oncol Prod, Rockville, MD 20857 USA. Genzyme Europe Res, Cambridge, England. RP Booth, BP (reprint author), US FDA, Off Clin Pharmacol, Div Clin Pharmacol, 5,10903 New Hamphire Ave,Bldg 21,Room 3668, Silver Spring, MD USA. NR 35 TC 38 Z9 38 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2007 VL 47 IS 1 BP 101 EP 111 DI 10.1177/0091270006295789 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 122LC UT WOS:000243227500013 PM 17192508 ER PT J AU Kadegowda, AKG Teter, BB Sampugna, J Delmonte, P Piperova, LS Erdman, RA AF Kadegowda, A. K. G. Teter, B. B. Sampugna, J. Delmonte, P. Piperova, L. S. Erdman, R. A. TI Trans-7-octadecenoic acid decreased milk fat and altered CLA composition in milk of lactating mice SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Dairy-Science-Association/Poultry-Science-Association-Asociacio n-Mexicana-de-Produccion-Animal/American-Society-of-Animal-Science CY JUL 08, 2007 CL San Antonio, TX SP Amer Diary Sci Assoc, Poultry Sci Assoc, Asociac Mexicana Prod Anim, Amer Soc Anim Sci DE trans fatty acids; CLA; milk fat C1 [Kadegowda, A. K. G.; Teter, B. B.; Sampugna, J.; Piperova, L. S.; Erdman, R. A.] Univ Maryland, College Pk, MD 20742 USA. [Delmonte, P.] Food & Drug Adm, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2007 VL 90 SU 1 BP 179 EP 180 PG 2 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 213UP UT WOS:000249692900555 ER PT J AU RodriLuez, CP Patazca, E Schlesser, JE AF RodriLuez, C. P. Patazca, E. Schlesser, J. E. TI Effects of High Pressure Processing on the reduction of Listeria monocytogenes in the manufacture of soft cheeses SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Dairy-Science-Association/Poultry-Science-Association-Asociacio n-Mexicana-de-Produccion-Animal/American-Society-of-Animal-Science CY JUL 08, 2007 CL San Antonio, TX SP Amer Diary Sci Assoc, Poultry Sci Assoc, Asociac Mexicana Prod Anim, Amer Soc Anim Sci DE Listeria monocytogenes; soft cheese; high pressure processing C1 [RodriLuez, C. P.; Patazca, E.] Natl Ctr Food Safety & Technol, IIT, Summit Argo, IL USA. [Schlesser, J. E.] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2007 VL 90 SU 1 BP 270 EP 270 PG 1 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 213UP UT WOS:000249692900839 ER PT J AU Chan, PC Xia, QS Fu, PP AF Chan, Po-Chuen Xia, Qingsu Fu, Peter P. TI Ginkgo biloba leave extract: Biological, medicinal, and toxicological effects SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Gingko biloba leave extract; biological and toxicological effects; ginkgolidc; quercetin ID HERB-DRUG INTERACTIONS; INDUCED NEURONAL DEATH; GLOBAL BRAIN ISCHEMIA; EGB 761 PROTECTS; DNA-DAMAGE; INDUCED NEPHROTOXICITY; INDUCED TOXICITY; NITRIC-OXIDE; IN-VITRO; CYTOCHROME-P450 PHENOTYPES AB Ginkgo biloba leave extract is among the most widely sold herbal dietary supplements in the United States. Its purported biological effects include: scavenging free radical; lowering oxidative stress; reducing neural damages, reducing platelets aggregation; anti-inflammation; anti-tumor activities; and anti-aging. Clinically, it has been prescribed to treat CNS disorders such as Alzheimer's disease and cognitive deficits. It exerts allergy and changes in bleeding time. While its mutagenicity or carcinogenic activity has not been reported, its components, quercetin, kaempferol and rutin have been shown to be genotoxic. There are no standards or guidelines regulating the constituent components of Ginkgo biloba leave extract nor are exposure limits imposed. Safety evaluation of Ginkgo biloba leave extract is being conducted by the U.S. National Toxicology Program. C1 [Chan, Po-Chuen] NIEHS, Res Triangle Pk, NC 27709 USA. [Xia, Qingsu; Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chan, PC (reprint author), NIEHS, Res Triangle Pk, Res Triangle Pk, NC 27709 USA. EM chanp@niehs.nih.gov NR 161 TC 114 Z9 124 U1 3 U2 49 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2007 VL 25 IS 3 BP 211 EP 244 DI 10.1080/10590500701569414 PG 34 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 264DD UT WOS:000253264800002 PM 17763047 ER PT J AU Chen, JJ Chen, YJ Cheng, KF AF Chen, James J. Chen, Yi-Ju Cheng, Kuang Fu TI Statistics for risk assessment of chemical carcinogens SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE benchmark dose; Carcinogenicity Bioassay; chemical mixture; cumulative risk; hierarchical model; point of departure; Probabilistic risk assessment; reference dose ID DOSE-RESPONSE ASSESSMENT; ADVERSE EFFECT LEVELS; DEVELOPMENTAL TOXICITY; ANIMAL BIOASSAYS; POTENCY DATABASE; CHRONOLOGICAL SUPPLEMENT; PROBABILISTIC FRAMEWORK; MODEL; EXPOSURES; TIME AB Risk assessment is a scientific process of evaluation of potential health risks of chemical exposures to humans from available information. It involves analysis of the relationship between exposure and health related outcomes to derive an allowable exposure level. Because of lack of human exposure data, the major source of information for studying potential health effects of chemicals on humans is generally obtained from animal dose response experiments. Animal data are often evaluated in two aspects via statistical analysis: qualitative testing and quantitative estimation. The qualitative testing is to determine if the chemical causes an adverse health effect, i.e., if there is a statistically significant difference between treated and control animals. Quantitative estimation involves fitting a dose-response model to derive an allowable exposure level for humans. This paper reviews statistical principles and procedures for qualitative and quantitative approaches to human risk assessment. C1 [Chen, James J.] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR USA. [Chen, James J.; Cheng, Kuang Fu] China Med Univ, Sch Publ Hlth, Ctr Biostat, Taichung, Taiwan. [Chen, Yi-Ju] Natl Chung Cheng Univ, Dept Math, Chiayi, Taiwan. RP Chen, JJ (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov NR 114 TC 2 Z9 2 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2007 VL 25 IS 4 BP 281 EP 312 DI 10.1080/10590500701703989 PG 32 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 264DF UT WOS:000253265000001 PM 18000784 ER PT J AU Kinde, H Mikolon, A Rodriguez-Lainz, A Adams, C Walker, RL Cernek-Hoskins, S Treviso, S Ginsberg, M Rast, R Harris, B Payeur, JB Waterman, S Ardans, A AF Kinde, Hailu Mikolon, Andrea Rodriguez-Lainz, Alfonso Adams, Cathy Walker, Richard L. Cernek-Hoskins, Shannon Treviso, Scarlett Ginsberg, Michele Rast, Robert Harris, Beth Payeur, Janet B. Waterman, Steve Ardans, Alex TI Recovery of Salmonella, Listeria monocytogenes, and Mycobacterium bovis from cheese entering the United States through a noncommercial land port of entry SO JOURNAL OF FOOD PROTECTION LA English DT Article AB A joint multiagency project was initiated in response to a Salmonella outbreak in San Diego County, California, in 2004. Samples of cheese were collected during four I-day operations at the San Ysidro port of entry, along the United States-Mexico border. Surveyed participants were persons crossing the border as pedestrians or in vehicles who had a minimum of 2.27 kg of cheese, which may suggest a potential diversion to illegal marketing. In addition, data were collected about the cheese to identify risk factors for cheese contamination. Two hundred four cheese samples were submitted to the California Animal Health and Food Safety Laboratory System-San Bernardino Branch and analyzed for potential food pathogens. Ninety-four percent (190 of 203) of the samples tested positive for alkaline phosphatase. Salmonella was detected from 13% (27 of 204) of the samples comprising I I serogroups and 28 serotypes. Pulsed-field gel electrophoresis DNA fingerprinting analysis, performed following standardized methods, determined that an isolate obtained from this study had an indistinguishable pattern from a recent Salmonella enterica serovar Typhimurium var. Copenhagen epidemic in the San Diego County that was linked to 14 illnesses. Listeria spp. were detected from 4% (8 of 204) of the samples, and of these, half were identified as L. monocytogenes. Escherichia coli O157:H7 was not detected from any of the samples. Mycobacterium bovis was detected from one panela-style cheese sample. Nine additional samples yielded Mycobacterium spp. C1 Calif Anim Hlth & Food Safety Lab Syst, CAHFS, San Bernardino Branch, San Bernardino, CA 92408 USA. Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. Calif Dept Food & Agr, Anim Hlth & Food Safety Serv Div, Sacramento, CA 95814 USA. Calif Dept Hlth Serv, Calif Off Binatl Border Hlth, San Diego, CA 92138 USA. San Diego Cty Publ Hlth Lab, San Diego, CA 92110 USA. CAHFS Davis, Davis, CA 95616 USA. Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. Cty San Diego Hlth & Human Serv, Community Epidemiol Div, San Diego, CA 92186 USA. US FDA, San Diego, CA 92154 USA. USDA, Natl Vet Serv Labs, Anim & Plant Hlth Inspect Serv, Ames, IA 50010 USA. Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, San Diego, CA 92138 USA. RP Kinde, H (reprint author), Calif Anim Hlth & Food Safety Lab Syst, CAHFS, San Bernardino Branch, 105 W Cent Ave, San Bernardino, CA 92408 USA. EM hkinde@ucdavis.edu NR 16 TC 22 Z9 22 U1 0 U2 4 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2007 VL 70 IS 1 BP 47 EP 52 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 127HI UT WOS:000243575700008 PM 17265859 ER PT J AU Shieh, YC Khudyakov, YE Xia, G Ganova-Raeva, LM Khambaty, FM Woods, JW Veazey, JE Motes, ML Glatzer, MB Bialek, SR Fiore, AE AF Shieh, Y. C. Khudyakov, Y. E. Xia, G. Ganova-Raeva, L. M. Khambaty, F. M. Woods, J. W. Veazey, J. E. Motes, M. L. Glatzer, M. B. Bialek, S. R. Fiore, A. E. TI Molecular confirmation of oysters as the vector for hepatitis A in a 2005 multistate outbreak SO JOURNAL OF FOOD PROTECTION LA English DT Article ID NORWALK-LIKE VIRUS; UNITED-STATES; GREEN ONIONS; RAW OYSTERS; EPIDEMIOLOGY; CONSUMPTION; INFECTION; SEQUENCE; ILLNESS; STRAINS AB Numerous hepatitis A outbreaks were linked to the consumption of raw molluscan shellfish in the United States between 1960 and 1989. However, there had been no major molluscan shellfish-associated hepatitis A outbreaks reported in the United States for more than a decade (1989 to 2004). Beginning in late August 2005, at least 10 clusters of hepatitis A illnesses, totaling 39 persons, occurred in four states among restaurant patrons who ate oysters. Epidemiologic data indicated that oysters were the source of the outbreak. Traceback information showed that the implicated oysters were harvested from specific Gulf Coast areas. A voluntary recall of oysters was initiated in September. Hepatitis A virus (HAV) was detected in multiple 25-g portions in one of two recalled samples, indicating that as many as 1 of every 15 oysters from this source was contaminated. Comparing 315 nucleotides within the HAV VP1-2B region, 100% homology was found among four amplicons recovered from a total of six independent experiments of the implicated oysters, and an identical HAV sequence was detected in sera from all 28 patient serum specimens tested. Ten percent heterogeneity over 315 nucleotides (31 variants) was observed between the outbreak strain (subgenotype 1A) and an HM-175 strain (subgenotype 113) used in the laboratory where the oysters were processed. To our knowledge, this investigation is the first in the United States to identify an HAV-identical strain in persons with hepatitis A as well as in the food that was implicated as the source of their infections. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA 30333 USA. US FDA, Off Regulatory Affairs, Baton Rouge, LA 70809 USA. US FDA, Off Regulatory Affairs, Mobile, AL 36606 USA. US FDA, Off Regulatory Affairs, Tallahassee, FL 32301 USA. RP Shieh, YC (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. EM carol.shieh@fda.hhs.gov NR 25 TC 43 Z9 46 U1 0 U2 2 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2007 VL 70 IS 1 BP 145 EP 150 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 127HI UT WOS:000243575700022 PM 17265873 ER PT J AU Ponomarev, ED Shriver, LP Maresz, K Pedras-Vasconcelos, J Verthelyi, D Dittel, BN AF Ponomarev, Eugene D. Shriver, Leah P. Maresz, Katarzyna Pedras-Vasconcelos, Joao Verthelyi, Daniela Dittel, Bonnie N. TI GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; CENTRAL-NERVOUS-SYSTEM; FACTOR-DEFICIENT MICE; MULTIPLE-SCLEROSIS; IFN-GAMMA; CNS; INFLAMMATION; PROLIFERATION; IMMUNE; MACROPHAGES AB Multiple sclerosis (MS) is a CNS autoimmune disease believed to be triggered by T cells secreting Th1-specific proinflammatory cytokines, such as GM-CSF. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), Th1 but not Th2 cells have been shown to induce disease; however, to date, no single encephalitogenic T cell-derived cytokine has been shown to be required for EAE onset. Because GM-CSF-deficient mice have been shown to be resistant to EAE following immunization with myelin self-Ag, we investigated the cellular source of the required GM-CSF and found that GM-CSF production by encephalitogenic T cells, but not CNS resident or other peripheral cells, was required for EAE induction. Furthermore, we showed that microglial cell activation, but not peripheral macrophage activation, was a GM-CSF-dependent process. Activation of microglial cells by the injection of LPS abrogated the GM-CSF requirement for EAE induction, suggesting that microglial cell activation is required for EAE onset. These data also demonstrate that GM-CSF is a critical Th1 cell-derived cytokine required for the initiation of CNS inflammation associated with EAE, and likely MS. C1 Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53201 USA. Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA. US FDA, Immunol Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Dittel, BN (reprint author), Blood Ctr SE Wisconsin Inc, Blood Res Inst, POB 2178, Milwaukee, WI 53201 USA. EM bonnie.dittel@bcw.edu FU NINDS NIH HHS [R01 NS46662-01A1] NR 36 TC 154 Z9 156 U1 1 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2007 VL 178 IS 1 BP 39 EP 48 PG 10 WC Immunology SC Immunology GA 120XU UT WOS:000243120900005 PM 17182538 ER PT J AU Benfeldt, E Hansen, SH Volund, A Menne, T Shah, VP AF Benfeldt, Eva Hansen, Steen H. Volund, Aage Menne, Torkil Shah, Vinod P. TI Bioequivalence of topical formulations in humans: Evaluation by dermal microdialysis sampling and the dermatopharmacokinetic method SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID IN-VIVO; STRATUM-CORNEUM; PENETRATION; BIOAVAILABILITY; QUANTIFICATION; SKIN AB The aim of this study was to evaluate the relationship between dermal microdialysis (DMD) sampling and the dermatopharmacokinetic method when employed simultaneously for bioequivalence (BE) investigations of topical formulations. Topical lidocaine cream and ointment (both 5%) was investigated in eight healthy human volunteers (four male, four female). On one forearm, four microdialysis probes in two penetration areas sampled for 5 hours, and on the other arm, tape stripping was performed 30 and 120 minutes after product application. Lidocaine content in samples was analyzed by HPLC-mass spectrometry. The two methods were in agreement showing 3- to 5-fold higher liclocaine penetration from cream formulation than from ointment. A rank-order correlation between the two methods was demonstrated for lidocaine contents in microdialysates versus tape strip at 120 minutes, significant for the ointment formulation and for both formulations analyzed together. Analysis of variance demonstrated reproducible lidocaine concentrations in microdialysates with an intrasubject variability of 19% between probes and 20% between the two penetration areas. Thus, intersubject variability accounted for 61% of the variance. DMD sampling proved effective and variability analyses demonstrated the feasibility of BE studies in as little as 18 subjects. C1 Univ Copenhagen, Gentofte Hosp, Dept Dermatol, Hellerup, Denmark. Danish Univ Pharmaceut Sci, Dept Pharmaceut & Analyt Chem, Copenhagen, Denmark. Novo Nordisk AS, Dept Biostat, DK-2880 Bagsvaerd, Denmark. US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Benfeldt, E (reprint author), Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, D 40,Bispebjerg Bakke, DK-2400 Copenhagen NV, Denmark. EM benfeldt@post5.tele.dk RI Honore Hansen, Steen/A-5179-2011 NR 27 TC 44 Z9 50 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2007 VL 127 IS 1 BP 170 EP 178 DI 10.1038/sj.jid.5700495 PG 9 WC Dermatology SC Dermatology GA 121YF UT WOS:000243192200024 PM 16874309 ER PT J AU Pogribny, IP Tryndyak, VP Muskhelishvili, L Rusyn, I Ross, SA AF Pogribny, Igor P. Tryndyak, Volodymyr P. Muskhelishvili, Levan Rusyn, Ivan Ross, Sharon A. TI Methyl deficiency, alterations in global histone modifications, and carcinogenesis SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition, and Cancer CY JUL 13-14, 2006 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, Calif Walnut Commiss, Campbell Soup Co, Cranberry Inst, Hormel Inst, IP 6 Int Inc, Kyushu Univ, Japan Grad Sch Agr, Natl Fisheries Inst, United Soybean Board ID C57BL/6J MALE-MICE; DNA-DAMAGE; PRENEOPLASTIC LESIONS; LYSINE METHYLATION; CHOLINE-DEFICIENT; GENE-EXPRESSION; HUMAN-DISEASE; HUMAN CANCERS; H3 LYSINE-9; RAT-LIVER AB The methyl-deficient model of endogenous hepatocarcinogenesis in rodents is unique in that dietary omission rather than the addition of chemical carcinogens leads to tumor formation. Thus, the biochemical and molecular events predisposing to cancer in this model result from chronic metabolic stress and provide an ideal model system to study progressive alterations that occur during carcinogenesis. Moreover, epigenetic alterations imposed by this diet are believed to be 1 of the main mechanisms responsible for malignant transformation of rat liver cells. In this study we examined the changes in global histone modification patterns in liver during hepatocarcinogenesis induced by methyl deficiency. Feeding animals the methyl-deficient diet (MDD) led to progressive loss of histone H4 lysine 20 trimethylation (H4K20me3), H3 lysine 9 trimethylation (H3K9me3), and histone H3 lysine 9 H3K9ac) and histone H4 lysine 16(H4K16ac) acetylation. A considerable decrease of H4K20me3 and H3K9ac was also detected in liver tumors induced by MDD. In contrast, liver tumors displayed an increase in H3K9me3 and H4K16ac. To determine the possible mechanism of alterations of histone modifications, we analyzed the expression of histone-modifying enzymes in liver during hepatocarcinogenesis. The expression of Suv4-2Oh2 and RIZ1 histone methyltransferases (HMTs) steadily decreased along with the development of liver tumors and reached its lowest level in tumor tissue, whereas the expression of Suv39-h1 HMT and histone acetyltransferase 1(HAT1) substantially increased in tumors. These results illustrate the complexity and importance of histone modification changes in the etiology of hepatocarcinogenesis induced by MDD. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. NCI, Rockville, MD 20852 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI Rusyn, Ivan/S-2426-2016 NR 68 TC 60 Z9 63 U1 0 U2 7 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2007 VL 137 IS 1 SU S BP 216S EP 222S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 123XQ UT WOS:000243330800011 PM 17182829 ER PT J AU Chen, Q Lee, JH Zhang, LQ Sun, A Krishna, MC Espey, MG Pooput, C Kirk, K Choyke, P Buettner, GR Shacter, E Levine, M AF Chen, Qi Lee, Je-Hyuk Zhang, Liqun Sun, Andrew Krishna, Murali C. Espey, Michael G. Pooput, Chaya Kirk, Kenneth Choyke, Peter Buettner, Garry R. Shacter, Emily Levine, Mark TI Pharmacologic ascorbate concentrations selectively kill cancer cells: Ascorbic acid as a prodrug for ascorbate radical or H2O2 delivery to tissues SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 13-14, 2006 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, Calif Walnut Commiss, Campbell Soup Co, Cranberry Inst, Hormel Inst, IP 6 Int Inc, Kyushu Univ, Japan Grad Sch Agr, Natl Fisheries Inst, United Soybean Board C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Med, Iowa City, IA USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2007 VL 137 IS 1 SU S BP 293S EP 293S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 123XQ UT WOS:000243330800079 ER PT J AU Ali, SF Imam, S Itzhak, Y AF Ali, Syed F. Imam, Syed Itzhak, Yossef TI Role of nitric oxide and peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Coral Gables, FL 33124 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2007 VL 103 SU 1 BP 38P EP 38P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148AI UT WOS:000245046500107 ER PT J AU Hsueh, HM Tsai, CA Chen, JJ AF Hsueh, Huey-Miin Tsai, Chen-An Chen, James J. TI Incorporating the number of true null hypotheses to improve power in multiple testing: application to gene microarray data SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION LA English DT Article DE complete null hypothesis; false discovery rate (FDR); family-wise error rate (FWE); number of true null hypotheses; p-values ID FALSE DISCOVERY RATE AB Testing for significance with gene expression data from DNA microarray experiments involves simultaneous comparisons of hundreds or thousands of genes. In common exploratory microarray experiments, most genes are not expected to be differentially expressed. The family-wise error (FWE) rate and false discovery rate (FDR) are two common approaches used to account for multiple hypothesis tests to identify differentially expressed genes. When the number of hypotheses is very large and some null hypotheses are expected to be true, the power of an FWE or FDR procedure can be improved if the number of null hypotheses is known. The mean of differences ( MD) of ranked p-values has been proposed to estimate the number of true null hypotheses under the independence model. This article proposes to incorporate the MD estimate into an FWE or FDR approach for gene identification. Simulation results show that the procedure appears to control the FWE and FDR well at the FWE = 0.05 and FDR = 0.05 significant levels; it exceeds the nominal level for FDR = 0.01 when the null hypotheses are highly correlated, a correlation of 0.941. The proposed approach is applied to a public colon tumor data set for illustration. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Acad Sinica, Inst Stat Sci, Taipei, Taiwan. Natl Chengchi Univ, Dept Stat, Taipei, Taiwan. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov OI Tsai, Chen-An/0000-0002-7490-4331; HSUEH, HUEY-MIIN/0000-0003-0536-9440 NR 11 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0094-9655 J9 J STAT COMPUT SIM JI J. Stat. Comput. Simul. PY 2007 VL 77 IS 9 BP 757 EP 767 DI 10.1080/10629360600648651 PG 11 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 221LL UT WOS:000250228800003 ER PT J AU Luecke, RH Pearce, BA Wosilait, WD Slikker, W Young, JF AF Luecke, Richard H. Pearce, Bruce A. Wosilait, Walter D. Slikker, William, Jr. Young, John F. TI Postnatal growth considerations for PBPK modeling SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID STRAINS CPB-S; ORGAN WEIGHTS; PHARMACOKINETIC MODELS; METHOTREXATE PHARMACOKINETICS; ALLOMETRIC ANALYSIS; BODY-WEIGHT; CHEMICALS; DYNAMICS; CHILDREN; INFANTS AB A physiologically based pharmacokinetic (PBPK) model and Windows-based program (called PostNatal) was developed that focuses on postnatal growth, from birth through adulthood, using appropriate growth curves for each species and gender. Postnatal growth algorithms relating organs/tissues weights with total body weight for male and female humans, dogs, rats, and mice are an integral part of the software and are utilized to assign the appropriate weight and blood flow for each of 22 organs/tissues for each simulation. Upper limits of body weight were chosen that reflect the available data used to define the algorithms; above these limits a set percent body weight was assigned to all organs/tissues. C1 Univ Missouri, Dept Chem Engn, Columbia, MO 65211 USA. US FDA, Natl Ctr Toxicol Res, Off Informat Technol, DHHS, Jefferson, AR 72079 USA. Univ Missouri, Dept Pharmacol, Columbia, MO 65211 USA. US FDA, Natl Ctr Toxicol Res, Off Director, DHHS, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, DHHS, Jefferson, AR 72079 USA. RP Luecke, RH (reprint author), Univ Missouri, Dept Chem Engn, Columbia, MO 65211 USA. EM LueckeR@missouri.edu NR 30 TC 9 Z9 9 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2007 VL 70 IS 11-12 BP 1027 EP 1037 DI 10.1080/15287390601172056 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 169GG UT WOS:000246580100021 PM 17497414 ER PT J AU Chen, X Yu, HN Shen, SR Yin, JJ AF Chen, Xun Yu, Haining Shen, Shengrong Yin, Junjie TI Role of Zn2+ in epigallocatechin gallate affecting the growth of PC-3 cells SO JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY LA English DT Article DE EGCG; Zn2+; PC-3 cells; green tea ID PROSTATE-CANCER CELLS; IN-VITRO; ZINC; CATECHINS; STABILITY; DISEASE; HEALTH; CU2+ AB Green tea has chemo-preventive effects to human carcinoma including prostate cancer. Epigallocatechin gallate (EGCG) is the major active component in green tea. Zn2+ is indispensable to our health, and plays an important role in the normal function and pathology of the prostate gland, and might be a good marker for diagnosing prostate cancer. Effects of Zn2+, EGCG and their interactions on the growth of androgen-insensitive prostate cancer cell (PC-3) were investigated in the present paper. The results show that Zn2+ and EGCG inhibited the growth of PC-3 cells in a time- and dose-dependent manner, but effects of interactions of EGCG with Zn2+ were extremely dependent on their concentrations and added orders. Inhibitory effects of Zn2+ were significantly decreased in the presence of EGCG on PC-3 cell growth. Therefore, we hypothesize that complexation of EGCG with Zn2+ might be responsible for the observed decrease of the bioactivities of Zn2+ against PC-3 cells. (C) 2007 Elsevier GrnbH. All rights reserved. C1 Zhejiang Univ, Dept Food Sci & Nutr, Coll Biosyst Engn & Food Sci, Hangzhou 310029, Peoples R China. Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310032, Peoples R China. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Shen, SR (reprint author), Zhejiang Univ, Dept Food Sci & Nutr, Coll Biosyst Engn & Food Sci, Hangzhou 310029, Peoples R China. EM shrshen@zju.edu.cn RI Yin, Jun Jie /E-5619-2014 NR 30 TC 12 Z9 15 U1 1 U2 6 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0946-672X J9 J TRACE ELEM MED BIO JI J. Trace Elem. Med. Biol. PY 2007 VL 21 IS 2 BP 125 EP 131 DI 10.1016/j.jtemb.2006.12.007 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 181IY UT WOS:000247431600008 PM 17499153 ER PT J AU Crim, RL Audet, SA Feldman, SA Mostowski, HS Beeler, JA AF Crim, Roberta L. Audet, Susette A. Feldman, Steven A. Mostowski, Howard S. Beeler, Judy A. TI Identification of linear heparin-binding peptides derived from human respiratory syncytial virus fusion glycoprotein that inhibit infectivity SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-SURFACE PROTEOGLYCANS; NEWCASTLE-DISEASE VIRUS; HERPES-SIMPLEX-VIRUS; REPLICATION IN-VITRO; ATTACHMENT PROTEIN; HOST-CELLS; MOLECULAR POLYMORPHISM; PROTEOLYTIC ACTIVATION; SULFATE PROTEOGLYCAN; ANTITHROMBIN-III AB It has been shown previously that the fusion glycoprotein of human respiratory syncytial virus (RSV-F) interacts with cellular heparan sulfate. Synthetic overlapping peptides derived from the F-protein sequence of RSV subtype A (strain A2) were tested for their ability to bind heparin using heparin-agarose affinity chromatography (HAAC). This evaluation identified 15 peptides representing eight linear heparin-binding domains (HBDs) located within F-1 and F-2 and spanning the protease cleavage activation site. All peptides bound to Vero and A549 cells, and binding was inhibited by soluble heparins and diminished by either enzymatic treatment to remove cell surface glycosaminoglycans or by treatment with sodium chlorate to decrease cellular sulfation. RSV-F HBD peptides were less likely to bind to glycosaminoglycan-deficient CHO-745 cells than parental CHO-K1 cells that express these molecules. Three RSV-F HBD peptides (F16, F26, and F55) inhibited virus infectivity; two of these peptides (F16 and F55) inhibited binding of virus to Vero cells, while the third (F26) did not. These studies provided evidence that two of the linear HBDs mapped by peptides F16 and F55 may mediate one of the first steps in the attachment of virus to cells while the third, F26, inhibited infectivity at a postattachment step, suggesting that interactions with cell surface glycosaminoglycans may play a role in infectivity of some RSV strains. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Cell & Gene Therapy, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Beeler, JA (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29A,Rm 3b05,HFM-463,1401 Rockville Pike, Rockville, MD 20852 USA. EM judy.beeler@fda.hhs.gov NR 65 TC 25 Z9 25 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2007 VL 81 IS 1 BP 261 EP 271 DI 10.1128/JVI.01226-06 PG 11 WC Virology SC Virology GA 118RE UT WOS:000242958600024 PM 17050595 ER PT J AU Bradley, JS Guidos, R Baragona, S Bartlett, JG Rubinstein, E Zhanel, GG Tino, MD Pompliano, DL Tally, F Tipirneni, P Tillotson, GS Powers, JH Tillotson, GS AF Bradley, John S. Guidos, Robert Baragona, Steve Bartlett, John G. Rubinstein, Ethan Zhanel, George G. Tino, Michael D. Pompliano, David L. Tally, Frank Tipirneni, Praveen Tillotson, Glenn S. Powers, John H. Tillotson, Glenn S. TI Anti-infective research and development - problems, challenges, and solutions SO LANCET INFECTIOUS DISEASES LA English DT Article ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; VENTILATOR-ASSOCIATED PNEUMONIA; SURROGATE END-POINTS; INFECTIOUS-DISEASES; CLINICAL-TRIALS; THERAPY; DURATION; ADULTS; DRUGS AB in communities and hospitals around the world, the number of patients with antibiotic-resistant infections continues to climb. Our current armamentarium of drugs are gradually becoming ineffective and a new pipeline of robust compounds is needed urgently. In this Forum, we present several perspectives on the problems and pitfalls of drug discovery and development, the challenges faced by the practising physician, and potential solutions to protecting and safeguarding the public health of future generations. C1 Antimicrobial Availabil Task Force Infect Dis Soc, Alexandria, VA USA. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. Univ Manitoba, Dept Med, Winnipeg, MB, Canada. GlaxoSmithKline Inc, Infect Dis Ctr Excellence Drug Discovery, Collegeville, PA USA. Cubist Pharmaceut, Lexington, MA USA. Replidyne Inc, Sci Affairs, Louisville, CO USA. George Washington Univ, Sch Med, Washington, DC 20052 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. US FDA, Antimicrobial Drug Dev & Resistance Initiat, Rockville, MD 20857 USA. RP Bradley, JS (reprint author), Antimicrobial Availabil Task Force Infect Dis Soc, Alexandria, VA USA. EM jbradley@chsd.org; erubins@yahoo.com; mike69md@yahoo.com; David.L.Pompliano@gsk.com; praveen.tipirneni@cubist.com; gtillotson@Replidyne.com; powersjohn@niaid.nih.gov; gtillotson@Replidyne.com NR 28 TC 55 Z9 55 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JAN PY 2007 VL 7 IS 1 BP 68 EP 78 DI 10.1016/S1473-3099(06)70689-2 PG 11 WC Infectious Diseases SC Infectious Diseases GA 123DO UT WOS:000243276700032 PM 17182346 ER PT J AU Fahey, M Tata, D Waynant, R Mitra, K AF Fahey, Molly Tata, Darrell Waynant, Ronald Mitra, Kunal TI Non-thermal dental ablation using ultra-short pulsed, near infrared laser SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 11-15, 2007 CL Grapevine, TX SP Amer Soc Laser Med & Surg C1 Florida Inst Technol, Melbourne, FL 32901 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2007 SU 19 MA 159 BP 49 EP 49 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 154XF UT WOS:000245540600144 ER PT J AU Gessain, A Dezzutti, CS Cowan, EP Lal, RB AF Gessain, Antoine Dezzutti, Charlene S. Cowan, Elliot P. Lal, Renu B. BE Baron, EJ Jorgensen, JH Landry, ML Pfaller, MA TI Human T-Cell Lymphotropic Virus Types 1 and 2 SO MANUAL OF CLINICAL MICROBIOLOGY, 9TH ED LA English DT Article; Book Chapter ID POLYMERASE-CHAIN-REACTION; HTLV TYPE-I; WESTERN-BLOT PATTERNS; CENTRAL-AFRICA; PROVIRAL LOAD; NEUROLOGICAL DISEASE; VIRAL-INFECTIONS; SEROLOGIC ASSAYS; LEUKEMIA; I/II C1 [Gessain, Antoine] Inst Pasteur, EEMI Dept, EPVO Unit, F-75015 Paris, France. [Dezzutti, Charlene S.] Ctr Dis Control & Prevent, Branch Lab, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. [Cowan, Elliot P.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Lal, Renu B.] Ctr Dis Control & Prevent, Epidemiol Branch, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. RP Gessain, A (reprint author), Inst Pasteur, EEMI Dept, EPVO Unit, F-75015 Paris, France. NR 61 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-371-0 PY 2007 BP 1330 EP 1339 PG 10 WC Microbiology SC Microbiology GA BOY07 UT WOS:000278004500085 ER PT S AU Tata, DB Fahey, M Mitra, K Anders, J Waynant, RW AF Tata, Darrell B. Fahey, Molly Mitra, Kunal Anders, Juanita Waynant, Ronald W. BE Hamblin, MR Waynant, RW Anders, J TI Near-IR induced suppression of metabolic activity in aggressive cancers - art. no. 64280E SO Mechanisms for Low-Light Therapy II SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Mechanisms for Low-High Therapy II CY JAN 21, 2007 CL San Jose, CA ID LASER IRRADIATION; CELLS; RESPONSES; OXIDANTS; LIGHT AB The role of low light intensity in suppressing metabolic activity of transformed cell lines was investigated through the applications of a 1,552nm wavelength pulsed picosecond laser. Human malignant glioblastoma, human leukemia HL-60, and the NIH 3T3 cell lines were used. The cells were grown in 96 well plates and exposed in their respective growth culture media with 10% (v/v) fetal bovine serum under various fluence exposure conditions ranging from 0.115 - 100 J/cm(2). All cell lines were exposed at a constant average intensity value of 0.115 W/cm(2); 25 kHz repetition rate with 1.6 micro-joule per pulse; pulse duration = 2.93 picosecond. The human malignant glioblastoma and the HL-60 cell lines exhibited a monotonic decline in metabolic activity (down 50 - 60%) relative to their respective sham exposed control counterparts between the fluence values of 0.115 J/cm(2) to 10 J/cm(2). The NIH 3T3 cells exhibited a maximum suppression of metabolic activity at the fluence value of 50 J/cm2. Metabolic activity was measured through the colorimetric NITS metabolic assay. Interestingly, for all cell lines the metabolic activity was found to return back to the sham exposed control levels as the fluence of exposure was increased up to 100J/cm(2). C1 US FDA, Rockville, MD 20857 USA. RP Tata, DB (reprint author), US FDA, Rockville, MD 20857 USA. RI Mitra, Kunal/C-6560-2016 OI Mitra, Kunal/0000-0002-7277-4908 NR 12 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6541-2 J9 P SOC PHOTO-OPT INS PY 2007 VL 6428 BP E4280 EP E4280 AR 64280E DI 10.1117/12.699120 PG 12 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BGF72 UT WOS:000246491900010 ER PT S AU Gavrielides, MA Petrick, N Myers, KJ AF Gavrielides, Marios A. Petrick, Nicholas Myers, Kyle J. BE Giger, ML Karssemeijer, N TI Automated alignment of serial thoracic scans using home structure descriptors - art. no. 65143C SO Medical Imaging 2007: Computer-Aided Diagnosis, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm AB In this manuscript we present an automated algorithm for the alignment of thoracic scans using descriptors of bone structures. Bone structures were utilized because they are expected to be less susceptible to sources of errors such as patient positioning and breath hold. The algorithm employed the positioning of ribs relative to the spinal cord along with a description of the scapula. The spinal cord centroid was detected by extracting local maxima of the distance transform followed by point tracing along consecutive slices. Ribs were segmented using adaptive thresholding followed by the watershed algorithm to detach ribs from the vertebra, and by imposing requirements of rib proximity to the lung border. The angles formed between the spinal cord centroid and segmented rib centroids were used to describe rib positioning. Additionally, the length of the scapula was extracted in each slice. A cost function incorporating the difference of features from rib positioning and scapula length between two slices was derived and used to match slices. The method was evaluated on a set of 12 pairs of full and partial CT scans acquired on the same day. Evaluation was based on whether the slices showing a nodule at its maximum diameter in each scan were matched. Full-to-partial and partial-tofull alignment were performed. Results showed that the proposed metric matched nodule slices within an average distance of 1.08 and 1.17 slices from the target for full-to-partial and partial-to-full alignment respectively. These preliminary results are encouraging for using this method as a first step in an overall process of temporally analyzing CT lung nodules. C1 US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Gavrielides, MA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6632-7 J9 P SOC PHOTO-OPT INS PY 2007 VL 6514 BP C5143 EP C5143 AR 65143C DI 10.1117/12.711506 PN 1-2 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI25 UT WOS:000247298700117 ER PT S AU Paquerault, S Wade, DI Petrick, N Myers, KJ Samuelson, FW AF Paquerault, Sophie Wade, Darin I. Petrick, Nicholas Myers, Kyle J. Samuelson, Frank W. BE Jiang, Y Sahiner, B TI Observer evaluation of computer-aided detection: Second reader versus concurrent reader scenario - art. no. 65151N SO Medical Imaging 2007: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE computer-aided detection; CAD second reader; CAD concurrent reader; multiple readers multiple cases (MRMC) study; free-response receiver operating characteristic; bootstrap ID BREAST-CANCER DETECTION; SCREENING MAMMOGRAPHY; DETECTION SYSTEM; PERFORMANCE; DIAGNOSIS; PROGRAM AB We are comparing the performance of computer-aided detection (CAD) used as a second reader to concurrent-use CAD. We have designed a multi-reader multi-case (MRMC) observer study using fixed-size mammographic background images with fixed intensity Gaussian signals added in two experiments. A CAD system was developed to automatically detect these signals. The two experiments utilized signals of different contrast levels to assess the impact of CAD when the standalone CAD sensitivity was superior (low contrast) or equivalent (high contrast) to the average reader in the study. Seven readers participated in the study and were asked to review 100 images, identify signal locations, and rate each on a 100-point scale. A rating of 50 was used as a cutpoint and provided a binary classification of each candidate. Readers read the case set using CAD in both the second-reader and concurrent-reader scenarios. Results from the different signal intensities and reading paradigms were analyzed using the area under the Free-response Receiver Operating Characteristics curves. Sensitivity and the average number of FPs/image were also determined. The results showed that CAD, either used as a second reader or as a concurrent reader, can increase reader sensitivity but with an increase in FPs. The study demonstrated that readers may benefit from concurrent CAD when CAD standalone performance outperforms average reader sensitivity. However, this trend was not observed when CAD performance was equivalent to the sensitivity of the average reader. C1 US FDA, CDRH Lab Assessment Med Imaging Syst, NIBIB, Rockville, MD 20857 USA. RP Paquerault, S (reprint author), US FDA, CDRH Lab Assessment Med Imaging Syst, NIBIB, Rockville, MD 20857 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6633-4 J9 P SOC PHOTO-OPT INS PY 2007 VL 6515 BP N5151 EP N5151 AR 65151N DI 10.1117/12.707778 PG 8 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ28 UT WOS:000247398600054 ER PT S AU Park, S Badano, A Callas, BD Myers, KJ AF Park, Subok Badano, Aldo Callas, Brandon D. Myers, Kyle J. BE Jiang, Y Sahiner, B TI A contrast-sensitive channelized-Hotelling observer to predict human performance in a detection task using lumpy backgrounds and Gaussian signals - art. no. 65150V SO Medical Imaging 2007: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE anthropomorphic model observer; human contrast sensitivity; channelized-Hotelling observer; lumpy backgrounds ID MODEL AB Previously, a non-prewhitening matched filter (NPWMF) incorporating a model for the contrast sensitivity of the human visual system was introduced for modeling human performance in detection tasks with different viewing angles and white-noise backgrounds by Badano et al. But NPWMF observers do not perform well detection tasks involving complex backgrounds since they do not account for random backgrounds. A channelized-Hotelling observer (CHO) using difference-of-Gaussians (DOG) channels has been shown to track human performance well 14 in detection tasks using lumpy backgrounds. 2 In this work, a CHO with DOG channels, incorporating the model of the human contrast sensitivity, was developed similarly. We call this new observer a contrast-sensitive CHO (CS-CHO). The Barten model was the basis of our human contrast sensitivity model. A scalar was multiplied to the Barten model and varied to control the thresholding effect of the contrast sensitivity on luminance-valued images and hence the performance-prediction ability of the CS-CHO. The performance of the CS-CHO was compared to the average human performance from the psychophysical study by Park et al., where the task was to detect a known Gaussian signal in non-Gaussian distributed lumpy backgrounds. Six different signal-intensity values were used in this study. We chose the free parameter of our model to match the mean human performance in the detection experiment at the strongest signal intensity. Then we compared the model to the human at five different signal-intensity values in order to see if the performance of the CS-CHO matched human performance. Our results indicate that the CS-CHO with the chosen scalar for the contrast sensitivity predicts human performance closely as a function of signal intensity. C1 US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20850 USA. RP Park, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20850 USA. OI badano, aldo/0000-0003-3712-6670 NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6633-4 J9 P SOC PHOTO-OPT INS PY 2007 VL 6515 BP V5150 EP V5150 AR 65150V DI 10.1117/12.708582 PG 8 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ28 UT WOS:000247398600028 ER PT S AU Liang, H Park, S Gallas, BD Badano, A AF Liang, Hongye Park, Subok Gallas, Brandon D. Badano, Aldo BE Jiang, Y Sahiner, B TI Effect of slow display on stack-mode reading of volumetric image datasets using an anthropomorphic observer - art. no. 65150W SO Medical Imaging 2007: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm ID NOISE AB Active-matrix liquid crystal displays (LCDs) are becoming widely used in medical imaging applications. With the increasing volume of CT images to be interpreted per day, the ability of showing a fast sequence of images in stack mode is preferable for a medical display. Slow temporal response of LCD display can compromise the image quality/fidelity when the images are browsed in a fast sequence. In this paper, we report on the effect of the LCD response time at different image browsing speeds based on the performance of a contrast-sensitive channelized-Hotelling observer. A correlated stack of simulated cluster lumpy background images with a signal present in some of the images was used. The effect of different browsing speeds is calculated with LCD temporal response measurements established in our previous work. The image set is then analyzed by the model observer, which has been shown to predict human detection performance in non-Gaussian lumpy backgrounds. This allows us to quantify the effect of slow temporal response of medical liquid crystal displays on the performance of the anthropomorphic observer. Slow temporal response of the display device greatly affects the lesion contrast and observer performance. This methodology, after validation with human observers, could be used to set limits for the rendering speed of large volumetric image datasets (from CT, MR, or tomosynthesis) read in stack-mode. C1 US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Liang, H (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6633-4 J9 P SOC PHOTO-OPT INS PY 2007 VL 6515 BP W5150 EP W5150 AR 65150W DI 10.1117/12.708993 PG 8 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ28 UT WOS:000247398600029 ER PT S AU Banh, DPT Kyprianou, IS Paquerault, S Myers, KJ AF Banh, Diem Phuc T. Kyprianou, Iacovos S. Paquerault, Sophie Myers, Kyle J. BE Pluim, JPW Reinhardt, JM TI Morphology-based three-dimensional segmentation of coronary artery tree from CTA scans - art. no. 65122I SO Medical Imaging 2007: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE coronary; 3D segmentation; cardiac CT scans; heart modeling AB We developed an algorithm based on a rule-based threshold framework to segment the coronary arteries from angiographic computed tomography (CTA) data. Computerized segmentation of the coronary arteries is a challenging gprocedure due to the presence of diverse anatomical structures surrounding the heart on cardiac CTA data. The proposed algorithm incorporates various levels of image processing and organ information including region, connectivity and morphology operations. It consists of three successive stages. The first stage involves the extraction of the three-dimensional scaffold of the heart envelope. This stage is semiautomatic requiring a reader to review the CTA scans and manually select points along the heart envelope in slices. These points are further processed using a surface spline-fitting technique to automatically generate the heart envelope. The second stage consists of segmenting the left heart chambers and coronary arteries using grayscale threshold, size and connectivity criteria. This is followed by applying morphology operations to further detach the left and right coronary arteries from the aorta. In the final stage, the 3D vessel tree is reconstructed and labeled using an Isolated Connected Threshold technique. The algorithm was developed and tested on a patient coronary artery CTA that was graciously shared by the Department of Radiology of the Massachusetts General Hospital. The test showed that our method constantly segmented the vessels above 79% of the maximum gray-level and automatically extracted 55 of the 58 coronary segments that can be seen on the CTA scan by a reader. These results are an encouraging step toward our objective of generating high resolution models of the male and female heart that will be subsequently used as phantoms for medical imaging system optimization studies. C1 US FDA, NIBIB, Lab Assessment Med Imaging Syst, CDRH, Rockville, MD 20857 USA. RP Banh, DPT (reprint author), US FDA, NIBIB, Lab Assessment Med Imaging Syst, CDRH, HFZ-140,12720 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6630-3 J9 P SOC PHOTO-OPT INS PY 2007 VL 6512 BP I5122 EP I5122 AR 65122I DI 10.1117/12.710122 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGE24 UT WOS:000246288500087 ER PT S AU Saha, A Liang, HY Badano, A AF Saha, Anindita Liang, Hongye Badano, Aldo BE Horii, SC Andriole, KP TI Characterization of mobile display systems for use in medical imaging - art. no. 651610 SO Medical Imaging 2007: PACS and Imaging Informatics SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm ID PERFORMANCE AB We compare the image quality characteristics of state-of-the-art mobile display systems based on different types of liquid crystal and organic light-emitting materials with respect to luminance and color, viewing angle, resolution, temporal response, and reflectance. The results for a reflective liquid crystal display suggest that the changes in angular contrast and color shifts are more severe than for other LCDs, particularly for medical LCDs, where no color or grayscale inversion is present within the entire hemisphere of viewing directions. A prototype light-emitting device showed a wide viewing angle and large small-spot contrast. Display reflectance and resolution were affected by the additional touch-screen coatings. The methodology developed provides a framework for the comparison of alternative technologies for display of diagnostic images in small portable devices. C1 US FDA, CDRH, Rockville, MD 20857 USA. RP Saha, A (reprint author), US FDA, CDRH, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6634-1 J9 P SOC PHOTO-OPT INS PY 2007 VL 6516 BP 51610 EP 51610 AR 651610 DI 10.1117/12.709002 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BGJ19 UT WOS:000247396000035 ER PT S AU Saha, A Liang, HY Badano, A Kelley, EF AF Saha, Anindita Liang, Hongye Badano, Aldo Kelley, Edward F. BE Horii, SC Andriole, KP TI Accurate color measurement methods for medical displays - art. no. 651612 SO Medical Imaging 2007: PACS and Imaging Informatics SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm ID LIQUID-CRYSTAL DISPLAYS; VIEWING-ANGLE; PERFORMANCE AB We report on the characterization of two novel probes for Measuring display color without contamination from other screen areas or off-normal emissions. The probes are characterized with a scanning slit method and a 0 moving laser and LED arrangement. The tails of the scans indicate the spread in signal due to light from 0 0 areas outside the intended measuring spot. A dual-laser setup sugests that color purity of the reading can be maintained up to a few tens of millimeters outside of the measurement spot, and a dual-LED setup shows the effects of secondary light emissions in the readings. The first design, color probe A, is then used to quantify display color, maximum color difference, luminance uniformity, graylevel tracking, and angular color shifts of medical liquid crystal displays and mobile displays. C1 US FDA, CDRH, Rockville, MD 20857 USA. RP Saha, A (reprint author), US FDA, CDRH, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6634-1 J9 P SOC PHOTO-OPT INS PY 2007 VL 6516 BP 51612 EP 51612 AR 651612 DI 10.1117/12.708998 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BGJ19 UT WOS:000247396000037 ER PT S AU Badal, A Kyprianou, I Badano, A Sempau, J Myers, KJ AF Badal, Andreu Kyprianou, Iacovos Badano, Aldo Sempau, Josep Myers, Kyle J. BE Hsieh, J Flynn, MJ TI Monte Carlo package for simulating radiographic images of realistic anthropomorphic phantoms described.Fby triangle meshes SO Medical Imaging 2007: Physics of Medical Imaging, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE Monte Carlo simulation; PENELOPE; NCAT; angiography; computer-aided design; computer graphics ID PHOTON TRANSPORT; PENELOPE; CODE AB X-ray imaging system optimization increases the benefit-to-cost ratio by reducing the radiation dose to the patient while maximizing image quality. We present a new simulation tool for the generation of realistic medical x-ray images for assessment and optimization of complete imaging systems. The Monte Carlo code simulates radiation transport physics using the subroutine package PENELOPE, which accurately simulates the transport of electrons and photons within the typical medical imaging energy range. The new code implements a novel object-oriented geometry package that allows simulations with homogeneous objects of arbitrary shapes described by triangle meshes. The flexibility of this code, which uses the industry standard PLY input-file format, allows the use of detailed anatomical models developed using computer-aided design tools applied to segmented CT and MRI data. The use of triangle meshes highly simplifies the ray-tracing algorithm without reducing the generality of the code, since most surface models can be tessellated into triangles while retaining their geometric details. Our algorithm incorporates an octree spatial data structure to sort the triangles and accelerate the simulation, reaching execution speeds comparable to the original quadric geometry model of PENELOPE. Coronary angiograms were simulated using a tessellated version of the NURBS-based Cardiac-Torso (NCAT) phantom: The phantom models 330 objects, comprised in total of 5 million triangles. The dose received by each organ and the contribution of the different scattering processes to the final image were studied in detail. C1 US FDA, CDRH NIBIB, Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP Badal, A (reprint author), US FDA, CDRH NIBIB, Lab Assessment Med Imaging Syst, 12720 Twinbrook Parkway, Rockville, MD 20852 USA. RI Sempau, Josep/J-7834-2013 OI Sempau, Josep/0000-0002-2754-7685 NR 26 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6628-0 J9 P SOC PHOTO-OPT INS PY 2007 VL 6510 BP U339 EP U350 DI 10.1117/12.707934 PN 1-3 PG 12 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI21 UT WOS:000247292100034 ER PT S AU Badano, A Kyprianou, IS Tang, KH Saha, A AF Badano, Aldo Kyprianou, Iacovos S. Tang, Katherine H. Saha, Anindita BE Hsieh, J Flynn, MJ TI Validation of simulated point response of columnar phosphor screens SO Medical Imaging 2007: Physics of Medical Imaging, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm AB Typical methods to measure the resolution properties of x-ray detectors use slit or edge devices. However, complete models of imaging systems for system optimization require knowledge of the point-response function of the detector. In this paper, we report on the experimental methods developed for the validation of the point-response function of an indirect columnar CsI:T1 detector predicted by Monte Carlo using MANTIS. We describe simulation results that replicate experimental resolution measurements using edge and pinhole devices. The experimental setup consists of a high-resolution CCD camera with a 1-to-1 fiber optic faceplate that allows measurements for different scintillation screens. The results of these experiments and simulations constitute a resource for the development and validation of the columnar models of phosphor screens proposed as part of previous work with MANTIS. We compare experimental high-resolution pinhole responses of two different CsI(T1) screens to predictions from MANTIS. The simulated response matches reasonably well the measurements at normal and off-normal x-ray incidence angle when a realistic pinhole is used in the simulation geometry. Our results will be combined with results on Swank factors determined from Monte Carlo pulse-height spectra to provide a comprehensive validation of the phosphor models, therefore allowing their use for in silico system optimization. C1 CDRH FDA, Rockville, MD 20857 USA. RP Badano, A (reprint author), CDRH FDA, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 5 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6628-0 J9 P SOC PHOTO-OPT INS PY 2007 VL 6510 BP U334 EP U338 DI 10.1117/12.709686 PN 1-3 PG 5 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI21 UT WOS:000247292100033 ER PT S AU Freed, M Kupinski, MA Furenlid, LR Barrett, HH AF Freed, Melanie Kupinski, Matthew A. Furenlid, Lars R. Barrett, Harrison H. BE Hsieh, J Flynn, MJ TI A prototype instrument for adaptive SPECT imaging SO Medical Imaging 2007: Physics of Medical Imaging, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE SPECT; imaging; instrumentation; adaptive AB We have designed and constructed a small-animal adaptive SPECT imaging system as a prototype for quantifying the potential benefit of adaptive SPECT imaging over the traditional fixed geometry approach. The optical design of the system is based on filling the detector with the object for each viewing angle, maximizing the sensitivity, and optimizing the resolution in the projection images. Additional feedback rules for determining the optimal geometry of the system can be easily added to the existing control software. Preliminary data have been taken of a phantom with a small, hot, offset lesion in a flat background in both adaptive and fixed geometry modes. Comparison of the predicted system behavior with the actual system behavior is presented along with recommendations for system improvements. C1 US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Tucson, AZ USA. RP Freed, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Tucson, AZ USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6628-0 J9 P SOC PHOTO-OPT INS PY 2007 VL 6510 BP U302 EP U313 DI 10.1117/12.708818 PN 1-3 PG 12 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI21 UT WOS:000247292100030 ER PT S AU Kyprianou, IS Badano, A Gallas, BD Myers, KJ AF Kyprianou, Iacovos S. Badano, Aldo Gallas, Brandon D. Myers, Kyle J. BE Hsieh, J Flynn, MJ TI A method to estimate the point response function of digital x-ray detectors from edge measurements SO MEDICAL IMAGING 2007: PHYSICS OF MEDICAL IMAGING, PTS 1-3 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE point response function; edge; pinhole; MTF; Monte Carlo; PENELOPE; MANTIS ID MODULATION TRANSFER-FUNCTION; IMAGING DETECTORS; MTF; RADIOGRAPHY; SYSTEMS AB Currently, the most accurate measurement of the detector point response can be performed with the pinhole method. The small size of the pinhole however, severely reduces the x-ray intensity output, requiring multiple long exposures, something that can potentially reduce the x-ray tube life-cycle. Even though deriving the 1D Line Response Function (LRF) of the detector using the edge method is much more efficient, the measurement process introduces a convolution with a line, in addition to the common pixel sampling, effectively broadening the LRE. We propose a practical method to recover the detector point response function by removing the effects of the line and the pixel from a set of Edge Response Function (ERF) measurements. We use the imaging equation to study the effects of the edge, line and pixel measurements, and derive an analytical formula for the recovered detector point response function based on a gaussian mixture model. The method allows for limited recovery of asymmetries in the detector response function. We verify the method with pinhole and edge measurements of a digital flat panel detector. Monte Carlo simulations are also performed, using the MANTIS x-ray and optical photon and electron' transport simulation package, for comparison. We show that the standard LRF underestimates the detector performance when compared with the recovered response. Our simulation results suggest that both the edge and pinhole methods for estimating the detector response have limitations in that they cannot completely capture rotational asymmetries or other morphological details smaller than the detector pixel size. C1 NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Kyprianou, IS (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Parkway, Rockville, MD 20857 USA. EM iacovos.kyprianou@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6628-0 J9 PROC SPIE PY 2007 VL 6510 DI 10.1117/12.709517 PN 1-3 PG 12 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI21 UT WOS:000247292100010 ER PT S AU Kyprianou, IS Badal, A Badano, A Banh, D Freed, M Myers, KJ Thompson, L AF Kyprianou, Iacovos S. Badal, Andreu Badano, Aldo Banh, Diemphuc Freed, Melanie Myers, Kyle J. Thompson, Laura BE Cleary, KR Miga, MI TI Monte Carlo simulated coronary angiograms of realistic anatomy and pathology models SO MEDICAL IMAGING 2007: VISUALIZATION AND IMAGE-GUIDED PROCEDURES, PTS 1 AND 2 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE angiography; coronary; phantom; Monte; Carlo; PENELOPE; NURBS; NCAT ID RAY IMAGE INTENSIFIER; MICROANGIOGRAPHIC SYSTEM; SCATTER AB We have constructed a fourth generation anthropomorphic phantom which, in addition to the realistic description of the human anatomy, includes a coronary artery disease model. A watertight version of the NURBS-based Cardiac-Torso (NCAT) phantom was generated by converting the individual NURBS surfaces of each organ into closed, manifold and non-self-intersecting tessellated surfaces. The resulting 330 surfaces of the phantom organs and tissues are now comprised of similar to 5 x 10(6) triangles whose size depends on the individual organ surface normals. A database of the elemental composition of each organ was generated, and material properties such as density and scattering cross-sections were defined using PENELOPE. A 300 pm resolution model of a heart with 55 coronary vessel segments was constructed by fitting smooth triangular meshes to a high resolution cardiac CT scan we have segmented, and was consequently registered inside the torso model. A coronary artery disease model that uses hemodynamic properties such as blood viscosity and resistivity was used to randomly place plaque within the artery tree. To generate x-ray images of the aforementioned phantom, our group has developed an efficient Monte Carlo radiation transport code based on the subroutine package PENELOPE, which employs an octree spatial data-structure that stores and traverses the phantom triangles. X-ray angiography images were generated under realistic imaging conditions (90 kVp, 10 degrees W anode spectra with 3 mm Al filtration, similar to 5 x 10(11) x-ray source photons, and 10% per volume iodine contrast in the coronaries). The images will be used in an optimization algorithm to select the optimal technique parameters for a variety of imaging tasks. C1 NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Kyprianou, IS (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Parkway, Rockville, MD 20857 USA. EM iacovos.kyprianou@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 24 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6627-3 J9 PROC SPIE PY 2007 VL 6509 AR 65090O DI 10.1117/12.709553 PN 1-2 PG 11 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI23 UT WOS:000247294800023 ER PT J AU Parent, MA Goenka, R Murphy, E LeVier, K Carreiro, N Golding, B Ferguson, G Roop, RM Walker, GC Baldwin, CL AF Parent, Michelle A. Goenka, Radhika Murphy, Erin LeVier, Kristen Carreiro, Nuno Golding, Basil Ferguson, Gail Roop, R. Martin, II Walker, Graham C. Baldwin, Cynthia L. TI Brucella abortus bacA mutant induces greater pro-inflammatory cytokines than the wild-type parent strain SO MICROBES AND INFECTION LA English DT Article DE Brucella; brucellosis; intracellular bacterial; bacA ID TOLL-LIKE RECEPTOR-4; INTRACELLULAR SURVIVAL; MACROPHAGE CONTROL; ESCHERICHIA-COLI; BALB/C MICE; INFECTION; LIPOPOLYSACCHARIDE; RESISTANCE; BACTERIA; VACCINES AB The inner-membrane protein BacA affects Brucella LPS structure. A bacA deletion mutant of Brucella abortus, known as KL7 (bacA(mut)-KL7), is attenuated in BALB/c mice and protects against challenge. Thus, bacA mutation was a candidate for incorporation into live attenuated vaccines. We assessed bacA(mut)-KL7 in 2 additional mouse strains: the more resistant C57BL/6 that produces interferon-gamma throughout the infection and the highly susceptible interferon-gamma-deficient C57BL/6 in which brucellae exhibit continual exponential growth. While it was hypothesized that bacA(mut)-KL7 would exhibit even greater attenuation relative to its parent strain B. abortus 2308 in C57BL/6 mice than it did in BALB/c mice, this was not the case. Moreover, it was more pathogenic in C57BL/6 interferon-gamma-deficient mice than 2308 causing abscesses and wasting even though the splenic loads of bacA(mut)-KL7 were significantly lower. These 2 observations were correlated, respectively, with an ability of IFN gamma-activated macrophages to equivalently control strains 2308 and bacA(mut)-KL7 and the ability of bacA(mut)-KL7 organism and its LPS to induce greater amounts of pro-inflammatory cytokines than 2308. We conclude that attenuation properties of bacA mutation are dependent upon the nature of the host but more importantly that bacterial gene deletion can result in increased host pathology without an increase in bacterial load, crucial considerations for vaccine design. (c) 2006 Elsevier Masson SAS. All rights reserved. C1 Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. E Carolina Univ, Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. RP Baldwin, CL (reprint author), Univ Massachusetts, Dept Vet & Anim Sci, 161 Holdsworthy, Amherst, MA 01003 USA. EM cbaldwin@vasci.umass.edu OI /0000-0001-7243-8261 FU Medical Research Council [G0501107] NR 29 TC 15 Z9 18 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2007 VL 9 IS 1 BP 55 EP 62 DI 10.1016/j.micinf.2006.10.008 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 141NU UT WOS:000244586400009 PM 17196866 ER PT J AU Whiting, RC Buchanan, RL AF Whiting, Richard C. Buchanan, Robert L. BE Schaffner, DW TI Using Risk Assessment Principles in an Emerging Paradigm for Controlling the Microbial Safety of Foods SO MICROBIAL RISK ANALYSIS IN FOODS SE Emerging Issues in Food Safety LA English DT Article; Book Chapter C1 [Whiting, Richard C.; Buchanan, Robert L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Whiting, RC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 23 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-575-2 J9 EMERG ISS FOOD SAF JI Emerg. Iss. Food Safety PY 2007 BP 29 EP 50 PG 22 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPD95 UT WOS:000278638700004 ER PT J AU Dennis, SB Kause, J Losikoff, M Engeljohn, DL Buchanan, RL AF Dennis, Sherri B. Kause, Janell Losikoff, Mary Engeljohn, Daniel L. Buchanan, Robert L. BE Schaffner, DW TI Using Risk Analysis for Microbial Food Safety Regulatory Decision Making SO MICROBIAL RISK ANALYSIS IN FOODS SE Emerging Issues in Food Safety LA English DT Article; Book Chapter C1 [Dennis, Sherri B.; Losikoff, Mary; Buchanan, Robert L.] US FDA, Dept Hlth & Human Serv, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Kause, Janell; Engeljohn, Daniel L.] US Food Safety & Inspect Serv, USDA, Washington, DC 20250 USA. RP Dennis, SB (reprint author), US FDA, Dept Hlth & Human Serv, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 38 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-575-2 J9 EMERG ISS FOOD SAF JI Emerg. Iss. Food Safety PY 2007 BP 137 EP 175 PG 39 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPD95 UT WOS:000278638700007 ER PT J AU van Gijssel, HE Leil, TA Weinberg, WC Divi, RL Olivero, OA Poirier, MC AF van Gijssel, Hilde E. Leil, Tarek A. Weinberg, Wendy C. Divi, Rao L. Olivero, Ofelia A. Poirier, Miriam C. TI Cisplatin-DNA damage in p21(WAF1/Cip1) deficient mouse keratinocytes exposed to cisplatin SO MUTAGENESIS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; DEPENDENT KINASE INHIBITOR; MALIGNANT CONVERSION; SKIN CARCINOGENESIS; HUMAN FIBROBLASTS; ADDUCT FORMATION; CELL-CYCLE; IN-VITRO; P53 LOSS; P21 AB In response to DNA damage, cell cycle arrest, apoptosis, and DNA repair are mediated by a TP53 pathway that induces p21(WAF1/Cip1). The chemotherapeutic drug cis-diamminedichloroplatinum-II (cisplatin) damages cellular DNA by forming cis-diammineplatinum-N-7-d[GpG] and cis-diammine-platinum-N-7-d[ApG] adducts. To investigate the role of p21, skin keratinocytes from p21(WAF1/Cip1) wild-type (+/+), heterozygous (+/-), and null (-/-) mice, cultured in calcium levels designed to maintain a proliferating state, were exposed to 5 mu M cisplatin continuously for 0, 8, 24, 48 and 72 h. At all time points the (+/-) cells had the fewest Pt-DNA adducts, and at 24 h mean Pt-DNA adduct levels were 541, 153 and 779 fmol adduct/mu g DNA for p21(WAF1/Cip1) (+/+), (+/-) and (-/-) cells, respectively [P < 0.05 for (+/+) versus (+/-) and (-/-) versus (+/-)]. In order to understand underlying events, we examined p21(WAF1/Cip1) messenger RNA (mRNA), cell cycle arrest, and apoptosis in these cells. At 48 h of cisplatin exposure p21(WAF1/Cip1) mRNA expression was 2-fold higher in the (+/+) cells, compared to the (+/-) cells. At 24 h, the % of cells in S-phase in cisplatin-exposed cultures, compared to unexposed cultures, was decreased by 51, 40 and 11% in p21(WAF1/Cip1) (+/+), (+/-) and (-/-) cells, respectively (P = 0.04, ANOVA). At 24, 48 and 72 h the % of cisplatin-exposed (+/+) cells in apoptosis was 9.4-10.5%, while the cisplatin-exposed (+/-) and (-/-) cells had 1.2-3.7% of cells in apoptosis. The data support the interpretation that DNA replication arrest and apoptosis do not completely explain the low levels of Pt-DNA adducts in the (+/-) cells, and suggest that p21(WAF1/Cip1) controls activity resulting in either low Pt-DNA adduct formation or enhanced Pt-DNA adduct removal. C1 NCI, Carcinogen DNA Interact Sect, NIH, Lab Cellular Carcinogenesis & Tumor Promot,CCR, Bethesda, MD 20892 USA. US FDA, CDER, Off Biotechnol Prod, Immunobiol Lab, Bethesda, MD 20892 USA. Valley City State Univ, Valley City, ND 58072 USA. Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, NIH, Lab Cellular Carcinogenesis & Tumor Promot,CCR, Bldg 37,Room 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov RI Weinberg, Wendy/A-8920-2009 FU Intramural NIH HHS NR 33 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JAN PY 2007 VL 22 IS 1 BP 49 EP 54 DI 10.1093/mutage/gel050 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 123WN UT WOS:000243327000006 PM 17158520 ER PT J AU Rudenko, L Matheson, JC Sundlof, SF AF Rudenko, Larisa Matheson, John C. Sundlof, Stephen F. TI Animal cloning and the FDA - the risk assessment paradigm under public scrutiny SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID BOVINE PREIMPLANTATION EMBRYOS; PRIMORDIAL GERM-CELLS; CLONED CATTLE; SOMATIC-CELLS; NUCLEAR TRANSFER; DNA METHYLATION; X-CHROMOSOME; DONOR GENOME; DEMETHYLATION; EPIGENETICS AB The evidence gathered thus far - ultimately to be published in the Draft Risk Assessment on Animal Cloning indicates that there are no unique risks associated with animal cloning. C1 US FDA, Ctr Vet Med, Dept Hlth & Human Serv, Rockville, MD 20855 USA. RP Rudenko, L (reprint author), US FDA, Ctr Vet Med, Dept Hlth & Human Serv, 7500 Standish Pl, Rockville, MD 20855 USA. EM larisa.rudenko@fda.hhs.gov NR 39 TC 21 Z9 23 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2007 VL 25 IS 1 BP 39 EP 43 DI 10.1038/nbt0107-39 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 126CY UT WOS:000243491000021 PM 17211392 ER PT J AU Hopwood, D Levy, S Wenzel, RP Georgopapadakou, N Baltz, RH Bhavnani, S Cox, E AF Hopwood, David Levy, Stuart Wenzel, Richard P. Georgopapadakou, Nafsika Baltz, Richard H. Bhavnani, Sujata Cox, Edward TI A call to arms SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material AB Widespread resistance to our arsenal of antibiotics is no longer a threat - it is reality. With no new antibacterial drugs expected to reach the market any time soon, immediate action is needed to avert a looming healthcare disaster. But antibacterial discovery faces immense scientific and business challenges. What needs to be done to turn the tide? As part of this special Focus issue on Antibacterials, Nature Reviews Drug Discovery asked representatives from industry, academia, the FDA and the clinic working on different aspects of antibacterial research to give their own perspectives on where the next generation of antibiotics will come from. C1 John Innes Ctr Plant Sci Res, Norwich NR4 7UH, Norfolk, England. Tufts Univ, Medford, MA 02155 USA. Virginia Commonwealth Univ, Richmond, VA 23284 USA. Cubist Pharmaceut, Cambridge, MA USA. Ordway Res Inst, Albany, NY USA. US FDA, Rockville, MD 20857 USA. RP Hopwood, D (reprint author), John Innes Ctr Plant Sci Res, Norwich NR4 7UH, Norfolk, England. NR 0 TC 13 Z9 14 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JAN PY 2007 VL 6 IS 1 BP 8 EP 12 DI 10.1038/nrd2225 PG 5 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 122VR UT WOS:000243255700003 ER PT J AU Kainz, W AF Kainz, Wolfgang TI Response to Shellock et al. "Vagus nerve stimulation therapy system: In vitro evaluation of magnetic resonance imaging-related heating and function at 1.5 and 3 Tesla" SO NEUROMODULATION LA English DT Letter C1 US FDA, Div Phys, Off Sci, Ctr Devices & Radiol Hlth,US Dept Hlth & Human Se, Rockville, MD 20857 USA. US FDA, Div Phys, Engn Labs, Ctr Devices & Radiol Hlth,US Dept Hlth & Human Se, Rockville, MD 20857 USA. RP Kainz, W (reprint author), US FDA, Div Phys, Off Sci, Ctr Devices & Radiol Hlth,US Dept Hlth & Human Se, HFZ-130, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1094-7159 J9 NEUROMODULATION JI Neuromodulation PD JAN PY 2007 VL 10 IS 1 BP 76 EP 77 DI 10.1111/j.1525-1403.2007.00090.x PG 2 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA 124XK UT WOS:000243405500012 PM 22151815 ER PT J AU Kainz, W AF Kainz, Wolfgang TI Response to Shellock et al. "Vagus nerve stimulation therapy system: In vitro evaluation of magnetic resonance imaging-related heating and function at 1.5 and 3 Tesla" - Response to Kainz - Response to Shellock SO NEUROMODULATION LA English DT Letter C1 US FDA, Div Phys, Off Sci, Ctr Devices & Radiol Hlth,US Dept Hlth & Human Se, Rockville, MD 20857 USA. US FDA, Div Phys, Engn Labs, Ctr Devices & Radiol Hlth,US Dept Hlth & Human Se, Rockville, MD 20857 USA. RP Kainz, W (reprint author), US FDA, Div Phys, Off Sci, Ctr Devices & Radiol Hlth,US Dept Hlth & Human Se, HFZ-130, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1094-7159 J9 NEUROMODULATION JI Neuromodulation PD JAN PY 2007 VL 10 IS 1 BP 80 EP 81 DI 10.1111/j.1525-1403.2007.00094.x PG 2 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA 124XK UT WOS:000243405500014 PM 22151817 ER PT S AU Virmania, A Binienda, ZK Ali, SF Gaetani, F AF Virmania, Ashraf Binienda, Zbigniew K. Ali, Syed F. Gaetani, Franco BE Slikker, W Andrew, RJ Trembly, B TI Metabolic syndrome in drug abuse SO NEUROPROTECTIVE AGENTS: EIGHTH INTERNATIONAL NEUROPROTECTION SOCIETY MEETING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th International Conference on Neuroprotective Agents CY SEP 18-20, 2006 CL Mackinac Isl, MI SP Int Neuroprotect Soc DE nutrition; drug abuse; metabolic syndrome; L-carnitine; acetyl-L-carnitine; creatine; selenium; lipoic acid; resveratrol; cocaine; ecstasy; methamphetamine; polyunsaturated fatty acids; alcohol; brain; liver; metabolic compromise; metabolic modifier; hyperinsulinemia; hypertension; dyslipidemia; abdominal obesity; free radicals; reactive oxygen species; vitamins; zinc; thiamine; supplements; diabetes; amphetamines ID TYPE-2 DIABETES-MELLITUS; NECROSIS-FACTOR-ALPHA; ACETYL-L-CARNITINE; N-3 FATTY-ACIDS; INSULIN-RESISTANCE; COENZYME Q(10); LIPOIC ACID; MITOCHONDRIAL DYSFUNCTION; GENETIC-DETERMINANTS; OXIDATIVE STRESS AB Drug abuse is associated with significant health risk. Whether drug abusers are at a higher risk of suffering the metabolic syndrome is not widely known. The metabolic syndrome is a cluster of metabolic abnormalities, including hyperinsulinemia, hypertension, dyslipidemia, and abdominal obesity, and is probably triggered by initial imbalances at the cellular level in various critical metabolic pathways. These initially small metabolic imbalances are believed to cascade with time and lead to larger problems. Some indications that drug abuse may increase the risk of the metabolic syndrome include the following: Drug-abusing patients have higher rates of diabetes complications. Substance abuse is a significant contributing factor for treatment noncompliance in diabetes. Nutrition education can enhance substance abuse treatment outcomes. Each type of drug/substance abuse has a unique profile of toxicity. For example, the amphetamines generally affect the cardiovascular and neurological systems, worsening the risk factors for the metabolic syndrome. Methamphetamine (meth) abusers suffer cognitive deficits and abnormal metabolic activity, which affect nutritional status. This condition is further worsened by a drastic reduction in oral health in meth abusers, resulting in improper chewing and, therefore, digestion. Nutritional deficiency in combination with drug abuse would increase the risk of developing the metabolic syndrome by increasing cell damage, augmenting excitotoxicity, reducing energy production, and lowering the antioxidant potential of the cells. Another potential risk factor in the development of the metabolic syndrome is genetic vulnerability, especially in combination with drug abuse and nutritional deficiencies. The strategies available to treat this problem include pharmacological agents as well as dietary antioxidants. Such measures may be useful in reducing drug abuse-related toxicity that may lead to the metabolic syndrome. C1 [Virmania, Ashraf; Ali, Syed F.; Gaetani, Franco] Sigma Tau Hlth Sci, Res & Dev, I-00040 Pomezia, Italy. [Binienda, Zbigniew K.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurophysiol Lab, Jefferson, AR USA. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR USA. RP Virmania, A (reprint author), Sigma Tau Hlth Sci, Res & Dev, Via Treviso 4, I-00040 Pomezia, Italy. EM ashraf.virmani@st-hs.it NR 123 TC 8 Z9 8 U1 2 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-685-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1122 BP 50 EP 68 DI 10.1196/annals.1403.004 PG 19 WC Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BHD20 UT WOS:000252267100004 PM 18077564 ER PT S AU Sharma, HS Ali, SF Dong, W Tian, ZR Patnaik, R Patnaik, S Sharma, A Boman, A Lek, P Seifert, E Lundstedt, T AF Sharma, Hari Shanker Ali, Syed F. Dong, W. Tian, Z. Ryan Patnaik, R. Patnaik, S. Sharma, Aruna Boman, Arne Lek, Per Seifert, Elisabeth Lundstedt, Torbjorn BE Slikker, W Andrew, RJ Trembly, B TI Drug delivery to the spinal cord tagged with nanowire enhances neuroprotective efficacy and functional recovery following trauma to the rat spinal cord SO NEUROPROTECTIVE AGENTS: EIGHTH INTERNATIONAL NEUROPROTECTION SOCIETY MEETING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th International Conference on Neuroprotective Agents CY SEP 18-20, 2006 CL Mackinac Isl, MI SP Int Neuroprotect Soc DE nanowires; spinal cord injury; spinal cord edema; bloodspinal cord barrier; functional paralysis; Evans blue; radioiodine; protein tracer; spinal cord damage ID BLOOD-BRAIN-BARRIER; TOPICAL APPLICATION; EDEMA FORMATION; NITRIC-OXIDE; MICROVASCULAR PERMEABILITY; MELANOCORTIN RECEPTORS; NEUROTROPHIC FACTORS; CONTROLLED-RELEASE; UP-REGULATION; FOCAL TRAUMA AB The possibility that drugs attached to innocuous nanowires enhance their delivery within the central nervous system (CNS) and thereby increase their therapeutic efficacy was examined in a rat model of spinal cord injury (SCI). Three compounds-AP173 (SCI-1), AP713 (SCI-2), and AP364 (SCI-5) (Acure Pharma, Uppsala, Sweden)-were tagged with TiO2-based nanowires using standard procedure. Normal compounds were used for comparison. SCI was produced by making a longitudinal incision into the right dorsal horn of the T10-T11 segments under Equithesin anesthesia. The compounds, either alone or tagged with nanowires, were applied topically within 5 to 10 min after SCI. In these rats, behavioral outcome, blood-spinal cord barrier (BSCB) permeability, edema formation, and cell injury were examined at 5 h after injury. Topical application of normal compounds in high quantity (10 mu g in 20 mu L) attenuated behavioral dysfunction (3 h after trauma), edema formation, and cell injury, as well as reducing BSCB permeability to Evans blue albumin and I-131. These beneficial effects are most pronounced with AP713 (SCI-2) treatment. Interestingly, when these compounds were administered in identical conditions after tagging with nanowires, their beneficial effects on functional recovery and spinal cord pathology were further enhanced. However, topical administration of nanowires alone did not influence trauma-induced spinal cord pathology or motor functions. Taken together, our results, probably for the first time, indicate that drug delivery and therapeutic efficacy are enhanced when the compounds are administered with nanowires. C1 [Sharma, Hari Shanker; Sharma, Aruna] Uppsala Univ, Univ Hosp, Dept Surg Sci Anaesthesiol & Intens Care Med, Lab Cerebrovasc Res, Uppsala, Sweden. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. [Dong, W.; Tian, Z. Ryan] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. [Patnaik, R.; Patnaik, S.] Banaras Hindu Univ, Inst Technol, Dept Pharm & Biomat, Varanasi 221005, Uttar Pradesh, India. [Boman, Arne; Lek, Per; Seifert, Elisabeth; Lundstedt, Torbjorn] AcurePharma AB, Uppsala, Sweden. [Lundstedt, Torbjorn] Uppsala Univ, Div Organ Pharmaceut Chem, Dept Med Chem, Uppsala, Sweden. RP Sharma, HS (reprint author), Frodingsgatan 12 28, SE-75421 Uppsala, Sweden. EM sharrna@surgsci.uu.se RI Sharma, Aruna/D-4430-2011; Sharma, Hari/G-4508-2016; Tian, Z. Ryan /R-6671-2016; OI Tian, Z. Ryan /0000-0002-5644-8483; Patnaik, Ranjana/0000-0002-8131-177X NR 54 TC 37 Z9 37 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-685-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1122 BP 197 EP 218 DI 10.1196/annals.1403.014 PG 22 WC Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BHD20 UT WOS:000252267100014 PM 18077574 ER PT J AU Boyko, A Kathiria, P Zemp, FJ Yao, YL Pogribny, I Kovalchuk, I AF Boyko, Alexander Kathiria, Palak Zemp, Franz J. Yao, Youli Pogribny, Igor Kovalchuk, Igor TI Transgenerational changes in the genome stability and methylation in pathogen-infected plants (Virus-induced plant genome instability) SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RIBOSOMAL-RNA GENES; DNA METHYLATION; CYTOSINE METHYLATION; BALANCING SELECTION; CROSS-TALK; RESISTANCE; STRESS; ARABIDOPSIS; POLYMORPHISM; EXPRESSION AB Previously, we reported the generation of a virus-induced systemic signal that increased the somatic and meiotic recombination rates in tobacco mosaic virus (TMV)-infected tobacco plants. Here, we analyzed the progeny of plants that received the signal and found that these plants also have a higher frequency of rearrangements in the loci carrying the homology to LRR region of the gene of resistance to TMV (N-gene). Analysis of the stability of repetitive elements from Nicotiana tabacum loci and 5.8S ribosomal RNA loci did not show any changes. Further analysis of the changes in the progeny of infected plants revealed that they had substantially hypermethylated genomes. At the same time, loci-specific methylation analysis showed: (1) profound hypomethylation in several LRR-containing loci; (2) substantial hypermethylation of actin loci and (3) no change in methylation in the loci of repetitive elements from N. tabacum or 5.8S ribosomal RNA. Global genome hypermethylation of the progeny is believed to be part of a general protection mechanism against stress, whereas locus-specific hypomethylation is associated with a higher frequency of rearrangements. Increased recombination events combined with the specific methylation pattern induced by pathogen attack could be a sign of an adaptive response by plants. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, I (reprint author), Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. EM igor.kovalchuk@uleth.ca NR 53 TC 130 Z9 153 U1 4 U2 42 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2007 VL 35 IS 5 BP 1714 EP 1725 DI 10.1093/nar/gkm029 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 166IA UT WOS:000246371200029 PM 17311811 ER PT J AU Zhang, JJ Dhakal, I Stone, A Ning, BT Greene, G Lang, NP Kadlubar, FF AF Zhang, Jianjun Dhakal, Ishwori Stone, Angie Ning, Baitang Greene, Graham Lang, Nicholas P. Kadlubar, Fred F. TI Plasma carotenoids and prostate cancer: A population-based case-control study in Arkansas SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID RETINOL EFFICACY TRIAL; DIETARY BETA-CAROTENE; SERUM MICRONUTRIENTS; PROSPECTIVE COHORT; AFRICAN-AMERICANS; TOMATO PRODUCTS; LUNG-CANCER; VITAMIN-C; FOLLOW-UP; RISK AB Carotenoids possess antioxidant properties and thus may protect against prostate cancer. Epidemiological studies of dietary carotenoids and this malignancy were inconsistent, partially due to dietary assessment error. In this study, we aimed to investigate the relation between plasma concentrations of carotenoids and the risk of prostate cancer in a population-based case-control study in Arkansas. Cases (n = 193) were men with prostate cancer diagnosed in 3 major hospitals, and controls (n = 197) were matched to cases by age, race, and county of residence. After adjustment for confounders, plasma levels of lycopene, lutein/zeaxanthin, and beta-cryptoxanthin were inversely associated with prostate cancer risk. Subjects in the highest quartile of plasma lycopene (513.7 mu g/l) had a 55% lower risk of prostate cancer than those in the lowest quartile (140.5 mu g/l; P trend = 0.042). No apparent association was observed for plasma alpha-carotene and beta-carotene. Further adjustment for the other 4 carotenoids did not materially alter the risk estimates for plasma lycopene, lutein/zeaxanthin, and beta-cryptoxanthin but appeared to result in an elevated risk with high levels of plasma alpha-carotene and beta-carotene. The results of all analyses did not vary substantially by age, race, and smoking status. This study added to the emerging evidence that high circulating levels of lycopene, lutein/zeaxanthin, and beta-cryptoxanthin are associated with a low risk of prostate cancer. C1 Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Coll Med, Dept Surg, Little Rock, AR 72205 USA. RP Zhang, JJ (reprint author), Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Dept Epidemiol, 4301 W Markham St,Slot 820, Little Rock, AR 72205 USA. EM Zhangjianjun@uams.edu FU NIA NIH HHS [1 R01 AG15722] NR 45 TC 22 Z9 22 U1 0 U2 6 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2007 VL 59 IS 1 BP 46 EP 53 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 217SN UT WOS:000249967700007 PM 17927501 ER PT J AU Axume, J Smith, SS Pogribny, IP Moriarty, DJ Caudill, MA AF Axume, Juan Smith, Steven S. Pogribny, Igor P. Moriarty, David J. Caudill, Marie A. TI The methylenetetrahydrofolate reductase 677TT genotype and folate intake interact to lower global leukocyte DNA methylation in young Mexican American women SO NUTRITION RESEARCH LA English DT Article DE MTHFR; folate; folic acid; women; DNA methylation; human ID COMMON MUTATION; HOMOCYSTEINE; POLYMORPHISM; DECREASES; DEPLETION AB DNA methylation is an epigenetic feature associated with X chromosome inactivation, genomic imprinting, transcriptional silencing of genes, and genomic stability. Folate provides a labile source of methyl groups that may be used for cellular methylation reactions, including DNA methylation. The methyl enetetrahydrofo late reductase (MTHFR) 677C -> T variant is an important determinant of folate nutriture and may influence DNA methylation. This study sought to assess the influence of the MTHFR C677T genotype on global leukocyte DNA methylation in young (age range = 18-45 years) Mexican American women (N = 43: CC, n = 14; CT, n = 12; TT, n = 17). Subjects consumed a folate-restricted diet (135 /ig of dietary folate equivalents per day) for 7 weeks followed by folate treatment with 400 or 800 mu g of dietary folate equivalents per day for another 7 weeks. Global leukocyte DNA methylation was assessed via the cytosine extension assay at weeks 0, 7 (after folate restriction), and 14 (after folate treatment). No main effect of MTHFR C677T genotype or folate intake was detected at any time point during the study. However, at the end of folate treatment (week 14), DNA methylation was lower (P <.05) among women with the MTHFR 677TT genotype than among those with the CT or CC genotype. Because it is unlikely that folate treatment would result in methyl group loss, we suggest that there was a delay in the DNA methylation response to folate intake. Overall, these data suggest that the MTHFR 677TT genotype and folate interact to lower global leukocyte DNA methylation patterns in young Mexican American women. (c) 2007 Elsevier Inc. All rights reserved. C1 Calif State Polytech Univ Pomona, Human Nutr & Food Sci Dept, Pomona, CA 91768 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Beckman Res Inst, Duarte, CA 91010 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Calif State Polytech Univ Pomona, Dept Biol Sci, Pomona, CA 91768 USA. RP Caudill, MA (reprint author), Calif State Polytech Univ Pomona, Human Nutr & Food Sci Dept, Pomona, CA 91768 USA. EM macaudill@csupomona.edu NR 17 TC 11 Z9 11 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JAN PY 2007 VL 27 IS 1 BP 13 EP 17 DI 10.1016/j.nutres.2006.12.006 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 137AT UT WOS:000244265900002 ER PT J AU Rock, EP Goodman, V Jiang, JX Mahjoob, K Verbois, SL Morse, D Dagher, R Justice, R Pazdur, R AF Rock, Edwin P. Goodman, Vicki Jiang, Janet X. Mahjoob, Kooros Verbois, S. Leigh Morse, David Dagher, Ramzi Justice, Robert Pazdur, Richard TI Food and drug administration drug approval summary: Sunitinib malate for the treatment of gastrointestinal stromal tumor and advanced renal cell carcinoma SO ONCOLOGIST LA English DT Article DE sunitinib; sutent; gastrointestinal stromal tumor; renal cell carcinoma ID IMATINIB MESYLATE AB On January 26, 2006, sunitinib (Sutent) received regular approval as monotherapy for the treatment of patients with gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate (Gleevec). Time-to-tumor progression (TTP) of sunitinib-treated patients was superior to that of placebo-treated patients. Median TTP of sunitinib-treated patients was 27.3 weeks, compared with 6.4 weeks for placebo-treated patients (p < .0001). Partial responses were observed in 6.8% of sunitinib-treated patients and no placebo-treated patients. Sunitinib also received accelerated approval on January 26, 2006, as monotherapy for treatment of advanced renal cell carcinoma (RCC). In two single-arm trials of sunitinib in patients with metastatic RCC, partial responses were observed in 25.5% (95% confidence interval [CI], 17.5, 34.9) and 36.5% (95% CI, 24.7, 49.6) of patients. Median response durations in the two trials were 27.1 weeks (95% CI, 24.4, incalculable) and 54 weeks (95% CI, 34.3, 70.1). Treatment-emergent adverse events in sunitinib-treated patients included diarrhea, mucositis, skin abnormalities, altered taste, electrolyte abnormalities, hypertension, and diminution in left ventricular ejection fraction. Cardiac safety of sunitinib in patients with preexisting cardiac abnormalities remains unknown. Based on nonclinical findings, physicians prescribing sunitinib should monitor for adrenal insufficiency in patients who undergo stressors such as surgery, trauma, or severe infection. Caution should be exercised when administering sunitinib in combination with known CYP3A4 inducers or inhibitors. C1 US FDA, Div Drug Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Rock, EP (reprint author), US FDA, Div Drug Oncol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Rm 2133, Silver Spring, MD 20903 USA. EM edwin.rock@fda.hhs.gov NR 8 TC 151 Z9 171 U1 1 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 1 BP 107 EP 113 DI 10.1634/theoncologist.12-1-107 PG 7 WC Oncology SC Oncology GA 127NY UT WOS:000243594600011 PM 17227905 ER PT J AU Zerhouni, EA Sanders, CA von Eschenbach, AC AF Zerhouni, Elias A. Sanders, Charles A. von Eschenbach, Andrew C. TI The biomarkers consortium: Public and private sectors working in partnership to improve the public health SO ONCOLOGIST LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. RP Zerhouni, EA (reprint author), NIH, Bldg 1,Room 126,1 Ctr Dr,MSC 0148, Bethesda, MD 20892 USA. EM ZerhounE@od.nih.gov NR 0 TC 15 Z9 15 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 3 BP 250 EP 252 DI 10.1634/theoncologist.12-3-250 PG 3 WC Oncology SC Oncology GA 154YE UT WOS:000245543600003 PM 17405889 ER PT J AU Cohen, MH Gootenberg, J Keegan, P Pazdur, R AF Cohen, Martin H. Gootenberg, Joe Keegan, Patricia Pazdur, Richard TI FDA drug approval summary: Bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer SO ONCOLOGIST LA English DT Article DE colorectal cancer; advanced disease; second-line therapy; bevacizumab; FOLFOX4 AB On June 20, 2006, the U. S. Food and Drug Administration (FDA) approved bevacizumab (Avastin(R); Genentech, Inc., South San Francisco, CA), administered in combination with FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin) for the second-line treatment of metastatic carcinoma of the colon or rectum. Efficacy and safety were demonstrated in one Eastern Cooperative Oncology Group (ECOG) open-label, multicenter, randomized, three-arm, active-controlled trial enrolling 829 adult patients. Patients had received a fluoropyrimidine- and irinotecan-based regimen as initial therapy for metastatic disease; or they had received prior adjuvant irinotecan-based chemotherapy and had recurred within 6 months of completing therapy. Treatments included bevacizumab, 10 mg/kg, as a 90-minute i.v. infusion on day 1, every 2 weeks, either alone or in combination with FOLFOX4, or FOLFOX4 alone. The bevacizumab monotherapy arm was closed to accrual after an interim efficacy analysis suggested a possibly shorter survival in that arm. Overall survival (OS), the primary study endpoint, was significantly longer for patients receiving bevacizumab in combination with FOLFOX4 than for those receiving FOLFOX4 alone. The objective response rate was significantly higher in the FOLFOX4 plus bevacizumab arm than in the FOLFOX4 alone arm. The duration of response was approximately 6 months for both treatment arms. Patients treated with the bevacizumab combination were also reported, based on investigator assessment, to have significantly longer progression-free survival. There were no new bevacizumab safety signals. The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound-healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, and congestive heart failure. C1 US FDA, Ctr Drug Evaluat & Res, Div Biol Oncol Prod, Off Oncol Drug Prod, Silver Spring, MD USA. RP Cohen, MH (reprint author), US FDA, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. EM cohenma@cder.fda.gov NR 4 TC 102 Z9 106 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 3 BP 356 EP 361 DI 10.1634/theoncologist.12-3-356 PG 6 WC Oncology SC Oncology GA 154YE UT WOS:000245543600015 PM 17405901 ER PT J AU Giusti, RM Shastri, KA Cohen, MH Keegan, P Pazdur, R AF Giusti, Ruthann M. Shastri, Kaushikkumar A. Cohen, Martin H. Keegan, Patricia Pazdur, Richard TI FDA drug approval summary: Panitumumab (Vectibix (TM)) SO ONCOLOGIST LA English DT Article DE panitumumab; colorectal cancer; advanced resistant/refractory disease; drug approval ID METASTATIC COLORECTAL-CANCER; PLUS IRINOTECAN; ERBB RECEPTORS; GROWTH-FACTOR; FLUOROURACIL; LEUCOVORIN; INHIBITORS; HER-2 AB On September 27, 2006, the U. S. Food and Drug Administration granted approval to panitumumab (Vectibix (TM), Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Panitumumab approval is based on the results of a single, open-label, randomized, multinational study that enrolled 463 patients with EGFR-expressing ( at least 1+ membrane staining in >= 1% of tumor cells) metastatic colorectal cancer. Patients were randomized to either best supportive care (BSC) alone or BSC plus panitumumab, 6 mg/kg i.v., every other week. The primary study endpoint was progression-free survival (PFS), determined by an independent review committee that was blinded as to treatment assignment. BSC patients who progressed were eligible to receive panitumumab. The study patients' median age was 62 years, with 40% aged >= 65; 63% were male, 99% were white, 86% had a baseline Eastern Cooperative Oncology Group performance status score of 0 or 1, and 67% had colon cancer. The median time from diagnosis of metastases was approximately 19 months and the median number of prior therapies was 2.4. The PFS duration was significantly longer among patients randomized to receive panitumumab in addition to BSC ( n = 231) compared with BSC alone ( n = 232). The median and mean PFS times were 56 and 96.4 days, respectively, for patients receiving panitumumab and 51 and 59.7 days, respectively, for patients receiving BSC alone. Nineteen partial responses (8%, 95% confidence interval [CI], 5.3% - 12.5%) were observed in panitumumab treated patients. The median duration of response was 17 weeks ( 95% CI, 16 - 25 weeks). Approximately 75% of patients in the BSC alone arm crossed over to receive panitumumab after disease progression. There was no difference in overall survival between the two study arms. The most common adverse events were skin rash, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea. The most serious adverse events were pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, diarrhea, and constipation. C1 US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Giusti, RM (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ruthann.giusti@fda.hhs.gov NR 14 TC 103 Z9 105 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 5 BP 577 EP 583 DI 10.1634/theoncologist.12-5-577 PG 7 WC Oncology SC Oncology GA 172JE UT WOS:000246799400012 PM 17522246 ER PT J AU Cohen, MH Gootenberg, J Keegan, P Pazdur, R AF Cohen, Martin H. Gootenberg, Joe Keegan, Patricia Pazdur, Richard TI FDA drug approval summary: Bevacizumab (Avastin (R)) plus carboplatin and paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer SO ONCOLOGIST LA English DT Article DE bevacizumab; Avastin (R); nonsquamous; non-small cell lung cancer; first-line advanced/metastatic disease ID CHEMOTHERAPY REGIMENS; TRIAL; DOCETAXEL; ERLOTINIB AB On October 11, 2006, the U. S. Food and Drug Administration granted approval for bevacizumab (Avastin(R); Genentech, Inc., South San Francisco, CA), administered in combination with carboplatin and paclitaxel, for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic, nonsquamous, non-small cell lung cancer (NSCLC). Approval is based on a significant improvement in overall survival (OS). A randomized, open label, multicenter clinical trial, conducted by the Eastern Cooperative Oncology Group (ECOG), in chemotherapy- naive patients with stage IIIB/IV nonsquamous NSCLC, evaluated bevacizumab plus carboplatin and paclitaxel (BV/CP, n = 434) versus carboplatin and paclitaxel alone (CP, n = 444). Exclusion of patients with squamous or predominantly squamous histology was based on life-threatening or fatal hemoptysis occurring in 4 of 13 patients with squamous histology who received a BV/CP regimen in a phase II study. Among the 878 randomized patients, the median age was 63, 46% were female, 76% had stage IV disease, 12% had stage IIIB disease with malignant pleural effusion, 11% had recurrent disease, and 40% had an ECOG performance status score of 0. OS was significantly longer in patients receiving BV/CP than in those receiving CP alone (median OS, 12.3 versus 10.3 months; hazard ratio [HR], 0.80; p = .013, stratified log rank test). Although a consistent effect was observed across most subgroups, in an exploratory analysis, evidence of a survival benefit was not observed in women (HR, 0.99; 95% confidence interval, 0.79-1.25). Severe and life-threatening adverse events occurring more frequently in patients receiving BV/CP were neutropenia (27% versus 17%), fatigue (16% versus 13%), hypertension (8% versus 0.7%), infection without neutropenia (7% versus 3%), thrombosis/embolism (5% versus 3%), pneumonitis or pulmonary infiltrate (5% versus 3%), infection with grade 3 or 4 neutropenia (5% versus 2%), febrile neutropenia (5% versus 2%), hyponatremia (4% versus 1%), proteinuria (3% versus 0), and headache (3% versus 0.5%). Fatal, treatment-related adverse events in patients receiving bevacizumab were pulmonary hemorrhage (2.3% versus 0.5%), gastrointestinal hemorrhage, central nervous system infarction, gastrointestinal perforation, myocardial infarction, and neutropenic sepsis. The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, congestive heart failure, and neutropenic sepsis. The most common adverse events in patients receiving bevacizumab are asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis, and proteinuria. C1 US FDA, Div Biol Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Div Biol Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, White Oak Campus,10903 New Hampshire Ave,Bldg 22,, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov NR 10 TC 206 Z9 220 U1 0 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 6 BP 713 EP 718 DI 10.1634/theoncologist.12-6-713 PG 6 WC Oncology SC Oncology GA 186UI UT WOS:000247803400008 PM 17602060 ER PT J AU Dinndorf, PA Gootenberg, J Cohen, MH Keegan, P Pazdur, R AF Dinndorf, Patricia Anne Gootenberg, Joseph Cohen, Martin H. Keegan, Patricia Pazdur, Richard TI FDA drug approval summary: Pegaspargase (Oncaspar (R)) for the first-line treatment of children with acute lymphoblastic leukemia (ALL) SO ONCOLOGIST LA English DT Article DE pegaspargase; Oncaspar (R); pediatric ALL ID ACUTE LYMPHOCYTIC-LEUKEMIA; L-ASPARAGINASE; STANDARD-RISK; INDUCTION; REMISSION; ONCOLOGY; THERAPY AB July 24, 2006, the U. S. Food and Drug Administration granted approval to pegaspargase (Oncaspar (R); Enzon Pharmaceuticals, Inc., Bridgewater, NJ; hereafter, O) for the first-line treatment of patients with acute lymphoblastic leukemia (ALL) as a component of a multiagent chemotherapy regimen. O was previously approved in February 1994 for the treatment of patients with ALL who were hypersensitive to native forms of Lasparaginase. The trial supporting this new indication was an open label, randomized, multicenter clinical trial that enrolled 118 children (age, 1-9 years) with previously untreated, standard risk ALL. Patients received either native Escherichia coli asparaginase (Elspar (R); Merck, Whitehouse Station, NJ; hereafter, E) or O along with multiagent chemotherapy during remission induction and delayed intensification (DI) phases of treatment. O, at a dose of 2,500 IU/m(2), was administered i.m. on day 3 of the 4-week induction phase and on day 3 of each of two 8-week DI phases. E, at a dose of 6,000 IU/m(2), was administered i.m. three times weekly for nine doses during induction and for six doses during each DI phase. This study allowed direct comparison of O and E for asparagine depletion, asparaginase activity, and development of asparaginase antibodies. An unplanned comparison of event-free survival (EFS) was conducted to rule out a deleterious O efficacy effect. Following induction and DI treatment there was complete (<= 1 mu M) or moderate (1-10 mu M) depletion of serum asparagine levels in the large majority of samples tested over the 4-week period in both O-treated and E-treated subjects. Similarly, depletion of cerebrospinal fluid asparagine levels during induction was similar between O-treated and E-treated subjects. The number of days asparaginase activity exceeded >0.03 IU/ml in O-treated subjects was greater than the number of days in E-treated subjects during both the induction and DI phases of treatment. There was no correlation, however, between asparaginase activity and serum asparagine levels, making the former determination less clinically relevant. Using the protocol-prespecified threshold for a positive result of >2.5 times the control, 7 of 56 (12%) subjects tested at any time during the study demonstrated antiasparaginase antibodies and 16 of 57 (28%) E subjects tested at any time during the study had antiasparaginase antibodies. In both study arms EFS was in the range of 80% at 3 years. The most serious, sometimes fatal, O toxicities were anaphylaxis, other serious allergic reactions, thrombosis (including sagittal sinus thrombosis), pancreatitis, glucose intolerance, and coagulopathy. The most common adverse events were allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system thrombosis, coagulopathy, hyperbilirubinemia, and elevated transaminases. C1 US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, White Oak Campus,10903 New Hampshire Ave,Bldg 22,, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov NR 16 TC 87 Z9 99 U1 4 U2 25 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 8 BP 991 EP 998 DI 10.1634/theoncologist.12-8-991 PG 8 WC Oncology SC Oncology GA 206QB UT WOS:000249196900012 PM 17766659 ER PT J AU Mann, BS Johnson, JR Cohen, MH Justice, R Pazdur, R AF Mann, Bhupinder S. Johnson, John R. Cohen, Martin H. Justice, Robert Pazdur, Richard TI FDA approval summary: Vorinostat for treatment of advanced primary cutaneous T-cell lymphoma SO ONCOLOGIST LA English DT Article DE vorinostat; histone deacetylase inhibitor; HDAC; cutaneous T-cell lymphoma; CTCL ID HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; III TRIAL; PHASE-I; CANCER; SAHA; DEPSIPEPTIDE; MALIGNANCIES; PERSISTENT; BEXAROTENE AB On October 6, 2006, the U. S. Food and Drug Administration granted regular approval to vorinostat ( Zolinza (R); Merck & Co., Inc., Whitehouse Station, NJ), a histone deacetylase inhibitor, for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma ( CTCL) in patients with progressive, persistent, or recurrent disease on or following two systemic therapies. The pivotal study supporting approval was a single-arm open-label phase II trial that enrolled 74 patients with stage IB and higher CTCL who had failed two systemic therapies ( one of which must have contained bexarotene). Patients received vorinostat at a dose of 400 mg orally once daily, which could be reduced for toxicity to 300 mg daily or 300 mg 5 days a week. The median age of patients was 61 years. Sixty-one patients ( 82%) had stage IIB or higher CTCL and 30 patients ( 41%) had Sezary syndrome. The median duration of protocol treatment was 118 days. The primary efficacy endpoint was objective response assessed by the Severity-Weighted Assessment Tool. The objective response rate was 30% ( 95% confidence interval [ CI], 19.7% - 41.5%), the estimated median response duration was 168 days, and the median time to tumor progression was 202 days. An additional single-center study enrolled 33 patients with similar baseline and demographic features as the pivotal trial. Thirteen of the 33 received vorinostat ( 400 mg/day). The response rate in these 13 patients was 31% ( 95% CI, 9.1% - 61.4%). The most common clinical adverse events ( AEs) of any grade were diarrhea ( 52%), fatigue ( 52%), nausea ( 41%), and anorexia 24%). Grade 3 or 4 clinical AEs included fatigue ( 4%) and pulmonary embolism ( 5%). Hematologic laboratory abnormalities included thrombocytopenia ( 26%) and anemia ( 14%). Chemistry laboratory abnormalities included increased creatinine ( 16%), increased serum glucose ( 69%), and proteinuria ( 51%). Most abnormalities were National Cancer Institute Common Terminology Criteria for Adverse Events grade 1 or 2. Grade 3 or greater chemistry abnormalities included hyperglycemia, hypertriglyceridemia, and hyperuricemia, hypoglycemia, hypokalemia, hyponatremia, hyperkalemia, hypercholesterolemia, hypophosphatemia, and increased creatinine. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Mann, BS (reprint author), US FDA, White Oak Campus,10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM bhupinder.mann@fda.hhs.gov NR 18 TC 492 Z9 506 U1 5 U2 41 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 10 BP 1247 EP 1252 DI 10.1634/theoncologist.12-10-1247 PG 6 WC Oncology SC Oncology GA 229AF UT WOS:000250773000010 PM 17962618 ER PT J AU Fullerton, KE Ingram, LA Jones, TF Anderson, BJ McCarthy, PV Hurd, S Shiferaw, B Vugia, D Haubert, N Hayes, T Wedel, S Scallan, E Henao, O Angulo, FJ AF Fullerton, Kathleen E. Ingram, L. Amanda Jones, Timothy F. Anderson, Bridget J. McCarthy, Patrick V. Hurd, Sharon Shiferaw, Beletshachew Vugia, Duc Haubert, Nicole Hayes, Tameka Wedel, Stephanie Scallan, Elaine Henao, Olga Angulo, Frederick J. TI Sporadic Campylobacter infection in infants - A population-based surveillance case-control study SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Campylobacter; infants; Campylobacter infections; campylobacteriosis; case-control studies ID JEJUNI-COLI ENTERITIS; RISK-FACTORS; RAW-MILK; FOODBORNE PATHOGENS; CROSS-CONTAMINATION; ESCHERICHIA-COLI; KITCHEN SURFACES; YOUNG-CHILDREN; UNITED-STATES; DIARRHEA AB Background: Campylobacter is an important cause of foodbome illness in infants (younger than I year of age), but little is known about the sources of infection in this age group. Methods: Eight sites in the Foodborne Diseases Active Surveillance Network (FoodNet) participated in a 24-month population-based case-control study conducted in 2002-2004. Cases were infants with laboratory-confirmed Campylobacter infection ascertained through active laboratory surveillance, and controls were infants in the community. Results: We enrolled 123 cases and 928 controls. Infants 0-6 months of age with Campylobacter infection were less likely to be breast-fed than controls [odds ratio (OR); 0.2; 95% confidence interval (CI), 0.1-0.6]. Risk factors for infants 0-6 months of age included drinking well water (OR 4.4; CI, 1.4-14) and riding in a shopping cart next to meat or poultry (OR 4.0; CI, 1.2-13.0). Risk factors for infants 7-11 months of age included visiting or living on a farm (OR 6.2; CI, 2.2-17), having a pet with diarrhea in the home (OR 7.6; CI, 2.1-28) and eating fruits and vegetables prepared in the home (OR 2.5, CI 1.2-4.9). Campylobacter infection was associated with travel outside the United States at all ages (OR 19.3; CI, 4.5-82.1). Conclusions: Several unique protective and risk factors were identified among infants, and these risk factors vary by age, suggesting that prevention measures be targeted accordingly. Breast-feeding was protective for the youngest infants and should continue to be encouraged. C1 MPH, Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Atlanta Res & Educ Fdn, Decatur, GA USA. Tennessee Dept Hlth, Nashville, TN USA. New York State, Dept Hlth, Albany, NY USA. Ctr Food Safety & Nutrit, US FDA, Washington, DC USA. Connecticut Emerging Infect Program, New Haven, CT USA. Oregon Div Hlth, Portland, OR USA. Calif Dept Hlth Serv, Berkeley, CA USA. Dept Publ Hlth & Environm, Denver, CO USA. Georgia Div Publ Hlth, Atlanta, GA USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. RP Fullerton, KE (reprint author), MPH, Ctr Dis Control & Prevent, 1600 Clifton Rd,MS D63, Atlanta, GA 30333 USA. EM kfullerton@cdc.gov NR 53 TC 43 Z9 45 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2007 VL 26 IS 1 BP 19 EP 24 DI 10.1097/01.inf.0000247137.43495.34 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 122PD UT WOS:000243238000004 PM 17195700 ER PT J AU Abdolpour, F Shahverdi, AR Rafii, F Fazeli, MR Amini, M AF Abdolpour, Farid Shahverdi, Ahmad-Reza Rafii, Fatemeh Fazeli, Mohammad-Reza Amini, Mohsen TI Effects of piperitone on the antimicrobial activity of nitrofurantoin and on nitrofurantoin metabolism by Enterobacter cloacae SO PHARMACEUTICAL BIOLOGY LA English DT Article DE metabolism; nitrofurantoin; nitroreductase; piperitone; synergism ID PERFORMANCE LIQUID-CHROMATOGRAPHY; URINARY-TRACT-INFECTIONS; RESISTANCE; CATHETERIZATION; METRONIDAZOLE; MECHANISM AB Monoterpenes, including piperitone, increase nitrofurantoin susceptibility in members of the family Enterobacteriaceae. To understand interactions of these compounds, a nitrofurantoin-resistant clinical strain of Enterobacter cloacae was subjected to two-dimensional checkerboard dilutions of piperitone and nitrofurantoin. Synergy was demonstrated with all combinations of these compounds. HPLC analysis showed that E. cloacae metabolized nitrofurantoin to compounds that were not detectable by chromatography with UV detection and lacked bactericidal activity. E. cloacae produced a cell-associated nitroreductase, whose activity was reduced by piperitone in a dose-dependent manner. More than one mechanism may be involved in the synergistic interaction of these compounds. C1 Univ Tehran, Fac Pharm, Dept Pharmaceut Biotechnol, Tehran, Iran. Univ Tehran, Fac Pharm, Biotechnol Res Ctr, Tehran, Iran. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Tehran, Fac Pharm, Dept Food & Drug Control, Tehran, Iran. Univ Tehran, Fac Pharm, Dept Med Chem, Tehran, Iran. RP Shahverdi, AR (reprint author), Univ Tehran, Fac Pharm, Dept Pharmaceut Biotechnol, POB 14155-6451, Tehran, Iran. EM shahverd@sina.tums.ac.ir NR 14 TC 5 Z9 5 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2007 VL 45 IS 3 BP 230 EP 234 DI 10.1080/13880200701213161 PG 5 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 167HQ UT WOS:000246442700011 ER PT J AU Nutan, MTH Vaithiyalingam, SR Khan, MA AF Nutan, Mohammad T. H. Vaithiyalingam, Sivakumar R. Khan, Mansoor A. TI Controlled release multiparticulate beads coated with starch acetate: Material characterization, and identification of critical formulation and process variables SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE starch acetate; coating; screening of variables; Plackett-Burman; controlled-release drug; multiparticulate bead ID DRUG-RELEASE; POLYMER; FILMS; DISPERSION; COATINGS AB The objectives of the present investigation were to prepare and characterize starch acetate (SA) with high degree of substitution (dS) and to study its prospect as film-forming agent in a controlled-release multiparticulate drug delivery system. As a part of the development process by quality by design, the objectives also included identification of critical formulation and process variables that affect the release of a drug. SA, a relatively new polymer, was characterized because it showed good film-forming properties. SA with dS 2.9 was synthesized from corn starch by paste disruption technique. It was compared with the raw material, starch, by Fourier transform infrared spectroscopy, X-ray diffraction, and molecular mass analysis. Viscosity of SA solution increased logarithmically with the polymer concentration. At higher polymer concentrations (1.5-5.0%), the solutions showed pseudoplastic behavior. Among the plasticizers tested, triacetin and triethyl citrate yielded free films with acceptable mechanical properties. The glass transition temperature (T-g) of the films could be well controlled by these plasticizers. Unplasticized film showed a T-g of 31.8 degrees C. A trend was found that increase in triacetin concentration in SA films resulted in increase in permeability coefficient for tritiated water. Scanning electron microscopic photographs showed a clear and smooth plasticized film compared to rough unplasticized film. Dyphylline-loaded beads were coated with highly substituted SA to evaluate the main effects of the formulation and process variables on the release of the drug and to figure out the reliability of the screening design. A seven-factor, twelve-run Plackett-Burman screening design was used. The response variables were cumulative percent of drug released in 0.5, 1, 4, 8, and 12 hr. Quantitative evaluation of the design revealed that coating weight gain, plasticizer concentration, and post-drying temperature had greater influence on the drug release than the others. The main effects on drug release after 12 hr decreased in the following order: coating weight gain (-7.81), plasticizer concentration (4.96), postdrying temperature (-2.51), SA concentration (-0.80), inlet temperature (0.51), postdrying time (-0.31), and atomizing pressure (-0.28). C1 Texas A&M Univ, Hlth Sci Ctr, Irma Lerma Rangel Coll Pharm, Dept Pharmaceut Sci, Kingsville, TX USA. Barr Labs Inc, Res & Dev, Pomona, NY USA. Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX USA. RP Khan, MA (reprint author), FDA, CDER, DPQR, LS Bldg 64,HFD-940,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Mansoor.Khan@fda.hhs.gov NR 32 TC 7 Z9 7 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1083-7450 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PY 2007 VL 12 IS 3 BP 307 EP 320 DI 10.1080/10837450701247483 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 186MQ UT WOS:000247783200009 PM 17613894 ER PT J AU Chen, ML Straughn, AB Sadrieh, N Meyer, M Faustino, PJ Ciavarella, AB Meibohm, B Yates, CR Hussain, AS AF Chen, M. -L. Straughn, A. B. Sadrieh, N. Meyer, M. Faustino, P. J. Ciavarella, A. B. Meibohm, B. Yates, C. R. Hussain, A. S. TI A modern view of excipient effects on bioequivalence: Case study of sorbitol SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioavailability; bioequivalence; excipient; permeability; sorbitol ID GASTROINTESTINAL TRANSIT; ACTIVATED-CHARCOAL; CARBOHYDRATE-ABSORPTION; INTESTINAL-ABSORPTION; CLASSIFICATION-SYSTEM; DRUG DISPOSITION; YOUNG-CHILDREN; CREMOPHOR EL; HUMAN PLASMA; FRUIT JUICE AB Purpose. To examine the effect of common excipients such as sugars (sorbitol versus sucrose) on bioequivalence between pharmaceutical formulations, using ranitidine and metoprolol as model drugs. Methods. Two single-dose, replicated, crossover studies were first conducted in healthy volunteers (N=20 each) to compare the effect of 5 Gm of sorbitol and sucrose on bioequivalence of 150 mg ranitidine or 50 mg metoprolol in aqueous solution, followed by a single-dose, nonreplicated, crossover study (N=24) to determine the threshold of sorbitol effect on bioequivalence of 150 mg ranitidine in solution. Results. Ranitidine Cmax and AUC(0-infinity) were decreased by similar to 50% and 45%, respectively, in the presence of sorbitol versus sucrose. Similarly, sorbitol reduced metoprolol Cmax by 23% but had no significant effect on AUC(0-infinity). An appreciable subject-by-formulation interaction was found for ranitidine Cmax and AUC(0-infinity), as well as metoprolol Cmax. Sorbitol decreased the systemic exposure of ranitidine in a dose-dependent manner and affected bioequivalence at a level of 1.25 Gm or greater. Conclusions. As exemplified by sorbitol, some common excipients have unexpected effect on bioavailability/bioequivalence, depending on the pharmacokinetic characteristics of the drug, as well as the type and amount of the excipient present in the formulation. More research is warranted to examine other 'common' excipients that may have unintended influence on bioavailability/bioequivalence. C1 Res Food & Drug Adm, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Food & Drug Adm, Silver Spring, MD 20993 USA. RP Chen, ML (reprint author), Res Food & Drug Adm, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Ave Bldg 21,Rm 3644, Silver Spring, MD 20993 USA. EM meiling.chen@fda.hhs.gov NR 66 TC 32 Z9 35 U1 1 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD JAN PY 2007 VL 24 IS 1 BP 73 EP 80 DI 10.1007/s11095-006-9120-4 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 113WE UT WOS:000242627900008 PM 17048115 ER PT J AU Vernon, JA AF Vernon, John A. TI Letter from the Commissioner's office at the USFDA SO PHARMACOECONOMICS LA English DT Editorial Material C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. Univ Connecticut, Grad Sch Business, Dept Finance, Storrs, CT 06269 USA. RP Vernon, JA (reprint author), US FDA, Off Commissioner, Rockville, MD 20857 USA. EM john.vemon@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2007 VL 25 IS 1 BP 1 EP 2 DI 10.2165/00019053-200725010-00001 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 128OI UT WOS:000243666800001 PM 17192113 ER PT J AU Vernon, JA AF Vernon, John A. TI Letter from the Commissioner's Office at the US FDA SO PHARMACOECONOMICS LA English DT Editorial Material C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Vernon, JA (reprint author), US FDA, Off Commissioner, Rockville, MD 20857 USA. EM john.vernon@fda.hhs.gov NR 5 TC 0 Z9 0 U1 1 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2007 VL 25 IS 2 BP 89 EP 90 DI 10.2165/00019053-200725020-00001 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 136AT UT WOS:000244195700001 PM 17249851 ER PT J AU Vernon, JA AF Vernon, John A. TI Letter from the Commissioner's Office at the US FDA SO PHARMACOECONOMICS LA English DT Editorial Material C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Vernon, JA (reprint author), US FDA, Off Commissioner, 5600 Fishers Lane, Rockville, MD 20857 USA. EM john.vernon@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2007 VL 25 IS 4 BP 267 EP 268 DI 10.2165/00019053-200725040-00001 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 159JJ UT WOS:000245861600001 PM 17402801 ER PT J AU Vernon, JA AF Vernon, John A. TI Perspectives on dynamic optimisation and control theory in treating hyperlipidaemia SO PHARMACOECONOMICS LA English DT Editorial Material C1 Univ Connecticut, Dept Finance, Sch Business, Storrs, CT 06069 USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Vernon, JA (reprint author), Univ Connecticut, Dept Finance, Sch Business, 2100 Hillside Rd, Storrs, CT 06069 USA. EM jvernon@business.uconn.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2007 VL 25 IS 7 BP 533 EP 535 DI 10.2165/00019053-200725070-00001 PG 3 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 195DS UT WOS:000248393300001 PM 17610335 ER PT J AU Morrato, EH Staffa, JA AF Morrato, Elaine H. Staffa, Judy A. TI Effectiveness of risk management plans: a case study of pemoline using pharmacy claims data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE attention-deficit/hyperactivity disorder; pemoline; labeling; risk management; pharmacy claims ID POSTMARKETING SURVEILLANCE; LIVER-TRANSPLANTATION; AUTOIMMUNE HEPATITIS; FDA RECOMMENDATIONS; PRACTICE GUIDELINE; HEPATOTOXICITY; CHILDREN; THERAPY; FAILURE; MEDICATIONS AB Purpose To assess the effectiveness of a pharmaceutical risk management plan using pemoline as a case study and pharmacy claims as the data source. Methods Prescription claims from a continuously enrolled US population (September 1, 2000-September 30, 2002) from Caremark, a pharmacy benefit manager, were evaluated for patients with one or more pemoline claims. Patients were categorized using pemoline as second-line or first-line therapy depending on presence or absence of other central nervous system (CNS) stimulants prescriptions 90 days prior to the first pemoline claim. Logistic regression was performed to compare second-line and first-line usage with regard to patient age, gender and prescribing physician specialty and region of practice. Results Of 1279 296 prescription claims for CNS stimulants, 17 256 (1.3%) were for pemoline. Nine hundred thirteen patients received pemoline and had 90 days or more prior enrollment. Overall, 10% of patients receiving pemoline received it as second-line therapy (95%CI: 8-12%). After adjusting for age, gender, specialty, and region, the odds of receiving pemoline as second-line therapy were significantly greater in pediatrics relative to adults (OR = 2.82, 95%CI: 1.58-5.03), and among those whose prescribers were psychiatrists versus primary care physicians (OR=2.48, 95%CI: 1.37-4.50). Children treated by a psychiatrist had the greatest likelihood for use as second-line therapy (36%, 95%CI: 19-56%). Conclusions Among patients who received pernoline, concordance with second-line therapy recommendations was low, even among the primary target audience of children. These results in a large geographically diverse patient population are consistent with an earlier regional study. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Silver Spring, MD 20993 USA. Univ Colorado Denver & Hlth Sci Ctr, Denver, CO USA. RP Staffa, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, 10903 New Hampshire Ave,Mailstop 4447, Silver Spring, MD 20993 USA. EM judy.staffa@fda.hhs.gov NR 50 TC 5 Z9 5 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2007 VL 16 IS 1 BP 104 EP 112 DI 10.1002/pds.1279 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 128ZV UT WOS:000243699100014 PM 16821248 ER PT J AU Kimchi-Sarfaty, C Marple, AH Shinar, S Kimchi, AM Scavol, D Roma, MI Kim, IW Jones, A Arora, M Gribar, J Gurwitz, D Gottesman, MM AF Kimchi-Sarfaty, Chava Marple, Andrew H. Shinar, Shiri Kimchi, Avraham M. Scavol, David Roma, M. Isabella Kim, In-Wha Jones, Adam Arora, Mili Gribar, John Gurwitz, David Gottesman, Michael M. TI Ethnicity-related polymorphisms and haplotypes in the human ABCB1 gene SO PHARMACOGENOMICS LA English DT Article DE ABCB1; ethnicity; haplotypes; P-glycoprotein; SNPs ID ASHKENAZI-JEWISH POPULATION; MDR1 MULTIDRUG TRANSPORTER; P-GLYCOPROTEIN EXPRESSION; C3435T POLYMORPHISM; DRUG-TRANSPORTER; PARKINSONS-DISEASE; CYSTIC-FIBROSIS; CROHN-DISEASE; RESISTANCE; CANCER AB Introduction: The human multidrug resistance gene ATP-binding cassette B1 (ABCB1) codes for P-glycoprotein (P-gp), an important membrane-bound efflux transporter known to confer anticancer drug resistance as well as affect the pharmacokinetics of many drugs and xenobiotics. A number of single nucleotide polymorphisms (SNPs) have been identified throughout the ABCB1 gene that may have an effect on P-gp expression levels and function. Haplotype as well as genotype analysis of SNPs is becoming increasingly important in identifying genetic variants underlying susceptibility to human disease. Three SNPs, 1236C -> T, 2677G -> T and 3435C -> T, have been repeatedly shown to predict changes in the function of P-gp. The frequencies with which these polymorphisms exist in a population have also been shown to be ethnically related. Methods: In this study, 95 individuals representative of the entire ethnic make-up of the USA were compared with 101 individuals from an Ashkenazi-Jewish population. These individuals were analyzed by genomic sequencing and polymerase chain reaction, using restriction fragment length polymorphisms, to calculate their genotype frequencies. Results: A total of 25 SNPs were located in the exons of the ABCB1 gene. All of the polymorphisms identified were in parts of the ABCB1 gene product predicted to be intracellular, and 16 appear to be novel as compared with those listed by the National Center for Biotechnological Information. Frequencies of the 1236C -> T and 2677G -> T/A/C SNPs were similar for the US and Ashkenazi populations (64.2 and 60.4%, respectively for 1236C -> T [chi(2): 0.30; p <= 1]; 55.8 and 64.4%, respectively for 2677G -> T/A/C [chi(2): 1.49; p <= 1]), but were different for 3435C -> T (24.2% for the US population and 69.3% for the Ashkenazi population [chi 2: 39.927; p <= 0.001]). The 1236T/ 2677T/3435T haplotype occurred in 23.6% (standard error: 0.013) of the Ashkenazi population. Conclusion: The SNP at location 3435C -> T plays a significant role in the ABCB1 gene. The haplotype and genotype analysis from these data may be used as a basis for studies on the relationship between ABCB1 genotypes and drug efficacy, drug toxicity, disease susceptibility or other phenotypes. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. NIH, Natl Ctr Bioinformat, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Mol Genet & Biochem, Natl Lab Genet Israeli Populat, IL-69978 Tel Aviv, Israel. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Gurwitz, David/E-7642-2013 OI Gurwitz, David/0000-0002-9363-1869 FU Intramural NIH HHS [Z01 BC005598-16] NR 56 TC 55 Z9 58 U1 1 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2007 VL 8 IS 1 BP 29 EP 39 DI 10.2217/14622416.8.1.29 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 129YJ UT WOS:000243765700011 PM 17187507 ER PT J AU Kadegowda, AKG Teter, BB Sampugna, J Delmont, P Piperova, LS Erdman, RA AF Kadegowda, A. K. G. Teter, B. B. Sampugna, J. Delmonte, P. Piperova, L. S. Erdman, R. A. TI Trans-7-octadecenoic acid decreased milk fat and altered CLA composition in milk of lactating mice SO POULTRY SCIENCE LA English DT Meeting Abstract DE trans fatty acids; CLA; milk fat C1 [Kadegowda, A. K. G.; Piperova, L. S.; Erdman, R. A.] Univ Maryland, College Pk, MD 20742 USA. [Delmonte, P.] Food & Drug Adm, College Pk, MD 20742 USA. RI Erdman, Richard/F-6195-2010 OI Erdman, Richard/0000-0001-6954-4282 NR 0 TC 0 Z9 0 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PY 2007 VL 86 SU 1 BP 179 EP 180 PG 2 WC Agriculture, Dairy & Animal Science SC Agriculture GA 213UM UT WOS:000249692600555 ER PT J AU Rodriguez, CP Patazca, E Schlesser, JE AF Rodriguez, C. P. Patazca, E. Schlesser, J. E. TI Effects of High Pressure Processing on the reduction of Listeria monocytogenes in the manufacture of soft cheeses SO POULTRY SCIENCE LA English DT Meeting Abstract DE Listeria monocytogenes; soft cheese; high pressure processing C1 [Rodriguez, C. P.; Patazca, E.] Natl Ctr Food Safety & Technol Illinois, Inst Technol, Summit Argo, IL USA. [Schlesser, J. E.] Natl Ctr Food Safety & Technol Illinois, FDA, Summit Argo, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PY 2007 VL 86 SU 1 BP 270 EP 270 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA 213UM UT WOS:000249692600840 ER PT J AU Zoon, KC Yetter, RA AF Zoon, Kathryn C. Yetter, Robert A. BE Gallin, JI Ognibene, FP TI The Regulation of Drugs and Biological Products by the Food and Drug Administration SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 [Zoon, Kathryn C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Yetter, Robert A.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Zoon, KC (reprint author), NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 97 EP 107 DI 10.1016/B978-012369440-9/50011-6 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900010 ER PT B AU Lesko, LJ Sahajwalla, CG AF Lesko, Lawrence J. Sahajwalla, Chandra G. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Role of the FDA in Guiding Drug Development SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter C1 [Lesko, Lawrence J.; Sahajwalla, Chandra G.] US FDA, Off Clin Pharmacol & Biopharmaceut, CDER, Rockville, MD 20857 USA. RP Lesko, LJ (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, CDER, Rockville, MD 20857 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 519 EP 525 DI 10.1016/B978-012369417-1/50074-2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900036 ER PT J AU Reeve, BB Burke, LB Chiang, YP Clauser, SB Colpe, LJ Elias, JW Fleishman, J Hohmann, AA Johnson-Taylor, WL Lawrence, W Claudia, SM Quatrano, LA Riley, WT Smothers, BA Werner, EM AF Reeve, Bryce B. Burke, Laurie B. Chiang, Yen-Pin Clauser, Steven B. Colpe, Lisa J. Elias, Jeffrey W. Fleishman, John Hohmann, Ann A. Johnson-Taylor, Wendy L. Lawrence, William Claudia, S. Moy Quatrano, Louis A. Riley, William T. Smothers, Barbara A. Werner, Ellen M. TI Enhancing measurement in health outcomes research supported by Agencies within the US Department of Health and Human Services SO QUALITY OF LIFE RESEARCH LA English DT Article DE item response theory; computerized adaptive testing; patient-reported outcomes; health-related quality of life ID CONSUMER ASSESSMENT; OBESITY; CARE; PERCEPTIONS; DIAGNOSIS; CRITERIA; MODELS; PLANS AB Many of the Institutes, Agencies and Centers that make up the US Department of Health and Human Services (DHHS) have recognized the need for better instrumentation in health outcomes research, and provide support, both internally and externally, for research utilizing advances in measurement theory and computer technology (informatics). In this paper, representatives from several DHHS agencies and institutes will discuss their need for better instruments within their discipline and describe current or future initiatives for exploring the benefits of these technologies. Together, the perspectives underscore the importance of developing valid, precise, and efficient measures to capture the full burden of disease and treatment on patients. Initiatives, like the Patient-Reported Outcomes Measurement Information System (PROMIS) to create health-related quality of life item banks, represent a trans-DHHS effort to develop a standard set of measures for informing decision making in clinical research, practice, and health policy. C1 NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD USA. Agcy Healthcare Res & Qual, Rockville, MD USA. NIH, Rockville, MD USA. Natl Inst Aging, Bethesda, MD USA. NIMH, Bethesda, MD 20892 USA. Div Nutr Res Coordinat, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Natl Ctr Med Rehabil Res, Bethesda, MD USA. NICHHD, Bethesda, MD 20892 USA. NINR, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. RP Reeve, BB (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, EPN 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM reeveb@mail.nih.gov NR 51 TC 21 Z9 23 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PY 2007 VL 16 SU 1 BP 175 EP 186 DI 10.1007/s11136-007-9190-8 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 194VJ UT WOS:000248371600015 PM 17530449 ER PT J AU Heller, DN AF Heller, David N. TI Ruggedness testing of quantitative atmospheric pressure ionization mass spectrometry methods: the effect of co-injected matrix on matrix effects SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID SIGNAL SUPPRESSION; ION-SUPPRESSION; MILLILITER CONCENTRATIONS; DRUG DISCOVERY; HUMAN PLASMA; ESI-MS; VALIDATION; BIOANALYSIS; PICOGRAM; ASSAYS AB A number of techniques have been suggested to date for assessing matrix effects on quantitative atmospheric pressure ionization mass spectrometry (API-LC/MS) methods. A newly designed experiment has the aim of efficiently simulating the quantitative behavior of an LC/MS method as a function of the amount of co-injected matrix extract. Two sets of mixtures were prepared in different formats to study matrix effects as a function of analyte or matrix amount. Chromatographic conditions were varied as well, to alter the separation between analyte and co-extractants, and thereby provide different matrix effect conditions for testing the same mixtures. Graphical presentation of the results was used to gain insight into the matrix effect phenomenon. The results suggest that ruggedness for API-LC/MS methods may be defined as the absence of significant variation in results as a function of the amount of co-injected matrix. That is, a non-rugged API-LC/MS method may give consistent results only if a fixed amount of matrix is co-injected on a specific instrument. The results also point to the existence of a specific matrix concentration for the onset of matrix effects, below which these effects are not significant. These issues are important to the US FDA Center for Veterinary Medicine, which has regulatory authority for methods used to monitor for drug residues in food tissues from animals. The ruggedness testing technique suggested here may be an important factor in determining that a method is ready for multi-laboratory testing on multiple instruments. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM david.heller@fda.hhs.gov NR 24 TC 31 Z9 36 U1 0 U2 13 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2007 VL 21 IS 5 BP 644 EP 652 DI 10.1002/rcm.2882 PG 9 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 141ZR UT WOS:000244618400004 PM 17279489 ER PT J AU Tareke, E Bowyer, JF Doerge, DR AF Tareke, Eden Bowyer, John F. Doerge, Daniel R. TI Quantification of rat brain neurotransmitters and metabolites using liquid chromatography/electrospray tandem mass spectrometry and comparison with liquid chromatography/electrochemical detection SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID METHAMPHETAMINE-INDUCED NEUROTOXICITY; 3,4-DIHYDROXYPHENYLACETIC ACID; ELECTROCHEMICAL DETECTION; HOMOVANILLIC-ACID; DOPAMINE; SEROTONIN; REGIONS; AMPHETAMINE; ACRYLAMIDE; STRIATUM AB Analytical methodology based on solid-phase extraction, polar reversed-phase liquid chromatography, and electrospray tandem mass spectrometry (LC/MS/MS) with isotope dilution was developed and validated for quantifying the neurotransmitters, dopamine and serotonin, and their major metabolites in brain tissue. Limits of detection (0.1-20 pg/mg tissue) were sufficient for analysis of multiple neurotransmitters in rat brain regions, including parietal cortex, hypothalamus, pituitary, substantia nigra, and striatum. Method performance was compared with contemporaneous measurements using a well-established procedure based on ion-pairing reversed-phase liquid chromatography and amperometric detection. The principal advantages of the LC/MS/MS method include a more robust sample purification procedure, an optimized chromatographic separation, and the qualitative and quantitative assurance that comes from coeluting isotopically labeled internal standards; however, sensitivity did not consistently improve upon that provided by amperometric detection. This methodology may be particularly useful for applications in which simultaneous determinations are required for drugs and their affected neurotransmitters in specific brain regions. Published in 2007 by John Wiley & Sons, Ltd. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov FU PHS HHS [224-93-0001] NR 14 TC 34 Z9 34 U1 1 U2 20 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2007 VL 21 IS 23 BP 3898 EP 3904 DI 10.1002/rcm.3295 PG 7 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 236FA UT WOS:000251287200016 PM 17979107 ER PT S AU Rahamimoff, H Elbaz, B Alperovich, A Kimchi-Sarfaty, C Gottesman, MM Lichtenstein, Y Eskin-Shwartz, M Kasir, J AF Rahamimoff, H. Elbaz, B. Alperovich, A. Kimchi-Sarfaty, C. Gottesman, M. M. Lichtenstein, Y. Eskin-Shwartz, M. Kasir, J. BE Herchuelz, A Blaustein, MP Lytton, J Philipson, KD TI Cyclosporin A-dependent Downregulation of the Na+/Ca2+ exchanger expression SO SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Sodium-Calcium Exchange CY AUG 23-27, 2006 CL Brussels, BELGIUM DE Na+/Ca2+ exchanger expression; cyclosporin A; cyclophilin A; proline mutagenesis ID CIS-TRANS ISOMERASE; NA+-CA2+ EXCHANGER; SURFACE EXPRESSION; FUNCTIONAL EXPRESSION; RAT; PROTEIN; CLONING; CYCLOPHILIN; CHANNELS; RBE-1 AB Cyclosporin A (CsA) is an immunosuppressive drug commonly given to transplant patients. Its application is accompanied by severe side effects related to calcium, among them hypertension and nephrotoxicity. The Na+/Ca (2+) exchanger (NCX) is a major calcium regulator expressed in the surface membrane of all excitable and many nonexcitable tissues. Three genes, NCX1, NCX2, and NCX3 code for Na+/Ca2+ exchange activity. NCX1 gene products are the most abundant. We have shown previously that exposure of NCX1-transfected HEK 293 cells to CsA, leads to concentration-dependent reduction of Na+/Ca2+ exchange activity and surface expression, without a reduction in total cell-expressed NCX1 protein. We show now that the effect of CsA on NCX1 protein expression is not restricted to transfected cells overexpressing the NCX1 protein but exhibited also in cells expressing endogenously the NCX1 protein (L6, H9c2, and primary smooth muscle cells). Exposure of NCX2- and NCX3-transfected cells to CsA results also in reduction of Na+/Ca2+ exchange activity and surface expression, though the sensitivity to the drug was lower than in NCX1-transfected cells. Studying the molecular mechanism of CsA-NCX interaction suggests that cyclophilin (Cyp) is involved in NCX1 protein expression and its modulation by CsA. Deletion of 426 amino acids from the large cytoplasmic loop of the protein retains the CsA-dependent downregulation of the truncated NCX1 suggesting that CsA-Cyp-NCX interaction involves the remaining protein domains. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Hematol, Bethesda, MD 20892 USA. RP Rahamimoff, H (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. EM Hannah.Rahamimoff@huji.ac.il OI Elbaz, Benayahu/0000-0001-5202-4598 NR 19 TC 7 Z9 8 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-649-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1099 BP 204 EP 214 DI 10.1196/annals.1387.046 PG 11 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BGC24 UT WOS:000245982300024 PM 17446460 ER PT J AU Lachenbruch, PA Miller, FW Rider, LG AF Lachenbruch, Peter A. Miller, Frederick W. Rider, Lisa G. TI Developing international consensus on measures of improvement for patients with myositis SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; PRELIMINARY CORE SET; RHEUMATOID-ARTHRITIS; OUTCOME ASSESSMENT; DISEASE; ADULT AB We discuss methods of developing consensus in measuring improvement in myositis. We consider selecting candidate variables, reliability and validity, percentage improvement/worsening rules, rules based on CART and logistic regression. We discuss criteria for determining an acceptable rule that include both numerical measures and physician acceptance. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Lachenbruch, PA (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM lachenbruchpa@aol.com OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS NR 12 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PY 2007 VL 16 IS 1 BP 51 EP 64 DI 10.1177/0962280206070652 PG 14 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 138ED UT WOS:000244345000005 PM 17338294 ER PT J AU Rudenko, L Matheson, JC AF Rudenko, Larisa Matheson, John C. TI The USFDA and animal cloning: Risk and regulatory approach SO THERIOGENOLOGY LA English DT Article; Proceedings Paper CT Symposium on Assisted Reproductive Technologies and Food Safety in Farm Animals CY JAN 06, 2007 CL Kyoto, JAPAN SP IETS DE livestock cloning; risk assessment; food; FDA ID ADULT SOMATIC-CELLS; BOVINE PREIMPLANTATION EMBRYOS; CLONED TRANSGENIC CALVES; IN-VITRO SYSTEMS; NUCLEAR TRANSFER; FIBROBLAST CELLS; FETAL FIBROBLASTS; DNA METHYLATION; DONOR GENOME; MAJOR CAUSE AB The Food and Drug Administration's (FDA's) Center for Veterinary Medicine issued a voluntary request to producers of livestock clones not to introduce food from clones or their progeny into commerce until the agency had assessed whether production of cattle, swine, sheep, or goats by somatic cell nuclear transfer (SCNT) posed any unique risks to the animal(s) involved in the process, humans, or other animals by consuming food from those animals, compared with any other assisted reproductive technology (ART) currently in use. Following a comprehensive review, no anomalies were observed in animals produced by cloning that have not also been observed in animals produced by other ARTs and natural mating. Further systematic review on the health of, and composition of meat and milk from, cattle, swine, and goat clones and the progeny of cattle and sheep did not result in the identification of any food-consumption hazards. The agency therefore concluded that food from cattle, swine, and goat clones was as safe to eat as food from animals of those species derived by conventional means. The agency also concluded that food from the progeny of the clone of any species normally consumed for food is as safe to eat as those animals. The article also describes the methodology used by the agency to analyze data and draw these conclusions, the plans the agency has proposed to manage any identified risks, and the risk communication approaches the agency has used. Published by Elsevier Inc. C1 US FDA, Ctr Vet Med, Dept Hlth & Human Serv, Rockville, MD 20855 USA. RP Rudenko, L (reprint author), US FDA, Ctr Vet Med, Dept Hlth & Human Serv, 7500 Standish Pl,HFV-100, Rockville, MD 20855 USA. EM larisa.rudenko@fda.hhs.gov NR 76 TC 25 Z9 25 U1 5 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD JAN 1 PY 2007 VL 67 IS 1 BP 198 EP 206 DI 10.1016/j.theriogenology.2006.09.033 PG 9 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA 120FZ UT WOS:000243071200025 PM 17055042 ER PT S AU Mattamal, GJ AF Mattamal, George J. BE Chandra, T Tsuzaki, K Militzer, M Ravindran, C TI USFDA perspective on the regulation of cyanoacrylate polymer tissue adhesives in clinical applications SO THERMEC 2006, Pts 1-5 SE MATERIALS SCIENCE FORUM LA English DT Proceedings Paper CT 5th International Conference on Processing and Manufacturing of Advanced Materials CY JUL 04-08, 2006 CL Vancouver, CANADA SP Minerals, Met & Mat Soc DE tissue adhesives; blood; sealant; protein; polymeric; cyanoacrylate; monomer; skin; embolic. toxic; degrade; Class I, II, and IDE, PMA; regulation; dental cement; orthodontic; neurological; cardiovascular AB A brief description of the uses and clinical applications of synthetic cyanoacrylate polymer adhesive/glues that have been cleared and/or approved as medical devices by FDA since the Medical Device Amendments of 1976 were enacted. This includes cyanoacrylate Class I devices (Exempt and not Exempt devices), Class II cyanoacrylate devices such as Dental Cements and Orthodontic Bracket Adhesives, and Class III (PMA) devices such as Dermabond (TM), Indermil (TM) Tissue Adhesive, and Trufill (R) n-Butyl Cyanoacrylate Embolic Agent. By citing an example of recently FDA approved Class III (PMA) devices in the Cyanoacrylate technology, the author provides a brief discussion of the FDA approval process of medical devices. It includes the FDA issues regarding the published guidance document for "Cyanoacrylate Topical Tissue Adhesives" that will provide guidance to regulatory personnel and manufacturers ill the preparation of IDE applications and in the development of valid scientific evidence to support PMA applications for cyanocrylate tissue adhesives intended for topical approximation of skin and others. Also, the author provides a short regulatory description of US FDA; under what laws its operates, how FDA evaluates new devices for marketing, and how the device regulatory system works, for example, Class I, Class II, and Class III cyanoacrylate medical devices. C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Gen Restorat & Neurol Devices, Rockville, MD 20850 USA. RP Mattamal, GJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Gen Restorat & Neurol Devices, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 2 TC 2 Z9 2 U1 0 U2 2 PU TRANS TECH PUBLICATIONS LTD PI STAFA-ZURICH PA LAUBLSRUTISTR 24, CH-8717 STAFA-ZURICH, SWITZERLAND SN 0255-5476 BN 978-0-87849-428-6 J9 MATER SCI FORUM PY 2007 VL 539-543 BP 692 EP 697 PN 1-5 PG 6 WC Engineering, Manufacturing; Materials Science, Multidisciplinary SC Engineering; Materials Science GA BFW58 UT WOS:000245106100113 ER PT B AU Post, LO AF Post, Lynn O. BE Gupta, RC TI Regulatory considerations in veterinary toxicology SO VETERINARY TOXICOLOGY: BASIC AND CLINICAL PRINCIPLES LA English DT Article; Book Chapter C1 US FDA, CVM, Falling Waters, WV USA. RP Post, LO (reprint author), US FDA, CVM, Falling Waters, WV USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-048160-9 PY 2007 BP 92 EP 109 DI 10.1016/B978-012370467-2/50104-8 D2 10.5005/jp/books/10078 PG 18 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA BCU08 UT WOS:000311390700009 ER PT B AU Choudhuri, S Arvidson, K Chanderbhan, R AF Choudhuri, Supratim Arvidson, Kirk Chanderbhan, Ronald BE Gupta, RC TI Carcinogenesis: mechanisms and models SO VETERINARY TOXICOLOGY: BASIC AND CLINICAL PRINCIPLES LA English DT Article; Book Chapter ID NATIONAL TOXICOLOGY PROGRAM; K-RAS ONCOGENE; TRANSGENIC MICE; MISMATCH-REPAIR; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; CHEMICAL-STRUCTURE; MAMMALIAN-CELLS; AFLATOXIN B-1; MGMT PROTECTS; CANCER C1 [Choudhuri, Supratim; Chanderbhan, Ronald] US FDA, Div Biotechnol, College Pk, MD USA. [Choudhuri, Supratim; Chanderbhan, Ronald] US FDA, GRAS Notice Review, College Pk, MD USA. [Arvidson, Kirk] US FDA, Div Food Contact Notificat, College Pk, MD USA. RP Choudhuri, S (reprint author), US FDA, Div Biotechnol, College Pk, MD USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-048160-9 PY 2007 BP 343 EP 359 DI 10.1016/B978-012370467-2/50119-X D2 10.5005/jp/books/10078 PG 17 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA BCU08 UT WOS:000311390700024 ER PT J AU Tubaro, A Hungerford, J AF Tubaro, Aurelia Hungerford, James BE Gupta, RC TI Toxicology of marine toxins SO VETERINARY TOXICOLOGY: BASIC AND CLINICAL PRINCIPLES LA English DT Article; Book Chapter ID BLOOD COLLECTION CARDS; DINOFLAGELLATE ALEXANDRIUM-OSTENFELDII; PERFORMANCE LIQUID-CHROMATOGRAPHY; 7-EPI-PECTENOTOXIN-2 SECO ACID; OKADAIC ACID; DOMOIC ACID; NEW-ZEALAND; SHELLFISH TOXIN; PROTOCERATIUM-RETICULATUM; BREVETOXIN PBTX-3 C1 [Tubaro, Aurelia] Univ Trieste, DEMREP, Dept Mat & Nat Subst, Trieste, Italy. [Hungerford, James] AOAC Task Force Marine & Freshwater Toxins, Bothell, WA USA. [Hungerford, James] US FDA, Seafood Prod Res Ctr, Bothell, WA USA. RP Tubaro, A (reprint author), Univ Trieste, DEMREP, Dept Mat & Nat Subst, Trieste, Italy. NR 173 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-048160-9 PY 2007 BP 725 EP 752 DI 10.1016/B978-012370467-2/50157-7 D2 10.5005/jp/books/10078 PG 28 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA BCU08 UT WOS:000311390700062 ER PT S AU Fu, PP Xia, QS Boudreau, MD Howard, PC Tolleson, WH Wamer, WG AF Fu, Peter P. Xia, Qingsu Boudreau, Mary D. Howard, Paul C. Tolleson, William H. Wamer, Wayne G. BE Litwack, G TI Physiological role of retinyl palmitate in the skin SO VITAMIN A SE Vitamins and Hormones LA English DT Review; Book Chapter ID HUMAN EPIDERMAL-KERATINOCYTES; LEBER CONGENITAL AMAUROSIS; ALL-TRANS-RETINOL; VITAMIN-A ACETATE; BINDING-PROTEIN; TOPICAL RETINOIDS; IN-VIVO; PHOTODECOMPOSITION PRODUCTS; MATRIX METALLOPROTEINASES; CONTACT HYPERSENSITIVITY AB The skin is similar to other organs in how it absorbs, stores, and metabolizes vitamin A. However, because of the anatomical location of skin and the specialized physiological roles it plays, there are ways in which the skin is rather unique. The stratified structure of the epidermis results from the orchestration of retinoid-influenced cellular division and differentiation. Similarly, many of the physiological responses of the skin, such as dermal aging, immune defense, and wound healing, are significantly affected by retinoids. While much is known about the molecular events through which retinoids affect the skin's responses, more remains to be learned. Interest in the effects of retinol, retinyl palmitate, and other retinoids on the skin, fueled in part by the promise of improved dermatologic and cosmetic products, will undoubtedly make the effects of retinoids on skin a subject for continued intense investigation. (c) 2007 Elsevier Inc. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 139 TC 14 Z9 14 U1 2 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 978-0-12-709875-3 J9 VITAM HORM JI Vitam. Horm. PY 2007 VL 75 BP 223 EP + DI 10.1016/S0083-6729(06)75009-9 PG 36 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BFZ30 UT WOS:000245587800009 PM 17368318 ER PT J AU McDermott, PF English, LL Hall-Robinson, E White, DG Zhao, S AF McDermott, P. F. English, L. L. Hall-Robinson, E. White, D. G. Zhao, S. TI Antimicrobial resistance among Campylobacter from retail meats in the United States, 2002-2005 SO ZOONOSES AND PUBLIC HEALTH LA English DT Meeting Abstract C1 [McDermott, P. F.; English, L. L.; Hall-Robinson, E.; White, D. G.; Zhao, S.] US FDA, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1863-1959 J9 ZOONOSES PUBLIC HLTH JI Zoonoses Public Health PY 2007 VL 54 SU 1 BP 10 EP 10 PG 1 WC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences GA 225LK UT WOS:000250519200031 ER PT J AU Zhao, S Cullen, P Abbott, J Friedman, S English, L Hall-Robinson, E McDermott, P White, D AF Zhao, S. Cullen, P. Abbott, J. Friedman, S. English, L. Hall-Robinson, E. McDermott, P. White, D. TI Characterization of Campylobacter recovered from retail meat samples: National Antimicrobial Resistance Monitoring System (NARMS)-2005 SO ZOONOSES AND PUBLIC HEALTH LA English DT Meeting Abstract C1 [Zhao, S.; Cullen, P.; Abbott, J.; Friedman, S.; English, L.; Hall-Robinson, E.; McDermott, P.; White, D.] FDA, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1863-1959 J9 ZOONOSES PUBLIC HLTH JI Zoonoses Public Health PY 2007 VL 54 SU 1 BP 25 EP 26 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences GA 225LK UT WOS:000250519200078 ER PT J AU Shima, K Giri, CP Kopecko, DJ AF Shima, K. Giri, C. P. Kopecko, D. J. TI Role of lipid rafts in human epithelial cell invasion by Campylobacter jejuni SO ZOONOSES AND PUBLIC HEALTH LA English DT Meeting Abstract C1 [Shima, K.; Kopecko, D. J.] FDA CBER, Bethesda, MD USA. [Giri, C. P.] FDA CFSAN, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1863-1959 J9 ZOONOSES PUBLIC HLTH JI Zoonoses Public Health PY 2007 VL 54 SU 1 BP 90 EP 90 PG 1 WC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences GA 225LK UT WOS:000250519200305 ER PT J AU De Bosschere, H Wang, Z Orlandi, PA AF De Bosschere, H. Wang, Z. Orlandi, P. A. TI First diagnosis of Encephalitozoon intestinalis and E-hellem in a European brown hare (Lepus europaeus) with kidney lesions SO ZOONOSES AND PUBLIC HEALTH LA English DT Article DE Encephalitozoon intestinalis; E. hellem; European brown hare; diagnosis; kidney; molecular methods ID MICROSPORIDIOSIS; INFECTION; LOVEBIRD AB Encephalitozoon intestinalis and Encephalitozoon hellem were diagnosed in the kidneys of a free - ranging European brown hare (Lepus europaeus) with multi-focal wedge-shaped chronic interstitial nephritis using real-time PCR and microarray. This is the first description of these microsporidia species in a European brown hare, which are both potential zoonotic agents. C1 Vet Sect, Med Lab Bruyland, B-8500 Kortrijk, Belgium. USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, Laurel, MD 20708 USA. RP De Bosschere, H (reprint author), Vet Sect, Med Lab Bruyland, Meiweg 1A, B-8500 Kortrijk, Belgium. EM hendrik.de.bosschere@bruyland.be NR 11 TC 13 Z9 15 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1863-1959 J9 ZOONOSES PUBLIC HLTH JI Zoonoses Public Health PY 2007 VL 54 IS 3-4 BP 131 EP 134 DI 10.1111/j.1863-2378.2007.01034.x PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences GA 161BB UT WOS:000245988200004 PM 17456143 ER PT J AU Easley, CJ Karlinsey, JM Bienvenue, JM Legendre, LA Roper, MG Feldman, SH Hughes, MA Hewlett, EL Merkel, TJ Ferrance, JP Landers, JP AF Easley, Christopher J. Karlinsey, James M. Bienvenue, Joan M. Legendre, Lindsay A. Roper, Michael G. Feldman, Sanford H. Hughes, Molly A. Hewlett, Erik L. Merkel, Tod J. Ferrance, Jerome P. Landers, James P. TI A fully integrated microfluidic genetic analysis system with sample-in-answer-out capability SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE full integration; micro total analysis system; microdevice; pumping; valving ID CHEMICAL-ANALYSIS SYSTEMS; POLYMERASE-CHAIN-REACTION; BORDETELLA-PERTUSSIS; PRESSURE INJECTION; DNA AMPLIFICATION; CELL-LYSIS; DEVICE; GLASS; PCR; ELECTROPHORESIS AB We describe a microfluidic genetic analysis system that represents a previously undescribed integrated microfluidic device capable of accepting whole blood as a crude biological sample with the endpoint generation of a genetic profile. Upon loading the sample, the glass microfluidic genetic analysis system device carries out on-chip DNA purification and PCR-based amplification, followed by separation and detection in a manner that allows for microliter samples to be screened for infectious pathogens with sample-in-answer-out results in < 30 min. A single syringe pump delivers sample/reagents to the chip for nucleic acid purification from a biological sample. Elastomeric membrane valving isolates each distinct functional region of the device and, together with resistive flow, directs purified DNA and PCR reagents from the extraction domain into a 550-nl chamber for rapid target sequence PCR amplification. Repeated pressure-based injections of nanoliter ali-quots of amplicon (along with the DNA sizing standard) allow electrophoretic separation and detection to provide DNA fragment size information. The presence of Bacillus anthracis (anthrax) in 750 nl of whole blood from living asymptomatic infected mice and of Bordetella pertussis in 1 mu l of nasal aspirate from a patient suspected of having whooping cough are confirmed by the resultant genetic profile. C1 Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. Univ Virginia, Hlth Syst, Dept Comparat Med, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Syst, Dept Infect Dis, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Syst, Dept Pathol, Charlottesville, VA 22908 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Landers, JP (reprint author), Univ Virginia, Dept Chem, Mccormick Rd, Charlottesville, VA 22904 USA. EM landers@virginia.edu RI Roper, Michael/D-2386-2010; OI Ferrance, Jerome/0000-0003-1020-8289 FU NHGRI NIH HHS [R01 HG001832, R01 HG002613]; NIAID NIH HHS [U54 AI057168] NR 35 TC 356 Z9 358 U1 9 U2 130 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 19 PY 2006 VL 103 IS 51 BP 19272 EP 19277 DI 10.1073/pnas.0604663103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121OJ UT WOS:000243166600012 PM 17159153 ER PT J AU Calvert, RJ Tepper, S Kammouni, W Anderson, LM Kritchevsky, D AF Calvert, Richard J. Tepper, Shirley Kammouni, Wafa Anderson, Lucy M. Kritchevsky, David TI Elevated K-ras activity with cholestyramine and lovastatin, but not konjac mannan or niacin in lung - Importance of mouse strain SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE lung; mice; cholestyramine; lovastatin; konjac mannan; niacin; K-ras activity; cholesterol ID CORONARY ATHEROSCLEROSIS PREVENTION; SCANDINAVIAN SIMVASTATIN SURVIVAL; LONG-TERM TREATMENT; DIETARY FIBER; COLORECTAL-CANCER; CONTROLLED TRIAL; CLINICAL-TRIALS; BREAST-CANCER; STATIN USE; FOLLOW-UP AB Our previous work established that hypocholesterolemic agents altered K-ras intracellular localization in lung. Here, we examined K-ras activity to define further its potential importance in lung carcinogenesis. K-ras activity in lungs from male A/J, Swiss and CS7BL/6 mice was examined. For 3 weeks, mice consumed either 2 or 4% cholestyramine (CS), 1% niacin, 5% konjac marman (KM), or were injected with lovastatin 25 mg/kg three or five times weekly (Lov-3X and Lov-5X). A pair-fed (PF) group was fed the same quantity of diet consumed by the Lov-5X mice to control for lower body weights in Lov-5X mice. After 3 weeks, serum cholesterol was assayed with a commercial kit. Activated K-ras protein from lung was affinity precipitated with a Raf-1 ras binding domain- glutathione-S-transferase fusion protein bound to glutathione-agarose beads, followed by Western blotting, K-ras antibody treatment, and chemilumines cent detection. Only KM reduced serum cholesterol (in two of three mouse strains). In C56BL/6 mice treated with Lov-3X, lung K-ras activity increased 1.8-fold versus control (p = 0.009). In normal lung with wild-type K-ras, this would be expected to be associated with maintenance of differentiation. In A/J mice fed 4% CS, K-ras activity increased 2.1-fold (p = 0.02), which might be responsible for the reported enhancement of carcinogenesis in carcinogen-treated rats fed CS. KM feeding and PF treatment had no significant effects on K-ras activity. These data are consistent with the concept that K-ras in lung has an oncogenic function when mutated, but may act as a tumor suppressor when wild-type. Published by Elsevier Inc. C1 US FDA, Div Res & Appl Technol, Off Nutrit Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Calvert, RJ (reprint author), US FDA, Div Res & Appl Technol, Off Nutrit Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM calvert@mail.ncifcrf.gov FU NHLBI NIH HHS [K06 HL000734-45]; PHS HHS [00734, 03299] NR 34 TC 5 Z9 5 U1 1 U2 2 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 15 PY 2006 VL 72 IS 12 BP 1749 EP 1755 DI 10.1016/j.bcp.2006.08.026 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 118FT UT WOS:000242928500013 PM 17005160 ER PT J AU Kane, RC Farrell, AT Saber, H Tang, SH Williams, G Jee, JM Liang, CY Booth, B Chidambaram, N Morse, D Sridhara, R Garvey, P Justice, R Pazdur, R AF Kane, Robert C. Farrell, Ann T. Saber, Haleh Tang, Shenghui Williams, Gene Jee, Josephine M. Liang, Chengyi Booth, Brian Chidambaram, Nallaperumal Morse, David Sridhara, Rajeshwari Garvey, Patricia Justice, Robert Pazdur, Richard TI Sorafenib for the treatment of advanced renal cell carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID RANDOMIZED-TRIAL; INTERFERON-ALPHA; SURVIVAL; INTERLEUKIN-2 AB Purpose: This report describes the U.S. Food and Drug Administration (FDA) review and approval of sorafenib (Nexavar, BAY43-9006), a new small-molecule, oral, multi-kinase inhibitor for the treatment of patients with advanced renal cell carcinoma (RCC). Experimental Design: After meeting with sponsors during development studies of sorafenib, the FDA reviewed the phase 3 protocol under the Special Protocol Assessment mechanism. Following new drug application submission, FDA independently analyzed the results of two studies in advanced RCC: a large, randomized, double-blinded, phase 3 international trial of single-agent sorafenib and a supportive phase 2 study. Results: In the phase 3 trial, 902 patients with advanced progressive RCC after one prior systemic therapy were randomized to 400 mg sorafenib twice daily plus best supportive care or to a matching placebo plus best supportive care. Primary, study end points included overall survival and progression-free survival (PFS). A PFS analysis, pre-specified and conducted after a total of 342 events, showed statistically significant superiority for the sorafenib group (median = 167 days) compared with that for the controls (median = 84 days, log-rank P < 0.000001); the sorafenib/placebo hazard ratio was 0.44 (95% confidence interval, 0.35-0.55). Results were similar regardless of patient risk score, performance status, age, or prior therapy. The (partial) response rate to sorafenib was 2.1%. Overall survival results are preliminary. The principal toxicities in the sorafenib patients included reversible skin rashes in 40% and hand-foot skin reaction in 30%; diarrhea was reported in 43%, treatment-emergent hypertension was reported in 17%, and sensory neuropathic changes were reported in 13%. Grade 4 adverse events were uncommon. Grade 3 adverse events were hand-foot skin reaction (6%), fatigue (5%), and hypertension (3%). Laboratory findings included asymptomatic hypophosphatemia in 45% of sorafenib patients versus 11% in the placebo arm and elevation of serum lipase in 41% of sorafenib patients versus 30% in the placebo arm. Grade 4 pancreatitis,was reported in two sorafenib patients, although both patients subsequently resumed sorafenib, with one at full dose. Conclusions: Sorafenib received FDA regular approval on December 20, 2005 for the treatment of advanced RCC based on the persuasive magnitude of improvement in PFS with acceptable safety. The recommended dose is 400 mg (two 200-mg tablets) twice daily taken either 1 h before or 2 h after meals. Adverse events were accommodated by temporary dose interruptions or reductions. C1 US FDA, Div Drug Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Kane, RC (reprint author), US FDA, Div Drug Oncol Prod, Ctr Drug Evaluat & Res, Room 2109,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM robert.kane@fda.hhs.gov NR 16 TC 259 Z9 269 U1 0 U2 18 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 2006 VL 12 IS 24 BP 7271 EP 7278 DI 10.1158/1078-0432.CCR-06-1249 PG 8 WC Oncology SC Oncology GA 121NT UT WOS:000243165000011 PM 17189398 ER PT J AU Andreishcheva, EN Vann, WF AF Andreishcheva, Ekaterina N. Vann, Willie F. TI Escherichia coli BL21(DE3) chromosome contains a group II capsular gene cluster SO GENE LA English DT Article DE E. coli B; capsule gene cluster; polysaccharide ID POLYSIALIC ACID; EXPRESSION; K1; POLYSACCHARIDE; STRAINS; INFLUENZAE; PROTEINS; BACTERIA AB During our study of de novo synthesis of Escherichia coli K1 capsular polysaccharides, we found that E. coli BL21(DE3) has a capsular gene cluster, similar to those of group II capsular E. coli strains. Analysis of the nucleotide sequence of the E. coli BL21 (DE3) gene cluster showed homologues to all group II regions 1 and 3 genes and the presence of an IS1 element in one of the region 2 ORFs, which likely prevents capsule expression. Complementation analysis showed that region I and 3 genes encode functional proteins that are sufficient for the export of newly synthesized polysaccharide. The gene products of B121(DE3) kpsC and kpsS supported in vitro de novo synthesis of K1 polysaccharide when coexpressed with K1 NeuE and NeuS. Sequence homology between BL21(DE3) region 2 open reading frames and capsule-related genes in other bacteria such as Haemophilus influenzae serotype b, suggests that the encapsulated ancestor of BL21(DE3) may have produced a ribose/ribitol-phosphate containing polysaccharide. (c) 2006 Elsevier B.V. All rights reserved. C1 Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bldg 29,Room 103,8800 Rockville Pike, Bethesda, MD 20892 USA. EM wvann@helix.nih.gov NR 32 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 15 PY 2006 VL 384 BP 113 EP 119 DI 10.1016/j.gene.2006.07.020 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 115JY UT WOS:000242731800012 PM 16959439 ER PT J AU Binienda, ZK Ali, SF Virmani, A Amato, A Salem, N Przybyla, BD AF Binienda, Zbigniew K. Ali, Syed F. Virmani, Ashraf Amato, Antonino Salem, Nadia Przybyla, Beata D. TI Co-regulation of dopamine D-1 receptor and uncoupling protein-2 expression in 3-nitropropionic acid-induced neurotoxicity: Neuroprotective role of L-carnitine SO NEUROSCIENCE LETTERS LA English DT Article DE 3-nitropropionic acid; L-carnitine; striatum; uncoupling proteins; dopamine; rat ID FREE FATTY-ACIDS; SUCCINATE-DEHYDROGENASE; CELL-DEATH; RAT-BRAIN; ALPHA; DYSFUNCTION; ENERGY; 3-NPA AB This study tested the hypothesis that the expression of uncoupling proteins (UCPs) and dopamine (DA) system genes is responsive to 3-nitropropionic acid (3-NPA) neurotoxic effects and to the neuroprotective effects of the mitochondrial enhancer, L-camitine (LC), in the rat striatum. Inactivation of mitochondrial succinate dehydrogenase (SDH) by 3-NPA results in hypoxic brain damage. Hypoxic conditions induce uncoupling protein-2 (UCP-2). An increase in UCP-2 expression may lead to a decrease in production of reactive oxygen species (ROS) associated with energy depletion. However, this adaptive response can also lead to a reduction of ATP that may further contribute to energy deficit and mitochondrial dysfunction. Here, male adult Sprague-Dawley rats (n = 5/group) were injected either with saline or 3-NPA at 30 mg/kg, s.c. alone or 30 min after pre-treatment with LC (100 mg/kg, i.p.). Rectal temperature was monitored before treatment and 4 h following 3-NPA administration. Animals were sacrificed 4 h post-treatment. Total RNA was isolated from the striatum and transcripts of UCP-2, UCP-4 and UCP-5 genes, as well as genes related to dopamine metabolism, such as DA D-1 and D-2 receptors, tyrosine hydroxylase (TH), monoamine oxidase-B (MAO-B), and vesicular monoamine transporter-2 (VMAT-2), were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). While core temperature decreased significantly in 3-NPA-treated rats, LC significantly inhibited the hypothermic effect of 3-NPA (p < 0.05). 3-NPA caused a significant increase in UCP-2 and DA D, receptor gene expression in the striatum and both effects were attenuated by pre-treatment with LC. Since LC maintains the ATP/ADP ratio and was previously shown to be neuroprotective against 3-NPA toxicity, the modulation of UCP-2 expression by LC suggests that LC counteracts energy dissipation and thus prevents the negative effects of ATP decline on DA neurotransmission. Published by Elsevier Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Food & Drug Adm, Jefferson, AR 72079 USA. Sigma Tau Hlth Sci SpA, Res & Dev, Rome, Italy. Sigma Tau Res Inc, Gaithersburg, MD 20877 USA. Univ Arkansas Med Sci, Inst Aging, Little Rock, AR 72205 USA. RP Binienda, ZK (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Food & Drug Adm, Jefferson, AR 72079 USA. EM zbigniew.binienda@fda.hhs.gov NR 25 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 13 PY 2006 VL 410 IS 1 BP 62 EP 65 DI 10.1016/j.neulet.2006.09.070 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 111ZQ UT WOS:000242495100013 PM 17052844 ER PT J AU Notari, L Baladron, V Aroca-Aguilar, JD Balko, N Heredia, R Meyer, C Notario, PM Saravanamuthu, S Nueda, ML Sanchez-Sanchez, F Escribano, J Laborda, J Becerra, SP AF Notari, Luigi Baladron, Victoriano Aroca-Aguilar, J. Daniel Balko, Natalia Heredia, Raul Meyer, Christina Notario, Patricia M. Saravanamuthu, Senthil Nueda, Maria-Luisa Sanchez-Sanchez, Francisco Escribano, Julio Laborda, Jorge Becerra, S. Patricia TI Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; CEREBELLAR GRANULE CELLS; MEDIATED GENE-TRANSFER; FACTOR PEDF; DOCOSAHEXAENOIC ACID; MOTOR-NEURONS; CHOROIDAL NEOVASCULARIZATION; INTERPHOTORECEPTOR MATRIX; NEUROTROPHIC ACTIVITY; NEUROPROTECTIN D1 AB Pigment epithelium-derived factor (PEDF) is an extracellular multifunctional protein belonging to the serpin superfamily with demonstrable neurotrophic, gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. We have previously provided biochemical evidence for high affinity PEDF-binding sites and proteins in plasma membranes of retina, retinoblastoma, and CNS cells. This study was designed to reveal a receptor involved in the biological activities of PEDF. Using a yeast two-hybrid screening, we identified a novel gene from pigment epithelium of the human retina that codes for a PEDF-binding partner, which we term PEDF-R. The derived polypeptide has putative transmembrane, intracellular and extracellular regions, and a phospholipase domain. Recently, PEDF-R (TTS2.2/independent phospholipase A(2) (PLA(2))zeta and mouse desnutrin/ATGL) has been described in adipose cells as a member of the new calcium-independent PLA(2)/nutrin/patatin- like phospholipase domain-containing 2 (PNPLA2) family that possesses triglyceride lipase and acylglycerol transacylase activities. Here we describe the PEDF-R gene expression in the retina and its heterologous expression by bacterial and eukaryotic systems, and we demonstrate that its protein product has specific and high binding affinity for PEDF, has a potent phospholipase A(2) activity that liberates fatty acids, and is associated with eukaryotic cell membranes. Most importantly, PEDF binding stimulates the enzymatic phospholipase A(2) activity of PEDF-R. In conclusion, we have identified a novel PEDF-R gene in the retina for a phospholipase-linked membrane protein with high affinity for PEDF, suggesting a molecular pathway by which ligand/receptor interaction on the cell surface could generate a cellular signal. C1 NEI, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC 20057 USA. Univ Castilla La Mancha, Sch Med, Ctr Reg Invest Biomed, Albacete 02071, Spain. RP Becerra, SP (reprint author), NEI, NIH, Bldg 7,Rm 304,7 Mem Dr,MSC 0706, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov RI Nueda, Maria-Luisa/L-3044-2014; Laborda, Jorge/L-5726-2014; Baladron, Victoriano/L-1758-2014; Aroca-Aguilar, J.Daniel/B-7842-2008; OI Laborda, Jorge/0000-0002-9210-838X; Baladron, Victoriano/0000-0003-4574-8760; Aroca-Aguilar, J.Daniel/0000-0001-6487-1612; Escribano, Julio/0000-0002-8919-8134 FU Intramural NIH HHS NR 72 TC 161 Z9 170 U1 2 U2 11 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 8 PY 2006 VL 281 IS 49 BP 38022 EP 38037 DI 10.1074/jbc.M600353200 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100081 PM 17032652 ER PT J AU Turk, DC Dworkin, RH Burke, LB Gershon, R Rothman, M Scott, J Allen, RR Atkinson, JH Chandler, J Cleeland, C Cowan, P Dimitrova, R Dionne, R Farrar, JT Haythornthwaite, JA Hertz, S Jadad, AR Jensen, MP Kellstein, D Kerns, RD Manning, DC Martin, S Max, MB McDermott, MP McGrath, P Moulin, DE Nurmikko, T Quessy, S Raja, S Rappaport, BA Rauschkolb, C Robinson, JP Royal, MA Simon, L Stauffer, JW Stucki, G Tollett, J von Stein, T Wallace, MS Wernicke, J White, RE Williams, AC Witter, J Wyrwich, KW AF Turk, Dennis C. Dworkin, Robert H. Burke, Laurie B. Gershon, Richard Rothman, Margaret Scott, Jane Allen, Robert R. Atkinson, J. Hampton Chandler, Julie Cleeland, Charles Cowan, Penny Dimitrova, Rozalina Dionne, Raymond Farrar, John T. Haythornthwaite, Jennifer A. Hertz, Sharon Jadad, Alejandro R. Jensen, Mark P. Kellstein, David Kerns, Robert D. Manning, Donald C. Martin, Susan Max, Mitchell B. McDermott, Michael P. McGrath, Patrick Moulin, Dwight E. Nurmikko, Turo Quessy, Steve Raja, Srinivasa Rappaport, Bob A. Rauschkolb, Christine Robinson, James P. Royal, Mike A. Simon, Lee Stauffer, Joseph W. Stucki, Gerold Tollett, Jane von Stein, Thorsten Wallace, Mark S. Wernicke, Joachim White, Richard E. Williams, Amanda C. Witter, James Wyrwich, Kathleen W. TI Developing patient-reported outcome measures for pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Review ID PATIENTS PERSPECTIVE; END-POINTS; PERCEPTIONS; ASSESSMENTS C1 Univ Washington, Seattle, WA 98195 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. US FDA, Rockville, MD 20857 USA. Northwestern Univ, Chicago, IL 60611 USA. Johnson & Johnson, Raritan, NY USA. AstraZeneca, Wilmington, DE USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Merck & Co Inc, Blue Bell, PA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Amer Chron Pain Assoc, Rocklin, CA USA. Allergan Pharmaceut Inc, Irvine, CA 92715 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Hlth Network, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Novartis Pharmaceut, E Hanover, NJ USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, New Haven, CT 06520 USA. Celgene Corp, Warren, NJ USA. Pfizer Global Res & Dev, Ann Arbor, MI USA. Dalhousie Univ, Halifax, NS, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Johnson & Johnson, Raritan, NJ USA. Alpharma, Elizabeth, NJ USA. Harvard Univ, Sch Med, Boston, MA USA. Alpharma, Piscataway, NJ USA. Univ Munich, Munich, Germany. US Dept Vet Affairs, Washington, DC USA. NeurogesX Inc, San Carlos, CA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. St Thomas Hosp, London, England. St Louis Univ, St Louis, MO 63103 USA. RP Turk, DC (reprint author), Univ Washington, Seattle, WA 98195 USA. EM Turkdc@u.washington.edu RI Williams, Amanda/C-7816-2009; Farrar, John/A-1037-2007; OI Farrar, John/0000-0001-8656-5157; Yang, Shuman/0000-0002-9638-0890; Williams, Amanda/0000-0003-3761-8704; McGrath, Patrick/0000-0002-9568-2571 NR 23 TC 129 Z9 132 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC 5 PY 2006 VL 125 IS 3 BP 208 EP 215 DI 10.1016/j.pain.2006.09.028 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 114NO UT WOS:000242673100005 PM 17069973 ER PT J AU Summers, RM Huang, A Yao, J Campbell, SR Dempsey, JE Dwyer, AJ Franaszek, M Brickman, DS Bitter, I Petrick, N Hara, AK AF Summers, Ronald M. Huang, Adam Yao, Jianhua Campbell, Shannon R. Dempsey, Jennifer E. Dwyer, Andrew J. Franaszek, Marek Brickman, Danny S. Bitter, Ingmar Petrick, Nicholas Hara, Amy K. TI Assessment of polyp and mass histopathology by intravenous contrast-enhanced CT colonography SO ACADEMIC RADIOLOGY LA English DT Article DE CT; colon; CT; 3D reconstruction; colon cancer; image processing; intravenous contrast enhancement ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL NEOPLASIA; VIRTUAL COLONOSCOPY; LESIONS; CANCER; SCREEN AB Rationale and Objectives. We sought to demonstrate that intravenous contrast-enhanced CT colonography (CTC) can distinguish colonic adenomas from carcinomas. Methods. Supine intravenous contrast-enhanced CTC with colonoscopic and/or surgical correlation was performed on 25 patients with colonic adenomas or carcinomas. Standard deviation of mean polyp CT attenuation was computed and assessed using ANOVA and receiver-operating characteristic analyses. Results. Colonoscopy confirmed 32 polyps or masses 1 to 8 cm in size. The standard deviations of CT attenuation were carcinomas (n = 13; 36 +/- 6 HU; range 28-48 HU) and adenomas (n = 19; 49 +/- 14 HU; range 31-100 HU) (P = 0.005). At a standard deviation threshold of 42 HU, the sensitivity and specificity for classifying a polyp or mass as a carcinoma were 92% and 79%, respectively. The area under the receiver-operating characteristic curve was 0.89 +/- 0.06 (95% confidence interval 0.73-0.96). Conclusions. Measurement of the standard deviation of CT attenuation on intravenous contrast-enhanced CTC permits histopathologic classification of polyps 1 cm or larger as carcinomas versus adenomas. The presence of ulceration or absence of muscular invasion in carcinomas creates overlap with adenomas, reducing the specificity of carcinoma classification. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Mayo Clin, Dept Radiol, Scottsdale, AZ 85259 USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C351, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 15 TC 5 Z9 6 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2006 VL 13 IS 12 BP 1490 EP 1495 DI 10.1016/j.acra.2006.09.051 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 115LY UT WOS:000242737000007 PM 17138117 ER PT J AU Tomashek, KM Qin, C Hsia, J Lyasu, S Barfield, WD Flowers, LM AF Tomashek, Kay M. Qin, Cheng Hsia, Jason Lyasu, Solomon Barfield, Wanda D. Flowers, Lisa M. TI Infant mortality trends and differences between American Indian/Alaska native infants and white infants in the United States, 1989-1991 and 1998-2000 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ALASKA NATIVES; SOUTH-CAROLINA; INDIANS; POPULATION; DELIVERY; OUTCOMES; HEALTH; LEVEL AB Objectives. To describe changes in infant mortality rates, including birthweight-specific rates and rates by age at death and cause. Methods. We analyzed US linked birth/infant-death data for 1989-1991 and 1998-2000 for American Indians/Alaska Native (AIAN) and White singleton infants at >= 20 weeks' gestation born to US residents. We calculated birthweight-specific infant mortality rates (deaths in each birthweight category per 1000 live births in that category), and overall and cause-specific infant mortality rates (deaths per 100000 live births) in infancy (0-364 days) and in the neonatal (0-27 days) and postneonatal (28-364 days) periods. Results. Birthweight-specific infant mortality rates declined among AIAN and White infants across all birthweight categories, but AIAN infants generally had higher birthweight-specific infant mortality rates. Infant mortality rates declined for both groups, yet in 1998-2000, AIAN infants were still 1.7 times more likely to die than White infants. Most of the disparity was because of elevated postneonatal mortality, especially from sudden infant death syndrome, accidents, and pneumonia and influenza. Conclusions. Although birthweight-specific infant mortality rates and infant mortality rates declined among both AIAN and White infants, disparities in infant mortality persist. Preventable causes of infant mortality identified in this analysis should be targeted to reduce excess deaths among AIAN communities. C1 Ctr Dis Control & Prevent, Matenal & Infant Hlth Branch, Div Reprod Hlth, Atlanta, GA 30341 USA. CDC, Stat & Surveillance Branch, Div Reprod Hlth, Atlanta, GA 30341 USA. US FDA, Off Counterterrorism & Pediat Drug Dev, Div Pediat Drug Dev, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Tomashek, KM (reprint author), Ctr Dis Control & Prevent, Matenal & Infant Hlth Branch, Div Reprod Hlth, Mail Stop K-23,4770 Buford Highway, Atlanta, GA 30341 USA. EM kct9@cdc.gov NR 32 TC 32 Z9 33 U1 2 U2 8 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2006 VL 96 IS 12 BP 2222 EP 2227 DI 10.2105/AJPH.2004.053744 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 111SJ UT WOS:000242474500023 PM 17077400 ER PT J AU Zhang, ZW Rockette, HE AF Zhang, Zhiwei Rockette, Howard E. TI Semiparametric maximum likelihood for missing covariates in parametric regression SO ANNALS OF THE INSTITUTE OF STATISTICAL MATHEMATICS LA English DT Article DE asymptotic normality; efficiency; infinite-dimensional M-estimation; missing at random; missing covariates; parametric regression; profile likelihood; semiparametric likelihood ID MODELS; 2-PHASE AB We consider parameter estimation in parametric regression models with covariates missing at random. This problem admits a semiparametric maximum likelihood approach which requires no parametric specification of the selection mechanism or the covariate distribution. The semiparametric maximum likelihood estimator (MLE) has been found to be consistent. We show here, for some specific models, that the semiparametric MLE converges weakly to a zero-mean Gaussian process in a suitable space. The regression parameter estimate, in particular, achieves the semiparametric information bound, which can be consistently estimated by perturbing the profile log-likelihood. Furthermore, the profile likelihood ratio statistic is asymptotically chi-squared. The techniques used here extend to other models. C1 US FDA, Div Biostat, Rockville, MD 20850 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. RP Zhang, ZW (reprint author), US FDA, Div Biostat, 1350 Piccard Dr, Rockville, MD 20850 USA. EM zhiwei.zhang@fda.hhs.gov NR 24 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0020-3157 J9 ANN I STAT MATH JI Ann. Inst. Stat. Math. PD DEC PY 2006 VL 58 IS 4 BP 687 EP 706 DI 10.1007/s10463-006-0047-7 PG 20 WC Statistics & Probability SC Mathematics GA 112AF UT WOS:000242496700003 ER PT J AU Gonzalez-Escalona, N Blackstone, GM DePaola, A AF Gonzalez-Escalona, Narjol Blackstone, George M. DePaola, Angelo TI Characterization of a Vibrio alginolyticus strain, isolated from Alaskan oysters, carrying a hemolysin gene similar to the thermostable direct hemolysin-related hemolysin gene (trh) of Vibrio parahaemolyticus SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID THERMOLABILE HEMOLYSIN; SEQUENCE; PCR; SPREAD; EMERGENCE; SHELLFISH; DIARRHEA; O3-K6; CLONE; TDH AB A Vibrio strain isolated from Alaskan oysters and classified by its biochemical characteristics as Vibrio alginolyticus possessed a thermostable direct hemolysin-related hemolysin (trh) gene previously reported only in Vibrio parahaemolyticus. This trh-like gene was cloned and sequenced and was 98% identical to the trh2 gene of V. parahaemolyticus. This gene seems to be functional since it was transcriptionally active in early-stationary-phase growing cells. To our knowledge, this is the first report of V. alginolyticus possessing a trh gene. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. RP Gonzalez-Escalona, N (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM narjol@gmail.com RI Gonzalez-Escalona, Narjol/A-7598-2009; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 NR 25 TC 43 Z9 48 U1 2 U2 4 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 2006 VL 72 IS 12 BP 7925 EP 7929 DI 10.1128/AEM.01548-06 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 114QS UT WOS:000242681300067 PM 17056701 ER PT J AU Balls, M Amcoff, P Bremer, S Casati, S Coecke, S Clothier, R Combes, R Corvi, R Curren, R Eskes, C Fentem, J Gribaldo, L Halder, M Hartung, T Hoffmann, S Schechtman, L Scott, L Spielmann, H Stokes, W Tice, R Wagner, D Zuang, V AF Balls, Michael Amcoff, Patric Bremer, Susanne Casati, Silvia Coecke, Sandra Clothier, Richard Combes, Robert Corvi, Raffaella Curren, Rodger Eskes, Chantra Fentem, Julia Gribaldo, Laura Halder, Marlies Hartung, Thomas Hoffmann, Sebastian Schechtman, Leonard Scott, Laurie Spielmann, Horst Stokes, William Tice, Raymond Wagner, Drew Zuang, Valerie TI The principles of weight of evidence validation of test methods and testing strategies - The report and recommendations of ECVAM Workshop 58(a) SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article ID EVIDENCE-BASED TOXICOLOGY; TOXICITY TEST PROCEDURES; TEST ACCURACY; METAANALYSIS; DIAGNOSIS; REVIEWS C1 European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, I-21020 Ispra, VA, Italy. FRAME, Nottingham, England. OECD, Environm Directorate, Paris, France. Univ Nottingham, Sch Biomed Sci, Nottingham NG7 2RD, England. Inst In Vitro Sci, Gaithersburg, MD USA. Unilever, SEAC, Sharnbrook, Beds, England. Natl Ctr Toxicol Res, Food & Drug Adm, Rockville, MD USA. Fed Inst Risk Assessment, ZEBET, Berlin, Germany. Natl Inst Environm Hlth Sci, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Res Triangle Pk, NC USA. RP Balls, M (reprint author), European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, I-21020 Ispra, VA, Italy. EM michael.balls@btopenworld.com; valerie.zuang@jrc.it FU Intramural NIH HHS [Z99 ES999999] NR 58 TC 40 Z9 40 U1 0 U2 4 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD DEC PY 2006 VL 34 IS 6 BP 603 EP 620 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 132MT UT WOS:000243947600022 PM 17266393 ER PT J AU Wang, HL Del Grosso, AV May, JC AF Wang, Hsiaoling Del Grosso, Alfred V. May, Joan C. TI Determination of benzethonium chloride in anthrax vaccine adsorbed by HPLC SO BIOLOGICALS LA English DT Article DE benzethonium chloride; HPLC; anthrax vaccine ID LIQUID-CHROMATOGRAPHY; QUATERNARY AMMONIUM; PHASE AB A novel and sensitive HPLC method for the determination of benzethonium chloride (BZC) in anthrax vaccine was developed. Adjuvant Alhydrogel was removed by syringe filter after a simple sample pretreatment-acidification prior to injection. Chromatography was performed by isocratic reverse phase separation with methanol/262 mM ammonium acetate (80/20, v/v) on an endcapped C18 column with diode array detector (DAD). The method showed excellent recovery (100 +/- 1.5%). The results indicated that this method could accurately determine BZC at the limit of detection (LOD) of 0.5 ppm and the limit of quantitation (LOQ) of 1.5 ppm with dynamic range up to 100 ppm. The comparison of analysis between new HPLC and old titrimetric methods is also reported. The HPLC method is proven to be more accurate and precise with much less vaccine sample and human labor required. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 US FDA, Ctr Biol Evaluat & Res, Analyt Chem Lab, Off Vaccine Res & Review, Rockville, MD 20852 USA. RP Wang, HL (reprint author), US FDA, Ctr Biol Evaluat & Res, Analyt Chem Lab, Off Vaccine Res & Review, 1401 Rockville Pike HFM-406, Rockville, MD 20852 USA. EM wangh@cber.fda.gov NR 13 TC 3 Z9 5 U1 2 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD DEC PY 2006 VL 34 IS 4 BP 257 EP 263 DI 10.1016/j.biologicals.2005.11.004 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 114QG UT WOS:000242680100002 PM 16492397 ER PT J AU Mohan, KVK Glass, RI Atreya, CD AF Mohan, K. V. K. Glass, R. I. Atreya, C. D. TI Comparative molecular characterization of gene segment 11-derived NSP6 from lamb rotavirus LLR strain used as a human vaccine in China SO BIOLOGICALS LA English DT Article DE gene 11; NSP6; phosphorylation; rotavirus; vaccine ID NUCLEOTIDE-SEQUENCE; IN-VIVO; PHOSPHORYLATION; PROTEINS; LOCALIZATION; MICE AB Sequence-length polymorphism is known for rotavirus genetic segment 11 (encodes non-structural protein, NSP6). With the exception of 11 strains that have the coding potential for a 98-residue NSP6, majority of the strains have the potential for a 92-residue NSP6. In nine strains, the coding potential for this protein is even shorter. This report focuses on the NSP6 gene nucleotide sequence of Lanzhou Lamb Rotavirus (LLR) strain and its comparative molecular characterization. The LLR strain is a G 10 PI 2 type, which is in use as a licensed human vaccine in China. The LLR NSP6 was compared with 56 other rotaviral NSP6 sequences including a rhesus strain (RRV) available in the database. Analyses indicate that while RRV-NSP6 belongs to the majority (92-residue) group, the LLR NSP6 belongs to the 98-residue group. When the rotavirus NSP6 protein was expressed in cells as GFP fusion protein from human, simian and the LLR strains, they all demonstrated punctate cytoplasmic distribution and. contrary to the computer-aided prediction, the NSP6 did not undergo phosphorylation, which in itself is a novel observation for the rotavirus NSP6. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 US FDA, CBER, Div Viral Prod, Sect Viral Pathogenesis & Vaccine Adverse React, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Viral Gastroenteritis Sect, Resp & Enter Viruses Branch, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. RP Atreya, CD (reprint author), US FDA, CBER, Div Viral Prod, Sect Viral Pathogenesis & Vaccine Adverse React, Bldg 29A,Room 2C-11,HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA. EM atreya@cber.fda.gov NR 20 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD DEC PY 2006 VL 34 IS 4 BP 265 EP 272 DI 10.1016/j.biologicals.2005.11.005 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 114QG UT WOS:000242680100003 PM 16492399 ER PT J AU Zhang, ZW AF Zhang, Zhiwei TI Non-inferiority testing with a variable margin SO BIOMETRICAL JOURNAL LA English DT Article DE delta method; likelihood ratio test; non-inferiority; power; sample size; score test; wald test ID STATISTICAL CONSIDERATIONS; THERAPEUTIC EQUIVALENCE; TRIALS; DIFFERENCE AB There has been growing interest, when comparing an experimental treatment with an active control with respect to a binary outcome, in allowing the non-inferiority margin to depend on the unknown success rate in the control group. It does not seem universally recognized, however, that the statistical test should appropriately adjust for the uncertainty surrounding the non-inferiority margin. In this paper, we inspect a naive procedure that treats an "observed margin" as if it were fixed a priori, and explain why it might not be valid. We then derive a class of tests based on the delta method, including the Wald test and the score test, for a smooth margin. An alternative derivation is given for the asymptotic distribution of the likelihood ratio statistic, again for a smooth margin. We discuss the asymptotic behavior of these tests when applied to a piecewise smooth margin. A simple condition on the margin function is given which allows the likelihood ratio test to carry over to a piecewise smooth margin using the same critical value as for a smooth margin. Simulation experiments are conducted, under a smooth margin and a piecewise linear margin, to evaluate the finite-sample performance of the asymptotic tests studied. C1 US FDA, CDRH, OSB, Div Biostat, Rockville, MD 20850 USA. RP Zhang, ZW (reprint author), US FDA, CDRH, OSB, Div Biostat, HFZ-550,1350 Piccard Dr, Rockville, MD 20850 USA. EM zhiwei.zhang@fda.hhs.gov NR 20 TC 7 Z9 7 U1 1 U2 3 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD DEC PY 2006 VL 48 IS 6 BP 948 EP 965 DI 10.1002/bimj.200610271 PG 18 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 123SA UT WOS:000243314700007 PM 17240654 ER PT J AU Rozman, KK Bhatia, J Calafat, AM Chambers, C Culty, M Etzel, RA Flaws, JA Hansen, DK Hoyer, PB Jeffery, EH Kesner, JS Marty, S Thomas, JA Umbach, D AF Rozman, Karl K. Bhatia, Jatinder Calafat, Antonia M. Chambers, Christina Culty, Martine Etzel, Ruth A. Flaws, Jodi A. Hansen, Deborah K. Hoyer, Patricia B. Jeffery, Elizabeth H. Kesner, James S. Marty, Sue Thomas, John A. Umbach, David TI NTP-CERHR expert panel report on the reproductive and developmental toxicity of genistein SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID SPRAGUE-DAWLEY RATS; MAMMARY-GLAND DEVELOPMENT; CHROMATOGRAPHY-MASS SPECTROMETRY; LUTEINIZING-HORMONE SECRETION; NATURALLY-OCCURRING ESTROGENS; TYROSINE KINASE INHIBITORS; SEXUALLY DIMORPHIC NUCLEUS; MATERNAL DIETARY EXPOSURE; PURIFIED SOY ISOFLAVONES; EPIDERMAL-GROWTH-FACTOR C1 Univ Kansas, Med Ctr, Dept Pharmacol & Toxicol, Kansas City, KS 66103 USA. Med Coll Georgia, Dept Pediat, Div Neonatol, Augusta, GA 30912 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Univ Calif San Diego, Med Ctr, Dept Pediat, San Diego, CA 92103 USA. Univ Calif San Diego, Med Ctr, Dept Family & Prevent Med, San Diego, CA 92103 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. George Washington Univ, Sch Publ Hlth & Hlth Sci, Washington, DC USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Arizona, Dept Physiol, Tucson, AZ USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. NIOSH, Cincinnati, OH 45226 USA. Dow Chem Co USA, Toxicol Res Lab, Midland, MI 48674 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Rozman, KK (reprint author), NIEHS EC-32,POB 12233, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z01 ES045002-12] NR 235 TC 42 Z9 43 U1 1 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD DEC PY 2006 VL 77 IS 6 BP 485 EP 638 DI 10.1002/bdrb.20087 PG 154 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 119AD UT WOS:000242983700001 PM 17186522 ER PT J AU Rubinstein, DB Karmely, M Ziv, R Benhar, I Leitner, O Baron, S Katz, BZ Wreschner, DH AF Rubinstein, Daniel B. Karmely, Maya Ziv, Ravit Benhar, Itai Leitner, Orit Baron, Shoshana Katz, Ben-Zion Wreschner, Daniel H. TI MUC1/X protein immunization enhances cDNA immunization in generating Anti-MUC1 alpha/beta junction antibodies that target malignant cells SO CANCER RESEARCH LA English DT Article ID POLYMORPHIC EPITHELIAL MUCIN; BREAST-CANCER; TYROSINE PHOSPHORYLATION; PREFERENTIAL EXPRESSION; MOLECULAR-CLONING; SPLICE VARIANTS; SEA MODULE; DOMAIN; RECEPTOR; TUMORS AB MUC1 has generated considerable interest as a tumor marker and potential target for tumor killing. To date, most antibodies against MUC1 recognize epitopes within the highly immunogenic alpha chain tandem repeat array. A major shortcoming of such antibodies is that the MUC1 alpha chain is shed into the peripheral circulation, sequesters circulating antitandem repeat array antibodies, and limits their ability to even reach targeted MUC1-expressing cells. Antibodies recognizing MUC1 epitopes tethered to the cell surface would likely be more effective. MUC1 alpha subunit binding the membrane-tethered subunit provides such an epitope. By use of a novel protocol entailing immunization with cDNA encoding fall-length MUC1 (MUC1/TM) followed by boosting with the alternatively spliced MUC1/X isoform from which the tandem repeat array has been deleted, we generated monoclonal antibodies, designated DMC209, which specifically bind the MUC1 alpha/beta junction. DMC209 is exquisitely unique for this site; amino acid mutations, which abrogate MUC1 cleavage, also abrogate DMC209 binding. Additionally, DMC209 specifically binds the MUC1 alpha/beta junction on full-length MUC1/TM expressed by breast and ovarian cancer cell lines and on freshly obtained, unmanipulated MUC1-positive malignant plasma cells of multiple myeloma. DMC209 is likely to have clinical application by targeting MUC1-expressing cells directly and as an immunotoxin conjugate. Moreover, the novel immunization procedure used in generating DMC209 can be used to generate additional anti-MUC1 alpha/beta junction antibodies, which may, analogously to Herceptin, have cytotoxic activity. Lastly, sequential immunization with MUC1/TM cDNA acting as a nonspecific adjuvant followed by protein of interest may prove to be a generalizable method to yield high-titer specific antibodies. C1 Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. US FDA, Silver Spring, MD USA. Biomodifying LLC, San Diego, CA USA. Weizmann Inst Sci, Antibody Unit, IL-76100 Rehovot, Israel. Sourasky Med Ctr, Dept Hematol, Tel Aviv, Israel. RP Wreschner, DH (reprint author), Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. EM danielhw@post.tau.ac.il NR 45 TC 13 Z9 13 U1 0 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 1 PY 2006 VL 66 IS 23 BP 11247 EP 11253 DI 10.1158/0008-5472.CAN-06-1486 PG 7 WC Oncology SC Oncology GA 113RF UT WOS:000242614300024 PM 17145869 ER PT J AU Davis-Bruno, KL Atrakchi, A AF Davis-Bruno, Karen L. Atrakchi, Aisar TI A regulatory perspective on issues and approaches in characterizing human metabolites SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article AB This document captures the current thinking within FDA/CDER on the non-clinical safety assessment of human drug metabolites in new drug products. Examples are provided, which define a scientific based approach to the safety evaluation of human metabolites in new drug candidates. A discussion of the need for, and the adequacy of, the assessment of human drug metabolites with specific regard to their potential as mediators of toxicity is presented from a regulatory perspective. C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. RP Davis-Bruno, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. EM karen.davisbruno@fda.hhs.gov NR 6 TC 45 Z9 46 U1 1 U2 1 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 2006 VL 19 IS 12 BP 1561 EP 1563 DI 10.1021/tx060203m PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 119FD UT WOS:000242997300002 PM 17173368 ER PT J AU Churchwell, MI Yan, J Xia, QS Fu, PP Beland, FA Doerge, DR AF Churchwell, Mona I. Yan, Jian Xia, Qingsu Fu, Peter P. Beland, Frederick A. Doerge, Daniel R. TI LC/MS/MS analysis of benzo[a]pyrene DNA adducts derived from diol epoxide and cation radical pathways. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 232nd ACS National Meeting CY SEP 10-14, 2006 CL San Francisco, CA SP Amer Chem Soc, Div Chem Toxicol C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2006 VL 19 IS 12 MA 52 BP 1687 EP 1687 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 119FD UT WOS:000242997300066 ER PT J AU Tareke, E Churchwell, MI McDaniel, LP Twaddle, NC Doerge, DR AF Tareke, Eden Churchwell, Mona I. McDaniel, L. Patrice Twaddle, Nathan C. Doerge, Daniel R. TI Correlation between hemoglobin adducts and DNA adducts following acrylamide and glycidamide exposures in Fischer 344 rats and B6C3F1 mice. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 232nd ACS National Meeting CY SEP 10-14, 2006 CL San Francisco, CA SP Amer Chem Soc, Div Chem Toxicol C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2006 VL 19 IS 12 MA 63 BP 1690 EP 1690 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 119FD UT WOS:000242997300077 ER PT J AU Hotchkiss, CE Latendresse, J Ferguson, SA AF Hotchkiss, Charlotte E. Latendresse, John Ferguson, Sherry A. TI Oral treatment with retinoic acid decreases bone mass in rats SO COMPARATIVE MEDICINE LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; STEADY-STATE PHARMACOKINETICS; 13-CIS-RETINOIC ACID; ISOTRETINOIN THERAPY; SEVERE ACNE; METABOLISM; RESORPTION; TOXICITY; HYPERVITAMINOSIS; OSTEOPOROSIS AB 13-cis-retinoic acid (13-cis-RA, isotretinoin) is used to treat severe recalcitrant acne. Other retinoids have adverse effects on bone. Recent studies of human patients treated with 13-cis-RA have had varying results, perhaps because of variability among patients and the lack of control groups. The effects of retinoids have been studied in rodents, but little information is available regarding the effects of clinically relevant retinoid doses as evaluated by use of bone densitometric techniques. We treated rats for 15 or 20 wk with 13-cis-RA, all-trans-RA, or soybean oil (control) by gavage. We used dual-energy X-ray absorptiometry, histomorphometry, and histologic evaluation to evaluate effects on bone. Spontaneous long bone fractures occurred in some rats treated with 15 mg/kg all-trans-RA daily. Bone mineral density, bone mineral content, bone diameter, and cortical thickness of the femur were reduced in rats treated daily with 10 or 15 mg/kg all-trans-RA or 30 mg/kg 13-cis-RA. The lumbar spine was not affected. Although the effects of 13-cis-RA were not as dramatic as those of all-trans-RA, further study of the effects of 13-cis-RA on long bones is warranted. C1 NCTR, Biometr Corp, Jefferson, AR USA. NCTR, Toxicol Pathol Associates, Jefferson, AR USA. NCTR, Div Neurotoxicol, Jefferson, AR USA. RP Hotchkiss, CE (reprint author), NCTR, Biometr Corp, Jefferson, AR USA. EM charlotte.hotchkiss@fda.hhs.gov NR 47 TC 13 Z9 15 U1 0 U2 0 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 2006 VL 56 IS 6 BP 502 EP 511 PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 119CH UT WOS:000242989300008 PM 17219781 ER PT J AU Klaschik, S Gursel, I Klinman, DM AF Klaschik, Sven Gursel, Ihsan Klinman, Dennis M. TI Microarray based network analysis of CpG-mediated changes in gene expression of immune cells. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 FDA CBER, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 2006 VL 34 IS 12 SU S SI SI MA 139 BP A35 EP A35 DI 10.1097/00003246-200612002-00120 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400121 ER PT J AU Karpinets, TV Greenwood, DJ Pogribny, IP Samatova, NF AF Karpinets, T. V. Greenwood, D. J. Pogribny, I. P. Samatova, N. F. TI Bacterial stationary-state mutagenesis and mammalian tumorigenesis as stress-induced cellular adaptations and the role of epigenetics SO CURRENT GENOMICS LA English DT Review DE adaptive mutagenesis; bacteria; cancer; stress; histone-like proteins; epigenetic alterations ID PROTEIN H-NS; ESCHERICHIA-COLI K-12; GENOME-WIDE HYPERMUTATION; DNA ADENINE METHYLATION; SMALL RNA REGULATORS; GTP-BINDING PROTEIN; LONG-TERM SURVIVAL; ADAPTIVE MUTATION; PSEUDOMONAS-PUTIDA; BACILLUS-SUBTILIS AB Mechanisms of cellular adaptation may have some commonalities across different organisms. Revealing these common mechanisms may provide insight in the organismal level of adaptation and suggest solutions to important problems related to the adaptation. An increased rate of mutations, referred as the mutator phenotype, and beneficial nature of these mutations are common features of the bacterial stationary-state mutagenesis and of the tumorigenic transformations in mammalian cells. We argue that these commonalities of mammalian and bacterial cells result from their stress-induced adaptation that may be described in terms of a common model. Specifically, in both organisms the mutator phenotype is activated in a subpopulation of proliferating stressed cells as a strategy to survival. This strategy is an alternative to other survival strategies, such as senescence and programmed cell death, which are also activated in the stressed cells by different subpopulations. Sustained stress-related proliferative signalling and epigenetic mechanisms play a decisive role in the choice of the mutator phenotype survival strategy in the cells. They reprogram cellular functions by epigenetic silencing of cell-cycle inhibitors, DNA repair, programmed cell death, and by activation of repetitive DNA elements. This reprogramming leads to the mutator phenotype that is implemented by error-prone cell divisions with the involvement of Y family polymerases. Studies supporting the proposed model of stress-induced cellular adaptation are discussed. Cellular mechanisms involved in the bacterial stress-induced adaptation are considered in more detail. C1 Oak Ridge Natl Lab, Computat Biol Inst, Comp Sci & Math Div, Oak Ridge, TN 37831 USA. Univ Tennessee, Dept Plant Sci, Knoxville, TN 37996 USA. Hort Res Int, Wellesbourne CV35 9EF, Warwick, England. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Karpinets, TV (reprint author), Oak Ridge Natl Lab, Computat Biol Inst, Comp Sci & Math Div, POB 2008,MS6164, Oak Ridge, TN 37831 USA. EM karpinetstv@ornl.gov NR 139 TC 9 Z9 9 U1 3 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2029 J9 CURR GENOMICS JI Curr. Genomics PD DEC PY 2006 VL 7 IS 8 BP 481 EP 496 DI 10.2174/138920206779315764 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 128CC UT WOS:000243632500003 PM 18369407 ER PT J AU Sun, D Xu, D Zhang, BL AF Sun, Di Xu, Duo Zhang, Baolin TI Rac signaling in tumorigenesis and as target for anticancer drug development SO DRUG RESISTANCE UPDATES LA English DT Review DE Rac GTPases; tumor progression; metastasis; angiogenesis; therapeutic targets; anticancer drugs ID GUANINE-NUCLEOTIDE-EXCHANGE; RHO-FAMILY GTPASES; GTP-BINDING-PROTEIN; BREAST-CANCER CELLS; HUMAN BRAIN-TUMORS; GDP DISSOCIATION INHIBITORS; HUMAN LYMPHOMA-CELLS; FACTOR-KAPPA-B; NADPH-OXIDASE; INDUCED APOPTOSIS AB Rac GTPases are crucial signaling regulators in eukaryotic cells, acting downstream of many cell surface receptors. They play essential roles in diverse cellular functions including cytoskeleton dynamics, cell motility, cell survival and apoptosis. Their activities are controlled by a tightly regulated GDP/GTP cycle coupled with an alternation between cytoplasm and membrane compartments. Aberrant Rac signaling is found in some human cancers as a result of changes in the GTPase itself or in its regulation loops. This review highlights recent findings regarding the molecular and functional aspects of Rac that mediate tumorigenic transformation and metastasis. It also describes the cellular mechanisms that potentially explain the complex role of Rac in tumorigenesis. Finally, it discusses approaches for modulating Rac function as a potential anticancer strategy. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, CDER, OBP,DTP, Bethesda, MD 20892 USA. Duke Univ, Pratt Sch Engn, Dept Biomed Engn, Durham, NC 27708 USA. RP Zhang, BL (reprint author), US FDA, Ctr Biol Evaluat & Res, CDER, OBP,DTP, 29 Lincoln Dr,Bldg 29A,Rm 2A-01, Bethesda, MD 20892 USA. EM Baolin.Zhang@FDA.HHS.GOV NR 165 TC 38 Z9 41 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD DEC PY 2006 VL 9 IS 6 BP 274 EP 287 DI 10.1016/j.drup.2006.12.001 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 154YK UT WOS:000245544300002 PM 17234445 ER PT J AU Bernard, SM Anderson, SA AF Bernard, Susan M. Anderson, Steven A. TI Qualitative assessment of risk for monkeypox associated with domestic trade in certain animal species, United States SO EMERGING INFECTIOUS DISEASES LA English DT Article ID EXPERIMENTAL-INFECTION; VIRUS-INFECTION; PRAIRIE DOGS; DISEASE; CONGO; TRANSMISSION; SQUIRRELS; ZOONOSIS; AFRICA AB In 2003, US officials identified several human monkeypox cases and traced the virus exposure to infected captive prairie dogs. The virus was likely introduced through a shipment of imported African rodents, which were kept with other mammals, including prairie dogs, in a pet distribution facility in the Midwest. To prevent the further introduction and spread of the virus, federal agencies restricted the importation of African rodents and restricted the domestic trade or movement of prairie dogs and certain other rodents. In this qualitative assessment of the risk for monkeypox associated with the 2003 outbreak, we conclude that the probability of further human infection is low; the risk is further mitigated by rodent import restrictions. Were this zoonotic disease to become established domestically, the public health effects could be substantial. C1 US FDA, College Pk, MD 20740 USA. RP Bernard, SM (reprint author), US FDA, 3100 Paint Branch Pkwy,HFS-004, College Pk, MD 20740 USA. EM susan.bernard@fda.hhs.gov NR 38 TC 9 Z9 11 U1 1 U2 9 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2006 VL 12 IS 12 BP 1827 EP 1833 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 109IR UT WOS:000242301900004 PM 17326932 ER PT J AU Altekruse, SF Bauer, N Chanlongbutra, A DeSagun, R Naugle, A Schlosser, W Umholtz, R White, P AF Altekruse, Sean F. Bauer, Nathan Chanlongbutra, Amy DeSagun, Robert Naugle, Alecia Schlosser, Wayne Umholtz, Robert White, Patricia TI Salmonella enteritidis in broiler chickens, United States, 2000-2005 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID PHAGE TYPES; INFECTIONS; EGGS AB US Department of Agriculture Food Safety and Inspection Service (FSIS) data on Salmonella enterica serotype Enteritidis in broiler chicken carcass rinses collected from 2000 through 2005 showed the annual number of isolates increased > 4-fold and the proportion of establishments with Salmonella Enteritidis-positive rinses increased nearly 3-fold (test for trend, p < 0.0001). The number of states with Salmonella Enteritidis in broiler rinses increased from 14 to 24. The predominant phage types (PT) were PT 13 and PT 8, 2 strains that a recent Foodborne Diseases Active Surveillance Network (FoodNet) case-control study associated with eating chicken. FSIS is directing more sampling resources toward plants with marginal Salmonella control to reduce prevalence in products including broilers. The policy targets establishments with common Salmonella serotypes of human illness, including Salmonella Enteritidis. Voluntary interventions should be implemented by industry. C1 USDA, Food Safety & Inspect Serv, Off Policy Program & Employee Dev, Washington, DC 20250 USA. Ctr Food Safety & Appl Nutr, USDA, College Stn, TX USA. US Food Safety & Inspect Serv, USDA, Omaha, NE USA. RP Altekruse, SF (reprint author), USDA, Food Safety & Inspect Serv, Off Policy Program & Employee Dev, 300 12th St SW,Rm 412, Washington, DC 20250 USA. EM sean.altekruse@fsis.usda.gov NR 19 TC 54 Z9 57 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2006 VL 12 IS 12 BP 1848 EP 1852 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 109IR UT WOS:000242301900007 PM 17326935 ER PT J AU Strosnider, H Azziz-Baumgartner, E Banziger, M Bhat, RV Breiman, R Brune, MN DeCock, K Dilley, A Groopman, J Hell, K Henry, SH Jeffers, D Jolly, C Jolly, P Kibata, GN Lewis, L Liu, XM Luber, G McCoy, L Mensah, P Miraglia, M Misore, A Njapau, H Ong, CN Onsongo, MTK Page, SW Park, D Patel, M Phillips, T Pineiro, M Pronczuk, J Rogers, HS Rubin, C Sabino, M Schaafsma, A Shephard, G Stroka, J Wild, C Williams, JT Wilson, D AF Strosnider, Heather Azziz-Baumgartner, Eduardo Banziger, Marianne Bhat, Ramesh V. Breiman, Robert Brune, Marie-Noel DeCock, Kevin Dilley, Abby Groopman, John Hell, Kerstin Henry, Sara H. Jeffers, Daniel Jolly, Curtis Jolly, Pauline Kibata, Gilbert N. Lewis, Lauren Liu, Xiumei Luber, George McCoy, Leslie Mensah, Patience Miraglia, Marina Misore, Ambrose Njapau, Henry Ong, Choon-Nam Onsongo, Mary T. K. Page, Samuel W. Park, Douglas Patel, Manish Phillips, Timothy Pineiro, Maya Pronczuk, Jenny Rogers, Helen Schurz Rubin, Carol Sabino, Myrna Schaafsma, Arthur Shephard, Gordon Stroka, Joerg Wild, Christopher Williams, Jonathan T. Wilson, David TI Workgroup report: Public health strategies for reducing aflatoxin exposure in developing countries SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE aflatoxins; biomonitoring; developing countries; food safety; hepatitis; hepatocellular carcinoma; public health; surveillance ID THIN-LAYER-CHROMATOGRAPHY; REPUBLIC-OF-CHINA; WEST-AFRICA; HEPATOCELLULAR-CARCINOMA; ASPERGILLUS-FLAVUS; LIVER-CANCER; DIETARY AFLATOXIN; ALBUMIN ADDUCTS; YOUNG-CHILDREN; MAIZE AB Consecutive outbreaks of acute aflatoxicosis in Kenya in 2004 and 2005 caused > 150 deaths. In,response, the Centers for Disease Control and Prevention and the World Health Organization convened a workgroup, of international experts and health officials in Geneva, Switzerland, in July 2005. After discussions concerning what is known about aflatoxins, the workgroup identified gaps in current knowledge about acute and chronic human health effects of aflatoxins, surveillance and food monitoring, analytic methods, and the efficacy of intervention strategies. The workgroup, also identified public health strategies that could be integrated with current agricultural approaches to resolve gaps in current knowledge and ultimately reduce morbidity and mortality associated with the consumption of aflatoxin-contaminated food in the developing world. Four issues that warrant immediate attention were identified: a) quantify the human health impacts and the burden of disease due to aflatoxin exposure; b) compile an inventory, evaluate the efficacy, and disseminate results of ongoing intervention strategies; c) develop and augment the disease surveillance, food monitoring, laboratory, and public health response capacity of affected regions; and 4 develop a response protocol that can be used in the event of an outbreak of acute aflatoxicosis. This report expands on the workgroup's discussions concerning aflatoxin in developing countries and summarizes the findings. C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Int Maize & Wheat Improvement Ctr, Nairobi, Kenya. Indian Council Med Res, Ctr Sci Soc & Culture, Hyderabad, Andhra Pradesh, India. Ctr Dis Control & Prevent, Kenya Med Res Inst, Nairobi, Kenya. WHO, CH-1211 Geneva, Switzerland. Ctr Dis Control & Prevent, Kenya Off, Nairobi, Kenya. Resolve, Washington, DC USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Int Inst Trop Agr, Biol Control Ctr Africa, Cotonou, Benin. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Int Maize & Wheat Improvement Ctr, Mexico City, DF, Mexico. Auburn Univ, Dept Agr Econ & Rural Sociol, Auburn, AL 36849 USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Chinese Ctr Dis Control & Prevent, Inst Nutr & Food Safety, Beijing, Peoples R China. WHO, Reg Off Africa, Brazzaville, Congo. Ist Super Sanita, Ctr Food Risk Assessment & Qual, I-00161 Rome, Italy. Kenya Minist Hlth, Nairobi, Kenya. Natl Univ Singapore, Dept Community Occupat & Family Med, Singapore 117548, Singapore. USDA, Foreign Agr Serv, Nairobi, Kenya. Texas A&M Univ, Ctr Food Safety, College Stn, TX USA. Food & Agr Org, Food Qual & Stand Serv, Rome, Italy. Inst Adolfo Lutz Registro, Sao Paulo, Brazil. Univ Guelph, Dept Plant Agr, Ridgetown, ON, Canada. S African MRC, Programme Mycotoxins & Expt Carcinogenesis, Tygerberg, South Africa. Commiss European Communities, Joint Res Ctr, Inst Reference Mat & Measurements, Geel, Belgium. Univ Leeds, Sch Med, Mol Epidemiol Unit, Leeds LS2 9JT, W Yorkshire, England. Univ Georgia, Peanut Collaborat Res Support Program, Griffin, GA USA. Univ Georgia, Coastal Plain Expt Stn, Dept Plant Pathol, Tifton, GA 31793 USA. RP Strosnider, H (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, 4770 Buford Hwy NE,Mailstop E19, Atlanta, GA 30341 USA. EM hks9@cdc.gov RI Ong, Choon Nam/E-8638-2010; OI Shephard, Gordon Seymour/0000-0002-1267-9036 NR 84 TC 103 Z9 106 U1 4 U2 29 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2006 VL 114 IS 12 BP 1898 EP 1903 DI 10.1289/ehp.9302 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 112BN UT WOS:000242500200038 PM 17185282 ER PT J AU Heo, J Factor, VM Uren, T Takahama, Y Lee, JS Major, M Feinstone, SM Thorgeirsson, SS AF Heo, Jeonghoon Factor, Valentina M. Uren, Tania Takahama, Yasushi Lee, Ju-Seog Major, Marian Feinstone, Stephen M. Thorgeirsson, Snorri S. TI Hepatic precursors derived from murine embryonic stem cells contribute to regeneration of injured liver SO HEPATOLOGY LA English DT Article ID IN-VITRO DIFFERENTIATION; HEPATOCYTE DIFFERENTIATION; GENE-EXPRESSION; MOUSE-LIVER; BODY CELLS; GENERATION; EFFICIENT; FUSION; MICE; DEFICIENCY AB We established an efficient system for differentiation, expansion and isolation of hepatic progenitor cells from mouse embryonic stem (ES) cells and evaluated their capacity to repopulate injured liver. Using mouse ES cells transfected with the green fluorescent protein (GFP) reporter gene regulated by albumin (ALB) enhancer/promoter, we found that a serum-free chemically defined medium supports formation of embryoid bodies (EBs) and differentiation of hepatic lineage cells in the absence of exogenous growth factors or feeder cell layers. The first GFP(+) cells expressing ALB were detected in dose proximity to "beating" myocytes after 7 days of EB cultures. GFP+ cells increased in number, acquired hepatocyte-like morphology and hepatocyte-specific markers (i.e., ALB, AAT, TO, and G6P), and by 28 days represented more than 30% of cells isolated from EB outgrowths. The FACS-purified GFP(+) cells developed into functional hepatocytes without evidence of cell ftision and participated in the repairing of diseased liver when transplanted into MUP-uPA/SCID mice. The ES cell-derived hepatocytes were responsive to normal growth regulation and proliferated at the same rate as the host hepatocytes after an additional growth stimulus from CCl4-induced liver injury. The transplanted GFP+ cells also differentiated into biliary epithelial cells. In conclusion, a highly enriched population of committed hepatocyte precursors can be generated from ES cells in vitro for effective cell replacement therapy. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Lab Hepatitis Viruses, Div Viral Prod, CBER, Bethesda, MD 20014 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 4146, Bethesda, MD 20892 USA. EM snorri_s_thorgeirsson@nih.gov FU Intramural NIH HHS NR 37 TC 98 Z9 110 U1 3 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2006 VL 44 IS 6 BP 1478 EP 1486 DI 10.1002/hep.21441 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 112QC UT WOS:000242540700017 PM 17133486 ER PT J AU Wu, DG Shamsi, S Chen, J Kainz, W AF Wu, Dagang Shamsi, Saad Chen, Ji Kainz, Wolfgang TI Evaluations of specific absorption rate and temperature increase within pregnant female models in magnetic resonance imaging birdcage coils SO IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES LA English DT Article DE electromagnetic heating; finite-difference method; magnetic resonance imaging (MRI); pregnant woman; safety standards ID HUMAN HEAD; MR EXPOSURE; SAR; PERFUSION; CHICK AB This paper presents a detailed numerical study of specific absorption rate (SAR) and temperature increase calculations within pregnant female models exposed to magnetic resonance imaging (MRI). Nine pregnant female models, representing different pregnant stages, were used for this study. SAR and temperature increase within and around fetuses at different pregnancy stages were calculated for two MRI operating modes (normal mode and first-level controlled mode) at 64 and 128 MHz. Local fetus energy deposition exceeds the International Electrotechnical Commission limit of 10 W/kg in the first-level controlled mode at 64 MHz. Fetus temperature exceeds or approaches 38 C for both frequencies in the first-level controlled mode at later stages of pregnancy. The core temperature limits for both modes and both frequencies are not exceeded. The results show higher maximum SAR and higher temperature at 64 MHz and during later pregnancy stages with a significant increase starting with the fifth month of pregnancy. Based on the results of this study, radiologists can minimize local fetus heating, especially late in pregnancy, by using normal mode sequences, which minimize the whole body SAR in the mother. C1 Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wu, DG (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. EM jchen18@mail.uh.edu; wolfgang.kainz@fda.hhs.gov NR 34 TC 33 Z9 33 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9480 J9 IEEE T MICROW THEORY JI IEEE Trans. Microw. Theory Tech. PD DEC PY 2006 VL 54 IS 12 BP 4472 EP 4478 DI 10.1109/TMTT.2006.884655 PN 2 PG 7 WC Engineering, Electrical & Electronic SC Engineering GA 118NM UT WOS:000242949000022 ER PT J AU Chan-Tack, KM Greisman, LA AF Chan-Tack, Kirk M. Greisman, Lisa A. TI Combination efavirenz and lopinavir/ritonavir as a nucleoside-sparing regimen for HIV infection SO INFECTIONS IN MEDICINE LA English DT Article DE efavirenz; HIV; lopinavir/ritonavir; nucleoside-sparing regimen ID REVERSE-TRANSCRIPTASE INHIBITOR; ANTIRETROVIRAL THERAPY; HEPATITIS-C; HIV-1-INFECTED CHILDREN; LOPINAVIR-RITONAVIR; RISK-FACTORS; HEPATOTOXICITY; VIRUS; NELFINAVIR; METABOLISM AB Highly active antiretroviral therapy usually comprises 2 nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor or protease inhibitor (PI). However, NRTI resistance frequently confers variable cross-resistance within this class, and long-term NRTI use is associated with mitochondrial toxicity. Therapeutic alternatives, including NRTI-sparing regimens, are needed. Based on limited data, efavirenz (EFV) combined With lopinavir/ritonavir (LPV/r) shows potential as an NRTI-sparing regimen. We review the studies of this regimen and discuss the potential of combination EFV and LPV/r therapy for HIV infection. C1 Univ Maryland, Sch Med, Inst Human Virol, Div Infect Dis, Baltimore, MD 21201 USA. RP Chan-Tack, KM (reprint author), US FDA, Rockville, MD 20857 USA. NR 23 TC 0 Z9 0 U1 0 U2 1 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD DEC PY 2006 VL 23 IS 12 BP 594 EP + PG 5 WC Infectious Diseases SC Infectious Diseases GA 116DO UT WOS:000242782900009 ER PT J AU Li, J Yao, JH Summers, RM Petrick, N Manry, MT Hara, AK AF Li, Jiang Yao, Jianhua Summers, Ronald M. Petrick, Nicholas Manry, Michael T. Hara, Amy K. TI An efficient feature selection algorithm for computer-aided polyp detection SO INTERNATIONAL JOURNAL ON ARTIFICIAL INTELLIGENCE TOOLS LA English DT Article; Proceedings Paper CT 18th International Florida-Artificial-Intelligence-Research-Society Conference CY MAY 15-17, 2005 CL Clearwater, FL SP Florida Artificial Intelligence Res Soc DE feature selection; CAD; piecewise linear network; orthonormal least squares; branch and bound; floating search ID FEATURE SUBSET-SELECTION; SELF-ORGANIZING MAP; GENETIC ALGORITHMS; VARIABLE SELECTION; CT COLONOGRAPHY; IDENTIFICATION; NETWORK AB We present an efficient feature selection algorithm for computer aided detection (CAD) computed tomographic (CT) colonography. The algorithm (1) determines an appropriate piecewise linear network (PLN) model by cross validation, (2) applies the orthonormal least square (OLS) procedure to the PLN model utilizing a Modified Schmidt procedure, and (3) uses a floating search algorithm to select features that minimize the output variance. The undesirable "nesting effect" is prevented by the floating search approach, and the piecewise linear OLS procedure makes this algorithm very computationally efficient because the Modified Schmidt procedure only requires one data pass during the whole searching process. The selected features are compared to those obtained by other methods, through cross validation with support vector machines (SVMS). C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NIBIB, CDRH, Joint Lab Assessment Med Imaging Syst, FDA, Rockville, MD 20852 USA. Univ Texas, Dept Elect Engn, Arlington, TX 76019 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. RP Li, J (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM lij3@cc.nih.gov; jyao@cc.nih.gov; rms@cc.nih.gov; nicholas.petrick@fda.hhs.gov; manry@uta.edu; hara.amy@mayo.edu NR 31 TC 8 Z9 8 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-2130 J9 INT J ARTIF INTELL T JI Int. J. Artif. Intell. Tools PD DEC PY 2006 VL 15 IS 6 BP 893 EP 915 DI 10.1142/S021821300600303X PG 23 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Computer Science GA 120WW UT WOS:000243118500004 ER PT J AU Rosenthal, JM Kim, J de Monastario, F Thompson, DJS Bone, RA Landrum, JT de Moura, FF Khachik, F Chen, H Schleicher, RL Ferris, FL Chew, EY AF Rosenthal, Julie M. Kim, Jonghyeon de Monastario, Francisco Thompson, Darby J. S. Bone, Richard A. Landrum, John T. de Moura, Fabiana F. Khachik, Frederick Chen, Huiping Schleicher, Rosemary L. Ferris, Frederick L., III Chew, Emily Y. TI Dose-ranging study of lutein supplementation in persons aged 60 years or older SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; RESONANCE RAMAN MEASUREMENT; RANDOMIZED CLINICAL-TRIALS; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; BIOLOGICAL VARIATION; BEVACIZUMAB AVASTIN; BETA-CAROTENE AB PURPOSE. To examine the dose-response relationship between oral lutein supplementation and serum lutein concentrations in persons aged 60 years and older, with or without age- related macular degeneration (AMD). METHODS. Forty-five participants with no AMD, large drusen, or advanced AMD, were randomized to receive one of three doses (2.5, 5, or 10 mg) of lutein for 6 months and to be observed for 6 additional months after the cessation of lutein supplementation. RESULTS. The mean age of the participants (33 women) was 71 years (range: 60-91). The serum lutein concentrations of each dose group were similar before supplementation, increased at 1 month, and peaked by 3 months. Median serum concentrations of the 2.5- ,5-, and 10-mg groups from baseline to month 6 increased from 18.7 to 35.1 mu g/dL (2-fold increase), from 17.8 to 59.2 mu g/dL (2.9-fold increase), and from 15.1 to 66.8 mu g/dL (4-fold increase), respectively (all P < 0.001). The increases in lutein serum concentrations did not vary with AMD disease severity (P = 0.98). No toxicity was observed with any dose of lutein. No significant changes were detected in visual acuity or visual field tests. CONCLUSIONS. Increasing doses of lutein supplements significantly increased the serum levels of lutein and zeaxanthin, and doses up to 10 mg were safely administered. A long-term large clinical trial is necessary to investigate the safety and efficacy of lutein in reducing the risk of the development of advanced AMD. C1 NEI, Clin Trials Branch, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. NEI, Off Clin Director, NIH, Bethesda, MD 20892 USA. Florida Int Univ, Dept Chem & Biochem, Miami, FL 33199 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Chew, EY (reprint author), CRC, Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov RI Khachik, Frederick/C-5055-2009; OI De Moura, Fabiana F./0000-0001-8176-5352 FU Intramural NIH HHS [Z99 EY999999, ZIA EY000485-01]; NIGMS NIH HHS [S06GM0825] NR 35 TC 32 Z9 39 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2006 VL 47 IS 12 BP 5227 EP 5233 DI 10.1167/iovs.05-1513 PG 7 WC Ophthalmology SC Ophthalmology GA 110TW UT WOS:000242404900016 PM 17122107 ER PT J AU Khachik, F de Moura, FF Chew, EY Douglass, LW Ferris, FL Kim, J Thompson, DJS AF Khachik, Frederick de Moura, Fabiana F. Chew, Emily Y. Douglass, Larry W. Ferris, Frederick L., III Kim, Jonghyeon Thompson, Darby J. S. TI The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MACULAR DEGENERATION; STRUCTURAL ELUCIDATION; HUMAN PLASMA; GEOMETRICAL-ISOMERS; OXIDATION-PRODUCTS; IDENTIFICATION; MACULOPATHY; EXTRACTS; RETINAS; TISSUES AB PURPOSE. To investigate the effect of lutein supplementation at doses of 2.5, 5.0, and 10 mg/d for 6 months on distribution of these carotenoids and their metabolites in the serum of elderly human subjects, with and without age-related macular degeneration. To determine whether supplementation with lutein can interact with the serum levels of other dietary carotenoids, retinol, and alpha-tocopherol. METHODS. Forty-five subjects received daily supplements of lutein (containing 5% zeaxanthin) for 6 months and were followed up for another 6 months after supplementation. Blood was collected at various intervals and lutein, zeaxanthin, and their metabolites in the sera were quantified by normal-phase high-performance liquid chromatography (HPLC)-UV/visible detection. Other dietary carotenoids, retinol, and alpha-to-copherol were identified and quantified on a C-18 reversed phase HPLC column. RESULTS. After 6 months of supplementation with 10 mg of lutein, the increases in the mean serum levels from baseline were: 210 to 1000 nM/L (P < 0.0001) for lutein and 56 to 95 nM/L (P < 0.0001) for zeaxanthin. Similarly, the mean concentrations (nM/L) of carotenoid metabolites increased from 49 to 98 (P < 0.0001) for 3-hydroxy-ss, epsilon-caroten-3'-one (3'-oxolutein); 31 to 80 (P < 0.0001) for 3'- hydroxy-epsilon,epsilon-caroten-3-one; and 19 to 25 (P < 0.0001) for epsilon, epsilon-carotene- 3,3'-dione. The serum levels of these carotenoids gradually decline within 6 months after supplementation. CONCLUSIONS. The increase in the serum levels of lutein/zeaxanthin correlates with increases in the serum levels of their metabolites that have previously been identified in the ocular tissues. Elderly human subjects with and without AMD can safely take supplements of lutein up to 10 mg/d for 6 months with no apparent toxicity or side effects. C1 Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Univ Maryland, Dept Avian Sci, College Pk, MD 20742 USA. NEI, Clin Trials Branch, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. RP Khachik, F (reprint author), Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, Bldg 091, College Pk, MD 20742 USA. EM khachik@umd.edu RI Khachik, Frederick/C-5055-2009; OI De Moura, Fabiana F./0000-0001-8176-5352 FU Intramural NIH HHS [Z99 EY999999, ZIA EY000485-01] NR 30 TC 32 Z9 39 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2006 VL 47 IS 12 BP 5234 EP 5242 DI 10.1167/iovs.06-0504 PG 9 WC Ophthalmology SC Ophthalmology GA 110TW UT WOS:000242404900017 PM 17122108 ER PT J AU Khan, AA Cheng, CM Van, KT West, CS Nawaz, MS Khan, SA AF Khan, Ashraf A. Cheng, Chorng-Ming Van, Khanh T. West, Christine Summage Nawaz, M. S. Khan, S. A. TI Characterization of class 1 integron resistance gene cassettes in Salmonella enterica serovars Oslo and Bareily from imported seafood SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Letter DE S. enterica; antibiotic resistance; mobile genetic elements ID TYPHIMURIUM DT104; UNITED-STATES C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, PRL SW, Irvine, CA USA. RP Khan, AA (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Ashraf.khan@fda.hhs.gov NR 9 TC 14 Z9 14 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 2006 VL 58 IS 6 BP 1308 EP 1310 DI 10.1093/jac/dkl416 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 115EC UT WOS:000242716600037 PM 17068008 ER PT J AU Hill, LL Foote, JC Erickson, BD Cerniglia, CE Denny, GS AF Hill, L. L. Foote, J. C. Erickson, B. D. Cerniglia, C. E. Denny, G. S. TI Echinacea purpurea supplementation stimulates select groups of human gastrointestinal tract microbiota SO JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS LA English DT Article DE botanical supplement; dietary supplement; Echinacea purpurea; gastrointestinal microbiota; herbal supplement; human ID ENTEROTOXIGENIC BACTEROIDES-FRAGILIS; INFLAMMATORY-BOWEL-DISEASE; LISTERIA-MONOCYTOGENES; FECAL MICROFLORA; HUMAN VOLUNTEERS; HEALTHY CONTROLS; BIFIDOBACTERIUM; INHIBITION; DIARRHEA; PCR AB Background and objective: The objective of this research was to determine the effects of the dietary supplement Echinacea purpurea on aerobic and anaerobic bacteria common to the human gastrointestinal (GI) tract. Botanical extracts have shown in vitro antimicrobial effects against certain pathogenic bacteria. It is uncertain if medicinal herbs have any effect against pathogenic bacteria or on the native GI microbiota. Methods: Fifteen human subjects consumed 1000 mg of standardized E. purpurea for 10 days. Faecal samples were collected at baseline, 10 days and 17-18 days following supplementation. Samples were tested for select aerobic and anaerobic bacteria using plate culture microbiological methods. Results and discussion: Significant increases were found for total aerobic bacteria, Bacteroides group and Bacteroides fragilis after E. purpurea exposure. Supplementation did not significantly alter the number of enteric bacteria, enterococci, lactobacilli, bifidobacteria or total anaerobic bacteria. Conclusion: Echinacea supplementation has altered the GI microbiota. The health consequences associated with this change are unknown but previous research has shown increased Bacteroides concentrations associated with diarrhoea, inflammatory bowel disease and increased risk of colon cancer. Additional research should delineate the role of Echinacea in the stimulation of Bacteroides and describe the effects of other botanical supplements to the GI microbiota. C1 Univ Arkansas, Dept Human Environm Sci, Fayetteville, AR 72701 USA. Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Univ Arkansas, Coll Educ & Hlth Profess, Fayetteville, AR 72701 USA. RP Hill, LL (reprint author), Univ Arkansas, Dept Human Environm Sci, Fayetteville, AR 72701 USA. EM llhill@uark.edu NR 27 TC 5 Z9 5 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-4727 J9 J CLIN PHARM THER JI J. Clin. Pharm. Ther. PD DEC PY 2006 VL 31 IS 6 BP 599 EP 604 DI 10.1111/j.1365-2710.2006.00781.x PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 108IG UT WOS:000242232900009 PM 17176365 ER PT J AU El Kasmi, KC Holst, J Coffre, M Mielke, L de Pauw, A Lhocine, N Smith, AM Rutschman, R Kaushal, D Shen, Y Suda, T Donnelly, RP Myers, MG Alexander, W Vignali, DAA Watowich, SS Ernst, M Hilton, DJ Murray, PJ AF El Kasmi, Karim C. Holst, Jeff Coffre, Maryaline Mielke, Lisa de Pauw, Antoine Lhocine, Nouara Smith, Amber M. Rutschman, Robert Kaushal, Deepak Shen, Yuhong Suda, Takashi Donnelly, Raymond P. Myers, Martin G., Jr. Alexander, Warren Vignali, Dario A. A. Watowich, Stephanie S. Ernst, Matthias Hilton, Douglas J. Murray, Peter J. TI General nature of the STAT3-activated anti-inflammatory response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MICE LACKING STAT3; CYTOKINE SIGNALING-3; IN-VIVO; INTERLEUKIN-10 RECEPTOR; LEPTIN RECEPTOR; PROINFLAMMATORY CYTOKINE; CHRONIC ENTEROCOLITIS; FEEDBACK INHIBITION; HUMAN MACROPHAGES; IMMUNE-RESPONSES AB Although many cytokine receptors generate their signals via the STAT3 pathway, the IL-10R appears unique in promoting a potent anti-inflammatory response (AIR) via STAT3 to antagonize proinflammatory signals that activate the innate immune response. We found that heterologous cytokine receptor systems that activate STAT3 but are naturally refractory (the IL-22R), or engineered to be refractory (the IL-6, leptin, and erythropoietin receptors), to suppressor of cytokine signaling-3-mediated inhibition activate an AIR indistinguishable from IL-10. We conclude that the AIR is a generic cytokine signaling pathway dependent on STAT3 but not unique to the IL-10R. C1 St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA. St Jude Childrens Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA. Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. Royal Melbourne Hosp, Ludwig Inst Canc Res, Parkville, Vic 3050, Australia. Rockefeller Univ, Mol Cell Biol Lab, New York, NY 10016 USA. Kanazawa Univ, Canc Res Inst, Ctr Dev Mol Target Drugs, Kanazawa, Ishikawa 920, Japan. US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. RP Murray, PJ (reprint author), St Jude Childrens Hosp, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA. EM peter.murray@stjude.org RI Ernst, Matthias/D-5111-2012; Holst, Jeff/H-7634-2012; Hilton, Douglas/C-7250-2013; OI Holst, Jeff/0000-0002-0377-9318; Hilton, Douglas/0000-0002-7698-2392; Watowich, Stephanie/0000-0003-1969-659X FU NCI NIH HHS [P30 CA 21765]; NIAID NIH HHS [AI 062961] NR 63 TC 119 Z9 124 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 1 PY 2006 VL 177 IS 11 BP 7880 EP 7888 PG 9 WC Immunology SC Immunology GA 108TJ UT WOS:000242261800046 PM 17114459 ER PT J AU Myers, MR AF Myers, Matthew R. TI Long-time temperature rise due to absorption of focused Gaussian beams in tissue SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID HEAT TRANSFER EQUATION; RADIATION-FORCE; ULTRASOUND; DEFORMATION AB An analytical technique previously developed to study tissue displacement due to acoustic radiation force is extended to analyze temperature rise in tissue for exposure times that are comparable to, or longer than, the tissue perfusion time. A focused transducer with Gaussian amplitude shading is assumed to radiate into a perfused tissue medium with constant thermal and acoustic properties. A simple closed-form expression is derived for the steady-state temperature rise, and a transient correction term is constructed that allows for computation of the equilibrium time of the medium. Comparisons with temperature calculations for non-Gaussian transducers show that the model may be applied to more general intensity profiles. (c) 2006 Acoustical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-170, Rockville, MD 20852 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 2006 VL 120 IS 6 BP 4064 EP 4070 DI 10.1121/1.2359695 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 118RM UT WOS:000242959400059 PM 17225432 ER PT J AU Timbo, BB Ross, MP McCarthy, PV Lin, CTJ AF Timbo, Babgaleh B. Ross, Marianne P. McCarthy, Patrick V. Lin, Chung-Tung J. TI Dietary supplements in a national survey: Prevalence of use and reports of adverse events SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID POISON CONTROL CENTERS; UNITED-STATES; TRENDS; VITAMIN; NONVITAMIN; MEDICATION; ADULTS AB Objective To examine information collected from the 2002 Health and Diet Survey regarding the use dietary supplements and self-reported health problems that the survey participants believed were related to dietary supplements. Methods The US Food and Drug Administration sponsors a Health and Diet Survey to track trends of consumer awareness, attitudes, and practices related to health and diet issues. By telephone, the 2002 Health and Diet Survey staff interviewed English-speaking noninstitutionalized adults aged 18 years or older in households in the 50 states and District of Columbia. Survey respondents were queried as to whether or not they had taken a dietary supplement during the past year and if they had experienced any health problem that they attributed to supplement use. Results Seventy-three percent of US noninstitutionalized adults aged 18 years or older who spoke English and resided in households with telephones used a dietary supplement in the previous 12 months and 4% of them had experienced an adverse event that they believed might be related to dietary supplement use. Eighty-five percent of supplement users reported taking multivitamins/multiminerals and 13.3% of adverse events reported were attributed to multivitamins/multiminerals. A higher proportion of supplement users with adverse events than users without adverse events were concurrently taking supplements and prescription drugs or were taking supplements instead of prescription drug to treat or prevent a health condition. Conclusions This self-reported data describes the prevalence of supplement use and related adverse events. Multivitamins/multiminerals accounted for much of the supplements use and was attributed to a little more than 10% of the adverse events reported. Food and nutrition-professionals and other health care professionals should take special care to learn about their patients' use of these products. C1 US FDA, Epidemiol Team, Off Sci Anal & Support, College Pk, MD 20740 USA. US FDA, Consumer Studies Staff, Off Regulat & Policy, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Timbo, BB (reprint author), US FDA, Epidemiol Team, Off Sci Anal & Support, HFS-728,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM btimbo@cfsan.fda.gov NR 27 TC 140 Z9 146 U1 1 U2 10 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 2006 VL 106 IS 12 BP 1966 EP 1974 DI 10.1016/j.jada.2006.09.002 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 112YH UT WOS:000242563600012 PM 17126626 ER PT J AU Barrett, HH Myers, KJ Devaney, N Dainty, C AF Barrett, Harrison H. Myers, Kyle J. Devaney, Nicholas Dainty, Christopher TI Objective assessment of image quality. IV. Application to adaptive optics SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID OBSERVER DETECTION PERFORMANCE; HOTELLING TRACE CRITERION; NOISE; COMPANION; MODEL; VARIABILITY; SPECKLES; SIGNALS; SYSTEMS; FILTERS AB The methodology of objective assessment, which defines image quality in terms of the performance of specific observers on specific tasks of interest, is extended to temporal sequences of images with random point spread functions and applied to adaptive imaging in astronomy. The tasks considered include both detection and estimation, and the observers are the optimal linear discriminant (Hotelling observer) and the optimal linear estimator (Wiener). A general theory of first- and second-order spatiotemporal statistics in adaptive optics is developed. It is shown that the covariance matrix can be rigorously decomposed into three terms representing the effect of measurement noise, random point spread function, and random nature of the astronomical scene. Figures of merit are developed, and computational methods are discussed. (c) 2006 Optical Society of America. C1 Univ Arizona, Coll Opt Sci, Tucson, AZ 85724 USA. Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20850 USA. Natl Univ Ireland Univ Coll Galway, Dept Phys, Galway, Ireland. RP Barrett, HH (reprint author), Univ Arizona, Coll Opt Sci, Tucson, AZ 85724 USA. EM hhb@email.arizona.edu; kyle.myers@fda.hhs.gov; nicholas.devaney@nuigalway.ie; c.dainty@nuigalway.ie FU NIBIB NIH HHS [P41 EB002035, P41 EB002035-08, R37 EB000803, R37 EB000803-16] NR 61 TC 26 Z9 26 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD DEC PY 2006 VL 23 IS 12 BP 3080 EP 3105 DI 10.1364/JOSAA.23.003080 PG 26 WC Optics SC Optics GA 109RN UT WOS:000242326400011 PM 17106464 ER PT J AU Martinez, MN Kawalek, JC Howard, KD Ward, JL Marroum, P Marnane, W Bensley, D Pelsor, FR Hoag, S Tatavarti, AS Xie, L Fahmy, R AF Martinez, M. N. Kawalek, J. C. Howard, K. D. Ward, J. L. Marroum, P. Marnane, W. Bensley, D. Pelsor, F. R. Hoag, S. Tatavarti, A. S. Xie, L. Fahmy, R. TI Comparison of bovine in vivo bioavailability of two sulfamethazine oral boluses exhibiting different in vitro dissolution profiles SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID HYDROXY METABOLITES; DOSAGE FORMS; DISPOSITION; PHARMACOKINETICS; CLASSIFICATION; PLASMA; SHEEP; TIME; COWS AB The bolus (or oblet) is a dosage form that can be used for the oral administration of pharmaceutical compounds to ruminating species. Unlike traditional tablets, oral boluses may contain quantities of drug on the order of grams rather than milligrams. Due to its size, it is only recently that USP-like in vitro dissolution methods have been developed for this dosage form. However, whether or not these dissolution tests can predict product in vivo performance has yet to be determined. The importance of this issue is apparent when the U.S. Food and Drug Administration Center for Veterinary Medicine is faced with the decision of whether to require additional in vivo bioequivalence study data to support the approval of changes in product chemistry or manufacturing method. The current study was undertaken to determine whether an in vivo/in vitro correlation can be established for bovine sulfamethazine oral boluses and to acquire insight into the magnitude of changes in in vitro product performance that can occur before corresponding changes are seen in in vivo blood level profiles. Based upon the results of this investigation, it is concluded that marked changes in in vitro sulfamethazine bolus performance can be tolerated before resulting in altered in vivo blood level profiles. However, the data also suggest that rumenal absorption may occur for some compounds. Therefore the degree to which variation in product in vitro dissolution profiles can be tolerated may be compound specific. C1 FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD USA. FDA, Ctr Vet Med, Res Off, Laurel, MD USA. FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA. Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. RP Martinez, MN (reprint author), FDA, Ctr Vet Med, Off New Anim Drug Evaluat, 7500 Standish Pl,HFV-130, Rockville, MD USA. EM marilyn.martinez@fda.hhs.gov NR 26 TC 2 Z9 2 U1 2 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD DEC PY 2006 VL 29 IS 6 BP 459 EP 467 DI 10.1111/j.1365-2885.2006.00781.x PG 9 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 101JS UT WOS:000241737700002 PM 17083449 ER PT J AU Shaikh, B Rummel, N Gieseker, C Reimschuessel, R AF Shaikh, B. Rummel, N. Gieseker, C. Reimschuessel, R. TI Metabolism and depletion of albendazole in the muscle tissue of channel catfish following oral treatment SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID FLAVIN-CONTAINING MONOOXYGENASES; AQUATIC ORGANISMS; ATLANTIC SALMON; RAINBOW-TROUT; FENBENDAZOLE; TILAPIA AB The residue depletion of albendazole (ABZ) and its metabolites was studied in channel catfish muscle tissue. Channel catfish were dosed once with 10 mg/kg ABZ via stomach tube with manual restraint. Muscle tissue samples were collected at 8, 16, 24, 48, 72, 96 and 120 h postdose. A high-performance liquid chromatographic method was used to assay ABZ and its major metabolites: ABZ sulfoxide (ABZ-SO), ABZ sulfone (ABZ-SO2) and ABZ aminosulfone (ABZ-2-NH2SO2) in the muscle tissue. The results indicate that ABZ and ABZ-SO were present in low concentrations, i.e. < 15 and < 10 mu g/kg, respectively, at 8 h postdose in catfish muscle with and without skin. ABZ-SO2 was present at 1 mu g/kg concentration levels until 48 h in muscle alone and 72 h in muscle with skin. ABZ-2-NH2SO2 was not detected at any withdrawal periods. C1 US FDA, CVM Off Res, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, CVM Off Res, Laurel, MD 20708 USA. EM badaruddin.shaikh@fda.hhs.gov NR 12 TC 6 Z9 6 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD DEC PY 2006 VL 29 IS 6 BP 525 EP 530 DI 10.1111/j.1365-2885.2006.00799.x PG 6 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 101JS UT WOS:000241737700009 PM 17083456 ER PT J AU Xin, KQ Mizukami, H Urabe, M Toda, Y Shinoda, K Yoshida, A Oomura, K Kojima, Y Ichino, M Klinman, D Ozawa, K Okuda, K AF Xin, Ke-Qin Mizukami, Hiroaki Urabe, Masashi Toda, Yoshihiko Shinoda, Kaori Yoshida, Atsushi Oomura, Kenji Kojima, Yoshitsugu Ichino, Motohide Klinman, Dennis Ozawa, Keiya Okuda, Kenji TI Induction of robust immune responses against human immunodeficiency virus is supported by the inherent tropism of adeno-associated virus type 5 for dendritic cells SO JOURNAL OF VIROLOGY LA English DT Article ID PRIME-BOOST VACCINATION; CYTOTOXIC T-LYMPHOCYTES; DIRECTED GENE-TRANSFER; SMALL INTERFERING RNA; VIRAL VECTORS; FACTOR-IX; IN-VIVO; AAV SEROTYPES; MUSCLE-TISSUE; HEMOPHILIA-B AB The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2 vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1, AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An immunogenicity study of AAV serotypes indicates that AAV1, AAV5, AAV7, and AAV8 vectors expressing the Env gp160 gene induced higher HIV-specific humoral and cell-mediated immune responses than the AAV2 vector did, with the AAV5 vector producing the best responses. Furthermore, mice injected with DCs that had been transduced ex vivo with an AAV5 vector expressing the gp160 gene elicited higher HIV-specific cell-mediated immune responses than did DCs transduced with AAV1 and AAV2 vectors. We also found that AAV vectors produced by HEK293 cells and insect cells elicit similar levels of antigen-specific immune responses. These results demonstrate that the immunogenicity of AAV vectors depends on their tropism for both antigen-presenting cells (such as DCs) and non-antigen-presenting cells (such as muscular cells) and that AAV5 is a better vector than other AAV serotypes. These results may aid in the development of AAV-based vaccine and gene therapy. C1 Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Grad Sch Med, Dept Immunol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Jichi Med Sch, Ctr Mol Med, Div Genet Therapeut, Minami Kawachi, Tochigi 3290498, Japan. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Okuda, K (reprint author), Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM kokuda@med.yokohama-cu.ac.jp RI Mizukami, Hiroaki/D-7674-2013 OI Mizukami, Hiroaki/0000-0001-8954-874X NR 70 TC 52 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2006 VL 80 IS 24 BP 11899 EP 11910 DI 10.1128/JVI.00890-06 PG 12 WC Virology SC Virology GA 113SP UT WOS:000242617900001 PM 17005662 ER PT J AU Ovanesov, MV Sauder, C Rubin, SA Richt, J Nath, A Carbone, KM Pletnikov, MV AF Ovanesov, Mikhail V. Sauder, Christian Rubin, Steven A. Richt, Jurgen Nath, Avindra Carbone, Kathryn M. Pletnikov, Mikhail V. TI Activation of microglia by Borna disease virus infection: In vitro study SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; RECEPTOR GENE-EXPRESSION; NECROSIS-FACTOR-ALPHA; IMMUNODEFICIENCY-VIRUS; NITRIC-OXIDE; CELLS; ASTROCYTES; NEURONS; BRAIN; RATS AB Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to the certain neuronal populations. Since persistent BDV infection of neurons in vitro is noncytolytic and noncytopathic, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brain have not been investigated. To address these issues, activation of primary rat microglial cells was studied following exposure to purified BDV or to persistently BDV-infected primary cortical neurons or after BDV infection of primary mixed neuron-glial cultures. Neither purified virus nor BDV-infected neurons alone activated primary microglia as assessed by the changes in cell shape or production of the proinflammatory cytokines. In contrast, in the BDV-infected primary mixed cultures, we observed proliferation of microglia cells that acquired the round morphology and expressed major histocompatibility complex molecules of classes I and II. These manifestations of microglia activation were observed in the absence of direct BDV infection of microglia or overt neuronal toxicity. In addition, compared to uninfected mixed cultures, activation of microglia in BDV-infected mixed cultures was associated with a significantly greater lipopolysaccharide-induced release of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 10. Taken together, the present data are the first in vitro evidence that persistent BDV infection of neurons and astrocytes rather than direct exposure to the virus or dying neurons is critical for activating microglia. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, Baltimore, MD 21287 USA. US FDA, CBER, Bethesda, MD 20014 USA. Natl Anim Dis Ctr, Ames, IA USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, 600 N Wolfe St,CMSC 8-121, Baltimore, MD 21287 USA. EM mpletnik@jhmi.edu FU NIMH NIH HHS [R01MH048948, R01 MH048948] NR 46 TC 14 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2006 VL 80 IS 24 BP 12141 EP 12148 DI 10.1128/JVI.01648-06 PG 8 WC Virology SC Virology GA 113SP UT WOS:000242617900026 PM 17020949 ER PT J AU Mei, N Arlt, VM Phillips, DH Heflich, RH Chen, T AF Mei, Nan Arlt, Volker M. Phillips, David H. Heflich, Robert H. Chen, Tao TI DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE aristolochic acid; DNA adduct; mutagenicity; transgenic rat ID CHINESE HERBS NEPHROPATHY; P-32 POSTLABELING ANALYSIS; CYTOCHROMES P450 1A1; REDUCTIVE ACTIVATION; P53 MUTATIONS; SALMONELLA-TYPHIMURIUM; UROTHELIAL CARCINOMA; METABOLIC-ACTIVATION; RENAL-FAILURE; GENE AB Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed I day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by P-32-postlabeling and mutant frequency (MF) was determined using the lambda Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N-6-yl]aristolactam 1, 7-[deoxyadenosin-N-6-yl]-aristolactam 11 and 7-[deoxyguanosin-N-2-yl]-aristolactam 1) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10(8) nucleotides in liver and 95-4598 adducts/10(8) nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10(-6) in liver compared with the MFs of 78-1319 x 10(-6) that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T -> T:A transversion was the predominant mutation in AA-treated rats; whereas G:C -> A:T transition was the main type of mutation in control rats. These results indicate that the AA treatment that eventually results in kidney tumors in rats also results in significant increases in DNA adduct formation and cII MF in kidney. Although the same treatment does not produce tumors in rat liver, it does induce DNA adducts and mutations in this tissue, albeit at lower levels than in kidney. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Inst Canc Res, Sect Mol Carcinogenesis, Sutton SM2 5NG, Surrey, England. RP Mei, N (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM nan.mei@fda.hhs.gov RI mei, nan/E-8915-2011; OI mei, nan/0000-0002-3501-9014; Phillips, David/0000-0001-8509-3485; Arlt, Volker Manfred/0000-0003-4314-9318 NR 56 TC 61 Z9 64 U1 1 U2 7 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 1 PY 2006 VL 602 IS 1-2 BP 83 EP 91 DI 10.1016/j.mrfmmm.2006.08.004 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 112XX UT WOS:000242562400010 PM 17010389 ER PT J AU Lin, GX He, XM Ji, HL Shi, LM Davis, RW Zhong, S AF Lin, Guixian He, Xuming Ji, Hanlee Shi, Leming Davis, Ronald W. Zhong, Sheng TI Reproducibility Probability Score - incorporating measurement variability across laboratories for gene selection SO NATURE BIOTECHNOLOGY LA English DT Letter C1 Univ Illinois, Dept Stat, Champaign, IL 61820 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. Univ Illinois, Dept Stat & Comp Sci, Urbana, IL 61801 USA. Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA. RP Lin, GX (reprint author), Univ Illinois, Dept Stat, 725 S Wright St, Champaign, IL 61820 USA. EM szhong@uiuc.edu FU NCI NIH HHS [K08-CA96879, R21-CA109190]; NHGRI NIH HHS [P01 HG000205] NR 4 TC 21 Z9 21 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2006 VL 24 IS 12 BP 1476 EP 1477 DI 10.1038/nbt1206-1476 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 116IL UT WOS:000242795800015 PM 17160039 ER PT J AU Banoo, S Bell, D Bossuyt, P Herring, A Mabey, D Poole, F Smith, PG Sriram, N Wongsrichanalai, C Linke, R O'Brien, R Perkins, M Cunningham, J Matsoso, P Nathanson, CM Olliaro, P Peeling, RW Ramsay, A AF Banoo, Shabir Bell, David Bossuyt, Patrick Herring, Alan Mabey, David Poole, Freddie Smith, Peter G. Sriram, N. Wongsrichanalai, Chansudo Linke, Ralf O'Brien, Rick Perkins, Mark Cunningham, Jane Matsoso, Precious Nathanson, Carl Michael Olliaro, Piero Peeling, Rosanna W. Ramsay, Andy CA TDR Diagnostics Evaluation Expert TI Evaluation of diagnostic tests for infectious diseases: general principles SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID ACCURACY; MEDICINE C1 Med Control Council S Africa, Pretoria, South Africa. WHO, Reg Off Western Pacific, Manila, Philippines. Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol & Biostat, NL-1012 WX Amsterdam, Netherlands. Univ Bristol, Sch Vet, Bristol BS8 1TH, Avon, England. London Sch Hyg & Trop Med, Clin Res Unit, London WC1, England. US FDA, Ctr Biol Evaluat & Res, Div Microbiol Devices, Rockville, MD 20857 USA. London Sch Hyg & Trop Med, Epidemiol Unit, London WC1, England. Tulip Grp Co, Goa, India. USN, Med Res Unit 2, Jakarta, Indonesia. FIND, Geneva, Switzerland. WHO, World Bank, UNICEF,UNDP, Special Programme Res Dev & Res Training Huma, CH-1211 Geneva, Switzerland. RP Banoo, S (reprint author), Med Control Council S Africa, Pretoria, South Africa. EM peelingr@who.int RI Bossuyt, Patrick/B-4557-2016; OI Bossuyt, Patrick/0000-0003-4427-0128; Mabey, David/0000-0002-0031-8276 NR 16 TC 7 Z9 9 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD DEC PY 2006 BP S20 EP S32 DI 10.1038/nrmicro1570 PG 13 WC Microbiology SC Microbiology GA 110XC UT WOS:000242413600004 PM 17366684 ER PT J AU Wang, C AF Wang, Cheng TI NMDA-type glutamate receptors and anesthetic-induced neuronal oxidative stress during development SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1166 EP 1166 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300078 ER PT J AU Garey, J Ferguson, SA Paule, MG AF Garey, J. Ferguson, S. A. Paule, M. G. TI Behavioral effects of acrylamide in rats exposed to daily low doses from gestation day 6 through 6 months of age. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1180 EP 1181 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300120 ER PT J AU Garey, J Ferguson, SA Paule, MG AF Garey, J. Ferguson, S. A. Paule, M. G. TI Effects of chronic low-dose acrylamide exposure on progressive ratio performance in rats. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR DE neurotoxicology; development; behavior C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1181 EP 1181 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300121 ER PT J AU Paule, MG Ferguson, SA Garey, J AF Paule, M. G. Ferguson, S. A. Garey, J. TI Developmental neurotoxicity assessment of low-level acrylamide exposure in fischer 344 rats. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1181 EP 1181 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300122 ER PT J AU Wright, LKM Patterson, TA Pearson, E Hammond, T Paule, MG AF Wright, L. K. M. Patterson, T. A. Pearson, E. Hammond, T. Paule, M. G. TI Evaluation of hippocampal gene expression changes associated with chronic ketamine or remacemide exposure in rats. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR DE gene expression; operant behavior; NMDA receptor C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. AstraZeneca Safety Assesssment, Loughborough, Leics, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1186 EP 1186 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300138 ER PT J AU Bowyer, JF AF Bowyer, John F. TI The recovery of dopaminergic innervation and the repair of neurodegeneration is nearly complete in the basal ganglia within 6 months after a severe acute neurotoxic exposure to amphetamine. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR DE basal ganglia; dopamine; axonal regeneration C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1187 EP 1188 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300141 ER PT J AU Zou, X Sadovova, N Scallet, AC Divine, B Hotchkiss, C Patterson, TA Paule, MG Slikker, W Wang, C AF Zou, X. Sadovova, N. Scallet, A. C. Divine, B. Hotchkiss, C. Patterson, T. A. Paule, M. G. Slikker, W. Wang, C. TI Gaseous anesthetic drug combinations induce developmental neuro-apoptosis in the rat frontal cortex. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR DE gaseous anesthetics; neurodegeneration; rat C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1187 EP 1187 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300140 ER PT J AU Wang, JY Xu, ZJ Fang, H Duhart, HM Patterson, TA Ali, SF AF Wang, Jianyong Xu, Zengjun Fang, Hong Duhart, Helen M. Patterson, Tucker A. Ali, Syed F. TI Gene expression profiling of MPP+-treated MN9D cells: A mechanism of toxicity study. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR DE MPP+; MN9D cell; gene expression C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1188 EP 1188 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300142 ER PT J AU Wang, C Sadovova, N Zou, X Scallet, AC Hotchkiss, C Patterson, TA Hanig, J Paule, MG Slikker, W AF Wang, C. Sadovova, N. Zou, X. Scallet, A. C. Hotchkiss, C. Patterson, T. A. Hanig, J. Paule, M. G. Slikker, W. TI Ketamine produces oxidative DNA damage and loss of monkey frontal cortical neurons in culture. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR DE ketamine; DNA damage; DNA-repair C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1190 EP 1190 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300148 ER PT J AU Puig, M Grajkowski, A Boczkowska, M Ausin, C Beaucage, SL Verthelyi, D AF Puig, Montserrat Grajkowski, Andrzej Boczkowska, Malgorzata Ausin, Cristina Beaucage, Serge L. Verthelyi, Daniela TI Use of thermolytic protective groups to prevent G-tetrad formation in CpG ODN type D: structural studies and immunomodulatory activity in primates SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; TOLL-LIKE-RECEPTOR-9 ACTIVATION; CUTANEOUS LEISHMANIASIS; DNA OLIGONUCLEOTIDES; OLIGODEOXYNUCLEOTIDES; MOTIFS; IDENTIFICATION; INDUCTION; MACAQUES AB CpG oligodeoxynucleotides (ODN) show promise as immunoprotective agents and vaccine adjuvants. CpG ODN type D were shown to improve clinical outcome in rhesus macaques challenged with Leishmania major. These ODN have a self-complementary core sequence and a 3' end poly(G) track that favors G-tetrad formation leading to multimerization. Although multimerization appears necessary for localization to early endosomes and signaling via Toll-like receptor 9 (TLR-9), it can result in product polymorphisms, aggregation and precipitation, thereby hampering their clinical applications. This study shows that functionalizing the poly(G) track of D ODN with thermolytic 2-(N-formyl-N-methyl)aminoethyl (fma) phosphate/thiophosphate protecting groups (pro-D ODN) reduces G-tetrad formation in solution, while allowing tetrad formation inside the cell where the potassium concentration is higher. Temperature-dependent cleavage of the fma groups over time further promoted formation of stable G-tetrads. Peripheral blood cells internalized pro-D ODN efficiently, inducing high levels of IFN alpha, IL-6, IFN gamma and IP-10 and triggering dendritic cell maturation. Administration of pro-D35 to macaques challenged with L.major significantly increased the number of antigen-specific IFN gamma-secreting PBMC and reduced the severity of the skin lesions demonstrating immunoprotective activity of pro-D ODN in vivo. This technology fosters the development of more efficient immunotherapeutic oligonucleotide formulations for the treatment of allergies, cancer and infectious diseases. C1 US FDA, Immunol Lab, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. RP Verthelyi, D (reprint author), US FDA, Immunol Lab, Ctr Drug Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM daniela.verthelyi@fda.hhs.gov NR 28 TC 17 Z9 18 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2006 VL 34 IS 22 BP 6488 EP 6495 DI 10.1093/nar/gkl867 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121XY UT WOS:000243191500015 PM 17130156 ER PT J AU Shashaty, G Frankewich, R Chakraborti, T Choudary, J Al-Fayoumi, S Kacuba, A Castillo, S Robie-Suh, K Rieves, D Weiss, K Pazdur, R AF Shashaty, George Frankewich, Raymond Chakraborti, Tamal Choudary, Jasti Al-Fayoumi, Suliman Kacuba, Alice Castillo, Sonia Robie-Suh, Kathy Rieves, Dwaine Weiss, Karen Pazdur, Richard TI Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis SO ONCOLOGY-NEW YORK LA English DT Article AB Purpose: This report describes the Food and Drug Administration's review of data and analyses leading to the approval of the oral iron chelator, deferasirox for the treatment of chronic iron overload due to transfusional hemosiderosis. Experimental Design: The FDA reviewed findings of a controlled, open-label, randomized multicenter phase III study of deferasirox vs deferoxamine in 586 patients with beta-thalessemia and transfusional hemosiderosis. The study results as well as the results of the FDA review of chemistry, preclinical pharmacology, and supportive studies are described. Results: Following 48 weeks of treatment in the phase III study, patients' liver iron concentrations (a key endpoint variable) had decreased an average of 2.4 mg of iron (Fe)/g dry weight (dw) and 2.9 mg Fe/g dw in the deferasirox and deferoxamine groups, respectively, despite continued blood transfusions in both cohorts. Deferasirox was associated with serum creatinine increases in approximately a third of patients. Common adverse events included gastrointestinal symptoms and skin rash. Other data provided supportive evidence of deferasirox safety and efficacy. Conclusions: The FDA granted deferasirox accelerated approval on November 2, 2005, for use in treating chronic iron overload due to transfusional hemosiderosis in patients >= 2 years of age. The sponsor must obtain clinical data demonstrating the drug's long-term safety and effectiveness. C1 US FDA, White Oak CDER Off, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Shashaty, G (reprint author), US FDA, White Oak CDER Off, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 19 TC 16 Z9 16 U1 1 U2 3 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2006 VL 20 IS 14 BP 1799 EP + PG 9 WC Oncology SC Oncology GA V44BM UT WOS:000202978200009 PM 17263129 ER PT J AU Jones, TF Ingram, LA Fullerton, KE Marcus, R Anderson, BJ McCarthy, PV Vugia, D Shiferaw, B Haubert, N Wedel, S Angulo, FJ AF Jones, Timothy F. Ingram, L. Amanda Fullerton, Kathleen E. Marcus, Ruthanne Anderson, Bridget J. McCarthy, Patrick V. Vugia, Duc Shiferaw, Beletshachew Haubert, Nicole Wedel, Stephanie Angulo, Frederick J. TI A case-control study of the epidemiology of sporadic Salmonella infection in infants SO PEDIATRICS LA English DT Article DE Salmonella; infant; epidemiology ID SEROTYPE ENTERITIDIS INFECTIONS; UNITED-STATES; FOODNET SITES; OUTBREAK; DIARRHEA; RISK; TRANSMISSION; CONSUMPTION; VIRCHOW; MILK AB OBJECTIVE. Rates of Salmonella infection are highest in infants, but little is known about potential sources of infection in this high-risk population. We performed a case-control study to identify dietary and environmental risk factors for sporadic salmonellosis among infants. PATIENTS AND METHODS. In 2002-2004, the Foodborne Diseases Active Surveillance Network conducted a population-based, case-control study of sporadic salmonellosis among infants < 1 year of age in 8 states. Cases were identified via active laboratory-based surveillance. Healthy controls were frequency matched by age and identified through birth registries or published birth announcements. We assessed diet and environmental exposures in the 5 days before illness onset or interview. Data were analyzed by using logistic regression adjusting for age. RESULTS. The study enrolled 442 subjects and 928 controls. Compared with healthy controls, infants with Salmonella infection were less likely to have been breastfed and more likely to have had exposure to reptiles, to have ridden in a shopping cart next to meat or poultry, or to have consumed concentrated liquid infant formula during the 5-day exposure period. Travel outside the United States was associated with illness in infants 3 to 6 and > 6 months of age. Attending day care with a child with diarrhea was associated with salmonellosis in infants > 6 months of age. CONCLUSIONS. We identified a number of modifiable protective and risk factors for salmonellosis in infants. Attention should be directed at developing effective preventive measures for this high-risk population. C1 Tennessee Dept Hlth, Communicable & Environm Dis Serv, Nashville, TN 37247 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Connecticut Emerging Infect Program, New Haven, CT USA. New York State Dept Hlth, Albany, NY 12237 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Calif Dept Hlth Serv, Berkeley, CA USA. Oregon Dept Human Serv, Portland, OR USA. Colorado Dept Publ Hlth & Environm, Denver, CO USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. RP Jones, TF (reprint author), Tennessee Dept Hlth, Communicable & Environm Dis Serv, 4th Floor,Cordell Hull Bldg,425 5th Ave N, Nashville, TN 37247 USA. EM tim.f.jones@state.tn.us NR 35 TC 45 Z9 49 U1 0 U2 14 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2006 VL 118 IS 6 BP 2380 EP 2387 DI 10.1542/peds.2006-1218 PG 8 WC Pediatrics SC Pediatrics GA 111TX UT WOS:000242478900014 PM 17142522 ER PT J AU Gutman, S Hackett, J AF Gutman, Steven Hackett, Joseph TI Search for shortcuts on the critical path to market: USFDA perspectives from the diagnostic side SO PHARMACOGENOMICS LA English DT Article DE biomarkers; critical path; co-development of drugs and diagnostics; regulatory tools AB The US FDA has been regulating medical devices (including laboratory tests) since 1976. Premarket review is well defined and may include requirements for both analytical and clinical information. In 2004, the US FDA initiated the Critical Path initiative to help foster development of new medical products. Biomarkers were seen as an important part of this new program for both traditional diagnostic purposes and to aid in drug development. The US FDA has created programs to foster use of biomarkers both for routine diagnostic and for drug development purposes. There is growing methodology to serve as road maps for efficient and scientifically sound development in this area. The US FDA has a flexible regulatory tool box to apply to biomarker development, and has the clear aim of working as a partner to bring these important medical devices quickly to the medical marketplace. C1 US FDA, Off Vitro Diagnost Dev Evaluat & Safety, Ctr Dev & Radiol Hlth, Rockville, MD 20857 USA. RP Gutman, S (reprint author), US FDA, Off Vitro Diagnost Dev Evaluat & Safety, Ctr Dev & Radiol Hlth, 5600 Fishers Lane, Rockville, MD 20857 USA. EM steve.gutman@fda.hhs.gov; joseph.hackett@fda.hhs.gov NR 3 TC 5 Z9 6 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD DEC PY 2006 VL 7 IS 8 BP 1223 EP 1227 DI 10.2217/14622416.7.8.1223 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 126CF UT WOS:000243489100017 PM 17184209 ER PT J AU Letterio, J Rudikoff, E Voong, N Bauer, SR AF Letterio, John Rudikoff, Eva Voong, Nga Bauer, Steven R. TI Transforming growth factor-beta 1 sensitivity is altered in abl-myc- and raf-myc-induced mouse pre-B-cell tumors SO STEM CELLS LA English DT Article DE transforming growth factor-beta 1; pre-B tumors; myc; abl; raf ID GROWTH-FACTOR-BETA; TGF-BETA; RECEPTOR EXPRESSION; APOPTOSIS; MICE; TGF-BETA-1; LYMPHOCYTES; LINES; PLASMACYTOMAS; ACTIVATION AB Understanding the mechanisms leading to transformation of early B-lineage precursors is an important step leading to rational design of new treatments for precursor (pre)-B-cell leukemia. We used normal mouse pre-B cells to determine if and how transforming growth factor (TGF)-beta 1 affects these precursors to the B-cell lineage and whether transformed pre-B cells respond to TGF-beta 1. We found that normal pre-B cells proliferating in the presence of interleukin (IL)-7 enter cell-cycle arrest after exposure to TGF-beta 1. However, clonally related IL-7-independent tumors induced by oncogenes abl + myc or raf + myc have reduced sensitivity to TGF-beta 1. In contrast, tumor cells induced by myc alone remain sensitive to TGF-beta 1 growth suppression. These results suggest that lesions in different molecular signaling pathways can lead to loss of TGF-beta 1 sensitivity in a single cell type. The approach of using normal pre-B-cell lines and transformation by overexpression of different oncogenes provides a system to compare and contrast molecular pathways that lead to full malignancy. C1 US FDA, Ctr Biol Evaluat & Res, Cell & Tissue Therapy Branch, Rockville, MD 20852 USA. Case Western Reserve Univ, Div Pediat Hematol Oncol, Ireland Canc Ctr, Cleveland, OH 44106 USA. NCI, NIH, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Bauer, SR (reprint author), US FDA, Ctr Biol Evaluat & Res, Cell & Tissue Therapy Branch, NIH Bldg 29B,Room 2NN10,HFM-740,1401 Rockville Pi, Rockville, MD 20852 USA. EM Steven.Bauer@fda.hhs.gov RI Bauer, Steven/G-5559-2012; OI Bauer, Steven/0000-0003-2831-846X FU Intramural NIH HHS NR 27 TC 2 Z9 3 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD DEC PY 2006 VL 24 IS 12 BP 2611 EP 2617 DI 10.1634/stemcells.2005-0623 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 114WL UT WOS:000242696200002 PM 16945999 ER PT J AU Bowyer, JF Ali, S AF Bowyer, John F. Ali, Syed TI High doses of methamphetamine that cause disruption of the blood-brain barrier in limbic regions produce extensive neuronal degeneration in mouse hippocampus SO SYNAPSE LA English DT Article DE methamphetamine; hippocampus; neurodegeneration; blood-brain barrier; seizures; Fluoro-Jade C ID DOMOIC ACID; INDUCED NEURODEGENERATION; SOMATOSENSORY CORTEX; FORMER AMPHETAMINE; RAT FOREBRAIN; NEUROTOXICITY; INDIVIDUALS; IMPAIRMENT; MICROGLIA; EXPOSURE AB Histological examination of brain after a single high (40 mg/kg) dose Of D-methamphetamine (METH) was used to determine the relationships between blood-brain barrier (BBB) disruption, hyperthermia, intense seizure activity, and extensive degeneration that this exposure often produces. In very hyperthermic mice (body temperatures > 40.5 degrees C) exhibiting status epilepticus, increase in mouse IgG immunoreactivity (IgGIR) in the medial and ventral amygdala was observed within 90 min after METH exposure. In a few instances, where body temperature was in the 40.0 degrees C range, such IgGlR was also seen in animals that had exhibited status epilepticus. Variable increases in IgGIR, which correlated with neurodegeneration, also occurred within 12 h in the hippocampus, indicating BBB disruption in this region also. Degenerating neurons, Fluoro-Jade C (FJ-C) labeled, were first detected 4 h after METH in the amygdala and hippocampus. Extensive neurodegeneration occurred in the amygdaloid and hippocampal pyramidal cell regions in animals with marked IgGIR increase in these regions by 12 and 24 h after METH. A very rapid activation of brain microglia and/or infiltration of macrophages in regions of notable IgGIR increase with intense neurodegeneration were seen within 24 h. The phagocytosis rate of neurons in the hippocampus was so rapid that FJ-C labeling was virtually nonexistent 3 days after METH. METH did not produce IgGIR increase or neurodegeneration in the limbic regions in the absence of hyperthermia and seizures. Thus, high doses of METH can cause damage to the BBB when hyperthermia occurs, resulting in rapid and extensive hippocampal and amygdalar damage. The BBB disruption in the medial amygdala occurs first, and may well be contributing to the induction and severity of seizures, while BBB disruption in the hippocampus is likely a result of the seizures and hyperthermia. This hippocampal damage should be sufficient to compromise learning and memory. Published 2006 Wiley-Liss, lnc. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. EM jbowyer@nctr.fda.gov NR 46 TC 80 Z9 83 U1 3 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC 1 PY 2006 VL 60 IS 7 BP 521 EP 532 DI 10.1002/syn.20324 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 093FI UT WOS:000241153000005 PM 16952162 ER PT J AU Bloom, SL Spong, CY Thom, E Varner, MW Rouse, DJ Weininger, S Ramin, SM Caritis, SN Peaceman, A Sorokin, Y Sciscione, A Carpenter, M Mercer, B Thorp, J Malone, F Harper, M Iams, J Anderson, G AF Bloom, Steven L. Spong, Catherine Y. Thom, Elizabeth Varner, Michael W. Rouse, Dwight J. Weininger, Sandy Ramin, Susan M. Caritis, Steve N. Peaceman, Alan Sorokin, Yoram Sciscione, Anthony Carpenter, Marshall Mercer, Brian Thorp, John Malone, Fergal Harper, Margaret Iams, Jay Anderson, Garland CA Natl Inst Child Hlth Human Dev Mat TI Fetal pulse oximetry and cesarean delivery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02, 2006 CL Miami, FL SP Soc Maternal Fetal Med AB Background: Knowledge of fetal oxygen saturation, as an adjunct to electronic fetal monitoring, may be associated with a significant change in the rate of cesarean deliveries or the infant's condition at birth. Methods: We randomly assigned 5341 nulliparous women who were at term and in early labor to either "open" or "masked" fetal pulse oximetry. In the open group, fetal oxygen saturation values were displayed to the clinician. In the masked group, the fetal oxygen sensor was inserted and the values were recorded by computer, but the data were hidden. Labor complicated by a nonreassuring fetal heart rate before randomization was documented for subsequent analysis. Results: There was no significant difference in the overall rates of cesarean delivery between the open and masked groups (26.3% and 27.5%, respectively; P=0.31). The rates of cesarean delivery associated with the separate indications of a nonreassuring fetal heart rate (7.1% and 7.9%, respectively; P=0.30) and dystocia (18.6% and 19.2%, respectively; P=0.59) were similar between the two groups. Similar findings were observed in the subgroup of 2168 women in whom a nonreassuring fetal heart rate was detected before randomization. The condition of the infants at birth did not differ significantly between the two groups. Conclusions: Knowledge of the fetal oxygen saturation is not associated with a reduction in the rate of cesarean delivery or with improvement in the condition of the newborn. (ClinicalTrials.gov number, NCT00098709.). C1 Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75390 USA. NICHHD, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Univ Utah, Salt Lake City, UT USA. Univ Alabama, Birmingham, AL USA. US FDA, Rockville, MD 20857 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Univ Pittsburgh, Pittsburgh, PA USA. Northwestern Univ, Chicago, IL 60611 USA. Wayne State Univ, Detroit, MI USA. Drexel Univ, Philadelphia, PA 19104 USA. Brown Univ, Providence, RI 02912 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ N Carolina, Chapel Hill, NC USA. Columbia Univ, New York, NY USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Bloom, SL (reprint author), Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM steven.bloom@utsouthwestern.edu RI Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD27915, HD27869, HD27860, HD27917, HD21410, HD34116, HD34136, HD34208, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 14 TC 50 Z9 52 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 NOV 23 PY 2006 VL 355 IS 21 BP 2195 EP 2202 DI 10.1056/NEJMoa061170 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 107KQ UT WOS:000242170900006 PM 17124017 ER PT J AU Graham, DJ AF Graham, David J. TI Telithromycin and acute liver failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Graham, DJ (reprint author), US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. EM david.graham1@fda.hhs.gov NR 6 TC 12 Z9 13 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 NOV 23 PY 2006 VL 355 IS 21 BP 2260 EP 2261 DI 10.1056/NEJMc066372 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 107KQ UT WOS:000242170900027 PM 17124030 ER PT J AU Rieves, RD Weiss, KD AF Rieves, R. Dwaine Weiss, Karen D. TI Judging the safety of aprotinin SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CARDIAC-SURGERY C1 US FDA, Silver Spring, MD 20903 USA. RP Rieves, RD (reprint author), US FDA, Silver Spring, MD 20903 USA. NR 2 TC 3 Z9 3 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 NOV 23 PY 2006 VL 355 IS 21 BP 2262 EP 2262 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 107KQ UT WOS:000242170900029 PM 17131514 ER PT J AU Heemstra, JM Kerrigan, SA Doerge, DR Helferich, WG Boulanger, WA AF Heemstra, Jennifer M. Kerrigan, Sean A. Doerge, Daniel R. Helferich, William G. Boulanger, William A. TI Total synthesis of (S)-equol SO ORGANIC LETTERS LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; ENANTIOSELECTIVE SYNTHESIS; S-EQUOL; PHYTOESTROGENS; ISOFLAVONES; METABOLITE; BETA; SOY AB The first enantioselective total synthesis of (S)-equol is reported. The described route relies on an Evans alkylation to form the stereocenter and an intramolecular Buchwald etherification to generate the chroman ring. Key features of this method include its brevity, its scalability, and the low cost of starting materials. C1 Obiter Res LLC, Urbana, IL 61802 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. RP Heemstra, JM (reprint author), Obiter Res LLC, 2004 S Wright St Extended,Suite 110, Urbana, IL 61802 USA. EM waboulanger@obiterresearch.com FU NCI NIH HHS [CA77355]; NIA NIH HHS [P01 AG024387] NR 15 TC 30 Z9 32 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD NOV 23 PY 2006 VL 8 IS 24 BP 5441 EP 5443 DI 10.1021/ol0620444 PG 3 WC Chemistry, Organic SC Chemistry GA 105PZ UT WOS:000242046100006 PM 17107042 ER PT J AU Churchwell, MI Beland, FA Doerge, DR AF Churchwell, Mona I. Beland, Frederick A. Doerge, Daniel R. TI Quantification of O-6-methyl and O-6-ethyl deoxyguanosine adducts in C57BL/6N/Tk(+/-) mice using LUMSIMS SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE O-6-methyl-2 '-deoxyguanosine; O-6-ethyl-2 '-deoxyguanosine; mass spectrometry; DNA adducts ID TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; DEOXYRIBONUCLEIC-ACID; DNA-ADDUCTS; QUANTITATION; ALKYLATION; CARCINOGENS; METHYL AB The carcinogenicity of many alkylating agents is derived from their ability to form persistent DNA adducts that induce mutations. This paper presents and validates methodology, based on LC with tandem mass spectrometry, for the separate or concurrent quantification by isotope dilution of O-6-methyl-2'-deoxyguanosine ((OMe)-Me-6-dG) and O-6-ethyl-2'-deoxyguanosine ((OEt)-Et-6-dG) DNA adducts. The limits of quantification were estimated to be <= 0.2 adducts/10(8) nucleotides for either adduct. This sensitivity permitted evaluation of adduct levels in livers from separate groups of untreated adult C57BL/6N/Tk(+/-) and C57BL/6N X Sv129 mice (undetectable to 5.5 +/- 6.7 (OMe)-Me-6-dG/10(8) nucleotides; undetectable to 0.04 (OEt)-Et-6-dG/10(8) nucleotides). Treatment of adult C57BL/6N/Tk(+/-) mice with equimolar doses (342 mu mol/kg body weight) of N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea produced adduct levels in liver of 1700 +/- 80 (OMe)-Me-6-dG/10(8) nucleotides and 260 +/- 60 (OEt)-Et-6-dG/10(8) nucleotides, respectively, when assessed 4 h after dosing. These methods should be useful for evaluations of DNA adducts in relation to cellular processes that modify carcinogenic and toxicological responses in experimental animals and humans. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov NR 21 TC 12 Z9 12 U1 0 U2 3 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 NOV 21 PY 2006 VL 844 IS 1 BP 60 EP 66 DI 10.1016/j.jchromb.2006.06.042 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 109SG UT WOS:000242328300009 PM 16931193 ER PT J AU Turnipseed, SB Clark, SB Andersen, WC Karbiwnyk, CM Miller, KE Hurlbut, JA AF Turnipseed, Sherri B. Clark, Susan B. Andersen, Wendy C. Karbiwnyk, Christine M. Miller, Keith E. Hurlbut, Jeffrey A. TI Confirmation of diminazene diaceturate in bovine plasma using electrospray liquid chromatography-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE diminazene diaceturate; bovine plasma; mass spectrometry AB Diminazene diaceturate is used as a trypanocide for cattle in tropical regions. This paper describes a LC-MSn method to confirm the presence of diminazene in bovine plasma. Bound diminazene in plasma samples was freed with dilute phosphoric acid, then concentrated on a bonded C-18 SPE cartridge. The LC-MSn method utilized electrospray ionization coupled with an ion trap mass spectrometer. Ions observed in MS2 and MS3 product ion spectra, as well as those from the MS1 spectrum, were monitored. The method was validated with plasma samples fortified with diminazene diaceturate (4-100 ng/mL). Diminazene was confirmed in samples fortified with diminazene diaceturate at levels of 6.4 ng/mL or higher. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Lakewood, CO 80225 USA. US FDA, Denver Dist Lab, Denver Fed Ctr, Lakewood, CO 80225 USA. Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA. Western Washington Univ, Dept Chem, Bellingham, WA 98225 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, POB 25087, Lakewood, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 12 TC 6 Z9 7 U1 0 U2 8 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 NOV 21 PY 2006 VL 844 IS 1 BP 127 EP 133 DI 10.1016/j.jchromb.2006.07.016 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 109SG UT WOS:000242328300017 PM 16891161 ER PT J AU Mei, N Xia, QS Chen, L Moore, MM Chen, T Fu, PP AF Mei, Nan Xia, Qingsu Chen, Ling Moore, Martha M. Chen, Tao Fu, Peter P. TI Photomutagenicity of anhydroretinol and 5,6-epoxyretinyl palmitate in mouse lymphoma cells SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID THYMIDINE KINASE GENE; RETINYL-PALMITATE; INTERNATIONAL WORKSHOP; VITAMIN-A; PHOTODECOMPOSITION PRODUCTS; LIPID-PEROXIDATION; HUMAN-NUTRITION; MUTATION ASSAY; GENOTOXICITY; SKIN AB Retinyl palmitate (RP) is frequently used as an ingredient in cosmetics and other retail products. We previously reported that, under UVA light irradiation, RP is facilely decomposed into multiple products, including anhydroretinol (AR) and 5,6-epoxyretinyl palmitate (5,6-epoxy-RP). We also determined that combined treatment of mouse lymphoma cells with RP and UVA irradiation produced a photomutagenic effect. In this study, we evaluated the photomutagenicity of AR and 5,6-epoxy-RP, in L5178Y/Tk+/mouse lymphoma cells. Treatment of cells with AR or 5,6-epoxy-RP alone at 10 and 25 mu g/mL for 4 h did not show a positive mutagenic response. However, because these doses did not induce the required amount of cytotoxicity for mouse lymphoma assay, we are unable to determine whether or not these two compounds are mutagenic. Treatment of cells with 1-25 mu g/mL AR or 5,6-epoxy-RP under UVA light (315-400 nm) for 30 min (1.38 mW/cm(2)) produced a synergistic photomutagenic effect. At 10 mu g/mL (37.3 mu M) AR with UVA exposure, the mutant frequency (MF) was about 3-fold higher than that for UVA exposure alone, whereas the MF for 25 mu g/mL (46.3 mu M) of 5,6-epoxy-RP + UVA was approximately 2-fold higher than that for UVA exposure alone. Compared with previous results for RP + UVA treatment, the potency of the induced phototoxicity and photomutagenicity was AR > RP > 5,6-epoxy-RP. To elucidate the underlying photomutagenic mechanism, we examined the loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11 for mutants induced by AR or 5,6-epoxy-RP. Most mutants lost the Tk(+) allele, and more than 70% of the chromosome damage extended to 38 cM in chromosome length. AR + UVA induced about twice as many mutants that lost all four microsatellite markers from the chromosome 11 carrying the Tk(+) allele as RP + UVA or 5,6-epoxy- RP + UVA. These results suggest that two of RP's photodecomposition products are photomutagenic in mouse lymphoma cells, causing events that affect a large segment of the chromosome. C1 US FDA, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Mei, N (reprint author), US FDA, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM nan.mei@fda.hhs.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 30 TC 16 Z9 16 U1 1 U2 1 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 NOV 20 PY 2006 VL 19 IS 11 BP 1435 EP 1440 DI 10.1021/tx0600907 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 106TK UT WOS:000242124100006 PM 17112230 ER PT J AU Bowers, DC Liu, Y Leisenring, W McNeil, E Stovall, M Gurney, JG Robison, LL Packer, RJ Oeffinger, KC AF Bowers, Daniel C. Liu, Yan Leisenring, Wendy McNeil, Elizabeth Stovall, Marilyn Gurney, James G. Robison, Leslie L. Packer, Roger J. Oeffinger, Kevin C. TI Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: A report from the childhood cancer survivor study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID ACUTE LYMPHOBLASTIC-LEUKEMIA; YOUNG-ADULTS; RADIATION-THERAPY; ISCHEMIC-STROKE; VASCULOPATHY; CHILDREN; SEQUELAE; GLIOMA AB Purpose This report examines the incidence of and risk factors for strokes that occur in >= 5-year survivors of childhood leukemia and brain tumors. Patients and Methods The rate of first occurrence of self-reported late-occurring strokes was determined for leukemia survivors (n = 4,828), brain tumor survivors (n = 1,871), and a comparison group of a random sample of cancer survivor siblings (n = 3,846). Relative risks (RRs) and 95% confidence intervals (Cls) of stroke by treatment exposures were examined by multivariate analyses. Results Thirty-seven leukemia survivors and 63 brain tumor survivors reported a late-occurring stroke. The rate of late-occurring stroke for leukemia survivors was 57.9 per 100,000 person-years (95% Cl, 41.2 to 78.7). The BR of stroke for leukemia survivors compared with the sibling comparison group was 6.4 (95% Cl, 3.0 to 13.8, P <.0001). The rate of late-occurring stroke for brain tumor survivors was 267.6 per 100,000 person-years (95% Cl, 206.8 to 339.2). The RR of stroke for brain tumor survivors compared with the sibling comparison group was 29.0 (95% Cl, 13.8 to 60.6; P <.0001). Mean cranial radiation therapy (CRT) dose of >= 30 Gy was associated with an increased risk in both leukemia and brain tumor survivors in a dose-dependent fashion, with the highest risk after doses of >= 50 Gy CRT. Conclusion Survivors of childhood leukemia and brain tumors, particularly those with brain tumors treated with CRT at doses of greater than 30 Gy, are at an increased risk of stroke. C1 Univ Texas, SW Med Sch, SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. US FDA, Rockville, MD 20857 USA. Univ Michigan, Ann Arbor, MI 48109 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Bowers, DC (reprint author), Univ Texas, SW Med Sch, SW Med Ctr Dallas, Dept Pediat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Daniel.Bowers@utsouthwestern.edu FU NCI NIH HHS [U24-CA-55727] NR 21 TC 170 Z9 171 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2006 VL 24 IS 33 BP 5277 EP 5282 DI 10.1200/JCO.2006.07.2884 PG 6 WC Oncology SC Oncology GA 109XL UT WOS:000242342800015 PM 17088567 ER PT J AU Yoon, SI Logsdon, NJ Sheikh, F Donnelly, RP Walter, MR AF Yoon, Sung Il Logsdon, Naomi J. Sheikh, Faruk Donnelly, Raymond P. Walter, Mark R. TI Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID X-RAY-DIFFRACTION; CRYSTAL-STRUCTURE; SOLUBLE RECEPTOR; GROWTH-HORMONE; INTERLEUKIN-22; CELLS; CHAIN; CRYSTALLIZATION; CYTOKINES; HOMOLOG AB Interleukin-10 receptor 2 (IL-10R2) is a critical component of the IL-10 center dot IL-10R1 center dot IL-10R2 complex which regulates IL-10-mediated immunomodulatory responses. The ternary IL-10 signaling complex is assembled in a sequential order with the IL-10 center dot IL-10R1 interaction occurring first followed by engagement of the IL-10R2 chain. In this study we map the IL-10R2 binding site on IL-10 using surface plasmon resonance and cell-based assays. Critical IL-10R2 binding residues are located in helix A adjacent to the previously identified IL-10R1 recognition surface. Interestingly, IL-10R2 binding residues located in the N-terminal end of helix A exhibit large structural differences between unbound cIL-10 and cIL-10 center dot IL-10R1 crystal structures. This suggests IL-10R1-induced conformational changes regulate IL-10R2 binding and assembly of the ternary IL-10 center dot IL10R1 center dot IL-10R2 complex. The basic mechanistic features of the assembly process are likely shared by six additional class-2 cytokines (viral IL-10s, IL-22, IL-26, IL-28A, IL28B, and IL-29) to promote IL-10R2 binding to six additional receptor complexes. These studies highlight the importance of structure in regulating low affinity protein-protein interactions and IL-10 signal transduction. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Biophys Sci & Engn, Birmingham, AL 35294 USA. US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Walter, MR (reprint author), Univ Alabama, Dept Microbiol, CBSE Rm 144,1025 18th St S, Birmingham, AL 35294 USA. EM walter@uab.edu FU NIAID NIH HHS [R01 AI047300, AI47300] NR 39 TC 61 Z9 63 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 NOV 17 PY 2006 VL 281 IS 46 BP 35088 EP 35096 DI 10.1074/jbc.M606791200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 104CN UT WOS:000241933700042 PM 16982608 ER PT J AU Morgan, DA Fitzsimmons, J Argaw, T Wilson, C AF Morgan, Doris A. Fitzsimmons, John Argaw, Takele Wilson, Carolyn TI Productive infection of human cord blood stem cells and lineage progenitors by porcine endogenous retrovirus (PERV). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. CBER, FDA, Div Cellular & Gene Therapies, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4178 BP 124B EP 124B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440400458 ER PT J AU Gelderman-Fuhrmann, MP Siddiqui, SF Vostal, JG AF Gelderman-Fuhrmann, Monique P. Siddiqui, Sheena F. Vostal, Jaroslav G. TI Detection of UV induced damage to human platelets by an in vivo animal model. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 US FDA, CBER, Lab Cellular Hematol, Rockville, MD USA. NR 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 582 BP 175A EP 176A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000583 ER PT J AU Miura, YJ Lee, E Gibellini, F White, T Marti, G Wilson, W Wiesmer, A AF Miura, Yuji Lee, Elinor Gibellini, Federica White, Therese Marti, Gerald Wilson, Wyndham Wiesmer, Adrian TI ZAP-70 expression is associated with increased migration to SDF-1 in chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, NCI, Canc Res Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 587 BP 177A EP 177A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000588 ER PT J AU Holada, K Simak, J Vostal, JG AF Holada, Karel Simak, Jan Vostal, Jaroslav G. TI The post-transfusion recovery and survival of red blood cells in mice is affected by the expression of cellular prion protein. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Charles Univ Prague, Fac Med 1, Inst Microbiol & Immunol, Prague, Czech Republic. US FDA, Lab Cellular Hematol, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 959 BP 286A EP 286A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001219 ER PT J AU Lee, E Xu, XL Munson, P Cooper, R Raghavachari, N White, T Marti, GE Wilson, WH Wiestner, A AF Lee, Elinor Xu, Xiuli Munson, Peter Cooper, Ronald Raghavachari, Nalini White, Therese Marti, Gerald E. Wilson, Wyndham H. Wiestner, Adrian TI Rituximab induces an interferon gene expression signature in patients with CLL. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 NIH, NHLBI, Hematol Branch, Bethesda, MD USA. NIH, NHLBI, Bethesda, MD USA. NIH, NCI, Ctr Canc Res, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 4988 BP 335B EP 335B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402107 ER PT J AU Gelderman-Fuhrmann, MP Simakova, O Siddiqui, SF Vostal, AC Simak, J AF Gelderman-Fuhrmann, Monique P. Simakova, Olga Siddiqui, Sheena F. Vostal, Alexander C. Simak, Jan TI Adverse effects of fullerenes on endothelial cells: Fullerenol C-60(OH)(24) induced tissue factor and ICAM-1 membrane expression and caused apoptosis in vitro. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 US FDA, CBER, Rockville, MD 20857 USA. USUHS, Sch Med, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 NR 0 TC 2 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 1801 BP 511A EP 511A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002319 ER PT J AU Gelderman-Fuhrmann, MP Schiffmann, R Simak, J AF Gelderman-Fuhrmann, Monique P. Schiffmann, Raphael Simak, Jan TI Elevated counts of circulating endothelial microparticles in pediatric Fabry patients decreased after enzyme replacement therapy. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 US FDA, CBER, LCH, Rockville, MD 20857 USA. NIH, NINDS, DMNB, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1818 BP 515A EP 515A PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002336 ER PT J AU Angeles-Boza, AM Chifotides, HT Aguirre, JD Chouai, A Fu, PKL Dunbar, KR Turro, C AF Angeles-Boza, Alfredo M. Chifotides, Helen T. Aguirre, J. Dafhne Chouai, Abdellatif Fu, Patty K. -L. Dunbar, Kim R. Turro, Claudia TI Dirhodium(II,II) complexes: Molecular characteristics that affect in vitro activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RHODIUM(II) CARBOXYLATES; PARTITION-COEFFICIENTS; STRUCTURAL EVIDENCE; ANTITUMOR AGENTS; AMINE COMPOUNDS; LEAVING GROUPS; METAL-BINDING; DNA; PLATINUM; MECHANISM AB In the series Rh-2(O2CR)(4) (R) CH3, 1; R) CF3, 2), [Rh-2(O2CR)(2)(phen)(2)](2+) (R) CH3, 3; R) CF3, 4), and [Rh-2(O2CR)(2)( dppz)(2)](2+) (R) CH3, 5; R) CF3, 6), 2, 4, and 6 are twice as cytotoxic as 1, 3, and 5, respectively. The substitution reactions of 2 with 9-ethylguanine at various temperatures take place at faster rates than those of 1, and the activation energy E-a(1) = 69 +/- 4 kJ/mol is twice E-a(2) = 35 +/- 2 kJ/mol. The higher cytotoxicities of [Rh-2(mu-O2CCH3) 2(eta(1)-O2CCH3) L(MeOH)](+) (L = dppz, 7; L = dppn, 8) relative to [Rh-2(mu-O2CCH3)(2)(bpy) L](2+) (L) dppz, 10; L = dppn, 11) are attributed to the labile equatorial groups in 7 and 8 not present in 10 and 11. The toxicities of complexes 1-8 are not related to their charge or the ease by which they transverse the cellular membrane but to the lability of the ligands on the dirhodium core. C1 Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. US FDA, College Pk, MD 20740 USA. RP Dunbar, KR (reprint author), Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. EM dunbar@mail.chem.tamu.edu; turro@chemistry.ohio-state.edu RI Angeles-Boza, Alfredo/C-6563-2008; Dunbar, Kim/B-6488-2015; Turro, Claudia/H-5335-2015 OI Angeles-Boza, Alfredo/0000-0002-5560-4405; Dunbar, Kim/0000-0001-5728-7805; Turro, Claudia/0000-0003-3202-5870 FU NIGMS NIH HHS [R01 GM64040-01] NR 58 TC 88 Z9 89 U1 0 U2 30 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 NOV 16 PY 2006 VL 49 IS 23 BP 6841 EP 6847 DI 10.1021/jm060592h PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 103NP UT WOS:000241894000026 PM 17154514 ER PT J AU Wang, LL Abbasi, F Gaigalas, AK Vogt, RF Marti, GE AF Wang, Lili Abbasi, Fatima Gaigalas, Adolfas K. Vogt, Robert F. Marti, Gerald E. TI Comparison of fluorescein and phycoerythrin conjugates for quantifying CD20 expression on normal and leukemic B-cells SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE CD20; CD4; QuantiBRITE (TM) PE quantification kits; ABC value; MESF value; RM (TM) 8640; B-cell chronic lymphocytic leukemia ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PERIPHERAL-BLOOD; FLOW-CYTOMETRY; MESF VALUES; INTENSITY; ANTIGEN; SUBSETS; DENSITY AB Background: Numerous methods for quantitative fluorescence calibration (QFC) have been developed to quantify receptor expression on lymphocytes as potential disease biomarkers. CD20 expression in B-cell chronic lymphocytic leukemia (B-CLL) is one of the best examples of such a biomarker, but results from the use of different QFC methods vary considerably. Methods: We measured CD20 expression on normal and B-CLL B-cells, using FITC and PE conjugates from the same monoclonal antibody (Mab). As a biological control and calibrator, we also measured CD4 expression on T-cells with FITC and PE Mab. Calibration curves were constructed using the CLSI (formerly NCCLS) consensus guidelines for QFC. Calibration with QuantiBRITE (TM) PE-labeled microspheres and the use of unimolar PE conjugates provided direct measurement of antibody bound per cell (ABC) for CD4 and CD20. Calibration for FITC conjugates was based on molecules of equivalent soluble fluorochrome (MESF), as determined by NIST RM 8640 microsphere standards. These MESF values were then converted to ABC, using the CD4 T-cell as a biologic calibrator, to normalize FITC and PE results for CD20 expression. Results: On normal B cells, the mean ABC value for unimolar CD20-PE conjugate was 143,500 (CV +/- 19.1%). The mean ABC value for B-CLL B-cells stained with the same conjugate was 21,700 (CV +/- 42.0%). Using the CD4 T-cell as a biologic calibrator for FITC conjugate, the mean ABC value for CD20FITC on normal B-cells was 199,300. CD20-FITC staining an B-CLL cells was generally too weak for accurate quantification. On normal T-cells, the mean ABC value for CD4 unimolar PE conjugate was (36,800 +/- 10.4)%, and it did not differ significantly in CLL samples. Conclusion: The expression of CD20 on normal and B-CLL lymphocytes can he quantified in ABC units using unimolar CD20-PE conjugates. In addition, CD4 expression on T-cells can be used as a biological calibrator to quantify CD20-FITC ABC, with reasonable agreement between the two conjugates with different fluorochromes. Issues regarding the accuracy of MESF microsphere calibrators and effective F/P ratios for FITC conjugates will require additional laboratory studies. (c) 2006 International Society for Analytical Cytology. C1 Natl Inst Stand & Technol, Biochem Sci Div, Gaithersburg, MD 20899 USA. US FDA, Ctr Biol Evaluat & Res, NIH, Gaithersburg, MD 20899 USA. CDC, Div Sci Lab, Atlanta, GA 30341 USA. RP Wang, LL (reprint author), Natl Inst Stand & Technol, Biochem Sci Div, 100 Bur Dr,Stop 8312, Gaithersburg, MD 20899 USA. EM lili.wang@nist.gov; gemarti@helix.nih.gov NR 17 TC 20 Z9 21 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV 15 PY 2006 VL 70B IS 6 BP 410 EP 415 DI 10.1002/cyto.b.20140 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 099UY UT WOS:000241623100004 PM 16967494 ER PT J AU Fujimoto, C Yu, CR Shi, GP Vistica, BP Wawrousek, EF Klinman, DM Chan, CC Egwuagu, CE Gery, I AF Fujimoto, Chiaki Yu, Cheng-Rong Shi, Guangpu Vistica, Barbara P. Wawrousek, Eric F. Klinman, Dennis M. Chan, Chi-Chao Egwuagu, Charles E. Gery, Igal TI Pertussis toxin is superior to TLR ligands in enhancing pathogenic autolimmunity, targeted at a neo-self antigen, by triggering robust expansion of Th1 cells and their cytokine production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; ACTIVATED PROTEIN-KINASE; CENTRAL-NERVOUS-SYSTEM; T-CELLS; DENDRITIC CELLS; OCULAR INFLAMMATION; EFFECTOR FUNCTIONS; ADJUVANT ACTION; IN-VIVO AB Microbial products are assumed to play a major role in triggering pathogenic autoimmunity. Recently accumulated data have shown that these products stimulate the immune system by interacting with TLRs, expressed on APCs. To examine the capacity of various TLR ligands to trigger pathogenic autoimmunity, we used a system in which naive CD4 cells, specific against hen egg lysozyme (HEL), are injected into recipient mice expressing HEL in their eyes. Only when stimulated, the naive cells acquire pathogenic capacity and induce ocular inflammation. Seven TLR ligands were tested in this system: lipoteichoic acid/peptidoglycan, zymosan, poly (I:C), LPS, pertussis toxin (PTX), flagellin, and CpG oligodeoxynucleotide. Treatment of recipient mice with HEL alone stimulated proliferation of the transferred cells, but no disease, whereas ocular inflammation did develop in recipient mice coinjected with HEL and any one of the seven TLR ligands. Inflammation induced by PTX surpassed by its severity those induced by all other tested TLR ligands and was accompanied by a dramatic increase in number of the transferred cells that acquired features of effector Th1 lymphocytes. Ocular inflammation and number of transferred cells in recipients injected with PTX and HEL were substantially reduced by treatment with Abs against IFN-gamma or IL-12, thus indicating the role of these cytokines in the PTX effect. Overall, our observations demonstrate that various TLR ligands are capable of triggering pathogenic autoimmunity and that PTX surpasses other microbial products in this activity, by stimulating excessive proliferation and polarization toward Th1 of naive T cells. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res Food & Drug Adm, Bethesda, MD 20892 USA. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N208, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov RI Wawrousek, Eric/A-4547-2008 FU Intramural NIH HHS NR 48 TC 27 Z9 27 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2006 VL 177 IS 10 BP 6896 EP 6903 PG 8 WC Immunology SC Immunology GA 105DN UT WOS:000242009700039 PM 17082604 ER PT J AU Sandhu, SK Priest, JW Lammie, PJ Hubbard, A Colford, JM Eisenberg, JNS AF Sandhu, Sukhminder K. Priest, Jeffrey W. Lammie, Patrick J. Hubbard, Alan Colford, John M., Jr. Eisenberg, Joseph N. S. TI The natural history of antibody responses to Cryptosporidium parasites in men at high risk of HIV infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNOGLOBULIN-G ANTIBODIES; EPIDEMIOLOGIC ASPECTS; ENZYME-IMMUNOASSAY; BISEXUAL MEN; PARVUM; ANTIGENS; TRANSMISSION; INDIVIDUALS; CONNECTICUT; OUTBREAK AB Background. Although the clinical severity of cryptosporidiosis is altered by human immunodeficiency virus (HIV)-related immunosuppression, little is known about how risk for Cryptosporidium infection is altered by HIV. Methods. A retrospective cohort study was conducted among 78 participants of the San Francisco Men's Health Study, using stored serological specimens from 8.5 years of follow-up. Cryptosporidium infection was defined as an antibody response to both the recombinant 27-kDa (r27) and native Triton-extracted 17-kDa (TX17) Cryptosporidium antigens. Results. Cryptosporidium infections were detected more frequently by assessment of antibody responses than by routine clinical follow-up (195 [95% confidence interval {CI}, 154-241] vs. 11 [95% CI, 3-30] infections/1000 person-years, respectively). HIV-positive individuals (59%) were more likely than HIV-negative individuals (30%) to have had at least 1 serologically defined infection (P=.028). The estimated infection rate was 230 (95% CI, 175-293) infections/1000 person-years and 140 (95% CI, 86-210) infections/1000 person-years for HIV-positive and HIV-negative individuals, respectively. Median decay time to half-life ranged from 13.8 to 15.1 months. Conclusions. Our study emphasizes that Cryptosporidium infections are common in this population. Although HIV status altered the risk of Cryptosporidium infection, further studies are needed to adequately examine the effect of CD4 cell count. C1 Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. Atlanta Res & Educ Fdn, Atlanta, GA USA. Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA. RP Sandhu, SK (reprint author), VSB, OBE VE, CBER, FDA, 1401 Rockville Pike,Ste 227 S,HFM-222, Rockville, MD 20852 USA. EM sukhminder.sandhu@fda.hhs.gov FU PHS HHS [U50/CCU915546] NR 33 TC 12 Z9 14 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 NOV 15 PY 2006 VL 194 IS 10 BP 1428 EP 1437 DI 10.1086/508194 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 102OB UT WOS:000241820500012 PM 17054073 ER PT J AU Tareke, E Twaddle, NC McDaniel, LP Churchwell, MI Young, JF Doerge, DR AF Tareke, Eden Twaddle, Nathan C. McDaniel, L. Patrice Churchwell, Mona I. Young, John F. Doerge, Daniel R. TI Relationships between biomarkers of exposure and toxicokinetics in Fischer 344 rats and B6C3F(1) mice administered single doses of acrylamide and glycidamide and multiple doses of acrylamide SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE acrylamide; glycidamide; DNA adduct; hemoglobin adduct; toxicokinetics ID HEMOGLOBIN ADDUCT FORMATION; METABOLITE GLYCIDAMIDE; MERCAPTURIC ACIDS; DRINKING-WATER; DNA; GENOTOXICITY; HUMANS; ONCOGENICITY; CYP2E1-NULL; TOXICITY AB Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells and carcinogenic in rodents. AA is also formed in many commonly consumed starchy foods during cooking. Our previous toxicokinetic investigations of AA and its important genotoxic metabolite, glycidamide (GA), in rodents showed that AA is highly bioavailable from oral routes of administration, is widely distributed to tissues and that the dietary route, in particular, favors metabolism to GA. Measurements of DNA adducts in many tissues supported the hypothesis that AA is carcinogenic in rodent bioassays through metabolism to GA, The current investigation describes the development and validation of methodology for measuring hemoglobin (Hb) adducts with AA and GA in the same rodents previously used for toxicokinctic and DNA adduct measurements. The goal was to investigate possible relationships between these circulating biomarkers of exposure and serum toxicokinetic parameters for AA and GA and tissue GA-DNA adducts in rodents from both single and repeated dosing with AA. Significant correlations were observed between GA-Hb and liver GA-DNA adducts for either single or multiple dosing regimens with AA. Using available GA-Hb adduct data, empirical and allometric relationships permitted estimation of liver DNA adducts in humans in the range of 0.06-0.3 adducts/10(8) nucleotides. This approach may prove useful in extrapolating human cancer risks from findings in rodent bioassays. (c) 2006 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov NR 44 TC 38 Z9 38 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2006 VL 217 IS 1 BP 63 EP 75 DI 10.1016/j.taap.2006.07.013 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 104DT UT WOS:000241937100008 PM 17007897 ER PT J AU Vionnet, J Kempner, ES Vann, WF AF Vionnet, Justine Kempner, Ellis S. Vann, Willie F. TI Functional molecular mass of Escherichia coli K92 polysialyltransferase as determined by radiation target analysis SO BIOCHEMISTRY LA English DT Article ID POLYSIALIC ACID; INACTIVATION ANALYSIS; K1; PROTEIN; WEIGHT AB The polysialyltransferase of Escherichia coli K92 catalyzes the transfer of sialic acid from CMP-sialic acid to a growing chain of polysialic acid at the nonreducing end. The enzyme encoded by the neuS gene is membrane-associated and has been suggested to be organized within a complex of several proteins encoded by the K92 gene cluster. Attempts to prepare a soluble active NeuS enzyme have been unsuccessful. Recent results suggest that de novo synthesis of polysialic acid requires coexpression of four genes from the cluster: neuS, neuE, kpsC, and kpsS. However, elongation of preexisting polysialic acid chains only requires expression of neuS. The molecular organization of the catalytic unit of bacterial polysialyltransferases has not been described. We used radiation inactivation to measure the size of the minimum functional unit catalyzing the polysialyltransferase chain extension and de novo reactions. Membranes harboring NeuS in the presence and absence of other products of the K92 gene cluster were exposed to high-energy electrons. The rate of loss of polysialyltransferase activity reveals the mass of the molecules essential for catalytic activity. We observed that the transfer of neuNAc from CMP-neuNAc to a polysialic acid acceptor is catalyzed by a complex with a target size larger than that of monomeric NeuS. The target size of the unit catalyzing the extension of existing polysialic acid chains does not differ significantly from the size of the unit catalyzing transfer of sialic acid to the endogenous acceptor. Parallel samples of membranes containing NeuS and a green fluorescent protein (GFP) chimera were compared by target analysis. The target size of this structural unit was estimated by analysis of the rate of decay of the GFP-NeuS chimera band migrating in the immunoblots. The target size of the structural unit is larger than expected for a monomer. The results of these experiments show that while the target size of the catalytic activity for K92 polysialyltransferase is larger than a monomer of NeuS, a large complex is not required for catalysis. C1 US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMSD, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Bldg 29,Room 103,8800 Rockville Pike, Bethesda, MD 20892 USA. EM wvann@helix.nih.gov NR 18 TC 7 Z9 7 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 14 PY 2006 VL 45 IS 45 BP 13511 EP 13516 DI 10.1021/bi061486k PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102JZ UT WOS:000241808300011 PM 17087504 ER PT J AU Okada, SK Siegel, JN AF Okada, Sarah K. Siegel, Jeffrey N. TI Risk of serious infections and malignancies with anti-TNF antibody therapy in rheumatoid arthritis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 2, Div Anesthesia Analgesia & Rheumatol Prod, Silver Spring, MD USA. RP Okada, SK (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 2, Div Anesthesia Analgesia & Rheumatol Prod, Silver Spring, MD USA. EM Jeffrey.Siegel@fda.hhs.gov NR 7 TC 28 Z9 29 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 8 PY 2006 VL 296 IS 18 BP 2201 EP 2202 DI 10.1001/jama.296.18.2201-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 102QM UT WOS:000241827700012 PM 17090760 ER PT J AU Goldkind, SF AF Goldkind, Sara F. TI Ethics and research with children SO AMERICAN JOURNAL OF BIOETHICS LA English DT Book Review C1 US FDA, Rockville, MD 20857 USA. RP Goldkind, SF (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD NOV-DEC PY 2006 VL 6 IS 6 BP 71 EP 72 DI 10.1080/15265160600939243 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 102ER UT WOS:000241794300027 ER PT J AU Trumbo, PR Ellwood, KC AF Trumbo, Paula R. Ellwood, Kathleen C. TI Lutein and zeaxanthin intakes and risk of age-related macular degeneration and cataracts: an evaluation using the Food and Drug Administration's evidence-based review system for health claims SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE lutein; zeaxanthin; age-related macular degeneration; cataracts; health claims ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; BEAVER DAM EYE; PIGMENT DENSITY; SERUM CONCENTRATIONS; CAROTENOID CONCENTRATIONS; EPIDEMIOLOGIC EVIDENCE; TISSUE CONCENTRATIONS; TERM SUPPLEMENTATION; NUTRIENT EXPOSURES AB The labeling of health claims that meet the significant scientific agreement standard and of qualified health claims on conventional foods and dietary supplements requires premarket approval by the Food and Drug Administration (FDA). The FDA conducts an evidence-based review to ascertain whether sufficient evidence exists to support a significant scientific agreement standard or a qualified health claim. The FDA recently reviewed intervention and observational studies that evaluated the role of lutein and zeaxanthin in reducing the risk of age-related macular degeneration and cataracts. On the basis of this evidence-based review, the FDA concluded that no credible evidence exists for a health claim about the intake of lutein or zeaxanthin (or both) and the risk of age-related macular degeneration or cataracts. C1 US FDA, Div Nutr Programs & Labeling, College Pk, MD USA. RP Trumbo, PR (reprint author), HFS-830,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paula.trumbo@fda.gov NR 55 TC 52 Z9 58 U1 0 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 NOV PY 2006 VL 84 IS 5 BP 971 EP 974 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 104DZ UT WOS:000241937700004 PM 17093145 ER PT J AU Rathore, D Jani, D Nagarkatti, R Beatty, W Kumar, S Iannaccone, G AF Rathore, Dharmendar Jani, Dewal Nagarkatti, Rana Beatty, Wandy Kumar, Sanjai Iannaccone, Geno TI Identification and characterization of a novel Plasmodium protein responsible for hemozoin formation - Implications for antimalarial drug development SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Virginia Bioinformat Inst, Blacksburg, VA USA. Univ Washington, Sch Med, St Louis, MO USA. US FDA, Bethesda, MD 20014 USA. Virginia Tech, Blacksburg, VA USA. NR 0 TC 0 Z9 0 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 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2006 VL 75 IS 5 SU S MA 332 BP 96 EP 97 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900333 ER PT J AU Qvarnstrom, YL Moura, I Frazar, C Orlandi, PA da Silva, AJ AF Qvarnstrom, Yvonne L. Moura, Iaci Frazar, Christian Orlandi, Palmer A. da Silva, Alexandre J. TI Comparison of real-time PCR protocols for detection of cyclospora cayetanensis in stool samples SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Atlanta Res & Educ Fdn, Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Laurel, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2006 VL 75 IS 5 SU S MA 453 BP 133 EP 133 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900454 ER PT J AU Miller, RA Reimschuessel, R AF Miller, Ron A. Reimschuessel, Renate TI Epiderniologic cutoff values for antimicrobial agents against Aeromonas salmonicida isolates determined by frequency distributions of minimal inhibitory concentration and diameter of zone of inhibition data SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article; Proceedings Paper CT Annual Conference on Antimicrobial Resistance CY JUN, 2006 CL Bethesda, MD SP Natl Fdn Infect Dis ID POLYMERASE CHAIN-REACTION; AQUATIC BACTERIA; SUSCEPTIBILITY; FISH AB Objective-To develop epidemiologic cutoff values by use of frequency distributions for susceptibility to 4 antimicrobial agents when tested against a representative population of a major aquaculture pathogen, Aeromonas salmonicida. Sample Population-217 typical and atypical A salmonicida isolates obtained from 20 states and 12 countries. Procedures-Species identification of A salmonicida isolates was confirmed by detection of specific nucleotide sequences by use of a PCR assay. Minimal inhibitory concentration (MIC) and diameter of the zone of inhibition for oxytetracycline, ormetoprim-sulfadimethoxine, oxolinic acid, and florfenicol were determined for each isolate in accordance with standardized antimicrobial susceptibility testing methods that have been approved by the Clinical and Laboratory Standards Institute for bacterial isolates from aquatic animals. Susceptibility data were tabulated in a scattergram and analyzed by use of error rate bounding. Results-Susceptibility tests for oxytetracycline, ormetoprim-sulfadimethoxine, and oxolinic acid revealed 2 distinct populations of bacteria. Isolates tested against florfenicol clustered into a single population. Oxolinic acid susceptibility data revealed higher MICs in the non-United States A salmonicida isolates. Slow-growing (atypical) A salmonicida isolates were generally more susceptible than typical isolates for all antimicrobials, except oxolinic acid. Conclusions and Clinical Relevance Use of frequency distributions of susceptibility results to develop epidemiologic cutoff values appears to be applicable to aquatic isolates. Frequency distributions of susceptibility results for A salmonicida revealed clear divisions between isolate susceptibilities. This type of data, considered in conjunction with pharmacokinetic and efficacy data, may be useful for developing clinical breakpoints for use in aquaculture. C1 US FDA, Ctr Vet Med, Res Off, Div Anim Res, Laurel, MD 20708 USA. RP Miller, RA (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim Res, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 18 TC 23 Z9 23 U1 0 U2 4 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD NOV PY 2006 VL 67 IS 11 BP 1837 EP 1843 DI 10.2460/ajvr.67.11.1837 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 105OG UT WOS:000242039400004 PM 17078743 ER PT J AU Wysowski, DK Pollock, ML AF Wysowski, Diane K. Pollock, Martin L. TI Reports of death with use of propofol (diprivan) for nonprocedural (long-term) sedation and literature review SO ANESTHESIOLOGY LA English DT Review ID FATAL MYOCARDIAL FAILURE; PEDIATRIC INTENSIVE-CARE; BLOCK FOLLOWING PROPOFOL; CRITICALLY-ILL CHILDREN; INFUSION SYNDROME; METABOLIC-ACIDOSIS; LACTIC-ACIDOSIS; CARDIOVASCULAR COLLAPSE; STATUS EPILEPTICUS; ADULT C1 US FDA, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, HFD 430,White Oak Bldg 22,Room 3424 10903 New Ham, Silver Spring, MD 20993 USA. EM diane.wysowski@fda.hhs.gov NR 71 TC 41 Z9 42 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2006 VL 105 IS 5 BP 1047 EP 1051 DI 10.1097/00000542-200611000-00027 PG 5 WC Anesthesiology SC Anesthesiology GA 101MS UT WOS:000241745500026 PM 17065900 ER PT J AU Harbottle, H Thakur, S Zhao, S White, DG AF Harbottle, H. Thakur, S. Zhao, S. White, D. G. TI Genetics of antimicrobial resistance SO ANIMAL BIOTECHNOLOGY LA English DT Article; Proceedings Paper CT 2nd Conference on Antibiotic Use in Animal Agriculture CY APR 27-28, 2006 CL Urbana, IL SP Dept Anim Sci, Univ Illinois, Natl Pork Board DE antimicrobial resistance genes; antimicrobial resistance mechanisms; conjugation; integron; plasmid; transposon ID MULTIPLE-DRUG RESISTANCE; MEDIATED QUINOLONE RESISTANCE; SALMONELLA-TYPHIMURIUM DT104; GRAM-NEGATIVE BACTERIA; ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI; BETA-LACTAMASES; MULTIDRUG-RESISTANCE; VIBRIO-CHOLERAE; UNITED-STATES AB Antimicrobial resistant strains of bacteria are an increasing threat to animal and human health. Resistance mechanisms to circumvent the toxic action of antimicrobials have been identified and described for all known antimicrobials currently available for clinical use in human and veterinary medicine. Acquired bacterial antibiotic resistance can result from the mutation of normal cellular genes, the acquisition of foreign resistance genes, or a combination of these two mechanisms. The most common resistance mechanisms employed by bacteria include enzymatic degradation or alteration of the antimicrobial, mutation in the antimicrobial target site, decreased cell wall permeability to antimicrobials, and active efflux of the antimicrobial across the cell membrane. The spread of mobile genetic elements such as plasmids, transposons, and integrons has greatly contributed to the rapid dissemination of antimicrobial resistance among several bacterial genera of human and veterinary importance. Antimicrobial resistance genes have been shown to accumulate on mobile elements, leading to a situation where multidrug resistance phenotypes can be transferred to a susceptible recipient via a single genetic event. The increasing prevalence of antimicrobial resistant bacterial pathogens has severe implications for the future treatment and prevention of infectious diseases in both animals and humans. The versatility with which bacteria adapt to their environment and exchange DNA between different genera highlights the need to implement effective antimicrobial stewardship and infection control programs in both human and veterinary medicine. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Harbottle, H (reprint author), US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. EM heather.harbottle@fda.hhs.gov NR 89 TC 40 Z9 43 U1 9 U2 30 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1049-5398 J9 ANIM BIOTECHNOL JI Anim. Biotechnol. PD NOV PY 2006 VL 17 IS 2 BP 111 EP 124 DI 10.1080/10495390600957092 PG 14 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology SC Agriculture; Biotechnology & Applied Microbiology GA 108BZ UT WOS:000242216600002 PM 17127523 ER PT J AU O'Hanlon, TP Rider, LG Mamyrova, G Targoff, IN Arnett, FC Reveille, JD Carrington, M Gao, XJ Oddis, CV Morel, PA Malley, JD Malley, K Shamim, EA Chanock, SJ Foster, CB Bunch, T Reed, AM Love, LA Miller, FW AF O'Hanlon, Terrance P. Rider, Lisa G. Mamyrova, Gulnara Targoff, Ira N. Arnett, Frank C. Reveille, John D. Carrington, Mary Gao, Xiaojiang Oddis, Chester V. Morel, Penelope A. Malley, James D. Malley, Karen Shamim, Ejaz A. Chanock, Stephen J. Foster, Charles B. Bunch, Thomas Reed, Ann M. Love, Lori A. Miller, Frederick W. TI HLA polymorphisms in African Americans with idiopathic inflammatory myopathy - Allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSFER RNA-SYNTHETASES; MAJOR POPULATION GROUPS; CLASS-II ALLELES; PROTECTIVE FACTORS; DRB3 ASSOCIATIONS; UNITED-STATES; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; IMMUNOGENETIC RISK AB Objective. To investigate possible associations of HLA polymorphisms with idiopathic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM. Methods. Molecular genetic analyses of HLA-A, B, Cw, DRB1, and DQA1 polymorphisms were performed in a large population of African American. patients with IIM (n = 262) in whom the major clinical and autoantibody subgroups were represented. These data were compared with similar information previously obtained from European American patients with IIM (n = 571). Results. In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti-jo-I autoantibodies shared the risk factor HLA-DRBI*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti-signal recognition particle (DQAI*0102) and anti-Mi-2 autoantibodies (DRBI*0302). DRB1*0302 and the European American-, anti-Mi-2-associated risk factor DRBI*0701 were found to share a 4-amino-acid sequence motif, which was predicted by comparative homology analyses to have identical 3-dimensional orientations within the peptide-binding groove. Conclusion. These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to date, add additional support to the hypothesis that the myositis syndromes comprise multiple, distinct disease entities, perhaps arising from divergent pathogenic mechanisms and/or different gene-environment interactions. C1 NIEHS, NIH, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. SAIC Frederick, Natl Canc Inst, Frederick, MD USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Ctr Informat Technol, NIH, Bethesda, MD USA. Malley Res Programming, Rockville, MD USA. Johns Hopkins Univ, Baltimore, MD USA. Mayo Clin, Rochester, MN USA. US FDA, Rockville, MD 20857 USA. RP O'Hanlon, TP (reprint author), NIEHS, NIH, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA. EM ohanlont@niehs.nih.gov OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593; Morel, Penelope/0000-0002-1743-3676 FU Intramural NIH HHS NR 51 TC 28 Z9 29 U1 1 U2 3 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 NOV PY 2006 VL 54 IS 11 BP 3670 EP 3681 DI 10.1002/art.22205 PG 12 WC Rheumatology SC Rheumatology GA 104TH UT WOS:000241981800035 PM 17075818 ER PT J AU Dunne, J Caron, A Menu, P Alayash, AI Buehler, PW Wilson, MT Silaghi-Dumitrescu, R Faivre, B Cooper, CE AF Dunne, Jacqueline Caron, Alexis Menu, Patrick Alayash, Abdu I. Buehler, Paul W. Wilson, Michael T. Silaghi-Dumitrescu, Radu Faivre, Beatrice Cooper, Chris E. TI Ascorbate removes key precursors to oxidative damage by cell-free haemoglobin in vitro and in vivo SO BIOCHEMICAL JOURNAL LA English DT Article DE ascorbate; blood substitute; ferryl; free radical; haemoglobin; oxidative stress ID MYOGLOBIN REDOX CYCLE; HYDROGEN-PEROXIDE; CROSS-LINKING; LIPID-PEROXIDATION; TOXICOLOGICAL IMPLICATIONS; HUMAN ERYTHROCYTES; ELECTRON-TRANSFER; FREE-RADICALS; HUMAN-BLOOD; RAT-HEART AB Haemoglobin initiates free radical chemistry. In particular, the interactions of peroxides with the ferric (met) species of haemoglobin generate two strong oxidants: ferryl iron and a protein-bound free radical. We have studied the endogenous defences to this reactive chemistry in a rabbit model following 20% exchange transfusion with cell-free haemoglobin stabilized in tetrameric form [via cross-linking with bis-(3,5-dibromosalicyl)fumarate]. The transfusate contained 95% oxyhaemoglobin, 5% methaemoglobin and 25 mu M free iron. EPR spectroscopy revealed that the free iron in the transfusate was rendered redox inactive by rapid binding to transferrin. Methaemoglobin was reduced to oxyhaemoglobin by a slower process (t1/2 = 1 h). No globin-bound free radicals were detected in the plasma. These redox defences could be fully attributed to a novel multifunctional role of plasma ascorbate in removing key precursors of oxidative damage. Ascorbate is able to effectively reduce plasma methaemoglobin, ferryl haemoglobin and globin radicals. The ascorbyl free radicals formed are efficiently re-reduced by the erythrocyte membranebound reductase (which itself uses intra-erythrocyte ascorbate as an electron donor). As well as relating to the toxicity of haemoglobin-based oxygen carriers, these findings have implications for situations where haem proteins exist outside the protective cell environment, e.g. haemolytic anaemias, subarachnoid haemorrhage, rhabdomyolysis. C1 Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England. Univ Henri Poincare, Fac Pharm, Lab Hematol Physiol, F-54001 Nancy, France. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. RP Cooper, CE (reprint author), Univ Essex, Dept Biol Sci, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. EM ccooper@essex.ac.uk RI FAIVRE , Beatrice/B-7535-2012; Silaghi-Dumitrescu, Radu/A-2883-2008; OI Silaghi-Dumitrescu, Radu/0000-0003-3038-7747; Cooper, Chris/0000-0003-0381-3990 FU Wellcome Trust NR 65 TC 48 Z9 52 U1 1 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2006 VL 399 BP 513 EP 524 DI 10.1042/BJ20060341 PN 3 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 104ED UT WOS:000241938300016 PM 16848758 ER PT J AU Cummings, DJ AF Cummings, David J. TI FDA regulatory efforts in a changing environment SO CHIMICA OGGI-CHEMISTRY TODAY LA English DT Article AB In the face of the Food and Drug Administration's (FDA's) Pharmaceutical CGMPs for the 2 Is' Century Initiative (the Initiative), the FDA finds itself in the position of re-establishing its own "design space". The Agency efforts include adopting a Quality Management S stems (QMS) approach for the development of pharmaceuticals with emphasis on manufacturing process control strategies and risk activities to better manage the lifecycle, of a drug product. The Office of Pharmaceutical Science (OPS) is exploring ways to apply the standard QMS approach to the chemistry manufacturing, and controls assessment process and policy development efforts. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, PARS, Silver Spring, MD 20993 USA. RP Cummings, DJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, PARS, 10903 New Hampshire Ave,Room 3525, Silver Spring, MD 20993 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TEKNOSCIENZE PUBL PI MILAN PA VIA AURELIO SAFFI 23, 20123 MILAN, ITALY SN 0392-839X J9 CHIM OGGI JI Chim. Oggi-Chem. Today PD NOV-DEC PY 2006 VL 24 IS 6 BP 39 EP 41 PG 3 WC Biotechnology & Applied Microbiology; Chemistry, Multidisciplinary SC Biotechnology & Applied Microbiology; Chemistry GA 132SH UT WOS:000243962000011 ER PT J AU Chen, HZ Hopper, SL Li, XL Ljungdahl, LG Cerniglia, CE AF Chen, Huizhong Hopper, Sherryll L. Li, Xin-ang Li Ljungdahl, Lars G. Cerniglia, Carl E. TI Isolation of extremely AT-rich genomic DNA and analysis of genes encoding carbohydrate-degrading enzymes from Orpinomyces sp strain PC-2 SO CURRENT MICROBIOLOGY LA English DT Article ID PIROMYCES SP E2; ANAEROBIC FUNGUS NEOCALLIMASTIX; BETA-GLUCOSIDASE; SEQUENCE; RUMEN; EQUI AB An effective method for extraction of intact genomic DNA from the extremely AT-rich polycentric anaerobic fungus Orpinomyces sp. strain PC-2 has been developed. This procedure involves removal of glycogen-like storage polysaccharides using hexadecyltrimethylammonium bromide (CTAB) and high salt washes. The DNA was digested with various restriction enzymes and was suitable for use as a PCR template, for Southern blotting, and for genomic library construction. Genomic DNA analysis of three representative genes (celE, bgl1, and xynA) encoding (hemi-) cellulolytic enzymes of the fungus revealed multiplicity of family 5 endocellulase genes (celE-like), and family 1 beta-glucosidase genes (bgl1-like), but only a single copy of family 11 xylanase gene (xynA). C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. USDA ARS, Fermentat Biotechnol Res Unit, Natl Ctr Agr Utilizat Res, Peoria, IL 61604 USA. Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. Univ Georgia, Ctr Biol Resource Recovery, Athens, GA 30602 USA. RP Chen, HZ (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov NR 21 TC 10 Z9 11 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD NOV PY 2006 VL 53 IS 5 BP 396 EP 400 DI 10.1007/s00284-006-0098-2 PG 5 WC Microbiology SC Microbiology GA 101FX UT WOS:000241726400009 PM 17019643 ER PT J AU Haffner, ME Maher, PD AF Haffner, Marlene E. Maher, Paul D. TI The impact of the Orphan Drug Act on drug discovery SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review AB For nearly a quarter of a century the FDA Office of Orphan Products Development has administered the US Orphan Drug Act, which assists in bringing a wide variety of drug and biological (drug) products to treat rare diseases to market. Enthusiasm for rare disease product development has been sustained, seen throughout a wide spectrum of product types and disease conditions, and has resulted in clinically meaningful medical advances. Development of programmes for rare disease treatment worldwide, coupled with the development of drugs for diseases affecting developing countries, attests to the strength of this legislation. The marketing of almost 300 products in the US for rare diseases also testifies to the depth and intensity of scientific endeavour in this area. C1 [Haffner, Marlene E.; Maher, Paul D.] US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. RP Haffner, ME (reprint author), US FDA, Off Orphan Prod Dev, HF-35,5600 Fishers Lane, Rockville, MD 20857 USA. EM Marlene.Haffner@FDA.HHS.Gov; Paul.Maher@FDA.HHS.Gov NR 14 TC 4 Z9 4 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD NOV PY 2006 VL 1 IS 6 BP 521 EP 524 DI 10.1517/17460441.1.6.521 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V12RL UT WOS:000207616200003 PM 23506063 ER PT J AU Sapirstein, W Chen, E Swain, J Zuckerman, B AF Sapirstein, Wolf Chen, Eric Swain, Julie Zuckerman, Bram TI USFDA perspective on regulatory issues affecting circulatory assist devices SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Editorial Material DE bridge to transplant; end-stage heart failure; mechanical circulatory assist; regulatory procedures; ventricular assist devices ID SUPPORT; HEART; SYSTEM; BRIDGE AB There has been a rapid development in mechanical circulatory support systems in the decade since the US FDA first approved a mechanical device to provide the circulatory support lacking from a failing heart. Devices are presently approved for marketing by the FDA to replace a failing ventricle, the Ventricular Assist Device or the entire heart, Total Artificial Heart. Contemporaneous with, and permitted by, improvement in technology and design, devices have evolved from units located extracorporeally to paracorporeal systems and totally implanted devices. Clinical studies have demonstrated a parallel improvement in the homeostatic adequacy of the circulatory support provided. Thus, while the circulatory support was initially tolerated for short periods to permit recovery of cardiac function, this technology eventually provided effective circulatory support for increasing periods that permitted the FDA to approve devices for bridging patients in end-stage cardiac failure awaiting transplant and eventually a device for destination therapy where patients in end-stage heart failure are not cardiac transplant candidates. The approved devices have relied on displacement pumps that mimic the pulsatility of the physiological system. Accelerated development of more compact devices that rely on alternative pump mechanisms have challenged both the FDA and device manufacturers to assure that the regulatory requirements for safety and effectiveness are met for use of mechanical circulatory support systems in expanded target populations. An FDA regulatory perspective is reviewed of what can be a potentially critical healthcare issue. C1 US FDA, Ctr Devices & Radiol Hlth, Div Cardiovasc Devices, Off Device Evaluat, Rockville, MD 20850 USA. RP Sapirstein, W (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Cardiovasc Devices, Off Device Evaluat, 9200 Corp Blvd, Rockville, MD 20850 USA. EM wys@cdrh.fda.gov NR 16 TC 3 Z9 3 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD NOV PY 2006 VL 3 IS 6 BP 749 EP 753 DI 10.1586/17434440.3.6.749 PG 5 WC Engineering, Biomedical SC Engineering GA 124DT UT WOS:000243348400015 PM 17280539 ER PT J AU Kioi, M Seetharam, S Puri, RK AF Kioi, Mitomu Seetharam, Saraswathy Puri, Raj K. TI N-linked glycosylation of IL-13R alpha 2 is essential for optimal IL-13 inhibitory activity SO FASEB JOURNAL LA English DT Article DE type I cytokine receptor; ECD; allergic and inflammatory diseases; cancer ID RECEPTOR-ALPHA CHAIN; INTERLEUKIN-13 RECEPTOR; SIGNAL-TRANSDUCTION; PSEUDOMONAS EXOTOXIN; EXTRACELLULAR DOMAIN; GLIOMA-CELLS; BINDING; PROTEIN; COMPONENT; CLONING AB A high-affinity receptor for interleukin (IL)-13 (interleukin-13R alpha 2) is over-expressed in disease-related fibroblasts and neoplastic cells and is involved in cancer, allergic, and inflammatory diseases. The extracellular domain of IL-13R alpha 2 (ECD alpha 2) could be cleaved, which serves as a decoy receptor. We have expressed and purified ECD alpha 2 in both Escherichia coli ( E. coli) and mammalian systems as a soluble fragment and studied its biological activities. Although both products of ECD alpha 2 showed IL-13 inhibitory activities, mammalian cell-derived ECD alpha 2 appeared to be superior compared with purified protein from E. coli. When expressed in E. coli, ECD alpha 2 appeared to be a monomer of 42 but a 60 kDa protein when purified from mammalian cells due to heavy glycosylation. The purified glycosylated ECD alpha 2 efficiently inhibited IL-13-induced STAT6 phosphorylation in immune and Hodgkin's lymphoma cell lines, IL-13 binding, and cytotoxicity of IL-13 cytotoxin in various cancer cell lines. The improved potency of mammalian cell-derived ECD alpha 2 was shown over ECD alpha 2/Fc fusion protein. The N-linked glycosylation of ECD alpha 2 was found to be essential for optimal IL-13 inhibitory activity as deglycosylation by PNGase F showed lower activity. ECD alpha 2 did not inhibit IL-4-induced STAT6 phosphorylation, indicating that inhibitory effects of ECD alpha 2 are receptor specific. These results indicate that glycosylated ECD alpha 2 can serve as a potent inhibitor of IL-13 in a variety of conditions in which IL-13 is a key mediator, e. g., pulmonary, allergic, fibrotic, and neoplastic diseases. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tumor Vaccines & Biotechnol Branch, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tumor Vaccines & Biotechnol Branch, NIH Bldg 29B,Rm 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 41 TC 17 Z9 19 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2006 VL 20 IS 13 BP 2378 EP + DI 10.1096/fj.06-5995fje PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 100XD UT WOS:000241702600026 PM 17023392 ER PT J AU Miller, HL AF Miller, Henry L. TI Biotech production is blooming in the tropics - But will important innovations be nipped in the bud? SO GENETIC ENGINEERING NEWS LA English DT Editorial Material C1 US FDA, Off Biotechnol, Rockville, MD 20857 USA. EM miller@hoover.stanford.edu NR 0 TC 1 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0270-6377 J9 GENET ENG NEWS JI Genet. Eng. News PD NOV 1 PY 2006 VL 26 IS 19 BP 6 EP 8 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 105MN UT WOS:000242034400004 ER PT J AU Stummeyer, K Freiberger, F Gunzel, A Muhlenhoff, M Vann, WF Gerardy-Schahn, R AF Stummeyer, Katharina Freiberger, Friedrich Guenzel, Almut Muehlenhoff, Martina Vann, Willie F. Gerardy-Schahn, Rita TI Comprehensive analysis of the polysialyltransferase from Neisseria meningitidis and identification of functional motifs in bacterial sialyltransferases SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 Hannover Med Sch, Hannover, Germany. Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 1 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 107 BP 1124 EP 1124 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300113 ER PT J AU Azurmendi, HF Wrightson, L Trinh, LB Shiloach, J Freedberg, DI AF Azurmendi, Hugo F. Wrightson, Lauren Trinh, Loc B. Shiloach, Joseph Freedberg, Daron I. TI Pathogen antigens probed by on-cell solution NMR SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 CBER, FDA, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 180 BP 1138 EP 1138 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300186 ER PT J AU Ilev, IK AF Ilev, Ilko K. TI Breaking the optical diffraction barrier with nanophatonics - Ultrahigh-resolution bioimaging and biosensing in the subwavelength nanometric range with nanobiophotonic technologies SO IEEE CIRCUITS & DEVICES LA English DT Article ID CONFOCAL MICROSCOPE; FIBER C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys,Opt Therapeut & Med Nanophoton Lab, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys,Opt Therapeut & Med Nanophoton Lab, Rockville, MD 20857 USA. EM ilko.ilev@fda.hhs.gov NR 16 TC 0 Z9 0 U1 1 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 8755-3996 J9 IEEE CIRCUITS DEVICE JI IEEE Circuits Devices PD NOV-DEC PY 2006 VL 22 IS 6 BP 60 EP 65 DI 10.1109/MCD.2006.307278 PG 6 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA 137AU UT WOS:000244266000010 ER PT J AU Yousef, WA Wagner, RF Loew, MH AF Yousef, Waleed A. Wagner, Robert F. Loew, Murray H. TI Assessing classifiers from two independent data sets using ROC analysis: A nonparametric approach SO IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE LA English DT Article DE classification; nonparametric statistics; ROC analysis ID CROSS-VALIDATION; VARIANCE; AREA AB This paper considers binary classification. We assess a classifier in terms of the Area Under the ROC Curve (AUC). We estimate three important parameters, the conditional AUC (conditional on a particular training set) and the mean and variance of this AUC. We derive, as well, a closed form expression of the variance of the estimator of the AUC. This expression exhibits several components of variance that facilitate an understanding for the sources of uncertainty of that estimate. In addition, we estimate this variance, i.e., the variance of the conditional AUC estimator. Our approach is nonparametric and based on general methods from U-statistics; it addresses the case where the data distribution is neither known nor modeled and where there are only two available data sets, the training and testing sets. Finally, we illustrate some simulation results for these estimators. C1 US FDA, CDRH, Rockville, MD 20852 USA. George Washington Univ, Washington, DC 20052 USA. RP Yousef, WA (reprint author), US FDA, CDRH, 12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM wyousef@aucegypt.edu; Robert.Wagner@fda.hhs.gov; loew@gwu.edu RI Yousef, Waleed/A-9082-2009 NR 25 TC 18 Z9 20 U1 1 U2 7 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0162-8828 J9 IEEE T PATTERN ANAL JI IEEE Trans. Pattern Anal. Mach. Intell. PD NOV PY 2006 VL 28 IS 11 BP 1809 EP 1817 DI 10.1109/TPAMI.2006.218 PG 9 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 083GC UT WOS:000240443400008 PM 17063685 ER PT J AU Lee, S Jeon, BY Bardarov, S Chen, M Morris, SL Jacobs, WR AF Lee, Sunhee Jeon, Bo-Young Bardarov, Svetoslav Chen, Mei Morris, Sheldon L. Jacobs, William R., Jr. TI Protection elicited by two glutamine auxotrophs of Mycobacterium tuberculosis and in vivo growth phenotypes of the four unique glutamine synthetase mutants in a murine model SO INFECTION AND IMMUNITY LA English DT Article ID STREPTOMYCES-COELICOLOR A3(2); PANTOTHENATE AUXOTROPH; GUINEA-PIGS; BOVIS BCG; GENE; LEUCINE; EFFICACY; VACCINES; LYSINE; GLNA1 AB We generated four individual glutamine synthetase (GS) mutants (Delta gInA1, Delta glnA2, Delta glnA3, and Delta glnA4) and one triple mutant (Delta glnAIEA2) of Mycobacterium tuberculosis to investigate the roles of GS enzymes. Subcutaneous immunization with the Delta glnA1EA2 and Delta glnA1 glutamine auxotrophic mutants conferred protection on C57BL/6 mice against an aerosol challenge with virulent M. tuberculosis, which was comparable to that provided by Mycobacterium bovis BCG vaccination. C1 Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Univ Massachusetts, Dept Pathol, Worcester, MA 01605 USA. RP Jacobs, WR (reprint author), Albert Einstein Coll Med, Howard Hughes Med Inst, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jacobsw@hhmi.org FU NIAID NIH HHS [AI26170, R01 AI026170, R37 AI026170] NR 27 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2006 VL 74 IS 11 BP 6491 EP 6495 DI 10.1128/IAI.00531-06 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 099NA UT WOS:000241600500053 PM 17057098 ER PT J AU Loree, J Koturbash, I Kutanzi, K Baker, M Pogribny, I Kovalchuk, O AF Loree, Jonathan Koturbash, Igor Kutanzi, Kristy Baker, Mike Pogribny, Igor Kovalchuk, Olga TI Radiation-induced molecular changes in rat mammary tissue: Possible implications for radiation-induced carcinogenesis SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article DE radiation; mammary tissue; DNA methylation; DNA repair; signaling; cellular proliferation; apoptosis ID PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; INTRACHROMOSOMAL HOMOLOGOUS RECOMBINATION; GLOBAL CANCER STATISTICS; BENIGN BREAST DISEASE; ATOMIC-BOMB SURVIVORS; BASE EXCISION-REPAIR; DNA METHYLATION; IONIZING-RADIATION; CELLS; DAMAGE AB Purpose: Ionizing radiation is a potent mammary gland carcinogen, yet the exact molecular etiology of radiation-induced breast cancer remains unknown. Materials and methods: Our study utilized a rat model of breast carcinogenesis to analyse the molecular and epigenetic changes induced in mammary gland tissue upon exposure to ionizing radiation (IR). Using a methylation-sensitive cytosine extension assay we studied the IR-induced changes in DNA methylation. In parallel, we analysed the expression of proteins involved in DNA methylation, DNA repair and cell proliferation control. Molecular changes were related to cellular proliferation and apoptosis. Results: We found that IR led to a loss of genomic cytosine methylation in the exposed mammary tissue. Global DNA hypomethylation was paralleled by reduction in the levels of maintenance (DNMT1) and de novo (DNMT3a and 3b) DNA methyltransferases and methyl-binding protein MeCP2. The observed DNA hypomethylation was linked, at least in part, to activation of DNA repair processes. Concurrently, we observed increased levels of phosphorylated extracellular signal-regulated kinase (p-ERK1/2), phosphorylated AKT kinase (p-AKT), cyclin D1 and proliferating cells nuclear antigen ( PCNA) proteins, suggesting IR alters intra-cellular signaling and cell cycle control mechanisms in mammary tissue. We also noted a significant induction of apoptosis in the exposed tissue 6 hours after irradiation. The observed apoptosis levels were paralleled by the slight elevation of cellular proliferation. Conclusions: We have demonstrated that a single exposure to 5 Gy of X rays leads to noticeable epigenetic changes in the rat mammary gland that occurred in the context of activation of DNA damage repair and alterations in the pro-survival growth-stimulatory cellular signaling pathways. The possible cellular repercussions of the observed changes in relationship to breast carcinogenesis are discussed. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AZ USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca NR 63 TC 34 Z9 42 U1 0 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD NOV PY 2006 VL 82 IS 11 BP 805 EP 815 DI 10.1080/09553000600960027 PG 11 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 120KP UT WOS:000243083900005 PM 17148264 ER PT J AU Khurana, S Needham, J Park, S Mathieson, B Busch, MP Nemo, G Nyambi, P Zolla-Pazner, S Laal, S Mulenga, J Chomba, E Hunter, E Allen, S McIntyre, J Hewlett, I Lee, S Tang, SX Cowan, E Beyrer, C Altfeld, M Yu, XG Tounkara, A Koita, O Kamali, A Nguyen, N Graham, BS Todd, D Mugenyi, P Anzala, O Sanders, E Ketter, N Fast, P Golding, H AF Khurana, Surender Needham, James Park, Susan Mathieson, Bonnie Busch, Michael P. Nemo, George Nyambi, Phillipe Zolla-Pazner, Susan Laal, Suman Mulenga, Joseph Chomba, Elwyn Hunter, Eric Allen, Susan McIntyre, James Hewlett, Indira Lee, Sherwin Tang, Shixing Cowan, Elliot Beyrer, Chris Altfeld, Marcus Yu, Xu G. Tounkara, Anatole Koita, Ousmane Kamali, Anatoli Nguyen, Nga Graham, Barney S. Todd, Deborah Mugenyi, Peter Anzala, Omu Sanders, Eduard Ketter, Nzeera Fast, Patricia Golding, Hana TI Novel approach for differential diagnosis of HIV infections in the face of vaccine-generated antibodies: Utility for detection of diverse HIV-1 subtypes SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; AIDS; diagnosis; vaccine; clinical trials; phage display; peptides; epitope mapping ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD-DONORS; EFFICACY TRIALS; RURAL VILLAGES; IMMUNOGENICITY; CAMEROON; LESSONS; RATES; RISK AB Because increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Most of the currently tested vaccines contain multiple viral components. As a result, many vaccine recipients give positive results in FDA-licensed HIV scrodetection tests. We have identified conserved sequences in Env-gp41 and Gag-p6, which are recognized soon after infection but are not included in most HIV vaccine candidates. A new HIV serodetection assay, the HIV-SELECTEST, was established that distinguishes between vaccine-induced antibodies and seroconversion due to true HIV infections. It is important to make this assay globally relevant, because many clinical trials are conducted around the world where most HIV infections are due to non-B subtype HIV-1. Therefore, the current study examined the reactivity of plasma samples from > 3000 infections with diverse HIV subtypes worldwide. The HIV-SELECTEST performed at > 99% specificity and sensitivity. Both recent and established infections with clades A, B, C, D, E, F, G, J, and CRFs were detected. Antibodies elicited by other vaccinations or infections endemic to the clinical trial sites did not react in this assay. Therefore, HIV-SELECTEST could be an important differential diagnostic tool for HIV vaccine trials, blood banks, and population screening worldwide. C1 FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. NIH, Off Aids Res, Bethesda, MD 20892 USA. Blood Syst Res Inst, San Francisco, CA USA. NHLBI, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Pathol, New York, NY USA. Zambia Emory HIV Res Project, Lusaka, Zambia. Zambia Blood Transfus Serv, Lusaka, Zambia. Emory Vaccine Res Ctr, Atlanta, GA USA. Emory Univ, Sch Publ Hlth, Atlanta, GA USA. Univ Witwatersrand, Chris Hani Baragwanath Hosp, Johannesburg, South Africa. FDA, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. MA Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Univ Bamako, Bamako, Mali. FDA, CBER, Core Facil, Bethesda, MD USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. Joint Clin Res Ctr, Mengo, Uganda. Int AIDS Vaccine Initiat, New York, NY USA. Univ Nairobi, Nairobi, Kenya. Ctr Geog Med Cost Res, Kilifi, Kenya. RP Golding, H (reprint author), FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Room 1A21,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov FU Intramural NIH HHS [Z99 AI999999]; NHLBI NIH HHS [BY1-HB-5026-01]; NIAID NIH HHS [R01 AI051231, AI-51231, AI36085, AI47053, R01 AI036085, R01 AI047053, R37 AI051231]; NICHD NIH HHS [HD-40125, R01 HD040125]; NIMH NIH HHS [MH-766767] NR 24 TC 19 Z9 22 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2006 VL 43 IS 3 BP 304 EP 312 DI 10.1097/01.qai.0000242465.50947.5f PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 099KB UT WOS:000241592000007 PM 17019363 ER PT J AU Sharpless, KE Anderson, DL Betz, JM Butler, TA Capar, SG Cheng, J Fraser, CA Gardner, G Gay, ML Howell, DW Ihara, T Khan, MA Lam, JW Long, SE McCooeye, M Mackey, EA Mindak, WR Mitvalsky, S Murphy, KE NguyenPho, A Phinney, KW Porter, BJ Roman, M Sander, LC Satterfield, MB Scriver, C Sturgeon, R Thomas, JB Vocke, RD Wise, SA Wood, LJ Yang, L Yen, JH Ziobro, GC AF Sharpless, Katherine E. Anderson, David L. Betz, Joseph M. Butler, Therese A. Capar, Stephen G. Cheng, John Fraser, Catharine A. Gardner, Graeme Gay, Martha L. Howell, Daniel W. Ihara, Toshihide Khan, Mansoor A. Lam, Joseph W. Long, Stephen E. McCooeye, Margaret Mackey, Elizabeth A. Mindak, William R. Mitvalsky, Staci Murphy, Karen E. NguyenPho, Agnes Phinney, Karen W. Porter, Barbara J. Roman, Mark Sander, Lane C. Satterfield, Mary B. Scriver, Christine Sturgeon, Ralph Thomas, Jeanice Brown Vocke, Robert D., Jr. Wise, Stephen A. Wood, Laura J. Yang, Lu Yen, James H. Ziobro, George C. TI Preparation and characterization of a suite of ephedra-containing standard reference materials SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PLASMA-MASS SPECTROMETRY; DIETARY-SUPPLEMENTS; ALKALOIDS; STEREOISOMERS AB The National Institute of Standards and Technology, the U.S. Food and Drug Administration, Center for Drug Evaluation and Research and Center for Food Safety and Applied Nutrition, and the National Institutes of Health, Office of Dietary Supplements, are collaborating to produce a series of Standard Reference Materials (SRMs) for dietary supplements. A suite of ephedra materials is the first in the series, and this paper describes the acquisition, preparation, and value assignment of these materials: SRMs 3240 Ephedra sinica Stapf Aerial Parts, 3241 E. sinca Stapf Native Extract, 3242 E. sinica Stapf Commercial Extract, 3243 Ephedra-Containing Solid Oral Dosage Form, and 3244 Ephedra-Containing Protein Powder. Values are assigned for ephedrine alkaloids and toxic elements in all 5 materials. Values are assigned for other analytes (e.g., caffeine, nutrient elements, proximates, etc.) in some of the materials, as appropriate. Materials in this suite of SRMs are intended for use as primary control materials when values are assigned to in-house (secondary) control materials and for validation of analytical methods for the measurement of alkaloids, toxic elements, and, in the case of SRM 3244, nutrients in similar materials. C1 Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Natl Res Council Canada, Ottawa, ON K1A 0R9, Canada. Food Prod Assoc, Washington, DC 20005 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. ChromaDex Inc, Clearwater, FL 33760 USA. Natl Inst Stand & Technol, Stat Engn Div, Gaithersburg, MD 20899 USA. RP Sharpless, KE (reprint author), Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. EM katherine.sharpless@nist.gov OI Lam, Joseph/0000-0001-6402-0535; Sturgeon, Ralph/0000-0001-7304-3034; McCooeye, Margaret/0000-0001-9424-9111; Yang, Lu/0000-0002-4351-2503 NR 28 TC 15 Z9 15 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2006 VL 89 IS 6 BP 1483 EP 1495 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 116SO UT WOS:000242822800006 PM 17225593 ER PT J AU Marks, HS Anderson, CR AF Marks, Heidi S. (Rupp) Anderson, Collin R. TI Rapid determination and confirmation of biogenic amines in tuna loin by gas chromatography/mass spectrometry using ethylchloroformate derivative SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; 9-FLUORENYLMETHYL CHLOROFORMATE; FLUOROMETRIC-DETERMINATION; PRECOLUMN DERIVATIZATION; FLUORESCENCE DETECTION; ACIDS; HISTAMINE; PUTRESCINE; POLYAMINES AB A gas chromatography-mass spectrometry (GC/MS) method is described for the easy rapid determination and simultaneous confirmation of the biogenic amines putrescine (PUT), cadaverine (CAD), histamine (HTA), and spermidine (SPD) in fresh frozen tuna loin. The method can also be used to monitor tyramine (TYR). The method involves homogenization of fish tissue, extraction of biogenic amines into trichloroacetic acid solution, centrifugation, alkalization, and derivatization of supernatant with ethylchloroformate. All seafood species were fortified to contain 2.5, 5.0, 10.0, 12.5, and 25.0 mu g/g (ppm) PUT, CAD, and SPD; and 10.0, 20.0, 40.0, 50.0, and 100.0 mu g/g (ppm) HTA. Determination was based on standard curves for each analyte using peak areas with matrix standards equivalent to a concentration range bracketing the spike level. A set of 5 matrix controls (unfortified tuna tissue) was also analyzed; only endogenous SPD was found in all samples. The interassay average recoveries ranged from 57 to 79% across analytes and spike levels. C1 US FDA, Pacific Reg Lab NW, Seafood Prod Res Ctr, Bothell, WA 98021 USA. RP Marks, HS (reprint author), US FDA, Pacific Reg Lab NW, Seafood Prod Res Ctr, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM heidi.marks@fda.hhs.gov NR 29 TC 10 Z9 11 U1 0 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2006 VL 89 IS 6 BP 1591 EP 1599 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 116SO UT WOS:000242822800020 PM 17225607 ER PT J AU McClure, FD Lee, JK AF McClure, Foster D. Lee, Jung K. TI On determining a 1-tailed upper limit for future sample HorRat values SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Two formulas were developed for use in computing 1-tailed upper limits for future HorRat values obtained from the collaborative study of materials. One formula is applicable when a future sample HorRat value (HorRat(1) = RSDR/0.02C(-0.1505) is computed based on a known concentration (e.g., C = spike level and RSDR is the sample relative reproducibility standard deviation) and the other formula is applicable when the true concentration (C) is unknown and a future sample HorRat value (HorRat(2) = RSDR/0.02 (y) over bar (0.1505) is computed using the sample mean (e.g., (y) over bar, the collaborative study overall mean for an analyte). A Monte Carlo simulation procedure was developed using the Statistical Analysis System (SAS) software to assess the accuracy of the 2 developed formulas. Based on the degree of closeness between the simulated and calculated limits, the formulas for computing upper limits for future sample HorRat values will prove to be useful to Study Directors in determining worst case scenarios concerning a method's reproducibility precision relative to that predicted using the "Horwitz equation." We also define the current empirical HorRat limits as 1-tailed 100p% upper limits to assess the statistical consequence, in a probability sense, of their application as an analytical methods screening tool. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math,Dept Hlth & Human Serv, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math,Dept Hlth & Human Serv, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM foster.mcclure@fda.hhs.gov NR 11 TC 4 Z9 4 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2006 VL 89 IS 6 BP 1650 EP 1663 PG 14 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 116SO UT WOS:000242822800028 PM 17233107 ER PT J AU Braun, MM Zinderman, CE Wood, JJ Malek, MA Frassica, FJ Polder, JA Cote, TR AF Braun, M. Miles Zinderman, Craig E. Wood, Jennifer J. Malek, Mark A. Frassica, Frank J. Polder, Jacquelyn A. Cote, Timothy R. TI Autologous cultured chondrocytes: Adverse events reports - Reply SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Braun, MM (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM braunm@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 2006 VL 88A IS 11 BP 2539 EP 2539 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 101VT UT WOS:000241769800040 ER PT J AU Shin, EC Seifert, U Kato, T Rice, CM Feinstone, SM Kloetzel, PM Rehermann, B AF Shin, Eui-Cheol Seifert, Ulrike Kato, Takanobu Rice, Charles M. Feinstone, Stephen M. Kloetzel, Peter-M. Rehermann, Barbara TI Virus-induced type IIFN stimulates generation of immunoproteasomes at the site of infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HEPATITIS-C VIRUS; CD8(+) T-CELLS; MHC CLASS-I; CELLULAR IMMUNE-RESPONSES; B-VIRUS; RIG-I; LYMPHOCYTE EPITOPE; ENDOTHELIAL-CELLS; INTERFERON-GAMMA; GENOMIC ANALYSIS AB IFN-gamma is known as the initial and primary inducer of immunoproteasomes during viral infections. We now report that type IIFN induced the transcription and translation of immunoproteasome subunits, their incorporation into the proteasome complex, and the generation of an immunoproteasome-dependent CD8 T cell epitope in vitro and provide in vivo evidence that this mechanism occurs prior to IFN-gamma responses at the site of viral infection. Type I IFN-mediated generation of immunoproteasomes was initiated by either poly(I:C) or HCV RNA in human hepatoma cells and was inhibited by neutralization of type IIFN. In serial liver biopsies of chimpanzees with acute HCV infection, increases in immunoproteasome subunit mRNA preceded intrahepatic IFN-gamma responses by several weeks, instead coinciding with intrahepatic type IIFN responses. Thus, viral RNA-induced innate immune responses regulate the antigen-processing machinery, which occurs prior to the detection of IFN-gamma at the site of infection. This mechanism may contribute to the high effectiveness (95%) of type IIFN-based therapies if administered early during HCV infection. C1 NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. Charite Univ Med Berlin CCM, Inst Biochem, Berlin, Germany. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10 Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011 FU Intramural NIH HHS; NCI NIH HHS [CA85883-01, R01 CA085883] NR 55 TC 80 Z9 83 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2006 VL 116 IS 11 BP 3006 EP 3014 DI 10.1172/JCI29832 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 102KW UT WOS:000241810900024 PM 17039255 ER PT J AU Nordstrom, JL Rangdale, R Vickery, MCL Phillips, AMB Murray, SL Wagley, S DePaola, A AF Nordstrom, Jessica L. Rangdale, Rachel Vickery, Michael C. L. Phillips, Andrea M. B. Murray, Shelley L. Wagley, Sariqa DePaola, Angelo TI Evaluation of an alkaline phosphatase-labeled oligonucleotide probe for the detection and enumeration of the thermostable-related hemolysin (trh) gene of Vibrio parahaemolyticus SO JOURNAL OF FOOD PROTECTION LA English DT Article ID TIME PCR DETECTION; UNITED-STATES; OYSTERS; VULNIFICUS; SHELLFISH; OUTBREAK; STRAINS; COAST; TDH AB Reliable methods are needed to detect total and pathogenic Vibrio parahaemolyticus. One marker of V. parahaemolyticus virulence is the thermostable-related hemolysin. We developed an alkaline phosphatase-labeled DNA probe method for the specific detection and enumeration of trh-positive V. parahaemolyticus by colony hybridization. The probe was tested against a panel of 200 bacterial strains and determined to be specific for trh-positive V. parahaemolyticus. Additionally, the trh alkaline phosphatase probe colony hybridization was successfully used to detect and enumerate trh-positive V. parahaemolyticus in seafood and water samples collected from the United States and the United Kingdom. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Cepheid, Sunnyvale, CA 94089 USA. Univ So Mississippi, Gulf Coast Res Lab, Ocean Springs, MS USA. Alaska Dept Environm Conservat, Anchorage, AK 99507 USA. RP Nordstrom, JL (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr,POB 158, Dauphin Isl, AL 36528 USA. EM jessica.nordstrom@fda.hhs.gov NR 20 TC 13 Z9 13 U1 0 U2 0 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2006 VL 69 IS 11 BP 2770 EP 2772 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 107FY UT WOS:000242157300030 PM 17133826 ER PT J AU Belyakov, IM Isakov, D Zhu, Q Dzutsev, A Klinman, D Berzofsky, JA AF Belyakov, Igor M. Isakov, Dmitry Zhu, Qing Dzutsev, Amiran Klinman, Dennis Berzofsky, Jay A. TI Enhancement of CD8(+) T cell immunity in the lung by CpG oligodeoxynucleotides increases protective efficacy of a modified vaccinia ankara vaccine against lethal poxvirus infection even in a CD4-deficient host SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ATTENUATED MVA STRAIN; SMALLPOX VACCINE; GENITAL-TRACT; INTRANASAL IMMUNIZATION; MUCOSAL IMMUNIZATION; INFLUENZA-VIRUS; DENDRITIC CELLS; RHESUS-MONKEYS; BACTERIAL-DNA AB Immunostimulatory CpG oligodeoxynucleotides (ODN) have proven effective as adjuvants for protein-based vaccines, but their impact on immune responses induced by live viral vectors is not known. We found that addition of CpG ODN to modified vaccinia Ankara (MVA) markedly improved the induction of longer-lasting adaptive protective immunity in BALB/c mice against intranasal pathogenic vaccinia virus (Western Reserve; WR). Protection was mediated primarily by CD8(+) T cells in the lung, as determined by CD8-depletion studies, protection in B cell-deficient mice, and greater protection correlating with CD8(+) IFN-gamma-producing cells in the lung but not with those in the spleen. Intranasal immunization was more effective at inducing CD8(+) T cell immunity in the lung, and protection, than i.m. immunization. Addition of CpG ODN increased the CD8(+) response but not the Ab response. Depletion of CD4 T cells before vaccination with MVA significantly diminished protection against pathogenic WR virus. However, CpG ODN delivered with MVA was able to substitute for CD4 help and protected CD4-depleted mice against WR vaccinia challenge. This study demonstrates for the first time a protective adjuvant effect of CpG ODN for a live viral vector vaccine that may overcome CD4 deficiency in the induction of protective CD8(+) T cell-mediated immunity. C1 NCI, Vaccine Branch, Ctr Canc Res, Mol Immunogenet & Vaccine Res Sect,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Belyakov, IM (reprint author), NCI, Vaccine Branch, Ctr Canc Res, Mol Immunogenet & Vaccine Res Sect,NIH, Bldg 10,Room 6B-12,10 Ctr Dr, Bethesda, MD 20892 USA. EM belyakov@mail.nih.gov NR 65 TC 37 Z9 40 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 NOV 1 PY 2006 VL 177 IS 9 BP 6336 EP 6343 PG 8 WC Immunology SC Immunology GA 097VN UT WOS:000241477400068 PM 17056564 ER PT J AU Britten, P Marcoe, K Yamini, S Davis, C AF Britten, Patricia Marcoe, Kristin Yamini, Sedigheh Davis, Carole TI Development of food intake patterns for the MyPyramid Food Guidance System SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE MyPyramid; food guides; food intake patterns; dietary guidance AB Objective: The purpose of this research was to design food intake patterns based on typical American food selections that would meet Dietary Guidelines and Dietary Reference Intake recommendations. Design: Analytic process to identify appropriate amounts from each food group that together will meet nutritional goals for various age/gender groups. Variables Measured: Projected intake of energy, 9 vitamins, 8 minerals, 8 macronutrients, and dietary fiber in each food intake pattern. Analysis: Iterative comparison of nutrients in each food intake pattern to Dietary Reference Intakes and Dietary Guidelines recommendations set as goals for that pattern. Results: Food intake patterns were established that met almost all nutrient goals within estimated energy needs. Intakes of vitamin E at all energy levels, potassium at lower energy levels, and sodium at higher energy levels did not meet goals. Conclusions and implications: The food intake patterns provide a foundation of food choices that will meet nutritional recommendations. They form the scientific basis for the MyPyramid Food Guidance System and can also be used as a starting point for developing other educational programs or materials. C1 USDA, Ctr Nutr Policy & Promot, Alexandria, VA 22302 USA. US FDA, Ctr Food Safety & Appl Nutr, Alexandria, VA 22302 USA. RP Britten, P (reprint author), USDA, Ctr Nutr Policy & Promot, 3101 Pk Ctr Dr,Room 1034, Alexandria, VA 22302 USA. EM Patricia.Britten@cnpp.usda.gov NR 26 TC 89 Z9 89 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD NOV-DEC PY 2006 VL 38 IS 6 SU S BP S78 EP S92 DI 10.1016/j.jneb.2006.08.007 PG 15 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 119JG UT WOS:000243008000003 PM 17116598 ER PT J AU Marcoe, K Juan, WY Yamini, S Carlson, A Britten, P AF Marcoe, Kristin Juan, WenYen Yamini, Sedigheh Carlson, Andrea Britten, Patricia TI Development of food group composites and nutrient profiles for the MyPyramid Food Guidance System SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE MyPyramid; food guides; dietary guidance; food intake patterns AB Objective: To identify food selections in each MyPyramid food group or subgroup reflective of typical consumption patterns by Americans, and the nutrient intake that can be expected from consuming a specified amount of these foods from each group, in a low-fat and no-added-sugars form. Design: An analytical process to identify food consumption choices within each food group and subgroup using national food consumption surveys, and to identify the expected nutrient content of each group using food composition databases. Variables Measured: Relative consumption of foods within each food group; nutrient content for each food group and subgroup (energy plus 27 nutrients). Analysis: Disaggregated foods from consumption surveys into component ingredients. Combined similar ingredients into "item clusters" and determined relative consumption of each. Calculated a consumption-weighted nutrient profile for each food group. Results: Consumption-weighted food intake selections and nutrient profiles were developed for all MyPyramid food groups and Subgroups. Conclusions and implications: This analytical process derived food group and subgroup composites which estimate typical food choices within each MyPyramid food group. These were used to assess the adequacy of the MyPyramid food intake patterns as they were being iteratively developed. C1 USDA, Ctr Nutr Policy & Promot, Alexandria, VA 22302 USA. US FDA, Ctr Food Safety & Appl Nutr, Alexandria, VA USA. RP Marcoe, K (reprint author), USDA, Ctr Nutr Policy & Promot, 3101 Pk Ctr Dr,Room 1034, Alexandria, VA 22302 USA. EM Kristin.Marcoe@cnpp.usda.gov NR 17 TC 37 Z9 37 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD NOV-DEC PY 2006 VL 38 IS 6 SU S BP S93 EP S107 DI 10.1016/j.jneb.2006.05.014 PG 15 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 119JG UT WOS:000243008000004 PM 17116599 ER PT J AU Yamini, S Juan, WY Marcoe, K Britten, P AF Yamini, Sedigheh Juan, WenYen Marcoe, Kristin Britten, Patricia TI Impact of using updated food consumption and composition data on selected MyPyramid food group nutrient profiles SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE MyPyramid; food intake patterns; food composition database ID UNITED-STATES AB Objective: To examine the changes observed in 5 nutrients of selected USDA food subgroups by partitioning the overall changes into those caused by consumption changes over time, and those caused by nutrient database revisions. Design: Population-weighted estimates of food group intakes (composites) were developed using 24-hour recall data from CSFII 1994-96 and NHANES 1999-2000. Nutrient profiles of these composites were developed using Standard Reference (SR) data (SR11 and SR16-1). Subjects: A total of 14,262 and 8070 individuals over the age of 2 years from CSFII and NHANES, respectively, composed the study sample. Outcome Measures: Absolute and percent change in food group nutrient content caused by food consumption changes and nutrient database updates. Analysis: Changes due to consumption differences were determined by comparing nutrient profiles created with CSFII and NHANES using SR11. Changes due to nutrient database differences were determined by comparing nutrient profiles created from NHANES data using SR11 and SR16-1 nutrient values. Results: Consumption differences resulted in some variations in the food group nutrient content, but a majority of the changes were associated with use of the updated nutrient database. For example, vitamin A level in the orange vegetable subgroup was increased by 2.4% owing to consumption (from CSFII to NHANES), whereas the level was decreased by 38% due to nutrient updates (from SR11 to SR16-1). Conclusion and implications: Consideration of the changes in nutrient databases, as well as in food consumption, is essential in monitoring both the trends in the food choices Americans make and the adequacy of their diets. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. USDA, Ctr Nutr Policy & Promot, Alexandria, VA USA. RP Yamini, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS830, College Pk, MD 20740 USA. EM Essie.Yamini@fda.hhs.gov NR 23 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD NOV-DEC PY 2006 VL 38 IS 6 SU S BP S136 EP S142 DI 10.1016/j.jneb.2006.08.003 PG 7 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 119JG UT WOS:000243008000007 PM 17116591 ER PT J AU Thompson, T Kane, RR Hager, MH AF Thompson, Tricia Kane, Rhonda R. Hager, Mary H. TI Food Allergen Labeling and Consumer Protection Act of 2004 in effect SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article C1 US FDA, Food Labeling & Stand Staff, College Pk, MD 20740 USA. ADA, Washington DC Off, Regulatory Affairs, Washington, DC USA. RP Thompson, T (reprint author), US FDA, Food Labeling & Stand Staff, College Pk, MD 20740 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 2006 VL 106 IS 11 BP 1742 EP + DI 10.1016/j.jada.2006.08.010 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 101CA UT WOS:000241715300005 PM 17081820 ER PT J AU Lee, S Wood, O Taffs, RE Hu, JJ Machuca, A Vallejo, A Hewlett, I AF Lee, Sherwin Wood, Owen Taffs, Rolf E. Hu, Jinjie Machuca, Ana Vallejo, Alejandro Hewlett, Indira TI Development and evaluation of HIV-1 subtype RNA panels for the standardization of HIV-1NAT assays SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1 RNA; NAT; working reagents; international standard ID TYPE-1; LOAD AB Multiple nucleic acid-based techniques (NAT) have been implemented for testing blood and plasma donors for HIV-1 RNA which may be detected, at an earlier stage of infection when HIV antigen or antibody is absent or below the limit of detection of current assays. The available NAT assays are based on different technologies. In order to evaluate the performance of nucleic acid-based techniques (NAT assays) and to allow accurate comparisons of results from different assays, it is essential to have well characterized specimens with known copy numbers as a standard. For this purpose, a comprehensive study was conducted to develop two HIV-1 RNA reference panels. The first (Panel 1) was prepared using a single specimen from the HIV-1 group M subtype B and consists of panel members with a wide range of HIV-1 RNA copy numbers. Panel 2 consists of 26 members representing HIV-1 group M subtypes A, C, D, E, F, G and groups O and N. For accurate determination of HIV-1 RNA copy numbers of each member of Panel 2, they were analyzed using various testing platforms/technologies available through the cooperation of five independent laboratories participating in the study. A consensus value for HIV RNA copy number was assigned to each member of Panel 2 based on statistical analysis of the data provided by the participants. Both panels could serve as reference panels to be used by manufacturers of HIV NAT tests to evaluate the sensitivity limits of their assays. (c) 2006 Published by Elsevier B.V. C1 US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Hewlett, I (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-315, Rockville, MD 20852 USA. EM indira.hewlett@fda.hhs.gov RI Vallejo, Alejandro/I-5881-2015 OI Vallejo, Alejandro/0000-0001-5360-878X NR 11 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 2006 VL 137 IS 2 BP 287 EP 291 DI 10.1016/j.jviromet.2006.07.001 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 097FM UT WOS:000241432400016 PM 16920201 ER PT J AU Yang, AX Mejido, J Bhattacharya, B Petersen, D Han, J Kawasaki, ES Puri, RK AF Yang, Amy X. Mejido, Josef Bhattacharya, Bhaskar Petersen, David Han, Jing Kawasaki, Ernest S. Puri, Raj K. TI Analysis of the quality of contact pin fabricated oligonucleotide microarrays SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE quality control; printed microarrays; 70-mer oligonucleotide array; autofluorescence 9-mer nucleotide hybridization; quality testing ID COMPLEMENTARY-DNA MICROARRAY; CDNA MICROARRAYS; GENE-EXPRESSION; IDENTIFICATION; ATTACHMENT; ARRAYS AB As the quality of microarrays is critical to successful experiments for data consistency and validity, a reliable and convenient quality control method is needed. We describe a systematic quality control method for large-scale genome oligonucleotide arrays. This method is comprised of three steps to assess the quality of printed arrays. The first step involves assessment of the autofluorescence property of DNA. This step is convenient, quick to perform, and allowed reuse of every array. The second step involves hybridization of arrays with Cy3-labeled 9-mer oligonucleotide target to assess the quality and stability of oligonucleotides. Because this step consumed arrays, one or two arrays from each batch were used to complement the quality control data from autofluorescence. The third step involves hybridization of arrays from every batch with transcripts derived from two cell lines to assess data consistency. These hybridizations were able to distinguish two closely related tissue samples by identifying a cluster of 20 genes that were differently expressed in U87MG and T98G glioblastoma cell lines. In addition, we standardized two parameters that significantly enhanced the quality of arrays. We found that longer pin contact time and crosslinking oligonucleotides at 400 mJ/cm(2) were optimal for the highest hybridization intensity. Taken together, these results indicate that the quality of spotted oligonucleotide arrays should be assessed by at least two methods, autofluorescence and 9-mer hybridization before arrays are used for hybridization experiments. C1 US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Ctr Canc Res, Gaithersburg, MD 20877 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, RM2NN20,Bldg 29B,8800 Rockville Pike, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 22 TC 6 Z9 6 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD NOV PY 2006 VL 34 IS 3 BP 303 EP 315 DI 10.1385/MB:34:3:303 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 112CH UT WOS:000242502300002 PM 17284778 ER PT J AU Wagner, RD AF Wagner, Robert Doug TI Efficacy and food safety considerations of poultry competitive exclusion products SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Review DE antimicrobial drug resistance; competitive exclusion; food safety; microbial ecology; poultry ID ENTERICA SEROVAR ENTERITIDIS; ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; SALMONELLA-ENTERITIDIS; CAMPYLOBACTER-JEJUNI; ENTEROCOCCUS-FAECALIS; PATHOGENICITY ISLAND; BROILER-CHICKENS; VANCOMYCIN-RESISTANT; CULTURE PREEMPT(TM) AB Competitive exclusion (CE) products are anaerobic cultures of bacteria that are applied to poultry hatchlings to establish a protective enteric microbiota that excludes intestinal colonization by human food-borne pathogens. For safety of the poultry flock and human consumers, the identities of bacteria in CE products need to be known. A CE product is a culture of intestinal contents from adult chickens. It may be microbiologically defined by analysis of bacteria isolated from the culture, but many bacteria are hard to reliably isolate, identify, and characterize with conventional techniques. Sequence analysis of 16S ribosomal RNA (rRNA) genes may be more reliable than conventional techniques to identify CE bacteria. Bacteria in CE products may contain antimicrobial drug resistance and virulence mechanisms that could be transferred to the enteric bacteria of the food animal and to the human consumer. Detection methods for specific antimicrobial drug resistance and virulence genes and the integrase genes of conjugative transposons, mostly utilizing PCR technology, are being developed that can be applied to assess these risks in CE bacteria. With improvements in efficacy, bacterial identification, and detection and control of the possible risks of gene transfer, CE product technology can be made a more effective food safety tool. C1 Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Wagner, RD (reprint author), Natl Ctr Toxicol Res, Div Microbiol, HFT-250,3900 NCTR Rd, Jefferson, AR 72079 USA. EM doug.wagner@fda.hhs.gov NR 88 TC 15 Z9 15 U1 2 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD NOV PY 2006 VL 50 IS 11 BP 1061 EP 1071 DI 10.1002/mnfr.200600058 PG 11 WC Food Science & Technology SC Food Science & Technology GA 108NG UT WOS:000242245900009 PM 17039457 ER PT J AU Takagi, T Ramachandran, C Bermejo, M Yamashita, S Yu, LX Amidon, GL AF Takagi, Toshihide Ramachandran, Chandrasekharan Bermejo, Marival Yamashita, Shinji Yu, Lawrence X. Amidon, Gordon L. TI A provisional biopharmaceutical classification of the top 200 oral drug products in the United States, Great Britain, Spain, and Japan SO MOLECULAR PHARMACEUTICS LA English DT Article DE BCS; solubility; dose number; permeability; partition coefficient; WHO essential drugs; top-selling US, European, Japanese drugs; BDDCS ID HUMAN PEPTIDE TRANSPORTER; BCS LITERATURE DATA; BIOWAIVER MONOGRAPHS; DOSAGE FORMS; SYSTEM BCS; IN-VIVO; ABSOLUTE BIOAVAILABILITY; PHARMACOKINETICS; PERMEABILITY; RANITIDINE AB Orally administered, immediate-release (IR) drug products in the top 200 drug product lists from the United States (US), Great Britain (GB), Spain (ES), and Japan (JP) were provisionally classified based on the Biopharmaceutics Classification System (BCS). The provisional classification is based on the aqueous solubility of the drugs reported in readily available reference literature and a correlation of human intestinal membrane permeability for a set of 29 reference drugs with their calculated partition coefficients. Oral IR drug products constituted more that 50% of the top 200 drug products on all four lists, and ranged from 102 to 113 in number. Drugs with dose numbers less than or equal to unity are defined as high-solubility drugs. More than 50% of the oral IR drug products on each list were determined to be high-solubility drugs (55-59%). The provisional classification of permeability is based on correlations of the human intestinal permeabilities of 29 reference drugs with the calculated Log P or CLogP lipophilicity values for the uncharged chemical form. The Log P and CLogP estimates were linearly correlated (r(2) = 0.79) for 187 drugs. Metoprolol was chosen as the reference compound for permeability and Log P or CLogP. A total of 62-69.0% and 56-60% of the drugs on the four lists exhibited CLogP and Log P estimates, respectively, greater than or equal to the corresponding metoprolol value and are provisionally classified as high-permeability drugs. We have compared the BCS classification in this study with the recently proposed BDDCS classification based on fraction dose metabolism. Although the two approaches are based on different in vivo processes, fraction dose metabolized and fraction dose absorbed are highly correlated and, while depending on the choice of reference drug for permeability classification, e.g., metoprolol vs cimetidine or atenolol, show excellent agreement in drug classification. In summary, more than 55% of the drug products were classified as high-solubility (Class 1 and Class 3) drugs in the four lists, suggesting that in vivo bioequivalence (BE) may be assured with a less expensive and more easily implemented in vitro dissolution test. C1 [Takagi, Toshihide; Ramachandran, Chandrasekharan; Amidon, Gordon L.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Bermejo, Marival] Univ Valencia, Dept Pharm & Technol, Valencia, Spain. [Yamashita, Shinji] Setsunan Univ, Fac Pharmaceut Sci, Osaka, Japan. [Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Amidon, GL (reprint author), Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA. EM glamidon@umich.edu RI Bermejo, Marival/A-4163-2009; Yu, Lawrence/L-6280-2016 OI Bermejo, Marival/0000-0001-5022-0544; FU NIH [R01-GM37188] FX This work is Supported in part by NIH Grant R01-GM37188. NR 51 TC 0 Z9 0 U1 9 U2 48 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD NOV-DEC PY 2006 VL 3 IS 6 BP 631 EP 643 DI 10.1021/mp0600182 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52JM UT WOS:000203539800002 ER PT J AU McKinzie, PB Delongchamp, RR Chen, T Parsons, BL AF McKinzie, Page B. Delongchamp, Robert R. Chen, Tao Parsons, Barbara L. TI ACB-PCR measurement of K-ras codon 12 mutant fractions in livers of Big Blue (R) rats treated with N-hydroxy-2-acetylaminofluorene SO MUTAGENESIS LA English DT Article ID COMPETITIVE BLOCKER PCR; GENOTYPIC SELECTION; GENE-MUTATIONS; F344 RATS; P53; ADENOMAS; TUMORS; CELLS; MUTAGENICITY; MICE AB K-ras codon 12 GGT -> GAT and GGT -> GTT mutations are the most frequently observed K-ras point mutations in human and rodent tumors and therefore are implicated in carcinogenesis for many tissues. Measurement of these mutations in rat models and human tissue could facilitate a more logical extrapolation of rodent tumorigenesis data to human disease. We have developed allele-specific competitive blocker PCR (ACB-PCR) assays for rat K-ras codon 12 GGT -> GTT and GGT -> GAT mutations that parallel the already published assays for human K-ras codon 12 mutations. Liver K-ras codon 12 mutant allele fractions were measured in vehicle-treated and N-hydroxy-2-acetylaminofluorene (N-OH-AAF)-treated Big Blue((R)) rats. The average K-ras codon 12 GGT -> GTT mutant fraction (MF) for four control rats was 50 x 10(-6) (95% CI: 27 x 10(-6), 95 x 10(-6)) and for four treated rats was 165 x 10(-6) (95% CI: 87 x 10(-6), 312 x 10(-6)), indicating a 3.3-fold increase with treatment (95% CI: 1.3-8.1). The average MF of K-ras codon 12 GGT -> GAT for control rats was 1320 x 10(-6) (95% CI: 498 x 10(-6), 3500 x 10(-6)) and for treated rats was 8450 x 10(-6) (95% CI: 3180 x 10(-6), 22 400 x 10(-6)), indicating a 6.4-fold increase with treatment (95% CI: 1.6-25.4). These transgenic rats were part of a study that included analysis of liver lacI mutations. Although data from lacI determinations show that this compound induces mostly G -> T mutations, using the ACB-PCR method both K-ras codon 12 GGT -> GTT and GGT -> GAT MFs were significantly increased in treated rats versus control rats. This data raises the possibility that N-OH-AAF may not only induce mutations by a genotoxic mechanism, but also by amplification of both de novo and pre-existing K-ras mutation. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Technol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP McKinzie, PB (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Technol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM page.mckinzie@fda.hhs.gov NR 27 TC 13 Z9 13 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 2006 VL 21 IS 6 BP 391 EP 397 DI 10.1093/mutage/gel041 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 102AI UT WOS:000241782700005 PM 17012303 ER PT J AU Garey, J Ferguson, SA Paule, MG AF Garey, J. Ferguson, S. A. Paule, M. G. TI Effects of chronic low-dose acrylamide exposure on progressive ratio performance in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Behavioral-Toxicology-Society CY SEP 16-17, 2006 CL Little Rock, AR SP Behav Toxicol Soc C1 Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD NOV-DEC PY 2006 VL 28 IS 6 MA 006 BP 708 EP 708 DI 10.1016/j.ntt.2006.09.012 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 121OY UT WOS:000243168100015 ER PT J AU von Eschenbach, AC AF von Eschenbach, Andrew C. TI Progress with a purpose: eliminating suffering and death due to cancer SO ONCOLOGY-NEW YORK LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP von Eschenbach, AC (reprint author), US FDA, 5600 Fishers Lane,Room 14-71, Rockville, MD 20857 USA. NR 12 TC 2 Z9 3 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2006 VL 20 IS 13 BP 1691 EP 1696 PG 6 WC Oncology SC Oncology GA V44BL UT WOS:000202978100007 PM 17175745 ER PT J AU Hinman, LM Huang, SM Hackett, J Koch, WH Love, PY Pennello, G Torres-Cabassa, A Webster, C AF Hinman, L. M. Huang, S-M Hackett, J. Koch, W. H. Love, P. Y. Pennello, G. Torres-Cabassa, A. Webster, C. TI The drug diagnostic co-development concept paper - Commentary from the 3rd FDA-DIA-PWG-PhRMA-BIO Pharmacogenomics Workshop SO PHARMACOGENOMICS JOURNAL LA English DT Editorial Material DE pharmacogenetics; drug/diagnostic co-development AB At the Washington DC Pharmacogenomics in Drug Development and Regulatory Decision-Making: Workshop III - Three Years of Promise, Proposals and Progress on Optimizing the Benefit/Risk of Medicines (11 - 13 April 2005), one break-out session (Track 2) focused on co-development of therapeutic drug and diagnostic products. The Food and Drug Administration (FDA) released a draft concept paper shortly before the workshop was to convene. Track 2 was a forum for initial discussion of the content of the concept paper, and industry's initial reactions. After the workshop, formal commentaries on the co-development concept paper were submitted by several trade associations (e. g., Pharmaceutical Research and Manufacturers of America (PhRMA), Advanced Medical Technology Association (AdvaMed), American Association for Clinical Chemistry) and individual companies to FDA's Docket No. 2004N-0279. This paper includes a summary of the key features of the draft concept paper, the discussion in Track 2 of the April, 2005 meeting and highlights of the industry comments submitted to the FDA docket following the meeting. C1 Hoffmann La Roche Inc, Nutley, NJ 07110 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Silver Spring, MD USA. US FDA, Off Vitro Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Roche Mol Syst, Pleasanton, CA USA. US FDA, Off Combinat Prod, Off Commissioner, Rockville, MD 20857 USA. US FDA, Diagnost Branch, Div Biostat, CDRH, Rockville, MD 20857 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Hinman, LM (reprint author), Hoffmann La Roche Inc, 340 Kingsland St, Nutley, NJ 07110 USA. EM lois.hinman@roche.com NR 7 TC 15 Z9 16 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD NOV PY 2006 VL 6 IS 6 BP 375 EP 380 DI 10.1038/sj.tpj.6500392 PG 6 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 110TL UT WOS:000242403500003 PM 16652120 ER PT J AU Smith, NM Lee, R Heitkemper, DT Cafferky, KD Haque, A Henderson, AK AF Smith, Nicole M. Lee, Robin Heitkemper, Douglas T. Cafferky, Katie DeNicola Haque, Abidul Henderson, Alden K. TI Inorganic arsenic in cooked rice and vegetables from Bangladeshi households SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article DE Bangladesh; arsenite; arsenate; dimethylarsinic acid; food; average daily intake ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ATOMIC FLUORESCENCE SPECTROMETRY; PLASMA-MASS SPECTROMETRY; WEST-BENGAL; DRINKING-WATER; FOOD COMPOSITES; AFFECTED AREA; INDIA; CONTAMINATION; SPECIATION AB Many Bangladeshi suffer from arsenic-related health concerns. Most mitigation activities focus on identifying contaminated wells and reducing the amount of arsenic ingested from well water. Food as a source of arsenic exposure has been recently documented. The objectives of this study were to measure the main types of arsenic in commonly consumed foods in Bangladesh and estimate the average daily intake (ADI) of arsenic from food and water. Total, organic and inorganic, arsenic were measured in drinking water and in cooked rice and vegetables from Bangladeshi households. The mean total arsenic level in 46 rice samples was 358 mu g/kg (range: 46 to 1110 mu g/kg dry weight) and 333 mu g/kg (range: 19 to 2334 mu g/kg dry weight) in 39 vegetable samples. Inorganic arsenic calculated as arsenite and arsenate made up 87% of the total arsenic measured in rice, and 96% of the total arsenic in vegetables. Total arsenic in water ranged from 200 to 500 mu g/L. Using individual, self-reported data on daily consumption of rice and drinking water the total arsenic ADI was 1176 mu g (range: 419 to 2053 mu g), 14% attributable to inorganic arsenic in cooked rice. The ADI is a conservative estimate; vegetable arsenic was not included due to limitations in self-reported daily consumption amounts. Given the arsenic levels measured in food and water and consumption of these items, cooked rice and vegetables are a substantial exposure pathway for inorganic arsenic. Intervention strategies must consider all sources of dietary arsenic intake. Published by Elsevier B.V. C1 Agcy Tox Substances & Dis Registry, Div Hlth Studies, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. Oak Ridge Associated Univ, Oak Ridge, TN 37831 USA. Natl Inst Prevent & Social Med, Dhaka 1212, Bangladesh. RP Henderson, AK (reprint author), Agcy Tox Substances & Dis Registry, Div Hlth Studies, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM AHenderson@cdc.gov NR 40 TC 73 Z9 77 U1 3 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD NOV 1 PY 2006 VL 370 IS 2-3 BP 294 EP 301 DI 10.1016/j.scitotenv.2006.06.010 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 100FH UT WOS:000241653000003 PM 16875714 ER PT J AU Wintz, H Yoo, LJ Loguinov, A Wu, YY Steevens, JA Holland, RD Beger, RD Perkins, EJ Hughes, O Vulpe, CD AF Wintz, Henri Yoo, Leslie J. Loguinov, Alex Wu, Ying-Ying Steevens, Jeffrey A. Holland, Ricky D. Beger, Richard D. Perkins, Edward J. Hughes, Owen Vulpe, Chris D. TI Gene expression profiles in fathead minnow exposed to 2,4-DNT: Correlation with toxicity in mammals SO TOXICOLOGICAL SCIENCES LA English DT Article DE dinitrotoluene; peroxisome proliferators; methemoglobinemia; microarrays; ecotoxicogenomics ID PROLIFERATOR-ACTIVATED-RECEPTOR; MITOCHONDRIAL TRANSCRIPTION FACTOR; COA OXIDASE ACTIVITY; PEROXISOME PROLIFERATORS; PIMEPHALES-PROMELAS; POOLING SAMPLES; ALPHA; MICROARRAYS; NERVE; ECOTOXICOLOGY AB Toxicogenomics, the genome-wide analysis of gene expression to study the effect of toxicants, has great potential for use in environmental toxicology. Applied to standard test organisms, it has possible applications in aquatic toxicology as a sensitive monitoring tool to detect the presence of contaminants while providing information on the mechanisms of action of these pollutants. We describe the use of a complementary DNA (cDNA) microarray of the fathead minnow (Pimephales promelas) a standard sentinel organism in aquatic toxicology, to better understand the mechanisms of toxicity of 2,4-dinitrotoluene (2,4-DNT) which is released in the environment through military and industrial use. We have constructed a fathead minnow microarray containing 5000 randomly picked anonymous cDNAs from a whole fish cDNA library. Expression profiles were analyzed in fish exposed to 2,4-DNT for 10 days at three concentrations (11, 22, and 44 mu M, respectively) below the measured median lethal concentration (58 mu M). Sequence analysis of cDNAs corresponding to differentially expressed genes affected by exposure revealed that lipid metabolism and oxygen transport genes were prominently affected in a dose-specific manner. We measured liver lipids and demonstrate that lipid metabolism is indeed perturbed following exposure. These observations correlate well with available toxicological data on 2,4-DNT. We present possible modes of action of 2,4-DNT toxicity and suggest that fathead minnow cDNA microarrays can be useful to identify mechanisms of toxicity in fish and as a predictive tool for toxicity in mammals. C1 Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. Univ Calif Berkeley, Berkeley Inst Environm, Berkeley, CA 94720 USA. USA, Corps Engineer, Ctr Res & Dev, Environm Lab, Vicksburg, MS 39180 USA. Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. Eon Corp, Davis, CA 95616 USA. RP Wintz, H (reprint author), Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Morgan Hall, Berkeley, CA 94720 USA. EM wintz@berkeley.edu NR 53 TC 38 Z9 39 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2006 VL 94 IS 1 BP 71 EP 82 DI 10.1093/toxsci/kfl080 PG 12 WC Toxicology SC Toxicology GA 092KL UT WOS:000241095300008 PM 16917068 ER PT J AU Dertinger, SD Bishop, ME McNamee, JP Hayashi, M Suzuki, T Asano, N Nakajima, M Saito, J Moore, M Torous, DK MacGregor, JT AF Dertinger, Stephen D. Bishop, Michelle E. McNamee, James P. Hayashi, Makoto Suzuki, Takayoshi Asano, Norihide Nakajima, Madoka Saito, Junichiro Moore, Martha Torous, Dorothea K. MacGregor, James T. TI Flow cytometric analysis of micronuclei in peripheral blood reticulocytes: I. Intra- and interlaboratory comparison with microscopic scoring SO TOXICOLOGICAL SCIENCES LA English DT Article DE flow cytometric analysis; reticulocytes; micronucleus test; CD71 ID BONE-MARROW; ASSAY; RAT; RODENT; CYCLOPHOSPHAMIDE; ERYTHROCYTES; ENUMERATION; INTEGRATION; PROTOCOL; DAMAGE AB Accumulating evidence suggests that reticulocytes (RETs) in the peripheral blood of rats may represent a suitable cell population for use in the micronucleus assay, despite the ability of the rat spleen to selectively remove micronucleated erythrocytes from the peripheral circulation. To evaluate the analytical performance of a previously described flow cytometric method (Torous et al., 2003, Toxicol. Sci. 74, 309-314) that may allow this assay to be conducted using peripheral blood in lieu of bone marrow sampling, we compared the sensitivity and performance characteristics of the flow cytometric technique with two established microscopy-based scoring methods. Peripheral blood samples from single Sprague-Dawley rats treated for 6 days with either vehicle or cyclophosphamide were prepared in replicate for scoring by the three methods at different laboratories. These blood-based measurements were compared to those derived from bone marrow specimens from the same animals, stained with acridine orange, and scored by microscopy. Through the analysis of replicate specimens, inter- and intralaboratory variability were evaluated for each method. Scoring reproducibility over time was also evaluated. These data support the premise that rat RETs harvested from peripheral blood are a suitable cell population to assess genotoxicant-induced micronucleus formation. The interlaboratory comparison provides evidence of the general robustness of the micronucleus endpoint using different analytical approaches. Furthermore, data presented herein demonstrate a clear advantage of flow cytometry-based scoring over microscopy-significantly lower inter- and intralaboratory variation and higher statistical sensitivity. C1 Litron Labs, Rochester, NY 14623 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. Natl Inst Hlth Sci, Tokyo 1588501, Japan. Nitto Denko Corp, Osaka 5678680, Japan. An Pyo Ctr, Shizuoka 4371213, Japan. Astellas Pharma Inc, Tokyo 1748511, Japan. US FDA, Natl Ctr Toxicol Res, Rockville, MD 21012 USA. RP MacGregor, JT (reprint author), Toxicol Consulting Serv, 201 Nomini Dr, Arnold, MD 21012 USA. EM jtmacgregor@earthlink.net OI McNamee, James/0000-0003-2772-3455 NR 22 TC 36 Z9 41 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2006 VL 94 IS 1 BP 83 EP 91 DI 10.1093/toxsci/kfl075 PG 9 WC Toxicology SC Toxicology GA 092KL UT WOS:000241095300009 PM 16888078 ER PT J AU MacGregor, JT Bishop, ME McNamee, JP Hayashi, M Asano, N Wakata, A Nakajima, M Saito, J Aidoo, A Moore, MM Dertinger, SD AF MacGregor, James T. Bishop, Michelle E. McNamee, James P. Hayashi, Makoto Asano, Norhide Wakata, Akihiro Nakajima, Madoka Saito, Junichiro Aidoo, Anane Moore, Martha M. Dertinger, Stephen D. TI Flow cytometric analysis of micronuclei in peripheral blood reticulocytes: II. An efficient method of monitoring chromosomal damage in the rat SO TOXICOLOGICAL SCIENCES LA English DT Article DE flow cytometric analysis; micronucleated reticulocytes; erythrocytes; cyclophosphamide, cis-platin; vinblastine ID CYTOGENETIC DAMAGE; BONE-MARROW; ERYTHROCYTES; ASSAY; ENUMERATION; INTEGRATION; RODENT; CYCLOPHOSPHAMIDE; GENOTOXICITY; TOXICITY AB We have evaluated a flow cytometric method that allows assessment of micronucleated reticulocytes (MN-RETs) in microliter quantities of peripheral blood and compared results using this assay with those of established microscopic methods of scoring bone marrow and peripheral blood from rats treated with well-characterized genotoxic agents. Young reticulocytes (RETs) are labeled with FITC-anti-CD71 (transferrin receptor) and micronuclei with propidium iodide (with RNase treatment). Red blood cells parasitized with Plasmodia serve as a calibration standard for DNA content. Microscopic scoring used acridine orange (AO) staining of methanol-fixed slides or supravital AO staining. The effect of the rat spleen on the parameters evaluated was determined by comparing age- and sex-matched normal and splenectomized rats treated with cyclophosphamide, cis-platin, or vinblastine under treatment conditions that established a steady-state frequency of MN-RETs in the bone marrow and peripheral blood compartments. The data demonstrate the sensitivity and reproducibility of the flow cytometric assay in the Sprague-Dawley rat, and comparative studies using identical blinded samples at multiple laboratories show that inter- and intra-laboratory reproducibility is much higher with the flow method than with the microscopic methods currently employed for regulatory studies. A significant effect of splenic selection against genotoxicant-induced MN-RETs was observed with each of the three scoring methodologies, despite the fact that the flow and supravital AO techniques restrict analysis to the youngest fraction of RETs. The high precision of flow-based measurements also demonstrated a slight but statistically significant level of selection against spontaneously arising MN-RET. Despite these spleen effects, assay sensitivity for blood-based analyses was maintained by the flow method as it was shown to have superior counting statistics, lower variability, and higher sensitivity than manual scoring. The data suggest that flow cytometric assessment of micronucleus induction can be integrated into routine toxicity testing, eliminating the need for a separate bioassay. C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 21012 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. Natl Inst Hlth Sci, Tokyo 1588501, Japan. Nitto Denko Corp, Osaka 5678680, Japan. Astellas Pharma Inc, Osaka 5328514, Japan. An Pyo Ctr, Shizuoka 4371213, Japan. Astellas Pharma Inc, Tokyo 1748511, Japan. Litron Labs, Rochester, NY 14623 USA. RP MacGregor, JT (reprint author), Toxicol Consulting Serv, 201 Nomini Dr, Arnold, MD 21012 USA. EM jtmacgregor@earthlink.net OI McNamee, James/0000-0003-2772-3455 NR 40 TC 50 Z9 55 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2006 VL 94 IS 1 BP 92 EP 107 DI 10.1093/toxsci/kfl076 PG 16 WC Toxicology SC Toxicology GA 092KL UT WOS:000241095300010 PM 16888079 ER PT J AU Shefcheck, KJ AF Shefcheck, Kevin J. TI Enzymic digestion confirms peanut allergens SO TRAC-TRENDS IN ANALYTICAL CHEMISTRY LA English DT News Item C1 US FDA, Bethesda, MD 20014 USA. RP Shefcheck, KJ (reprint author), US FDA, Bethesda, MD 20014 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-9936 J9 TRAC-TREND ANAL CHEM JI Trac-Trends Anal. Chem. PD NOV PY 2006 VL 25 IS 10 BP III EP IV PG 2 WC Chemistry, Analytical SC Chemistry GA 112VY UT WOS:000242557100002 ER PT J AU Leidy, NK Beusterien, K Sullivan, E Richner, R Muni, NI AF Leidy, Nancy Kline Beusterien, Kathleen Sullivan, Erin Richner, Randel Muni, Neal I. TI Integrating the patient's perspective into device evaluation trials SO VALUE IN HEALTH LA English DT Article DE device; patient-reported outcomes; quality of life ID QUALITY-OF-LIFE; REPORTED OUTCOMES; REGULATORY ISSUES; UNITED-STATES; END-POINTS; DEFIBRILLATORS; THERAPIES; CHILDREN AB Innovations in medical device technology have greatly expanded the range of therapeutic options available to physicians and their patients. The understanding of treatment effects from the patient's perspective is an essential component of a comprehensive assessment of any new therapy, including medical devices. The term "patient-reported outcomes" (PROs) has been growing in use to refer to a cluster of variables such as health-related quality of life, symptoms, physical functioning, psychological well-being, treatment satisfaction, and treatment preferences. As in drug trials, the use of PROs in device evaluation has several methodological challenges, ranging from general concerns about interpretation, to more specific issues related to study design and regulatory approval (use of PROs as primary end points, incorporation in labeling, and product promotion). Successful approaches for integrating PROs into device evaluation trials include the careful selection of appropriate, interpretable PRO end points, accounting for possible confounding factors, and the use of alternatives to placebo-controlled trial designs, such as single-arm pre-post, observational, and registry studies, when the use of placebo control groups is not feasible. This article discusses the potential value and difficulties in measuring PROs in device studies. C1 United BioSource Corp, Ctr Hlth Outcomes Res, Bethesda, MD 20814 USA. Boston Sci, Boston, MA USA. US FDA, Rockville, MD 20857 USA. RP Leidy, NK (reprint author), United BioSource Corp, Ctr Hlth Outcomes Res, 7101 Wisconsin Ave,Suite 600, Bethesda, MD 20814 USA. EM nancy.leidy@unitedbiosource.com NR 30 TC 10 Z9 12 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2006 VL 9 IS 6 BP 394 EP 401 DI 10.1111/j.1524-4733.2006.00132.x PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 090AC UT WOS:000240922000005 PM 17076870 ER PT J AU Mpanju, OM Towner, JS Dover, JE Nichol, ST Wilson, CA AF Mpanju, Onesmo M. Towner, Jonathan S. Dover, Jason E. Nichol, Stuart T. Wilson, Carolyn A. TI Identitication of two amino acid residues on Ebola virus glycoprotein 1 critical for cell entry SO VIRUS RESEARCH LA English DT Article DE filovirus; ebolavirus; glycoprotein; viral entry; mutagenesis ID FOLATE RECEPTOR-ALPHA; ENVELOPE GLYCOPROTEIN; INFECTION; IDENTIFICATION; PRIMATES; VACCINE; MURINE; SYSTEM AB Using site-directed mutagenesis and retroviral vector pseudotyping of the wild type or mutated glycoprotein of Zaire ebolavirus (ZEBOV), we analyzed 15 conserved residues in the N-terminus of the filovirus glycoprotein 1 (GP1) in order to identify residues critical for cell entry. Results from infectivity assays and Western blot analyses identified two phenylalanine residues at positions 88 and 159 that appear to be critical for ZEBOV entry in vitro. We extended this observation by introduction of alanines at either position 88 or 159 of Ivory Coast Ebolavirus (CIEBOV) and observed the same phenotype. Further, we showed that introduction of each of the two mutations in a recombinant full-length clone of ZEBOV (Mayinga strain) that also carried the coding sequence for GFP could not be rescued, suggesting the mutants rendered the virus non-infectious. The two phenylalanines that are critical for both ZEBOV and CIEBOV entry are found in two linear domains of GP1 that are highly conserved among filoviruses, and thus could provide a target for rational development of broadly cross-protective vaccines or antiviral therapies. Published by Elsevier B.V. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular Tissue & Gene Therapies, Gene Transfer & Immunogenic Branch, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Special Pathogens Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30329 USA. RP Wilson, CA (reprint author), Bldg 29B,Rm 2NN12,HFM-725,8800 Rockville Pike, Bethesda, MD 20892 USA. EM carolyn.wilson@fda.hhs.gov NR 29 TC 25 Z9 27 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD NOV PY 2006 VL 121 IS 2 BP 205 EP 214 DI 10.1016/j.virusres.2006.06.002 PG 10 WC Virology SC Virology GA 100CI UT WOS:000241644400012 PM 16839637 ER PT J AU Porter, C Bloom, ET Horvath-Arcidiacono, J Horvath, KA Mohiuddin, MM AF Porter, Cynthia Bloom, Eda T. Horvath-Arcidiacono, Judith Horvath, Keith A. Mohiuddin, Muhammad M. TI Baboon CD4(+) CD25(+) T regulatory cells inhibit anti porcine xenogeneic response SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 FDA, Gene Transfer & Immunogenic Branch, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 709 EP 710 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804517 ER PT J AU Kainz, W Nikoloski, N Oesch, W Berdinas-Torres, V Frohlich, J Neubauer, G Kuster, N AF Kainz, Wolfgang Nikoloski, Neviana Oesch, Walter Berdinas-Torres, Veronica Froehlich, Juerg Neubauer, Georg Kuster, Niels TI Development of novel whole-body exposure setups for rats providing high efficiency, National Toxicology Program (NTP) compatibility and well-characterized exposure SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID ELECTROMAGNETIC-FIELDS; IN-VIVO; RF EXPOSURE; LIMITING EXPOSURE; 300 GHZ; 900 MHZ; SYSTEM; GUIDELINES; MICROWAVES; RADIATION AB This paper presents the design, optimization, realization and verification of novel whole-body exposure setups for rats. The setups operating at 902 MHz and 1747 MHz provide highly efficient, National Toxicology Program (NTP) compatible and well-characterized exposures. They are compared to existing concepts of exposure setups with respect to efficiency, induced field uniformity, good laboratory practice (GLP) compatibility and cost. The novel exposure setup consists of a circular cascade of 17 sectorial waveguides excited by a novel loop antenna placed in the centre. The 70% overall efficiency of the exposure setup surpasses comparable values of existing setups. A field uniformity inside the phantom of more than 86% for the 1g cubical averaged specific absorption rate (SAR) within +/- 5 dB of the whole-body SAR (WB-SAR) was attained. The uniformity of the exposure inside the setup, defined as the variation of the WB-SAR between animals, was better than +/- 24%. Using only stainless steel, gold and polycarbonate in the vicinity of the animals ensured full GLP compatibility. The entire exposure system features fully automated computer controlled exposure and data monitoring, data storing and failure handling. Therefore, the proposed exposure system can be used to run blinded large scale, long-term exposure studies. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. ETH, Fdn Res Informat Technol, ITIS Fdn, CH-8092 Zurich, Switzerland. ARC Seibersdorf Res GmbH, A-1010 Vienna, Austria. RP Kainz, W (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM wolfgang.kainz@fda.hhs.gov RI Foundation, IT'IS/B-9559-2008 NR 22 TC 16 Z9 16 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 21 PY 2006 VL 51 IS 20 BP 5211 EP 5229 DI 10.1088/0031-9155/51/20/009 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 092GE UT WOS:000241084200009 PM 17019034 ER PT J AU Budnitz, DS Pollock, DA Weidenbach, KN Mendelsohn, AB Schroeder, TJ Annest, JL AF Budnitz, Daniel S. Pollock, Daniel A. Weidenbach, Kelly N. Mendelsohn, Aaron B. Schroeder, Thomas J. Annest, Joseph L. TI National surveillance of emergency department visits for outpatient adverse drug events SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GEOGRAPHIC-VARIATION; MYOCARDIAL-INFARCTION; AMBULATORY-CARE; SAFETY; INJURIES; ERRORS AB Context Adverse drug events are common and often preventable causes of medical injuries. However, timely, nationally representative information on outpatient adverse drug events is limited. Objective To describe the frequency and characteristics of adverse drug events that lead to emergency department visits in the United States. Design, Setting, and Participants Active surveillance from January 1, 2004, through December 31, 2005, through the National Electronic Injury Surveillance System Cooperative Adverse Drug Event Surveillance project. Main Outcome Measures National estimates of the numbers, population rates, and severity (measured by hospitalization) of individuals with adverse drug events treated in emergency departments. Results Over the 2-year study period, 21 298 adverse drug event cases were reported, producing weighted annual estimates of 701 547 individuals (95% confidence interval [CI], 509 642-893 452) or 2.4 individuals per 1000 population(95% CI, 1.7-3.0) treated in emergency departments. Of these cases, 3487 individuals required hospitalization (annual estimate, 117 318 [16.7%]; 95% CI, 13.1%-20.3%). Adverse drug events accounted for 2.5% (95% CI, 2.0%-3.1%) of estimated emergency department visits for all unintentional injuries and 6.7% (95% CI, 4.7%-8.7%) of those leading to hospitalization and accounted for 0.6% of estimated emergency department visits for all causes. Individuals aged 65 years or older were more likely than younger individuals to sustain adverse drug events (annual estimate, 4.9 vs 2.0 per 1000; rate ratio [RR], 2.4; 95% CI, 1.8-3.0) and more likely to require hospitalization (annual estimate, 1.6 vs 0.23 per 1000; RR, 6.8; 95% CI, 4.3-9.2). Drugs for which regular outpatient monitoring is used to prevent acute toxicity accounted for 41.5% of estimated hospitalizations overall (1381 cases; 95% CI, 30.9%-52.1%) and 54.4% of estimated hospitalizations among individuals aged 65 years or older (829 cases; 95% CI, 45.0%-63.7%). Conclusions Adverse drug events among outpatients that lead to emergency department visits are an important cause of morbidity in the United States, particularly among individuals aged 65 years or older. Ongoing, population-based surveillance can help monitor these events and target prevention strategies. C1 Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Coordinating Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Off Stat & Programming, Natl Ctr Injury Prevent & Control, Atlanta, GA 30333 USA. US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv, Off Workforce & Career Dev, Atlanta, GA 30333 USA. US Consumer Prod Safety Commiss, Bethesda, MD USA. RP Budnitz, DS (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Coordinating Ctr Infect Dis, 1600 Clifton Rd NE,Mailstop A-24, Atlanta, GA 30333 USA. EM dbudnitz@cdc.gov NR 46 TC 396 Z9 408 U1 1 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 18 PY 2006 VL 296 IS 15 BP 1858 EP 1866 DI 10.1001/jama.296.15.1858 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 095ST UT WOS:000241329300028 PM 17047216 ER PT J AU Shefcheck, KJ Callahan, JH Musser, SM AF Shefcheck, Kevin J. Callahan, John H. Musser, Steven M. TI Confirmation of peanut protein using peptide markers in dark chocolate using liquid chromatography-tandem mass spectrometry (LC-MS/MS) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE peanut protein; Ara h 1; dark chocolate; allergen ID DIAL TELEPHONE SURVEY; TREE NUT ALLERGY; ELISA TEST KITS; ARA-H-I; IGE-BINDING; ATOPIC-DERMATITIS; MILK CHOCOLATE; PREVALENCE; ARA-H-1; FOODS AB Detection of peptides from the peanut allergen Ara h 1 by liquid chromatography-mass spectrometry (LC-MS) was used to identify and estimate total peanut protein levels in dark chocolate. A comparison of enzymatic digestion subsequent to and following extraction of Ara h 1 from the food matrix revealed better limits of detection (LOD) for the pre-extraction digestion (20 ppm) than for the postextraction digestion (50 ppm). Evaluation of LC-MS instruments and scan modes showed the LOD could be further reduced to 10 ppm via a triple-quadrupole and multiple-reaction monitoring. Improvements in extraction techniques combined with an increase in the amount of chocolate extracted (1 g) improved the LOD to 2 ppm of peanut protein. This method provides an unambiguous means of confirming the presence of the peanut protein in foods using peptide markers from a major allergen, Ara h 1, and can easily be modified to detect other food allergens. C1 US FDA, College Pk, MD 20740 USA. RP Shefcheck, KJ (reprint author), US FDA, 5100 Paint Vranch Pkwy, College Pk, MD 20740 USA. EM kshefche@cfsan.fda.gov NR 27 TC 43 Z9 45 U1 3 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD OCT 18 PY 2006 VL 54 IS 21 BP 7953 EP 7959 DI 10.1021/jf060714e PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 093HB UT WOS:000241157800001 PM 17031994 ER PT J AU Kutay, H Bai, SM Datta, J Motiwala, T Pogribny, I Frankel, W Jacob, ST Ghoshal, K AF Kutay, Huban Bai, Shoumei Datta, Jharna Motiwala, Tasneem Pogribny, Igor Frankel, Wendy Jacob, Samson T. Ghoshal, Kalpana TI Downregulation of miR-122 in the rodent and human hepatocellular carcinomas SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE folate/methyl-deficient diet; hepatocellular carcinoma; microRNA; miR-122; miR-17-92; miR-21 ID MICRORNA PRECURSORS; EXPRESSION; GENE; METHYLATION; SUPPRESSION; BIOGENESIS; CANCERS; DNA AB MicroRNAs (miRs) are conserved small non-coding RNAs that negatively regulate gene expression. The miR profiles are markedly altered in cancers and some of them have a causal role in tumorigenesis. Here, we report changes in miR expression profile in hepatocellular carcinomas (HCCs) developed in male Fisher rats-fed folic acid, methionine, and choline-deficient (FMD) diet. Comparison of the miR profile by microarray analysis showed altered expression of some miRs in hepatomas compared to the livers from age-matched rats on the normal diet. While let-7a, miR-21, miR-23, miR-130, miR-190, and miR-17-92 family of genes was upregulated, miR-122, an abundant liver-specific miR, was downregulated in the tumors. The decrease in hepatic miR-122 was a tumor-specific event because it did not occur in the rats switched to the folate and methyl-adequate diet after 36 weeks on deficient diet, which did not lead to hepatocarcinogenesis. miR-122 was also silent in a transplanted rat hepatoma. Extrapolation of this study to human primary HCCs revealed that miR-122 expression was significantly (P = 0.013) reduced in 10 out of 20 tumors compared to the pair-matched control tissues. These findings suggest that the downregulation of miR-122 is associated with hepatocarcinogenesis and could be a potential biomarker for liver cancers. C1 Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Natl Ctr Toxicol Res, Food & Drug Adm, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Ghoshal, K (reprint author), Ohio State Univ, Dept Mol & Cellular Biochem, 319 Hamilton Hall, Columbus, OH 43210 USA. EM ghoshal.1@osu.edu FU NCI NIH HHS [R01 CA086978, CA86978, R01 CA086978-01A2] NR 23 TC 357 Z9 402 U1 5 U2 37 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 OCT 15 PY 2006 VL 99 IS 3 BP 671 EP 678 DI 10.1002/jcb.20982 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 088BZ UT WOS:000240787800002 PM 16924677 ER PT J AU Temple, R AF Temple, Robert TI FDA perspective on trials with interim efficacy evaluations SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Adaptive Clinical Trial Designs - Ready for Prime Time CY OCT 19, 2004 CL Univ Maryland, Gaithersburg, MD SP FDA, Harvard-MTT Div Hlth Sci & Technol HO Univ Maryland DE adaptive; enrichment; early stopping AB Over the years FDA has seen a variety of 'adaptive' approaches, including repeated calculation of p-values. More recently there has been interest in adjusting sample sizes based on event rates, easy if the treatment group rates remain blinded but possible even with unblinded analysis. In large trials, group sequential analytic approaches are routine. Early stopping however, can reduce available data and in cardiac trials we have generally urged use of only survival as the basis for stopping, even if the primary endpoint is a composite (death, new AMI, etc). Other possibilities include adaptive randomization and starting additional dose groups. Enrichment designs focus on populations with a higher event rate or on populations more likely to respond. They can reduce sample sizes and target therapy toward people most likely to benefit. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, WO22,Room 4212,10903 New Hampshire Ave, Silver Spring, MD USA. EM robert.temple@fda.hhs.gov NR 0 TC 9 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 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 15 PY 2006 VL 25 IS 19 BP 3245 EP 3249 DI 10.1002/sim.2631 PG 5 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 089KU UT WOS:000240880300004 PM 16847824 ER PT J AU Hung, HMJ AF Hung, Hsien-Ming James TI Papers from the 2004 Harvard-MIT Division of Health Science and Technology Workshop, "Adaptive Clinical Trial Designs: Ready for Prime Time?" - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hung, HMJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM hsienming.hung@fda.hhs.gov NR 1 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 15 PY 2006 VL 25 IS 19 BP 3313 EP 3314 DI 10.1002/sim.2647 PG 2 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 089KU UT WOS:000240880300010 ER PT J CA FDA Ctr Drug Evaluation Res FDA Ctr Biol Evaluation Res FDA Ctr Devices Radiological Hlth TI Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance SO HEALTH AND QUALITY OF LIFE OUTCOMES LA English DT Article AB This guidance describes how the FDA evaluates patient-reported outcome (PRO) instruments used as effectiveness endpoints in clinical trials. It also describes our current thinking on how sponsors can develop and use study results measured by PRO instruments to support claims in approved product labeling (see appendix point 1). It does not address the use of PRO instruments for purposes beyond evaluation of claims made about a drug or medical product in its labeling. By explicitly addressing the review issues identified in this guidance, sponsors can increase the efficiency of their endpoint discussions with the FDA during the product development process, streamline the FDA's review of PRO endpoint adequacy, and provide optimal information about the patient's perspective of treatment benefit at the time of product approval. A PRO is a measurement of any aspect of a patient's health status that comes directly from the patient (i.e., without the interpretation of the patient's responses by a physician or anyone else). In clinical trials, a PRO instrument can be used to measure the impact of an intervention on one or more aspects of patients' health status, hereafter referred to as PRO concepts, ranging from the purely symptomatic (response of a headache) to more complex concepts (e.g., ability to carry out activities of daily living), to extremely complex concepts such as quality of life, which is widely understood to be a multidomain concept with physical, psychological, and social components. Data generated by a PRO instrument can provide evidence of a treatment benefit from the patient perspective. For this data to be meaningful, however, there should be evidence that the PRO instrument effectively measures the particular concept that is studied. Generally, findings measured by PRO instruments may be used to support claims in approved product labeling if the claims are derived from adequate and well-controlled investigations that use PRO instruments that reliably and validly measure the specific concepts at issue. The glossary defines many of the terms used in this guidance. In particular, the term instrument refers to the actual questions or items contained in a questionnaire or interview schedule along with all the additional information and documentation that supports the use of these items in producing a PRO measure (e.g., interviewer training and instructions, scoring and interpretation manual). The term conceptual framework refers to how items are grouped according to subconcepts or domains (e.g., the item walking without help may be grouped with another item, walking with difficulty, within the domain of ambulation, and ambulation may be further grouped into the concept of physical ability). FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidance documents describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance documents means that something is suggested or recommended but not required. C1 US FDA, US Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, US Dept Hlth & Human Serv, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, US Dept Hlth & Human Serv, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP US FDA, US Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. EM toni.stifano@fda.hhs.gov; toni.stifano@fda.hhs.gov SXD@cdrh.fda.gov; SXD@cdrh.fda.gov NR 0 TC 0 Z9 0 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1477-7525 J9 HEALTH QUAL LIFE OUT JI Health Qual. Life Outcomes PD OCT 11 PY 2006 VL 4 AR 79 DI 10.1186/1477-7525-4-79 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 103GV UT WOS:000241874600001 ER PT J AU Saha, S Yoshida, S Ohba, K Matsui, K Matsuda, T Takeshita, F Umeda, K Tamura, Y Okuda, K Klinman, D Xin, KQ Okuda, K AF Saha, Sukumar Yoshida, Shinsuke Ohba, Kenji Matsui, Kiyohiko Matsuda, Tomoko Takeshita, Fumihiko Umeda, Kazunori Tamura, Yuichi Okuda, Kentaro Klinman, Dennis Xin, Ke-Qin Okuda, Kenji TI A fused gene of nucleoprotein (NIP) and herpes simplex virus genes (VP22) induces highly protective immunity against different subtypes of influenza virus SO VIROLOGY LA English DT Article DE influenza nucleoprotein (NP); herpes simplex virus gene protein 22 (VP22); DNA vaccine; A/PR/8/34; HSV-1; CD8(+) cells; CD4(+) cells; intercellular spreading ID CD8(+) T-CELLS; A VIRUS; DNA VACCINES; FUSION PROTEIN; IN-VIVO; ANTIBODY-RESPONSES; TYPE-1 VP22; VACCINATION; DELIVERY; ANTIGEN AB We evaluated the immunogenicity and protective activity of plasmid DNA vaccines encoding the influenza virus NP gene (pNP) alone or in combination with the herpes simplex virus type 1 protein 22 gene (pVP22). Optimal immune responses were observed in BALB/c mice immunized with the combination of pVP22 plus pNP, as assessed by enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICCS). These mice also showed maximal resistance following challenge with the A/PR/8/34 (H1N1) and A/Udron/72 (H3N2) strains of influenza virus. The susceptibility of immunized mice to virus infection was significantly increased following depletion of either CD4(+) or CD8(+) T cells. These results indicate that a plasmid DNA vaccine encoding pVP22 plus NP induces a high level of cross-protective immunity against influenza virus subtypes. (c) 2006 Elsevier Inc. All rights reserved. C1 Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. US FDA, CBER, Bethesda, MD 20892 USA. Kyushu Univ, Fac Med Sci, Dept Oral Hlth Technol & Epidemiol, Fukuoka 81285822, Japan. RP Okuda, K (reprint author), Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM kokuda@med.yokohama-cu.ac.jp NR 43 TC 48 Z9 60 U1 0 U2 5 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 OCT 10 PY 2006 VL 354 IS 1 BP 48 EP 57 DI 10.1016/j.virol.2006.04.015 PG 10 WC Virology SC Virology GA 093OV UT WOS:000241178500006 PM 16945400 ER PT J AU Wu, LQ McDermott, MK Zhu, C Ghodssi, R Payne, GE AF Wu, Li-Qun McDermott, Martin K. Zhu, Chao Ghodssi, Reza Payne, Gregory E. TI Mimicking biological phenol reaction cascades to confer mechanical function SO ADVANCED FUNCTIONAL MATERIALS LA English DT Article ID POLYPHENOL OXIDASE; MUSSEL BYSSUS; CROSS-LINKING; POLYMERS; CHITOSAN; ADHESIVE; HYDROGELS; GELATION; PH; POLYMERIZATION AB Phenol reaction cascades are commonly used in nature to create crosslinked materials that perform mechanical functions. These processes are mimicked by electrochemically initiating a reaction cascade to examine if the mechanical properties of a biopolymer film can be predictably altered. Specifically, thin films (approximate to 30-45 mu m) of the polysaccharide chitosan are cast onto gold-coated silicon wafers, the chitosan-coated wafers are immersed in catechol-containing solutions, and the phenol is anodically oxidized. The product of this oxidation is highly reactive and undergoes reaction with chitosan chains adjacent to the anode. After reaction, the flexible chitosan film can be peeled from the wafer. Chemical and physical evidence support the conclusion that electrochemically initiated reactions crosslink chitosan. When gold is patterned onto the wafer, the electrochemical crosslinking reactions are spatially localized and impart anisotropic mechanical properties to the chitosan film. Further, deswelling of chitosan films can reversibly transduce environmental stimuli into contractile forces. Films patterned to have spatial variations in crosslinking respond to such environmental stimuli by undergoing reversible changes in shape. These results suggest the potential to enlist electrochemically initiated reaction cascades to engineer chitosan films for actuator functions. C1 Univ Maryland, Ctr Biosyst Res, College Pk, MD 20742 USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Rockville, MD 20850 USA. Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA. Univ Maryland, Syst Res Inst, College Pk, MD 20742 USA. RP Wu, LQ (reprint author), Univ Maryland, Ctr Biosyst Res, 5115 Plant Sci Bldg, College Pk, MD 20742 USA. EM payne@umbi.umd.edu NR 48 TC 34 Z9 34 U1 2 U2 27 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1616-301X J9 ADV FUNCT MATER JI Adv. Funct. Mater. PD OCT 4 PY 2006 VL 16 IS 15 BP 1967 EP 1974 DI 10.1002/adfm.200500792 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 097UB UT WOS:000241473400006 ER PT J AU Graham, DJ AF Graham, David J. TI COX-2 inhibitors, other NSAIDs, and cardiovascular risk - The seduction of common sense SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACUTE MYOCARDIAL-INFARCTION; ROFECOXIB; CYCLOOXYGENASE-2; EVENTS; TRIAL; COMPLICATIONS; METAANALYSIS; PREVENTION; CELECOXIB C1 US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Graham, DJ (reprint author), US FDA, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,WO22,Room 4314, Silver Spring, MD 20993 USA. EM david.graham1@fda.hhs.gov NR 30 TC 62 Z9 66 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 4 PY 2006 VL 296 IS 13 BP 1653 EP 1656 DI 10.1001/jama.296.13.jed60058 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 090JS UT WOS:000240948200027 PM 16968830 ER PT J AU Jablonski, JE Schlesser, JE Mariappagoudar, P AF Jablonski, Joseph E. Schlesser, Joseph E. Mariappagoudar, Purnima TI HPLC-UV method for nicotine, strychnine, and aconitine in dairy products SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE nicotine; strychnine; aconitine; milk; skim milk; cream; HPLC; solid-phase extraction; partitioning ID SOLID-PHASE EXTRACTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; BODY-FLUIDS; COTININE; URINE; BLOOD; MILK; TOXICOLOGY; ALKALOIDS AB The toxic nitrogen alkaloids nicotine, strychnine, and aconitine were quantitated in whole milk, skim milk, and cream using solid-phase extraction cleanup and HPLC-UV with dual wavelength detection. Samples were extracted in McIlvaine's buffer with EDTA and then partitioned with aqueous acetonitrile and hexane. The aqueous phase was concentrated and passed through an OASIS HLB column. The column was eluted with methylene chloride/ammonium hydroxide, 1 mL/1 mu L, v/v. The eluent was acidified with hydrochloric acid and evaporated. The sample was diluted for HPLC with acetonitrile/phosphate buffer pH 7.4. Chromatography was performed on an Xterra RP-18 column using a gradient of acetonitrile and ammonium bicarbonate buffer at pH 9.8. Nicotine and strychnine were monitored at 260 nm; aconitine was monitored at 232 nm. Calibration curves were generated from external standards in the range 0.2-10 mu g/mL using 1/x weighting. Mean recoveries in whole milk spiked between 0.1 and 10 ppm were the following: nicotine 89.2%, strychnine 75.7%, and aconitine 85.1%. Mean recoveries in skim milk spiked between 0.1 and 10 ppm were the following: nicotine 72.1%, strychnine 78.2%, and aconitine 82.9%. Mean recoveries in cream spiked between 0.2 and 20 ppm were the following: nicotine 87.9%, strychnine 76.9%, and aconitine 82.0%. Relative standard deviations of recovery were less than 20% in each case. C1 US FDA, CFSAN, Summit Argo, IL 60501 USA. IIT, NCFST, Summit Argo, IL 60501 USA. RP Jablonski, JE (reprint author), US FDA, CFSAN, 6502 S Archer, Summit Argo, IL 60501 USA. EM joseph.jablonski@fda.hhs.gov; joseph.schlesser@fda.hhs.gov; maripur@iit.edu NR 30 TC 15 Z9 16 U1 3 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD OCT 4 PY 2006 VL 54 IS 20 BP 7460 EP 7465 DI 10.1021/jf061115a PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 088EW UT WOS:000240795400008 PM 17002408 ER PT J AU Brinker, AD AF Brinker, Allen D. TI Trends in the use of ipecac in the ED setting: data from the 1992-2002 NHAMCS-ED (letter) SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Letter ID SYRUP C1 US FDA, Div Drug Risk Evaluat, Off Drug Safety, CDER, Silver Spring, MD USA. RP Brinker, AD (reprint author), US FDA, Div Drug Risk Evaluat, Off Drug Safety, CDER, Silver Spring, MD USA. EM allen.brinker@fda.hhs.gov NR 6 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2006 VL 24 IS 6 BP 759 EP 761 DI 10.1016/j.ajem.2006.02.015 PG 3 WC Emergency Medicine SC Emergency Medicine GA 091GL UT WOS:000241015000031 PM 16984861 ER PT J AU Klontz, KC Timbo, BB Street, D AF Klontz, Karl C. Timbo, Babgaleh B. Street, Debra TI Consumption of dietary supplements containing Citrus aurantium (Bitter orange) - 2004 California Behavioral Risk Factor Surveillance Survey (BRFSS) SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE bitter orange; Citrus aurantium; dietary supplements ID UNITED-STATES; VITAMIN; NONVITAMIN; SYNEPHRINE AB BACKGROUND: Following the marketing ban of ephedra-containing supplements in April 2004, many manufacturers substituted the herb Citrus aurantium for ephedra and marketed the products as "ephedra-free" supplements. Extracts of C. aurantium contain synephrine, a sympathomimetic alkaloid. OBJECTIVE: To determine the prevalence of consumption of dietary supplements containing C. aurandum in California during 2004. METHODS: We used the 2004 California Behavioral Risk Factor Surveillance Survey to determine the prevalence of consumption of dietary supplements containing C. aurantium in California during 2004. RESULTS: Two percent (n = 70) of the 4140 survey respondents reported taking a dietary supplement containing C. aurantium in the previous year. Reasons stated included energy enhancement, weight loss, and appetite suppression. Compared with nonusers, users were more likely to report being single, aged 18-34 years, and Hispanic; consuming 3 or more alcoholic drinks on days that they imbibed; and having a heavier body mass index. Among the 5 users who reported experiencing an adverse event that they attributed to the supplement, 3 indicated that the severity was mild. CONCLUSIONS: Given that supplements containing ephedra were banned in April 2004, the results from this study may serve as a baseline estimate against which future studies of the use of C. aurantium, products may be compared. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Klontz, KC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branck Pkwy, College Pk, MD 20740 USA. EM karl.klontz@cfsan.fda.gov NR 12 TC 8 Z9 8 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD OCT PY 2006 VL 40 IS 10 BP 1747 EP 1751 DI 10.1345/aph.1H196 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 092XU UT WOS:000241131800006 PM 16968826 ER PT J AU Budowle, B Schutzer, SE Burans, JP Beecher, DJ Cebula, TA Chakraborty, R Cobb, WT Fletcher, J Hale, ML Harris, RB Heitkamp, MA Keller, FP Kuske, C LeClerc, JE Marrone, BL McKenna, TS Morse, SA Rodriguez, LL Valentine, NB Yadev, J AF Budowle, Bruce Schutzer, Steven E. Burans, James P. Beecher, Douglas J. Cebula, Thomas A. Chakraborty, Ranajit Cobb, William T. Fletcher, Jacqueline Hale, Martha L. Harris, Robert B. Heitkamp, Michael A. Keller, Frederick Paul Kuske, Cheryl LeClerc, Joseph E. Marrone, Babetta L. McKenna, Thomas S. Morse, Stephen A. Rodriguez, Luis L. Valentine, Nancy B. Yadev, Jagjit TI Quality sample collection, handling, and preservation for an effective microbial forensics program SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Review ID BACILLUS-ANTHRACIS CONTAMINATION; SPECIMEN COLLECTION; CEREBROSPINAL-FLUID; QUANTITATIVE PCR; UNITED-STATES; TRANSPORT; BACTERIA; GLYCEROL; BIOTERRORISM; VIABILITY AB Science can be part of an effective investigative response to a bioterrorism event or a biocrime by providing capabilities to analyze biological and associated signatures in collected evidence. Microbial forensics, a discipline comprised of several scientific fields, is dedicated to the analysis of evidence from such criminal acts to help determine the responsible party and to exonerate the innocent (6). A partnership among a number of government agencies, academia, and the private sector has been formed to better respond to and deter potential perpetrators of bioterrorism or biocrimes. This partnership leverages our national scientific and analytical capabilities to support activities of law enforcement agencies. The Department of Homeland Security (DHS), whose mission is, in part, to respond to and to prevent acts of terrorism against the United States, has established the National Bioforensics Analysis Center (NBFAC) (4,6). The NBFAC, in partnership with the Federal Bureau of Investigation (FBI), (i) provides a state-of-the-art central laboratory for analysis of microbial forensic evidence and (ii) serves as a nexus for integrating the national resources to increase the effectiveness of law enforcement in obtaining the highest level of attribution possible in criminal cases where the weapon is a biological agent. One approach used by the NBFAC to establish a sound foundation, to foster communication, and to facilitate integration across government and other agencies is to promote independent meetings, which address specific needs and provide a forum for input from the broader scientific community, on the best scientific practices in microbial forensics (5). As part of this ongoing effort, a series of meetings sponsored by DHS were held at the Banbury Center of the Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, to address specific issues for the enhancement of microbial forensic capability. One such meeting, held on 16 to 19 October 2005, focused on the collection, handling, and storage of samples. These issues had been identified at previous meetings (5, 6) as some of the most critical issues confronting a crime scene investigation and subsequent analysis of evidence. The participants represented diverse scientific entities within academia, the private sector, the national laboratories, and several federal agencies (Central Intelligence Agency, Centers for Disease Control and Prevention, DHS, FBI, Food and Drug Administration, and U.S. Department of Agriculture), some of which have been involved in evidence collection for purposes related to forensics, public health, or plant and animal health. The collection and preservation of microbial forensic evidence are paramount to efficient and successful investigation and attribution. If evidence (when available) is not collected, degrades, or is contaminated during collection, handling, transport, or storage, the downstream characterization and attribution analyses may be compromised. Retrieving sufficient quantities and maintaining the integrity of the evidence increase the chances of being able to characterize the material to obtain the highest level of attribution possible. This paper presents issues related to the practices of sample collection, handling, transportation, and storage and includes recommendations for future directions for the field of microbial forensics and people participating in it. The recommendations apply to the NBFAC, as well as to other facilities and practitioners. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. Fed Bur Invest, Div Labs, Quantico, VA 22135 USA. Dept Homeland Secur, Frederick, MD 21703 USA. US FDA, Laurel, MD 20708 USA. Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45267 USA. Cobb Consulting Serv, Kennewick, WA 99336 USA. Oklahoma State Univ, Dept Entomol & Plant Pathol, Stillwater, OK 74078 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Commonwealth Biotechnol Inc, Richmond, VA 23235 USA. Savannah River Natl Lab, Aiken, SC 29808 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. USDA ARS, FADDL, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. USDA ARS, Plum Isl Anim Dis Ctr, Foreign Anim Div Res Unit, Greenport, NY 11944 USA. Pacific NW Natl Lab, Richland, WA 99352 USA. RP Schutzer, SE (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, MSB E543,185 S Orange Ave, Newark, NJ 07103 USA. EM schutzer@umdnj.edu NR 48 TC 23 Z9 23 U1 3 U2 29 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 OCT PY 2006 VL 72 IS 10 BP 6431 EP 6438 DI 10.1128/AEM.01165-06 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 093LR UT WOS:000241170300001 PM 17021190 ER PT J AU Nawaz, M Sung, K Khan, SA Khan, AA Steele, R AF Nawaz, Mohamed Sung, Kidon Khan, Saeed A. Khan, Ashraf A. Steele, Roger TI Biochemical and molecular characterization of tetracycline-resistant Aeromonas veronii isolates from catfish SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID OXYTETRACYCLINE RESISTANCE; ANTIBIOTIC-RESISTANCE; DETERMINANTS; HYDROPHILA; MISIDENTIFICATION; IDENTIFICATION; ENVIRONMENTS; BACTERIA; VIBRIO; GENES AB Eighty-one tetracycline-resistant Aeromonas sp. strains were isolated from farm-raised catfish. Morphological and biochemical characteristics indicated that 23 of the 81 aeromonads were Aeromonas hydrophila, 7 isolates were Aeromonas trota, 6 isolates were Aeromonas caviae, 42 isolates were Aeromonas veronii, and 3 isolates were Aeromonas jandaei. However, the AluI and MboI restriction fragment length polymorphism (RFLP) patterns of the PCR-amplified 1.4-kb 16S rRNA gene from all 81 tetracycline-resistant aeromonads from catfish were identical to the RFLP banding patterns of A. veronii ATCC 35626, indicating that all 81 isolates were strains of A. veronii. A multiplex PCR assay successfully amplified the 5 tetracycline-resistant genes (tetA to E) from the genomic DNA of all 81 isolates. The assay determined that WE was the dominant gene occurring in 73/81 (90.0%) of the aeromonads. Plasmids (2.0 to 20 kb) were isolated from 33 of the 81 isolates. Dendrogram analysis of the SpeI pulsed-field gel electrophoresis identified 15 distinct macrorestriction patterns among the isolates. Our results indicate the need for use of 16S rRNA in the identification of Aeromonas spp. and the prevalence of catfish as a reservoir of tet genes. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Nawaz, M (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM mnawaz@nctr.fda.gov NR 33 TC 42 Z9 49 U1 0 U2 6 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 OCT PY 2006 VL 72 IS 10 BP 6461 EP 6466 DI 10.1128/AEM.00271-06 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 093LR UT WOS:000241170300004 PM 17021193 ER PT J AU Ali, L Khambaty, F Diachenko, G AF Ali, Laila Khambaty, Farukh Diachenko, Gregory TI Investigating the suitability of the Calgary Biofilm Device for assessing the antimicrobial efficacy of new agents SO BIORESOURCE TECHNOLOGY LA English DT Article DE biofilms; Calgary Biofilm Device; planktonic cells; disinfectants; Escherichia coli; Listeria innocua ID LISTERIA-MONOCYTOGENES; CHLORINE; SURFACES; ADHESION AB This study investigated the suitability of the Calgary Biofilm Device (CBD), originally designed as a test surrogate for indwelling medical devices. for assessing the efficacy of antimicrobials developed for food and food contact surface disinfection applications. The conditions for the development of uniform biofilms from pure and mixed bacterial cultures of wild type Escherichia coli and Listeria innocua were optimized. We were able to recover approximate to 2 x 10(6) colony forming units (CFU) from the biofilms formed on the individual pegs of the device in 24 h. Further, the parameters for the consistent release of the cells from the biofilms were optimized; test showed that the number of cells released was uniform and reproducible. The consistency and reproducibility of the biofilms formed on the pegs was evaluated using scanning electron microscopy and by plate count method. The efficacies of disinfectants on cells residing in biofilms versus planktonic cells were compared. For both species, higher concentrations of disinfectants were needed to eliminate attached cells as compared with planktonic cells. This study establishes the value of the CBD for generating consistent biofilms from either pure or mixed cultures. These biofilms can be used to assess efficacies of disinfectants against cells that have colonized the surfaces of foods and food-processing equipment. Such a system could serve as a standard surrogate for evaluating new disinfectants designed to reduce or eliminate biofilms from food-contact surfaces. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Chem Res & Environm Review, College Pk, MD 20740 USA. US FDA, Off Seafood, Ctr Food Safety & Appl Nutr, Div Sci Assessment & Technol, Dauphin Isl, AL 36528 USA. RP Ali, L (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Chem Res & Environm Review, 5100 Paint Branch Pkwy,Room BE-022,HFS-245, College Pk, MD 20740 USA. EM Laila.ali@cfsan.fda.gov NR 18 TC 24 Z9 24 U1 3 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0960-8524 J9 BIORESOURCE TECHNOL JI Bioresour. Technol. PD OCT PY 2006 VL 97 IS 15 BP 1887 EP 1893 DI 10.1016/j.biortech.2005.08.025 PG 7 WC Agricultural Engineering; Biotechnology & Applied Microbiology; Energy & Fuels SC Agriculture; Biotechnology & Applied Microbiology; Energy & Fuels GA 063DA UT WOS:000238995000019 PM 16256346 ER PT J AU Manjanatha, M Shelton, S Bishop, M Lyn-Cook, L Aidoo, A AF Manjanatha, Mugimane Shelton, Sharon Bishop, Michelle Lyn-Cook, Lascelles Aidoo, Anane TI Dietary effects of soy isoflavones daidzein and genistein on 7,12-dimethylbenz[a]anthracene-induced mammary mutagenesis and carcinogenesis in ovariectomized Big Blue transgenic rats SO CARCINOGENESIS LA English DT Article ID ENDOGENOUS HPRT GENE; DNA ADDUCT FORMATION; SPRAGUE-DAWLEY RATS; BREAST-CANCER RISK; STRAND BREAKS; HOT FLUSHES; ESTROGEN; ESTRADIOL; INDUCTION; TUMORS AB The major constituents of isoflavones daidzein (DZ) and genistein (GE) interact with the and estrogen receptors in several tissues including mammary tissues. In this study, we used ovariectomy (OVX) to model menopause and determined the effects of DZ, GE or 17 beta-estradiol (E-2) exposures on chemically induced mutagenesis and carcinogenesis in the mammary glands of female Big Blue transgenic rats. The rats were fed control diet containing the isoflavones and E-2 and treated with a single oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) at PND50. Animals were euthanized at 16 or 20 weeks post-carcinogen treatment to assess mutant frequencies (MFs) and histopathological parameters, respectively. The isoflavones or E-2 supplementation alone resulted in the lac I MFs that were not significantly different from the MFs measured in rats fed the control diet alone. DMBA exposure, however, induced significant increases in the lac I MFs in the mammary tissues of both OVX and INT rats and Hprt MFs in spleen lymphocytes (P < 0.01). In general, feeding the isoflavones or E-2 did not cause any significant changes in DMBA-induced mutagenicity in the mammary tissues. However, feeding the isoflavone mixture (daidzein + genistein; DZG) resulted in a significant reduction in the DMBA-induced lac I MFs (P < 0.05). Cell proliferation as measured by PCNA immunohistochemistry was increased in both OVX and INT rats exposed to DMBA as compared with rats fed control diet (P < 0.05). Mammary histology indicated that hyperplasia was induced in most of the treatment groups including control. Although DMBA did not induce mammary tumors in the OVX rats, adenoma and adenocarcinoma were detected in the mammary glands of INT rats. C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP Manjanatha, M (reprint author), US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. EM mmanjanatha@nctr.fda.gov NR 56 TC 8 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2006 VL 27 IS 10 BP 1970 EP 1979 DI 10.1093/carcin/bgl028 PG 10 WC Oncology SC Oncology GA 090CF UT WOS:000240927500005 PM 16709578 ER PT J AU Mididoddi, PK Prodduturi, S Repka, MA AF Mididoddi, P. K. Prodduturi, S. Repka, M. A. TI Influence of tartaric acid on the bioadhesion and mechanical properties of hot-melt extruded hydroxypropyl cellulose films for the human nail SO DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY LA English DT Article DE tartaric acid; hot-melt extrusion; bioadhesion; mechanical properties; thermogravimetric analysis (TGA); nail ID POLYETHYLENE OXIDE; ACRYLIC FILMS; EXTRUSION; ABSORPTION; DRUGS; DISPERSIONS; DEGRADATION; PELLETS AB The objective of this study was to investigate the influence of tartaric acid (TTA) on the bioadhesive, moisture sorption, and mechanical properties of hot-melt-extruded (HME) hydroxypropyl cellulose (HPC) films containing polymer additives. Two Klucel(R) EF and LF batches (HPC, MW: 80000 and 95000, respectively) containing the model antifungal drug ketoconazole (one batch of each MW with and without TTA 4%) were prepared into films by HME using a Killion extruder (Model KLB-100). The bioadhesive properties of the HPC films, with and without TTA, were investigated ex vivo on the human nails. The parameters measured were work of adhesion and peak adhesion force (PAF). A statistically significant increase in both the area under the curve (AUC) and PAF was seen for the HME films containing TTA than those without TTA. Moisture content of hot-melt extruded HPC films was determined using thermogravimetric analysis (TGA). TGA data collected at the two-week interval (25 degrees C/60% RH), measured higher moisture content for the TTA-containing films than those without TTA. Tensile strength and percent elongation were determined utilizing a TA.XT2i Texture Analyzer(R) equipped with a 50-kg load cell, TA-96 grips, and Texture Expert(TM) software. TTA functioned as an effective plasticizer, increasing percent elongation and decreasing tensile strength of the HPC films. TTA could potentially be a candidate for transnail applications in film devices prepared by hot-melt extrusion technology. C1 Univ Mississippi, Natl Ctr Nat Prod Res, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Dept Pharmaceut, University, MS 38677 USA. US FDA, Div Pharmaceut Anal, St Louis, MO USA. RP Repka, MA (reprint author), Univ Mississippi, Natl Ctr Nat Prod Res, University, MS 38677 USA. EM marepka@olemiss.edu NR 31 TC 21 Z9 21 U1 1 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0363-9045 J9 DRUG DEV IND PHARM JI Drug Dev. Ind. Pharm. PD OCT PY 2006 VL 32 IS 9 BP 1059 EP 1066 DI 10.1080/03639040600683410 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 090FM UT WOS:000240936100006 PM 17012118 ER PT J AU Bojanowski, CM Shen, DF Chew, EY Ning, BT Csaky, KG Green, WR Chan, CC Tuo, JS AF Bojanowski, Christine M. Shen, Defen Chew, Emily Y. Ning, Baitang Csaky, Karl G. Green, W. Richard Chan, Chi-Chao Tuo, Jingsheng TI An Apolipoprotein E variant may protect against age-related macular degeneration through cytokine regulation SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE age-related macular degeneration; apolipoprotein E; single nucleotide polymorphism; genetic susceptibility; cytokines ID COMPLEMENT FACTOR-H; C-REACTIVE PROTEIN; PIGMENT EPITHELIAL-CELLS; ENDOTHELIAL GROWTH-FACTOR; ALZHEIMERS-DISEASE; E GENE; CHOROIDAL NEOVASCULARIZATION; APOE GENOTYPE; AMYLOID-BETA; ANIMAL-MODEL AB Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among the elderly in Western countries. Genetic factors, age, cigarette smoking, nutrition, and exposure to light have been identified as AMD risk factors. In this study, we investigated the association between ApoE C112R/R158C single nucleotide polymorphisms (which determine the E2, E3, and E4 isoforms) and age-related macular degeneration (AMD), and the mechanism underlying the association. Genomic DNA was extracted from 133 clinically screened controls, 94 volunteers with a younger mean age, 120 patients with advanced AMD, and 40 archived ocular AMD slides for single nucleotide polymorphism typing. The effects of recombinant ApoE isoforms on CCL2 (a chemokine), CX3CR1 (a chemokine receptor), and VEGF (a cytokine) expression in cultured human retinal pigment epithelium (RIPE) cells were tested and serum cholesterol profiles of the clinically screened subjects were analyzed. ApoE112R (EA) distribution differed significantly between AMD patients and controls. ApoE112R allele frequency was 10.9% in the AMD group when compared with 16.5% in the younger controls and 18.8% in the clinically screened controls. The pathologically diagnosed archived AMD cases had the lowest allele frequency of 5%. No significant differences in ApoE158C (E2) distribution were observed among the groups. A meta-analysis of 8 cohorts including 4,289 subjects showed a strong association between AMD and 112R, but not 158C. In vitro studies found that recombinant ApoE suppresses CCL2 and VEGF expression in RIPE cells. However, the E4 isoform showed more suppression than E3 in both cases. These results further confirm the association between ApoE112R and a decreased risk of AMD development. The underlying mechanisms may involve differential regulation of both CCL2 and VEGF by the ApoE isoforms. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Div Pharmacogen & Mol Epidemiol, Jefferson, AR 72079 USA. NEI, Sect Retinal Dis & Therapeut, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Sch, Wilmer Eye Inst, Baltimore, MD USA. RP Tuo, JS (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20892 USA. EM tuoj@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU Intramural NIH HHS [Z99 EY999999, Z01 EY000418-04] NR 59 TC 35 Z9 38 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2006 VL 47 IS 8 BP 594 EP 602 DI 10.1002/em.20233 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 099TJ UT WOS:000241618600004 PM 16823865 ER PT J AU Landsberg, JH Hall, S Johannessen, JN White, KD Conrad, SM Abbott, JP Flewelling, LJ Richardson, RW Dickey, RW Jester, ELE Etheridge, SM Deeds, JR Van Dolah, FM Leighfield, TA Zou, YL Beaudry, CG Benner, RA Rogers, PL Scott, PS Kawabata, K Wolny, JL Steidinger, KA AF Landsberg, Jan H. Hall, Sherwood Johannessen, Jan N. White, Kevin D. Conrad, Stephen M. Abbott, Jay P. Flewelling, Leanne J. Richardson, R. William Dickey, Robert W. Jester, Edward L. E. Etheridge, Stacey M. Deeds, Jonathan R. Van Dolah, Frances M. Leighfield, Tod A. Zou, Yinglin Beaudry, Clarke G. Benner, Ronald A. Rogers, Patricia L. Scott, Paula S. Kawabata, Kenji Wolny, Jennifer L. Steidinger, Karen A. TI Saxitoxin puffer fish poisoning in the United States, with the first report of Pyrodinium bahamense as the putative toxin source SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE dinoflagellate; Florida; harmful algae; puffer fish; Pyrodinium bahamense; saxitoxin puffer fish poisoning; saxitoxins; Sphoeroides spp. ID INDIAN-RIVER LAGOON; RECEPTOR-BINDING ASSAY; FRESH-WATER PUFFERS; GENUS SPHOEROIDES; MARINE PUFFER; SHELLFISH; FLORIDA; TOXICITY; NORTHERN; COAST AB BACKGROUND: From January 2002 to May 2004, 28 puffer fish poisoning (PFP) cases in Florida, New Jersey, Virginia, and New York were linked to the Indian River Lagoon (IRL) in Florida. Saxitoxins (STXs) of unknown source were first identified in fillet remnants from a New Jersey PFP case in 2002. METHODS: We used the standard mouse bioassay (MBA), receptor binding assay (RBA), mouse neuroblastoma cytotoxicity assay (MNCA), Ridascreen ELISA, MIST Alert assay, HPLC, and liquid chromatography mass spectrometry (LC-MS) to determine the presence of STX, decarbamoyl STX (dc-STX), and N-sulfocarbamoyl (B1) toxin in puffer fish tissues, clonal cultures, and natural bloom samples of Pyrodinium bahamense from the IRL. RESULTS: We found STXs in 516 IRL southern (Sphoeroides nephelus), checkered (Sphoeroides testudineus), and handrail (Sphoeroides spengleri) puffer fish. During 36 months of monitoring, we detected STXs in skin, muscle, and viscera, with concentrations up to 22,104 jig STX equivalents (eq)/100 g tissue (action level, 80 mu g STX eq/100 g tissue) in ovaries. Puffer fish tissues, clonal cultures, and natural bloom samples of A bahmense from the IRL tested toxic in the MBA, RBA, MNCA, Ridascreen ELISA, and MIST Alert assay and positive for STX, dc-STX, and B1 toxin by HPLC and LC-MS. Skin mucus of IRL southern puffer fish captive for 1-year was highly toxic compared to Florida Gulf coast puffer fish. Therefore, we confirm puffer fish to be a hazardous reservoir of STXs in Florida's marine waters and implicate the dinoflagellate P. bahamense as the putative toxin source. CONCLUSIONS: Associated with fatal paralytic shellfish poisoning (PSP) in the Pacific but not known to be toxic in the western Atlantic, P. bahmense is an emerging public health threat. We propose characterizing this food poisoning syndrome as saxitoxin puffer fish poisoning (SPFP) to distinguish it from PFP, which is traditionally associated with tetrodotoxin, and from PSP caused by STXs in shellfish. C1 Florida Fish & Wildlife Conservat Commiss, Fish & Wildlife Res Inst, St Petersburg, FL 33701 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. US FDA, Ctr Food Safety & Appl Nutr, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. Natl Ocean & Atmospher Adm, Natl Ocean Serv, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC USA. State Ocean Adm, Inst Oceanog 1, Key Lab Sci & Engn Marine Ecol & Environm, Qingdao, Peoples R China. Univ S Florida, Florida Inst Oceanog, St Petersburg, FL 33620 USA. RP Landsberg, JH (reprint author), Florida Fish & Wildlife Conservat Commiss, Fish & Wildlife Res Inst, 100 8th Ave SE, St Petersburg, FL 33701 USA. EM jan.landsberg@myfwc.com OI Wolny, Jennifer L./0000-0002-3556-5015; DeGrasse, Stacey/0000-0001-7808-4193 NR 60 TC 67 Z9 69 U1 0 U2 16 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2006 VL 114 IS 10 BP 1502 EP 1507 DI 10.1289/ehp.8998 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 090RW UT WOS:000240969700024 PM 17035133 ER EF