FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Li, H AF Li, H TI The resolution of some paradoxes related to reliability and validity SO JOURNAL OF EDUCATIONAL AND BEHAVIORAL STATISTICS LA English DT Article DE coefficient alpha; hermeneutics; paradox; psychometrics; Spearmen-Brown formula ID MAXIMAL-RELIABILITY AB Attention is brought to the existence of incongruity in the definition of reliability in the literature, and some unnecessary controversies and confusions which result. A conventionalization of the meaning of reliability at a conceptual, model-free level is proposed. Through the exploration of two paradoxes, this article attempts to address some potential misconceptions about reliability, validity, and psychometrics. C1 Univ Rochester, Rochester, NY 14627 USA. RP Li, H (reprint author), US FDA, Ctr Devices & Radiol Hlth, 1350 Piccard Dr, Rockville, MD 20850 USA. NR 17 TC 7 Z9 9 U1 1 U2 2 PU AMER EDUCATIONAL RESEARCH ASSOC PI WASHINGTON PA 1230 17TH ST NW, WASHINGTON, DC 20036-3078 USA SN 1076-9986 J9 J EDUC BEHAV STAT JI J. Educ. Behav. Stat. PD SUM PY 2003 VL 28 IS 2 BP 89 EP 95 DI 10.3102/10769986028002089 PG 7 WC Education & Educational Research; Social Sciences, Mathematical Methods; Psychology, Mathematical SC Education & Educational Research; Mathematical Methods In Social Sciences; Psychology GA 729ET UT WOS:000185760400001 ER PT J AU Brandt, MB LeGault, LA AF Brandt, MB LeGault, LA TI What's new on nutrition labeling at the United States Food and Drug Administration? SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE nutrition labeling; trans fatty acids; voluntary nutrition labeling of raw produce and fish; Food Label and Package Survey; nutrition labeling databases; compliance AB The manuscript provides an overview of food labeling activities of the United States (USA) Food and Drug Administration (FDA). Highlights include: FDA will proceed with final rulemaking on trans fatty acid labeling after review of the National Academy of Sciences (NAS) Macronutrient Report. FDA, United States Department of Agriculture (USDA), and Health Canada are funding a 24-month NAS study on Dietary Reference Intakes in Nutrition Labeling to provide information that can be considered in the development of reference values for labeling in the USA and Canada. In March of 2002, FDA published a rule that proposes to amend the regulations to update the names and nutrition labeling values of the 20 most frequently consumed raw fruits, vegetables, and fish in the USA and to revise the guidelines for the voluntary nutrition labeling of these raw foods. For over 20 years, FDA has used the Food Label and Package Survey (FLAPS) to monitor the industry response to food label regulations. FLAPS is the only large-scale USA survey that routinely reviews food label information representative of the nation's food supply. Nutrition labeling databases are collections of nutrient data for specific products or commodities used to support nutrition label values. While selection of the source of the data used to calculate nutrition labeling values is the prerogative of the manufacturer, FDA recommends that the nutrient values for nutrition labeling be based on product composition as determined by laboratory analysis. Restaurants using claims must provide nutrition information relevant to the claim and may determine nutrient levels by nutrient databases, cookbooks, analyses, and by other reasonable bases that provide assurance that the food or meal meets the nutrient requirements for a claim. C1 USA Food & Drug Adm, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, HFS 840, College Pk, MD 20740 USA. RP Brandt, MB (reprint author), USA Food & Drug Adm, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, HFS 840, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 9 TC 6 Z9 6 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD JUN PY 2003 VL 16 IS 3 BP 383 EP 393 DI 10.1016/S0889-1575(03)00044-9 PG 11 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 692NQ UT WOS:000183667500018 ER PT J AU Myers, MJ Yancy, HF Farrell, DE AF Myers, MJ Yancy, HF Farrell, DE TI Characterization of a polymerase chain reaction-based approach for the simultaneous detection of multiple animal-derived materials in animal feed SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LENGTH-POLYMORPHISM ANALYSIS; MITOCHONDRIAL-DNA; SPECIES IDENTIFICATION; PCR; FEEDSTUFFS; MEAT AB In this study, a polymerase chain reaction (PCR) primer set capable of amplifying a mitochondrial DNA segment of multiple species (cattle, sheep, goats, deer, and elk) whose rendered remains are prohibited from being fed to ruminants was characterized. However, the primer set also amplifies DNA derived from the rendered remains of pigs and horses, which are exempt from the feed ban. PCR amplicons derived from pig DNA have a restriction endonuclease site recognized by Hinf1, while the horse DNA-derived amplicon has a unique restriction endonuclease site recognized by HypCH4III. This "universal" PCR primer produced an amplicon with DNA extracted from dairy feed containing either bovine meat and bone meal or pig blood meal. Enzymatic digestion of the PCR amplicons from these feed samples with Hinf1 resulted in cleavage products only from samples containing pig blood meal. However, Hinf1 digestion of these amplicons was not complete. Further analysis of the pig blood meal with primers specific for bovine or porcine DNA demonstrated the presence of both bovine- and porcine-derived DNA. Enzymatic digestion confirmed these findings. Additional testing was conducted with dry dog food samples labeled as containing either lamb, chicken, turkey, or chicken and fish. The universal PCR primer produced an amplicon only for the dog food containing lamb meal. This paper is the first to describe a simplified approach for the detection of the prohibited species of concern in the feed ban. C1 US FDA, Div Anim Res, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 10 TC 22 Z9 23 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 JUN PY 2003 VL 66 IS 6 BP 1085 EP 1089 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 687MD UT WOS:000183379800027 PM 12801014 ER PT J AU Wong-Chew, RM Beeler, JA Audet, S Santos, JI AF Wong-Chew, RM Beeler, JA Audet, S Santos, JI TI Cellular and humoral immune responses to measles in immune adults re-immunized with measles vaccine SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE cellular immunity; humoral immunity; measles vaccine; booster ID ANTIBODY PERSISTENCE; RUBELLA VACCINE; OLD INFANTS; FOLLOW-UP; MUMPS; VIRUS; IMMUNOGENICITY; REVACCINATION; CHILDREN; MOTHERS AB The objective of this study was to characterize the kinetics' of the cellular and humoral immune responses elicited by measles vaccine given to previously immune adults. The cellular and humoral immune responses to measles were measured in seven healthy adults, before vaccination and at 1, 2, 3, and 4 weeks and 3 months after vaccination, using measles-specific T-cell proliferation and plaque reduction neutralization assays. All study subjects had detectable measles antibodies, but only six (85%) showed protective titers, defined as >1:120, before immunization. However measles-specific T-cell proliferation was not detectable before vaccination in any of the subjects. The six subjects with protective titers showed a positive stimulation index (SI) of >3.0 within the first 4 weeks after vaccination, an SI of 5 at the 4th week, and an SI of 3 at 3 months after vaccination. The subject with a low antibody titer (1:99) before vaccination developed a high SI at 3 months after vaccination. This subject was the only participant whose neutralizing antibody titers increased more than 4-fold by 3 months after vaccination. No significant increases in geometric mean titers were detected in the other six subjects during the follow-up period. These data suggest that high measles antibody titers interfere with the humoral response in subjects who receive a booster immunization, whereas the cellular response is boosted at least transiently, after revaccination. C1 Univ Nacl Autonoma Mexico, Dept Expt Med, Fac Med, Hosp Gen Mexico,Lab Infectol Microbiol & Immunol, Mexico City 06726, DF, Mexico. Consejo Nacl Vacunac, Ctr Nacl Salud Infancia & Adolescencia, Secretaria Salud, Mexico City, DF, Mexico. US FDA, Div Viral Prod, Bethesda, MD USA. RP Wong-Chew, RM (reprint author), Univ Nacl Autonoma Mexico, Dept Expt Med, Fac Med, Hosp Gen Mexico,Lab Infectol Microbiol & Immunol, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico. EM rmwong@correo.unam.mx NR 27 TC 18 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 2003 VL 70 IS 2 BP 276 EP 280 DI 10.1002/jmv.10390 PG 5 WC Virology SC Virology GA 673DC UT WOS:000182564000015 PM 12696117 ER PT J AU Amexis, G Rubin, S Chatterjee, N Carbone, K Chumakov, K AF Amexis, G Rubin, S Chatterjee, N Carbone, K Chumakov, K TI Identification of a new genotype H wild-type mumps virus strain and its molecular relatedness to other virulent and attenuated strains SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE mumps; attenuation; wild-type isolate; genetic stability; quasispecies; vaccine AB A single clinical isolate of mumps virus designated 88-1961 was obtained from a patient hospitalized with a clinical history of upper respiratory tract infection, parotitis, severe headache, fever and lymphadenopathy. We have sequenced the full-length genome of 88-1961 and compared it against all available full-length sequences of mumps virus. Based upon its nucleotide sequence of the SH gene 88-1961 was identified as a genotype H mumps strain. The overall extent of nucleotide and amino acid differences between each individual gene and protein of 88-1961 and the full-length mumps samples showed that the missense to silent ratios were unevenly distributed. Upon evaluation of the consensus sequence of 88-1961, four positions were found to be clearly heterogeneous at the nucleotide level (NP 315C/T, NP 318C/T, F 271A/C, and HN 855C/T). Sequence analysis revealed that the amino acid sequences for the NP, M, and the L protein were the most conserved, whereas the SH protein exhibited the highest variability among the compared mumps genotypes A, B, and G. No identifying molecular patterns in the non-coding (intergenic) or coding regions of 88-1961 were found when we compared it against relatively virulent (Urabe AM9 B, Glouc1/UK96, 87-1004 and 87-1005) and non-virulent mumps strains (Jeryl Lynn and all Urabe Am9 A substrains). C1 US FDA, CBER, Rockville, MD 20852 USA. New York State Dept Hlth, Virus Isolat Lab, Wadsworth Ctr, Slingerland, NY USA. RP Amexis, G (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. NR 8 TC 19 Z9 19 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 2003 VL 70 IS 2 BP 284 EP 286 DI 10.1002/jmv.10392 PG 3 WC Virology SC Virology GA 673DC UT WOS:000182564000017 PM 12696119 ER PT J AU Derr, J Goldsmith, LJ AF Derr, J Goldsmith, LJ TI How to report nonsignificant results: Planning to make the best use of statistical power calculations SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. Univ Louisville, Dept Bioinformat & Biostat, Sch Publ Hlth & Informat Sci, Louisville, KY 40292 USA. RP Derr, J (reprint author), US FDA, Rockville, MD 20857 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU J O S P T, ALLIANCE GROUP COMMUNICATIONS PI LAWRENCE PA 810 EAST 10TH ST, PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD JUN PY 2003 VL 33 IS 6 BP 303 EP 306 PG 4 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 702GZ UT WOS:000184217300001 ER PT J AU Zuckerman, BD Sapirstein, W AF Zuckerman, BD Sapirstein, W TI Prosthetic cardiac valve replacement SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Letter C1 Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Cardiovasc Devices, Rockville, MD 20850 USA. RP Zuckerman, BD (reprint author), Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Cardiovasc Devices, Rockville, MD 20850 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 2003 VL 125 IS 6 BP 1563 EP 1563 DI 10.1016/S0022-5223(03)00120-X PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 696BG UT WOS:000183864700059 PM 12830091 ER PT J AU Miller, DL Balter, S Cole, PE Lu, HT Schueler, BA Geisinger, M Berenstein, A Albert, R Georgia, JD Noonan, PT Cardella, JF George, JS Russell, EJ Malisch, TW Vogelzang, RL Miller, GL Anderson, J AF Miller, DL Balter, S Cole, PE Lu, HT Schueler, BA Geisinger, M Berenstein, A Albert, R Georgia, JD Noonan, PT Cardella, JF George, JS Russell, EJ Malisch, TW Vogelzang, RL Miller, GL Anderson, J TI Radiation doses in interventional radiology procedures: The RAD-IR Study - Part I: Overall measures of dose SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID UTERINE ARTERY EMBOLIZATION; FLUOROSCOPICALLY GUIDED PROCEDURES; INDUCED SKIN INJURIES; CARDIAC-CATHETERIZATION; NEURORADIOLOGICAL PROCEDURES; AREA PRODUCT; PATIENT; EXPOSURE; DOSIMETRY; CARDIOLOGY AB PURPOSE: To determine patient radiation doses for interventional radiology and neuroradiology procedures, to identify procedures associated with higher radiation doses, and to determine the effects of various parameters on patient doses. MATERIALS AND METHODS: A prospective observational study was performed at seven academic medical centers. Each site contributed demographic and radiation dose data for subjects undergoing specific procedures in fluoroscopic suites equipped with built-in cumulative dose (CD) and dose-area-product (DAP) measurement capability compliant with International Electrotechnical Commission standard 60601-2-43. The accuracy of the dosimetry was confirmed by comprehensive measurements and by frequent consistency checks performed over the course of the study. RESULTS: Data were collected on 2,142 instances of interventional radiology procedures, 48 comprehensive physics evaluations, and 581 periodic consistency checks from the 12 fluoroscopic units in the study. There were wide variations in dose and statistically significant differences in fluoroscopy time, number of images, DAP, and CD for different instances of the same procedure, depending on the nature of the lesion, its anatomic location, and the complexity of the procedure. For the 2,142 instances, observed CD and DAP correlate well overall (r = 0.83, P < .000001), but correlation in individual instances is poor. The same is true for the correlation between fluoroscopy time and CD (r = 0.79, P < .000001). The correlation between fluoroscopy time and DAP (r = 0.60, P < .000001) is not as good. In 6% of instances (128 of 2,142), which were principally embolization procedures, transjugular intrahepatic portosystemic shunt (TIPS) procedures, and renal/visceral artery stent placements, CD was greater than 5 Gy. CONCLUSIONS: Most procedures studied can result in clinically significant radiation dose to the patient, even when performed by trained operators with use of dose-reducing technology and modem fluoroscopic equipment. Embolization procedures, TIPS creation, and renal/visceral artery stent placement are associated with a substantial likelihood of clinically significant patient dose. At minimum, patient dose data should be recorded in the medical record for these three types of procedures. These data should include indicators of the risk of deterministic effects as well as the risk of stochastic effects. C1 Natl Naval Med Ctr, Dept Radiol, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Radiol & Nucl Med, Bethesda, MD 20814 USA. Natl Canc Inst, Med Oncol Clin Res Unit, Canc Res Ctr, Bethesda, MD USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Lenox Hill Hosp, Dept Med, New York, NY 10021 USA. Beth Israel Deaconess Med Ctr, Hyman Newman Inst Neurol & Neurosurg, Ctr Endovasc Surg, New York, NY 10003 USA. SUNY Upstate Med Univ, Dept Radiol, Syracuse, NY USA. Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA. Mayo Clin, Dept Radiol, Rochester, MN USA. Cleveland Clin Fdn, Dept Radiol, Cleveland, OH 44195 USA. Northwestern Univ, Feinberg Sch Med, Northwestern Mem Hosp, Dept Radiol, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Dept Radiol, Dallas, TX 75230 USA. RP Natl Naval Med Ctr, Dept Radiol, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM dm72v@nih.gov NR 52 TC 177 Z9 183 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2003 VL 14 IS 6 BP 711 EP 727 DI 10.1097/01.RVI.0000079980.80153.4B PG 17 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 691UV UT WOS:000183625000004 PM 12817038 ER PT J AU Crawford, L AF Crawford, L TI Food safety and global security SO JOURNAL OF VETERINARY MEDICAL EDUCATION LA English DT Article; Proceedings Paper CT Conference on An Agenda for Action: Veterinary Medicines Role in Biodefense and Public Health CY NOV 01-03, 2002 CL WASHINGTON, D.C. C1 US FDA, Rockville, MD 20857 USA. RP Crawford, L (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU UNIV TORONTO PRESS INC PI TORONTO PA JOURNALS DIVISION, 5201 DUFFERIN ST, DOWNSVIEW, TORONTO, ON M3H 5T8, CANADA SN 0748-321X J9 J VET MED EDUC JI J. Vet. Med. Educ. PD SUM PY 2003 VL 30 IS 2 BP 110 EP 111 DI 10.3138/jvme.30.2.110 PG 2 WC Education, Scientific Disciplines; Veterinary Sciences SC Education & Educational Research; Veterinary Sciences GA 704WE UT WOS:000184363200006 PM 12970852 ER PT J AU Flowers, CM Racoosin, JA Lu, SL Beitz, JG AF Flowers, CM Racoosin, JA Lu, SL Beitz, JG TI The US Food and Drug Administration's registry of patients with pergolide-associated valuvular heart disease SO MAYO CLINIC PROCEEDINGS LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Flowers, CM (reprint author), 5600 Fishers Lane,HFD-430, Rockville, MD 20857 USA. NR 2 TC 52 Z9 56 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUN PY 2003 VL 78 IS 6 BP 730 EP 731 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 685NN UT WOS:000183270300009 PM 12934784 ER PT J AU Lopez, H AF Lopez, H TI Perspectives on image performance assessment I: Defining image performance criteria SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1360 EP 1360 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500181 ER PT J AU Suleiman, O Morin, R Poston, J AF Suleiman, O Morin, R Poston, J TI Terrorism and the medical physicist SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Mayo Clin, Jacksonville, FL 32224 USA. Texas A&M Univ, College Stn, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1371 EP 1371 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500230 ER PT J AU Moyal, A Spelic, D Kaczmarek, R AF Moyal, A Spelic, D Kaczmarek, R TI Preliminary results of the Nationwide Evaluation of X-ray Trends (NEXT) 2002 survey of A/P Abdomen and Lumbo-Sacral (LS) Spine Radiography SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1389 EP 1390 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500303 ER PT J AU Gagne, R AF Gagne, R TI Relationship of DQE to visual signal detection SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1403 EP 1403 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500362 ER PT J AU Thomas, J Chakrabarti, K Kaczmareck, R Romanyukha, A AF Thomas, J Chakrabarti, K Kaczmareck, R Romanyukha, A TI Effect of image surround and room illumination on contrast detail phantom interpretation (WIP) SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Ctr Devices & Radiol Hlth, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2003 VL 30 IS 6 BP 1439 EP 1440 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500523 ER PT J AU Thomas, J Chakrabarti, K Kaczmareck, R Romanyukha, A AF Thomas, J Chakrabarti, K Kaczmareck, R Romanyukha, A TI Comparison of Contrast-Detail scoring methodologies (WIP) SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Ctr Devices & Radiol Hlth, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2003 VL 30 IS 6 BP 1440 EP 1440 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500524 ER PT J AU Xu, B Bhattacharjee, A Roy, B Xu, HM Anthony, D Frank, DA Feldman, GM Cathcart, MK AF Xu, B Bhattacharjee, A Roy, B Xu, HM Anthony, D Frank, DA Feldman, GM Cathcart, MK TI Interleukin-13 induction of 15-lipoxygenase gene expression requires p38 mitogen-activated protein kinase-mediated serine 727 phosphorylation of Stat1 and Stat3 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN ATHEROSCLEROTIC PLAQUES; POLAR STEROL ESTERS; MAP KINASE; TRANSCRIPTIONAL ACTIVATION; JANUS KINASE; TYROSINE PHOSPHORYLATION; HUMAN MONOCYTES; GROWTH-HORMONE; C-DELTA; SER-727 PHOSPHORYLATION AB Interleukin-13 (IL-13) is a cytokine secreted by Th2 lymphocytes that is capable of inducing expression of 15-lipoxygenase (15-LO) in primary human monocytes. We recently demonstrated that induction of 15-LO requires the activation of Jak2 and Tyk2 kinases and Stats 1, 3, 5, and 6. Since IL-13-induced 15-LO expression was inhibited by H7 (a serine-threonine kinase inhibitor), we predicted that Stat serine phosphorylation may also be crucial for 15-LO expression. In this study, we present evidence indicating that IL-13-induced 15-LO mRNA expression was detectable as early as I h by real-time reverse transcription-PCR. We found that IL-13 induced a time-dependent serine phosphorylation of both Stat1 and Stat3, detectable at 15 min after IL-13 treatment. In addition, the activation of p38 mitogen-activated protein kinase (MAPK) was detected in a time-dependent fashion, with peak phosphorylation at 15 min after IL-13 treatment. SB202190, a p38 MAPK-specific inhibitor, markedly inhibited IL-13-induced Stat1 and Stat3 serine phosphorylation as well as DNA binding. Furthermore, treatment of cells with Stat1 or Stat3 decoys significantly impaired IL-13-induced 15-LO expression. Taken together, our results provide the first evidence that IL-13 induces p38 MAPK phosphorylation/activation, which regulates Stat1 and Stat3 serine 727 phosphorylation. Both of these events are important steps in IL-13-induced 15-LO expression in human monocytes. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. US FDA, Ctr Biolog Evaluat & Res, Off Therapeut Res & Review, Bethesda, MD 20892 USA. RP Cathcart, MK (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NHLBI NIH HHS [HL51068] NR 64 TC 61 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2003 VL 23 IS 11 BP 3918 EP 3928 DI 10.1128/MCB.23.11.3918-3928.2003 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 681HZ UT WOS:000183031900018 PM 12748293 ER PT J AU Westergaard, GC Suomi, SJ Chavanne, TJ Houser, L Hurley, A Cleveland, A Snoy, PJ Higley, JD AF Westergaard, GC Suomi, SJ Chavanne, TJ Houser, L Hurley, A Cleveland, A Snoy, PJ Higley, JD TI Physiological correlates of aggression and impulsivity in free-ranging female primates SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin; 5-HIAA; aggression; Macaca mulatta; females; impulsivity ID FLUID AMINE METABOLITES; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; CEREBROSPINAL-FLUID; CSF 5-HIAA; SEROTONERGIC RESPONSIVITY; HEALTHY-VOLUNTEERS; VIOLENT OFFENDERS; RHESUS-MONKEYS; FIRE SETTERS; INTERINDIVIDUAL DIFFERENCES AB We examined the relations among cerebrospinal fluid (CSF) monoamine metabolite concentrations, plasma hormone concentrations, aggression, and impulsive risk-taking behavior in a free-ranging population of female rhesus macaques. We selected 44 juvenile female rhesus macaques as subjects from a population of approximately 3000 macaques that inhabit a 475-acre Sea Island. We obtained CSF and blood samples, and recorded behavioral observations over a subsequent 18-month period. Our results indicate an inverse correlation between CSF concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the frequency of low-intensity restrained aggression typically associated with matrilineal defense of social status. In contrast, previous research with males has shown an inverse correlation between CSF 5-HIAA concentrations and levels of violent unstrained aggression typically associated with traumatic injury and death. We also noted a negative correlation between plasma concentrations of the stress hormone cortisol and the frequency of low-intensity aggressive acts, a finding not reported in our previous studies with males. Further examination revealed a negative correlation between CSF 5-HIAA concentrations and the rate of long dangerous leaps through the forest canopy, suggesting that the relation between low serotonergic functioning and impulsivity may generalize to both female and male primates. These results indicate that females with low CSF 5-HIAA concentrations, like their male counterparts, are at increased risk for impulsive temperament, but that unlike males, females may be buffered from this risk through intersexual differences in life history patterns and social affiliation. C1 LABS Virginia Inc, Div Res & Dev, Yemassee, SC 29945 USA. NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Westergaard, GC (reprint author), LABS Virginia Inc, Div Res, 95 Castle Hall Rd,POB 557, Yemassee, SC 29945 USA. FU NIAAA NIH HHS [N01AA02018] NR 59 TC 55 Z9 55 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2003 VL 28 IS 6 BP 1045 EP 1055 DI 10.1038/sj.npp.1300171 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 686HT UT WOS:000183316100004 PM 12700686 ER PT J AU Bowyer, JF Young, JF Slikker, W Itzak, Y Mayorga, AJ Newport, GD Ali, SF Frederick, DL Paule, MG AF Bowyer, JF Young, JF Slikker, W Itzak, Y Mayorga, AJ Newport, GD Ali, SF Frederick, DL Paule, MG TI Plasma levels of parent compound and metabolites after doses of either d-fenfluramine or d-3,4-methylenedioxymethamphetamine (MDMA) that produce long-term serotonergic alterations SO NEUROTOXICOLOGY LA English DT Article DE pharmacokinetics; fenfluramine; methylenedioxymethamphetamine; primates; behaviour and neurotoxicity; ecstasy ID BRAIN-SEROTONIN; 3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; METHYLENEDIOXYMETHAMPHETAMINE MDMA; NONHUMAN-PRIMATES; RHESUS-MONKEYS; PULMONARY-HYPERTENSION; BODY-TEMPERATURE; NERVE-TERMINALS; RISK ASSESSMENT; TEST BATTERY AB Plasma levels of parent compounds and metabolites were determined in adult rhesus monkeys after doses of either 5 mg/kg d-fenfluramine (FEN) or 10 mg/kg d-3, 4-methylenedioxymethamphetamine (MDMA) i.m. twice daily for four consecutive days. These treatment regimens have been previously shown to produce long-term serotonin (5-HT) depletions. Peak plasma levels of 2.0 +/- 0.4 muM FEN were reached within 40 min after the first dose of FEN, and then declined rapidly, while peak plasma levels (0.4 +/- 0.1 muM) of the metabolite norfenfluramine (NFEN) were not reached until 6 h after dosing. After the seventh (next to last) dose of FEN, peak plasma levels of FEN were 35% greater than after the first dose while peak NFEN-levels were 500% greater The t(1/2) for FEN was 2.6 +/- 0.3 h after the first dose and 3.2 +/- 0.2 h after the seventh. The estimated t(1/2) for NFEN was more than 37.6 +/- 20.5 h. Peak plasma levels of 9.5 +/- 2.5 muM MDMA were reached within 20 min after the first dose of MDMA, and then declined rapidly, while peak plasma levels (0.9 +/- 0.2 muM) of the metabolite 3,4-methylenedioxyamphetamine (MDA) were not reached until 3-6 h after dosing. After the seventh (next to last) dose of MDMA, peak plasma levels of MDMA were 30% greater than the first dose while peak MDA levels were elevated over 200%. The t(1/2) for MDMA was 2.8 +/- 0.4 h after the first and 3.9 +/- 1.1 h after the seventh dose. The estimated t(1/2)for MDA was about 8.3 +/- 1.0 h. Variability in plasma levels of MDMA and MDA between subjects was much greater than that for FEN and NFEN. This variability in MDMA and MDA exposure levels may have lead to variability in the subsequent disruption of some behaviors seen in these same subjects. There were 80% reductions in the plasma membrane-associated 5-HT transporters 6 months after either the FEN or MDMA dosing regimen indicating that both treatments produced long-term serotonergic effects. (C) 2003 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol & Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27516 USA. RP Bowyer, JF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol & Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 59 TC 29 Z9 29 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2003 VL 24 IS 3 BP 379 EP 390 DI 10.1016/S0161-813X(03)00030-5 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 691CK UT WOS:000183587100006 PM 12782103 ER PT J AU Seligman, PJ AF Seligman, PJ TI 'Dear Doctor... ' - Evaluating the impact of risk communication efforts SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material C1 US FDA, Off Pharmacoepidemiol & Stat Sci Ctr, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Seligman, PJ (reprint author), US FDA, Off Pharmacoepidemiol & Stat Sci Ctr, Ctr Drug Evaluat & Res, 5600 Fishers Lane,Room 15B-03, Rockville, MD 20857 USA. NR 7 TC 5 Z9 5 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUN PY 2003 VL 12 IS 4 BP 291 EP 293 DI 10.1002/pds.829 PG 3 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 685WM UT WOS:000183287100005 PM 12812008 ER PT J AU Koller, EA Cross, JT Doraiswamy, PM Schneider, BS AF Koller, EA Cross, JT Doraiswamy, PM Schneider, BS TI Risperidone-associated diabetes mellitus: A Pharmacovigilance Study SO PHARMACOTHERAPY LA English DT Review ID ANTIPSYCHOTIC-DRUGS; PC12 CELLS; INSULIN; QUETIAPINE; CLOZAPINE; HYPERGLYCEMIA; SCHIZOPHRENIA; PSYCHOSES; WEIGHT; LEPTIN AB Study Objective. To explore the clinical characteristics of hyperglycemia in patients treated with risperidone. Design. Pharmacovigilance survey of spontaneously reported adverse events in risperidone-treated patients, with reports of haloperidol-associated hyperglycemia used as a control. Setting. Government-affiliated drug evaluation center. Intervention. The Food and Drug Administration MedWatch surveillance program was queried (risperidone, 1993-February 2002; haloperidol, late 1970s-February 2002) and results pooled with published cases. Measurements and Main Results. We identified 131 reports of risperidone-associated hyperglycemia in addition to seven reports of patients with hyperglycemia who received combined risperidone-haloperidol therapy and six reports of acidosis that occurred in the absence of hyperglycemia. We found 13 reports of haloperidol-associated hyperglycemia and 11 reports of acidosis without hyperglycemia. Of the reports of risperidone-associated hyperglycemia (monotherapy), 78 patients had newly diagnosed hyperglycemia, 46 had exacerbated preexisting diabetes, and 7 could not be classified. Mean +/- SD age was 39.8 +/- 17.4 years (range 8-96 yrs). Patients with new-onset diabetes (mean +/- SD age 34.8 +/- 15.7 yrs) were younger than those with preexisting diabetes (mean +/- SD age 48.8 +/- 17.5 yrs). The overall male:female ratio was 1.5. In most patients, hyperglycemia appeared within 3 months of the start of risperidone therapy. Severity of disease ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. Twenty-six patients with acidosis or ketosis were reported. Four patients died. Conclusion. Atypical antipsychotic treatment may unmask or precipitate hyperglycemia. Although such cases attributed to clozapine or olanzapine are more numerous than those associated with risperidone, the number for risperidone-associated hyperglycemia is relatively higher than that observed with the conventional neuroleptic haloperidol. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Doraiswamy, PM (reprint author), Duke Univ, Med Ctr, Dept Psychiat, DUMC Box 3018, Durham, NC 27710 USA. NR 47 TC 113 Z9 115 U1 0 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUN PY 2003 VL 23 IS 6 BP 735 EP 744 DI 10.1592/phco.23.6.735.32178 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 684UH UT WOS:000183224600007 PM 12820816 ER PT J AU Fang, GC Chang, CN Chu, CC Wu, YS Fu, PPC Yang, IL Chen, MH AF Fang, GC Chang, CN Chu, CC Wu, YS Fu, PPC Yang, IL Chen, MH TI Characterization of particulate, metallic elements of TSP, PM2.5 and PM2.5-10 aerosols at a farm sampling site in Taiwan, Taichung SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article DE TSP; PM2.5; PM2.5-10; heavy metal; PCA ID SIZE DISTRIBUTIONS; TRACE-METALS; DEPOSITION; PARTICLES; MATTER AB Atmospheric aerosol particles and metallic concentrations were monitored at the Experimental Farm of Tunghai University (EFTU) sampling site in this study. Total suspended particulate matter (TSP) was collected by using a PS-I sampler at the farm-sampling site, in central Taiwan, from July 2001 to April 2002. At the same time, PM2.5 and PM2.5-10 were also measured with a Universal sampler from January 2002 to April 2002. Only subjects with the most complete data records on TSP sampling (N=43) and PM10 sampling (N=23) were used in this analysis. Taichung Industrial Park, Taichung Kang Road (traffic) and a Hospital Incinerator surround the Experimental Farm of Tunghai University. Atmospheric concentrations of metallic elements were analyzed by a flame atomic absorption spectrophotometer (AA-680/G). The results indicated that the metallic elements Mg, Cu and Mn were the largest components in the TSP fraction; the metallic elements Fe and Cd were the largest composition in the PM2.5-10 fraction; however, the metallic elements Ph, Zn, Cr and Ni were the largest abundance in the PM2.5 fraction. The atmospheric metallic elements in the TSP, PM2.5 and PM2.5-10 fractions came different emission sources, such as soil, traffic, industry and resuspended particles. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Hungkuang Inst technol, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. Chien Yu Reg Teaching Hosp, Chief Intens Care Unit, Dept Internal Med, Kaohsiung 832, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, GC (reprint author), Hungkuang Inst technol, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. NR 16 TC 80 Z9 83 U1 6 U2 42 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 JUN 1 PY 2003 VL 308 IS 1-3 BP 157 EP 166 AR PII S0048-9697(02)00648-4 DI 10.1016/S0048-9697(02)00648-4 PG 10 WC Environmental Sciences SC Environmental Sciences & Ecology GA 681QW UT WOS:000183047700013 PM 12738209 ER PT J AU MacGregor, JT AF MacGregor, JT TI SNPs and chips: Genomic data in safety evaluation and risk assessment SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material ID PHARMACOGENETICS C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP MacGregor, JT (reprint author), US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 2 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2003 VL 73 IS 2 BP 207 EP 208 DI 10.1093/toxsci/kfg099 PG 2 WC Toxicology SC Toxicology GA 681MP UT WOS:000183040200001 PM 12700407 ER PT J AU Goering, PL AF Goering, PL TI The road to elucidating the mechanism of manganese-bilirubin-induced cholestasis SO TOXICOLOGICAL SCIENCES LA English DT Article ID MEMBRANES AB The article highlighted in this issue is "Synergistic Role of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase and Cholesterol 7alpha-Hydroxylase in the Pathogenesis of Manganese-Bilirubin-Induced Cholestasis in Rats," by Marie-Yvonne Akoume, Shahid Perwaiz, Ibrahim A Yousef, and Gabriel L. Plaa (pp. 331-338). C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 7 TC 2 Z9 2 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 JUN PY 2003 VL 73 IS 2 BP 216 EP 219 DI 10.1093/toxsci/kfg112 PG 4 WC Toxicology SC Toxicology GA 681MP UT WOS:000183040200003 PM 12778929 ER PT J AU Shankar, K Vaidya, VS Apte, UM Manautou, JE Ronis, MJJ Bucci, TJ Mehendale, HM AF Shankar, K Vaidya, VS Apte, UM Manautou, JE Ronis, MJJ Bucci, TJ Mehendale, HM TI Type 1 diabetic mice are protected from acetaminophen hepatotoxicity SO TOXICOLOGICAL SCIENCES LA English DT Article DE covalent binding; CYP2E1; diabetes; species differences; tissue repair ID SELECTIVE PROTEIN ARYLATION; INDUCED HEPATIC NECROSIS; CARBON-TETRACHLORIDE HEPATOTOXICITY; ANTIMITOTIC AGENT COLCHICINE; POSTNATALLY DEVELOPING RATS; TISSUE-REPAIR UNDERLIES; BINDING LIVER PROTEINS; COVALENT BINDING; DECREASED SUSCEPTIBILITY; CULTURED-HEPATOCYTES AB Streptozotocin (STZ)-induced diabetic (DB) mice challenged with single ordinarily lethal doses of acetaminophen (APAP), carbon tetrachloride (CCl4), or bromobenzene (BB) were resistant to all three hepatotoxicants. Mechanisms of protection against APAP hepatotoxicity were investigated. Plasma alanine aminotransferase, aspartate aminotransferase, and liver histopathology revealed significantly lower hepatic injury in DB mice after APAP administration. HPLC analysis of plasma and urine revealed lower plasma t(1/2), increased volume of distribution (V-d) and increased plasma clearance (CLp) of APAP in the DB mice and no difference in APAP-glucuronide, a major metabolite in mice. Interestingly, covalent binding of C-14-labeled APAP to liver target proteins; arylation of APAP to 58, 56, and 44 kDa acetaminophen binding proteins (ABPs); and glutathione (GSH) depletion in the liver did not differ between nondiabetic (non-DB) and DB mice in spite of downregulated hepatic microsomal CYP2E1 and 1A2 proteins in, the DB mice, known to be involved in bioactivation of APAP. Compensatory cell division measured via H-3-thymidine pulse labeling and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) indicated earlier onset of S-phase in the DB mice after exposure to APAP. Antimitotic intervention of liver cell division by colchicine (CLC) after administration of APAP led to significantly higher mortality in the DB mice suggesting a pivotal role of liver cell division and tissue repair in the protection afforded by diabetes. In conclusion, the resistance of DB mice against hepatotoxic and lethal effects of APAP appears to be mediated by a combination of enhanced APAP clearance and robust compensatory tissue repair. C1 Univ Louisiana Monroe, Sch Pharm, Dept Toxicol, Monroe, LA 71209 USA. Univ Connecticut, Coll Pharm, Dept Pharmaceut Sci, Storrs, CT 06269 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72202 USA. Pathol Associates Int, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Sch Pharm, Dept Toxicol, Sugar Hall 306, Monroe, LA 71209 USA. NR 83 TC 33 Z9 34 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2003 VL 73 IS 2 BP 220 EP 234 DI 10.1093/toxsci/kfg059 PG 15 WC Toxicology SC Toxicology GA 681MP UT WOS:000183040200004 PM 12700423 ER PT J AU Sotomayor, RE Washington, M Nguyen, L Nyang'anyi, R Hinton, DM Chou, M AF Sotomayor, RE Washington, M Nguyen, L Nyang'anyi, R Hinton, DM Chou, M TI Effects of intermittent exposure to aflatoxin B-1 on DNA and RNA adduct formation in rat liver: Dose-response and temporal patterns SO TOXICOLOGICAL SCIENCES LA English DT Article DE intermittent exposure; aflatoxin B-1; DNA and RNA adducts; liver; rats ID GLUTATHIONE-S-TRANSFERASE; CANCER-RISK ASSESSMENT; BINDING; INVITRO; DEGRADATION; METABOLISM; INDUCTION; B1-DNA; INVIVO; MOUSE AB We studied the effects of intermittent exposure to aflatoxin B-1 (AFB(1)) on hepatic DNA and RNA adduct formation. Fisher-344 male rats were fed 0.01, 0.04, 0.4, or 1.6 ppm. of AFB(1) intermittently for 8, 12, 16, and 20 weeks, alternating with 4 weeks of dosing and 4 weeks of rest. Other groups of rats were fed 1.6 ppm of AFB(1) continuously for 4, 8, 12, and 16 weeks. Control rats received AFB(1)-free NIH-31 meal diet. AFB(1)-DNA and -RNA adducts were measured by HPLC with fluorescence detection. The data are presented as total DNA or RNA adducts. The DNA and RNA adduct levels increased or decreased depending on the cycles of dosing and rest. Rats removed from treatment 1 month after I or 2 dosing cycles (8 and 16 weeks of intermittent exposure) showed approximately a twofold decrease in DNA adduct levels and a two- to elevenfold decrease in RNA adduct levels compared with rats euthanized immediately after the last dosing cycle (12 and 20 weeks of intermittent exposure). Our data indicate that DNA and RNA adducts increased linearly, from 0.01 ppm to 1.6 ppm of AFB(1) after 12 and 20 weeks of intermittent treatment. A linear dose response was also apparent for DNA but not for RNA adducts after 8 and 16 weeks of treatment. As biomarkers of exposure, AFB(1)-RNA adducts were three to nine times more sensitive than AFB(1)-DNA adducts but showed greater variability. These results suggest that binding of AFB(1) to hepatic DNA is a linear function of the dose, regardless of the way this is administered. The dose-response relationship for RNA adducts depends on the length of the no-dosing cycles and on the turnover rate of RNA. C1 Univ Maryland, US FDA, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Univ Maryland, Ctr Food Safety & Appl Nutr, College Pk, MD 20742 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sotomayor, RE (reprint author), US FDA, 5100 Paint Branch Pkwy,HFS-275, College Pk, MD 20740 USA. NR 40 TC 10 Z9 12 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2003 VL 73 IS 2 BP 329 EP 338 DI 10.1093/toxsci/kfg076 PG 10 WC Toxicology SC Toxicology GA 681MP UT WOS:000183040200013 PM 12700393 ER PT J AU Hinton, DM Myers, MJ Raybourne, RA Francke-Carroll, S Sotomayor, RE Shaddock, J Warbritton, A Chou, MW AF Hinton, DM Myers, MJ Raybourne, RA Francke-Carroll, S Sotomayor, RE Shaddock, J Warbritton, A Chou, MW TI Immunotoxicity of aflatoxin B-1 in rats: Effects on lymphocytes and the inflammatory response in a chronic intermittent dosing study SO TOXICOLOGICAL SCIENCES LA English DT Article DE aflatoxin B-1; immunotoxicity; inflammatory response; intermittent dosing ID HEPATOCELLULAR-CARCINOMA; SPLENIC LYMPHOCYTES; CYTOKINE PRODUCTION; BROILER-CHICKENS; RISK ASSESSMENT; CANCER RISK; LIVER; SWINE; HEPATOTOXICITY; MACROPHAGES AB We investigated the effects of aflatoxin B-1 (AFB(1)) on isolated splenic lymphocytes and the histo-morphologic changes in the spleens and liver of Fisher-344 male rats. Weaned animals were fed chow diets that contained 0, 0.01, 0.04, 0.4, or 1.6 ppm AFB(1), using an intermittent dosing regimen (4 weeks on and 4 weeks off AFB(1)), for 40 weeks. An additional group of animals was fed the 1.6 ppm AFB(1) diet continuously. The intermittent dosing regimen was designed to evaluate effects of cumulative dose and exposure for risk assessment comparisons. The percentages of T and B cells were affected as shown by flow cytometric analysis after the dosing cycles. The observed changes appeared to reverse or compensate to some extent after the off cycles. Lymphocytes were stimulated in culture for analysis of the production of IL-2, IL-1, and IL-6. Significantly increased production of IL-1 and IL-6 was seen in the second dosing cycle (12 weeks) and the second "off" cycle (16 weeks) at the higher doses. Inflammatory infiltrates were seen in the liver after eight weeks of continuous and intermittent dosing and were increased in size and number at 12 weeks in both 1.6 ppm dose groups correlating with the peak production of Il-1 and IL-6. We concluded that AFB(1) effects on the immune system can be either stimulatory or suppressive dependent on a critical exposure window of dose and time. Immune cells in spleen such as T-lymphocytes and macrophages, both important mediators of inflammatory responses to tissue damage, were affected differently in the continuous and intermittent exposures to AFB(1). C1 US FDA, CFSAN, Module Res Labs 1, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hinton, DM (reprint author), US FDA, CFSAN, Module Res Labs 1, Laurel, MD 20708 USA. NR 47 TC 49 Z9 53 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2003 VL 73 IS 2 BP 362 EP 377 DI 10.1093/toxsci/kfg074 PG 16 WC Toxicology SC Toxicology GA 681MP UT WOS:000183040200016 PM 12700391 ER PT J AU Volpe, DA Warren, MK AF Volpe, DA Warren, MK TI Myeloid clonogenic assays for comparison of the in vitro toxicity of alkylating agents SO TOXICOLOGY IN VITRO LA English DT Article DE myelotoxicity; clonal assays; alkylators; neutropenia; progenitor cells; myeloid ID HEMATOPOIETIC PROGENITOR CELLS; HEMATOLOGICAL TOXICITY; DIFFERENTIAL TOXICITY; INVITRO MYELOTOXICITY; MURINE; PHARMACOKINETICS; CANINE; 3'-AZIDO-3'-DEOXYTHYMIDINE; THERAPY; MARROW AB A battery of clonal assays for myeloid progenitor cells (HPP-CFC, CFU-gemm, CFU-gm, CFU-g) was utilized to evaluate the myelotoxicity of a series of alkylating agents representing the spectrum of clinical times to nadir. Bone marrow aspirates from normal volunteers were incubated with mechlorethamine, busulfan, melphalan, carmustine or lomustine for 1 h and then cultured in methylcellulose with 30% serum and cytokines. There was a concentration-dependent inhibition of colony formation and often a differential toxicity to the myeloid progenitors with the alkylators tested. On a molar basis, mechlorethamine and melphalan were the most toxic of the alkylator drugs to the myeloid precursors. The most sensitive progenitor was CFU-gemm with the lowest inhibitory concentration IC70 concentrations for mechlorethamine, melphalan, carmustine and lomustine. Generally, there was great similarity for drug effects between CFU-g and CFU-gm with overlapping inhibition curves. HPP-CFC proved to be the least sensitive of the progenitors to the toxic actions of the drugs. While there was no correlation between the time to clinical neutropenic nadir and the most sensitive progenitor in the clonal assays, the CFU-gm assay remains a suitable method for determining the myelotoxic potential of cytotoxic agents. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Poiet Technol Inc, Gaithersburg, MD USA. RP Volpe, DA (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 25 TC 10 Z9 13 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD JUN PY 2003 VL 17 IS 3 BP 271 EP 277 DI 10.1016/S0887-2333(03)00012-2 PG 7 WC Toxicology SC Toxicology GA 693VB UT WOS:000183738100004 PM 12781205 ER PT J AU Biswas, R Tabor, E Hsia, CC Wright, DJ Laycock, ME Fiebig, EW Peddada, L Smith, R Schreiber, GB Epstein, JS Nemo, GJ Busch, MP AF Biswas, R Tabor, E Hsia, CC Wright, DJ Laycock, ME Fiebig, EW Peddada, L Smith, R Schreiber, GB Epstein, JS Nemo, GJ Busch, MP TI Comparative sensitivity of HBVNATs and HBsAg assays for detection of acute HBV infection SO TRANSFUSION LA English DT Article ID HEPATITIS-B VIRUS; BLOOD-TRANSFUSION; VIRAL-INFECTIONS; NAT; PREVALENCE; DONORS; SAFETY; RISK AB BACKGROUND: A study was designed to estimate relative analytic sensitivity and window-period (WP) closure and to project incremental yield of newer HBsAg tests, pooled-sample NAT, and single-sample NAT, compared to currently licensed HBsAg tests. STUDY DESIGN AND METHODS: HBV DNA and HBsAg test results for 23 HBV seroconversion (SC) panels were first analyzed to construct a model of primary HBV viremia. One-hundred representative samples were then selected from 10 panels and coded with 28 analytical controls. All 128 samples were tested by seven HBsAg tests and by four pooled-sample and three single-sample NAT assay formats. Results were analyzed to obtain differential times to HBV detection and combined with HBV incidence rates to project comparative yields. RESULTS: HBV doubling time during the ramp-up phase was estimated at 2.56 days. HBsAg concentrations at cutoff for new tests ranged from 0.07 to 0.12 ng per mL, compared with 0.13 to 0.62 ng per mL for licensed tests. Estimated viral load at cutoff ranged from 102 to 267 IU per mL for new tests and from 363 to 1069 IU per mL for licensed tests. HBsAg tests detected 31 to 63 percent of early ramp-up phase samples in the 100-member seroconversion panel study, while pooled-sample NAT detected 55 to 71 percent and single-sample NAT, 82 to 99 percent. Compared with currently licensed HBsAg assays, newer HBsAg assays would reduce the WP by 2 to 9 days; pooled-sample NAT would reduce the WP by 9 to 11 days; and single-sample NAT would reduce the WP by 25 to 36 days. CONCLUSION: Newer HBsAg tests would be expected to detect an additional 15 to 21 infected units per 107 donations, compared to licensed HBsAg tests. Sensitivity, WP closure, and yield projections for newer HBsAg assays and pooled-sample NAT are comparable. Single-sample NAT would increase yield by 13 to 15 units per 107 donations over pooled-sample NAT and newer HBsAg assays and by 35 to 50 units per 107 donations over currently licensed HBsAg assays. C1 Univ Calif San Francisco, Blood Ctr Pacific, San Francisco, CA 94118 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Westat Corp, Rockville, MD USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Alpha Therapeut Corp, Los Angeles, CA USA. Natl Genet Inst, Los Angeles, CA USA. NHLBI, Bethesda, MD 20892 USA. Blood Syst Inc, Scottsdale, AZ USA. RP Busch, MP (reprint author), Univ Calif San Francisco, Blood Ctr Pacific, 270 Masonic Ave, San Francisco, CA 94118 USA. NR 26 TC 169 Z9 191 U1 0 U2 4 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2003 VL 43 IS 6 BP 788 EP 798 DI 10.1046/j.1537-2995.2003.00424.x PG 11 WC Hematology SC Hematology GA 682YB UT WOS:000183119000017 PM 12757531 ER PT J AU da Silva, M Cerniglia, CE Pothuluri, JV Canhos, VP Esposito, E AF da Silva, M Cerniglia, CE Pothuluri, JV Canhos, VP Esposito, E TI Screening filamentous fungi isolated from estuarine sediments for the ability to oxidize polycyclic aromatic hydrocarbons SO WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE bioremediation; filamentous fungi; mycoremediation; PAH mixture; pyrene ID WHITE-ROT FUNGUS; WOOD-DECAYING FUNGI; PYRENE MINERALIZATION; NEMATOLOMA-FROWARDII; ASPERGILLUS-NIGER; SOIL FUNGI; METABOLISM; BIODEGRADATION; DEGRADATION; PHENANTHRENE AB Nineteen. lamentous fungi, isolated from estuarine sediments in Brazil, were screened for degradation of polycyclic aromatic hydrocarbons (PAH). The fungal isolates were incubated with pyrene. The cultures were extracted and metabolites in the extracts were detected by high performance liquid chromatography (HPLC) and u.v. spectral analyses. Six fungi were selected for further studies using [4,5,9,10-C-14] pyrene. Cyclothyrium sp., Penicillium simplicissimum, Psilocybe sp., and a sterile mycelium demonstrated the ability to transform pyrene. Cyclothyrium sp. was the most efficient fungus, transforming 48% of pyrene to pyrene trans-4,5-dihydrodiol, pyrene-1,6-quinone, pyrene-1,8-quinone and 1-hydroxypyrene. This fungus was also evaluated with a synthetic mixture of PAH. After 192 h of incubation, Cyclothyrium sp. was able to degrade simultaneously 70, 74, 59 and 38% of phenanthrene, pyrene, anthracene and benzo[a]pyrene, respectively. C1 State Univ Campinas, Sch Food Engn, Dept Food Sci, BR-13083970 Campinas, SP, Brazil. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Univ Mogi Cruzes, Dept Environm Sci, BR-08780911 Mogi Das Cruzes, SP, Brazil. RP da Silva, M (reprint author), Fdn Oswaldo Cruz, INCQS, Dept Microbiol, 4365 Ave Brasil, BR-21045900 Rio De Janeiro, Brazil. RI da Silva, Manuela/M-6211-2015 OI da Silva, Manuela/0000-0001-6073-8929 NR 42 TC 26 Z9 27 U1 1 U2 28 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0959-3993 J9 WORLD J MICROB BIOT JI World J. Microbiol. Biotechnol. PD JUN PY 2003 VL 19 IS 4 BP 399 EP 405 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 684KF UT WOS:000183204800010 ER PT J AU Marszal, E Danino, D Shrake, A AF Marszal, E Danino, D Shrake, A TI A novel mode of polymerization of alpha(1)-proteinase inhibitor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; ALPHA-1-PROTEINASE INHIBITOR; CIRCULAR-DICHROISM; CRYSTAL-STRUCTURE; CONFORMATIONAL DISEASE; ALPHA-1-ANTITRYPSIN; ALPHA(1)-ANTITRYPSIN; SERPINS; LIVER; DEFICIENCY AB Patients homozygous for the Z mutant form of alpha(1)-proteinase inhibitor (alpha(1)-PI) have an increased risk for the development of liver disease because of the accumulation in hepatocytes of inclusion bodies containing linear polymers of mutant alpha(1)-PI. The most widely accepted model of polymerization proposes that a linear, head-to-tail polymer forms by sequential insertion of the reactive center loop (RCL) of one alpha(1)-PI monomer between the central strands of the A beta-sheet of an adjacent monomer. This model derives primarily from two observations: peptides that are homologous with the RCL insert into the A beta-sheet of alpha(1)-PI monomer and this insertion prevents alpha(1)-PI polymerization. Normal alpha(1)-PI monomer does not spontaneously polymerize; however, here we show that the disulfide-linked dimer of normal alpha(1)-PI spontaneously forms linear polymers in buffer. The monomers within this dimer are joined head-to-head. Thus, the arrangement of monomers in these polymers must be different from that predicted by the loop-A sheet model. Therefore, we propose a new model for alpha(1)-PI polymer. In addition, polymerization of disulfide-linked dimer is not inhibited by the presence of the peptide even though dimer appears to interact with the peptide. Thus, RCL insertion into A beta-sheets may not occur during polymerization of this dimer. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Shrake, A (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. RI Danino, Dganit/D-6832-2016 OI Danino, Dganit/0000-0002-9782-4940 NR 58 TC 9 Z9 11 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 MAY 30 PY 2003 VL 278 IS 22 BP 19611 EP 19618 DI 10.1074/jbc.M210720200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 682EH UT WOS:000183078000008 PM 12649292 ER PT J AU Iwamoto, M Jernigan, DB Guasch, A Trepka, MJ Blackmore, CG Hellinger, WC Pham, SM Zaki, S Lanciotti, RS Lance-Parker, SE DiazGranados, CA Winquist, AG Perlino, CA Wiersma, S Hillyer, KL Goodman, JL Marfin, AA Chamberland, ME Petersen, LR Blake, P Bower, W Dowdy, L Fleming, J Guarner, J Jimenez, J Kuehnert, M Leguen, F Luu, T Mallon, S Moseley, R Nejman, A Page, P Pealer, L Qi, XS Rico, E Roehrig, J Rollin, P Salameh, M Shieh, WJ Tso, P Withum, D AF Iwamoto, M Jernigan, DB Guasch, A Trepka, MJ Blackmore, CG Hellinger, WC Pham, SM Zaki, S Lanciotti, RS Lance-Parker, SE DiazGranados, CA Winquist, AG Perlino, CA Wiersma, S Hillyer, KL Goodman, JL Marfin, AA Chamberland, ME Petersen, LR Blake, P Bower, W Dowdy, L Fleming, J Guarner, J Jimenez, J Kuehnert, M Leguen, F Luu, T Mallon, S Moseley, R Nejman, A Page, P Pealer, L Qi, XS Rico, E Roehrig, J Rollin, P Salameh, M Shieh, WJ Tso, P Withum, D CA West Nile Virus Transplant Recipie TI Transmission of West Nile virus from an organ donor to four transplant recipients SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NEW-YORK-CITY; ENCEPHALITIS; OUTBREAK; INFECTION; EPIDEMIC; DIAGNOSIS AB BACKGROUND: In August 2002, fever and mental-status changes developed in recipients of organs from a common donor. Transmission of West Nile virus through organ transplantation was suspected. METHODS: We reviewed medical records, conducted interviews, and collected blood and tissue samples for testing with a variety of assays. Persons who donated blood to the organ donor and associated blood components were identified and tested for West Nile virus. RESULTS: We identified West Nile virus infection in the organ donor and in all four organ recipients. Encephalitis developed in three of the organ recipients, and febrile illness developed in one. Three recipients became seropositive for West Nile virus IgM antibody; the fourth recipient had brain tissue that was positive for West Nile virus by isolation and nucleic acid and antigen assays. Serum specimens obtained from the organ donor before and immediately after blood transfusions showed no evidence of West Nile virus; however, serum and plasma samples obtained at the time of organ recovery were positive on viral nucleic acid testing and viral culture. The organ donor had received blood transfusions from 63 donors. A review of blood donors and follow-up testing identified one donor who had viremia at the time of donation and who became seropositive for West Nile virus IgM antibodies during the next two months. CONCLUSIONS: Our investigation of this cluster documents the transmission of West Nile virus by organ transplantation. Organ recipients receiving immunosuppressive drugs may be at high risk for severe disease after West Nile virus infection. Blood transfusion was the probable source of the West Nile virus viremia in the organ donor. C1 Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv, Natl Ctr Infect Dis, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Appl Publ Hlth Training, Natl Ctr Infect Dis, Atlanta, GA USA. Ctr Dis Control & Prevent, Epidemiol Program Off, Natl Ctr Infect Dis, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Atlanta, GA USA. Emory Univ, Sch Med, Atlanta, GA USA. Florida Dept Hlth, Tallahassee, FL USA. Mayo Clin, Jacksonville, FL 32224 USA. Univ Miami, Miami, FL 33152 USA. Georgia Dept Human Resources, Div Publ Hlth, Atlanta, GA USA. Amer Red Cross, Blood Serv, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. RP Iwamoto, M (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, 1600 Clifton Rd,MS A35, Atlanta, GA 30333 USA. RI Guarner, Jeannette/B-8273-2013 NR 22 TC 357 Z9 378 U1 1 U2 18 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 29 PY 2003 VL 348 IS 22 BP 2196 EP 2203 DI 10.1056/NEJMoa022987 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 683EK UT WOS:000183134700005 PM 12773646 ER PT J AU Winter-Vann, AM Kamen, BA Bergo, MO Young, SG Melnyk, S James, SJ Casey, PJ AF Winter-Vann, AM Kamen, BA Bergo, MO Young, SG Melnyk, S James, SJ Casey, PJ TI Targeting Ras signaling through inhibition of carboxyl methylation: An unexpected property of methotrexate SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID S-ADENOSYLMETHIONINE; PLASMA HOMOCYSTEINE; MEMBRANE ASSOCIATION; K-RAS; CANCER; CELLS; ADENOSYLHOMOCYSTEINE; METHYLTRANSFERASE; PROTEIN; MISLOCALIZATION AB The antifolate methotrexate is one of the most successful drugs in cancer chemotherapy. Although its efficacy is widely attributed to a decrease in nucleotide biosynthesis (1), methotrexate is known to increase homocysteine (2), a compound associated with an elevated risk of heart disease, Alzheimer's disease (3), and neural tube defects (4). A potential mechanism for the detrimental effects of homocysteine is cellular hypomethylation from an increase in S-adenosylhomocysteine (5), an inhibitor of methyltransferases including isoprenylcysteine carboxyl methyltransferase (Icmt). Among the substrates of Icmt is the monomeric G protein Ras, a critical component of many signaling pathways that regulate cell growth and differentiation. Because carboxyl methylation of Ras is important for proper plasma membrane localization and function (6), we investigated the role of Icmt in the antiproliferative effect of methotrexate. After methotrexate treatment of DKOB8 cells, Ras methylation is decreased by almost 90%. This hypomethylation is accompanied by a mislocalization of Ras to the cytosol and a 4-fold decrease in the activation of p44 mitogen-activated protein kinase and Akt. Additionally, cells lacking Icmt are highly resistant to methotrexate. Whereas cells expressing wild-type levels of Icmt are inhibited by methotrexate, stable expression of myristoylated H-Ras, which does not require carboxyl methylation for membrane attachment (7), confers resistance to methotrexate. These results suggest that inhibition of Icmt is a critical component of the anti proliferative effect of methotrexate, expanding our understanding of this widely used drug and identifying Icmt as a target for drug discovery. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Canc Inst New Jersey, New Brunswick, NJ 08901 USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, Cardiovasc Res Inst, San Francisco, CA 94141 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94141 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Casey, PJ (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, LSRC Bldg,Room C133,Res Drive, Durham, NC 27710 USA. FU NHLBI NIH HHS [HL41633, P01 HL041633]; NIA NIH HHS [AG15451]; NIGMS NIH HHS [GM46372, R01 GM046372] NR 36 TC 86 Z9 90 U1 0 U2 5 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 MAY 27 PY 2003 VL 100 IS 11 BP 6529 EP 6534 DI 10.1073/pnas.1135239100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 684DT UT WOS:000183190700044 PM 12750467 ER PT J AU Bolger, PM Schwetz, B AF Bolger, PM Schwetz, B TI Mercury and the risk of myocardial infarction - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, College Pk, MD 20740 USA. RP Bolger, PM (reprint author), US FDA, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 22 PY 2003 VL 348 IS 21 BP 2154 EP 2154 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 680YU UT WOS:000183008300027 ER PT J AU Shaikh, B Rummel, N Reimschuessel, R AF Shaikh, B Rummel, N Reimschuessel, R TI Determination of albendazole and its major metabolites in the muscle tissues of Atlantic salmon, tilapia, and rainbow trout by high performance liquid chromatography with fluorometric detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE albendazole; HPLC; tilapia; rainbow trout; Atlantic salmon; muscle tissue; depletion ID BENZIMIDAZOLE ANTHELMINTICS; MASS-SPECTROMETRY; MAIN METABOLITES; PLASMA; SULFOXIDE; MILK; RESIDUES; SULFONE; CATTLE; SHEEP AB A liquid chromatographic procedure for the determination of albendazole ([5-(propylthio)-1H-benzimidazol-2yl]carbamic acid methyl ester) and its major metabolites, albendazole sulfoxide, albendazole sulfone, and albendazole-2- aminosulfone in rainbow trout, tilapia, and salmon muscle with adhering skin tissue is described. The muscle tissue samples are made alkaline with potassium carbonate and extracted with ethyl acetate. The extracts are further subjected to cleanup by utilizing a number of liquid-liquid extraction steps. After solvent evaporation, the residue is reconstituted in mobile phase and chromatographed. The chromatography is carried out on a reversed phase Luna C-18 column, using acetonitrile/methanol/buffer as a mobile phase and a fluorescence detector. The average recoveries from the fortified muscle tissue of the three fish species for albendazole (25100 ppb), albendazole sulfoxide (15.5-62 ppb), albendazole sulfone (1-10 ppb), and albenclazole-2- aminosulfone (10-100 ppb) were 94, 77, 82, and 67%, respectively. The average CV for each compound was less than or equal to10%. The procedure was validated and then applied to the determination of albendazole and its three major metabolites in the muscle tissue of the three fish species obtained after orally dosing with albendazole. C1 US FDA, CVM, Res Off, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, CVM, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 25 TC 21 Z9 22 U1 2 U2 11 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 MAY 21 PY 2003 VL 51 IS 11 BP 3254 EP 3259 DI 10.1021/jf021176i PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 679QD UT WOS:000182932700009 PM 12744651 ER PT J AU Kwon, HJ Cote, TR Cuffe, MS Kramer, JM Braun, MM AF Kwon, HJ Cote, TR Cuffe, MS Kramer, JM Braun, MM TI Case reports of heart failure after therapy with a tumor necrosis factor antagonist SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID DILATED CARDIOMYOPATHY; TRANSGENIC MICE; FACTOR-ALPHA; ETANERCEPT; ENBREL AB Background: Etanercept and infliximab are U.S. Food and Drug Administration-approved tumor necrosis factor (TNF) antagonists. Objective: To describe adverse event reports of heart failure after TNF antagonist therapy. Design: Case series. Setting: The U.S. Food and Drug Administration's MedWatch program. Patients: 47 patients who developed new or worsening heart failure during TNF antagonist therapy. Measurements: Clinical and laboratory reports. Results: After TNF antagonist therapy, 38 patients developed new-onset heart failure and 9 patients experienced heart failure exacerbation. Of the 38 patients with new-onset heart failure, 19 (50%) had no identifiable risk factors. Ten patients younger than 50 years of age developed new-onset heart failure after receiving TNF antagonists. After TNF antagonist therapy was discontinued and heart failure therapy was started in these 10 patients, 3 had complete resolution of heart failure, 6 improved, and 1 died. Conclusion: in a fraction of patients, TNF antagonists might induce new-onset heart failure or exacerbate existing disease. C1 US FDA, Div Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Duke Clin Res Inst, Durham, NC USA. RP Kwon, HJ (reprint author), US FDA, Div Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Suite 200S,HFM-224, Rockville, MD 20852 USA. NR 15 TC 227 Z9 236 U1 0 U2 7 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 MAY 20 PY 2003 VL 138 IS 10 BP 807 EP 811 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 679KH UT WOS:000182920700004 PM 12755552 ER PT J AU Lee, LH Frasch, CE Falk, LA Klein, DL Deal, CD AF Lee, LH Frasch, CE Falk, LA Klein, DL Deal, CD TI Correlates of immunity for pneumococcal conjugate vaccines SO VACCINE LA English DT Article DE correlate; pneumococcal; conjugate vaccine ID STREPTOCOCCUS-PNEUMONIAE; CAPSULAR POLYSACCHARIDE; ANTIBODY AVIDITY; IGG ANTIBODY; INFANTS; EFFICACY; CHILDREN; IMMUNOGENICITY; IMMUNIZATION; VACCINATION AB The purpose of the NIAID/FDA joint workshop, "correlates of immunity for pneumococcal conjugate vaccines (PCVs)," was to discuss the present understanding of protective immunity against invasive pneumococcal disease and identify in vitro measures that may represent immunologic correlates in future clinical trials. Animal and clinical data support functional antibody as the basis for protection, but IgG antibody concentration has conventionally been the principle immunologic parameter for non-inferiority comparisons. No consensus for a pre-defined threshold antibody level was reached. Affinity maturation may contribute to protection, but its role has not been established. Opsonophagocytic activity, avidity and immunologic memory are important secondary measures to characterise functional antibody and long-term protective responses. Immunologic memory may also be useful for evaluation of new vaccine serotypes. More definitive qualitative and quantitative immunogenicity criteria for use by National Control Authorities still need to be established. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Div Vaccines & Related Prod Applicat, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Rockville, MD 20852 USA. NIAID, Div Microbiol & Infect Dis, Bethesda, MD 20817 USA. RP Lee, LH (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Vaccines & Related Prod Applicat, HFM-475,1401 Rockville Pike, Rockville, MD 20852 USA. NR 32 TC 39 Z9 41 U1 1 U2 3 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 MAY 16 PY 2003 VL 21 IS 17-18 BP 2190 EP 2196 DI 10.1016/S0264-410X(03)00025-2 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 682PF UT WOS:000183100200048 PM 12706710 ER PT J AU Khaidakov, M Heflich, RH Manjanatha, MG Myers, MB Aidoo, A AF Khaidakov, M Heflich, RH Manjanatha, MG Myers, MB Aidoo, A TI Accumulation of point mutations in mitochondrial DNA of aging mice SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE aging; D-loop region; mitochondrial DNA; mutation frequency; PCR ID EPITHELIAL-CELLS; OXIDATIVE DAMAGE; SOMATIC MUTATION; HUMAN BRAIN; IN-VIVO; HPRT; AGE; FREQUENCY; LIVER; RATS AB Mitochondrial DNA (mtDNA) exists in a highly genotoxic environment created by exposure to reactive oxygen species, somewhat deficient DNA repair, and the relatively low fidelity of polymerase gamma. Given the severity of the environment, it was anticipated that mutation accumulation in the mtDNA of aging animals should exceed that of nuclear genes by several orders of magnitude. We have analyzed fragments amplified from the D-loop region of mtDNA from 2 to 22-month-old mice. The amplified 432 bp fragments were cloned into plasmid vectors, and plasmid DNAs from individual clones were purified and sequenced. None of 110 fragments from young mice contained a mutation, while 9 of 87 clones originating from old animals contained base substitutions (chi square = 11.9, P < 0.001). The estimated mutation frequency in mtDNA from old mice was 11.6 +/- 2.7 or 25.4 +/- 7.8 per 10(5) nucleotides (depending on assumptions of clonality), which exceeds existing estimates for mutation frequencies for nuclear genes by approximately 1000-fold. Our data suggest that at 22 months of age, which roughly corresponds to 3/4 of the mouse natural life span, most mtDNA molecules carry multiple point mutations. Published by Elsevier Science B.V. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Dept Geriatr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci Hosp, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Aidoo, A (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 52 TC 69 Z9 73 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 MAY 15 PY 2003 VL 526 IS 1-2 BP 1 EP 7 DI 10.1016/S0027-5107(03)00010-1 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 676HX UT WOS:000182746200001 PM 12714177 ER PT J AU Harrington-Brock, K Collard, DD Chen, T AF Harrington-Brock, K Collard, DD Chen, T TI Bromate induces loss of heterozygosity in the Thymidine kinase gene of L5178Y/Tk(+/-)-3.7.2C mouse lymphoma cells SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE bromate; loss of heterozygosity; mouse lymphoma assay; mutation ID OXIDATIVE DNA-DAMAGE; RESISTANT TFT MUTANTS; ETHYL-N-NITROSOUREA; POTASSIUM BROMATE; RENAL CARCINOGEN; DRINKING-WATER; RAT-KIDNEY; V79 CELLS; IN-VITRO; MUTATIONS AB Potassium bromate (KBrO3) induces DNA damage and tumors in mice and rats, but is a relatively weak mutagen in microbial assays and the in vitro mammalian Hprt assay. Concern that there may be a human health risk associated with bromate, a disinfectant by-product of ozonation, has accompanied the increasing use of ozonation as an alternative to chlorination for treatment of drinking water. In this study, we have evaluated the mutagenicity of KBrO3 and sodium bromate (NaBrO3) in the Tk gene of mouse lymphoma cells. In contrast to the weak mutagenic activity seen in the previous studies, bromate induced a mutant frequency of over 100 x 10(-6) at 0.6 mM with minimal cytotoxicity (70-80% survival) and over 1300 x 10(-6) at 3 mM (similar to10% survival). The increase in the Tk mutant frequency was primarily due to the induction of small colony of Tk mutants. Loss of heterozygosity (LOH) analysis of 384 mutants from control and 2.7 nM KBrO3-treated cells showed that almost all (99%) bromate-induced mutants resulted from LOH, whereas in the control cultures 77% of the Tk mutants were LOH. Our results suggest that bromate is a potent mutagen in the Tk gene of mouse lymphoma cells, and the mechanism of action primarily involves LOH. The ability of the mouse lymphoma assay to detect a wider array of mutational events than the microbial or V79 Hprt assays may account for the potent mutagenic response. Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27709 USA. RP Chen, T (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 36 TC 23 Z9 23 U1 0 U2 0 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 MAY 9 PY 2003 VL 537 IS 1 BP 21 EP 28 DI 10.1016/S1383-5718(03)00044-5 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 685GM UT WOS:000183254000003 PM 12742504 ER PT J AU Brorson, K Sherrie, K Lee, K Hamilton, E Stein, K Xu, Y AF Brorson, K Sherrie, K Lee, K Hamilton, E Stein, K Xu, Y TI Bracketed generic inactivation of rodent retroviruses by low pH treatment for monoclonal antibodies and recombinant proteins SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE viral clearance; monoclonal antibodies; recombinant proteins; low pH unit operations ID INFLUENZA-VIRUS HEMAGGLUTININ; MEDIATED MEMBRANE-FUSION; CONFORMATIONAL CHANGE; MODEL SYSTEM; CELL-CULTURE; WEST NILE; GLYCOPROTEIN; ACTIVATION; STABILITY AB Viral safety is a predominant concern for monoclonal antibodies (mAbs) and other recombinant proteins (RPs) with pharmaceutical applications. Certain commercial purification modules, such as nanofiltration and low-pH inactivation, have been observed to reliably clear greater than 4 log(10) of large enveloped viruses, including enclogenous retrovirus. The concept of "bracketed generic clearance" has been proposed for these steps if it could be prospectively demonstrated that viral log(10) reduction value (LRV) is not impacted by operating parameters that can vary, within a reasonable range, between commercial processes. In the case of low-pH inactivation, a common step in mAb purification processes employed after protein A affinity chromatography, these parameters would include pH, time and temperature of incubation, the content of salts, protein concentration, aggregates, impurities, model protein pI, and buffer composition. In this report, we define bracketed generic clearance conditions, using a prospectively defined bracket/matrix approach, where low-pH inactivation consistently achieves greater than or equal to4.6 log clearance of xenotropic murine leukemia virus (X-MLV), a model for rodent enclogenous retrovirus. The mechanism of retrovirus inactivation by low-pH treatment was also investigated. (C) 2003 Wiley Periodicals, Inc. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. Genentech Inc, San Francisco, CA 94080 USA. RP Xu, Y (reprint author), MacroGen, 1500 E Gude Dr, Rockville, MD 20850 USA. EM xu.yuan@gene.com NR 28 TC 64 Z9 68 U1 0 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD MAY 5 PY 2003 VL 82 IS 3 BP 321 EP 329 DI 10.1002/bit.10574 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 659NU UT WOS:000181784100009 PM 12599259 ER PT J AU Jakubzick, C Choi, ES Kunkel, SL Joshi, BH Puri, RK Hogaboam, CM AF Jakubzick, C Choi, ES Kunkel, SL Joshi, BH Puri, RK Hogaboam, CM TI Impact of interleukin-13 responsiveness on the synthetic and proliferative properties of Th1- and Th2-type pulmonary granuloma fibroblasts SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN SYNOVIAL FIBROBLASTS; IL-13 RECEPTOR ALPHA-2; HUMAN LUNG FIBROBLASTS; COMMON GAMMA-CHAIN; SIGNAL-TRANSDUCTION; FUSION CYTOTOXIN; INTERFERON-GAMMA; INDUCED APOPTOSIS; FUNGAL ASTHMA; FIBROTIC LUNG AB Interleukin-13 (IL-13) has emerged as a major cytokine mediator of fibroblast activation and pulmonary fibrosis. Normal (from noninflamed lung), Th1-type (induced by the pulmonary embolization of purified peptide derivative-coated beads in mice sensitized to purified peptide derivative), and Th2-type (induced by the pulmonary embolization of Schistosoma mansoni egg antigen-coated beads in mice sensitized with S mansoni eggs) primary fibroblast cell lines all exhibited constitutive gene expression of two receptor chains that bind and signal IL-13-mediated cellular events: IL-4Ralpha and IL-13Ralpha1. However, all three fibroblast cell lines exhibited divergent synthetic and proliferative responses to the exogenous addition of either recombinant 11,13 or a chimeric protein comprised of 11,13 and a truncated version of Pseudomonas exotoxin (IL13-PE), which targets and kills IL-13 receptor overexpressing cells. The exogenous addition of IL-13 to Th1-type and Th2-type fibroblast cultures significantly increased the cellular expression of IL-13Ralpha2, which may function as an IL-13 decoy receptor. After a 24-hour exposure to IL-13, the total collagen generation and cellular proliferation by Th2-type fibroblasts were significantly higher than that observed in similar numbers of normal and Th1-type fibroblasts. In addition IL13-PE, which binds with highest affinity to 11-13Ralpha2, exhibited downregulatory effects on proliferation and matrix generation expression by Th1- and Th2-type, but not normal, fibroblasts. Thus, these data demonstrate that fibroblasts derived from murine pulmonary granulomas exhibit divergent expression of functional IL-13 receptor and this expression dictates the responsiveness and susceptibility to recombinant IL-13 and IL-13 immunotoxin, respectively. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD USA. RP Hogaboam, CM (reprint author), Univ Michigan, Sch Med, Dept Pathol, 1301 Catherine Rd, Ann Arbor, MI 48109 USA. RI hogaboam, cory /M-3578-2014 FU NIAID NIH HHS [T32 AI007413] NR 64 TC 37 Z9 40 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2003 VL 162 IS 5 BP 1475 EP 1486 DI 10.1016/S0002-9440(10)64280-0 PG 12 WC Pathology SC Pathology GA 670XE UT WOS:000182434700010 PM 12707030 ER PT J AU Hammoud, DA Belden, CJ Ho, AC Dal Pan, GJ Herskovits, EH Hilt, DC Brem, H Pomper, MG AF Hammoud, DA Belden, CJ Ho, AC Dal Pan, GJ Herskovits, EH Hilt, DC Brem, H Pomper, MG TI The surgical bed after BCNU polymer wafer placement for recurrent glioma: Serial assessment on CT and MR imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MALIGNANT GLIOMA; INTERSTITIAL CHEMOTHERAPY; BIODEGRADABLE POLYMERS; RESECTION; TRIAL AB OBJECTIVE. The objective of our study was to describe the CT and MR imaging appearances of the surgical bed in the brains of patients receiving biodegradable polymers impregnated with N, N'1, 3-Bis-(2-chloroethyl)-N-nitrosourea (BCNU) for recurrent glioma and to determine whether patients receiving placebos could be differentiated from those receiving BCNU based on the pattern and growth kinetics of tumor recurrence. MATERIALS AND METHODS. The CT and MR images of 20 patients who underwent surgery for resection of recurrent high-grade gliomas and placement of intratumoral wafers (11 received BCNU polymer wafers, nine received control wafers) were analyzed for wafer appearance, volume of gas in the tumor bed, and volume of enhancement on serial scans. RESULTS. Wafers appeared as linear hyperdense structures on CT and as linear low-signal-intensity structures on MR imaging and caused no significant enhancement. In the BCNU polymer group, gas volume was 4.0 +/- 3.4 cm(3) (mean +/- SD), whereas gas volume was 1.6 +/- 3.0 cm(3) for the placebo group (Mann-Whitney test, p = 0.03). A trend toward linear rather than exponential recurrent tumor growth was identified for the BCNU polymer group but not for the placebo group. CONCLUSION. BCNU polymer wafers have a specific appearance on CT and MR imaging with which radiologists should be familiar: gas in the surgical bed is an expected transient finding, and tumor regrowth in patients receiving BCNU polymer wafers appeared to occur at a slower rate than in those receiving the placebo. C1 Johns Hopkins Univ, Sch Med, Dept Radiol, Div Neuroradiol, Baltimore, MD 21287 USA. Brooke Army Med Ctr, Dept Radiol, Ft Sam Houston, TX 78234 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. Hosp Univ Penn, Dept Radiol, Div Neuroradiol, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21287 USA. Guilford Pharmaceut, Baltimore, MD 21224 USA. RP Pomper, MG (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, Div Neuroradiol, 600 N Wolfe St, Baltimore, MD 21287 USA. RI Hammoud, Dima/C-2286-2015 NR 17 TC 15 Z9 15 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2003 VL 180 IS 5 BP 1469 EP 1475 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 670RU UT WOS:000182423300046 PM 12704070 ER PT J AU Ge, BL White, DG McDermott, PF Girard, W Zhao, SH Hubert, S Meng, JH AF Ge, BL White, DG McDermott, PF Girard, W Zhao, SH Hubert, S Meng, JH TI Antimcrobial-resistant Campylobacter species from retail raw meats SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID DNA-SEQUENCE ANALYSIS; ANTIBIOTIC-RESISTANCE; GYRA GENE; JEJUNI; QUINOLONE; MUTATIONS; COLI; STRAINS; FOODS; SPP. AB The antimicrobial susceptibilities of 378 Campylobacter isolates were determined. Resistance to tetracycline was the most common (82%), followed by resistance to doxycycline (77%), erythromycin (54%), nalidixic acid (41%), and ciprofloxacin (35%). Campylobacter coli displayed significantly higher rates of resistance to ciprofloxacin and erythromycin than Campylobacter jejuni, and Campylobacter isolates from turkey meat showed a greater resistance than those from chicken meat. 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. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NR 23 TC 89 Z9 92 U1 1 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 MAY PY 2003 VL 69 IS 5 BP 3005 EP 3007 DI 10.1128/AEM.69.3005-3007.2003 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 677LD UT WOS:000182808300074 PM 12732579 ER PT J AU Gutman, S Meyer, D AF Gutman, S Meyer, D TI Lexicon for laboratories - Scaling the Tower of Babel SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SENSITIVITY C1 US FDA, Div Clin Lab Devices, Rockville, MD 20857 USA. NCCLS, Houston, TX USA. CHRISTUS Hlth, Houston, TX USA. RP Gutman, S (reprint author), HFZ-440,2098 Gaither Rd, Rockville, MD 20850 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2003 VL 127 IS 5 BP 625 EP 626 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 674XH UT WOS:000182662200020 PM 12708913 ER PT J AU Nayak, R Kenney, PB Keswani, J Ritz, C AF Nayak, R Kenney, PB Keswani, J Ritz, C TI Isolation and characterisation of Salmonella in a turkey production facility SO BRITISH POULTRY SCIENCE LA English DT Article ID POULTRY; CONTAMINATION; SEROTYPES; FEED; COLONIZATION; CARCASES; CHICKEN; FARMS AB 1. A comprehensive ecological survey was conducted from April 1997 to June 1999 on 4 turkey flocks (F1 to F4) to identify key pre-harvest sources/vectors of Salmonella colonisation. 2. Turkey caecal and crop content, litter, drinker, air, feed, feeder and environmental swab samples were collected. Conventional microbiological and serological procedures were used to isolate, identify, and confirm the presence or absence of Salmonella. 3. Salmonella was isolated from 13% of litter, 11% of turkey caeca, 10% of drinker, 5% of environmental swab, 3% of feed and 1% of feeder samples. Salmonella heidelberg (65%), S. senftenberg (19%), S. muenster (10%), S. anatum (3%), and S. worthington (3%) were identified. 4. Identifying environmental sources associated with Salmonella colonisation and characterising serotypes would assist in designing pre-harvest controls for this poultry-borne pathogen. integrators and poultry producers may be able to design hazard analysis and critical control point (HACCP) protocols to reduce the incidence of Salmonella arriving at the processing plant. C1 W Virginia Univ, Div Anim & Vet Sci, Morgantown, WV 26506 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIOSH, Ctr Dis Control & Prevent, Morgantown, WV USA. Univ Georgia, New Branch Expt Stn, Calhoun, GA USA. RP Kenney, PB (reprint author), W Virginia Univ, Div Anim & Vet Sci, Morgantown, WV 26506 USA. NR 36 TC 30 Z9 32 U1 0 U2 2 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0007-1668 J9 BRIT POULTRY SCI JI Br. Poult. Sci. PD MAY PY 2003 VL 44 IS 2 BP 192 EP 202 DI 10.1080/0007166031000088370 PG 11 WC Agriculture, Dairy & Animal Science SC Agriculture GA 688EQ UT WOS:000183420900006 PM 12828204 ER PT J AU Kawakami, K Kawakami, M Husain, SR Puri, RK AF Kawakami, K Kawakami, M Husain, SR Puri, RK TI Effect of interleukin (IL)-4 cytotoxin on breast tumor growth after in vivo gene transfer of IL-4 receptor alpha chain SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; CANCER-CELLS; KAPOSIS-SARCOMA; IN-VIVO; ANTITUMOR-ACTIVITY; SYSTEMIC DELIVERY; GAMMA-CHAIN; EXPRESSION AB Although human breast cancer cells express interleukin-4 receptors (IL-4Rs), a recombinant fusion protein, IL-4 cytotoxin, did not mediate desirable antitumor activity in tumor models of breast cancer. Recent studies have identified that a primary IL-4 binding protein, IL-4Ralpha chain, is internalized after binding to IL-4 in cancer cells. The consequent expression of high-level IL-4Ralpha in tumor cells sensitizes them to the cytotoxic effect of IL-4 cytotoxin in vitro. To assess whether overexpression of IL-4Ralpha chain in vivo by plasmid-mediated gene transfer can enhance antitumor activity of IL-4 cytotoxin in mouse models of breast tumor, we injected MDA-MB-231 human breast cancer cells in both flanks of athymic nude mice. Animals then received three intratumoral (i.t.) injections of either IL-4Ralpha encoding vector (left flank) or vector only (right flank) mixed with liposome followed by IL-4 cytotoxin administration. Both i.p. and i.t. administration of IL-4 cytotoxin profoundly reduced the growth of IL-4Ralpha plasmid-injected MDA-MB-231 tumors, compared with control. Innate immune cells, including macrophages and neutrophils, were found to infiltrate at the regressing tumor site. This study provides proof of principle that i.t. IL-4Ralpha plasmid injection followed by systemic or i.t. IL-4 cytotoxin administration may be a useful strategy for the treatment of breast cancer. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 67 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2003 VL 9 IS 5 BP 1826 EP 1836 PG 11 WC Oncology SC Oncology GA 677MY UT WOS:000182813200034 PM 12738741 ER PT J AU Mendelsohn, AB Chelluri, L AF Mendelsohn, AB Chelluri, L TI Interviews with intensive care unit survivors: Assessing post-intensive care quality of life and patients' preferences regarding intensive care and mechanical ventilation SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the University-of-Pittsburg-Medical-Center CY MAY, 2002 CL PITTSBURGH, PENNSYLVANIA SP Univ Pittsburg Med Ctr DE quality of life; preferences; intensive care; mechanical ventilation; patients; survivors ID OF-LIFE; SUSTAINING TREATMENTS; ELDERLY PATIENTS; CARDIAC-SURGERY; HEALTH VALUES; ILL; MORTALITY; ADMISSION; ASSESSMENTS; STABILITY C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA. RP Mendelsohn, AB (reprint author), US FDA, S600 Fishers Lane,Mail Stop HFD-410,room 15B23, Rockville, MD 20852 USA. FU NIA NIH HHS [AG11979] NR 55 TC 2 Z9 2 U1 5 U2 6 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 MAY PY 2003 VL 31 IS 5 SU S BP S400 EP S406 DI 10.1097/01.CCM.0000065278.90460.F0 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 681BK UT WOS:000183016700013 PM 12771591 ER PT J AU Mohan, AK Cote, TR Siegel, JN Braun, MM AF Mohan, AK Cote, TR Siegel, JN Braun, MM TI Infectious complications of biologic treatments of rheumatoid arthritis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review ID PNEUMOCYSTIS-CARINII PNEUMONIA; FACTOR-ALPHA ANTAGONISTS; CROHNS-DISEASE; TUBERCULOSIS ENTERITIS; INFLIXIMAB THERAPY; OPEN-LABEL; PATIENT; SAFETY; HISTOPLASMOSIS; IMMUNOTHERAPY AB Agents that block the action of tumor necrosis factor-alpha. and recombinant interleukin-1 have been shown to be effective biologic treatment modalities in patients with rheumatoid arthritis. Given the immunosuppressive effects of tumor necrosis factor-alpha and interleukin-1 blockers, infections have emerged as possible complications of using these agents, an observation foreshadowed in prelicensure animal studies. At this time, hundreds of thousands of patients have received these drugs, and a wide variety of infectious complications has been reported, among which reactivation tuberculosis is most notable. Case reports alone, however, do not necessarily reflect a causal association between a therapeutic product and an adverse event. The authors review the infectious complications of the use of these agents as reported in the medical literature from November 2001 through October 2002. C1 US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Rev, Rockville, MD 20852 USA. RP Mohan, AK (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Suite 200S, Rockville, MD 20852 USA. NR 57 TC 49 Z9 51 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAY PY 2003 VL 15 IS 3 BP 179 EP 184 DI 10.1097/00002281-200305000-00002 PG 6 WC Rheumatology SC Rheumatology GA 672VT UT WOS:000182544200002 PM 12707568 ER PT J AU Tabor, E AF Tabor, E TI Interferon for preventing and treating hepatocellular carcinoma associated with the hepatitis B and C viruses SO DIGESTIVE AND LIVER DISEASE LA English DT Article DE hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; interferon-alpha; interferon-beta; interferon-gamma ID HEPATOMA-CELL LINE; RANDOMIZED CONTROLLED TRIAL; CHRONIC VIRAL-HEPATITIS; LIVER-CANCER; LEUKOCYTE INTERFERON; ALPHA-INTERFERON; HBSAG PRODUCTION; I INTERFERONS; RISK-FACTORS; THERAPY AB The possibility that interferon-alpha might be effective for the prevention or treatment of hepatocellular carcinoma is suggested by its efficacy against the associated hepatitis B and C viruses, by its efficacy in the treatment of some other human tumours, and by evidence that interferon-alpha may inhibit the growth of human hepatocellular carcinoma cell lines and their production of hepatitis B surface antigen. Few studies support the use of interferon-alpha for preventing hepatitis B virus-associated hepatocellular carcinoma. In contrast, benefit from the use of interferon-alpha to prevent hepatitis C virus-associated hepatocellular carcinoma is suggested in a large number of studies, but most of these studies have weaknesses of study design that preclude definitive conclusions. Nevertheless, most of these studies suggest that the incidence of hepatocellular carcinoma is lower in hepatitis C virus-infected patients receiving interferon-alpha, particularly in patients with a sustained response to interferon-alpha, compared to nonresponders. As a treatment for hepatocellular carcinoma, interferon-a was only evaluated in a small number of patients with advanced disease; 'partial responses' and prolongation of survival times in a few of these studies suggest that additional studies should be done in patients with less advanced disease. Published by Elsevier Science Ireland Ltd. on behalf of Editrice Gastroenerologica Italiana S.r.l. C1 US FDA, CBER, Rockville, MD 20852 USA. RP Tabor, E (reprint author), US FDA, CBER, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. NR 74 TC 7 Z9 8 U1 0 U2 1 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD MAY PY 2003 VL 35 IS 5 BP 297 EP 305 DI 10.1016/S1590-8658(03)00071-9 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 692TL UT WOS:000183676300001 PM 12846400 ER PT J AU Crump, KS Canady, R Kogevinas, M AF Crump, KS Canady, R Kogevinas, M TI Meta-analysis of dioxin cancer dose response for three occupational cohorts SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE carcinogen; dioxin; dose-response assessment; meta-analysis; occupational cohorts ID FOLLOW-UP; RISK; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; 2,3,7,8-TCDD; MORTALITY; EXPOSURE; HUMANS AB This article presents a meta analysis of data from three cohorts occupationally exposed to TCDD and related compounds. A statistically significant (p = 0.02) trend was found in total cancer mortality,with increasing dioxin exposure. The trend tests show an increase in total cancer at cumulative TEQ (unit of measurement for TCDD-like compounds that is defined as the amount of TCDD that would produce the same toxicity as a mixture of TCDD-like compounds) serum levels that would result from lifetime intake of 7 pg TEQ/kg body weight/day, with no increase at 6 pg/kg/day. A linear dose response provided a good fit to the combined data and predicted an ED01 (dioxin exposure resulting in a 0.01 increase in lifetime risk of cancer mortality) of 45 pg/kg/day (95% confidence interval, 21-324). The U.S. Environmental Protection Agency estimates that current lifetime human exposures to dioxin average approximately 1 pg/kg/day (99% percentile: 3 pg/kg/day). Although it appears unlikely that current exposures through foods would reach either 7 pg/kg/day or the ED01, our analysis argues for careful consideration of the upper ranges of long-term average exposures for dioxins. C1 Environ Int Corp, Ruston, LA 71270 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Inst Municipal Invest Med, Resp & Environm Hlth Res Unit, E-08003 Barcelona, Spain. RP Crump, KS (reprint author), Environ Int Corp, 602 E Georgia Ave, Ruston, LA 71270 USA. RI Kogevinas, Manolis/C-3918-2017 NR 20 TC 38 Z9 39 U1 0 U2 13 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 MAY PY 2003 VL 111 IS 5 BP 681 EP 687 DI 10.1289/eph.5831 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 677CB UT WOS:000182788400023 PM 12727594 ER PT J AU Komolprasert, V McNeal, TP Begley, TH AF Komolprasert, V McNeal, TP Begley, TH TI Effects of gamma- and electron-beam irradiation on semi-rigid amorphous polyethylene terephthalate copolymers SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE polyethylene terephthalate; copolymer; volatiles; non-volatiles; ionizing radiation; gamma-irradiation; e-beam accelerator ID FOOD-PACKAGING MATERIALS; IONIZING-RADIATION; DEGRADATION PRODUCTS; SENSORY CHANGES; PVDC/PVC FILMS; GRADE PVC; OLIVE OIL; MIGRATION; POLY(ETHYLENE-TEREPHTHALATE); PLASTICIZERS AB Two semi-rigid amorphous polyethylene terephthalate copolymer materials (in both sheet and powder forms) containing 3% 1,4-cyclohexane dimethanol (CHDM) and 31% CHDM were irradiated at 5, 25 and 50 kGy at ambient temperature with a Co-60 radiator or an electron-beam accelerator. After irradiation, volatiles were determined using static headspace sampling with capillary gas chromatography and mass selective detection or flame ionization detection (HS/GC/MSD or FID). Non-volatiles were extracted with 10% aqueous ethanol and 100% n-heptane food-simulating solvents, maintained at 40degreesC for up to 10 days. The non-volatiles in the materials and those migrating into the food-simulating solvents were determined by high-performance liquid chromatography (HPLC) with ultraviolet and/or photodiode array, detection. The results obtained from the HS/GC/MSD suggest that no new chemicals were detected by either gamma- or e-beam irradiation when compared with non-irradiated specimens. The major volatiles in the copolymers were acetaldehyde and 2-methyl-1,3-dioxolane. The concentrations of acetaldehyde increased from 1.24-1.96 mg kg(-1) to 1.94-3.65, 352-7.23 and 5.45-15.37 mg kg(-1) after exposure to 5, 25 and 50 kGy doses, respectively. The concentrations of 2-methyl-1,3-dioxolane decreased from 2.49-5.26 mg kg(-1) to 2.07-3.13, 1.33-2.14 and 0.64-2.24 mg kg(-1) after exposure to 5, 25 and 50 kGy doses, respectively. The results of analysis of the copolymers for non-volatiles show, that irradiation did not produce any new delectable non-volatile chemicals. A 5 kGy close had no delectable effect on either copolymer. The 25 and 50 kGY doses had slightly different effects with respect to gamma- and e-beam irradiation on low, MW oligomers. However, these increased doses did not significantly affect migration. The concentration of most low molecular weight oligomers migrating into 10% ethanol and 100% heptane was less than or equal to2 ng g(-1) of each oligomer for both copolymers. The cyclic trimer migrating from the 3% CHDM copolymer was approximately 4 ng g(-1); it was 3 ng g(-1) for the 31% CHDM copolymer. The overall results suggest that irradiation significantly increased levels of acetaldehyde but had no effect on non-volatile compounds migrating into food simulants. C1 US FDA, Div Food Proc & Packaging, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Div Chem Res & Environm Review, Off Food Addit Safety, College Pk, MD 20740 USA. RP Komolprasert, V (reprint author), US FDA, Div Food Proc & Packaging, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 21 TC 13 Z9 13 U1 1 U2 8 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. PD MAY PY 2003 VL 20 IS 5 BP 505 EP 517 DI 10.1080/0265203031000070119 PG 13 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 688EX UT WOS:000183421500011 PM 12775470 ER PT J AU Ku, Y Jansen, O Oles, CJ Lazar, EZ Rader, JI AF Ku, Y Jansen, O Oles, CJ Lazar, EZ Rader, JI TI Precipitation of inulins and oligoglucoses by ethanol and other solvents SO FOOD CHEMISTRY LA English DT Article ID DIETARY FIBER AB We investigated the ethanol precipitation step of the gravimetric method of dietary fiber analysis (AOAC Official Method 985.29). Four different solvents: ethanol, propanol, acetone and acetonitrile at four ratios: 1:1, 2:1, 3:1 and 4:1 (solvent : supernatant, v/v) were studied. Using inulins that contain components with a full range of degree of polymerization values (DP), we found that the percents of precipitation by these solvents were proportional to the average DP of the products. Use of ethanol and propanol produced similar results. In general, acetonitrile and acetone precipitated more of the inulins than did ethanol. Supernatant solutions were analyzed by high performance anion exchange chromatography in order to determine the size of the components that were precipitated. Our data showed that components of inulin with DP 1-10 remain in solution after the addition of ethanol at a ratio of 4:1. However, significant amounts of molecules of DP 11 and 12 and smaller amounts of molecules of DP 14-18 also remain in solution. The precipitation patterns of oligoglucoses with DP 1-DP 7 were also investigated. Our data suggest that the precipitation behavior of oligoglucoses follows a pattern similar to that of inulins. C1 US FDA, Div Res & Appl Technol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Rader, JI (reprint author), US FDA, Div Res & Appl Technol, Ctr Food Safety & Appl Nutr, HFS-840,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. RI Jansen, Olav/D-2547-2010 NR 9 TC 27 Z9 28 U1 1 U2 9 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. PD MAY PY 2003 VL 81 IS 1 BP 125 EP 132 AR PII S0308-8146(02)00393-X DI 10.1016/S0308-8146(02)00393-X PG 8 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 654DW UT WOS:000181479600016 ER PT J AU Forbes, PD Beer, JZ Black, HS Cesarini, JP Cole, CA Davies, RE Davitt, JM DeGruijl, F Epstein, J Fourtanier, A Green, A Koval, T Ley, RD Mascotto, R Morison, W Osterberg, R Sliney, D Urbach, F van der Leun, JC Young, AR AF Forbes, PD Beer, JZ Black, HS Cesarini, JP Cole, CA Davies, RE Davitt, JM DeGruijl, F Epstein, J Fourtanier, A Green, A Koval, T Ley, RD Mascotto, R Morison, W Osterberg, R Sliney, D Urbach, F van der Leun, JC Young, AR TI Standardized protocols for photocarcinogenesis safety testing SO FRONTIERS IN BIOSCIENCE LA English DT Article DE photocarcinogenesis; protocols; laboratory models; Uv radiation; safety testing; toxicology; guidelines; review ID STRATOSPHERIC OZONE DEPLETION; A RADIATION PUVA; SKIN-CANCER; HAIRLESS MICE; ULTRAVIOLET-RADIATION; METHOXSALEN PSORALEN; RISK; 8-METHOXYPSORALEN; CARCINOGENESIS; PSORIASIS AB Solar ultraviolet radiation (UVR) is recognized as a major cause of non-melanoma skin cancer in man. Skin cancer occurs most frequently in the most heavily exposed areas and correlates with degree of outdoor exposure. The incidence of skin cancer is also increased by contact with photosensitizing drugs and chemicals such as psoralens, coal tars and petroleum stocks. Other substances which do not act as photosensitizers, such as immunosuppressants taken by organ transplant recipients, also increase the risk of skin cancer. The U. S. Food and Drug Administration requests, on a case-by-case basis, that risk of enhanced photocarcinogenesis is assessed for many classes of drugs. Health Canada's Therapeutic Products Programme has issued a Notice of Intent to regulate pharmaceutical products which may enhance carcinogenicity of the skin induced by ultraviolet radiation. Other national regulatory agencies review such data when they exist, but their own requirements emphasize batteries of short-term in vitro and in vivo tests. While they may support drug development strategies, short-term tests have yet to be validated as predictors of the ability of drugs or chemicals to enhance photocarcinogenesis. Published protocols now describe study designs and procedures capable of determining whether test agents enhance the rate of formation of UVR-induced skin tumors. C1 Charles River Labs Inc, Argus Res, Discovery & Dev Div, Horsham, PA 19044 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Fdn Rothchild, F-75019 Paris, France. Johnson & Johnson Consumer Prod Co, Skillman, NJ 08558 USA. Regulatory Affairs Serv, Silver Spring, MD 20904 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. LOreal, Grp Dermatobiol, F-92583 Paris, France. Queensland Inst Med Ctr, Brisbane, Qld 4029, Australia. NCRP, Bethesda, MD 20814 USA. Univ New Mexico, Albuquerque, NM 87131 USA. LOreal, Corp Res & Dev, F-92583 Paris, France. US FDA, Rockville, MD 20857 USA. USA, Environm Hyg Agcy, Aberdeen Proving Ground, MD 21010 USA. EcoSys, Utrecht, Netherlands. Kings Coll London, St Johns Inst Dermatol, London SE1 7EH, England. RP Forbes, PD (reprint author), Charles River Labs Inc, Argus Res, Discovery & Dev Div, 905 Sheehy Dr, Horsham, PA 19044 USA. EM forbes@toxarus.com NR 55 TC 7 Z9 7 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2003 VL 8 BP D848 EP D854 DI 10.2741/975 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 669LG UT WOS:000182352300036 PM 12700109 ER PT J AU Boivin, W Coletta, J Kerr, L AF Boivin, W Coletta, J Kerr, L TI Characterization of the magnetic fields around walk-through and hand-held metal detectors SO HEALTH PHYSICS LA English DT Article DE magnetic fields; electromagnetic fields; radiation, nonionizing; exposure, population AB Magnetic field strength measurements were made around eight hand-held and 10 walk-through metal detectors. The method was similar to that used in previous research for Electronic Article Surveillance units except a Cartesian rather than cylindrical coordinate system was used. Special magnetic field probes specifically designed for metal detector measurements were used. A non-metallic positioning apparatus was designed and fabricated. Magnetic field strength measurements were collected on one hand-held metal detector in the laboratory. The remaining data were collected at airport terminals, federal and state government buildings, and a local high school. Walk-through metal detectors had considerably higher magnetic field strengths [up to 299 Am-1 p-p (3,741 mG)] than hand-held metal detectors [up to 6 Am-1 p-p (76 mG)]. The frequencies of the magnetic field signal for walk-through detectors were between 0.1 kHz and 3.5 kHz while those for hand-held detectors were between 89 kHz and 133 kHz. Waveforms for all hand-held metal detectors were sinusoidal; those for walk-through metal detectors varied with most being saw-toothed or pulsed. Due to their higher field strengths and the pulsed nature of their magnetic fields, walk-through metal detectors likely pose a higher risk for medical device electromagnetic interference than do hand-held units. Root mean squared magnetic field strengths were calculated from the peak-to-peak values and compared to occupational and general public exposure limits. None of these limits were exceeded. Measurement repeatability was examined for one hand-held and two walk-through metal detectors. For the hand-held metal detector measurements at the location of the maximum magnetic field strength, measurements by three individuals had a repeatability (percent standard deviation) of 5.9%. Limited repeatability data were collected for on-site measurements of walk-through detectors. One unit showed repeatability of 0.1 to 4.5%; a multi-zone unit showed repeatability of 2.7 to 67.5%. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Boivin, W (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. EM wboivin@ora.fda.gov NR 19 TC 10 Z9 10 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 2003 VL 84 IS 5 BP 582 EP 593 DI 10.1097/00004032-200305000-00003 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 668AZ UT WOS:000182269300003 PM 12747477 ER PT J AU Waynant, RW AF Waynant, RW TI More benefits for you to Xplore SO IEEE CIRCUITS & DEVICES LA English DT Editorial Material C1 US FDA, CDRH, IEEE Circuits & Devices Magazine, Rockville, MD 20857 USA. RP Waynant, RW (reprint author), US FDA, CDRH, IEEE Circuits & Devices Magazine, 12757 Twinbrook Pkwy,Room 267,HFZ-134, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 8755-3996 J9 IEEE CIRCUITS DEVICE JI IEEE Circuits Devices PD MAY PY 2003 VL 19 IS 3 BP 2 EP 3 PG 2 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA 684QP UT WOS:000183218300001 ER PT J AU Tiffany, LJ Riblet, R Stein, KE AF Tiffany, LJ Riblet, R Stein, KE TI The Sr1 gene that controls diversity of the anti-inulin antibody response maps to mouse chromosome 14 SO IMMUNOGENETICS LA English DT Article DE antibodies; mouse; polysaccharide; repertoire; thymus independent ID INBRED MOUSE STRAINS; BALB-C; SUBCLASS RESTRICTION; INDEPENDENT ANTIGENS; TYPE-2 ANTIGENS; MICE; IDIOTYPE; HISTOCOMPATIBILITY; CARBOHYDRATE; ACTIVATION AB Previous studies demonstrated that the diversity of the antibody response of mice to the inulin (In) determinant of bacterial levan is regulated by the gene Spectrotype Regulation 1 (Sr1). BALB/c mice produce a monoclonal anti-In response as shown by isoelectric focusing analysis. In contrast, the anti-In antibody response of (BALB/cxC57BL/6)F1 mice is significantly more heterogeneous. We performed a backcross and a genome-wide scan with microsatellite markers and found that Sr1 is tightly linked to D14Mit121 on chromosome (Chr) 14. This location for Sr1 was supported by analysis of CXB Recombinant Inbred strains. We further confirmed this by finding that the Chr 14 congenic mouse strain B6.C-H8 lacks the C57BL/6 allele of the Sr1 gene, indicating that Sr1 is located in the segment of Chr 14 replaced with BALB/c donor DNA. These data place Sr1 near to or coincident with the Tcra/Tcrd T-cell receptor gene complex and suggest a role for T cells in diversifying the anti-In response. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. RP Tiffany, LJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NR 35 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAY PY 2003 VL 55 IS 2 BP 80 EP 86 DI 10.1007/s00251-003-0555-z PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 696ED UT WOS:000183872500002 ER PT J AU Ng, C Marshall, WE Rao, RM Bansode, RR Losso, JN AF Ng, C Marshall, WE Rao, RM Bansode, RR Losso, JN TI Activated carbon from pecan shell: process description and economic analysis SO INDUSTRIAL CROPS AND PRODUCTS LA English DT Article DE pecan shell; activated carbon; process flow diagram; production cost ID AGRICULTURAL BY-PRODUCTS; ADSORPTIVE PROPERTIES; ESTIMATED COST; ALMOND SHELLS; NUTSHELLS; METALS AB Granular activated carbons derived from pecan shells have been shown to adsorb a variety of metal and organic species in various processing wastewaters. Their effectiveness is equivalent to or exceeds comparable commercial carbons in this regard. The objectives of this study were to develop process flow diagrams for the large-scale production of pecan shell-based carbons derived from steam or phosphoric acid activation and to carry out an economic evaluation to estimate the cost to manufacture these carbons. On the basis of laboratory investigations with pecan shell-based carbons, process flow diagrams were established for scale-up, and an economic evaluation of carbon production costs was determined. Process flow diagrams were developed for steam and phosphoric acid activation of pecan shells. Major unit operations included shell preparation for pyrolysis, pyrolysis/activation, washing/drying and collection of the final product. Process parameters were calculated for a production facility processing 10 000 kg/day of shells. Final product yields were 13.7% for steam activation and 29.6% for phosphoric acid activation. Therefore, 1370 kg of steam-activated and 2964 kg of acid-activated pecan shell carbon could be produced per day. Mass losses were incurred during milling (20%), during pyrolysis/activation (82% for steam and 55% of acid), during washing/drying (13%) and during sieving (5%) of the final product. Based on an annual production cost of $1.22 million and an annual production of 448 000 kg of carbon, steam-activated carbon would cost about $2.72 per kg. For the phosphoric acid activation process, annual production costs were estimated at $2.78 million and annual production at 960 000 kg. Therefore, the estimated cost for acid-activated carbon would be $2.89 per kg. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA. US FDA, Dept Hlth & Human Serv, Kansas City Dist, Lenexa, KS 66285 USA. USDA ARS, So Reg Res Ctr, New Orleans, LA 70179 USA. RP Rao, RM (reprint author), Louisiana State Univ, Ctr Agr, Dept Food Sci, Food Sci Bldg, Baton Rouge, LA 70803 USA. RI Bansode, Rishipal/E-9293-2010 OI Bansode, Rishipal/0000-0001-7826-2711 NR 16 TC 29 Z9 29 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6690 J9 IND CROP PROD JI Ind. Crop. Prod. PD MAY PY 2003 VL 17 IS 3 BP 209 EP 217 DI 10.1016/S0926-6690(03)00002-5 PG 9 WC Agricultural Engineering; Agronomy SC Agriculture GA 671MD UT WOS:000182467800008 ER PT J AU Evans, DR Huang, MS Seganish, WM Fettinger, JC Williams, TL AF Evans, DR Huang, MS Seganish, WM Fettinger, JC Williams, TL TI Facile access to enantiomerically pure bis(sulfoxide) chelates of late transition metals SO INORGANIC CHEMISTRY COMMUNICATIONS LA English DT Article ID BIS-SULFOXIDES; ASYMMETRIC-SYNTHESIS; DIMETHYL-SULFOXIDE; COORDINATION CHEMISTRY; SULFINYL CHLORIDES; CHIRAL LIGANDS; COMPLEXES; HYDROGENATION; PALLADIUM(II) AB Herein contains a report detailing the synthesis and characterization of six, chiral, late-transition metal complexes all chelated using R-S, R-S-bis(p-tolylsulfinyl)ethane, R-S, R-S-BTSE. All complexes revealed S-ligation to the metal with an expected contraction of the sulfinyl-oxygen bond length when compared to free sulfoxide. The presented data serve to illustrate three attractive, yet unexplored, aspects of the bis(sulfoxide) bidentate ligand: (i) bidentate sulfoxide ligands, when chelated to a metal, give rise to complexes that are pseudo-C-2 symmetric in terms of both sterics and electronics, (ii) the sulfoxides, unlike typical N-, P-, and O-based ligands, present the coordination sphere with a significant amount of steric and electronic mismatch, and (iii) the data support the fact that sulfoxides are moderate sigma-donors and good-to-excellent pi-acceptors - an aspect that should afford such metal chelates with a wide degree of reactivity. Finally, X-ray crystallographic experiments, coupled with an extensive CCDC search, provide an opportunity to establish the following ligand-ranking scheme for bidentate ligands spanned by an ethylene bridge, R2N- < RS(O)- < RS- < R2P-, based on the trans influence of chloride salts of Pt(H). (C) 2003 Elsevier Science B.V. All rights reserved. C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Nutr, College Pk, MD 20741 USA. RP Evans, DR (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. NR 41 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-7003 J9 INORG CHEM COMMUN JI Inorg. Chem. Commun. PD MAY PY 2003 VL 6 IS 5 BP 462 EP 465 DI 10.1016/S1387-7003(03)00004-2 PG 4 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 661BL UT WOS:000181871300009 ER PT J AU Manger, RL Leja, LS Lee, SY Hungerford, JM Kirkpatrick, MA Yasumoto, T Wekell, MM AF Manger, RL Leja, LS Lee, SY Hungerford, JM Kirkpatrick, MA Yasumoto, T Wekell, MM TI Detection of paralytic shellfish poison by rapid cell bioassay: Antagonism of voltage-gated sodium channel active toxins in vitro SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TISSUE-CULTURE ASSAY; BREVE RED TIDE; MOUSE BIOASSAY; BREVETOXINS; CIGUATOXINS; SAXITOXINS; EXTRACTS AB Although cytotoxicity assays provide several advantages over mouse bloassays, sodium channel-blocking marine toxins, such as those associated with paralytic shellfish poison (PSP), require prolonged incubation periods of 24-48 h. This is in marked contrast to in vitro detection of sodium channel-enhancing marine toxins such as ciguatoxins or brevetoxins which can be accomplished in as few as 4-6 h. We developed a modified PSP. cell bioassay that is as rapid as in vitro methods for sodium channel-enhancing toxins. The cell bioassay is based on a saxitoxin-dependent antagonism of the rapid in vitro effects of brevetoxin or ciguatoxin. Comparative analysis of naturally incurred PSP residues by both antagonism cell bioassay and the mouse bioassay demonstrated significant correlation. The simplicity, sensitivity, and enhanced kinetics of the new antagonism cell bioassay format provide the basis for development of a practical alternative to conventional mouse testing for PSP. C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98041 USA. Washington State Dept Hlth, Shoreline, WA 98155 USA. Japan Food Res Labs, Tama Lab, Tokyo, Japan. US FDA, NE Reg Lab, Jamaica, NY USA. RP Manger, RL (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,CIM-027, Seattle, WA 98109 USA. EM rmanger@fhcrc.org NR 18 TC 29 Z9 31 U1 2 U2 9 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2003 VL 86 IS 3 BP 540 EP 543 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 690EY UT WOS:000183535500018 PM 12852573 ER PT J AU Perfetti, GA Diachenko, GW AF Perfetti, GA Diachenko, GW TI Determination of sulfite in dried garlic by reversed-phase ion-pairing liquid chromatography with post-column detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID BOUND SULFITE; FOODS AB A method is described for determining sulfite in dried garlic. Garlic is extracted with an HCl solution to inhibit the formation of allicin, which interferes with the determination of sulfite. After cleanup of the extract on a C-18 solid-phase extraction column, sulfite is converted to hydroxymethylsulfonate (HMS) by adding formaldehyde and heating to 50degreesC. HMS is determined by reversed-phase ion-pairing liquid chromatography with post-column detection. The post-column reaction system consists of the addition of KOH to convert HMS to sulfite ion, followed by the addition of 5,5'-dithiobis(2-nitrobenzoic acid) to produce 5-mercapto-2-nitrobenzoic acid which is detected spectrophotometrically at 450 nm. Background levels in unsulfited dried garlic equivalent to <20 ppm SO2 were found. Recoveries of HMS from spiked garlic averaged 94.8% with a coefficient of variation of 3.8%. Sulfite was found in 13 of 21 samples of dried garlic produced in China, with sulfite ranging from 114 to 445 ppm. Sulfite was found in 60% of commercial dried garlic products purchased locally. The suitability of the Monier-Williams method for determining sulfite in garlic is discussed. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Perfetti, GA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 10 TC 11 Z9 12 U1 3 U2 9 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 MAY-JUN PY 2003 VL 86 IS 3 BP 544 EP 550 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 690EY UT WOS:000183535500019 PM 12852574 ER PT J AU Anderson, DL AF Anderson, DL TI Multielement analysis of housewares and other food-related items by a Am-241 radioisotope X-ray fluorescence transportable spectrometer and handheld analyzers SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CERAMIC GLAZES; LEAD; IDENTIFICATION AB Radioisotopic X-ray fluorescence spectrometry (RXRFS) performed with an analyzer based on a Am-241 excitation source was investigated as a potential field method for screening housewares for the presence of toxic elements. A compact system based on commercially available detection and multichannel analyzer components was used to measure surface concentrations of Au, Ba, Bi, Cd, Ce, Co, Cs, Cu, Fe, La, Pb, Sb, Sn, Sr, Zn, and Zr in a wide variety of housewares and other food-related items. Certified reference material solders, glasses, and paint films and well-characterized oven-fired test tile glazes, solders, and metal can seams were analyzed to determine element sensitivities and analytical limits and to demonstrate the accuracy of the instrument. With analysis times of 3-5 min, the analyzer demonstrated 3sigma limits of detection of less than or equal to100 mug/cm(2) for elements with Z = 40-65 and Z > 70. Very good accuracy was demonstrated for glaze and thin-sample analyses, whereas analysis was possible for solders and metal can seams with greater uncertainties (20-40%). Two commercially available handheld RXRFS analyzers, evaluated as part of the study, yielded results that agreed well with those obtained with the Am-241-based RXRFS system. C1 US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch, College Pk, MD 20740 USA. NR 16 TC 8 Z9 8 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 MAY-JUN PY 2003 VL 86 IS 3 BP 583 EP 597 PG 15 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 690EY UT WOS:000183535500025 PM 12852580 ER PT J AU Cheng, YY Chen, MJ Tong, WD AF Cheng, YY Chen, MJ Tong, WD TI An approach to comparative analysis of chromatographic fingerprints for assuring the quality of botanical drugs SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ARTIFICIAL NEURAL NETWORKS; GINKGO-BILOBA; IDENTIFICATION; CLASSIFICATION; FLAVONOIDS AB The present study was focused on developing the chemometric methods for analysis of the chromatographic fingerprint to control the quality of botanical drugs, which has gained attention in Asia and other countries. We developed a novel approach to generate a set of fingerprint features, called Fisher components (FCs) that were extracted from the chromatographic fingerprint. The method greatly reduces the dimensionality of the fingerprint vector, and the resulting FCs still retain most discriminatory information of the original fingerprint. Choosing an example of relevance to contemporary botanical drugs, we applied the FCs to a set of Shenmai injection samples. We successfully identified the manufacturers of the samples using two classifiers, linear discriminant analysis (LDA) and k-Nearest Neighbor (k-NN) based on the FCs. We also applied a similarity assessment together with the visual analysis using the FCs to exam the products from different manufacturers. We found that the lot-to-lot consistency of products can be accurately determined using the FCs. Finally, we demonstrated that the application of chemometric methods for chromatographic fingerprinting offers reliability to detect suspected fraud samples. In summary, we demonstrated that the presented approaches could be useful to determine the identity, consistency, and authenticity of Shenmai injection through chromatographic fingerprinting. The methods are equally applicable to other botanical drugs. C1 Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310027, Peoples R China. US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. RP Cheng, YY (reprint author), Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310027, Peoples R China. NR 16 TC 41 Z9 49 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD MAY-JUN PY 2003 VL 43 IS 3 BP 1068 EP 1076 DI 10.1021/ci034034c PG 9 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 684LR UT WOS:000183209300038 PM 12767166 ER PT J AU Meyer, JM AF Meyer, JM TI Use of lactoferrin for Helicobacter pylori eradication SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Meyer, JM (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAY-JUN PY 2003 VL 36 IS 5 BP 384 EP 385 DI 10.1097/00004836-200305000-00003 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 669WZ UT WOS:000182374600003 PM 12702976 ER PT J AU Agnello, D Lankford, CSR Bream, J Morinobu, A Gadina, M O'Shea, JJ Frucht, DM AF Agnello, D Lankford, CSR Bream, J Morinobu, A Gadina, M O'Shea, JJ Frucht, DM TI Cytokines and transcription factors that regulate T helper cell differentiation: New players and new insights SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Review DE T helper (T-H) cells; differentiation; T(H)1 cells; T(H)2 cells; interferon-gamma; interleukin (IL)-4; IL-12; IL-23; IL-27; Stat1; Stat4; Stat6; GATA-3; c-Maf; NFATs ID IFN-GAMMA-PRODUCTION; INDUCED AIRWAY HYPERRESPONSIVENESS; STAT4 SERINE PHOSPHORYLATION; ACTIVATED PROTEIN-KINASE; MOUSE IL-12 RECEPTOR; DEVELOPING TH1 CELLS; NF-KAPPA-B; CUTTING EDGE; GENE-EXPRESSION; INTERFERON-GAMMA AB The differentiation of naive CD4(+) T cells into subsets of T helper cells is a pivotal process with major implications for host defense and the pathogenesis of immune-mediated diseases. Though the basic paradigm was discovered more than 15 years ago, new discoveries continue to be made that offer fresh insights into the regulation of this process (1). T helper (T-H)1 cells produce interferon (IFN)-gamma, promoting cell-mediated immunity and control of intracellular pathogens. We now know that T(H)1 differentiation is regulated by transcription factors such as T-bet, Stat1, and Stat4, as well as cytokines such as IL-12, IL-23, IL-27, type I IFNs, and IFN-gamma. In contrast, T(H)2 cells produce IL-4, which promotes allergic responses and is important in host defense against helminths. The transcription factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote T(H)2 differentiation. These key regulators of T-H differentiation are the subject of this review. C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20802 USA. US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Queens Univ Belfast, Dept Microbiol & Immunol, Belfast, Antrim, North Ireland. RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 9N262,10 Ctr Dr,MSC 1820, Bethesda, MD 20802 USA. NR 174 TC 231 Z9 250 U1 0 U2 7 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 2003 VL 23 IS 3 BP 147 EP 161 DI 10.1023/A:1023381027062 PG 15 WC Immunology SC Immunology GA 666FR UT WOS:000182166900001 PM 12797537 ER PT J AU Lathers, CM Schraeder, PL Claycamp, HG AF Lathers, CM Schraeder, PL Claycamp, HG TI Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: Comparison of efficacy and side effects using odds ratios SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review DE odds ratios; phenobarbital; topirimate; lamotrigine; efficacy; safety ID CARDIAC NEURAL DISCHARGE; SUDDEN UNEXPLAINED DEATH; EPILEPTOGENIC ACTIVITY; ANTIEPILEPTIC DRUGS; AUTONOMIC DYSFUNCTION; STATUS EPILEPTICUS; EPILEPSY; RISK; ANTICONVULSANT; MONOTHERAPY AB Clinical pharmacologists, neurologists, internists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug (AED) when determining which drug is best for a given patient. The first purpose of this paper is to address whether the "new" AEDs have advantages over the "old" drugs. The second purpose is to teach those interested in clinical pharmacology about the use of Web-based information access to answer a neurology/ clinical pharmacology problem: to compare the efficacy and side effects of topiramate versus lamotrigine versus phenobarbital using odds ratios. Cost of all three AEDs was also compared. A number of new AEDs, including topiramate and lamotrigine, have been developed for chronic focal and secondarily generalized epileptic seizures. Efficacy of these drugs as anticonvulsants does not seem to be superior to that of traditional anticonvulsants such as phenobarbital. However, the advantage of the new drugs is a different spectrum of possible adverse events. Newer AEDs may or may not induce sedation and may minimize noncompliance by reducing side effects of lethargy and cognitive impairment. The difficulty in achieving therapeutic dosage because of side effects makes one consider whether these agents are "better" than the oldest and most side effect prone AED, phenobarbital. The new AEDs have less frequent interactions, leading to improved tolerability with comedication. This exercise compares two "new" AEDs, topiramate and lamotrigine, with phenobarbital by evaluating efficacies and side effects using relative odds ratios, a method commonly used in drug development research. Development of new algorithms and/or new knowledge will bring beneficial tools to all clinical pharmacologists. (C) 2003 the American College of Clinical Pharmacology. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Lathers, CM (reprint author), US FDA, Ctr Vet Med, 7519 Standish Pl, Rockville, MD 20855 USA. NR 59 TC 10 Z9 10 U1 1 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 MAY PY 2003 VL 43 IS 5 BP 491 EP 503 DI 10.1177/0091270003251837 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 671AP UT WOS:000182442800004 PM 12751270 ER PT J AU Yeung, PSM DePaola, A Kaysner, CA Boor, KJ AF Yeung, PSM DePaola, A Kaysner, CA Boor, KJ TI A PCR assay for specific detection of the pandemic Vibrio parahaemolyticus 03 : K6 clone from shellfish SO JOURNAL OF FOOD SCIENCE LA English DT Article DE rapid detection; Vibrio parahaemolyticus 03 : K6; polymerase chain reaction (PCR); shellfish ID POLYMERASE-CHAIN-REACTION; DIRECT HEMOLYSIN GENE; MULTIPLEX PCR; O3-K6 CLONE; STRAINS; EMERGENCE; TDH; SEQUENCE; OYSTERS; TRH AB The current standard method for identifying Vibrio parahaemolyticus serotype O3:K6, an emerging pathogen with apparent enhanced virulence characteristics, typically takes 4 to 6 d to complete and requires serotyping. To provide a more rapid strategy, we optimized a polymerase chain reaction (PCR) -based assay for specific detection of V parahaemolyticus O3:K6. Of 78 V parahaemolyticus isolates and other related species; only strains classified into the V parahaemolyticus O3:K6 clonal group (n = 39) showed positive results in the PCR assay. The assay detected 2.3 cells/PCR reaction and 310 cells/g using bacterial cultures and inoculated oyster samples, respectively. Sensitive and specific detection of V parahaemolyticus O3:K6 was possible following a 6-h enrichment. C1 Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. RP Boor, KJ (reprint author), Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. RI Boor, Kathryn/B-3545-2009 OI Boor, Kathryn/0000-0001-6810-3434 NR 37 TC 7 Z9 7 U1 0 U2 1 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD MAY PY 2003 VL 68 IS 4 BP 1459 EP 1466 PG 8 WC Food Science & Technology SC Food Science & Technology GA 682BN UT WOS:000183070600055 ER PT J AU Snellings, SL Takenaka, NE Kim-Hayes, Y Miller, DW AF Snellings, SL Takenaka, NE Kim-Hayes, Y Miller, DW TI Rapid colorimetric method to detect indole in shrimp with gas chromatography mass spectrometry confirmation SO JOURNAL OF FOOD SCIENCE LA English DT Article DE colorimetry; indole; biogenic amines; 4-(dimethylamino) benzaldehyde; shrimp ID FISH PRODUCTS; TEMPERATURE; TRYPTOPHAN; 3-METHYLINDOLE; IDENTIFICATION; DERIVATIVES; REAGENT; AUXINS; COAST; ACID AB With increased public concern over the freshness and quality of seafood, more pressure is being applied to the industry to provide better products in the market place. Simple, fast, and inexpensive tests are needed to assess seafood quality. Seafood decomposition can be characterized by biogenic amine formation, such as the formation of indole in shrimp. We have developed a rapid colorimetric method using 4-(dimethylamino)benzaldehyde method that detects indole in decomposing shrimp. This method, as well as the confirmatory gas chromatography/mass spectrometry (GC/MS) method, is centered on a simple toluene extraction technique that recovers indole with high efficiency. Excellent agreement was obtained between the colorimetric and GUMS quantitative results for shrimp decomposition. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson Labs, Jefferson, AR 72079 USA. Brown & Williamson Tobacco Corp, Macon, GA 31217 USA. Magellan Labs Inc, Magellan Lab 160, Morrisville, NC 27560 USA. RP Miller, DW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson Labs, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM dmiller@nctr.fda.gov NR 53 TC 8 Z9 9 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1147 EI 1750-3841 J9 J FOOD SCI JI J. Food Sci. PD MAY PY 2003 VL 68 IS 4 BP 1548 EP 1553 DI 10.1111/j.1365-2621.2003.tb09682.x PG 6 WC Food Science & Technology SC Food Science & Technology GA 682BN UT WOS:000183070600070 ER PT J AU Xin, KQ Ooki, T Jounai, N Mizukami, H Hamajima, K Kojima, Y Ohba, K Toda, Y Hirai, SI Klinman, DM Ozawa, K Okuda, K AF Xin, KQ Ooki, T Jounai, N Mizukami, H Hamajima, K Kojima, Y Ohba, K Toda, Y Hirai, SI Klinman, DM Ozawa, K Okuda, K TI A DNA vaccine containing inverted terminal repeats from adeno-associated virus increases immunity to HIV SO JOURNAL OF GENE MEDICINE LA English DT Article DE AAV-ITR; DNA vaccine; immune response ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL-MEDIATED-IMMUNITY; SITE-SPECIFIC INTEGRATION; CATIONIC LIPOSOMES; EXPRESSION PLASMID; T-LYMPHOCYTES; IN-VIVO; PROTECTIVE IMMUNITY; ADJUVANT; IMMUNIZATION AB Background DNA vaccines have been used to induce both humoral and cellular immune responses against infectious microorganisms. This study explores whether DNA vaccine immunogenicity can be improved by introducing inverted terminal repeats (ITRs) from adeno-associated virus (AAV) into the regulatory region of the DNA plasmid. Methods CMV promoter-driven HIV Env expressing plasmid (pCMV-HIV) and the pCMV-HIV plasmid introduced ITRs (pITR/CMV-HIV) were transfected in HEK293 cells with LipofectAmine. The HIV Env expression was quantified with Western blot. Fifty mug of pCMV-HIV or pITR/CMV-HIV plasmid with RIBI adjuvant were immunized to BALB/c mice on days 0, 14 and 28 by intramuscular route, and HIV-specific serum IgG titer was detected 2, 6, 10, 14 and 18 weeks after the first immunization. HIV-specific tetramer assay and HIV-specific IFN-gamma ELIspot assay were performed 1 week after the last immunization. The immune mice were intravenously challenged with a vaccinia virus expressing the HIV env gene 1 week after the last immunization. Results Significantly higher level of HIV Env expression was achieved by pITR/CMV-HIV plasmid. BALB/c mice immunized with pITR/CMV-HIV plasmid generated significantly higher HIV-specific antibody, higher cellular immune responses and lower viral loading than animals immunized with pCMV-HIV plasmid. Conclusions AAV ITRs enhance CMV-dependent up-regulation of transgene expression and immunogenicity of DNA vaccine. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Yokohama City Univ, Dept Bacteriol, Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Jichi Med Sch, Ctr Mol Med, Div Genet Therapeut, Minami Kawachi, Tochigi 3290498, Japan. Yokohama City Univ, Dept Biochem, Sch Med, Yokohama, Kanagawa 2360004, Japan. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Okuda, K (reprint author), Yokohama City Univ, Dept Bacteriol, Sch Med, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. RI Mizukami, Hiroaki/D-7674-2013; Ohba, Kenji/D-8072-2015 OI Mizukami, Hiroaki/0000-0001-8954-874X; Ohba, Kenji/0000-0002-4936-8186 NR 31 TC 16 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAY PY 2003 VL 5 IS 5 BP 438 EP 445 DI 10.1002/jgm.356 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 689KZ UT WOS:000183493100009 PM 12731092 ER PT J AU Verthelyi, D Gursel, M Kenney, RT Lifson, JD Liu, SY Mican, J Klinman, DM AF Verthelyi, D Gursel, M Kenney, RT Lifson, JD Liu, SY Mican, J Klinman, DM TI CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN IMMUNE CELLS; BACTERIAL-DNA; CUTANEOUS LEISHMANIASIS; PERIPHERAL-BLOOD; INNATE IMMUNITY; HIV-1 INFECTION; CUTTING EDGE; IN-VIVO AB Oligodeoxynucleotides containing CpG motifs (CpG ODNs) mimic microbial DNA and activate effectors of the innate immune response, which limits the spread of pathogens and promotes an adaptive immune response. CpG ODNs have been shown to protect mice from infection with intracellular pathogens. Unfortunately, CpG motifs that optimally stimulate humans are only weakly active in mice, mandating the use of nonhuman primates to monitor the activity and safety of "human" CpG ODNs in vivo. This study demonstrates that CpG ODN treatment of rhesus macaques significantly reduces the severity of the lesions caused by a challenge with Leishmania. Leishmania superinfection is common in immunocompromised hosts, particularly those infected with HIV. This study shows that PBMCs from HIV-infected subjects respond to stimulation with CpG ODNs. To determine whether CpG ODNs can protect retrovirus-infected primates, SIV-infected macaques were treated with CpG ODNs and then challenged with Leishmania. Both lesion size and parasite load were significantly reduced in the CpG-treated animals. These findings support the clinical development of CpG ODNs as immunoprotective agents in normal and HIV-infected patients. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. NIAID, Immunoregulat Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Verthelyi, D (reprint author), Bldg 29A,Room 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Gursel, Mayda /H-1812-2012 FU NCI NIH HHS [N01-CO-12400] NR 44 TC 78 Z9 87 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2003 VL 170 IS 9 BP 4717 EP 4723 PG 7 WC Immunology SC Immunology GA 672NX UT WOS:000182528100038 PM 12707351 ER PT J AU Yeh, LH Alayash, AI AF Yeh, LH Alayash, AI TI Redox side reactions of haemoglobin and cell signalling mechanisms SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE blood substitutes; haemoglobin; hypoxia-inducible factor; signalling pathways ID HYPOXIA-INDUCIBLE FACTOR-1; HEME DEGRADATION; HYDROGEN-PEROXIDE; OXYGEN CARRIERS; BOVINE HEMOGLOBIN; BLOOD SUBSTITUTES; TRANSDUCTION; ACTIVATION; METHEMOGLOBIN; OXIDANTS AB Cell-free chemically modified or recombinant haemoglobins developed as oxygen therapeutics are designed to correct oxygen deficit caused by ischaemia in a variety of clinical settings. Oxidative processes, which are in some cases enhanced when modifications are introduced that lower oxygen affinity, can limit the safety of these proteins. Direct cytotoxic effects associated with haemoglobins have been ascribed to the redox reactions between haemoglobin and biological peroxides [i.e. hydrogen peroxide (H2O2), lipid peroxides (LOOH) and peroxynitrite (ONOO-)]. Biochemical changes at the cellular, tissue and organ levels have been documented to occur in response to haemoglobin oxidative reactions. These peroxides have been implicated as regulators of redox sensitive cell signalling pathways. The effects of reactions between haemoglobin and biologically relevant peroxides may be more subtle than oxidative damage and may thus involve perturbation of redox sensitive signalling pathways. In this review, a brief outline of the role of cell-free haemoglobin in oxidative and cell-signalling pathways and the implications of these reactions on the safety and efficacy evaluation of haemoglobin-based oxygen carries are presented. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, 8800 Rockville Pike,NIH Bldg 29,Rm 112, Bethesda, MD 20892 USA. NR 33 TC 19 Z9 20 U1 0 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD MAY PY 2003 VL 253 IS 5 BP 518 EP 526 DI 10.1046/j.1365-2796.2003.01152.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 668YA UT WOS:000182323100004 PM 12702029 ER PT J AU Hsia, CC Scudamore, CH Di Bisceglie, AM Tabor, E AF Hsia, CC Scudamore, CH Di Bisceglie, AM Tabor, E TI Molecular and serological aspects of HBsAg-negative hepatitis B virus infections in North America SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE silent HBV; genotype; CCC DNA; blood transfusion; hepatocellular carcinoma ID SURFACE-ANTIGEN; C VIRUS; HEPATOCELLULAR-CARCINOMA; POSTTRANSFUSION HEPATITIS; LIVER-DISEASE; X-GENE; DNA; SERUM; GENOTYPES; TRANSMISSION AB A few hepatitis B virus (HBV) infections are characterized by the presence of HBV DNA in serum or liver tissue, or both, in the absence of detectable hepatitis B surface antigen (HBsAg) in serum. However, such infections have rarely been described previously in North American patients. In the present study, 31 hepatocellular carcinoma (HCC) patients from the United States and Canada who had no detectable HBsAg in their serum were studied. In these 31 HBsAg-negative HCC patients, HBV DNA was detected in HCC and/or in adjacent nontumorous liver tissue using nested polymerase chain reaction (PCR) in 5/9 (56%) patients from the United States and in 12/22 (55%) from Canada. The 17 HBV DNA-positive/HBsAg-negative patients from the United States and Canada included 9 without any serological markers for HBV and 8 with detectable antibodies to hepatitis B core antigen. In these patients, HBV genotype C was the most prevalent genotype (11/17; 64%). HBV genotypes have not been previously reported in HCC patients from North America. Replicative intermediate forms of HBV (covalently closed circular HBV DNA) were detected in 2/17 (12%) HBV DNA-positive/HBsAg-negative patients, indicating that at least two of these patients had actively replicating HBV infections. The use of tests to detect HBV DNA permitted the identification of HBV infections in HBsAg-negative HCC patients from North America. Among these patients, those with antibody to hepatitis C virus (HCV) would otherwise have been designated "HCV-associated HCCs" based on serological tests alone. These findings provide a new perspective on determining the possible viral etiologies of HCCs in North America. (C) 2003 Wiley-Liss, Inc. C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. Vancouver Gen Hosp, Dept Surg, Vancouver, BC, Canada. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. RP Tabor, E (reprint author), 1401 Rockville Pike,HFM-300, Rockville, MD 20852 USA. NR 32 TC 14 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAY PY 2003 VL 70 IS 1 BP 20 EP 26 DI 10.1002/jmv.10353 PG 7 WC Virology SC Virology GA 682AN UT WOS:000183067800004 PM 12629639 ER PT J AU Afzal, MA Osterhaus, ADME Cosby, SL Jin, L Beeler, J Takeuchi, K Kawashima, H AF Afzal, MA Osterhaus, ADME Cosby, SL Jin, L Beeler, J Takeuchi, K Kawashima, H TI Comparative evaluation of measles virus-specific RT-PCR methods through an international collaborative study SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE measles virus; RT-PCR; diagnosis ID INFLAMMATORY-BOWEL-DISEASE; POLYMERASE-CHAIN-REACTION; PERIPHERAL MONONUCLEAR-CELLS; CROHNS-DISEASE; GENOME SEQUENCE; ABSENCE; SPECIMENS; INFECTION; CHILDREN; TISSUES AB Comparison of RT-PCR assays established in house at various places revealed that laboratories could differ insensitivity by as much as 1,000-fold in terms of the ability to detect measles virus sequences in clinical samples. The study indicates that PCR findings, positive or negative, are questionable if they are not supported by the associated data demonstrating the overall sensitivity of the assay applied. Measles virus-specific RT-PCR-based assays need to be validated using standard virus preparation or nucleic acid-based target templates. A correlation between real-time quantitative PCR and the conventional PCR for measles virus is highly desirable. (C) 2003 Wiley-Liss, Inc. C1 Natl Inst Biol Stand & Controls, Div Virol, Potters Bar EN6 3QG, Herts, England. Erasmus MC, Inst Virol, Rotterdam, Netherlands. Queens Univ Belfast, Dept Microbiol, Ctr Med Biol, Belfast, Antrim, North Ireland. WHO, Global Reference Lab Measles, Cent Publ Hlth Lab, London, England. US FDA, CBER, OVRR, Div Viral Prod,Lab Pediat & Resp Virus Dis, Bethesda, MD USA. Natl Inst Infect Dis, Dept Virol 3, Tokyo, Japan. Tokyo Med Univ, Dept Pediat, Tokyo, Japan. RP Afzal, MA (reprint author), Natl Inst Biol Stand & Controls, Div Virol, Potters Bar EN6 3QG, Herts, England. NR 21 TC 20 Z9 23 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAY PY 2003 VL 70 IS 1 BP 171 EP 176 DI 10.1002/jmv.10371 PG 6 WC Virology SC Virology GA 682AN UT WOS:000183067800025 PM 12629660 ER PT J AU Blackstone, GM Nordstrom, JL Vickery, MCL Bowen, MD Meyer, RF DePaola, A AF Blackstone, GM Nordstrom, JL Vickery, MCL Bowen, MD Meyer, RF DePaola, A TI Detection of pathogenic Vibrio parahaemolyticus in oyster enrichments by real time PCR SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Vibrio parahaemolyticus; oyster; real time PCR ID THERMOSTABLE DIRECT HEMOLYSIN; POLYMERASE-CHAIN-REACTION; UNITED-STATES; GENE; TDH; WASHINGTON; SHELLFISH; CHOLERAE; TRH AB A real time polymerase chain reaction (PCR) assay was developed and evaluated to detect the presence of the thermostable direct hemolysin gene (tdh), a current marker of pathogenicity in Fibrio parahaenzolyticus. The real time PCR fluorogenic probe and primer set was tested against a panel of numerous strains from 13 different bacterial species. Only V parahaemolyticus strains possessing the tdh gene generated a fluorescent signal, and no cross-reaction was observed with-tdh negative Vibrio or non-ribrio spp. The assay detected a single colony forming unit (CFU) per reaction of a pure culture template. This sensitivity was achieved when the same template amount per reaction was tested in the presence of 2.5 mul of a tdh negative oyster:APW enrichment (oyster homogenate enriched in alkaline peptone water overnight at 35 degreesC). This real time technique was used to test 131 oyster:APW enrichments from an environmental survey of Alabama oysters collected between March 1999 and September 2000. The results were compared to those previously obtained using a streak plate procedure for culture isolation from the oyster:APW enrichment combined with use of a non-radioactive DNA probe for detection of the tdh gene. Real time PCR detected tdh in 61 samples, whereas the streak plate/probe method detected tdh in 15 samples. Only 24 h was required for detection of pathogenic V parahaemolyticus in oyster:APW enrichments by real time PCR, whereas the streak plate/probe method required 3 days and was more resource intensive. This study demonstrated that real time PCR is a rapid and reliable technique for detecting V parahaemolyticus possessing the tdh gene in pure cultures and in oyster enrichments. Published by Elsevier Science B.V. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RP Blackstone, GM (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Isl, AL 36528 USA. NR 26 TC 106 Z9 128 U1 1 U2 20 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 MAY PY 2003 VL 53 IS 2 BP 149 EP 155 DI 10.1016/S0167-7012(03)00020-4 PG 7 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 668NB UT WOS:000182299100003 PM 12654486 ER PT J AU Yaes, RJ AF Yaes, RJ TI A simple method of estimating biologically equivalent doses for radiopharmaceutical therapy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 US FDA, HFD 160, Div Med Imaging & Radiopharmaceut Drug Products, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 332 BP 102P EP 102P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600333 ER PT J AU Sun, H Collins, JM Mangner, TJ Muzik, O Douglas, KA Shields, AF AF Sun, H Collins, JM Mangner, TJ Muzik, O Douglas, KA Shields, AF TI Imaging biodistribution of F-18-FAU via PET in patients with tumors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. FDA, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 1328 BP 372P EP 373P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601245 ER PT J AU Pershing, LK Nelson, JL Corlett, JL Shrivastava, SP Hare, DB Shah, VP AF Pershing, LK Nelson, JL Corlett, JL Shrivastava, SP Hare, DB Shah, VP TI Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID TRANS-RETINOIC ACID; 13-CIS-RETINOIC ACID; BIOAVAILABILITY; IDENTIFICATION; ISOTRETINOIN; EFFICACY; ACNE AB Background: A new dermatopharmacokinetic (DPK) approach has been proposed for bioequivalence determination of topical drug products by comparing the drug content kinetics in stratum corneum. Objective. We sought to establish any correlation between clinical safety/efficacy and DPK approach in bioequivalence determination of tretinoin get 0.025%. Methods: Tretinoin and isotretinoin were quantified in human volar forearm stratum corneum as a function of time with 3 tretinoin gel 0.025% products in 49 patients. Stratum corneum layers were harvested using multiple adhesive disks, which were subsequently extracted and quantified for both isomers by high-performance liquid chromatography. Results: Products with similar composition and therapeutic equivalence were found bioequivalent, and products with different composition and clinical profiles were found bioinequivalent by DPK methodology. Conclusions: There is a direct correlation between DPK parameters in healthy patients and clinical safety/efficacy of tretinoin gel products in patients with acne. Data support the use of DPK parameters and methodology in the bioequivalence assessment of topical tretinoin gel products. C1 Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84132 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Pershing, LK (reprint author), Univ Utah, Sch Med, Dept Dermatol, 50 N Med Dr, Salt Lake City, UT 84132 USA. FU ODCDC CDC HHS [D75006-00-01-CC-00] NR 19 TC 41 Z9 44 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2003 VL 48 IS 5 BP 740 EP 751 DI 10.1067/mjd.2003.175 PG 12 WC Dermatology SC Dermatology GA 680KT UT WOS:000182977200013 PM 12734504 ER PT J AU Bethem, R Boison, J Gale, J Heller, D Lehotay, S Loo, J Musser, S Price, P Stein, S AF Bethem, R Boison, J Gale, J Heller, D Lehotay, S Loo, J Musser, S Price, P Stein, S TI Establishing the fitness for purpose of mass spectrometric methods SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID DRUG RESIDUES; CONFIRMATION; IDENTIFICATION AB This report is submitted by a working group sponsored by the ASMS Measurements and Standards Committee. The group responded to a 1998 opinion piece dealing with mass spectrometry in trace analysis (Bethem, R. A.; Boyd, R. K. J. Am. Soc. Mass Spectrom. 1998, 9, 643-648) which proposed that the concept of fitness for purpose addresses the needs of a wide range of analytical problems. There is a need to define fitness for purpose within the current context of mass spectrometry and to recommend processes for developing and evaluating methods according to suitability for a particular purpose. The key element in our proposal is for the interested parties to define in advance the acceptable degree of measurement uncertainty and the desired degree of identification confidence. These choices can serve as guideposts during method development and targets for retrospective evaluation of methods. A series of more detailed recommendations are derived from basic principles and also from reviews of current practice. This report highlights some areas where consensus is evident, but also revealed the need for further work in other areas. The recommendations are aimed primarily for the laboratory analyst but we hope they will be accessible to the non-scientist as well. Our goal was to provide a framework that can support informed decisions and foster discussion of the issues, because ultimately it is the responsibility of the analyst to make choices, provide supporting data, and interpret results according to scientific principles and qualified judgment. (C) 2003 American Society for Mass Spectrometry. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Bristol Myers Squibb Co, New Brunswick, NJ USA. Canadian Food Inspect Agcy, Saskatoon, SK, Canada. Alta Analyt Lab, El Dorado Hills, CA USA. USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA USA. Pfizer, Global Res & Dev, Ann Arbor, MI USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Dow Chem Co USA, S Charleston, WV USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RP Heller, D (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 16 TC 63 Z9 63 U1 1 U2 14 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 MAY PY 2003 VL 14 IS 5 BP 528 EP 541 DI 10.1016/S1044-0305(03)00137-5 PG 14 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 683UV UT WOS:000183169400013 PM 12745222 ER PT J AU Hashimoto, Y Chen, HS Cunningham, C Malik, TH Lai, PK AF Hashimoto, Y Chen, HS Cunningham, C Malik, TH Lai, PK TI Two major histocompatibility complex class I-restricted epitopes of the Borna disease virus p10 protein identified by cytotoxic T lymphocytes induced by DNA-based immunization SO JOURNAL OF VIROLOGY LA English DT Article ID DENDRITIC CELLS; NERVOUS-SYSTEM; INFECTED RATS; BRAIN; NUCLEOPROTEIN; ANTIGEN; MENINGOENCEPHALOMYELITIS; INDUCTION; VACCINES; MHC AB Borna disease virus (BDV) infection of Lewis rats is the most studied animal model of Borna disease, an often fatal encephalomyelitis. In this experimental model, BDV-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a prominent role in the immunopathogenesis of infection by the noncytolytic, persistent BDV. Of the six open reading frames of BDV, CTLs to BDV X (p10) and the L-polymerase have never been studied. In this study, we used plasmid immunization to investigate the CTL response to BDV X and N. Plasmid-based immunization was a potent CTL inducer in Lewis rats. Anti-X CTLs were primed by a single injection of the p10 cDNA. Two codominant p10 epitopes, M1SSDLRLTLL10 and T8LLELVRRL16, associated with the RT1.A(1) major histocompatibility complex class I molecules of the Lewis rats, were identified. In addition, immunization with a BDV p40-expressing plasmid confirmed the previously reported RT1.V-restricted A(230)SYAQMTTY(238) peptide as the CTL target for BDV N. In contrast to the CTL responses, plasmid vaccination was a poor inducer of an antibody response to p10. Three injections of a recombinant eukaryotic expression plasmid of BDV p10 were needed to generate a weak anti-p10 immunoglobulin M response. However, the antibody response could be optimized by a protein boost after priming with cDNA. C1 Salem Int Univ, Dept Biosci, Salem, WV 26426 USA. W Virginia Univ, Sch Med, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. RP Lai, PK (reprint author), Salem Int Univ, Dept Biosci, 223 W Main St, Salem, WV 26426 USA. FU NCRR NIH HHS [P20RR16440, P20 RR016440, 1P20RR16477, P20 RR016477] NR 47 TC 4 Z9 5 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 MAY PY 2003 VL 77 IS 10 BP 6076 EP 6081 DI 10.1128/JVI.77.10.6076-6081.2003 PG 6 WC Virology SC Virology GA 674HJ UT WOS:000182631100055 PM 12719601 ER PT J AU Delmonte, P Roach, JAG Mossoba, MM Morehouse, KM Lehmann, L Yurawecz, MP AF Delmonte, P Roach, JAG Mossoba, MM Morehouse, KM Lehmann, L Yurawecz, MP TI Synthesis and isolation of trans-7,cis-9 octadecadienoic acid and other CLA isomers by base conjugation of partially hydrogenated gamma-linolenic acid SO LIPIDS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; DAIRY-COWS; SEPARATION; IDENTIFICATION; CHEESE; TISSUE; MILK AB CIA is of considerable interest because of reported potentially beneficial effects in animal studies. CLA, while not yet unambiguously defined, is a mixture of octaclecadienoic acids with conjugated double bonds. The major isomer in natural products is generally considered to be cis-9, trans-11-octadecadienoic acid (c9, t11), which represents 75% of the total CLA in most cases. Other isomers are drawing increased attention. The t7,c9 isomer, which is often the second-most prevalent CIA in natural products, has been reported to represent as much as 40% of total CLA in milk from cows fed a high-fat diet. The need for a reference material became apparent in a recent study directed specifically at measuring t7,c9-CLA in milk, plasma, and rumen. A suitable standard mixture was produced by stirring 0.5 g of gamma-linolenic acid (all cis-6,9,12-C-18:3) with 100 mL of 10% hydrazine hydrate in methanol for 2.5 h at 45degreesC. The solution was diluted with H2O and acidified with HCl. The resulting partially hydrogenated FA were extracted with ether/petroleum ether, dried with Na2SO4, and conjugated by adding of 6.6% KOH in ethlylene glycol and heating for 1.5 h at 150-160degreesC. Approximately 20 mg each of cis-6,trans-8; trans-7,cis-9; cis-9,trans-11; and trans-10,cis-12 were obtained along with other FA. Methyl esters (FAME) of these four cis/trans isomers were resolved by Ag+ HPLC (UV 233) and partially resolved by GC/(MS or FID) (CP-Sil 88). Treatment of these FAME with 12 yielded all possible cis/trans (geometric) isomers for the four positions 6,8; 7,9; 9,11; and 10,12. Paper no. L9189 in Lipids 38, 579-583 (May 2003). C1 US FDA, Ctr Food Safety & Appl Nutr, ONPLDS, DRAT, College Pk, MD 20740 USA. Univ Hamburg, Hamburg, Germany. RP Yurawecz, MP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, ONPLDS, DRAT, Room 1E-009,HFS-840,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 20 TC 16 Z9 19 U1 1 U2 7 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD MAY PY 2003 VL 38 IS 5 BP 579 EP 583 DI 10.1007/s11745-003-1499-5 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 695UY UT WOS:000183849800013 PM 12880116 ER PT J AU Li, BG Tsui, HCT LeClerc, JE Dey, M Winkler, ME Cebula, TA AF Li, BG Tsui, HCT LeClerc, JE Dey, M Winkler, ME Cebula, TA TI Molecular analysis of mutS expression and mutation in natural isolates of pathogenic Escherichia coli SO MICROBIOLOGY-SGM LA English DT Article ID MISMATCH REPAIR; PSEUDOMONAS-AERUGINOSA; HORIZONTAL TRANSFER; HIGH-FREQUENCY; STRAINS; POPULATIONS; EVOLUTION; K-12; GENES; REPLICATION AB Deficiencies in the MutS protein disrupt methyl-directed mismatch repair (MMR), generating a mutator phenotype typified by high mutation rates and promiscuous recombination. How such deficiencies might arise in the natural environment was determined by analysing pathogenic strains of Escherichia coli. Quantitative Western immunoblotting showed that the amount of MutS in a wild-type strain of the enterohaemorrhagic pathogen E. coli O157:H7 decreased about 26-fold in stationary-phase cells as compared with the amount present during exponential-phase growth. The depletion of MutS in O157:H7 is significantly greater than that observed for a laboratory attenuated E. coli K-12 strain. In the case of stable mutators, mutS defects in strains identified among natural isolates were analysed, including two E. coli O157:H7 strains, a diarrhoeagenic E. coli O55:H7 strain, and a uropathogenic strain from the E. coli reference (ECOR) collection. No MutS could be detected in the four strains by Western immunoblot analyses. RNase T2 protection assays showed that the strains were either deficient in mutS transcripts or produced transcripts truncated at the 3' end. Nucleotide sequence analysis revealed extensive deletions in the mutS region of three strains, ranging from 7.5 to 17.3 kb relative to E. coli K-12 sequence, while the ECOR mutator contained a premature stop codon in addition to other nucleotide changes in the mutS coding sequence. These results provide insights into the status of the mutS gene and its product in pathogenic strains of E. Coli. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. Univ Texas, Sch Med, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM tac@cfsan.fda.gov FU NCI NIH HHS [R01 CA77103] NR 49 TC 31 Z9 33 U1 1 U2 5 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD MAY PY 2003 VL 149 BP 1323 EP 1331 DI 10.1099/mic.0.26213-0 PN 5 PG 9 WC Microbiology SC Microbiology GA 681JL UT WOS:000183033000024 PM 12724393 ER PT J AU Wiese, FW Thompson, PA Warneke, J Einspahr, J Alberts, DS Kadlubar, FF AF Wiese, FW Thompson, PA Warneke, J Einspahr, J Alberts, DS Kadlubar, FF TI Variation in cyclooxygenase expression levels within the colorectum SO MOLECULAR CARCINOGENESIS LA English DT Article DE cyclooxygenases; colon cancer; COX-1; COX-2 ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FAMILIAL ADENOMATOUS POLYPOSIS; PROSTAGLANDIN G/H SYNTHASE-1; COLON-CANCER CELLS; HUMAN BREAST-CANCER; DIFFERENTIAL EXPRESSION; EPITHELIAL-CELLS; BCL-2 EXPRESSION; GENE-EXPRESSION; REDUCED RISK AB The positive association of decreased risk of colorectal cancer with nonsteroidal antiinflammatory drug (NSAID) use, combined with the observation that cyclooxygenase(COX)-2 is present in a majority of colorectal tumors, has led to the proposed use of isozyme-specific COX inhibitors as preventive agents in polyp and tumor formation in the colon. However, the exact biochemical mechanisms and disease stage at which reduced risk is mediated remain somewhat controversial, in part because of the complex biochemical changes that occur during the progression from aberrant crypt to polyp to tumor. In this study, COX-1 and COX-2 protein expression levels were determined in sets of tumor and normal colon tissue. Changes were characterized in COX-1 and COX-2 expression within individuals, in relation to such factors as sex, tumor grade, and location in the colorectum. COX-1 expression levels were found to be significantly reduced in tumors compared to matched normal tissues (Dunn's method, P < 0.05). Additionally, COX-1 expression was decreased in stage T3 tumors as compared to stage T2 tumors (Student's t-test, P=0.009). Similar to previous reports, COX-2 protein expression was present in 73% of the tumors studied and appeared to be independent of tumor grade and sex. Interestingly, decreased COX-2 expression correlated with tumor occurrence in rectal mucosa (Wilcoxon two-sample test, P<0.05). These results warrant further investigation, especially the identification of determinants that would predict which populations would be most responsive to COX-2 inhibition as a means of colorectal cancer chemoprevention. Published 2003 Wiley-Liss, Inc.(dagger). C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Div Toxicol, Little Rock, AR 72205 USA. Univ Arizona, Coll Med, Dept Surg, Tucson, AZ USA. Univ Arizona, Coll Med, Arizona Canc Ctr, Tucson, AZ 85724 USA. Univ Arizona, Coll Med, Dept Med, Hematol Oncol Sect, Tucson, AZ USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NR 42 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 2003 VL 37 IS 1 BP 25 EP 31 DI 10.1002/mc.10115 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 678BN UT WOS:000182845300004 PM 12720297 ER PT J AU Hoque, ATMS Smith, RH Kotin, RM Golding, B AF Hoque, ATMS Smith, RH Kotin, RM Golding, B TI High levels of foreign gene expression in hemophiliac mice after intravenous injection of a non-viral vector SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 OBRR, CBER, Food & Drug Adm, Lab Plasma Derivat,Div Hematol, Bethesda, MD USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 533 BP S208 EP S208 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300532 ER PT J AU Kawakami, K Kawakami, M Husain, SR Puri, RK AF Kawakami, K Kawakami, M Husain, SR Puri, RK TI Liposome-mediated IL-4R alpha gene transfer for targeted therapy of human breast cancer in a nude mouse model SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 332 BP S130 EP S131 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300332 ER PT J AU Lozier, JN AF Lozier, JN TI Mapping of gene(s) that may influence the immune response to human coagulation factor IX expressed in mice with adenovirus vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1025 BP S395 EP S395 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301024 ER PT J AU Smith, JS Tian, J Muller, J Byrnes, AP AF Smith, JS Tian, J Muller, J Byrnes, AP TI Chronic liver damage increases the pulmonary biodistribution of intravenously-injected adenoviral vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 CBER, FDA, Div Cellular & Gene Therapies, Bethesda, MD USA. CBER, FDA, Div Viral Prod, Bethesda, MD USA. RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 142 BP S56 EP S56 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300143 ER PT J AU Tsai, CA Chen, YJ Chen, JJ AF Tsai, CA Chen, YJ Chen, JJ TI Testing for differentially expressed genes with microarray data - art. no. 52 SO NUCLEIC ACIDS RESEARCH LA English DT Article AB This paper compares the type I error and power of the one- and two-sample t-tests, and the one- and two-sample permutation tests for detecting differences in gene expression between two microarray samples with replicates using Monte Carlo simulations. When data are generated from a normal distribution, type I errors and powers of the one-sample parametric t-test and one-sample permutation test are very close, as are the two-sample t-test and two-sample permutation test, provided that the number of replicates is adequate. When data are generated from a t-distribution, the permutation tests outperform the corresponding parametric tests if the number of replicates is at least five. For data from a two-color dye swap experiment, the one-sample test appears to perform better than the two-sample test since expression measurements for control and treatment samples from the same spot are correlated. For data from independent samples, such as the one-channel array or two-channel array experiment using reference design, the two-sample t-tests appear more powerful than the one-sample t-tests. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 19 TC 30 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 1 PY 2003 VL 31 IS 9 AR e52 DI 10.1093/nar/gng052 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 674FX UT WOS:000182627700006 PM 12711697 ER PT J AU Cote, CJ Alexander, J AF Cote, CJ Alexander, J TI Drug development for children: the past, the present, hope for the future SO PAEDIATRIC ANAESTHESIA LA English DT Editorial Material ID LABEL MEDICATION USE; OFF-LABEL; UNIT C1 Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Dept Pediat Anesthesiol, Chicago, IL 60614 USA. US FDA, Div Antiinfect Drug Prod, Rockville, MD 20857 USA. RP Cote, CJ (reprint author), Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Dept Pediat Anesthesiol, 2300 Childrens Plaza, Chicago, IL 60614 USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1155-5645 J9 PAEDIATR ANAESTH JI Paediatr. Anaesth. PD MAY PY 2003 VL 13 IS 4 BP 279 EP 283 DI 10.1046/j.1460-9592.2003.01071.x PG 5 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 677AD UT WOS:000182784000001 PM 12753438 ER PT J AU Krebs, NF Baker, RD Greer, FR Heyman, MB Jaksic, T Lifshitz, F AF Krebs, NF Baker, RD Greer, FR Heyman, MB Jaksic, T Lifshitz, F CA Comm Nutr TI Reimbursement for foods for special dietary use SO PEDIATRICS LA English DT Article AB Foods for special dietary use are recommended by physicians for chronic diseases or conditions of childhood, including inherited metabolic diseases. Although many states have created legislation requiring reimbursement for foods for special dietary use, legislation is now needed to mandate consistent coverage and reimbursement for foods for special dietary use and related support services with accepted medical benefit for children with designated medical conditions. C1 Amer Acad Pediat, Comm Nutr, Elk Grove Village, IL 60007 USA. US FDA, Rockville, MD 20857 USA. USDA, Washington, DC 20250 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NIDDKD, Bethesda, MD 20892 USA. RP Krebs, NF (reprint author), Amer Acad Pediat, Comm Nutr, Elk Grove Village, IL 60007 USA. NR 6 TC 2 Z9 2 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 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY 1 PY 2003 VL 111 IS 5 BP 1117 EP 1119 PG 3 WC Pediatrics SC Pediatrics GA 673KC UT WOS:000182579300049 ER PT J AU Uribarri, J Calvo, MS AF Uribarri, J Calvo, MS TI Hidden sources of phosphorus in the typical American diet: Does it matter in nephrology? SO SEMINARS IN DIALYSIS LA English DT Editorial Material ID HEMODIALYSIS; CALCIUM; BONE AB Elevated serum phosphorus is a major, preventable etiologic factor associated with the increased cardiovascular morbidity and mortality of dialysis patients. An important determinant of serum phosphorus is the dietary intake of this mineral; this makes dietary restriction of phosphorus a cornerstone for the prevention and treatment of hyperphosphatemia. The average daily dietary intake of phosphorus is about 1550 mg for males and 1000 mg for females. In general, foods high in protein are also high in phosphorus. These figures, however, are changing as phosphates are currently being added to a large number of processed foods including meats, cheeses, dressings, beverages, and bakery products. As a result, and depending on the food choices, such additives may increase the phosphorus intake by as a much as 1 g/day. Moreover, nutrient composition tables usually do not include the phosphorus from these additives, resulting in an underestimate of the dietary intake of phosphorus in our patients. Our goal is to convey an understanding of the phosphorus content of the current American diet to better equip nephrologists in their attempt to control hyperphosphatemia. C1 Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Washington, DC 20204 USA. RP Uribarri, J (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, 1Gustave Levy Pl, New York, NY 10029 USA. NR 14 TC 106 Z9 109 U1 0 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAY-JUN PY 2003 VL 16 IS 3 BP 186 EP 188 DI 10.1046/j.1525-139X.2003.16037.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 677AM UT WOS:000182784800002 PM 12753675 ER PT J AU Mancini, DJ Stecklov, G Stewart, JF AF Mancini, DJ Stecklov, G Stewart, JF TI The effect of structural characteristics on family planning program performance in Cote d'Ivoire and Nigeria SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE family planning; program placement; cost; Cote d'Ivoire; Nigeria ID CONTRACEPTIVE USE; REPRODUCTIVE HEALTH; QUALITY; FERTILITY; TANZANIA; SERVICES; IMPACT; PRICE AB This paper uses Cote d'Ivoire and Nigeria survey data on both supply and demand characteristics to examine how structural and demographic factors influence family planning provision and cost. The model, which takes into account the endogenous influence of service provision on average cost. explains provision well but poorly explains what influences service cost. We show that both size and specialization matter. In both countries. vertical (exclusive family planning) facilities provide significantly more contraception than integrated medical establishments. In the Nigeria sample, larger facilities also offer services at lower average cost. Since vertical facilities tend to be large, they at most incur no higher unit costs than integrated facilities. These results are consistent across most model specifications. and are robust to corrections for endogenous facility placement in Nigeria. Model results and cost recovery, information point to the relative efficiency of the International Planned Parenthood Federation. which operates large. mostly vertically organized facilities. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Hebrew Univ Jerusalem, Dept Populat Studies, IL-91905 Jerusalem, Israel. Hebrew Univ Jerusalem, Dept Sociol & Anthropol, IL-91905 Jerusalem, Israel. Univ N Carolina, Dept Econ, Chapel Hill, NC 27599 USA. RP Mancini, DJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-726,Room 2D-03,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 21 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAY PY 2003 VL 56 IS 10 BP 2123 EP 2137 AR PII S0277-9536(02)00206-X DI 10.1016/S0277-9536(02)00206-X PG 15 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 668VF UT WOS:000182313300010 PM 12697202 ER PT J AU Yim, SH Ward, JM Dragan, Y Yamada, A Scacheri, PC Kimura, S Gonzalez, FJ AF Yim, SH Ward, JM Dragan, Y Yamada, A Scacheri, PC Kimura, S Gonzalez, FJ TI Microarray analysis using amplified mRNA from laser capture microdissection of microscopic hepatocellular precancerous lesions and frozen hepatocellular carcinomas reveals unique and consistent gene expression profiles SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cDNA microarray; indirect labeling; amplified mRNA; laser capture microdissection ID MOLECULAR ANALYSIS; TISSUE; LIVER AB The indirect labeling cDNA microarray technique was used to evaluate gene expression profiles of pure cell populations from frozen sections of carcinomas and adenomas harvested from precancerous hepatocellular lesions by using laser capture microdissection (LCM). The levels of differentially expressed genes were investigated using a cDNA microarray with 9,984 features with only 2 ug of two-round amplified aRNA, equivalent to 35 cells from LCM-adenomas and frozen samples of carcinomas from simian virus 40 (SV40) large T antigen transgenic rats. A total of 855 genes were identified as being 3-fold or more differentially expressed in carcinomas or adenomas as compared to normal tissue controls. Among these 855 genes, 71 genes were differentially expressed in both carcinomas and adenomas. Commonly up-regulated genes in both carcinoma and adenomas were 28 while 41 of the 71 genes were commonly down-regulated. Two genes, Igh1 (immunoglobulin heavy chain 1(Serum IgG2a), Image clone ID: 875880) and EST clone (AI893585, Image clone ID: 596604) were more than 7-fold up-regulated in carcinomas and 6-fold down-regulated in adenomas. In Cy5 and Cy3 reciprocal experiments for screening out false positive signals, the amplified carcinomas showed higher Pearson Correlation Coefficient values (-0.94 and -0.92) than the LCM-amplified adenoma samples (-0.79 and -0.84). LCM-amplified samples provided higher signal intensities over backgrounds and a greater average of Cy5:Cy3 ratios. Expression levels of mRNAs from selected genes, determined by using traditional dot blot analysis, revealed that 36 of 40 tested expression profiles were consistent with the microarray data. Thus, amplified aRNA harvested from homogeneous cell types using LCM can be applied to study gene expression profiles by use of microarray analysis. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, Frederick, MD 21701 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 2A19,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 16 TC 20 Z9 21 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 2003 VL 31 IS 3 BP 295 EP 303 DI 10.1080/01926230390204333 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 712GA UT WOS:000184788400007 PM 12746117 ER PT J AU Ladics, GS Holsapple, MP Astwood, JD Kimber, I Knippels, LMJ Helm, RM Dong, WM AF Ladics, GS Holsapple, MP Astwood, JD Kimber, I Knippels, LMJ Helm, RM Dong, WM TI Workshop overview: Approaches to the assessment of the allergenic potential of food from genetically modified crops SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Society-of-Toxicology CY MAR 17-21, 2002 CL NASHVILLE, TENNESSEE SP Society Toxicol ID PROTEIN ALLERGENICITY; ANTIBODY-RESPONSES; ORAL SENSITIZATION; RATS; MODEL; STABILITY; OVALBUMIN; EXPOSURE; MICE AB There is a need to assess the safety of foods deriving from genetically modified (GM) crops, including the allergenic potential of novel gene products. Presently, there is no single in vitro or in vivo model that has been validated for the identification or characterization of potential food allergens. Instead, the evaluation focuses on risk factors such as source of the gene (i.e., allergenic vs. nonallergenic sources), physicochemical and genetic comparisons to known allergens, and exposure assessments. The purpose of this workshop was to gather together researchers working on various strategies for assessing protein allergenicity: (1) to describe the current state of knowledge and progress that has been made in the development and evaluation of appropriate testing strategies and (2) to identify critical issues that must now be addressed. This overview begins with a consideration of the current issues involved in assessing the allergenicity of GM foods. The second section presents information on in vitro models of digestibility, bioinformatics, and risk assessment in the context of clinical prevention and management of food allergy. Data on rodent models are presented in the next two sections. Finally, nonrodent models for assessing protein allergenicity are discussed. Collectively, these studies indicate that significant progress has been made in developing testing strategies. However, further efforts are needed to evaluate and validate the sensitivity, specificity, and reproducibility of many of these assays for determining the allergenicity potential of GM foods. C1 DuPont Co Inc, Haskell Lab, Newark, DE 19714 USA. ILSI Hlth & Environm Sci Inst, Washington, DC USA. Monsanto Co, Prod Safety Ctr, St Louis, MO USA. Syngenta Cent Toxicol Lab, Macclesfield, Cheshire, England. TNO Nutr & Food Res, NL-3700 AJ Zeist, Netherlands. Univ Arkansas Med Sci, Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72205 USA. US FDA, Washington, DC 20204 USA. RP Ladics, GS (reprint author), DuPont Co Inc, Haskell Lab, POB 50,Elkton Rd, Newark, DE 19714 USA. NR 35 TC 23 Z9 27 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2003 VL 73 IS 1 BP 8 EP 16 DI 10.1093/toxsci/kfg055 PG 9 WC Toxicology SC Toxicology GA 674FL UT WOS:000182626700003 PM 12700419 ER PT J AU Simak, J Holada, K Vostal, JG AF Simak, J Holada, K Vostal, JG TI The majority of cellular prion protein released from endothelial cells is soluble SO TRANSFUSION LA English DT Letter ID PLASMA C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20892 USA. RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, 8800 Rockville Pike,HFM-335, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2003 VL 43 IS 5 BP 678 EP 678 DI 10.1046/j.1537-2995.2003.00406.x PG 1 WC Hematology SC Hematology GA 670PV UT WOS:000182418300024 ER PT J AU Simak, J Holada, K Vostal, JG AF Simak, J Holada, K Vostal, JG TI Expression of cellular prion protein on vascular endothelial cells: more evidence than controversies SO TRANSFUSION LA English DT Letter ID PLASMA C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20892 USA. RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, 8800 Rockville Pike,HFM-335, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 5 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2003 VL 43 IS 5 BP 680 EP 681 DI 10.1046/j.1537-2995.2003.00366.x PG 2 WC Hematology SC Hematology GA 670PV UT WOS:000182418300026 ER PT J AU Herman, BA Myers, MR AF Herman, BA Myers, MR TI An analytic derivation for the transient temperature rise during an ultrasound pulse focused on bone SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE temperature rise; ultrasound; bone-at-focus; ultrasound heating ID MODELS AB An analytic derivation is given for the maximum transient temperature rise due to millisecond ultrasound (US) pulses focused on bone. The temperature rise is found to have, within a small correction factor, a square-root dependence on the pulse duration and is independent of the focal diameter. The equation developed is essentially the same as that found in a previous paper (Herman and Harris 2002) that obtained the formula by numerical methods and subsequent curve fitting. Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine Biology. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Herman, BA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9201 Corp Blvd,HFZ-132, Rockville, MD 20850 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD MAY PY 2003 VL 29 IS 5 BP 771 EP 773 DI 10.1016/S0301-5629(02)00772-X PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 681UL UT WOS:000183053900017 PM 12754077 ER PT J AU Wood, JM Levandowski, RA AF Wood, JM Levandowski, RA TI The influenza vaccine licensing process SO VACCINE LA English DT Article; Proceedings Paper CT 56th World Health Assembly Meeting CY MAY 19-28, 2003 CL GENEVA, SWITZERLAND DE influenza; vaccines; licensing; pandemic AB Influenza vaccines are unique because they require a licensing process which includes a procedure for rapid annual updates to vaccine strains. The licensing procedures in the European Union and the USA are described as examples. In the event of an influenza pandemic, vaccines will be required urgently and licensing process should reflect such needs. Published by Elsevier Science Ltd. C1 Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Wood, JM (reprint author), Natl Inst Biol Stand & Controls, Blanche Lane S Mimms, Potters Bar EN6 3QG, Herts, England. NR 8 TC 39 Z9 41 U1 0 U2 1 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 MAY 1 PY 2003 VL 21 IS 16 BP 1786 EP 1788 DI 10.1016/S0264-410X(03)00073-2 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 673HW UT WOS:000182575500010 PM 12686095 ER PT J AU Bright, RA Anderson, S Frost, T Wiessner, P Evans, RS Samore, MH AF Bright, RA Anderson, S Frost, T Wiessner, P Evans, RS Samore, MH TI Medical device problems in intensive care units: Detection, dangers,and diversity of types SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Food & Drug Adm, Rockville, MD USA. LDS Hosp, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. RI Bright, Roselie/D-2240-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2003 VL 6 IS 3 BP 217 EP 218 DI 10.1016/S1098-3015(10)63897-1 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 688DX UT WOS:000183419000099 ER PT J AU Samore, MH Anderson, S Frost, T Wiessner, P Evans, RS Bright, RA AF Samore, MH Anderson, S Frost, T Wiessner, P Evans, RS Bright, RA TI Direct observation in intensive care units: Medical device-related problems associated with alarms SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT USA. LDS Hosp, Salt Lake City, UT USA. US FDA, Rockville, MD 20857 USA. RI Bright, Roselie/D-2240-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2003 VL 6 IS 3 BP 219 EP 220 DI 10.1016/S1098-3015(10)63902-2 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 688DX UT WOS:000183419000104 ER PT J AU Bright, RA Kaye, R Samore, MH AF Bright, RA Kaye, R Samore, MH TI Patient safety research: A discussion of terminology, proposed definitions, and a conceptual model for adverse events involving medical devices SO VALUE IN HEALTH LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Univ Utah, Salt Lake City, UT USA. RI Bright, Roselie/D-2240-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2003 VL 6 IS 3 BP 294 EP 294 DI 10.1016/S1098-3015(10)64086-7 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 688DX UT WOS:000183419000288 ER PT J AU Santos, N Volotao, EM Soares, CC Carolina, M Albuquerque, M da Silva, FM Chizhikov, V Hoshino, Y AF Santos, N Volotao, EM Soares, CC Carolina, M Albuquerque, M da Silva, FM Chizhikov, V Hoshino, Y TI VP7 gene polymorphism of serotype G9 rotavirus strains and its impact on G genotype determination by PCR (vol 90, pg 1, 2002) SO VIRUS RESEARCH LA English DT Correction ID POLYMERASE CHAIN-REACTION; GROUP-A ROTAVIRUS; MOLECULAR CHARACTERIZATION; REVERSE TRANSCRIPTION; ACUTE GASTROENTERITIS; VACCINE DEVELOPMENT; BRAZILIAN CHILDREN; NUCLEIC-ACID; IDENTIFICATION; EMERGENCE AB Rotaviruses are the single most important etiologic agents of severe diarrhea of infants and young children worldwide. Surveillance of rotavirus serotypes/genotypes (both VP7[G] and VP4[P]) is in progress globally in which polymerase chain reaction (PCR) has been the assay of choice. We investigated polymorphism of the VP7 gene of serotype G9 rotavirus strains and its impact on the determination of VP7 gene genotype by PCR assay. By VP7 gene sequence analysis, we and others have previously shown that the G9 rotavirus strains belong to one of three VP7 gene lineages. By PCR assay using three different sets of commonly used primers specific for G1-4, 8 and 9, 23 Brazilian G9 strains and 5 well-characterized prototype G9 strains which collectively represented all three VP7 gene lineages were typed as: (i) G3; (ii) G4; (iii) G9; (iv) G3 and G9; or (v) G9 and G4 depending on a primer pool employed. This phenomenon appeared to be due to: (i) a VP7 gene lineage-specific polymorphism, more specifically mutation(s) in the primer binding region of the VP7 gene of G9 strain; and (ii) the magnitude of difference in nucleotide homology at respective primer binding site between homotypic (G9) and heterotypic (G3 or G4) primers present in a primer pool employed. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, BR-21941590 Rio De Janeiro, Brazil. US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Santos, N (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, Cidade Univ,CCS-Bl 1,Ilha Fundao, BR-21941590 Rio De Janeiro, Brazil. RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 62 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAY PY 2003 VL 93 IS 1 BP 125 EP + DI 10.1016/S0168-1702(03)00319-2 PG 13 WC Virology SC Virology GA 678LH UT WOS:000182868300014 ER PT J AU Roybal, JE Pfenning, AP Turnipseed, SB Gonzales, SA AF Roybal, JE Pfenning, AP Turnipseed, SB Gonzales, SA TI Application of size-exclusion chromatography to the analysis of shrimp for sulfonamide residues SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 4th International Symposium on Hormone and Veterinary Drug Residue Analysis CY JUN 04-07, 2002 CL ANTWERP, BELGIUM DE sulfonamides; shrimp; size-exclusion; liquid chromatography; sephadex LH-20 ID TETRACYCLINE AB The determination of several sulfonamide residues from shrimp tissue using size-exclusion chromatography is presented. Shrimp tissue is extracted with ethyl acetate. The extracted solution is evaporated to dryness and the re-dissolved residue is applied to a chromatographic column containing Sephadex LH-20 gel. Cleanup is performed using this size-exclusion procedure. Determination is accomplished utilizing liquid chromatography. Elution of the sulfonamides from a phenyl column is performed with a methanol: acetic acid: counter-ion mobile phase. Recovery of sulfonamide residues from shrimp range from 70 to 100%. Published by Elsevier Science B.V. C1 Denver Fed Ctr, Anim Drugs Res Ctr, Food & Drug Adm, Denver, CO 80225 USA. RP Roybal, JE (reprint author), Denver Fed Ctr, Anim Drugs Res Ctr, Food & Drug Adm, POB 25087, Denver, CO 80225 USA. NR 9 TC 11 Z9 14 U1 1 U2 3 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 APR 25 PY 2003 VL 483 IS 1-2 BP 147 EP 152 AR PII S0003-2670(02)01488-5 DI 10.1016/S0003-2670(02)01488-5 PG 6 WC Chemistry, Analytical SC Chemistry GA 673ZV UT WOS:000182612300016 ER PT J AU Turnipseed, SB Roybal, JE PFenning, AP Kijak, PJ AF Turnipseed, SB Roybal, JE PFenning, AP Kijak, PJ TI Use of ion-trap liquid chromatography-mass spectrometry to screen and confirm drug residues in aquacultured products SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 4th International Symposium on Hormone and Veterinary Drug Residue Analysis CY JUN 04-07, 2002 CL ANTWERP, BELGIUM DE ion-trap mass spectrometry; fluoroquinolones; chloramphenicol; aquaculture; screening ID GAS-CHROMATOGRAPHY; MILK; CHLORAMPHENICOL; ANTIBIOTICS; CATFISH; TISSUE; FLUOROQUINOLONES; EXTRACTION; CHICKEN; SHRIMP AB Ion-trap liquid chromatography-multiple mass spectrometry (LC-MSn) has been shown to be a valuable tool for the confirmation of animal drug residues. We have taken advantage of this to update several regulatory methods for the confirmation of drug residues in aquacultured products. Here we report two such examples. First, the use of an ion-trap electrospray instrument collecting data-dependent MS2 and MS3 scans to yield structurally significant ions has allowed multi-residue confirmation of fluoroquinolones in salmon tissue. Ciprofloxacin, enrofloxacin, sarafloxacin, and difloxacin residues were positively identified in salmon muscle fortified at 5-80 mug kg(-1). These residues were also confirmed in extracts from incurred salmon tissue with final drug concentrations ranging from 10 to 40 mug kg(-1). The second example deals with multi-residue confirmation of phenicols using ion-trap LC-MSn. Comparisons of these methods with related confirmation procedures are discussed, as well as the optimization of MSn parameters to meet confirmation criteria. Initial efforts to use this instrument in conjunction with generic extraction methods to screen multi-class residues in shrimp tissue are also presented. Published by Elsevier Science B.V. C1 Food & Drug Adm, Anim Drugs Res Ctr, Lakewood, CO 80225 USA. Food & Drug Adm, Ctr Vet Med, Laurel, MD 20708 USA. RP Turnipseed, SB (reprint author), Food & Drug Adm, Anim Drugs Res Ctr, POB 25087, Lakewood, CO 80225 USA. NR 30 TC 44 Z9 48 U1 1 U2 10 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 APR 25 PY 2003 VL 483 IS 1-2 BP 373 EP 386 DI 10.1016/S0003-2670(02)01567-2 PG 14 WC Chemistry, Analytical SC Chemistry GA 673ZV UT WOS:000182612300042 ER PT J AU Chou, MW Yan, J Nichols, J Xia, QS Beland, FA Chan, PC Fu, PP AF Chou, MW Yan, J Nichols, J Xia, QS Beland, FA Chan, PC Fu, PP TI Correlation of DNA adduct formation and riddelliine-induced liver tumorigenesis in F344 rats and B6C3F(1) mice SO CANCER LETTERS LA English DT Article DE riddelliine; pyrrolizidine alkaloid; DNA adducts; hemangiosarcomas ID PYRROLIZIDINE ALKALOIDS; HEPATOCYTES; HONEY; CELLS AB Riddelliine is a naturally occurring pyrrolizidine alkaloid that induces liver hemangiosarcomas in male and female F344 rats and male B6C3F(1) mice. We previously reported that eight dehydroretronecine (DHR)-derived DNA adducts were formed in liver DNA of rats treated with riddelliine. In order to examine the relationship between DNA adduct levels and the incidence of hemangiosarcomas, we have measured DHR-derived DNA adduct levels in purified rat and mouse liver endothelial cells, the cells of origin for the hemangiosarcomas. F344 rats and B6C3F(1) mice were treated by gavage 5 days per week for 2 weeks with riddelliine at 1.0 mg/kg for rats and 3.0 mg/kg for mice. One, 3, 7, and 28 days after the last dose, liver parenchymal and endothelial cell fractions were isolated, and the quantities of DHR-derived DNA adducts were determined by (32)Ppostlabeling/HPLC. The DHR-derived DNA adduct levels in the endothelial cells were significantly greater than in the parenchymal cells. The DNA adduct levels in rat endothelial cells were greater than in the mouse endothelial cells. These results indicate that the levels of riddelliine-induced DNA adducts in specific populations of liver cells correlate with the preferential induction of liver hemangiosarcomas by riddelliine. Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Inst Environm Hlth, Res Triangle Pk, NC 27709 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 15 TC 35 Z9 36 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 25 PY 2003 VL 193 IS 2 BP 119 EP 125 DI 10.1016/S0304-3835(03)00045-4 PG 7 WC Oncology SC Oncology GA 680CJ UT WOS:000182958500001 PM 12706867 ER PT J AU Graham, LJ Veri, MC DeBell, KE Noviello, C Rawat, R Jen, S Bonvini, E Rellahan, B AF Graham, LJ Veri, MC DeBell, KE Noviello, C Rawat, R Jen, S Bonvini, E Rellahan, B TI 70Z/3 Cbl induces PLC gamma 1 activation in T lymphocytes via an alternate Lat- and Slp-76-independent signaling mechanism SO ONCOGENE LA English DT Article DE T lymphocytes; T-cell receptor; signal transduction; PLC gamma 1; c-Cbl ID PHOSPHOTYROSINE-BINDING DOMAIN; EPIDERMAL GROWTH-FACTOR; PHOSPHOLIPASE C-GAMMA-1 PLC-GAMMA-1; TEC FAMILY KINASES; CELL RECEPTOR; C-CBL; TYROSINE PHOSPHORYLATION; NEGATIVE REGULATOR; SH2 DOMAIN; ZAP-70 AB The oncoprotein 70Z/3 Cbl signals in an autonomous fashion or through blockade of endogenous c-Cbl, a negative regulator of signaling. The mechanism of 70Z/3 Cbl-induced signaling was investigated by comparing the molecular requirements for 70Z/3 Cbl- and TCR-induced phospholipase Cgamma1 (PLCgamma1) activation. 70Z/3 Cbl-induced PLCgamma1 tyrosine phosphorylation required, in addition to the PLCgamma1 N-terminal SH2 domain, the C-terminal SH2 and SH3 domains that were dispensable for TCR-induced phosphorylation. Deletion of the leucine zipper of 70Z/3 Cbl did not eliminate 70Z/3 Cbl-induced PLCgamma1 phosphorylation, suggesting that blockage of c-Cbl via dimerization with 70Z/3 Cbl cannot fully explain 70Z/3 Cbl activating characteristics. The complete elimination of PLCgamma1 phosphorylation required deleting the SH3 domain-binding region of 70Z/3 Cbl, consistent with 70Z/3 Cbl binding the PLCgamma1 SH3 domain. 70Z/3 Cbl-induced PLCgamma1 phosphorylation required Zap-70, as for the TCR, and the tyrosine kinase binding domain of 70Z/3 Cbl, which binds Zap-70, but did not require PLCgamma1 binding to Lat, a crucial interaction in TCR-induced PLCgamma1 phosphorylation. Furthermore, 70Z/3 Cbl-induced activation of NFAT, a PLCgamma1/Ca2+-dependent transcriptional event, required Zap-70, but was independent of Slp-76, an adapter required for TCR-induced NFAT activation. These results suggest that 70Z/3 Cbl and PLCgamma1 form a TCR-, Lat- and Slp-76-independent complex that leads to PLCgamma1 phosphorylation and activation. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoc Antibodies, Immunobiol Lab, Bethesda, MD 20892 USA. RP Bonvini, E (reprint author), HFM-564,29B-3NN10,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 50 TC 4 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 24 PY 2003 VL 22 IS 16 BP 2493 EP 2503 DI 10.1038/sj.onc.1206318 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 670AD UT WOS:000182383500012 PM 12717426 ER PT J AU Lozier, JN AF Lozier, JN TI Tentative progress in hemophilia B gene therapy SO BLOOD LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Lozier, JN (reprint author), US FDA, Rockville, MD 20857 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 APR 15 PY 2003 VL 101 IS 8 BP 2903 EP 2903 PG 1 WC Hematology SC Hematology GA 665CE UT WOS:000182101400005 ER PT J AU Carmel, R Melnyk, S James, SJ AF Carmel, R Melnyk, S James, SJ TI Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism SO BLOOD LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Hematology CY DEC 08, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol ID COULOMETRIC ELECTROCHEMICAL DETECTION; S-ADENOSYLMETHIONINE; PLASMA HOMOCYSTEINE; FOLATE-DEFICIENCY; MEGALOBLASTIC-ANEMIA; ADENOSYLHOMOCYSTEINE; GLUTATHIONE; NEUROPATHY; CYSTEINE; SYNTHASE AB The unknown biochemical basis for neurologic dysfunction in cobalamin deficiency and the frequent divergence between neurologic and hematologic manifestations led us to study homocysteine metabolism in 22 patients with pernicious anemia. Serum levels of total homocysteine (tHcy), methionine, S-adenosylmethionine (AdoMet), cysteine, cysteinylglycine (cys-gly), and glutathione (GSH) were measured. Only levels of tHcy and cysteine were increased and only GSH was decreased in cobalamin deficiency as a whole, compared with 17 control subjects. AdoMet correlated only with methionine levels (P = .015) and cysteine only with cys-gly (P = .007) in healthy subjects, but in cobalamin-deficient patients AdoMet correlated instead with cysteine, cys-gly, and folate levels only (P = .008, P = .03, and P = .03, respectively). Significant differences appeared in clinically subgrouped cobalamin-deficient patients. The 11 patients with neurologic defects had higher mean levels of folate (27.9 versus 15.4 nM), AdoMet (117.2 versus 78.6 nM), cysteine (462 versus 325 muM), and cys-gly (85.0 versus 54.7 muM) than the 11 neurologically unaffected patients. Cobalamin therapy restored all metabolic changes to normal. The results indicate that changes in several metabolic pathways differ in patients with and without neurologic dysfunction. Cysteine levels were the most significant predictors of neurologic dysfunction, but it is unclear if they are direct or indirect indicators of neurotoxicity. The higher AdoMet levels in neurologically affected patients may result from inhibition of glycine N-methyltransferase by those patients' higher folate levels. The origin of the folate differences is unclear and possibly varied. Low AdoMet and GSH levels were independent predictors of anemia. (C) 2003 by The American Society of Hematology. C1 NY Methodist Hosp, Dept Med, Brooklyn, NY 11215 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Carmel, R (reprint author), NY Methodist Hosp, Dept Med, 506 6th St, Brooklyn, NY 11215 USA. FU NIDDK NIH HHS [DK32640] NR 48 TC 34 Z9 34 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2003 VL 101 IS 8 BP 3302 EP 3308 DI 10.1182/blood-2002-09-2746 PG 7 WC Hematology SC Hematology GA 665CE UT WOS:000182101400063 PM 12515717 ER PT J AU Bennett, JE Powers, J de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Rex, J Verweij, P Viscoli, C Walsh, T AF Bennett, JE Powers, J de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Rex, J Verweij, P Viscoli, C Walsh, T TI Forum report: Issues in the design of trials of drugs for the treatment of invasive aspergillosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT John E Bennett Forum on Deep Mycoses Study Design CY JAN 25-27, 2002 CL NEW YORK, NEW YORK ID AMPHOTERICIN-B; MANAGEMENT; CANCER AB A recent trial of drugs for invasive aspergillosis was used as a background for discussing critical features in the design of antifungal trials. The study under discussion allowed stopping either drug without classifying the patient as having treatment failure, so the trial should be understood as a comparison of 2 treatment strategies, not just 2 drugs. Although the study was a noninferiority trial, the outcome permitted a claim of superiority. Use of the category of "probable" in addition to "proven" aspergillosis permitted inclusion of patients for whom the diagnosis was less certain but who were still early enough in the disease progression to respond to therapy. Different opinions still exist about some of the criteria for the diagnosis of "probable" aspergillosis. A blinded data review committee was helpful in evaluating efficacy in this unblinded trial but had limited value in assessing toxicity. An understanding of these features of design of antifungal drug trials is important in applying the results to clinical practice. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. US FDA, Div Special Pathogen & Immunol Drug Prod, Rockville, MD USA. Univ Alabama, Birmingham, AL USA. VA Med Ctr, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. VA Med Ctr, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas, Sch Med, Houston, TX USA. Univ Nijmegen St Radboud Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Lausanne Hosp, Lausanne, Switzerland. Hop Hautepierre, Strasbourg, France. Univ Genoa, Natl Inst Canc Res, I-16126 Genoa, Italy. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. RI Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014 NR 6 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2003 VL 36 SU 3 BP S113 EP S116 DI 10.1086/367838 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MN UT WOS:000182125000003 PM 12679894 ER PT J AU Bennett, JE Powers, J Walsh, T Viscoli, C de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Rex, J Verweij, P AF Bennett, JE Powers, J Walsh, T Viscoli, C de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Rex, J Verweij, P TI Forum report: Issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT John E Bennett Forum on Deep Mycoses Study Design CY JAN 25-27, 2002 CL NEW YORK, NEW YORK ID LIPOSOMAL AMPHOTERICIN-B; PERSISTENT FEVER; RANDOMIZED TRIAL; CANCER AB There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated. Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication. Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively. Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of fever. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. US FDA, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. Univ Alabama, Birmingham, AL USA. VA Med Ctr, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. VA Med Ctr, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas, Sch Med, Houston, TX USA. Univ Nijmegen St Radboud Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Genoa, Natl Inst Canc Res, Genoa, Italy. Univ Lausanne Hosp, Lausanne, Switzerland. Hop Hautepierre, Strasbourg, France. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. RI Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014 NR 11 TC 40 Z9 41 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2003 VL 36 SU 3 BP S117 EP S122 DI 10.1086/367839 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MN UT WOS:000182125000004 PM 12679895 ER PT J AU Bennett, JE Kauffman, C Walsh, T de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Lee, J Pappas, P Powers, J Rex, J Verweij, P Viscoli, C AF Bennett, JE Kauffman, C Walsh, T de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Lee, J Pappas, P Powers, J Rex, J Verweij, P Viscoli, C TI Forum report: Issues in the evaluation of diagnostic tests, use of historical controls, and merits of the current multicenter collaborative groups SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT John E Bennett Forum on Deep Mycoses Study Design CY JAN 25-27, 2002 CL NEW YORK, NEW YORK ID ALTERNATIVE TRIAL DESIGNS; INVASIVE ASPERGILLOSIS; CANCER AB This forum report contains conclusions about 3 different issues relevant to conducting clinical trials in deep mycoses. (1) Trials of diagnostic tests for deep mycoses must define the population appropriate for testing and the clinical question being asked. The unanswered question for the serum Aspergillus galactomannan assay is whether knowledge of results can change use of empirical therapy to treat febrile patients at high risk of invasive aspergillosis. (2) Use of historical controls is suboptimal but offers a pragmatic solution for studying rare mycoses; use of contemporaneous controls, matched for critical variables and evaluated by a blinded data review committee using detailed criteria, appears optimal. (3) Established groups of independent investigators, such as the European Organization for Research on Treatment of Cancer's Invasive Fungal Infections Group and National Institute of Allergy and Infectious Diseases's Bacteriology and Mycology Study Group, provide a pool of experienced investigators, defined operating rules, impartiality, and specialized expertise. Considering the enormous investment required for adequately powered efficacy trials of antifungal agents and the importance of these trials to guide clinical practice, use of collaborative groups outweighs the extra administrative time that is sometimes required. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. US FDA, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. VA Med Ctr, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Alabama, Birmingham, AL USA. VA Med Ctr, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. Univ Texas, Sch Med, Houston, TX USA. Univ Nijmegen St Radboud Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Lausanne Hosp, Lausanne, Switzerland. Hop Hautepierre, Strasbourg, France. Univ Genoa, Natl Inst Canc Res, Genoa, Italy. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bldg 10,Room11C304, Bethesda, MD 20892 USA. RI Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014 NR 7 TC 7 Z9 8 U1 0 U2 2 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 APR 15 PY 2003 VL 36 SU 3 BP S123 EP S127 DI 10.1086/367840 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MN UT WOS:000182125000005 PM 12679896 ER PT J AU Bennett, JE de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Powers, J Rex, J Verweij, P Viscoli, C Walsh, T AF Bennett, JE de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Powers, J Rex, J Verweij, P Viscoli, C Walsh, T TI Introduction to the forum report on advances in the design of antifungal clinical trials SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 NIAID, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Univ Nijmegen St Radboud Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Alabama, Birmingham, AL USA. Univ Arizona, Tucson, AZ USA. Univ Lausanne Hosp, Lausanne, Switzerland. Hop Hautepierre, Strasbourg, France. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. Univ Michigan, Ann Arbor, MI 48109 USA. US FDA, Div Special Pathogen & Immunolog Drug Prod, Rockville, MD 20857 USA. Univ Texas, Sch Med, Houston, TX USA. Univ Genoa, Natl Inst Canc Res, Genoa, Italy. RP Bennett, JE (reprint author), NIH, Clin Mycol Sect, Clin Invest Lab, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. RI Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2003 VL 36 SU 3 BP S112 EP S112 DI 10.1086/367837 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MN UT WOS:000182125000002 ER PT J AU McKnew, DL Lynn, F Zenilman, JM Bash, MC AF McKnew, DL Lynn, F Zenilman, JM Bash, MC TI Porin variation among clinical isolates of Neisseria gonorrhoeae over a 10-year period, as determined by por variable region typing SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 25-28, 2001 CL SAN FRANCISCO, CALIFORNIA SP Infect Dis Soc Amer ID MEMBRANE PROTEIN PIB; MONOCLONAL-ANTIBODIES; SEQUENCE-ANALYSIS; GENE; EPIDEMIOLOGY; INFECTION; STRAINS AB The Neisseria gonorrhoeae porin protein (Por) is a potential vaccine target and is the antigenic determinant for serovar typing. Two classes of Por, PIA and PIB, and antigenically distinct variants within each class result from sequence variations in the por gene variable regions (VRs) encoding surface-exposed loops. Oligonucleotide probes to 5 VRs of each class were used in checkerboard hybridizations to type 282 clinical gonococcal isolates selected from strains collected over the course of 10 years. PIA strains (n = 63) showed limited por diversity, with 90% having 1 of 4 por types. PIB strains (n = 219) were more diverse, although several common por types were identified that persisted over time. Variation within individual VRs was found to be limited. The present study provides information about the diversity of Por in strains circulating in a single geographic region over time, illustrates the utility of a novel por typing method, and has implications for vaccine development. C1 US FDA, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Childrens Natl Med Ctr, Div Infect Dis, Washington, DC 20010 USA. RP Bash, MC (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, HFM-428,1401 Rockville Pike, Rockville, MD 20852 USA. FU NIAID NIH HHS [K24-AI01633] NR 24 TC 18 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2003 VL 187 IS 8 BP 1213 EP 1222 DI 10.1086/374563 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 662WL UT WOS:000181972000006 PM 12696000 ER PT J AU Vaidya, VS Shankar, K Lock, EA Bucci, TJ Mehendale, HM AF Vaidya, VS Shankar, K Lock, EA Bucci, TJ Mehendale, HM TI Renal injury and repair following S-1, 2 dichlorovinyl-L-cysteine administration to mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Society-of-Toxicology CY MAR 19-23, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Soc Toxicol DE BUN; cell division; cell proliferation; DCVC; nephrotoxicity; PCNA; renal injury; swiss-webster mice; S-(1,2-dichlorovinyl)-L-cysteine; tissue repair ID CONJUGATE BETA-LYASE; TISSUE-REPAIR; POSSIBLE EXPLANATION; URINARY METABOLITE; RAT-KIDNEY; S-OXIDASE; TOXICITY; NEPHROTOXICITY; MECHANISM; TRICHLOROETHYLENE AB S-(1,2-dichlorovinyl)-L-cysteine (DCVC), a metabolite of a common environmental contaminant, trichloroethylene, is a selective proximal tubular nephrotoxicant. The objective of our study was to examine the dose-response relationship of renal injury and repair following DCVC administration. Male Swiss-Webster mice were injected with DCVC [15, 30, or 75 mg/kg ip in distilled water (10 ml/kg)] and the extent of nephrotoxicity and tissue repair was assessed over a 14-day period. The renal injury due to the low and medium doses of DCVC peaked at 36 and 72 h after dosing, respectively, and then regressed over time due to a timely and adequate tissue repair response. At the highest dose tissue repair was inhibited, thereby causing progression of renal injury, which led to acute renal failure and death of the mice. The possibility that compromised tissue repair was a result of the extensive nephrotoxic injury attendant to the high dose of DCVC was investigated via an equinephrotoxicity study in which separate groups of mice received 40 (LD40) and 75 (LD90) mg DCVC/kg, respectively. Bioactivation-based renal proximal tubular injury measured in these two groups over a time course was identical but there was a marked difference in mortality due to an early and robust tissue repair in the first group relative to the second group. These results support the concept that quantitative evaluation of renal tissue repair in parallel with injury is useful in the assessment of the likely toxic outcome associated with exposure to nephrotoxic drugs and toxicants. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. ICI PLC, Cent Toxicol Lab, Syngenta, Macclesfield SK10 4TJ, Cheshire, England. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm, Dept Toxicol, 700 Univ Ave, Monroe, LA 71209 USA. FU NIDDK NIH HHS [DK-061650] NR 38 TC 35 Z9 37 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR 15 PY 2003 VL 188 IS 2 BP 110 EP 121 DI 10.1016/S0041-008X(02)00080-7 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 669EJ UT WOS:000182338700005 PM 12691729 ER PT J AU Shankar, K Vaidya, VS Wang, T Bucci, TJ Mehendale, HM AF Shankar, K Vaidya, VS Wang, T Bucci, TJ Mehendale, HM TI Streptozotocin-induced diabetic mice are resistant to lethal effects of thioacetamide hepatotoxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE bioactivation; liver injury; species difference; tissue repair ID CARBON-TETRACHLORIDE HEPATOTOXICITY; ANTIMITOTIC AGENT COLCHICINE; LIVER-TISSUE REPAIR; DECREASED SUSCEPTIBILITY; ANTIOXIDANT CAPACITY; RESTRICTED RATS; POTENTIATION; TOXICITY; GROWTH; INJURY AB The effect of Type 1 diabetes on the toxicity of thioacetamide was investigated in a murine model. In streptozotocin-induced diabetic C57BL6 mice a LD90 dose of thioacetamide (1000 mg/kg, ip in saline) caused only 10% mortality. Alanine aminotransferase activity revealed similar to2.7-fold less liver injury in the diabetic (DB) mice compared to the non-DB controls, at 36 h after thioacetamide (TA) administration, which was confirmed via histopathological analysis. HPLC analyses revealed lower plasma t(1/2) of TA in the DB mice. Covalent binding of [C-14]TA to liver tissue was lower in the DB mice, suggesting lower bioactivation of TA. Compensatory hepatic S-phase stimulation as assessed by [H-3]thymidine incorporation occurred much earlier and was substantially higher in the DB mice compared to the non-DB cohorts. Morphometric analysis of cells in various phases of cell division assessed via immunohistochemical. staining for proliferating cell nuclear antigen revealed more cells in G(1), S, G(2), and M phases in the DB mice, indicating robust tissue repair in concordance with the findings of [H-3]thymidine pulse labeling studies. The importance of tissue repair in the resistance of DB mice was further investigated by blocking cell division in the DB mice by colchicine (1 mg/kg, ip) at 40 h after TA administration, well after the bioactivation of TA. Antimitotic action of colchicine, confirmed by decreased S-phase stimulation, led to progression of liver injury and increased mortality in DB mice. These findings suggest that lower bioactivation of TA and early onset of liver tissue repair are the pivotal underpinnings for the resistance of DB mice. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. FU NIEHS NIH HHS [ES-09870] NR 48 TC 24 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR 15 PY 2003 VL 188 IS 2 BP 122 EP 134 DI 10.1016/S0041-008X(02)00037-6 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 669EJ UT WOS:000182338700006 PM 12691730 ER PT J AU Gorbachev, AV Fairchild, RL AF Gorbachev, AV Fairchild, RL TI CD4+CD25+T cells down-regulate contact hypersensitivity responses through FasL-dependent mechanism SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 14 PY 2003 VL 17 IS 7 SU S BP C84 EP C84 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000388 ER PT J AU Hoque, ATMS Smith, RH Kotin, RM Golding, B AF Hoque, ATMS Smith, RH Kotin, RM Golding, B TI Mechanism of tolerance against factor VIII in hemophiliac mice after intravenous injection of a non-viral vector SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 US FDA, Ctr Biol Evaluat & Res, OBRR DH, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 14 PY 2003 VL 17 IS 7 SU S BP C218 EP C218 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001009 ER PT J AU Lankford, CSR Nguyen, BV Yamane, H Rodriguez, RVC Paul, WE Frucht, DM AF Lankford, CSR Nguyen, BV Yamane, H Rodriguez, RVC Paul, WE Frucht, DM TI An important role for IFN-gamma R signaling in TH1 priming but not in IFN-gamma production by TH1 effector cells or antigen presenting cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 US FDA, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 14 PY 2003 VL 17 IS 7 SU S BP C202 EP C202 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000934 ER PT J AU Mikolajczyk, MG Eller, NL Kennedy, M Jones-Trower, A AF Mikolajczyk, MG Eller, NL Kennedy, M Jones-Trower, A TI Comparative analysis of the detection of vaccinia virus antigens by human polyclonal immune globulin preparations SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 14 PY 2003 VL 17 IS 7 SU S BP C28 EP C28 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000131 ER PT J AU Staton, RJ Pazik, FD Nipper, JC Williams, JL Bolch, WE AF Staton, RJ Pazik, FD Nipper, JC Williams, JL Bolch, WE TI A comparison of newborn stylized and tomographic models for dose assessment in paediatric radiology SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIATION PROTECTION; VOXEL MODELS; PHANTOMS AB Establishment of organ doses from diagnostic and interventional examinations is a key component to quantifying the radiation risks from medical exposures and for formulating corresponding dose-reduction strategies. Radiation transport models of human anatomy provide a convenient method for simulating radiological examinations. At present, two classes of models exist: stylized mathematical models and tomographic voxel models. In the present study, organ dose comparisons are made for projection radiographs of both a stylized and a tomographic model of the newborn patient. Sixteen separate radiographs were simulated for each model at x-ray technique factors typical of newborn examinations: chest, abdomen, thorax and head views in the AP, PA, left LAT and right LAT projection orientation. For AP and PA radiographs of the torso (chest, abdomen and thorax views), the effective dose assessed for the tomographic model exceeds that for the stylized model with per cent differences ranging from 19% (AP abdominal view) to 43% AP chest view. In contrast, the effective dose for the stylized model exceeds that for the tomographic model for all eight lateral views including those of the head, with per cent differences ranging from 9% (LLAT chest view) to 51 % (RLAT thorax view). While organ positioning differences do exist between the models, a major factor contributing to differences in effective dose is the models' exterior trunk shape. In the tomographic model, a more elliptical shape is seen thus providing for less tissue shielding for internal organs in the AP and PA directions, with corresponding increased tissue shielding in the lateral directions. This observation. is opposite of that seen in comparisons of stylized and tomographic models of the adult. C1 Univ Florida, Dept Nucl & Radiol Engn, Gainesville, FL 32611 USA. FDA, Ctr Device & Radiol Hlth, Rockville, MD USA. Univ Florida, Dept Radiol, Gainesville, FL 32611 USA. Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA. RP Staton, RJ (reprint author), Univ Florida, Dept Nucl & Radiol Engn, Gainesville, FL 32611 USA. FU NIBIB NIH HHS [R01 EB00267-03]; NICHD NIH HHS [R01 HD38932-02] NR 32 TC 22 Z9 22 U1 0 U2 0 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 APR 7 PY 2003 VL 48 IS 7 BP 805 EP 820 AR PII S0031-9155(03)58968-0 DI 10.1088/0031-9155/48/7/301 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 669YL UT WOS:000182379200001 PM 12701888 ER PT J AU Evans, L AF Evans, L TI Separation and quantitation of components in FD&C Red No. 3 using capillary electrophoresis SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE FD&C Red No. 3; dyes; erythrosine; color additives ID ZONE-ELECTROPHORESIS; REACTIVE DYES; AZO DYES; WATER AB The use of capillary electrophoresis as a technique to separate and quantitate components of FD&C Red No. 3 (erythrosine, color index No. 45430) is described. The fluorescein isomers, 2',4',5'-triiodofluorescein (2,4,5-I3F) and 2',4',7'-triiodofluorescein (2.4,7-I3F), the most abundant by-products formed during the preparation of the dye. were selected for quantitation studies. The separation of other lower halogenated impurities was also demonstrated. Electrophoretic mobility of the compounds was achieved in a 50 mM borate, 25 mM sodium dodecyl sulfate buffer at pH 9.3. The limits of quantitation were found to be 0.15% (w/w) (2.4,5-I3F) and 0,14% (w/w) (2,4,7-I3F) (relative to the mass of FD&C Red No. 3). The method is linear from 0.08 to 20.0% (w/w) for 2,4.5-I3F and between 0.06 and 17.0% (w/w) for 2,4,7-I3F. In addition, relative standard deviations of 2.03 and 5.11% were determined from precision studies in the repeat analysis of FD&C Red No. 3 for 2,4,5-I3F and 2,4,7-I3F, respectively, Overall. the CE method produced data in excellent agreement with the reference HPLC method, used considerably less solvent and sample, generated less waste and was found to be considerably more cost efficient. Published by Elsevier Science B.V. C1 US FDA, Colors Technol Branch, College Pk, MD 20740 USA. RP Evans, L (reprint author), US Pharmacopeia, 12601 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 17 TC 10 Z9 10 U1 1 U2 1 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 APR 4 PY 2003 VL 991 IS 2 BP 275 EP 280 DI 10.1016/S0021-9673(03)00244-9 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 664XY UT WOS:000182091100011 PM 12741605 ER PT J AU Schober, SE Sinks, TH Jones, RL Bolger, PM McDowell, M Osterloh, J Garrett, ES Canady, RA Dillon, CF Sun, Y Joseph, CB Mahaffey, KR AF Schober, SE Sinks, TH Jones, RL Bolger, PM McDowell, M Osterloh, J Garrett, ES Canady, RA Dillon, CF Sun, Y Joseph, CB Mahaffey, KR TI Blood mercury levels in US children and women of childbearing age, 1999-2000 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID METHYLMERCURY EXPOSURE; FISH CONSUMPTION; POPULATION; DISEASE; HAIR AB Context Humans are exposed to methylmercury, a well-established neurotoxin, through fish consumption. The fetus is most sensitive to the adverse effects of, exposure. The extent of exposure to methylmercury in US women of reproductive age is not known. Objective To describe the distribution of blood mercury levels in US children and women of childbearing age and the association with sociodemographic characteristics and fish consumption. Design and Setting The 1999-2000 data from, the National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population. Participants In 1999-2000,1250 children aged 1 to 5 years and 2314 women aged 16 to 49 years were selected to participate in the survey. Household interviews, physical examinations, and blood mercury levels assessments were performed on 705 children (56% response rate) and 1709 women (74% response rate). Main Outcome Measure Blood concentration of total mercury. Results Blood mercury levels were approximately 3-fold higher in women compared with children. The geometric mean concentration of total blood mercury was 0.34 mug/L (95% confidence interval [CI], 0.30-0.39 mug/L) in children and 1.02 mug/L (95% Cl, 0.85-1.20 mug/L) in women. Geometric mean mercury levels were almost 4-fold higher among women who ate 3 or more servings of fish in the past 30 days compared with women who ate no fish in that period (1.94 mug/L vs 0.51 mug/L; P<.001). Conclusions Measures of mercury exposure in women of childbearing age and young children generally fall below levels of concern. However, approximately 8% of women had concentrations higher than the US Environmental Protection Agency's recommended reference dose (5.8 μg/L), below which exposures are considered to be without adverse effects. Women who are pregnant or who intend to become pregnant should follow federal and state advisories on consumption of fish. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Natl Marine Fisheries Serv, Natl Ocean & Atmospher Adm, Pascagoula, MS USA. Orkand Corp, Falls Church, VA USA. US EPA, Off Sci Coordinat & Policy, Off Prevent Pesticides & Tox Subst, Washington, DC 20460 USA. RP Schober, SE (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 4210, Hyattsville, MD 20782 USA. EM sschober@cdc.gov NR 35 TC 179 Z9 186 U1 1 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 2 PY 2003 VL 289 IS 13 BP 1667 EP 1674 DI 10.1001/jama.289.13.1667 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 662JX UT WOS:000181944500030 PM 12672735 ER PT J AU Nasta, SD Hoff, PM George, CS Neubauer, M Cohen, SC Abbruzzese, J Winn, R Pazdur, RM AF Nasta, SD Hoff, PM George, CS Neubauer, M Cohen, SC Abbruzzese, J Winn, R Pazdur, RM TI Phase II study of MGI-114 administered intravenously for 5 days every 28 days to patients with metastatic colorectal cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE colon cancer; metastases; phase II study; novel therapeutic agent MGI-114 ID ILLUDIN-S; ANTITUMOR-ACTIVITY; 6-HYDROXYMETHYLACYLFULVENE; AGENTS; HMAF AB We examined the use of MGI-114 (6-hydroxymethyacylfulvene) for the treatment of patients with advanced colorectal carcinoma. Twenty-six patients were enrolled, with a median age of 60 years (range 41-75); 64% were male and all patients had a performance status of 0 or 1. We administered a dose of 11 mg/m(2)/d X 5 days every 4 weeks. With a median of two cycles (range 0-6) administered, no complete responses or partial responses were observed. Four patients had no change in disease (16%); 15 patients (57%) had progressive disease; seven patients were inevaluable (27%). Toxicity was evaluated in 25 of 26 patients. The main toxicities were hematologic, including granulocytopenia and thrombocytopenia. Neuropsychiatric adverse events included hallucination (7.7%), depression/anxiety (15.4%), and/or insomnia (19.2%). Given the lack of antitumor activity, further study of MGI-114 in colorectal cancer does not appear warranted. C1 Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX USA. Columbus Community Clin Oncol Program, Bryn Mawr, PA USA. Main Line Hlth Community Clin Oncol Program, Bryn Mawr, PA USA. Food & Drug Adm, Rockville, MD USA. RP Hoff, PM (reprint author), Albert Einstein Hosp, Ctr Clin Studies Canc NECC, Av Albert Einstein 627-701, BR-05651901 Sao Paulo, SP, Brazil. NR 11 TC 8 Z9 8 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2003 VL 26 IS 2 BP 132 EP 134 DI 10.1097/00000421-200304000-00006 PG 3 WC Oncology SC Oncology GA 672KQ UT WOS:000182520100006 PM 12714882 ER PT J AU Chen, H Sullivan, G Yue, LQ Katz, A Quon, MJ AF Chen, H Sullivan, G Yue, LQ Katz, A Quon, MJ TI QUICKI is a useful index of insulin sensitivity in subjects with hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin resistance; diabetes; glucose clamp ID HOMEOSTASIS MODEL ASSESSMENT; GLUCOSE-TOLERANCE TEST; MINIMAL-MODEL; CHECK INDEX; PREMATURE ADRENARCHE; 2-COMPARTMENT MODEL; DIABETES-MELLITUS; ACCURATE INDEX; RESISTANCE; DISEASE AB Insulin resistance may link disorders of metabolic homeostasis such as diabetes and obesity with disorders of hemodynamic homeostasis such as hypertension. Thus it is of interest to validate simple methods for quantifying insulin sensitivity in hypertensive patients. The quantitative insulin-sensitivity check index (QUICKI) is a novel mathematical transformation of fasting blood glucose and insulin levels. In obese and diabetic subjects, QUICKI has a significantly better linear correlation with glucose clamp determinations of insulin sensitivity than minimal-model estimates. To determine whether QUICKI is also useful in hypertensive subjects, we performed glucose clamps and frequently sampled intravenous glucose tolerance tests (FSIVGTT) on 27 hypertensive subjects taken off antihypertensive medication. Indexes of insulin sensitivity derived from glucose clamp studies (SIClamp) were compared with QUICKI, minimal-model analysis of FSIVGTTs (SIMM), and homeostasis model assessment (HOMA). The correlation between QUICKI and SIClamp (r = 0.84) was significantly better than that between SIMM and SIClamp (r = 0.65; P < 0.028). The correlation between QUICKI and SIClamp was comparable to that between 1/HOMA and SIClamp (r = 0.82). When studies were repeated in 14 subjects who had resumed antihypertensive medications, the percent changes in SIClamp for each of these patients were significantly correlated with percent changes in QUICKI (r = 0.61) and HOMA (r = -0.54) but not SIMM (r = -0.18). We conclude that QUICKI is a simple, robust index of insulin sensitivity that is useful for evaluating and following the insulin resistance of hypertensive subjects in both research studies and clinical practice. C1 NIH, Diabet Unit, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20850 USA. RP Quon, MJ (reprint author), NIH, Diabet Unit, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bldg 10,Rm 8C-218,10 Ctr Dr,MSC 1755, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 44 TC 63 Z9 64 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 2003 VL 284 IS 4 BP E804 EP E812 DI 10.1152/ajpendo.00330.2002 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 653GD UT WOS:000181426100019 PM 12678026 ER PT J AU Meyer, RJ AF Meyer, RJ TI FDA "black box" labeling SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 2, Rockville, MD 20857 USA. RP Meyer, RJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 2, 5600 Fishers Lane,Room 13B-28,HFD-102, Rockville, MD 20857 USA. NR 1 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2003 VL 41 IS 4 BP 559 EP 560 DI 10.1067/mem.2003.111 PG 2 WC Emergency Medicine SC Emergency Medicine GA 661CB UT WOS:000181872700017 PM 12658256 ER PT J AU Ruiz, ME Richards, JS Kerr, GS Kan, VL AF Ruiz, ME Richards, JS Kerr, GS Kan, VL TI Erysipelothrix rhusiopathiae septic arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DISEASE AB We describe herein the case of a man with Erysipelothrix rhusiopathiae septic arthritis and possible infective endocarditis. This is the first report in the English-language medical literature of septic arthritis caused by this organism. C1 US FDA, Rockville, MD 20857 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. RP Ruiz, ME (reprint author), US FDA, HFD-590,5600 Fishers Lane, Rockville, MD 20857 USA. NR 7 TC 3 Z9 5 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2003 VL 48 IS 4 BP 1156 EP 1157 DI 10.1002/art.10901 PG 2 WC Rheumatology SC Rheumatology GA 665HZ UT WOS:000182115300034 PM 12687560 ER PT J AU Hong, Y Liu, TR Hofacre, C Maier, M White, DG Ayers, S Wang, LH Maurer, JJ AF Hong, Y Liu, TR Hofacre, C Maier, M White, DG Ayers, S Wang, LH Maurer, JJ TI A restriction fragment length polymorphism-based polymerase chain reaction as an alternative to serotyping for identifying Salmonella serotypes SO AVIAN DISEASES LA English DT Article DE Salmonella; RFLP-PCR; flagellin; serotyping; poultry; typhimurium; enteritidis ID UNITED-STATES; ENTERITIDIS INFECTIONS; REFERENCE COLLECTION; COVALENT STRUCTURE; FLAGELLIN GENES; POULTRY; TYPHIMURIUM; ENTERICA; STRAINS; OUTBREAKS AB The phase 1 (fliC) and phase 2 (fljB) Salmonella flagella genes were analyzed by restriction fragment length polymorphism (RFLP)-polymerase chain reaction (PCR) to aid in the identification of different Salmonella serorypes. Twenty-four phase 1 flagellin and eight phase 2 flagellin genes could be differentiated among each other with restriction endonucleases Sau3A and HhaI in RFLP-PCR analysis. These flagellin genes comprise the major antigenic formulas for 52 serotypes of Salmonella sp., which include the common serotypes found in poultry and other important food animal species. With the knowledge of the 0 antigen composition determined from conventional O serotyping, 90% of the Salmonella serotypes could be identified by this double restriction enzyme RFLP analysis of fliC and fljB genes. This RFLP-PCR flagellar typing scheme was successfully applied to the identification of serotype for 112 Salmonella isolates obtained from poultry environment. There was a significant correlation between RFLP-PCR and conventional serotyping (chi-square, P < 0.001). Overall, PCR-RFLP proved to be a fast, accurate, and economical alternative approach to serotyping Salmonella sp. C1 Univ Georgia, Coll Vet Med, Dept Avian Med, Athens, GA 30602 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Univ Georgia, Sch Arts & Sci, Dept Stat, Athens, GA 30602 USA. Univ Georgia, Coll Agr & Environm Sci, Ctr Food Safety & Qual Enhancement, Griffin, GA 30223 USA. RP Maurer, JJ (reprint author), Univ Georgia, Coll Vet Med, Dept Avian Med, Athens, GA 30602 USA. NR 42 TC 14 Z9 15 U1 0 U2 1 PU AMER ASSOC AVIAN PATHOLOGISTS PI KENNETT SQ PA UNIV PENN, NEW BOLTON CENTER, KENNETT SQ, PA 19348-1692 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD APR-JUN PY 2003 VL 47 IS 2 BP 387 EP 395 DI 10.1637/0005-2086(2003)047[0387:ARFLPP]2.0.CO;2 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 697TQ UT WOS:000183959700015 PM 12887198 ER PT J AU Ferguson, SA Gray, EP Cada, AM AF Ferguson, SA Gray, EP Cada, AM TI Early behavioral development in the spontaneously hypertensive rat: A comparison with the Wistar-Kyoto and Sprague-Dawley strains SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RETINOIC ACID EXPOSURE; ANIMAL-MODEL; MATERNAL-BEHAVIOR; GENERAL MOVEMENTS; BRAIN METABOLISM; MONOAMINE LEVELS; BLOOD PRESSURES; YOUNG-RATS AB The spontaneously hypertensive rat (SHR) is often used as a model for childhood attention-deficit/hyperactivity disorder (ADHD). To investigate behavioral maturation in SHR, body weight, age at eye opening, and performance in several behavioral tasks in male and female SHR, Wistar-Kyoto (WKY), and Sprague-Dawley rats were compared. SHRs were slower in performing the righting reflex on PND 4 and negative geotaxis compared with WKY and Sprague-Dawley. Both SHR and WKY were delayed relative to Sprague-Dawley in eye opening and beam walking. Rotarod performance was comparable in the 3 strains. Males were faster to right themselves than females, but there were no other significant sex differences nor Sex x Strain interactions. Delayed development in SHR may be related to a maturational delay observed in children with ADHD. Research assessing early behaviors in SHR, WKY, and other strains will help determine the most appropriate model for childhood ADHD and may help predict later behavioral dysfunction. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 67 TC 16 Z9 16 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 2003 VL 117 IS 2 BP 263 EP 270 DI 10.1037/0735-7044.117.2.263 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 661FM UT WOS:000181880600009 PM 12708523 ER PT J AU Ferguson, SA Cada, AM AF Ferguson, SA Cada, AM TI A longitudinal study of short- and long-term activity levels in male and female spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rats SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID OPEN-FIELD BEHAVIOR; DEFICIT HYPERACTIVITY DISORDER; WKY RATS; ANIMAL-MODEL; STRAIN DIFFERENCES; LOCOMOTOR-ACTIVITY; CIRCADIAN-RHYTHMS; BRAIN METABOLISM; BLOOD-PRESSURE; HEART-RATE AB The pattern of locomotor activity across development was assessed in male and female spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. Open field activity did not indicate hyperactivity in the SHR. Instead, the SD strain was generally more active. Strains and sexes did not differ in open-field locomotor response to drug challenges. When short-term (10-12 min) activity in different apparatuses was compared, the SD were most active in the open field, the SHR in the residential figure-eight maze, and the WKY in the running wheel. Long-term tests indicated hyperactivity in the SHR in the residential figure-eight maze and hypoactivity in the SD in the running wheels. Until such strain differences in activity are thoroughly defined, the use of the SHR as a model of attention-deficit/hyperactivity disorder is limited. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 50 TC 40 Z9 40 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 2003 VL 117 IS 2 BP 271 EP 282 DI 10.1037/0735-7044.117.2.271 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 661FM UT WOS:000181880600010 PM 12708524 ER PT J AU Kassarov, L AF Kassarov, L TI Are birds the primary selective force leading to evolution of mimicry and aposematism in butterflies? An opposing point of view SO BEHAVIOUR LA English DT Article ID VISUAL-ACUITY; NEOTROPICAL BUTTERFLIES; ARTIFICIAL PREY; COLORATION; PALATABILITY; PREDATION; FALCON; FLIGHT AB Birds are universally considered to be the primary selective force leading to the evolution of mimicry in butterflies and the evolution of aposematic coloration. This concept does not take into account the visual capabilities of birds. In this paper it is argued that the aerial hawker insectivorous birds, which are the primary predators of butterflies, are not able to differentiate the separate elements in the color patterns of flying butterflies. They cannot distinguish details in color of the markings or their shape, size, and distribution. As a consequence, birds cannot serve as a selective force for evolution of mimicry and aposematic coloration in these insects. Many aspects of vision, and especially vision in birds, on which my conclusions are based are discussed in detail. The different morphological and behavioral characteristics of butterflies, especially their flight characteristics, correlate with their profitability as a source of energy and nutrients. The flight pattern of the butterfly is the first stimulus that the bird sees, not the color pattern. It is this characteristic flight pattern, not the bright aposematic coloration pattern, that birds are able to recognize and then learn rapidly to associate visually with the profitability of the prey. The characteristic flight behavior signals to the bird whether the prey is energetically profitable or not, thus whether to attack or ignore a potential prey. The ability to distinguish prey types by flight pattern allows the bird to conserve energy and maximize its feeding efficiency. C1 Florida State Collect Anthropods, DPI, FDACS, Gainesville, FL 32614 USA. RP Kassarov, L (reprint author), 130 Spruce St 28B, Philadelphia, PA 19106 USA. EM lukakassarov@cs.com NR 59 TC 10 Z9 11 U1 3 U2 21 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 EI 1568-539X J9 BEHAVIOUR JI Behaviour PD APR PY 2003 VL 140 BP 433 EP 451 DI 10.1163/156853903322127922 PN 4 PG 19 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA 704JX UT WOS:000184337500002 ER PT J AU Dougherty, J Mhatre, R Moore, S AF Dougherty, J Mhatre, R Moore, S TI Using peptide maps as identity and purity tests for lot release testing of recombinant therapeutic proteins SO BIOPHARM INTERNATIONAL-THE APPLIED TECHNOLOGIES OF BIOPHARMACEUTICAL DEVELOPMENT LA English DT Article ID VALIDATION AB FDA and biopharmaceutical industry stakeholders reach consensus on critical issues related to the use of peptide maps as identity tests for proteins and on their usefulness for lot release tests. The results of that discussion are presented here. C1 Eli Lilly & Co, Indianapolis, IN 46285 USA. Biogen Inc, Analyt Dev, Cambridge, MA 02142 USA. US FDA, Off New Drug Chem, Div New Drug Chem 2, Div Metab & Endocrine Drug Prod,Ctr Drug Evaluat, Rockville, MD 20857 USA. RP Dougherty, J (reprint author), Eli Lilly & Co, Drop Code 5617, Indianapolis, IN 46285 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD APR PY 2003 VL 16 IS 4 BP 54 EP + PG 3 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 669PT UT WOS:000182360200007 ER PT J AU Liotta, LA Espina, V Mehta, AI Calvert, V Rosenblatt, K Geho, D Munson, PJ Young, L Wulfkuhle, J Petricoin, EF AF Liotta, LA Espina, V Mehta, AI Calvert, V Rosenblatt, K Geho, D Munson, PJ Young, L Wulfkuhle, J Petricoin, EF TI Protein microarrays: Meeting analytical challenges for clinical applications SO CANCER CELL LA English DT Review ID CATALYZED REPORTER DEPOSITION; LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION ANALYSIS; SIGNAL AMPLIFICATION; ANTIBODY ARRAYS; CANCER; TECHNOLOGY; PROTEOMICS; MICROENVIRONMENT; IMMUNOASSAYS C1 NCI, FDA NCI Clin Proteom Program, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, FDA NCI Clin Proteom Program, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, FDA NCI Clin Proteom Program, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. OI Espina, Virginia/0000-0001-5080-5972 NR 53 TC 289 Z9 307 U1 4 U2 23 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2003 VL 3 IS 4 BP 317 EP 325 DI 10.1016/S1535-6108(03)00086-2 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 671TQ UT WOS:000182480500005 PM 12726858 ER PT J AU Kadlubar, FF Berkowitz, GS Delongehamp, RR Wang, C Green, BL Tang, G Lamba, J Schuetz, E Wolff, MS AF Kadlubar, FF Berkowitz, GS Delongehamp, RR Wang, C Green, BL Tang, G Lamba, J Schuetz, E Wolff, MS TI The CYP3A4*1B variant is related to the onset of puberty, a known risk factor for the development of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENETIC VARIANT; CLINICAL PRESENTATION; ESTROGEN METABOLISM; STEROID-METABOLISM; AFRICAN-AMERICAN; EARLY MENARCHE; GIRLS; CYP3A4; POLYMORPHISM; ESTRADIOL AB Breast development, one of the first signs of puberty, is closely associated with age at menarche; and early menarche is in turn a well-established risk factor for female breast cancer. We examined the relationships between the onset of puberty and gene variants for certain enzymes that regulate hormone metabolism among 137 healthy nine-year-old girls from two pediatric clinics. High-activity CYP17 alleles, involved in estrogen formation, and high-activity CYP1A2 and CYP1B1 alleles, whose gene products metabolize estradiol, were not associated with pubertal stage. High activity CYP3A4, but not CYP3A5, which primarily metabolizes testosterone, showed a striking association with the onset of puberty (adjusted odds ratio, 3.21; 95% confidence interval, 1.62-6.89 for the genotype 0-1-2 rapid alleles). Of the homozygous CYP3A4*1B/1B girls, 90% had reached puberty; whereas, for the low-activity homozygous CYP3A4*1A/1A individuals, only 40% had done so. In heterozygotes, 56% had reached puberty. CYP1B1, CYP3A4, and CYP3A5 rapid variants were more common in African-American than in Hispanic or Caucasian girls. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol HFT 100, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Mt Sinai Sch Med, Dept Community Med, New York, NY USA. Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol HFT 100, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM fkadlubar@nctr.fda.gov FU NCI NIH HHS [P30 CA21765]; NIEHS NIH HHS [ES 08658, ES 09584]; NIGMS NIH HHS [U01GM61374/93]; ODCDC CDC HHS [CCU300860] NR 39 TC 72 Z9 79 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2003 VL 12 IS 4 BP 327 EP 331 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 667WR UT WOS:000182258000006 PM 12692107 ER PT J AU Faraglia, B Chen, SY Gammon, MD Zhang, YJ Teitelbaum, SL Neugut, AI Ahsan, H Garbowski, GC Hibshoosh, H Lin, DX Kadlubar, FF Santella, RM AF Faraglia, B Chen, SY Gammon, MD Zhang, YJ Teitelbaum, SL Neugut, AI Ahsan, H Garbowski, GC Hibshoosh, H Lin, DX Kadlubar, FF Santella, RM TI Evaluation of 4-aminobiphenyl-DNA adducts in human breast cancer: the influence of tobacco smoke SO CARCINOGENESIS LA English DT Article ID HYDROCARBON-DNA ADDUCTS; POLYCYCLIC AROMATIC-HYDROCARBONS; GENETIC POLYMORPHISMS; IMMUNOHISTOCHEMICAL ANALYSIS; IMMUNOPEROXIDASE DETECTION; CARCINOGEN-METABOLISM; BLADDER-CANCER; TISSUE; ETIOLOGY; RISK AB Breast cancer is one of the major cancers around the world but its etiology is still not well understood. Only similar to50% of the disease is associated with known risk factors including highly penetrant genes and lifestyle factors. Thus, environmental carcinogens may play an important role in the etiology of breast cancer. The arylamine 4-aminobiphenyl (4-ABP) is a tobacco smoke constituent, an environmental contaminant, and a well-established bladder carcinogen in rodents and humans. In this study, we investigated the role of 4-ABP in the etiology of human breast cancer by measuring 4-ABP-DNA adducts using a monoclonal antibody based immunoperoxidase method that had been validated by comparison with gas chromatography/mass spectroscopy analysis of liver tissues from 4-ABP-treated mice. Adducts were analyzed in 150 paraffin-embedded breast tumors and in 55 adjacent normal tissues collected from cases in the Long Island Breast Cancer Study Project. The role of polymorphisms in genes involved in the metabolism of 4-ABP including N-acetyl transferase 2 (NAT2), cytochrome P4501A2 (CYP1A2) and glutathione S-transferase M1 (GSTM1) and the nucleotide excision repair gene XPD was also explored in the same patients. The mean log-transformed relative staining intensity for 4-ABP-DNA adducts was higher in normal (5.93 +/- 0.54) than in the corresponding tumor (5.44 +/- 0.62, P < 0.0001) tissues. However, a highly significant positive correlation was observed between the levels of 4-ABP-DNA in both tissues (r = 0.72, P < 0.0001). Smoking status was correlated with the levels of 4-ABP-DNA in tumor adjacent normal tissues with a significant linear trend (P = 0.04) for current, former and never smokers; adducts were not related to smoking status in tumor tissues. No correlation was observed between the levels of 4-ABP-DNA and polymorphisms in the genes analyzed even when subjects were stratified by smoking status. These results demonstrate that smoking is associated with increased levels of 4-ABP-DNA adducts in human mammary tissue. In this study, genetic polymorphisms did not significantly affect the formation of 4-ABP-DNA adducts in breast cancer cases, perhaps due to the small number of samples. C1 Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. CUNY Mt Sinai Sch Med, Dept Environm Hlth Sci, New York, NY 10029 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Santella, RM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, 701 W 168th St, New York, NY 10032 USA. FU NCI NIH HHS [CA/ES66572, CA77185]; NIEHS NIH HHS [ES10126, ES09089] NR 40 TC 52 Z9 52 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2003 VL 24 IS 4 BP 719 EP 725 DI 10.1093/carcin/bgg013 PG 7 WC Oncology SC Oncology GA 676HK UT WOS:000182745100013 PM 12727801 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Mass spectrometry-based diagnostics: The upcoming revolution in disease detection SO CLINICAL CHEMISTRY LA English DT Editorial Material ID BIOMARKER DISCOVERY; PROTEOMIC PATTERNS; PROSTATE-CANCER; PROTEIN; SERUM C1 NCI, US FDA, Clin Proteom Program, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, US FDA, Clin Proteom Program, Lab Pathol,Ctr Canc Res, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), NCI, US FDA, Clin Proteom Program, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 20 TC 71 Z9 73 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2003 VL 49 IS 4 BP 533 EP 534 DI 10.1373/49.4.533 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 660DK UT WOS:000181818400001 PM 12651801 ER PT J AU Rolan, P Atkinson, AJ Lesko, LJ AF Rolan, P Atkinson, AJ Lesko, LJ CA Sci Organizing Comm Conf Report Co TI Use of biomarkers from drug discovery through clinical practice: Report of the Ninth European Federation of Pharmaceutical Sciences Conference on Optimizing Drug Development SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID SURROGATE END-POINTS; MORTALITY AB The Ninth European Federation for Pharmaceutical Sciences (EUFEPS) Conference on Optimizing Drug Development was held in Basel, Switzerland, December 10-12, 2001. The overall objective of the conference was to find new ways of advancing the integration of biomarkers into drug development and clinical practice to make drug development more efficient and the clinical use of drugs more effective. The aim of this conference report is to summarize the key ideas and recommendations that were identified at the meeting, both by formal presentation and from the breakout sessions, which all participants were encouraged to join. Rather than providing a synopsis of each individual presentation, the report is organized along the key themes that emerged during the meeting. C1 Medeval Ltd, Manchester M15 6SH, Lancs, England. NIH, Ctr Clin, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Rolan, P (reprint author), Medeval Ltd, Manchester Sci Pk, Manchester M15 6SH, Lancs, England. NR 22 TC 57 Z9 59 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2003 VL 73 IS 4 BP 284 EP 291 DI 10.1016/S0009-9236(02)00025-5 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 666LM UT WOS:000182178800003 PM 12709718 ER PT J AU Kotsev, SN Dushkin, CD Ilev, IK Nagayama, K AF Kotsev, SN Dushkin, CD Ilev, IK Nagayama, K TI Refractive index of transparent nanoparticle films measured by surface plasmon microscopy SO COLLOID AND POLYMER SCIENCE LA English DT Article DE surface plasmon resonance; 2D-particle array; complex refractive index; ferritin; latex ID 2-DIMENSIONAL CRYSTALLIZATION; SEMICONDUCTOR NANOCRYSTALS; SPECTROSCOPIC ELLIPSOMETRY; CDSE NANOCRYSTALLITES; HYDROPHOBIC SURFACES; SELF-ORGANIZATION; PROTEIN LAYERS; GOLD SURFACES; ADSORPTION; RESONANCE AB Nanometer thin films of latex spheres or ferritin macromolecules are deposited on silver substrate and their structure is studied by means of the surface plasmon resonance method. A homogeneous particle layer is spread in a circular paraffin cell tightly attached to a silver film on glass. Appropriate drying of the suspension in the presence of surfactant creates a monolayer and multilayer of ordered nanoparticles. The layers modulate the surface plasmon and, hence, the deep and narrow minimum in film reflectivity. Specially designed experimental setup views the illuminated film area by an optical microscope and measures the layer reflectivity as a function of the incident angle. The brightness of image, obtained at the angle of minimum reflectivity, depends on the thickness of particle layer. The reflectivity data are fitted regarding plane parallel layer of a complex refractive index and using theoretical equations that separate the real and imaginary parts. The calculated layer thickness and the real part of refractive index are in a reasonable agreement with those known for similar systems. The imaginary part of the refractive index depends on the structural defects of the nanoparticle layers. C1 Univ Sofia, Lab Nanoparticle Sci & Technol, Dept Inorgan Chem, Fac Chem, BU-1126 Sofia, Bulgaria. Temple Univ, Dept Phys, Philadelphia, PA 19122 USA. US FDA, CDRH, Electro Opt Branch, Rockville, MD 20857 USA. Natl Inst Physiol Sci, Lab Ultrastruct Res, Dept Mol Physiol, Okazaki, Aichi 4448585, Japan. RP Dushkin, CD (reprint author), Univ Sofia, Lab Nanoparticle Sci & Technol, Dept Inorgan Chem, Fac Chem, Room 339,1 James Boucher Blvd, BU-1126 Sofia, Bulgaria. NR 72 TC 8 Z9 9 U1 2 U2 10 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0303-402X J9 COLLOID POLYM SCI JI Colloid Polym. Sci. PD APR PY 2003 VL 281 IS 4 BP 343 EP 352 DI 10.1007/s00396-002-0782-0 PG 10 WC Chemistry, Physical; Polymer Science SC Chemistry; Polymer Science GA 671HJ UT WOS:000182459000008 ER PT J AU Wang, SJ Hung, HMJ AF Wang, SJ Hung, HMJ TI Assessing treatment efficacy in noninferiority trials SO CONTROLLED CLINICAL TRIALS LA English DT Article DE treatment efficacy; preservation level of control effect; type I error; confidence interval method; synthesis test method ID ACTIVE-CONTROL TRIALS; CLINICAL-TRIALS; STATISTICAL-METHODS; PLACEBO AB Often one of the primary objectives of an active-controlled noninferiority trial without a placebo arm is to assert that an experimental treatment would have been more effective than a putative placebo had the placebo been included in the trial. This may be an important consideration for regulatory applications. To achieve this objective, such a noninferiority analysis entails cross-trial statistical inference. Because of the uncertainty and difficulty surrounding cross-trial inference, the noninferiority analysis often aims to demonstrate that the experimental treatment preserves a specified fraction of the effect of the active control. The rationale is that by demonstrating the percent effect retention, the efficacy of the experimental treatment can be established with a great level of confidence. The confidence interval approach and synthesized test approach have been used for inferring the percent effect preservation. In this work we evaluate the type I error rates of these approaches to the cross-trial statistical inference for establishing treatment efficacy. The evaluation provides guidance as to what percentage of the control effect needs to be preserved so that through noninferiority testing of effect retention one can assert the treatment efficacy within a desired level of the error rate. (C) 2003 Elsevier Science Inc. All rights reserved. C1 US FDA, Div Biometr 2, OB, CDER, Rockville, MD 20857 USA. US FDA, Div Biometr 1, Off Biostat, CDER, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, Div Biometr 2, OB, CDER, HFD-715,9B07,PKLN,5600 Fishers Lane, Rockville, MD 20857 USA. NR 12 TC 21 Z9 24 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD APR PY 2003 VL 24 IS 2 BP 147 EP 155 AR PII S0197-2456(02)00304-5 DI 10.1016/S0197-2456(02)00304-5 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 661PP UT WOS:000181899200004 PM 12689736 ER PT J AU Szepessy, E Nagy, G Jenei, Z Serfozo, Z Csuka, I James, J Banfalvi, G AF Szepessy, E Nagy, G Jenei, Z Serfozo, Z Csuka, I James, J Banfalvi, G TI Multiple subphases of DNA repair and poly (ADP-ribose) synthesis in Chinese hamster ovary (CHO-K1) cells SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE NAD; nucleotide incorporation; synchronization; centrifugal elutriation; cell cycle; permeable cells; replication; repair; DNA fragmentation ID S-PHASE; POLY(ADP-RIBOSE) POLYMERASE; BACILLUS-SUBTILIS; HUMAN FIBROBLASTS; PERMEABLE CELLS; CYCLE; REPLICATION; RIBOSYLATION; APOPTOSIS; CHAINS AB The two types of DNA synthesis as well as poly(ADP-ribose) biosynthesis were measured simultaneously in synchronized intact populations of CHO cells throughout the duration of S phase. Naturally occurring DNA fragmentation was detected by, random primed oligonucleotide synthesis (ROPS assay). Fractions of synchronous cell populations were obtained by counterflow centrifugal elutriation. By gradually increasing the resolution of centrifugal elutriation multiple non-overlapping repair and replication peaks were obtained. The elutriation profile of DNA repair peaks corresponded to the DNA fragmentation pattern measured by ROPS assay. The number and position of poly(ADP-ribose) peaks during S phase resembled those seen in the DNA replication profile. Our results indicate that PAR synthesis is coupled to DNA replication serving the purpose of genomic stability. C1 Univ Debrecen, Dept Anim Anat & Physiol, H-4010 Debrecen, Hungary. Semmelweis Univ, Sch Med, Dept Med Chem Mol Biol & Pathobiochem, Budapest, Hungary. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Banfalvi, G (reprint author), Univ Debrecen, Dept Anim Anat & Physiol, 1 Egyetem Sq, H-4010 Debrecen, Hungary. OI Szeman-Nagy, Gabor/0000-0003-1906-0188 NR 39 TC 2 Z9 4 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD APR PY 2003 VL 82 IS 4 BP 201 EP 207 DI 10.1078/0171-9335-00301 PG 7 WC Cell Biology SC Cell Biology GA 678CP UT WOS:000182847700006 PM 12751906 ER PT J AU Tadokoro, T Kobayashi, N Zmudzka, BZ Ito, S Wakamatsu, K Yamaguchi, Y Korossy, KS Miller, SA Beer, JZ Hearing, VJ AF Tadokoro, T Kobayashi, N Zmudzka, BZ Ito, S Wakamatsu, K Yamaguchi, Y Korossy, KS Miller, SA Beer, JZ Hearing, VJ TI UV-induced DNA damage and melanin content in human skin differing in racial/ethnic origin SO FASEB JOURNAL LA English DT Article DE melanocytes; skin color; photocarcinogenesis; cyclobutane pyrimidine dimers ID CYCLOBUTANE PYRIMIDINE DIMERS; CULTURED HUMAN MELANOCYTES; ULTRAVIOLET-B; 6-4 PHOTOPRODUCTS; MALIGNANT-MELANOMA; P53 GENE; CANCER; RADIATION; INDUCTION; EXPOSURE AB DNA damage induced by UV radiation is a critical event in skin photocarcinogenesis. However, the role of racial/ethnic origin in determining individual UV sensitivity remains unclear. In this study, we examined the relationships between melanin content and DNA damage induced by UV exposure in situ in normal human skin of different racial/ethnic groups, phototypes, and UV sensitivities. The minimal erythema dose (MED) was established for each subject exposed to UVA/UVB radiation, and skin was biopsied before as well as 7 min, 1 day, and 1 wk after UV exposure. There was great variation among individuals in the amount of DNA damage incurred and rates of its removal. The results show that after exposure to 1 MED of UV, the skin of subjects from all groups suffered significant DNA damage, and that increasing content of constitutive melanin inversely correlated with the amount of DNA damage. It is clear from these results that measured erythemal UV sensitivity of the skin (MED) is a more useful predictor of DNA photodamage than is racial/ethnic origin or skin phototype and that rates of DNA damage removal following UV radiation may be the critical determinant of the UV sensitivity (including predisposition to cancer) of the skin. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Aichi 4701192, Japan. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 NR 48 TC 148 Z9 155 U1 2 U2 10 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 APR PY 2003 VL 17 IS 6 BP 1177 EP + DI 10.1096/fj.02-0865fje PG 22 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 673KL UT WOS:000182580100042 PM 12692083 ER PT J AU Andrews, LS DeBlanc, S Veal, CD Park, DL AF Andrews, LS DeBlanc, S Veal, CD Park, DL TI Response of Vibrio parahaemolyticus 03 : K6 to a hot water/cold shock pasteurization process SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE oysters; pasteurization; Vibrio parahaemolyticus 03 : K6 AB Vibrio vulnificus and V. parahaemolyticus are natural inhabitants of estuarine environments world wide. Pathogenic strains of these bacteria are often transmitted to humans through consumption of raw oysters, which flourish in the same estuaries. Previous studies reported the effective use of hot water pasteurization followed by cold shock to eliminate from raw oysters naturally and artificially incurred environmental strains of V. vulnificus and V. parahaemolyticus common to the Gulf of Mexico. The present study focused on the use of the same pasteurization method to reduce a highly process resistant Vibrio strain, V. parahaemolyticus O-3:K6 to non-detectable levels. Oysters were artificially contaminated with 10(4) and 10(6) V. parahaemolyticus 03:K6 cfu g(-1) oyster meat. Contaminated oysters were pasteurized between 50 and 52degreesC for up to 22 min. Samples of processed oysters were enumerated for V. parahaemolyticus O3:K6 at 2-min intervals beginning after the 'come-up time' to achieve an oyster internal temperature of at least 50degreesC. The D value ( D(52)degreesC) was 1.3-1.6 min. V. parahaemolyticus O3:K6 proved more process resistant than non-pathogenic environmental strains found in Gulf of Mexico waters. A total processing time of at least 22 min at 52degreesC was recommended to reduce this bacterium to non-detectable levels (<3 g(-1) oyster meat). C1 Mississippi State Univ, Coastal Res & Extens Ctr, Biloxi, MS 39531 USA. US FDA, Div Nat Prod, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Andrews, LS (reprint author), Mississippi State Univ, Coastal Res & Extens Ctr, 2710 Beach Blvd,Suite 1E, Biloxi, MS 39531 USA. NR 8 TC 14 Z9 14 U1 1 U2 9 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. PD APR PY 2003 VL 20 IS 4 BP 331 EP 334 DI 10.1080/0265203021000060896 PG 4 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 678PE UT WOS:000182875000003 PM 12775474 ER PT J AU Juneja, VK Novak, JS Huang, LH Eblen, BS AF Juneja, VK Novak, JS Huang, LH Eblen, BS TI Increased thermotolerance of Clostridium perfringens spores following sublethal heat shock SO FOOD CONTROL LA English DT Article DE Clostridium perfringens; heat resistance; thermotolerance; heat shock ID THERMAL INACTIVATION; PHOSPHATE BUFFER; VEGETATIVE CELLS; GROWTH; TURKEY; MICROORGANISMS; RESISTANCE; PRODUCTS; DEATH AB Beef gravy samples inoculated with Clostridium perfringens spores were heat shocked at 75 degreesC for 20 min, and then thermotolerance at 100 degreesC was assessed using a submerged-coil heating apparatus. Survivors were enumerated on Shahidi Ferguson Perfringens agar. An association of the heat resistance with the origin of the C perfringens could not be established due to significant variations in the heat resistance among strains. Interestingly, deviations from classical logarithmic linear declines in the log numbers with time were not observed in both control and heat shocked samples. D-values at 100 degreesC for C. Perfringens spores ranged from 15.5 to 21.4 min. Heat shocked spores of 9 out of 10 strains had significantly higher (p < 0.05) D-values at 100 &DEG;C than unstressed spores. Proteins with epitopic and size similarity to Escherichia coli GroEL and Bacillus subtilis small acid-soluble protein, SspC, were present in spores. However, heat shock treated spores did not appear to significantly increase expression of these proteins. Acquired thermotolerance is of substantial practical importance to food processors and should provide useful information for designing thermal treatments to eliminate C. perfringens spores in ready-to-eat foods. Published by Elsevier Science Ltd. C1 ARS, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20250 USA. RP Juneja, VK (reprint author), ARS, USDA, Eastern Reg Res Ctr, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. NR 28 TC 20 Z9 21 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD APR PY 2003 VL 14 IS 3 BP 163 EP 168 AR PII S0956-7135(02)00060-9 DI 10.1016/S0956-7135(02)00060-9 PG 6 WC Food Science & Technology SC Food Science & Technology GA 652CG UT WOS:000181361500006 ER PT J AU Wear, KA AF Wear, KA TI Characterization of trabecular bone using the backscattered spectral centroid shift SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID QUANTITATIVE ULTRASOUND MEASUREMENTS; FREQUENCY-DEPENDENT ATTENUATION; BOVINE CANCELLOUS BONE; HUMAN CALCANEUS; MINERAL DENSITY; HIP FRACTURE; OS CALCIS; IN-VITRO; MECHANICAL-PROPERTIES; DISEASED LIVER AB Ultrasonic attenuation in bone in vivo is generally measured using a through-transmission method at the calcaneus. Although attenuation in calcaneus has been demonstrated to be a useful predictor for osteoporotic fracture risk, measurements at other clinically important sites' such as hip and spine, could potentially contain additional useful diagnostic information. Through-transmission measurements may not be feasible at these sites due to complex bone shapes and the increased amount of intervening soft tissue. Centroid shift from the backscattered signal is an index of attenuation slope and has been used previously to characterize soft tissues. In this paper, centroid shift from signals backscattered from 30 trabecular bone samples in vitro were measured. Attenuation slope also was measured using a through-transmission method. The correlation coefficient between centroid shift and attenuation slope was -0.71. The 95% confidence interval was (-0.86, -0.47). These results suggest that the backscattered spectral centroid shift may contain useful diagnostic information potentially applicable to hip and spine. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 60 TC 29 Z9 29 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 EI 1525-8955 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD APR PY 2003 VL 50 IS 4 BP 402 EP 407 DI 10.1109/TUFFC.2003.1197963 PG 6 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 675CD UT WOS:000182674700007 PM 12744396 ER PT J AU Bertholet, S Dickensheets, HL Sheikh, F Gam, AA Donnelly, RP Kenney, RT AF Bertholet, S Dickensheets, HL Sheikh, F Gam, AA Donnelly, RP Kenney, RT TI Leishmania donovani-induced expression of suppressor of cytokine signaling 3 in human macrophages: A novel mechanism for intracellular parasite suppression of activation SO INFECTION AND IMMUNITY LA English DT Article ID IFN-GAMMA; MOUSE MACROPHAGES; SOCS BOX; INHIBITION; TRANSDUCTION; INDUCTION; RESPONSES; RECEPTOR; PROTEINS; PHOSPHORYLATION AB Leishmania donovani protozoan parasites, the causative agent of visceral leishmaniasis, establish an infection partly by interfering with cytokine signaling in the host macrophages. Therefore, we investigated the expression of the suppressor of cytokine signaling (SOCS) genes in human macrophages infected with L. donovani. The expression of SOCS3 mRNA was induced transiently after exposure to live or heat-killed parasites, but not purified lipophosphoglycan, while that of other SOCS genes remained unchanged. SOCS3 gene expression was not dependent on phagocytosis or on cytokines released by L. donovani-infected macrophages, such as interleukin-1beta or tumor necrosis factor alpha. In addition, Leishmania used a different signaling pathway(s) than bacterial lipopolysaccharide to induce SOCS3 mRNA, as indicated by the kinetics of induction and sensitivity to polymyxin B inhibition. Finally, phosphorylation of the STAT1 transcription factor was significantly reduced in L. donovani-infected macrophages and required de novo transcription. The induction of SOCS3 provides a potent inhibitory mechanism by which intracellular microorganisms may suppress macrophage activation and interfere with the host immune response. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Kenney, RT (reprint author), Iomai Corp, 20 Firstfield Rd,Suite 250, Gaithersburg, MD 20878 USA. NR 30 TC 43 Z9 47 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 APR PY 2003 VL 71 IS 4 BP 2095 EP 2101 DI 10.1128/IAI.71.4.2095-2101.2003 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 662BQ UT WOS:000181926200060 PM 12654831 ER PT J AU Myers, MJ Farrell, DE Palmer, DC Post, LO AF Myers, MJ Farrell, DE Palmer, DC Post, LO TI Inflammatory mediator production in swine following endotoxin challenge with or without co-administration of dexamethasone SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE endotoxin challenge; dexamethasone; lipopolysaccharide ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; FACTOR TNF PRODUCTION; HUMAN WHOLE-BLOOD; FACTOR-ALPHA; GENE-EXPRESSION; TIME-COURSE; BACTERIAL LIPOPOLYSACCHARIDE; CYTOKINE PRODUCTION; ESCHERICHIA-COLI AB The inflammatory response in swine challenged with lipopolysaccharide (LPS) has only been partially characterized. As swine are increasingly used in biomedical research, it is important to determine if they respond to endotoxin challenge in a manner similar to other model systems. Accordingly, 24 Poland China X Landrace barrows were treated with saline, LPS, dexamethasone, or LPS and dexamethasone, with six animals in each treatment group. The kinetics of TNFalpha IL-1beta, 11,6, IL-8, IL-10, nitric oxide (nitrate/nitrite), and neopterin production in swine plasma were examined at 1, 3, 6, 9, and 24 h after acute LPS challenge. Lipopolysaccharide increased plasma TNFalpha levels, which peaked I h post-challenge. Dexamethasone decreased LPS-induced TNFalpha by approximately 60%. Plasma EL-6 levels peaked 3 h post-LPS challenge, returning to basal levels by 9 h. Swine given both LPS and dexamethasone had minimal IL-6 levels. Control and dexamethasone-only treated animals never exhibited systemic TNFalpha or IL-6 levels. Lipopolysaccharide increased plasma IL-10 I h after challenge. Dexamethasone did not alter plasma IL-10 levels in LPS-challenged swine. Interleukin-1beta was constitutively present in plasma and was not altered by any combination of treatments. Plasma IL-8 was not observed in any treatment group. Plasma nitrate/nitrite levels were maximal 24 h post-challenge. Dexamethasone treatment prevented increases in plasma nitrate/nitrite levels in LPS-treated animals. Lipopolysaccharide induced levels of neopterin; dexamethasone served to further increase plasma neopterin levels in LPS-challenged animals. The discordant regulation of inflammatory mediators suggests that the immunological responses by swine to LPS are distinct from the responses seen in rodent and human studies. (C) 2003 Elsevier Science B.V. All rights reserved. C1 US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. US FDA, Div Surveillance, Ctr Vet Med, Rockville, MD 20885 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. RI Palmer, Douglas/B-9454-2008 OI Palmer, Douglas/0000-0001-5018-5734 NR 62 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD APR PY 2003 VL 3 IS 4 BP 571 EP 579 DI 10.1016/S1567-5769(03)00048-1 PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 676DZ UT WOS:000182718800011 PM 12689661 ER PT J AU Grimm, TA Beer, BE Hirsch, VM Clouse, KA AF Grimm, TA Beer, BE Hirsch, VM Clouse, KA TI Simian immunodeficiency viruses from multiple lineages infect human macrophages: Implications for cross-species transmission SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE simian immunodeficiency virus; HIV; human macrophages; cross-species transmission; infection; primate model ID AFRICAN-GREEN MONKEYS; BLOOD MONONUCLEAR-CELLS; RED-CAPPED MANGABEY; PRIMATE LENTIVIRUSES; NATURAL INFECTION; MANDRILLUS SPHINX; SOOTY MANGABEYS; CYCLE ARREST; SIV; HIV-1 AB Zoonotic transfer of simian immunodeficiency virus (SIV) from chimpanzees and sooty mangabeys to humans has been documented on at least seven occasions. Several recently identified SIV isolates have also been shown to replicate efficiently in human peripheral blood mononuclear cells (PBMCs) in vitro, indicative of the potential for additional cross-species transmission via T cell infection. Although SIV predominantly uses the macrophage-tropic HIV chemokine coreceptor CCR5, little is known about the ability of SIV to infect human macrophages. In this study, 16 SIV isolates belonging to five different primate lentivirus lineages were tested for their ability to infect human monocyte-derived macrophages (MDMs). Twelve of the viruses were capable of infecting MDMs, and 11 of these were also able to replicate in human PBMCs. The replication capacity of the isolates differed within and between the various families and was dependent on particular donor macrophages. Our results suggest that most simian lentiviruses characterized to date not only have the ability to infect primary human T lymphocytes but also replicate efficiently in macrophages, thereby increasing the potential for cross-species transmission into the human population. Comparative studies using these isolates may facilitate the identification of characteristics that contribute to virus infectivity and pathogenicity. C1 US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Off Therapeut Res & Review,Ctr Biol Evaluat & Rev, Rockville, MD 20852 USA. NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. RP Clouse, KA (reprint author), US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Off Therapeut Res & Review,Ctr Biol Evaluat & Rev, HFM-558,1401 Rockville Pike, Rockville, MD 20852 USA. NR 49 TC 22 Z9 22 U1 0 U2 1 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 APR 1 PY 2003 VL 32 IS 4 BP 362 EP 369 DI 10.1097/00126334-200304010-00003 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 661FB UT WOS:000181879600003 PM 12640192 ER PT J AU Trivedi, L Valerio, C Slater, JE AF Trivedi, L Valerio, C Slater, JE TI Endotoxin content of standardized allergen vaccines SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE endotoxin; lipopolysaccharide; allergen; allergen vaccine; allergen immunotherapy; Limulus amebocyte lysate; endotoxin-neutralizing protein; standardization; protease ID LIMULUS AMEBOCYTE LYSATE; SYSTEMIC REACTIONS; ASTHMA; IMMUNOTHERAPY; MITE; EXPOSURE; LAL AB Background: Endotoxin is a ubiquitous and potent proinflammatory agent. Previous limited studies suggest that it is present in allergen vaccines and that this could affect the safety and efficacy of allergen immunotherapy. The endotoxin content of standardized allergen vaccines is unknown. Objective: The purpose of this study was to quantify the amount of endotoxin contained in standardized allergen vaccines. Methods: The endotoxin content of 14 allergen vaccines was measured by using the Limulus amebocyte lysate (LAL) gel-clot assay. To account for (1,3)-beta-D-glucan and protease interference, vaccines were selectively depleted of endotoxin and then retested with the gel-clot assay. Proteases were also heat-inactivated in selected vaccines. Fifty-eight lots of vaccines were tested, including at least two manufacturers per vaccine. Results: The endotoxin content of the 58 vaccines ranged from undetectable to 34,000 EU/mL. Cat pelt (12,735 EU/mL; range, 5177 to 33,805) had significantly more endotoxin activity than cat hair (2883 EU/mL; range, 1 to 16,962), and Dermatophagoides farinae extracts (4619 EU/mL; range, 849 to 8485) had more than Dermatophagoides pteronyssinus (11 EU/mL; range, 1 to 34). Grass (160 EU/mL; range, 3 to 1561) and ragweed pollen (341 EU/mL; range, 8 to 1697) vaccines contained less endotoxin. (1,3)-beta-D-glucan interference was significant (>10%) only in three ragweed vaccines and two grass vaccines. Heat inactivation had no effect. There were considerable differences in endotoxin content of the same vaccines made by different manufacturers. Conclusions: The endotoxin content of standardized allergen vaccines is extremely variable. Interference by proteases and (1,3)-beta-D-glucans is minimal. The effects of the high levels of endotoxin in some vaccines on the immunomodulatory changes associated with allergen immunotherapy require further study. C1 NIAID, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Slater, JE (reprint author), US FDA, Ctr Drug Evaluat & Res, Lab Immunobiochem HFM422, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 34 TC 3 Z9 4 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2003 VL 111 IS 4 BP 777 EP 783 DI 10.1067/mai.2003.1338 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 667WW UT WOS:000182258500017 ER PT J AU Pfefer, TJ Matchette, LS Bennett, CL Gall, JA Wilke, JN Durkin, AJ Ediger, MN AF Pfefer, TJ Matchette, LS Bennett, CL Gall, JA Wilke, JN Durkin, AJ Ediger, MN TI Reflectance-based determination of optical properties in highly attenuating tissue SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fiber optic sensors; neural networks; optical properties; reflectance; simulations; tissue optics ID HUMAN COLON TISSUE; CHROMOPHORE CONCENTRATIONS; TURBID MEDIA; NONINVASIVE DETERMINATION; IN-VIVO; SCATTERING; LIGHT; SPECTROSCOPY; FLUORESCENCE; SPECTRA AB Accurate data on in vivo tissue optical properties in the ultraviolet A (UVA) to visible (VIS) range are needed to elucidate light propagation effects and to aid in identifying safe exposure limits for biomedical optical spectroscopy. We have performed a preliminary study toward the development of a diffuse reflectance system with maximum fiber separation distance of less than 2.5 mm. The ultimate objective, is to perform endoscopic measurement of optical properties in the UVA to VIS. Optical property sets. with uniformly and randomly distributed values were developed within the range of interest: absorption coefficients from 1 to 25 cm(-1) and reduced scattering coefficients from 5 to 25 cm(-1). Reflectance datasets were generated by direct measurement of Intralipid-dye tissue phantoms at lambda=675 nm and Monte Carlo simulation of light propagation. Multivariate calibration models were generated using feed-forward artificial neural network or partial least squares algorithms. Models were calibrated and evaluated using simulated or measured reflectance datasets. The most accurate models developed-those based on a neural network and uniform optical property intervals-were able to determine absorption and reduced scattering coefficients with root mean square errors of 2 and 3 cm(-1), respectively. Measurements of ex vivo bovine liver at 543 and 633 nm were within 5 to 30% of values reported in the literature. While our technique for determination of optical properties appears feasible and moderately accurate, enhanced accuracy may be achieved through modification of the experimental system and processing algorithms. (C) 2003 Society of Photo-Optical Instrumentation Engineers. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53201 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RI Pfefer, Josh/I-9055-2012; OI Durkin, Anthony/0000-0001-9124-6388 NR 31 TC 57 Z9 59 U1 1 U2 11 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD APR PY 2003 VL 8 IS 2 BP 206 EP 215 DI 10.1117/1.1559487 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 669XE UT WOS:000182375200006 PM 12683846 ER PT J AU McDermott, PF Walker, RD AF McDermott, PF Walker, RD TI Standardizing antimicrobial susceptibility testing of Campylobacter species SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter C1 US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. RP McDermott, PF (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2003 VL 41 IS 4 BP 1810 EP 1810 DI 10.1128/JCM.41.4.1810.2003 PG 1 WC Microbiology SC Microbiology GA 666LZ UT WOS:000182179900084 PM 12682196 ER PT J AU Johnson, JR Williams, G Pazdur, R AF Johnson, JR Williams, G Pazdur, R TI End points and United States food and drug administration approval of oncology drugs SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-TRIALS; BREAST-CANCER; GROWTH AB Purpose: To summarize the end points used by the United States Food and Drug Administration (FDA) to approve new cancer drug applications over the last 13 years. Materials and Methods: The FDA granted marketing approval to 71 oncology drug applications between January 1, 1990, and November 1, 2002. The end points used as the approval basis for each application are presented, and the rationale for each end point is discussed. Results: The FDA grants either regular marketing approval or accelerated marketing approval for oncology drug applications. Regular approval is based on end points that demonstrate that the drug provides a longer life, a better life, or a favorable effect on an established surrogate for a longer life or a better life. Accelerated approval (AA) is based on a surrogate end point that is less well established but that is reasonably likely to predict a longer or a better life. Tumor response was the approval basis in 26 of 57 regular approvals, supported by relief of tumor-specific symptoms in nine of these 26 regular approvals. Relief of tumor-specific symptoms provided critical support for approval in 13 of 57 regular approvals. Approval was based on tumor response in 12 of 14 AAs. Conclusion: End points other than survival were the approval basis for 68% (39 of 57) of oncology drug marketing applications granted regular approval and for all 14 applications granted accelerated approval from January 1, 1990, to November 1, 2002. (C) 2003 by American Society of Clinical Oncology. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Johnson, JR (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 15 TC 269 Z9 284 U1 0 U2 4 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 APR 1 PY 2003 VL 21 IS 7 BP 1404 EP 1411 DI 10.1200/JCO.2003.08.072 PG 8 WC Oncology SC Oncology GA 662XB UT WOS:000181973400031 PM 12663734 ER PT J AU Lesko, LJ Salerno, RA Spear, BB Anderson, DC Anderson, T Brazell, C Collins, J Dorner, A Essayan, D Gomez-Mancilla, B Hackett, J Huang, SM Ide, S Killinger, J Leighton, J Mansfield, E Meyer, R Ryan, SG Schmith, V Shaw, P Sistare, F Watson, M Worobec, A AF Lesko, LJ Salerno, RA Spear, BB Anderson, DC Anderson, T Brazell, C Collins, J Dorner, A Essayan, D Gomez-Mancilla, B Hackett, J Huang, SM Ide, S Killinger, J Leighton, J Mansfield, E Meyer, R Ryan, SG Schmith, V Shaw, P Sistare, F Watson, M Worobec, A TI Pharmacogenetics and pharmacogenomics in drug development and regulatory decision making: Report of the first FDA-PWG-PhRMA-DruSafe workshop SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE pharmacogenetics; pharmacogenomics; drug development process; regulatory agencies; safe harbor ID HYPERSENSITIVITY; ASSOCIATION; ABACAVIR; GENE AB The use of pharmacogenetics and pharmacogenomics in the drug development process, and in the assessment of such data submitted to regulatory agencies by industry, has generated significant enthusiasm as well as important reservations within the scientific and medical communities. This situation has arisen because of the increasing number of exploratory and confirmatory investigations into variations in RNA expression patterns and DNA sequences being conducted in the preclinical and clinical phases of drug development, and the uncertainty surrounding the acceptance of these data by regulatory agencies. This report summarizes the outcome of a workshop cosponsored by the Food and Drug Administration (FDA), the Pharmacogenetics Working Group (PWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the PhRMA Preclinical Safety Committee (DruSafe). The specific aim of the workshop was to identify key issues associated with the application of pharmacogenetics and pharmacogenomics, including the feasibility of a regulatory "safe harbor" for exploratory genome-based data, and to provide a forum for industry-regulatory agency dialogue on these important issues. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20857 USA. Wyeth Res, WorldWide Regulatory Affairs, St Davids, PA USA. Abbott Labs, Pharmacogenet, Abbott Pk, IL 60064 USA. Pharmacia corp, Kalamazoo, MI USA. Pfizer Inc, Groton, CT 06340 USA. GlaxoSmithKline, Genet Res, Greenford, Middx, England. Wyeth Res, Andover, MA USA. Wyeth Res, Chazy, NY USA. US FDA, Ctr Biol Evaluat & Res, Off Therapeut, Div Clin Trial Design & Anal, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Off Vitro Diagnost Device Evaluat & Safety, Rockville, MD 20857 USA. NHGRI, NIH, Gaithersburg, MD USA. Novartis, Gaithersburg, MD USA. AstraZeneca Pharmaceut, Wilmington, DE USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Bristol Myers Squibb Co, Pharmacogenom & Human Genet, Princeton, NJ 08543 USA. Merck & Co Inc, Clin Genom, W Point, PA USA. RP Lesko, LJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 21 TC 77 Z9 83 U1 0 U2 2 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 APR PY 2003 VL 43 IS 4 BP 342 EP 358 DI 10.1177/0091270003252244 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 660VX UT WOS:000181855700003 PM 12723455 ER PT J AU Englberger, L Aalbersberg, W Ravi, P Bonnin, E Marks, GC Fitzgerald, MH Elymore, J AF Englberger, L Aalbersberg, W Ravi, P Bonnin, E Marks, GC Fitzgerald, MH Elymore, J TI Further analyses on Micronesian banana, taro, breadfruit and other foods for provitamin A carotenoids and minerals SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE banana; taro; breadfruit; cultivars; alpha-carotene; beta-carotene; zinc; minerals; vitamin A deficiency; micronesia; HPLC; ICP ID VITAMIN-A-DEFICIENCY AB Few Micronesian foods have been analyzed for nutrient content. Information is needed on locally grown, culturally acceptable foods that could be promoted to alleviate, vitamin A deficiency in the Federated States of Micronesia. Using an ethnographic approach that included key informant interviews and observation, Micronesian cultivars with potential for high-carotenoid content according to their coloration were identified. These cultivars of banana, giant swamp taro, breadfruit and other foods were analyzed for alpha- and beta-carotene using high-performance liquid chromatography (HPLC) and for nine minerals using inductively coupled plasma (ICP). A wide range of provitamin A carotenoid levels was found in banana, taro, and breadfruit cultivars, some containing very high levels (beta-carotene content from 515 to 6360 mug/100 g in banana, 260 to 1651 mug/100 g in taro, and 295 to 868 mug/100 g in breadfruit, edible portion). Other cultivars contained moderate levels, but as they can be eaten in large quantities, they may contribute significantly to vitamin A status. The taro samples contained very high levels of zinc (mean 5.9 mg/100 g) and significant levels of other minerals (mean content of calcium was 120 mg/100 g). These staples with cultural acceptability and high availability potentially could play a role in vitamin A, micronutrient, and chronic disease programs in the Pacific. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Queensland, Sch Populat Hlth, Div Int Hlth, Nutr Program, Brisbane, Qld, Australia. Univ S Pacific, Inst Appl Sci, Suva, Fiji. US FDA, Atlanta Ctr Nutrient Anal, Atlanta, GA USA. Univ Sydney, Sch Occupat & Leisure Sci, Sydney, NSW 2006, Australia. Dept Hlth Educ & Social Affairs, Ponape, Micronesia. RP Englberger, L (reprint author), POB 2299, Kolonia 96941, Pohnpei, Micronesia. NR 39 TC 61 Z9 63 U1 5 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD APR PY 2003 VL 16 IS 2 BP 219 EP 236 DI 10.1016/S0889-1575(02)00171-0 PG 18 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 675BQ UT WOS:000182673500012 ER PT J AU Jackson, LS Beacham-Bowden, T Keller, SE Adhikari, C Taylor, KT Chirtel, SJ Merker, RI AF Jackson, LS Beacham-Bowden, T Keller, SE Adhikari, C Taylor, KT Chirtel, SJ Merker, RI TI Apple quality, storage, and washing treatments affect patulin levels in apple cider SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CONTROLLED ATMOSPHERE; PENICILLIUM-EXPANSUM; JUICE; PRODUCTS; FRUIT; VARIABILITY; MYCOTOXINS; CULTIVARS; SAFETY; PEAR AB Patulin is a mycotoxin produced primarily by Penicillium expansum, a mold responsible for rot in apples and other fruits. The growth of this fungus and the production of patulin are common in fruit that has been damaged. However, patulin can be detected in visibly sound fruit. The purpose of this project was to determine how apple quality, storage, and washing treatments affect patulin levels in apple cider. Patulin was not detected in cider pressed from fresh tree-picked apples (seven cultivars) but was found at levels of 40.2 to 374 mug/liter in cider pressed from four cultivars of fresh ground-harvested (dropped) apples. Patulin was not detected in cider pressed from culled tree-picked apples stored for 4 to 6 weeks at 0 to 2degreesC but was found at levels of 0.97 to 64.0 mug/liter in cider pressed from unculled fruit stored under the same conditions. Cider from controlled-atmosphere-stored apples that were culled before pressing contained 0 to 15.1 mug of patulin per liter, while cider made from unculled fruit contained 59.9 to 120.5 mug of patulin per liter. The washing of ground-harvested apples before pressing reduced patulin levels in cider by 10 to 100%, depending on the initial patulin levels and the type of wash solution used. These results indicate that patulin is a good indicator of the quality of the apples used to manufacture cider. The avoidance of ground-harvested apples and the careful culling of apples before pressing are good methods for reducing patulin levels in cider. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. El Dorado Cty Dept Agr, Placerville, CA 95667 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Jackson, LS (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM lauren.jackson@cfsan.fda.gov FU FDA HHS [FD-000431] NR 49 TC 40 Z9 40 U1 0 U2 15 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 APR PY 2003 VL 66 IS 4 BP 618 EP 624 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 665PY UT WOS:000182130900012 PM 12696685 ER PT J AU De Rezende, CLE Joseph, SW Teicher, E Carr, LE Tall, B Weiner, RM AF De Rezende, CLE Joseph, SW Teicher, E Carr, LE Tall, B Weiner, RM TI Calcofluor as a fluorescent probe to detect biofilms of foodborne pathogens SO JOURNAL OF FOOD SAFETY LA English DT Article ID VIBRIO-CHOLERAE; SALMONELLA CONTAMINATION; POLYSACCHARIDE; EXOPOLYSACCHARIDE; FARMS AB Biofilms enable foodborne pathogens to resist removal from surfaces, survive disinfection and elude detection. This study evaluated the use of Calcofluor, which binds to polysaccharides containing beta-D-glucans, to detect biofilms produced by Salmonella enterica serovar Berta and Salmonella enterica serovar Typhimurium DT104 (St DT104), Escherichia colt Aeromonas hydrophila, Vibrio cholerae 0139 and Hyphomonas adhaerens. Biofilms produced by St DT104, S. berta and V. cholerae on five types of surfaces (glass, polypropylene, Teflon(TM), stainless steel and aluminum) were detected by Calcofluor. Results suggest the potential use of Calcofluor as probes of foodborne pathogens in biofilms. C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. Univ Maryland, Dept Biol Resources Engn, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Natl Sci Fdn, Div Mol & Cellular Biosci, Arlington, VA 22230 USA. RP Weiner, RM (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. EM rw19@umail.umd.edu OI Tall, Ben/0000-0003-0399-3629 NR 17 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0149-6085 EI 1745-4565 J9 J FOOD SAFETY JI J. Food Saf. PD APR PY 2003 VL 23 IS 1 BP 25 EP 33 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 673YT UT WOS:000182609400003 ER PT J AU Whiting, RC Golden, MH AF Whiting, RC Golden, MH TI Modeling temperature, pH, NaCl, nitrite and lactate on the survival of Escherichia coli O157 : H7 in broth SO JOURNAL OF FOOD SAFETY LA English DT Article ID LISTERIA-MONOCYTOGENES; APPLE CIDER; NONTHERMAL INACTIVATION; SALMONELLA-TYPHIMURIUM; ACID TOLERANCE; GROUND-BEEF; DRY SAUSAGE; GROWTH; STORAGE; CHEESE AB A model was developed to estimate the survival times for a four-strain cocktail of Escherichia coli O157:H7 in BHI broths with pH values from 3.5 to 7.0, NaCl from 0.5 to 15%, Na lactate from 0.0 to 2.0% and NaNO2 from 0 to 75 ppm. Broths were stored between 4 and 37C for up to 6 months. Samples were removed and enumerated at appropriate intervals. A primary level model with a shoulder period (no decline) and a subsequent log-linear decline was fitted to the survival data and the times for 3, 4, 5, and 6 log(10)-units of decline determined A secondary level second-order regression equation with the environmental conditions and declines being the independent variables was fitted to the survival times. Confidence limits about the estimated mean were also estimated. In foods with equivalent conditions that do not permit E. coli O157:H7 growth, this model provides an initial estimate of the survival times. C1 USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. RP Whiting, RC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 49 TC 4 Z9 4 U1 0 U2 2 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 USA SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD APR PY 2003 VL 23 IS 1 BP 61 EP 74 DI 10.1111/j.1745-4565.2003.tb00352.x PG 14 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 673YT UT WOS:000182609400006 ER PT J AU Navarro, A Anand-Apte, B Tanabe, Y Feldman, G Larner, AC AF Navarro, A Anand-Apte, B Tanabe, Y Feldman, G Larner, AC TI A PI-3 kinase-dependent, Stat1-independent signaling pathway regulates interferon-stimulated monocyte adhesion SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Jak; Akt; cytokine; MAPK; ERK ID GUANYLATE-BINDING-PROTEIN; GENE-EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE KINASE; IFN-GAMMA; SERINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; STAT PROTEINS; ALPHA; ACTIVATION AB Type I interferon (IFN)-alpha/beta and type II IFN-gamma induce the expression of early response genes through activation of the Janus tyrosine kinase/signal transducer and activator of transcription (Stat) pathway. Although IFNs regulate a variety of other signaling cascades, little is known about how they contribute to the biological activities of these cytokines. In this study, we demonstrate that IFN-beta or IFN-gamma induces the phosphorylation of the serine/threonine kinase Akt in primary human peripheral blood monocytes. Abrogation of the IFN-stimulated Akt activation by phosphatidylinositol-3 kinase (PI-3K) inhibitors prevents IFN-induced adhesion in these cells, and IFN activation of the Stat1-dependent guanylate-binding protein (GBP) gene is not affected. Importantly, Stat1-deficient bone marrow macrophages displayed a similar level of IFN-gamma-stimulated adhesion compared with macrophages derived from wild-type littermates. These findings demonstrate for the first time that IFN stimulation of a PI-3K signaling cascade modulates the ability of these cytokines to regulate monocyte adhesion, and this process does not require the expression of Stat1, a primary mediator of IFN-gamma signaling. J. Leukoc. Biol. 73: 540-545; 2003. C1 Cleveland Clin Fdn, Dept Immunol, Lerner Res Inst, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. Univ Calif San Diego, Div Biol, San Diego, CA USA. Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. RP Larner, AC (reprint author), Cleveland Clin Fdn, Dept Immunol, Lerner Res Inst, 9500 Euclid Ave,NB3-30, Cleveland, OH 44195 USA. FU NEI NIH HHS [R29 EY012109] NR 40 TC 49 Z9 51 U1 2 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 2003 VL 73 IS 4 BP 540 EP 545 DI 10.1189/jlb.1002508 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755EX UT WOS:000187391700014 PM 12660229 ER PT J AU Brooks, P Tugwell, P Strand, CV Simon, L Boers, M AF Brooks, P Tugwell, P Strand, CV Simon, L Boers, M TI OMERACT 6: International Consensus Conference on Outcome Measures in Rheumatology SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material C1 Univ Queensland, Fac Hlth Sci, Brisbane, Qld, Australia. Univ Ottawa, Dept Med, Ottawa, ON, Canada. Stanford Univ, Sch Med, Stanford, CA 94305 USA. US FDA, Rockville, MD 20857 USA. VU Univ Hosp, Dept Clin Epidemiol, Amsterdam, Netherlands. RP Brooks, P (reprint author), Univ Queensland, Fac Hlth Sci, Brisbane, Qld, Australia. OI Tugwell, Peter/0000-0001-5062-0556 NR 0 TC 4 Z9 4 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 2003 VL 30 IS 4 BP 866 EP 867 PG 2 WC Rheumatology SC Rheumatology GA 663UU UT WOS:000182025300040 ER PT J AU Willy, ME Graham, DJ Manda, B Shatin, D Drinkard, CR AF Willy, ME Graham, DJ Manda, B Shatin, D Drinkard, CR TI Compliance with FDA recommendations for pemoline - Reply SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 US FDA, Off Drug Safety, Rockville, MD 20857 USA. UnitedHlth Grp, Ctr Hlth Care Policy & Evaluat, Minneapolis, MN USA. RP Willy, ME (reprint author), US FDA, Off Drug Safety, Rockville, MD 20857 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 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2003 VL 42 IS 4 BP 383 EP 383 DI 10.1097/01.CHI.0000052507.98293.3A PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 658DN UT WOS:000181706500002 ER PT J AU Greenhill, LL Jensen, PS Abikoff, H Blumer, JL DeVeaugh-Geiss, J Fisher, C Hoagwood, K Kratochvil, CJ Lahey, BB Laughren, T Leckman, J Petti, TA Pope, K Shaffer, D Vitiello, B Zeanah, C AF Greenhill, LL Jensen, PS Abikoff, H Blumer, JL DeVeaugh-Geiss, J Fisher, C Hoagwood, K Kratochvil, CJ Lahey, BB Laughren, T Leckman, J Petti, TA Pope, K Shaffer, D Vitiello, B Zeanah, C TI Developing strategies for psychopharmacological studies in preschool children SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE preschool children; clinical trials; ethics; diagnosis ID YOUNG-CHILDREN; DISORDER AB Objective: To identify the obstacles and special challenges-ethical, practical, scientific, and regulatory-faced by investigators who attempt to conduct psychopharmacological studies in preschoolers. Method: In a workshop held at the 47th Annual Meeting of the American Academy of Child and Adolescent Psychiatry, featuring interactive sessions designed to elicit discussion of the theory and feasibility of research in this young population, several key domains were identified: diagnosis and assessment, ethics, research design, special considerations for preschoolers, regulatory/industry issues, and education/training. Results: A Pediatric Psychopharmacology Initiative is needed to consolidate recommendations from this and other workshops and current federal, research, and regulatory committees. A scholarly review and a guide for institutional review boards and investigators should be prepared on issues related to preschoolers. Developmental specialists provide valuable expertise that can strengthen studies of pediatric psychopharmacology. "N of 1" case studies can provide valuable information to clinicians. Only preschoolers with severe symptoms that occur in several interpersonal contexts should be entered into trials. Indications for the study of symptom complexes (e.g., aggression) rather than specific diagnoses should be examined and considered for regulatory activities. Psychopharmacology practice parameters for preschoolers are needed. Conclusions: With preschoolers being increasingly treated with psychopharmacological agents, the need for investigations to address the safety and efficacy of these medications is becoming a central issue for researchers from many disciplines. C1 New York State Psychiat Inst & Hosp, New York, NY 10032 USA. NYU, Ctr Child Study, New York, NY 10012 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Fordham Univ, Bronx, NY 10458 USA. Univ Nebraska, Lincoln, NE 68583 USA. Univ Chicago, Chicago, IL 60637 USA. Yale Univ, New Haven, CT 06520 USA. Indiana Univ, Bloomington, IN 47405 USA. NIMH, Bethesda, MD 20892 USA. Tulane Univ, New Orleans, LA 70118 USA. US FDA, Rockville, MD 20857 USA. RP Greenhill, LL (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr, New York, NY 10032 USA. EM LarryLGreenhill@cs.com OI Jensen, Peter/0000-0003-2387-0650 FU NIMH NIH HHS [U01-MH50453, U01-MH50461, MH50467] NR 19 TC 25 Z9 26 U1 0 U2 3 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 APR PY 2003 VL 42 IS 4 BP 406 EP 414 DI 10.1097/01.CHI.0000064812.95464.FA PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 658DN UT WOS:000181706500006 PM 12649627 ER PT J AU Williams, TL Andrzejewski, D Lay, JO Musser, SM AF Williams, TL Andrzejewski, D Lay, JO Musser, SM TI Experimental factors affecting the quality and reproducibility of MALDI TOF mass spectra obtained from whole bacteria cells SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID ASSISTED-LASER-DESORPTION/IONIZATION; RAPID IDENTIFICATION; INTACT MICROORGANISMS; SPECTROMETRY; PROTEINS; IRRADIATION; ILLNESS AB Numerous experimental factors are shown to significantly influence the spectra obtained when bacteria are analyzed by MALDI TOF/MS. Detailed investigation of the instrument parameters and sample preparation are all shown to influence the spectra. Of these, the preanalysis sample preparation steps incorporate the most important elements influencing the quality and reproducibility of the spectra. Some of the most important sample preparation factors include the method employed for sterilization, the type of matrix, the matrix solvent and concentration of cells in the matrix, as well as the type and concentration of acid added to the matrix. The effects of these parameters, as well as other aspects of sample preparation and the effects of several instrumental parameters on spectra are presented. Optimization and control of all experimental variables leads to a stable protocol for analysis of bacteria. The protocol employs a Nd:Yag laser and describes both sample handling and instrument conditions which consistently yield reproducible MALDI TOF mass spectra with greater than 25 peaks from both gram-positive and gram-negative bacteria. C1 US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Musser, SM (reprint author), US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-717, College Pk, MD 20740 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 26 TC 127 Z9 134 U1 2 U2 24 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 APR PY 2003 VL 14 IS 4 BP 342 EP 351 DI 10.1016/S1044-0305(03)00065-5 PG 10 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 668EC UT WOS:000182276500007 PM 12686481 ER PT J AU Abel, DB AF Abel, DB TI Ongoing FDA evaluation of approved endovascular grafts SO JOURNAL OF VASCULAR SURGERY LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Abel, DB (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 2003 VL 37 IS 4 BP 902 EP 903 DI 10.1067/mva.2003.312 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 664GY UT WOS:000182054400032 PM 12663998 ER PT J AU Nascimbeni, M Mizukoshi, E Bosmann, M Major, ME Mihalik, K Rice, CM Feinstone, SM Rehermann, B AF Nascimbeni, M Mizukoshi, E Bosmann, M Major, ME Mihalik, K Rice, CM Feinstone, SM Rehermann, B TI Kinetics of CD4(+) and CD8(+) memory T-cell responses during hepatitis C virus rechallenge of previously recovered chimpanzees SO JOURNAL OF VIROLOGY LA English DT Article ID EX-VIVO ANALYSIS; B VIRUS; IMMUNE-RESPONSE; IN-VIVO; IMMUNOLOGICAL SIGNIFICANCE; CIRCULATING LYMPHOCYTES; PROTECTIVE IMMUNITY; VIRAL CLEARANCE; CTL RESPONSES; HUMAN LIVER AB The immunological correlates of hepatitis C virus (HCV)-specific immunity are not well understood. Antibodies to HCV structural proteins do not appear to play a key role in clearance of the virus and do not persist after recovery. Here, we studied the kinetics of the cellular immune responses of three HCV-recovered chimpanzees during rechallenge with increasing doses of homologous HCV. Although HCV envelope antibodies remained undetectable throughout the rechallenge, all animals mounted rapid HCV-specific T-cell responses. The pattern of the cellular immune response in blood and liver correlated with the virological outcome. The animal that most rapidly cleared circulating HCV as determined by nested reverse transcription-PCR (RT-PCR) displayed the most vigorous and sustained response of gamma interferon (IFN-gamma)-producing and proliferating CD4(+) T cells in the blood. Vigorous CD4(+) T-cell proliferation during viremia was followed by an increased frequency and a phenotypic and functional change of the tetramer(+) CD8(+) T-cell population. The second animal cleared HCV initially with strong peripheral and intrahepatic CD4(+) T-cell responses but experienced low-level HCV recrudescence 12 weeks later, when HCV-specific T cells became undetectable. The third animal maintained minute amounts of circulating HCV, detectable only by nested RT-PCR, in the face of a weak IFN-gamma(+) T-cell response. Collectively, the results suggest protective rather than sterilizing immunity after recovery from hepatitis C. The rate of HCV clearance following reexposure depends on the cellular immune response, the quality and quantity of which may vary among chimpanzees that recovered from HCV infection. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Res, Bethesda, MD 20892 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA85883-01, R01 CA085883] NR 65 TC 139 Z9 141 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2003 VL 77 IS 8 BP 4781 EP 4793 DI 10.1128/JVI.77.8.4781-4793.2003 PG 13 WC Virology SC Virology GA 662VU UT WOS:000181970200032 PM 12663785 ER PT J AU Kieffer, TL Cowley, S Nano, FE Elkins, KL AF Kieffer, TL Cowley, S Nano, FE Elkins, KL TI Francisella novicida LPS has greater immunobiological activity in mice than F-tularensis LPS, and contributes to F-novicida murine pathogenesis SO MICROBES AND INFECTION LA English DT Article DE Francisella tularensis; lipopolysaccharide; macrophages; tumor necrosis factor alpha; interleukin-12; immunity, natural ID LIVE VACCINE STRAIN; EARLY PROTECTIVE IMMUNITY; GAMMA-INTERFERON; B-CELLS; LIPOPOLYSACCHARIDE; INFECTION; LVS; TULAREMIA; GROWTH; SUSCEPTIBILITY AB To further understand the role of LPS in the pathogenesis of Francisella infection, we characterized murine infection with E novicida, and compared immunobiological activities of F novicida LPS and the LPS from E tularensis live vaccine strain (LVS). E novicida had a lower intradermal LD50 in BALB/cByJ mice than E tularensis LVS, and mice given a lethal E novicida dose intraperitoneally died faster than those given the same lethal E tularensis LVS dose. However, the pattern of in vivo dissemination was similar, and in vitro growth of both bacteria in bone marrow-derived macrophages was comparable. F novicida LPS stimulated very modest in vitro proliferation of mouse splenocytes at high doses, but F tularensis LVS LPS did not. Murine bone marrow macrophages treated in vitro with E novicida LPS produced IL12 and TNF-alpha, but did not produce detectable interferon-gamma, IL10, or nitric oxide; in contrast, murine macrophages treated with F tularensis LVS LPS produced none of these mediators. In contrast to clear differences in stimulation of proliferation and especially cytokines, both types of purified LPS stimulated early protection against lethal challenge of mice with F tularensis LVS, but not against lethal challenge with E novicida. Thus, although LPS recognition may not be a major factor in engendering protection, the ability of F novicida LPS to stimulate the production of proinflammatory cytokines including TNF-alpha likely contributes to the increased virulence for mice of F novicida compared to E tularensis LVS. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 US FDA, Lab Mycobacterial Dis & Cellular Immun, Div Bacterial & Parasit Prod, CBER, Rockville, MD 20852 USA. Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada. RP Elkins, KL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immun, Div Bacterial & Parasit Prod, CBER, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. NR 28 TC 82 Z9 83 U1 0 U2 5 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2003 VL 5 IS 5 BP 397 EP 403 DI 10.1016/S1286-4579(03)00052-2 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 683FR UT WOS:000183138000007 PM 12737995 ER PT J AU Guo, GZ Yan-Sanders, Y Lyn-Cook, BD Wang, TL Tamae, D Ogi, J Khaletskiy, A Li, ZK Weydert, C Longmate, JA Huang, TT Spitz, DR Oberley, LW Li, JJ AF Guo, GZ Yan-Sanders, Y Lyn-Cook, BD Wang, TL Tamae, D Ogi, J Khaletskiy, A Li, ZK Weydert, C Longmate, JA Huang, TT Spitz, DR Oberley, LW Li, JJ TI Manganese superoxide dismutase-mediated gene expression in radiation-induced adaptive responses SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; BREAST-CANCER CELLS; IONIZING-RADIATION; TRANSCRIPTION FACTOR; INDUCED APOPTOSIS; GENOTOXIC STRESS; OXIDATIVE DAMAGE; REDOX REGULATION; FACTOR-ALPHA AB Antioxidant enzymes are critical in oxidative stress responses. Radioresistant variants isolated from MCF-7 human carcinoma cells following fractionated ionizing radiation (MCF+FIR cells) or overexpression of manganese superoxide dismutase (MCF+SOD cells) demonstrated dose-modifying factors at 10% isosurvivall of 1.8 and 2.3, respectively. MCF+FIR and MCF-7 cells (exposed to single-dose radiation) demonstrated 5- to 10-fold increases in MnSOD activity, mRNA, and immunoreactive protein. Radioresistance in MCF+FIR and MCF+SOD cells was reduced following expression of antisense MnSOD. DNA microarray analysis and immunoblotting identified p21, Myc, 14-3-3 zeta, cyclin A, cyclin B1, and GADD153 as genes constitutively overexpressed (2- to 10-fold) in both MCF+FIR and MCF+SOD cells. Radiation-induced expression of these six genes was suppressed in fibroblasts from Sod2 knockout mice (-/-) as well as in MCF+FIR and MCF+SOD cells expressing antisense MnSOD. Inhibiting NF-kappaB transcriptional activity in MCF+FIR cells, by using mutant IkappaBalpha, inhibited radioresistance as well as reducing steady-state levels of MnSOD, 14-3-3 zeta, GADD153, cyclin A, and cyclin B1 mRNA. In contrast, mutant IkappaBalpha was unable to inhibit radioresistance or reduce 14-3-3 zeta, GADD153, cyclin A, and cyclin B1 mRNAs in MCF+SOD cells, where MnSOD overexpression was independent of NF-kappaB. These results support the hypothesis that NF-kappaB is capable of regulating the expression of MnSOD, which in turn is capable of increasing the expression of genes that participate in radiation-induced adaptive responses. C1 City Hope Natl Med Ctr, Beckman Res Inst, Div Radiat Oncol, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Beckman Res Inst, Div Biostat, Duarte, CA 91010 USA. US FDA, Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Iowa, Free Rad & Radiat Biol Program, Dept Radiat Oncol, Iowa City, IA 52242 USA. Stanford Univ, Palo Alto, CA 94304 USA. RP Li, JJ (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Div Radiat Oncol, H115 Halper S Bldg,1500 Duarte Rd, Duarte, CA 91010 USA. EM jjli@coh.org OI Longmate, Jeffrey/0000-0002-0869-7928 FU NCI NIH HHS [P01 CA66081, P01 CA066081, T32 CA078586, T32CA78586]; NHLBI NIH HHS [R01 HL051469, R01 HL51469] NR 68 TC 187 Z9 195 U1 0 U2 7 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 APR PY 2003 VL 23 IS 7 BP 2362 EP 2378 DI 10.1128/MCB.23.7.2362-2378.2003 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 658QJ UT WOS:000181731400013 PM 12640121 ER PT J AU Basta, M Van Goor, F Luccioli, S Billings, EM Vortmeyer, AO Baranyi, L Szebeni, J Alving, CR Carroll, MC Berkower, I Stojilkovic, SS Metcalfe, DD AF Basta, M Van Goor, F Luccioli, S Billings, EM Vortmeyer, AO Baranyi, L Szebeni, J Alving, CR Carroll, MC Berkower, I Stojilkovic, SS Metcalfe, DD TI F(ab)'(2)-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins SO NATURE MEDICINE LA English DT Article ID DOSE INTRAVENOUS IMMUNOGLOBULIN; IMMUNE GLOBULIN; COMPLEMENT; RECEPTORS; ASTHMA; PATHOGENESIS; MODULATION; ACTIVATION; COMPONENTS; FRAGMENTS AB High-dose intravenous immunoglobulin (IVIG) prevents immune damage by scavenging complement fragments C3b and C4b. We tested the hypothesis that exogenous immunoglobulin molecules also bind anaphylatoxins C3a and C5a, thereby neutralizing their pro-inflammatory effects. Single-cell calcium measurements in HMC-1 human mast cells showed that a rise in intracellular calcium caused by C3a and C5a was inhibited in a concentration-dependent manner by IVIG, F(ab)'(2)-IVIG and irrelevant human monoclonal antibody. C3a- and C5a-induced thromboxane (TXB2) generation and histamine release from HMC-1 cells and whole-blood basophils were also suppressed by exogenous immunoglobulins. In a mouse model of asthma, immunoglobulin treatment reduced cellular migration to the lung. Lethal C5a-mediated circulatory collapse in pigs was prevented by pretreatment with F(ab)'(2)-IVIG. Molecular modeling, surface plasmon resonance (SPR) and western blot analyses suggested a physical association between anaphylatoxins and the constant region of F(ab)'(2). This binding could interfere with the role of C3a and C5a in inflammation. C1 NINDS, Neuronal Excitabil Sect, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NHLBI, Computat Biophys Sect, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Membrane Biochem, Silver Spring, MD USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. US FDA, Immunoregulat Lab, Off Vaccines, Ctr Biol, Bethesda, MD 20014 USA. RP Basta, M (reprint author), NINDS, Neuronal Excitabil Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. OI Basta, Milan/0000-0001-5958-9241 NR 38 TC 138 Z9 142 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2003 VL 9 IS 4 BP 431 EP 438 DI 10.1038/nm836 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 663CD UT WOS:000181987400033 PM 12612546 ER PT J AU Wulfkuhle, JD Liotta, LA Petricoin, EF AF Wulfkuhle, JD Liotta, LA Petricoin, EF TI Proteomic applications for the early detection of cancer SO NATURE REVIEWS CANCER LA English DT Review ID LASER CAPTURE MICRODISSECTION; PROTEIN IDENTIFICATION TECHNOLOGY; ARTIFICIAL NEURAL NETWORKS; IMAGING MASS-SPECTROMETRY; PROSTATE-SPECIFIC ANTIGEN; IMMOBILIZED PH GRADIENTS; BREAST DUCTAL CARCINOMA; OVARIAN-CANCER; GENE-EXPRESSION; ANTIBODY ARRAYS AB The ability of physicians to effectively treat and cure cancer is directly dependent on their ability to detect cancers at their earliest stages. Proteomic analyses of early-stage cancers have provided new insights into the changes that occur in the early phases of tumorigenesis and represent a new resource of candidate biomarkers for early-stage disease. Studies that profile proteomic patterns in body fluids also present new opportunities for the development of novel, highly sensitive diagnostic tools for the early detection of cancer. C1 NCI FDA Clin Proteom Program, Off Director, Ctr Biol Evaluat & Res, FDA, Bethesda, MD 20892 USA. NCI, NCI FDA Clin Proteom Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), NCI FDA Clin Proteom Program, Off Director, Ctr Biol Evaluat & Res, FDA, Bethesda, MD 20892 USA. NR 82 TC 518 Z9 554 U1 15 U2 96 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD APR PY 2003 VL 3 IS 4 BP 267 EP 275 DI 10.1038/nrc.1043 PG 9 WC Oncology SC Oncology GA 664NB UT WOS:000182066200012 PM 12671665 ER PT J AU Mangner, TJ Klecker, RW Anderson, L Shields, AF AF Mangner, TJ Klecker, RW Anderson, L Shields, AF TI Synthesis of 2 '-deoxy-2 '-[F-18]fluoro-beta-D-arabinofuranosyl nucleosides, [F-18]FAU, [F-18]FMAU, [F-18]FBAU and [F-18]FIAU, as potential PET agents for imaging cellular proliferation - Synthesis of [F-18]labeled FAU, FMAU, FBAU, FIAU SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE fluorine-18; 2 '-[F-18]fluoro-2 '-deoxy-beta-D-arabinofuranosyl nucleosides; FAU; FMAU; FBAU; FIAU ID POSITRON-EMISSION-TOMOGRAPHY; VIRUS THYMIDINE KINASE; IN-VIVO; GENE-TRANSFER; EXPRESSION; ANALOG; THERAPY AB An efficient and reliable synthesis of 2'-deoxy-2'-[F-18]fluoro-beta-D-arabinofuranosyl nucleosides is presented. Overall decay-corrected radiochemical yields of 35-45% of 4 analogs, FAU, FMAU, FBAU and FIAU are routinely obtained in >98% radiochemical purity and with specific activities of greater than 3 Ci/mumol (110 MBq/mumol) in a synthesis time of approximately 3 hours. When similar to220 mCi (8.15 GBq) of starting [F-18]fluoride is used, 25-30 mCi (0.93-1.11 GBq) of product (enough to image two patients sequentially) is typically obtained. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Wayne State Univ, Childrens Hosp Michigan, PET Ctr, Detroit, MI 48201 USA. US FDA, Lab Clin Pharmacol, Rockville, MD 20857 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. RP Mangner, TJ (reprint author), Wayne State Univ, Childrens Hosp Michigan, PET Ctr, 3901 Beaubien Blvd, Detroit, MI 48201 USA. FU NCI NIH HHS [CA83131] NR 18 TC 90 Z9 90 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 2003 VL 30 IS 3 BP 215 EP 224 DI 10.1016/S0969-8051(02)00445-6 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 681MX UT WOS:000183040900001 PM 12745012 ER PT J AU Piroozi, A Melnyk, S Maclennan, NK Chiu, CT James, SJ Lane, RH AF Piroozi, A Melnyk, S Maclennan, NK Chiu, CT James, SJ Lane, RH TI Uteroplacental insufficiency alters fetal one carbon metabolism in an IUGR rat model characterized by altered DNA methylation SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Cedars Sinai Hosp Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Los Angeles, CA 90024 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 327 BP 58A EP 58A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897900328 ER PT J AU Freedman, SB Reed, JH Burwen, DR Wise, RP Weiss, A Ball, R AF Freedman, SB Reed, JH Burwen, DR Wise, RP Weiss, A Ball, R TI Benign idiopathic bulging fontanelle after vaccination: Review of the vaccine adverse events reporting system (VAERS) database SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Childrens Mem Hosp, Chicago, IL 60614 USA. US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 703 BP 123A EP 123A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897900704 ER PT J AU Rodriguez, WJ Murphy, MD Roberts, R Crescenzi, TL AF Rodriguez, WJ Murphy, MD Roberts, R Crescenzi, TL TI The FDA initiatives in pediatrics result in valuable information for caregivers SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1435 BP 251A EP 251A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901435 ER PT J AU Hoke, EM Shacter, E AF Hoke, EM Shacter, E TI Desferal inhibits breast tumor growth and does not interfere with the tumoricidal activity of doxorubicin SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. US FDA, Ctr Biol Evaluat & Res, Biochem Lab, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1573 BP 275A EP 276A PN 2 PG 2 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901572 ER PT J AU Bohlke, KJ Davis, RL Marcy, SM Braun, MM DeStefano, F Black, SB Mullooly, JP Thompson, RS AF Bohlke, KJ Davis, RL Marcy, SM Braun, MM DeStefano, F Black, SB Mullooly, JP Thompson, RS TI The risk of anaphylaxis following vaccination of children and adolescents SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. Kaiser Fdn Hosp, Panorama City, CA USA. US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, Rockville, MD 20857 USA. Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. No Calif Kaiser Control & Prevent, Pediat Vaccine Study Ctr, Oakland, CA USA. NW Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. Grp Hlth Cooperat Puget Sound, Dept Prevent Care, Seattle, WA 98121 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1756 BP 307A EP 308A PN 2 PG 2 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901755 ER PT J AU Coleman, E AF Coleman, E TI Ethylmercury in vaccines SO PEDIATRICS LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Coleman, E (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 3 TC 1 Z9 2 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 APR PY 2003 VL 111 IS 4 BP 922 EP 923 DI 10.1542/peds.111.4.922-a PG 3 WC Pediatrics SC Pediatrics GA 662RA UT WOS:000181960600043 PM 12671140 ER PT J AU Yu, LX Furness, MS Raw, A Outlaw, KPW Nashed, NE Ramos, E Miller, SPF Adams, RC Fang, F Patel, RM Holcombe, FO Chiu, YY Hussain, AS AF Yu, LX Furness, MS Raw, A Outlaw, KPW Nashed, NE Ramos, E Miller, SPF Adams, RC Fang, F Patel, RM Holcombe, FO Chiu, YY Hussain, AS TI Scientific considerations of pharmaceutical solid polymorphism in abbreviated new drug applications SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE polymorphism; polymorph; Abbreviated New Drug Application (ANDA); drug substance; drug product; pharmaceutical solid ID BIOAVAILABILITY; CLASSIFICATION; CARBAMAZEPINE; DIHYDRATE; STATE AB Purpose. This commentary is intended to provide a scientific perspective on pharmaceutical solid polymorphism in Abbreviated New Drug Applications ( ANDAs). Methods. This report proposes recommendations for monitoring and controlling drug substance polymorphs and describes scientific considerations of pharmaceutical solid polymorphism in the determination of drug substance sameness. Results. It presents three decision trees for solid oral dosage forms or liquids containing undissolved drug substances to provide a process for evaluating when and how polymorphs of drug substances are monitored and controlled in ANDA submissions. Conclusions. It is scientifically concluded that differences in polymorphic composition of drug substances in generic drug products and reference- listed drugs are not directly relevant in the determination of drug substance sameness in ANDAs. C1 US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. US FDA, CDER, Off New Drug Chem, Rockville, MD 20857 USA. US FDA, CDER, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Yu, LX (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. NR 25 TC 62 Z9 64 U1 3 U2 13 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD APR PY 2003 VL 20 IS 4 BP 531 EP 536 DI 10.1023/A:1023285627778 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 665RW UT WOS:000182135900001 PM 12739758 ER PT J AU Koti, KM AF Koti, KM TI Gamma failure-time mixture models: yet another way to establish efficacy SO PHARMACEUTICAL STATISTICS LA English DT Article DE clinical trial; survival data; log-rank test; cure model; incomplete gamma function; Hybrid approximation; Wald test ID RISK AB Using a Yamaguchi-type generalized gamma failure-time mixture model, we analyse the data from a study of autologous and allogeneic bone marrow transplantation in the treatment of high-risk refractory acute lymphoblastic leukaemia, focusing on the time to recurrence of disease. We develop maximum likelihood techniques for the joint estimation of the surviving fractions and the survivor functions. This includes an approximation to the derivative of the survivor function with respect to the shape parameter. We obtain the maximum likelihood estimates of the model parameters. We also compute the variance-covariance matrix of the parameter estimators. The extended family of generalized gamma failure-time mixture models is flexible enough to include many commonly used failure-time distributions as special cases. Yet these models are not used in practice because of computational difficulties. We claim that we have overcome this problem. The proposed approximation to the derivative of the survivor function with respect to the shape parameter can be used in any statistical package. We also address the issue of lack of identifiabiliy. We point out that there can be a substantial advantage to using the gamma failure-time mixture models over nonparametric methods. Copyright (C) 2003 John Wiley Sons Ltd. C1 US FDA, Rockville, MD 20852 USA. RP Koti, KM (reprint author), US FDA, 1401 Rockville Pike,Suite 200S,CBER HFM 219, Rockville, MD 20852 USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD APR-JUN PY 2003 VL 2 IS 2 BP 133 EP 144 DI 10.1002/pst.036 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 750XB UT WOS:000187022800005 ER PT J AU Shaffer, D Armstrong, G Higgins, K Honig, P Coyne, P Boxwell, D Beitz, J Leissa, B Murphy, D AF Shaffer, D Armstrong, G Higgins, K Honig, P Coyne, P Boxwell, D Beitz, J Leissa, B Murphy, D TI Increased US prescription trends associated with the CDC Bacillus anthracis antimicrobial postexposure prophylaxis campaign SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE anthrax; ciprofloxacin; doxycycline; amoxicillin; postexposure; prophylaxis; drug utilization ID BIOTERRORISM; RESISTANCE AB Purpose We evaluated national outpatient antimicrobial prescription trends in relation to the first United States case of inhalational anthrax due to the intentional delivery of Bacillus anthracis (B. anthracis) spores. Methods We queried IMS HEALTH's National Prescription Audit PIus7(TM) database for two 6-month periods (July-December) in 2001 and 2000 to describe outpatient prescription trends of antimicrobials recommended during the Centers for Disease Control and Prevention's (CDC) postexposure prophylaxis campaign. Results Overall, antimicrobial utilization for the referent 6-month time frame was greater in 2000 compared to 2001. In contrast, ciprofloxacin utilization was greater in 2001 during October, the month following the index case, increasing by more than 40% over utilization in October 2000. Similarly, doxycycline utilization increased by 30% during October/November. This corresponded to relative increases in US utilization for ciprofloxacin of approximately 160000 prescriptions for the month of October and for doxycycline of approximately 96000 prescriptions during October and 120000 prescriptions for November. Conclusions We conclude more widespread prescribing of ciprofloxacin and doxycycline occurred in response to the first US bioterrorist-associated anthrax attacks than was warranted based upon confirmed or suspected B. anthracis exposure alone. Published in 2003 by John Wiley Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Rockville, MD 20857 USA. RP Beitz, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, HFD 400,Rm 15B-08,5600 Fishers Lane, Rockville, MD 20857 USA. NR 17 TC 12 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR-MAY PY 2003 VL 12 IS 3 BP 177 EP 182 DI 10.1002/pds.828 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 664YM UT WOS:000182092600001 PM 12733470 ER PT J AU Tavris, DR Gallauresi, B Rich, S Bell, C AF Tavris, DR Gallauresi, B Rich, S Bell, C TI Relative risks of reported serious injury and death associated with hemostasis devices by gender SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE hemostasis device; cardiac catheterization; medical device reporting ID CARDIAC-CATHETERIZATION; RANDOMIZED TRIAL; COMPLICATIONS; ANGIOPLASTY; CLOSURE; COLLAGEN; SITE AB Purpose To assess relative risks by gender of reported serious injuries and deaths associated with the use of hemostasis devices, stratified by year of report, type of injury, and type of device. Methods Reports from the Food and Drug Administration's Medical Device Reporting system and National Center for Health Statistics data on use of cardiac catheterization were used to estimate relative risks of reported serious injuries and deaths by gender. Results Estimated risks of reported serious injuries and deaths associated with hemostasis devices were two to three times greater in females than in males for hemorrhage and hematoma (p < 0.0001), but there was no significant difference in risks by gender for infection. Conclusions Cardiac catheterization is sometimes associated with serious injuries and deaths. Among patients who receive hemostasis devices. the risk of these events are disproportionately greater in women. Published in 2003 by John Wiley Sons, Ltd. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Postmarket Surveillance,Epidemiol Branch, Rockville, MD 20850 USA. RP Tavris, DR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Postmarket Surveillance,Epidemiol Branch, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. NR 16 TC 3 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR-MAY PY 2003 VL 12 IS 3 BP 237 EP 241 DI 10.1002/pds.802 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 664YM UT WOS:000182092600008 PM 12733477 ER PT J AU Godar, DE Urbach, F Gasparro, FP van der Leun, JC AF Godar, DE Urbach, F Gasparro, FP van der Leun, JC TI UV doses of young adults SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID NONMELANOMA SKIN-CANCER; ULTRAVIOLET-IRRADIATION; WAVELENGTH DEPENDENCE; SOUTHEAST QUEENSLAND; OZONE DEPLETION; SUN EXPOSURE; CHILDREN; ADOLESCENTS; CHILDHOOD; MELANOMA AB Since 1986, people have been informed that they get about 80% of their lifetime ultraviolet (UV) dose by the age of 18. This belief originated from the mathematical conclusion that diligent use of sunscreens (sun protection factor 15 or higher) during the first 18 years of life would reduce the lifetime incidence of nonmelanoma skin cancers by 78%. These data were misconstrued to mean that individuals also got about 80% of their lifetime dose of UV by the age of 18 (linear relationship). However, these calculations were based on the incidence of nonmelanoma skin cancers being related to the square of the UV dose. Careful analysis of UV exposure data shows that Americans actually get less than 25% of their lifetime UV dose by the age of 18. This finding also appears to be true worldwide because Australia, UK and The Netherlands report a similar UV exposure pattern. UV-initiated damage early in life can be promoted by subsequent exposures to progress into tumors later in life. For example, the nonmelanoma skin cancer, squamous cell carcinoma, is dependent on the cumulative UV dose. Thus, a better educational approach for reducing skin cancers would be to instruct fair-skinned individuals to protect themselves throughout their lives from being exposed to too much UV radiation. C1 US FDA, Radiat Biol Branch, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Temple Univ, Sch Med, Dept Dermatol, Philadelphia, PA 19122 USA. Thomas Jefferson Univ, Dept Dermatol, Philadelphia, PA 19107 USA. Ecofys, Utrecht, Netherlands. RP Godar, DE (reprint author), US FDA, Radiat Biol Branch, Ctr Devices & Radiol Hlth, HFZ-114,12709 Twinbrook pkwy, Rockville, MD 20852 USA. NR 37 TC 62 Z9 63 U1 0 U2 1 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 APR PY 2003 VL 77 IS 4 BP 453 EP 457 DI 10.1562/0031-8655(2003)077<0453:UDOYA>2.0.CO;2 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 667UJ UT WOS:000182251700016 PM 12733658 ER PT J AU Shiverick, KT Slikker, W Rogerson, SJ Miller, RK AF Shiverick, KT Slikker, W Rogerson, SJ Miller, RK TI Drugs and the placenta - A workshop report SO PLACENTA LA English DT Editorial Material ID INTERMITTENT SULFADOXINE-PYRIMETHAMINE; RESISTANT PLASMODIUM-FALCIPARUM; PHARMACOLOGICAL THERAPY; P-GLYCOPROTEIN; PREGNANCY; MALARIA; PREVENTION; SECONDARY; EFFICACY C1 Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Melbourne, Dept Med, Melbourne, Vic, Australia. Univ Rochester, Dept Obstet & Gynecol, Rochester, NY USA. RP Shiverick, KT (reprint author), Univ Florida, Dept Pharmacol & Therapeut, 1600 SW Archer Rd,Box 100267 Hlth Ctr, Gainesville, FL 32610 USA. OI Rogerson, Stephen/0000-0003-4287-1982 FU PHS HHS [P42 07375] NR 33 TC 6 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD APR PY 2003 VL 24 SU A BP S55 EP S59 DI 10.1053/plac.2002.0957 PG 5 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 673CR UT WOS:000182562500011 PM 12842414 ER PT J AU Ahram, M Flaig, MJ Gillespie, JW Duray, PH Linehan, WM Ornstein, DK Niu, SL Zhao, YM Petricoin, EF Emmert-Buck, MR AF Ahram, M Flaig, MJ Gillespie, JW Duray, PH Linehan, WM Ornstein, DK Niu, SL Zhao, YM Petricoin, EF Emmert-Buck, MR TI Evaluation of ethanol-fixed, paraffin-embedded tissues for proteomic applications SO PROTEOMICS LA English DT Article DE ethanol fixation; laser capture microdissection; prostate cancer; tissue staining ID DIFFERENTIALLY EXPRESSED GENES; TRANSITIONAL-CELL CARCINOMAS; IMMUNOHISTOCHEMICAL DEMONSTRATION; MOLECULAR CLASSIFICATION; PROSTATE-CANCER; FIXATION; IDENTIFICATION; FORMALIN; PROTEIN; KERATINS AB We previously reported that ethanol fixation and paraffin embedding of tissues produce excellent histomorphology and good preservation of macromolecules. Here, we present a detailed evaluation of ethanol-fixed tissues for proteomic initiatives. When proteins were extracted from ethanol-fixed, paraffin-embedded prostate tissue, resolved by two-dimensional gel electrophoresis (2-DE), and stained by standard methods, several hundred protein molecules could be detected and successfully analyzed by mass spectrometry. Protein profiles obtained from ethanol-fixed tissues were highly similar to those observed from frozen tissues, in contrast to the poor protein recovery from formalin-fixed material. The protein content of specific cells that were microdissected from ethanol-fixed tissue sections using laser capture microdissection could also be successfully analyzed by 2-DE. We observed that eosin staining of tissue sections had a detrimental effect on protein separation,,whereas hematoxylin staining had minimal consequence. In order to illustrate the applicability of ethanol-fixed tissues for proteomic discovery studies, we compared the protein profiles of patient-matched, normal prostatic epithelial cells and invasive adenocarcinoma cells obtained from ethanol-fixed, paraffin-embedded tissues. A number of differentially expressed proteins was discovered and identified by mass spectrometry. Immunohistochemical analyses performed on ethanol-fixed tissue sections were in agreement with the proteomic discovery findings. In light of these results, we conclude that ethanol-fixed tissues can be successfully utilized for proteomic analyses. C1 NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Urol, Chapel Hill, NC USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA. US FDA, Tissue Proteom Unit, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 2A33, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA85146] NR 25 TC 122 Z9 132 U1 0 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD APR PY 2003 VL 3 IS 4 BP 413 EP 421 DI 10.1002/pmic.200390056 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666WQ UT WOS:000182199800005 PM 12687609 ER PT J AU Walkers, JD Fang, H Perkins, R Tong, WD AF Walkers, JD Fang, H Perkins, R Tong, WD TI QSARs for endocrine disruption priority setting database 2: The integrated 4-phase model SO QSAR & COMBINATORIAL SCIENCE LA English DT Article; Proceedings Paper CT 10th International Workshop on Quantitative Structure-Activity Relationships in Environmental Sciences (QSAR 2002) CY MAY 25-29, 2002 CL OTTAWA, CANADA DE QSARs; receptor binding; estrogen; EDPSD; integrated 4-phase ID ESTROGEN-RECEPTOR BINDING; ASSAY; PREDICTION; CHEMICALS; SYSTEM; SMILES AB Version 2 of the Endocrine Disruption Priority Setting Database (EDPSD2) is a decision support tool developed by the U.S. Environmental Protection Agency. EDPSD2 is organized into 4 categories (exposure-related, effects-related, combined exposure-and effects-related and. specially-targeted priorities) that are supported by several compartments and information sources. The effects-related category includes a Quantitative Structure Activity Relationship compartment that is supported by two models for predicting estrogen receptor binding affinities of chemicals in EDPSD2. This paper describes the categories and compartments of EDPSD2 and the use of the Integrated 4-Phase model to predict the estrogen receptor binding affinities of chemicals in EDPSD2. C1 US EPA, TSCA Interagcy Testing Comm, Washington, DC 20460 USA. Northrop Grumman Informat Technol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Walkers, JD (reprint author), US EPA, TSCA Interagcy Testing Comm, Washington, DC 20460 USA. NR 14 TC 6 Z9 6 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1611-020X J9 QSAR COMB SCI JI QSAR Comb. Sci. PD APR PY 2003 VL 22 IS 1 BP 89 EP 105 DI 10.1002/qsar.200390009 PG 17 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 709VV UT WOS:000184647900009 ER PT J AU Zeuner, RA Klinman, DM Illei, G Yarboro, C Ishii, KJ Gursel, M Verthelyi, D AF Zeuner, RA Klinman, DM Illei, G Yarboro, C Ishii, KJ Gursel, M Verthelyi, D TI Response of peripheral blood mononuclear cells from lupus patients to stimulation by CpG oligodeoxynucleotides SO RHEUMATOLOGY LA English DT Article DE SLE; innate immune system; CpG oligodeoxynucleotide; toll-like receptor; dendritic cells ID NATURAL-KILLER-CELLS; STRANDED DNA ANTIBODIES; SEX-HORMONE LEVELS; DENDRITIC CELLS; CYTOKINE PRODUCTION; REVISED CRITERIA; BACTERIAL-DNA; IFN-ALPHA; IN-VITRO; T-CELLS AB Objectives. Increased levels of hypomethylated CpG-containing DNA in sera from patients with systemic lupus erythematosus (SLE) may contribute to the initiation and/or perpetuation of the disease. This study characterizes the in vitro response of peripheral blood mononuclear cells (PBMC) from SLE patients to CpG DNA. Methods. Secretion of cytokines and IgM, cell proliferation and up-regulation of co-stimulatory molecules were evaluated in PBMC from SLE patients (n = 24) and normal controls (n = 24) after stimulation with synthetic oligodeoxynucleotides (ODN) containing CpG motifs. Results. Up-regulation of co-stimulatory molecules and the secretion of interferon-alpha and interleukin-6 (IL-6) in response to CpG ODN was significantly reduced in monocytes and dendritic cells from SLE patients. Secretion of interferon-gamma by natural killer (NK) cells was also reduced. In contrast, the IgM and IL-10 response of B cells to CpG ODN was normal. Conclusion. Monocytes, dendritic cells and NK cells from SLE patients respond abnormally to CpG ODN stimulation, which may contribute to the cytokine imbalance observed in SLE. C1 US FDA, Sect Retroviral Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD USA. Univ Kiel, Med Clin 2, D-24098 Kiel, Germany. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Res, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D10, Bethesda, MD 20892 USA. RI Gursel, Mayda /H-1812-2012; Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Mayda/0000-0003-0044-9054 NR 29 TC 20 Z9 22 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2003 VL 42 IS 4 BP 563 EP 569 DI 10.1093/rheumatology/keg191 PG 7 WC Rheumatology SC Rheumatology GA 666YK UT WOS:000182203900010 PM 12649404 ER PT J AU Apte, UM Limaye, PB Desaiah, D Bucci, TJ Warbritton, A Mehendale, HM AF Apte, UM Limaye, PB Desaiah, D Bucci, TJ Warbritton, A Mehendale, HM TI Mechanisms of increased liver tissue repair and survival in diet-restricted rats treated with equitoxic doses of thioacetamide SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 22nd Annual Conference of the American-College-of-Toxicology CY NOV 04-08, 2001 CL WASHINGTON, D.C. SP American Coll Toxicol DE apoptosis; HGF; IL-6; iNOS; TGF-alpha; tissue repair; thioacetamide; caloric restriction; cytokines; growth factors; toxic challenge ID GROWTH-FACTOR-ALPHA; PARTIAL-HEPATECTOMY; CALORIE RESTRICTION; TRANSGENIC MICE; DNA-REPLICATION; TGF-ALPHA; C-MYC; REGENERATION; INJURY; EXPRESSION AB Moderate dietary or caloric restriction (DR) modulates animal physiology in a beneficial fashion. Previously, we have reported an equitoxic dose experiment where liver injury in DR male Sprague-Dawley rats exposed to a low dose of thioacetamide (TA, 50 mg/kg) was similar to that observed in ad libitum fed (AL) rats exposed to a 12-fold higher dose (600 mg/kg). Paradoxically, the AL rats experienced 90% mortality while all of the DR rats, with the same amount of initial bioactivation-mediated liver injury, survived. The protection observed in the DR rats was due to efficient compensatory liver tissue repair, which was delayed and attenuated in the AL rats, leading to progression of liver injury. The objective of the present study was to investigate the molecular mechanisms of the enhanced tissue repair in the DR rats upon equitoxic challenge with TA. Promitogenic mechanisms and mediators such as proinflammatory cytokines (TNF-alpha and IL-6), growth factors (TGF-alpha and HGF), and inducible nitric oxide synthase (iNOS) were estimated over a time course after equitoxic challenge (50 mg/kg to DR vs. 600 mg/kg to AL rats). Except for TNF-a, all other molecules were expressed earlier and in greater amount in the DR rats. IL-6 was 10-fold greater and peaked 12 h earlier; HGF also peaked 12 h sooner in the DR rats, when it was 2.5-fold greater than the value in the AL rats. TGF-a expression in livers of DR rats increased after TA administration and peaked at 24 h. In the AL rats, it was lower and peaked at 36 h. Diet restriction alone induced iNOS 2-fold in the DR rats and remained elevated until 12 h after TA administration, then declined thereafter. The lower iNOS activity in the AL rats further decreased after TA injection. DR rats exhibited higher apoptosis after thioacetamide administration, which further increased the efficiency of tissue repair. Taken together, these data indicate that even though the liver injury is near equal in AL and DR rats, sluggish signal transduction leads to delayed liver regeneration, progression of liver injury, and death in the AL rats. The equitoxic dose experiment indicates that stimulation of tissue repair is independent of the extent of initial liver injury and is governed by physiology of diet restriction. DR stimulates promitogenic signaling leading to a quick and timely response upon liver injury, arrest of progressive injury on one hand, and recovery from injury on the other, paving the way, for survival of the DR rats. C1 Univ Louisville, Dept Toxicol, Monroe, LA 71209 USA. Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. Natl Ctr Toxicol Res, Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisville, Dept Toxicol, 700 Univ Ave,Sugar Hall 306B, Monroe, LA 71209 USA. FU NIEHS NIH HHS [ES-09870] NR 52 TC 27 Z9 28 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 APR PY 2003 VL 72 IS 2 BP 272 EP 282 DI 10.1093/toxsci/kfg021 PG 11 WC Toxicology SC Toxicology GA 662DP UT WOS:000181931200013 PM 12655029 ER PT J AU Scallet, AC Wofford, M Meredith, JC Allaben, WT Ferguson, SA AF Scallet, AC Wofford, M Meredith, JC Allaben, WT Ferguson, SA TI Dietary exposure to genistein increases vasopressin but does not alter beta-endorphin in the rat hypothalamus SO TOXICOLOGICAL SCIENCES LA English DT Article DE endocrine disruptors; isoflavones; pituitary; phytoestrogens; estrogens; blood pressure ID MESSENGER-RIBONUCLEIC-ACID; ARGININE-VASOPRESSIN; GENE-EXPRESSION; SEX-DIFFERENCES; FEMALE RAT; ALPHA-MSH; ESTRADIOL; ESTROGEN; MODULATION; OXYTOCIN AB Genistein is a plant-derived estrogenic isoflavone commonly found in soy-based products such as soymilk and soy-based dietary supplements for treating menopausal symptoms, for example. Vasopressin is a neurosecretory nonapeptide synthesized primarily in neurons of the hypothalamus and secreted into the bloodstream from the posterior lobe of the pituitary. The endogenous opiate peptide beta-endorphin is synthesized both in neurons of the hypothalamus and in pituitary cells, primarily of the neurointermediate lobe. It has been reported that exposure to 17beta-estradiol or diethylstilbesterol increased the vasopressin content of the hypothalamus, and that estradiol valerate selectively damages hypothalamic beta-endorphin-containing neurons. Since little was known of the potential effects of estrogenic endocrine-disruptor compounds on hypothalamic neuropeptides, we fed Sprague-Dawley fetuses from day 7 in utero until sacrifice at postnatal day 77, with either a control diet (<1 ppm) or an experimental diet containing 25, 250, or 1250 ppm of genistein. We then conducted ELISA assays for hypothalamic content of both beta-endorphin and vasopressin immunoreactivity. Whereas there were no statistically reliable effects of dietary genistein on hypothalamic beta-endorphin content, vasopressin levels were significantly elevated in the 1250-ppm genistein group (p < 0.05). Elevated vasopressin levels may be associated with fluid balance, altered blood pressure, and cardiovascular effects. These data are consistent with the known actions of estradiol and may serve to explain our finding in a previous study that estrogenic endocrine-disruptors such as genistein increased sodium preference in rats exposed through their diet. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 28 TC 18 Z9 18 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2003 VL 72 IS 2 BP 296 EP 300 DI 10.1093/toxsci/kfg029 PG 5 WC Toxicology SC Toxicology GA 662DP UT WOS:000181931200016 PM 12660364 ER PT J AU Sahu, SC AF Sahu, SC TI Hepatocyte culture as an in vitro model for evaluating the hepatotoxicity of food-borne toxicants and microbial pathogens: A review SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE food toxicants; hepatocytes; hepatotoxicity; liver toxicity; microbial pathogens ID ISOLATED RAT HEPATOCYTES; INDUCED OXIDATIVE STRESS; OXYGEN-FREE-RADICALS; HEP G2 CELLS; IN-VITRO; LISTERIA-MONOCYTOGENES; CYTO-TOXICITY; LIVER SLICES; SALMONELLA-TYPHIMURIUM; INFECTED HEPATOCYTES AB Hepatocyte culture is a well-established, well-characterized, and widely used in vitro tool for pharamacological and toxicological studies. The hepatocytes of a wide range of species, including humans, can be maintained in culture with a high metabolizing capacity for several days under closely controlled and easily manipulated conditions. Numerous studies have reported good correlation between in vitro hepatocytes and in vivo siutations. They have been widely used for studies of the metabolism and of the toxicity and mechanisms of action of chemicals and drugs, for the screening of mutagens, carcinogens, and micotoxins, for virulence assessment of microbial pathogens and viruses, for qualitative and quantitative interspecies comparison, and for genomics and proteiomics studies. Hepatocytes, especially human hepatocytes, are used for preclinical drug evaluation and screening as well as for studies of drug metabolism, toxicity, interactions, and structure-activity relationships. They can be used for evaluating the hepatotoxicity of herbal products, dietary supplements, food additives, food-borne toxicants, and microbial pathogens. The results obtained from such in vitro screenings can be used for in vivo studies to asses the safety of test materials of interest. At the present time, there is insufficient evidence for their use in quantitative risk assessment. However, they are suitable for use in qualitative hazard assessment, which may be used for quantitative risk analysis. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div In Vitro & Biochem Toxicol, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div In Vitro & Biochem Toxicol, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 163 TC 2 Z9 2 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD APR-JUN PY 2003 VL 13 IS 2 BP 111 EP 119 DI 10.1080/15376510390196581 PG 9 WC Toxicology SC Toxicology GA 672XL UT WOS:000182549000005 PM 20021189 ER PT J AU Bhandoola, A Rosenberg, AS Singer, A AF Bhandoola, A Rosenberg, AS Singer, A TI CD4(+) T-cell responses to self-peptide-MHC SO TRENDS IN IMMUNOLOGY LA English DT Letter C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. US FDA, Div Therapeut Prot, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD APR PY 2003 VL 24 IS 4 BP 171 EP 171 DI 10.1016/S1471-4906(03)00061-9 PG 1 WC Immunology SC Immunology GA 676DD UT WOS:000182735900007 PM 12697444 ER PT J AU Zhu, PX Klutch, MJ Derrick, JP Prince, SM Tsng, RSW Tsai, CM AF Zhu, PX Klutch, MJ Derrick, JP Prince, SM Tsng, RSW Tsai, CM TI Identification of opcA gene in Neisseria polysaccharea: interspecies diversity of Opc protein family SO GENE LA English DT Article DE Neisseria; Neisseria polysaccharea; opcA gene ID OUTER-MEMBRANE PROTEIN; ENDOTHELIAL-CELLS; PATHOGENIC NEISSERIAE; SP-NOV; MENINGITIDIS; EXPRESSION; MENINGOCOCCI; INVASION; IMMUNIZATION; BIOSYNTHESIS AB The gene encoding the outer membrane adhesin/invasin protein OpcA was previously described in the genomes of two pathogenic Neisseria species, N. meningitidis (Nm) and N. gonorrhoeae (Ng). In order to understand the presence or absence of opcA in nonpathogenic Neisseria species, 13 strains of N. polysaccharea (Np), four strains of N. lactantica, three strains of N. subflava and nine strains of other species were examined by DNA hybridization, polymerase chain reaction (PCR) and nucleotide sequencing. The opcA gene was found in two Np strains (85322 and 89357). The Np-opcA gene is a novel member of this gene family with 93% homology to Ng-opcA. Comparison of opcA-surrounding regions among eight Neisseria strains revealed five types of genetic organization at the opcA locus in Neisseria, which result from insertion or deletion of genetic elements at the upstream region of opcA. Comparison of the deduced peptide sequences from two Np strains, two representative Ng strains, two representative Nm strains and 13 Nm sequence variants demonstrates interspecies diversity of the OpcA protein family with conserved transmembrane regions and species-specific polymorphism at the surface-exposed loops and periplasmic turns. Reverse transcription-PCR analysis and Northern blotting showed that Np-opcA was transcribable. From an alignment of the Np-OpcA and Ng-OpcA sequences against the three-dimensional crystal structure of Nm-OpcA we conclude that there is no obvious structural reason why these proteins would not be able to form stable, folded, outer membrane proteins. The data presented here provide additional information for understanding the distribution, variation and expression of opcA in Neisseria. Published by Elsevier Science B.V. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. UMIST, Dept Biomol Sci, Manchester M60 1QD, Lancs, England. Natl Microbiol Lab, Populat & Publ Hlth Branch, Hlth Winnipeg, Winnipeg, MB, Canada. RP Tsai, CM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. OI Prince, Stephen/0000-0003-0929-0254 FU FDA HHS [369VFFD018551] NR 38 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 27 PY 2003 VL 307 BP 31 EP 40 DI 10.1016/S0378-1119(02)01208-8 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 677EC UT WOS:000182793100004 PM 12706886 ER PT J AU Bae, MA Rhee, H Song, BJ AF Bae, MA Rhee, H Song, BJ TI Troglitazone but not rosiglitazone induces G1 cell cycle arrest and apopiosis in human and rat hepatoma cell lines SO TOXICOLOGY LETTERS LA English DT Article DE troglitazone; rosiglitazone; p53; p21; cell cycle arrest; cyclin-dependent kinases; apoptosis ID ACTIVATED RECEPTOR-GAMMA; SMOOTH-MUSCLE CELLS; INHIBITS GROWTH; CARCINOMA CELLS; CANCER CELLS; PPAR-GAMMA; APOPTOSIS; THIAZOLIDINEDIONE; DIFFERENTIATION; P27(KIP1) AB Rosiglitazone (RSG), an agonist of peroxisome proliferator-activated receptor gamma (PPARgamma), induces minor toxicity in humans relative to another PPARgamma agonist, troglitazone (TRO). In contrast, recent reports suggest that RSG causes growth arrest and apoptosis of normal and cancerous cells. Therefore, in this study, we investigated the relative toxicities of TRO and RSG on three different hepatoma cell lines, and observed that TRO, but not RSG, was cytotoxic. Additionally, we studied the mechanism by which TRO induced damage to HepG2 hepatoma cells. Our results indicated that TRO increased the levels of p53, p27, and p21, while it reduced the levels of cyclin D1 and phospho-Rb in a time-dependent manner. Increased p27 and p21 levels coincided with reduced activities of cell cycle dependent kinases (cdk) such as cdk2- and cyclin A-protein kinases 24 h after TRO treatment. These results demonstrate that TRO, but not RSG, causes G1 arrest of hepatoma cells, most likely through changing the levels of cell cycle regulators. Furthermore, because RSG did not affect the levels of cell cycle regulators, TRO-mediated growth inhibition appears independent of PPARgamma activation. Published by Elsevier Science Ireland Ltd. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 12420 Parklawn Dr, Rockville, MD 20852 USA. EM bjs@mail.nih.gov NR 37 TC 40 Z9 42 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR 20 PY 2003 VL 139 IS 1 BP 67 EP 75 DI 10.1016/S037842740200468X PG 9 WC Toxicology SC Toxicology GA 660RM UT WOS:000181846600007 PM 12595159 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Re: Serum proteomic patterns for detection of prostate cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Off Director, Ctr Biol Evaluat & Res, US FDA,Clin Proteom Program,NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, US FDA,Clin Proteom Program,NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), Bldg 29A,Rm 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 1 U2 1 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 MAR 19 PY 2003 VL 95 IS 6 BP 490 EP 491 PG 2 WC Oncology SC Oncology GA 655NV UT WOS:000181559700018 ER PT J AU Bhattacharjee, A Xu, B Roy, B Frank, DA Feldman, GM Cathcart, MK AF Bhattacharjee, A Xu, B Roy, B Frank, DA Feldman, GM Cathcart, MK TI PKCdelta regulates IL-13-induced Stat3 serine (727) phosphorylation and 15-lipoxygenase gene expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 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 MAR 17 PY 2003 VL 17 IS 5 SU S BP A1354 EP A1354 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902836 ER PT J AU Poirier, LA Wise, CK Delongchamp, RR Buffington, CK Cowans, GSM Feuers, R AF Poirier, LA Wise, CK Delongchamp, RR Buffington, CK Cowans, GSM Feuers, R TI Methyl intermediates in the blood of gastric bypass patients SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Tennessee, Sch Med, Memphis, TN USA. NR 0 TC 0 Z9 0 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 MAR 17 PY 2003 VL 17 IS 5 SU S BP A1089 EP A1089 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901587 ER PT J AU Reddy, MB Vattam, S Whittaker, P Turner, EA AF Reddy, MB Vattam, S Whittaker, P Turner, EA TI Iron bioavailability of tortillas made from corn masa flour fortified with elemental iron powders SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Iowa State Univ, Ames, IA 50011 USA. US FDA, College Pk, MD USA. SUSTAIN, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAR 17 PY 2003 VL 17 IS 5 SU S BP A1133 EP A1133 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901790 ER PT J AU Satchithanandam, S Oles, C Yurawecz, MP Rader, JI AF Satchithanandam, S Oles, C Yurawecz, MP Rader, JI TI Distribution of types of fat in selected foods in the US market SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 US FDA, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 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 MAR 17 PY 2003 VL 17 IS 5 SU S BP A766 EP A766 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900056 ER PT J AU Xu, B Bhattacharjee, A Roy, B Xu, HM Frank, DA Feldman, GM Cathcart, MK AF Xu, B Bhattacharjee, A Roy, B Xu, HM Frank, DA Feldman, GM Cathcart, MK TI IL-13 induction of 15-Lipoxygenase gene expression requires p38 MAPK-dependent serine phosphorylation of Stat1 and Stat3 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 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 MAR 17 PY 2003 VL 17 IS 5 SU S BP A1354 EP A1354 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902835 ER PT J AU Hirschfeld, S Ho, PTC Smith, M Pazdur, R AF Hirschfeld, S Ho, PTC Smith, M Pazdur, R TI Regulatory approvals of pediatric oncology drugs: Previous experience and new initiatives SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHILDHOOD LYMPHOCYTIC-LEUKEMIA; CHILDRENS-CANCER-GROUP; CYTOSINE-ARABINOSIDE; NEUROBLASTOMA; VM-26 AB Purpose: To review the Food and Drug Administration (FDA) experience with approvals of new drugs for pediatric oncology and to discuss new regulatory initiatives directed at pediatric oncology. Methods: A retrospective review of FDA archival documents and the published literature. Results: More than 100 drugs have been approved by the Division of Oncology Drug Products of the FDA for the treatment of malignancies. Only 15 have pediatric use information in their labeling, which is less than 50% of the drugs commonly used in the treatment of pediatric malignancies. In the past 20 years, there have been six submissions to the FDA for pediatric oncology indications. To illustrate principles of the approval process, each submission is discussed. Conclusion: Potential reasons for a lack of New Drug Application submissions for pediatric oncology include the small pediatric oncology market compared with the adult oncology market and perceived barriers to performing studies in children. Reasons for failure to approve pediatric indications include small numbers of patients, lack of appropriate controls, and failure to demonstrate patient benefit. Approval criteria include the use of controlled trials, prospective data collection, and disease-appropriate end points. Regulatory initiatives to promote pediatric therapeutic development and product labeling are discussed. J Clin Oncol 21:1066-1073. (C) 2003 by American Society of Clinical Oncology. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. GlaxoSmithKline, Philadelphia, PA USA. RP Hirschfeld, S (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,1451 Rockville Pike, Rockville, MD 20852 USA. EM hirschfelds@cder.fda.gov RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 20 TC 26 Z9 26 U1 0 U2 0 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 15 PY 2003 VL 21 IS 6 BP 1066 EP 1073 DI 10.1200/JCO.2003.11.138 PG 8 WC Oncology SC Oncology GA 657QR UT WOS:000181678300017 PM 12637472 ER PT J AU Puccioni-Sohler, M Chimelli, L Mercon, M Goncalves, RR Pimenta, G Bianco, C Rios, M Jacobson, S AF Puccioni-Sohler, M Chimelli, L Mercon, M Goncalves, RR Pimenta, G Bianco, C Rios, M Jacobson, S TI Pathological and virological assessment of acute HTLV-1-associated myelopathy complicated with encephalopathy and systemic inflammation SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Symposium on NeuroVirology CY SEP 14-16, 2000 CL SAN FRANCISCO, CALIFORNIA SP NINDS, NIMH, Penn State Univ, Life Sci Consortium, Integrat Biosci Grad Program, Temple Univ, Coll Sci & Technol, Ctr Neurovirol & Canc Biol, Adv Biosci Resources, Inc, Pharmacia & Upjohn Inc DE HTLV-1; CSF; HTLV-1-associated myelopathy/tropical spastic paraparesis; HAM/TSP; quantitative PCR; viral load; HTLV-1 antibody index ID I-ASSOCIATED MYELOPATHY; CENTRAL-NERVOUS-SYSTEM; HAM/TSP; LOAD; DISEASE; CSF; DNA AB HTLV-I-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP), is a chronic inflammatory disease of the spinal cord. Acute cases are uncommon. We report the case of a 41-year-old woman with acute HAM/TSP complicated with encephalitis, an intense inflammatory reaction of the nervous system and lymphocytic infiltration of skeletal muscles, liver, salivary, adrenal and pituitary glands. The immunohistochemical studies of the lymphocytes surrounding blood vessels showed both B- and T-lymphocytes, in similar proportion, with both CD4- and CD8-positive cells. In addition, many perivascular and scattered macrophages were observed. Adult T-cell leukemia/lymphoma (ATL) was ruled out. The marrow aspirate was normal. Serial cerebrospinal fluid (CSF) analysis showed presence of HTLV-1 antibodies, but without intrathecal synthesis of specific antibodies. Determination of HTLV-1 viral loads demonstrated increased levels in the CSF relative to the peripheral blood and may be associated with widespread inflammation. The pathological and immunological findings may help understand the role of immune-reactive cells in the pathogenesis of HTLV-I-associated myelopathy. (C) 2002 Elsevier Science B.V. All rights reserved. C1 UFRJ, HUCFF, Clin Pathol Serv, CSF Lab,Dept Med, BR-22280030 Rio De Janeiro, Brazil. UFRJ, HUCFF, Dept Pathol, BR-22280030 Rio De Janeiro, Brazil. CSF Lab Neurolife, BR-22210010 Rio De Janeiro, Brazil. NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Amer Blood Ctr, Washington, DC 20005 USA. US FDA, Bethesda, MD 20817 USA. RP Puccioni-Sohler, M (reprint author), UFRJ, HUCFF, Clin Pathol Serv, CSF Lab,Dept Med, Rua Dezenove Fevereiro 185-705, BR-22280030 Rio De Janeiro, Brazil. NR 13 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAR 15 PY 2003 VL 207 IS 1-2 BP 87 EP 93 AR PII S0022-510X(02)00413-6 DI 10.1016/S0022-510X(02)00413-6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 655CJ UT WOS:000181533500014 PM 12614936 ER PT J AU Chamberlain, PL Fowler, BA Sexton, MJ Peggins, JO von Bredow, J AF Chamberlain, PL Fowler, BA Sexton, MJ Peggins, JO von Bredow, J TI Preliminary studies of offspring exposure to phenylbutazone and ivermectin during the perinatal period in a Holstein cow-calf model SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE animal modeling; pregnant Holstein cows; phenylbutazone; ivermectin; perinatal drug exposure ID HUMAN-BREAST-MILK; LIQUID-CHROMATOGRAPHY; P-GLYCOPROTEIN; DAIRY-COWS; PHARMACOKINETICS; DRUGS; EXCRETION; PLASMA; DISPOSITION; DORAMECTIN AB The pregnant Holstein cow and her newborn calf were evaluated as an animal model to study in utero and for lactational drug transfer and offspring exposure. A nonsteroidal antimflammatory drug, phenylbutazone, and an antiparasitic drug, ivermectin, were tested in the model. Prior to parturition, pregnant cows were dosed orally to steady state with phenylbutazone at 4 g/day or given a single subcutaneous injection of 200 mug ivermectin/kg body wt. The level of drug transferred to calves exposed in utero, in utero combined with lactational exposure, and via lactational exposure only, was measured from days 1 through 7 postpartum. At birth the plasma level in phenylbutazone-exposed calves was approximately one-half the dam's steady-state level. For ivermectin-exposed calves, plasma levels were at or below the limit of quantitation (0.5 ng/ml) at birth, suggesting that placental transfer of ivermectin is limited in the cow. For both drugs, rapid accumulation of the drug in calf plasma occurred with lactational exposure to a mean daily dose of 2 mug ivermectin/kg body wt or 0.1 mg phenylbutazone/kg body wt/day for the first 7 days of life. The accumulation observed in the newborn calf is attributed to the lipid solubility and long elimination half-lives of these drugs. These results demonstrate that drug transfer and offspring exposure can be studied using the cow-calf model. The data also highlight the importance of considering not only the dose but also physicochemical characteristics and pharmacokinetics of the drug in the offspring when evaluating the safety of a newborn's exposure to a drug in breast milk. (C) 2003 Elsevier Science (USA). All rights reserved. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Univ Maryland, Sch Med, Toxicol Program, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Chamberlain, PL (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. NR 32 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 15 PY 2003 VL 187 IS 3 BP 198 EP 208 DI 10.1016/S0041-008X(03)00074-1 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 710WP UT WOS:000184706100007 PM 12662903 ER PT J AU Alshafie, TA Brown, AT Eidt, JF Wang, YF Poirier, LA Moursi, MM AF Alshafie, TA Brown, AT Eidt, JF Wang, YF Poirier, LA Moursi, MM TI The effect of gender, estrus status and plasma homocysteine on intimal hyperplasia after a rat carotid endarterectomy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Cent Arkansas Vet Healthcare Syst, Vasc Surg, Little Rock, AR USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A362 EP A362 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101721 ER PT J AU Baldwin, AL Cudilo, E Riggs, J Alayash, A AF Baldwin, AL Cudilo, E Riggs, J Alayash, A TI Nitric oxide reduces hemoglobin-induced venular leaks but not mast cell degranulation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Arizona, Coll Med, Tucson, AZ 85724 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A135 EP A135 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100648 ER PT J AU Fitzgerald, RT Qureshi, I Brown, AT Wang, YF Eidt, JF Poirier, LA Moursi, MM AF Fitzgerald, RT Qureshi, I Brown, AT Wang, YF Eidt, JF Poirier, LA Moursi, MM TI Homocysteine increases endothelial proliferation and replication via N-methyl D-aspartate (NMDA) receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A737 EP A737 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103464 ER PT J AU Jakubzick, CV Choi, ES Kunkel, SL Joshi, BH Keane, MP Puri, RK Hogaboam, CM AF Jakubzick, CV Choi, ES Kunkel, SL Joshi, BH Keane, MP Puri, RK Hogaboam, CM TI Reversal of experimental interstitial pulmonary fibrosis via targeting of IL-4- and IL-13-responsive cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Michigan, Ann Arbor, MI 48109 USA. US FDA, Lab Mol Tumor Biol, Bethesda, MD 20014 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RI hogaboam, cory /M-3578-2014 NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A662 EP A662 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103119 ER PT J AU James, SJ Pogribna, M Melnyk, S Slikker, W New, E Jernigan, S AF James, SJ Pogribna, M Melnyk, S Slikker, W New, E Jernigan, S TI Prevention of Thimerosal-induced neurotoxicity by glutathione (GSH) and cysteine, but not methionine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A309 EP A309 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101471 ER PT J AU James, SJ Melnyk, S Pogribna, M Pogribny, IP AF James, SJ Melnyk, S Pogribna, M Pogribny, IP TI Regulatory activity of S-adenosylhomocysteine (SAH) on levels of methionine/transsulfuration metabolites and DNA methylation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A309 EP A309 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101470 ER PT J AU Leak, LVLV Petricoin, EF Liotta, LA Jones, M AF Leak, LVLV Petricoin, EF Liotta, LA Jones, M TI Proteomic technologies to study lymphangiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Howard Univ, Coll Med, Washington, DC 20059 USA. US FDA, Div Therapeut Prod, Bethesda, MD USA. NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A554 EP A554 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102606 ER PT J AU Paule, MG Fogle, CM Allen, RR Pearson, E Hammond, T Popke, EJ AF Paule, MG Fogle, CM Allen, RR Pearson, E Hammond, T Popke, EJ TI Chronic exposure to sodium channel and NMDA receptor blockers during development in rats and monkeys: long-term effects on cognitive function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Peak Stat Serv, Div Neurotoxicol, Evergreen, CO USA. AstraZenaca R&D Charnwood, Safety Assessment, Loughborough, Leics, England. Wyeth Ayerst, CNS Safety Pharmacol, Chazy, NY USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A624 EP A624 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102941 ER PT J AU Paule, MG Fogle, CM Allen, RR Pearson, E Hammond, T Popke, EJ AF Paule, MG Fogle, CM Allen, RR Pearson, E Hammond, T Popke, EJ TI Chronic exposure to sodium channel and NMDA receptor blockers during development in rats and monkeys: long-term effects on cognitive function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Peak Stat Serv, Div Neurotoxicol, Evergreen, CO USA. AstraZeneca R&D Charnwood, Safety Assessment, Loughborough, Leics, England. Wyeth Ayerst, CNS Safety Pharmacol, Chazy, NY USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A610 EP A610 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102874 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI FDA-NCI clinical proteomics progam: Applications at the bedside SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, FDA, Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A380 EP A380 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101807 ER PT J AU Sawant, SP Dnyanmote, AV Shankar, K Latendresse, HM AF Sawant, SP Dnyanmote, AV Shankar, K Latendresse, HM TI Inhibited Tissue Repair as a Mechanism of CCl4-induced acute liver failure in type 2 Diabetes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Louisiana Monroe, Dept Toxicol, Coll Pharm, Monroe, LA 71209 USA. Pathol Associates Int, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A614 EP A614 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102895 ER PT J AU Sealey, WM Mock, DM Hansen, D AF Sealey, WM Mock, DM Hansen, D TI Supplementation with biotin in vitro fails to ameliorate in vivo biotin deficiency-induced clefting SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A720 EP A720 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103387 ER PT J AU Whittaker, P Mossoba, MM Tall, BD Al-Khaldi, SF Fry, FS Yurawecz, MP Dunkel, VC AF Whittaker, P Mossoba, MM Tall, BD Al-Khaldi, SF Fry, FS Yurawecz, MP Dunkel, VC TI Identification of food-borne bacteria pathogens by infrared spectroscopy based on cellular fatty acids SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 US FDA, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 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 MAR 14 PY 2003 VL 17 IS 4 SU S BP A585 EP A585 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102755 ER PT J AU Lenz, P Bacot, SM Frazier-Jessen, MR Feldman, GM AF Lenz, P Bacot, SM Frazier-Jessen, MR Feldman, GM TI Nucleoporation of dendritic cells: efficient, gene transfer by electroporation into human monocyte-derived dendritic cells SO FEBS LETTERS LA English DT Article DE electroporation; dendritic cell; gene therapy; monocyte; nucleofection; green fluorescent protein ID CENTRIFUGAL ELUTRIATION CCE; ANTIGEN-PRESENTING CELLS; ADENOASSOCIATED VIRUS; ANTITUMOR IMMUNITY; MESSENGER-RNA; MEDIATED TRANSFECTION; NONVIRAL TRANSFECTION; ENRICHED FRACTIONS; TRANSDUCTION; RESPONSES AB Dendritic cells (DCs) are ideal accessory cells in the developing field of gene therapy. Although viral transfection of DO has become widespread, non-viral transfection of DCs has shown disappointing results. Recently, a new technique for transfecting primary cells has become available - the Amaxa Nucleofector(TM). Here, we describe the use of this device in the successful non-viral transfection of human monocyte-derived DCs. Using enhanced green fluorescent protein as a reporter gene DCs were transfectable with efficiencies approaching 60%, remaining responsive to lipopolysaccharide-stimulated cytokine production in short-term experiments (though long-term functional assays were hampered by loss of viability). Although these data demonstrate the ease and efficiency with which human monocyte-derived DCs can now be non-virally transfected, they also suggest the limitations of this technology due to the gradual loss of cell viability. The potential use of this system in the development of DC-based cell and gene therapies will be hampered until cell viability can be maintained. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 US FDA, Div Monclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Feldman, GM (reprint author), US FDA, Div Monclonal Antibodies, Ctr Biol Evaluat & Res, HFM-564,Bldg 29A,Rm 3C24,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 44 TC 59 Z9 66 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 13 PY 2003 VL 538 IS 1-3 BP 149 EP 154 DI 10.1016/S0014-5793(03)00169-8 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 655RV UT WOS:000181567200027 PM 12633869 ER PT J AU Billedeau, SM Heinze, TM Siitonen, PH AF Billedeau, SM Heinze, TM Siitonen, PH TI Liquid chromatography analysis of erythromycin A in salmon tissue by electrochemical detection with confirmation by electrospray ionization mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE macrolide antibiotics; erythromycin A; electrochemical detection; mass spectrometry; salmon ID RESIDUES AB A rapid and sensitive method is described for the quantitation of erythromycin A (EA) in edible salmon tissue by liquid chromatography (LC) analysis using either electrochemical detection (ED) or electrospray ionization mass spectrometric (ESINS) detection. The salmon tissue is extracted with 10 mM ammonium formate. The extract is then purified by solid phase extraction using a hydrophilic-lipophilic balanced (HLB) polymeric-based C18 packing, followed by partitioning of EA into methylene chloride at alkaline pH, evaporation, and final dilution. The mean recoveries of EA at 50, 100, 200, and 400 ppb levels in fortified salmon tissue were 63.8 +/- 16.0 and 75.5 +/- 5.4% by LC-ED and LC-ESI/MS, respectively. There was no evidence of formation of the anhydro-EA (m/z 716) decomposition product of EA (m/z 734) that was reported to occur by other published methods. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Billedeau, SM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 16 TC 13 Z9 13 U1 1 U2 9 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 MAR 12 PY 2003 VL 51 IS 6 BP 1534 EP 1538 DI 10.1021/jf0209138 PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 652VK UT WOS:000181401400005 PM 12617579 ER PT J AU Henderson, TJ Venable, RM Egan, W AF Henderson, TJ Venable, RM Egan, W TI Conformational flexibility of the group B meningococcal polysaccharide in solution SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SIALIC-ACID POLYSACCHARIDE; MOLECULAR-DYNAMICS SIMULATIONS; NUCLEAR MAGNETIC-RESONANCE; MENINGITIDIS SEROGROUP-B; ESCHERICHIA-COLI K1; NEISSERIA-MENINGITIDIS; CAPSULAR POLYSACCHARIDE; CORRELATION TIMES; POLYSIALIC ACID; COLOMINIC ACID AB To elucidate the role of secondary structure in the immune response against alpha(2-->8)-linked polysialic acid, the capsular polysaccharide of Group B meningococci, we have investigated its solution dynamics by using specific models of molecular motion and hydrodynamic modeling to interpret experimental NMR data. (13)C-{(1)H} NMR relaxation times and steady-state NOE enhancements were measured for two aqueous solutions of alpha(2-->8)-linked sialic acid polysaccharides. Each contained a unique distribution of polysaccharide chain lengths, with average lengths estimated at 40 or 400 residues. Models for rigid molecule tumbling, including two based on helical conformations proposed for the polysaccharide,3' could not explain the NMR measurements. In general for these helices, the correlation times for their overall tumbling that best account for the NMR data correspond to polysaccharide chains between 9 and 18 residues in length, far short of the average lengths estimated for either solution. The effects of internal motions incorporated into these helices was modeled with an effective correlation time representing helix tumbling as well as internal motion. This modeling demonstrated that even with extreme amounts of internal motion, "flexible helices" of 25 residues or more still could not produce the NMR measurements. All data are consistent with internal and segmental motions dominating the nuclear magnetic relaxation of the polysaccharide and not molecular tumbling. Statistical distributions of correlation times have been found specifically for the pyranose rings, linkage groups, and methoxy groups that can account for the measured relaxation times and NOE enhancements. The distributions suggest that considerable flexibility attends the polysaccharide in solution, and the ranges of motional frequencies for the linkage groups and pyranose rings are comparable. We conclude that the Group B meningococcal polysaccharide is a random coil chain in solution, and therefore, does not have antigenic epitopes dependent upon a rigid, ordered conformation. C1 Battelle Mem Inst, Edgewood Operat, Edgewood Chem Biol Forens Analyt Ctr, Aberdeen, MD 21001 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Henderson, TJ (reprint author), Battelle Mem Inst, Edgewood Operat, Edgewood Chem Biol Forens Analyt Ctr, 1204 Technol Dr, Aberdeen, MD 21001 USA. EM txhender@sbccom.apgea.army.mil NR 59 TC 23 Z9 23 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 12 PY 2003 VL 125 IS 10 BP 2930 EP 2939 DI 10.1021/ja0210087 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 652YY UT WOS:000181409500040 PM 12617660 ER PT J AU Brorson, K Brown, J Hamilton, E Stein, KE AF Brorson, K Brown, J Hamilton, E Stein, KE TI Identification of protein A media performance attributes that can be monitored as surrogates for retrovirus clearance during extended re-use SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 15th Symposium on Preparative and Process Chromatography CY JUN 16-19, 2002 CL WASHINGTON, D.C. DE viruses; monoclonal antibodies; protein A; proteins; reverse transcriptase ID REVERSE-TRANSCRIPTASE ASSAY; MAB CELL-CULTURE; MONOCLONAL-ANTIBODIES; AFFINITY-CHROMATOGRAPHY; FAST-FLOW; PURIFICATION; VIRUS; COLUMN; SCALE; VALIDATION AB A potential safety concern in biotechnology purification schemes that employ re-use of column media, often for large numbers of chromatography runs, is loss of the virus removal capacity of the chromatographic purification operation over time. To define chromatography performance attributes that best predict retrovirus clearance during extended re-use of protein A media, small-scale protein A columns were cycled 150 to 460 times using concentrates of murine hybridoma cell culture supernatants, standard low pH elution buffers and different cleaning solutions (6 M urea, 6 M guanidine, 100 MM NaOH or 500 mM NaOH). Load, flow-through and eluate samples were taken periodically and assayed for reverse transcriptase (RT, an enzyme component of retroviruses) activity, bovine IgG (a component of the culture media), genomic DNA, leached protein A, and mouse IgG. Under all cleaning conditions tested, the log(10) reduction value (LRV) of RT activity did not decrease and impurity co-elution did not increase during the 150 to 460 purification/cleaning cycles. In the two studies in which the columns were cleaned with NaOH, the chromatography performance attribute that best predicted the column media lifespan was column capacity, as measured by antibody (Ab) step yield and breakthrough. In both studies, Ab capture decayed in a biphasic manner starting at cycle 200 (100 mM NaOH) or cycle 50 (500 mM NaOH). For media cycled 300+ times using 6 M urea or 6 M guanidine cleaning buffers, column performance, including RT activity LRV, was more stable, although small upward trends in Ab breakthrough were evident. In summary, our studies identify Ab step yield and breakthrough as performance attributes that decay prior to retrovirus LRV when protein A media is multiply-cycled. Thus, we propose that virus removal validation studies should be performed on new media only and these attributes can be monitored during protein A unit operations in lieu of performing virus removal validation studies with cycled protein A media. Published by Elsevier Science B.V. C1 US FDA, Div Monoclonal Antibodies, Off Therapeut Res & Rev, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Metab & Endocrine Drug Prod, Off New Drug Chem HFD510, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Brorson, K (reprint author), US FDA, Div Monoclonal Antibodies, Off Therapeut Res & Rev, Ctr Biol Evaluat & Res, HFM-561,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 32 TC 45 Z9 48 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAR 7 PY 2003 VL 989 IS 1 BP 155 EP 163 AR PII S0021-9673(02)01697-7 DI 10.1016/S0021-9673(02)01697-7 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 649TZ UT WOS:000181225200015 PM 12641291 ER PT J AU Fang, H Tong, WD Welsh, WJ Sheehan, DM AF Fang, H Tong, WD Welsh, WJ Sheehan, DM TI QSAR models in receptor-mediated effects: the nuclear receptor superfamily SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Review DE receptor-mediated effects; nuclear receptors; quantitative structure-activity relationships; estrogen receptor; endocrine disrupting chemicals ID MOLECULAR-FIELD ANALYSIS; LIGAND-BINDING DOMAIN; R(2)-GUIDED REGION SELECTION; LARGE DIVERSE SET; ESTROGEN-RECEPTOR; QUANTITATIVE STRUCTURE; 3D QSAR; ANDROGEN RECEPTOR; CRYSTAL-STRUCTURE; SURFACE PROPERTIES AB The nuclear receptor (NR) superfamily is ligand-dependent transcriptional factors that mediate gene expression in humans and wildlife. These receptor-mediated effects are stimulated and/or inhibited by endogenous cognate ligands for each NR but also by exogenous substances including natural products and synthetic chemicals. The NRs and their ligands have thus attracted broad scientific interest, particularly in the pharmaceutical industry for drug discovery and in toxicology and environmental science for risk assessment as, for example, pertaining to endocrine disrupting chemicals. Besides advancing our fundamental knowledge of NR biology, these scientific efforts are generating relevant biological data on NR ligands particularly with respect to their binding affinities, receptor specificities, and agonist versus antagonist activities. These data from diverse sources serve as input for construction of quantitative structure-activity relationship (QSAR) models and related approaches that employ statistical regression techniques to correlate variations between the biological activities of NR ligands and their calculated structural and physicochemical properties. In this review, we attempt to summarize the substantial body of work in the published literature related to QSAR models for NR ligands, with special emphasis on different computational approaches and specific applications. Special attention is placed on the estrogen receptor, for which the greatest amount of relevant information is known at present. We also describe efforts to create 'benchmark' sets of high-quality biological data on NR ligands that may serve as resources for building statistically robust and predictive QSAR models. Published by Elsevier Science B.V. C1 Logicon ROW Sci, Jefferson, AR 72079 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), Logicon ROW Sci, 3900 NCTR Rd,MC 910, Jefferson, AR 72079 USA. NR 123 TC 26 Z9 26 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD MAR 7 PY 2003 VL 622 IS 1-2 BP 113 EP 125 AR PII S0166-1280(02)00623-1 DI 10.1016/S0166-1280(02)00623-1 PG 13 WC Chemistry, Physical SC Chemistry GA 652ZB UT WOS:000181409800010 ER PT J AU Birenbaum, D Mattison, DR AF Birenbaum, D Mattison, DR TI Analgesics for the treatment of pain in children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. NIH, Bethesda, MD 20892 USA. RP Birenbaum, D (reprint author), US FDA, Rockville, MD 20852 USA. RI Mattison, Donald/C-2015-2009 NR 2 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 6 PY 2003 VL 348 IS 10 BP 959 EP 960 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 651UU UT WOS:000181341100031 PM 12621144 ER PT J AU Armstrong, DJ AF Armstrong, DJ TI FDA overview of immune-enhancing foods. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, NCFST, Summit Argo, IL 60501 USA. EM David.Armstrong@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA AGFD-011 BP U70 EP U70 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800224 ER PT J AU Billedeau, SM Heinze, TM Siitonen, PH Reimschuessel, R Gieseker, C Moffitt, CM AF Billedeau, SM Heinze, TM Siitonen, PH Reimschuessel, R Gieseker, C Moffitt, CM TI Analysis of erythromycin a and its metabolites in incurred and fortified salmon tissue by LC/ED and LC/ESI-MS. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NCTR, FDA, Div Chem, Jefferson, AR 72079 USA. Univ Idaho, Vet Adm Med Ctr, Food & Drug Adm, Dept Fish & Wildlife Resources, Moscow, ID 83843 USA. EM SBILLEDEAU@NCTR.FDA.GOV NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA AGFD-048 BP U76 EP U76 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800261 ER PT J AU Brorson, K AF Brorson, K TI Product-directed research in the division of monoclonal antibodies. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM brorson@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 177-BIOT BP U212 EP U212 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800867 ER PT J AU Del Grosso, A May, J AF Del Grosso, A May, J TI Analytical methods development at FDA CBER: Analytical chemistry staff, office of vaccines research and review. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Ctr Biol Evaluat & Res, Off Vacines Res & Review, Rockville, MD 20852 USA. EM del_grosso@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 175-BIOT BP U211 EP U211 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800865 ER PT J AU Falci, KJ Vierk, KA AF Falci, KJ Vierk, KA TI Food allergen regulatory issues. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Off Sci Anal & Support, College Pk, MD 20740 USA. EM kenneth.falci@cfsan.fda.gov; katherine.vierk@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA AGFD-096 BP U84 EP U84 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800308 ER PT J AU Falci, KJ AF Falci, KJ TI Fda approaches to food allergens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Off Sci Anal & Support, College Pk, MD 20740 USA. EM kenneth.falci@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA AGFD-037 BP U74 EP U74 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800250 ER PT J AU Frasch, CE Lee, CH Hang, JZ AF Frasch, CE Lee, CH Hang, JZ TI Antibody responses to encapsulated group C meningococcal polysaccharide-tetanus toxoid conjugates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM frasch@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 146-BIOT BP U207 EP U207 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800836 ER PT J AU Fu, TJ AF Fu, TJ TI Impact of processing on the stability and allergenicity of food allergens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. EM tfu@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA AGFD-081 BP U81 EP U81 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800294 ER PT J AU Gendel, SM AF Gendel, SM TI Application of bioinformatics to food allergy. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 Biotechnol Studies Branch, Food & Drug Adm, Summit Argo, IL 60501 USA. EM sgendel@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA AGFD-040 BP U75 EP U75 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800253 ER PT J AU Krynitsky, AJ Schermerhorn, PG Golden, PE Podhorniak, LV AF Krynitsky, AJ Schermerhorn, PG Golden, PE Podhorniak, LV TI LC/MS/MS as a practical tool for developing multiresidue methods for pesticide residues. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US EPA, Off Pesticide Programs, Res Triangle Pk, NC USA. EM Alex.Krynitsky@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 0069-AGRO BP U101 EP U102 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800397 ER PT J AU Lehotay, SJ Mastovska, K AF Lehotay, SJ Mastovska, K TI New developments in the quick, easy, cheap, effective, rugged, and safe (QuEChERS) approach to pesticide residue analysis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. US FDA, Rockville, MD 20857 USA. EM slehotay@arserrc.gov RI Mastovska, Katerina/B-1077-2008 NR 0 TC 3 Z9 3 U1 5 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 0065-AGRO BP U101 EP U101 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800393 ER PT J AU Maynard, J Relman, D Iverson, B Merkel, T Georgiou, G AF Maynard, J Relman, D Iverson, B Merkel, T Georgiou, G TI Engineered antibodies to treat whooping cough. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Univ Texas, Dept Chem Engn, Austin, TX 78712 USA. US FDA, CBER, Rockville, MD 20857 USA. EM jamaynard@stanford.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 085-BIOT BP U196 EP U196 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800775 ER PT J AU Mercer, GE AF Mercer, GE TI Expanding the role of GC/MSD in the pesticide monitoring program at FDA. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Seattle Dist Lab, Bothell, WA 98021 USA. EM GMercer@ora.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 0066-AGRO BP U101 EP U101 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800394 ER PT J AU Moore, SK AF Moore, SK TI FDA CDER's perspective on specifications for peptide maps SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Ctr Drug Evaluat & Res, Off New Drug Chem, Rockville, MD 20852 USA. EM moorest@cder.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 176-BIOT BP U211 EP U212 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800866 ER PT J AU Shefcheck, K Trucksess, MW Musser, SM AF Shefcheck, K Trucksess, MW Musser, SM TI Liquid chromatographic/mass spectrometric methods for confirmation of peanut protein in foods. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA AGFD-075 BP U81 EP U81 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800288 ER PT J AU Sundaram, A Vann, W AF Sundaram, A Vann, W TI Substrate specificity studies on' recombinant Campylobacter jejuni N-acetyl neuraminic acid synthetase. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD 20892 USA. EM sundaram@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 179-BIOT BP U212 EP U212 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800869 ER PT J AU Swann, PG AF Swann, PG TI Regulatory considerations for rapid development of biological products. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM swannp@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 178-BIOT BP U212 EP U212 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800868 ER PT J AU Williams, KM Trucksess, MW AF Williams, KM Trucksess, MW TI Troubleshooting and quality assurance indicators of immunoassays for food allergens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM kwillia2@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA AGFD-071 BP U80 EP U80 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800284 ER PT J AU Graham, DJ Green, L Senior, JR Nourjah, P AF Graham, DJ Green, L Senior, JR Nourjah, P TI Troglitazone-induced liver failure: A case study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ADVERSE DRUG-REACTIONS; INDUCED FULMINANT-HEPATITIS; CHOLESTATIC HEPATITIS; HEPATOTOXICITY; APOPTOSIS; CELLS; PATIENT; LIGAND AB BACKGROUND: Troglitazone was removed from the U.S. market because its use was associated with an increased risk of liver failure. We evaluated the clinical features of all cases reported to the Food and Drug Administration and estimated the duration and magnitude of the risk of liver failure associated with continued use of the drug. METHODS: Data from cases of liver failure associated with troglitazone use were abstracted and analyzed. The extent of troglitazone use was determined from national marketing data, and the duration of use was estimated with data from a large, multistate, health care company. Survival analysis was performed to estimate monthly incidence rates and the cumulative risk of liver failure. RESULTS: Ninety-four cases of liver failure (89 acute, 5 chronic) were reported. Of the acute cases, 58 (67%) were women and only 11 (13%) recovered without liver transplantation. Progression from normal hepatic functioning to irreversible liver injury occurred within I month in 19 patients who were indistinguishable clinically from the 70 patients who had an unknown time course to irreversibility, except for the post hoc observation that prior cholecystectomy was less common in those with rapid onset. The incidence of liver failure was elevated from the first through at least the 26th month of troglitazone use. Accounting for case underreporting, the number needed to harm from troglitazone use was between 600 to 1500 patients at 26 months. CONCLUSION: The progression to irreversible liver injury probably occurred within a 1-month interval in most patients, casting doubt on the value of monthly monitoring of serum aminotransferase levels as a means of preventing troglitazone-induced acute liver failure. The cumulative risk of hepatic failure increased with continued use. (C) 2003 by Excerpta Medica Inc. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Rockville, MD 20857 USA. RP Graham, DJ (reprint author), 5600 Fishers Lane,HFD-400,Room 15B-32, Rockville, MD 20857 USA. NR 61 TC 105 Z9 109 U1 0 U2 7 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 2003 VL 114 IS 4 BP 299 EP 306 DI 10.1016/S0002-9343(02)01529-2 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 666JF UT WOS:000182173600008 PM 12681458 ER PT J AU Madhi, SA Radebe, K Crewe-Browns, H Frasch, CE Arakere, G Mokhachane, M Kimura, A AF Madhi, SA Radebe, K Crewe-Browns, H Frasch, CE Arakere, G Mokhachane, M Kimura, A TI High burden of invasive Streptococcus agalactiae disease in South African infants SO ANNALS OF TROPICAL PAEDIATRICS LA English DT Article ID GROUP-B STREPTOCOCCI; EARLY-ONSET; PREVENTION POLICY; BIRTH; INFECTIONS; CARRIAGE; SEPSIS AB The epidemiology of invasive Streptococcus agalactiae (GBS) disease was evaluated in South African children. Records of 208/220 children in whom GBS was isolated between January 1997 and December 1999 were reviewed. These included 63%, 31.7% and 5.3% children with early- (EOD, <7 days of age), late- (LOD, age 7-90 days) and childhood-onset disease (COD, age >90 days), respectively. The overall burden of EOD and LOD were 2.06 and 1/1000 live births, respectively. The overall mortality was 19.8% and 13.6% for infants with EOD and LOD, respectively. Risk factors for mortality in infants with EOD and LOD included septic shock (82.1% vs 1.9%), prematurity (35.2% vs 9.6%), low birthweight (29.2% vs 11.0%) and a leucocyte count <5000/mm(3) (43.5% vs 18.6%). Eight (72.7%) of 11 children with COD had an immunosuppressive, predisposing cause for invasive bacterial disease. In infants with EOD and LOD, serotype III isolates caused 49.2% and 75.7% of disease, respectively, and, together with serotype Ia isolates, caused 78.9% and 100% of invasive disease, respectively. Invasive GBS disease is common in South African infants and current strategies aimed at reducing the burden of the disease should be reconsidered. C1 Baragwanath Hosp, SAIMR, NHLS Wits MRC Pneumococcal Dis Res Unit, ZA-2013 Bertsham, South Africa. Baragwanath Hosp, Paediat Infect Dis Res Unit, ZA-2013 Bertsham, South Africa. Baragwanath Hosp, Natl Hlth Lab Serv, ZA-2013 Bertsham, South Africa. Univ Witwatersrand, Dept Paediat, Johannesburg, South Africa. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Biochem Pharma, Northborough, MA USA. RP Madhi, SA (reprint author), Baragwanath Hosp, SAIMR, NHLS Wits MRC Pneumococcal Dis Res Unit, Room 11,PO Bertsham, ZA-2013 Bertsham, South Africa. NR 25 TC 41 Z9 42 U1 0 U2 2 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0272-4936 J9 ANN TROP PAEDIATR JI Ann. Trop. Paediatr. PD MAR PY 2003 VL 23 IS 1 BP 15 EP 23 DI 10.1179/000349803125002814 PG 9 WC Pediatrics; Tropical Medicine SC Pediatrics; Tropical Medicine GA 655HP UT WOS:000181545500003 PM 12648320 ER PT J AU DePaola, A Nordstrom, JL Bowers, JC Wells, JG Cook, DW AF DePaola, A Nordstrom, JL Bowers, JC Wells, JG Cook, DW TI Seasonal abundance of total and pathogenic Vibrio parahaemolyticus in Alabama oysters SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID UNITED-STATES; ENVIRONMENT; FLORIDA; BAY; ENUMERATION; VULNIFICUS; INFECTIONS; WASHINGTON; EMERGENCE; CHOLERAE AB Recent Vibrio parahaemolyticus outbreaks associated with consumption of raw shellfish in the United States focused attention on the occurrence of this organism in shellfish. From March 1999 through September 2000, paired oyster samples were collected biweekly from two shellfish-growing areas in Mobile Bay, Ala. The presence and densities of V parahaemolyticus were determined by using DNA probes targeting the thermolabile hemolysin (tlh) and thermostable direct hemolysin (tdh) genes for confirmation of total and pathogenic E parahaemolyticus, respectively. V. parahaemolyticus was detected in all samples with densities ranging from < 10 to 12,000 g(-1). Higher V. parahaemolyticus densities were associated with higher water temperatures. Pathogenic strains were detected in 34 (21.8%) of 156 samples by direct plating or enrichment. Forty-six of 6,018 and 31 of 6,992 V. parahaemolyticus isolates from enrichments and direct plates, respectively, hybridized with the tdh probe. There was an apparent inverse relationship between water temperature and the prevalence of pathogenic strains. Pathogenic strains were of diverse serotypes, and 97% produced urease and possessed a tdh-related hemolysin (trh) gene. The O-3:K-6 serotype associated with pandemic spread and recent outbreaks in the United States was not detected. The efficient screening of numerous isolates by colony lift and DNA probe procedures may account for the higher prevalence of samples with tdh(+) V. parahaemolyticus than previously reported. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. US FDA, Div Math & Stat, College Pk, MD 20740 USA. Ctr Dis Control & Prevent, Foodborne Dis Lab Sect, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. NR 37 TC 187 Z9 201 U1 5 U2 14 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 MAR PY 2003 VL 69 IS 3 BP 1521 EP 1526 DI 10.1128/AEM.69.3.1521-1526 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 653LA UT WOS:000181435600025 PM 12620838 ER PT J AU Klinman, D AF Klinman, D TI Does activation of the innate immune system contribute to the development of rheumatoid arthritis? SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID TOLL-LIKE RECEPTORS; NF-KAPPA-B; POLYMERASE-CHAIN-REACTION; BACTERIAL-DNA; CPG MOTIFS; SYNOVIAL-FLUID; CELL ACTIVATION; PERIPHERAL-BLOOD; INTERLEUKIN-12; AUTOIMMUNITY C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, D (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D10, Bethesda, MD 20892 USA. NR 38 TC 17 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 2003 VL 48 IS 3 BP 590 EP 593 DI 10.1002/art.10852 PG 4 WC Rheumatology SC Rheumatology GA 653LY UT WOS:000181438800002 PM 12632408 ER PT J AU Amexis, G Ridge, J Cervenakova, L Enterline, JC Chumakov, KM Asher, DM AF Amexis, G Ridge, J Cervenakova, L Enterline, JC Chumakov, KM Asher, DM TI Stability of the prion protein-encoding (PRNP) gene in HeLa cells SO BIOLOGICALS LA English DT Article DE PRNP; PrP protein; Creutzfeldt-Jakob disease; transmissible spongiform encephalopathies; prion; HeLa cell; gene stability AB To assess the risk of the de novo emergence of the agent of transmissible spongiform encephalopathies in cultured cells, we examined the stability of the prion protein-encoding (PRNP) gene in HeLa cells and in cultures contaminated with HeLa cells that have been passaged extensively for over 50 years. Various sub-lineages of HeLa cells showed that some contained a mixture of a truncated PRNP gene (R3-R4 deletion) and a full-length PRNP gene, while others were homozygous for the R3-R4 deletion. That finding suggests that the progenitor of several popular sub-lineages of HeLa must have lost part or all of chromosome 20 early in the history of HeLa cells. No mutations were found in the PRNP genes. We conclude that the spontaneous appearance of mutations leading to expression of abnormal prion proteins in continuously passaged heteroploid cell lines is unlikely to pose a substantial risk for the safe production of biologicals in such cells. (C) 2003 The International Association for Biologicals. Published by Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Amer Red Cross, Holland Labs, Rockville, MD 20855 USA. RP Asher, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-313, Rockville, MD 20852 USA. NR 6 TC 2 Z9 2 U1 1 U2 2 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 MAR PY 2003 VL 31 IS 1 BP 83 EP 86 DI 10.1016/S1045-1056(02)00069-6 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 655KE UT WOS:000181550200010 PM 12623063 ER PT J AU Haverkos, HW Soon, GX Steckley, SL Pickworth, W AF Haverkos, HW Soon, GX Steckley, SL Pickworth, W TI Cigarette smoking and cervical cancer: Part I: a meta-analysis SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE cigarette smoking; cervical cancer; meta-analysis ID HUMAN-PAPILLOMAVIRUS INFECTION; ORAL-CONTRACEPTIVE USE; SIMPLEX VIRUS TYPE-2; HIGH-GRADE DYSPLASIA; RISK-FACTORS; INTRAEPITHELIAL NEOPLASIA; SEXUAL-BEHAVIOR; UTERINE CERVIX; CARCINOMA INSITU; UNITED-STATES AB Cancer of the cervix is the third most common cancer among women worldwide and its etiology is not clearly understood. Human papillomavirus can be found in approximately 95% of cervical cancers, but it does not appear to be necessary or sufficient to. induce malignancy. In 1977, Winkelstein suggested that cigarette smoking was a causative factor in the development of cervical cancer. We report a meta-analysis of cigarette smoking and cervical disease and conclude that the data support a role for cigarette smoking as a risk factor for cervical cancer. We propose a multifactorial hypothesis involving a virus-tar interaction as the etiology of cervical cancer. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Walter Reed Army Med Ctr, Dept Med, Infect Dis Serv, Washington, DC 20307 USA. US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, Rockville, MD 20857 USA. NIDA, Baltimore, MD USA. RP Haverkos, HW (reprint author), Walter Reed Army Med Ctr, Dept Med, Infect Dis Serv, Washington, DC 20307 USA. NR 107 TC 43 Z9 46 U1 0 U2 7 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD MAR PY 2003 VL 57 IS 2 BP 67 EP 77 DI 10.1016/S0753-3322(02)00341-4 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 677BX UT WOS:000182788000001 PM 12854514 ER PT J AU Tabacova, S Kimmel, CA Wall, K Hansen, D AF Tabacova, S Kimmel, CA Wall, K Hansen, D TI Atenolol developmental toxicity: Animal-to-human comparisons SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID PREGNANCY-ASSOCIATED HYPERTENSION; CONTROLLED-TRIAL; BETA-BLOCKERS; PREECLAMPSIA; ANTAGONISTS; OUTCOMES; INFANTS AB BACKGROUND: Atenolol, 4-2'-hydroxy-3'-isopropyl-aminopropoxy) phenylacetamide, is a beta-adrenoreceptor blocker used for treatment of hypertension in pregnancy. Beta-blockers are reported to cause fetal harm (such as decreased birth weight) when administered to a pregnant woman. We evaluate published human and animal evidence of atenolol developmental toxicity and compare the manifestations in humans and in routinely-used animal models. METHODS: The comparison is based on the following criteria: comparability of pharmacokinetic/pharmacodynamic characteristics, type of adverse outcome, lowest adverse effect levels, and specificity and selectivity of effect. RESULTS: Manifestations of atenolol prenatal toxicity (placental changes, intrauterine growth retardation and changes in fetal weight in the absence of structural malformations) are similar in the tested animal species (rats and rabbits) and humans. The human seems to be more sensitive, however, because adverse embryo-fetal effects are reported at doses much lower than those in the tested species. In humans and rats, adverse embryo-fetal effects are induced by doses that are not maternally toxic. In the rabbit, however, such effects are seen only at maternally toxic doses, suggesting that in this species, developmental toxicity may be maternally mediated. CONCLUSIONS: The available data suggest animal-human concordance with regard to the nature and manifestations of atenolol prenatal toxicity. The animal models "predicted" developmental toxicity manifests as placental changes, intrauterine growth retardation and fetal weight decrease in the absence of structural malformations. Thus far, this is concordant with the data from humans, in whom intrauterine growth retardation has been observed but not structural abnormalities. (C) 2003 Wiley-Liss, Inc. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tabacova, S (reprint author), NDPDP, FDA, 5600 Fishers Lane,HFD 120, Rockville, MD 20857 USA. NR 32 TC 15 Z9 15 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAR PY 2003 VL 67 IS 3 BP 181 EP 192 DI 10.1002/bdra.10011 PG 12 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 720XD UT WOS:000185286600007 PM 12797460 ER PT J AU Abrams, P Blaivas, JG Fowler, CJ Fourcroy, JL Macdiarmid, SA Siegel, SW Van Kerrebroeck, P AF Abrams, P Blaivas, JG Fowler, CJ Fourcroy, JL Macdiarmid, SA Siegel, SW Van Kerrebroeck, P TI The role of neuromodulation in the management of urinary urge incontinence SO BJU INTERNATIONAL LA English DT Article DE urinary urge incontinence; neuromodulation; neurourology; outcome ID SACRAL NERVE-STIMULATION; ELECTRICAL-STIMULATION; ROOT NEUROMODULATION; DETRUSOR INSTABILITY; OVERACTIVE BLADDER; EFFICACY; OXYBUTYNIN; SYMPTOMS; TRIAL AB OBJECTIVE To examine the benefit-risk profile of neuromodulation in treating refractory urinary urge incontinence and other voiding disorders. PATIENTS AND METHODS The outcome measures from all patients in pivotal clinical trials who had undergone sacral nerve stimulation were analysed retrospectively. RESULTS Neuromodulation was effective in several clinical studies; the response is durable and the benefit-risk profile good. CONCLUSION Sacral nerve stimulation is becoming the standard of care for refractory overactive bladder and retention problems. The potential benefit of neuromodulation should be included in female urology and gynaecology training programmes. C1 Southmead Gen Hosp, Bristol Urol Inst, Bristol, Avon, England. Uroctr New York, New York, NY USA. UCL Natl Hosp Neurol & Neurosurg, Dept Uroneurol, London WC1N 3BG, England. US FDA, Off Hlth Affairs, Bethesda, MD 20014 USA. Univ Tennessee, Dept Urol, Memphis, TN USA. Metropolitan Urol Specialists, Ctr Continence Care, St Paul, MN USA. Univ Hosp Maastricht, Dept Urol, Maastricht, Netherlands. RP Abrams, P (reprint author), Southmead Gen Hosp, Bristol Urol Inst, Bristol, Avon, England. EM paul_abrams@bui.ac.uk RI Fowler, Clare /B-2812-2009 NR 22 TC 36 Z9 41 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD MAR PY 2003 VL 91 IS 4 BP 355 EP 359 DI 10.1046/j.1464-4096.2003.04105.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 649VH UT WOS:000181228300018 PM 12603414 ER PT J AU Kimura, S Kawabe, M Yu, AM Morishima, H Fernandez-Salguero, P Hammons, GJ Ward, JM Kadlubar, FF Gonzalez, FJ AF Kimura, S Kawabe, M Yu, AM Morishima, H Fernandez-Salguero, P Hammons, GJ Ward, JM Kadlubar, FF Gonzalez, FJ TI Carcinogenesis of the food mutagen PhIP in mice is independent of CYP1A2 SO CARCINOGENESIS LA English DT Article ID AROMATIC-AMINES; COLORECTAL-CANCER; AH RECEPTOR; METABOLISM; CAFFEINE; PHENOTYPES; INDUCTION; MOUSE; RISK AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant of the heterocyclic amines found in cooked meat. Based on in vitro studies with rats and humans, CYP1A2 is believed to be the primary enzyme responsible for N-2-hydroxylation, the initial step in the metabolic activation of PhIP. To determine whether CYP1A2 is the primary P450 responsible for metabolic activation of PhIP in mice that leads to tumor formation, neonatal Cyp1a2-null and wild-type mice were treated with similar to11 (low dose) and similar to22 (high dose) mg/kg PhIP at days 8 and 15, corresponding cumulatively to 600 and 1200 nmol PhIP, and analyzed at 19-21 months of age. Three major induced tumors were found; lymphomas and tumors in lung and liver. The incidence of lymphoma was higher in Cyp1a2-null females than wild-type females treated with low dose (600 nmol) PhIP whereas no significant differences were observed in other treatment groups of mice. Overall differences in incidences of lung adenoma/adenocarcinoma were in general not consistent among sexes, genotypes and PhIP doses used, although reduced incidences of lung tumors were found in Cyp1a2-null males with low dose (600 nmol) and null females with high dose (1200 nmol) PhIP. Higher incidences of hepatocellular adenoma were observed in Cyp1a2-null female and male mice as compared with wild-type mice. In vitro studies using Cyp1a2-null and wild-type mouse liver microsomes revealed that CYP1A2 is the major enzyme required for PhIP N2-hydroxylation in mouse, the initial metabolic activation of PhIP that is thought to lead to tumor formation. These in vivo and in vitro results suggest that although the metabolic activation of PhIP is carried out primarily by CYP1A2, an unknown pathway unrelated to CYP1A2 appears to be responsible for PhIP carcinogenesis in mouse when examined in the neonatal bioassay. In fact, CYP1A2 may even be protective against all transformation, especially in females. C1 NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, Ft Detrick, MD 21702 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kimura, S (reprint author), NIH, Bldg 37,Room 2A19, Bethesda, MD 20892 USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 FU NCI NIH HHS [N01-CO-56000] NR 22 TC 32 Z9 34 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 MAR PY 2003 VL 24 IS 3 BP 583 EP 587 DI 10.1093/carcin/24.3.583 PG 5 WC Oncology SC Oncology GA 666AV UT WOS:000182154200030 PM 12663521 ER PT J AU Horvath-Arcidiacono, JA Tsuyuki, S Mostowski, H Bloom, ET AF Horvath-Arcidiacono, JA Tsuyuki, S Mostowski, H Bloom, ET TI Human natural killer cell activity against porcine targets: modulation by control of the oxidation-reduction environment and role of adhesion molecule interactions SO CELLULAR IMMUNOLOGY LA English DT Article DE NK cells; endothelial cells; adhesion molecules; transplantation; human ID HUMAN NK CELLS; DELAYED XENOGRAFT REJECTION; HUMAN ENDOTHELIAL-CELLS; LIVER SUPPORT SYSTEM; IN-VITRO; TRANSENDOTHELIAL MIGRATION; SIGNAL-TRANSDUCTION; REDOX REGULATION; NITRIC-OXIDE; T-CELLS AB Xenotransplantation, especially using porcine sources, has been proposed as a means to alleviate the shortage of human organs for transplantation. NK cells appear to be important mediators of the xenogeneic immune responses, including the human anti-pig response. Having previously established the redox regulation of NK cell activity against tumor target cells, we now report that the interaction of human NK cells with porcine target cells is also regulated by redox. Thiol-deprivation strongly diminished the capacity of IL-2-activated human NK cells to kill porcine endothelial cells. This inhibition correlated with reduced proliferation and interferon (IFN)-gamma production by IL-2-activated NK cells. For fresh NK cells, pretreatment with diethyl maleate (DEM), which was used to deplete intracellular thiols, reduced lysis of porcine and human targets. Because many adhesion molecules exhibit interspecies recognition, we further investigated whether changes in expression of adhesion molecules might explain our observations. DEM treatment reduced the expression of CD11b and CD29 on fresh NK cells. Monoclonal antibody blocking studies showed that the combination of mAb to CD11b and CD18 reduced lytic activity against both PAEC as well as K562, although other qualitative differences were observed between the porcine and human target cells. These findings suggest that the oxidative stress-induced downregulation of CD18 may be important in modulating cytotoxic activity of fresh NK cells against PAEC and K562 targets through reduced formation of the CD11b/CD18 heterodimer. Thus, the appropriate manipulation of redox status may provide a means to enhance survival of non-human animal tissues in humans through modulation of adhesion molecule expression/interactions. Published by Elsevier Science (USA). C1 US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Virol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Virol, Div Cellular & Gene Therapies, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 73 TC 4 Z9 5 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR PY 2003 VL 222 IS 1 BP 35 EP 44 DI 10.1016/S0008-8749(03)00082-0 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 689UL UT WOS:000183511300004 PM 12798306 ER PT J AU Cho, BP Yang, TL Blankenship, LR Moody, JD Churchwell, M Beland, FA Culp, SJ AF Cho, BP Yang, TL Blankenship, LR Moody, JD Churchwell, M Beland, FA Culp, SJ TI Synthesis and characterization of N-demethylated metabolites of malachite green and leucomalachite green SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ICTALURUS-PUNCTATUS TISSUE; LIQUID-CHROMATOGRAPHY; STABLE CARBOCATIONS; CHARGE DELOCALIZATION; TRIPHENYLMETHANE DYES; MASS-SPECTROMETRY; GENTIAN-VIOLET; CONFIRMATION; DERIVATIVES; INHIBITION AB Malachite green (MG), a triphenylmethane dye used to treat fungal and protozoan infections in fish, undergoes sequential oxidation to produce various N-demethylated derivatives (monodes-, dides(sym)-, dides(unsym)-, trides-, and tetrades-) both before and after reduction to leucomalachite green (LMG). The close structure resemblance of the metabolites with aromatic amine carcinogens implicates a potential genotoxicity from exposure to MG. The availability of the synthetic standards is important for metabolic and DNA adduct studies of MG. This paper describes a simple and versatile method for the synthesis of MG, LMG, and their N-demethylated metabolites. The synthesis involves a coupling of 4-(dimethylamino)benzophenone or 4-nitrobenzophenone with the aryllithium reagents derived from appropriately substituted 4-bromoaniline derivatives, followed by treatment with HCl in methanol. The resulting cationic MG and their leuco analogues showed systematic UV/vis spectral and tandem mass fragmentation patterns consistent with sequential N-demethylation. The extensive H-1 and C-13 spectral assignments of the metabolites were aided by the availability of C-13(7)-labeled MG and LMG. The results indicate the existence of a resonance structure with the cationic charge located in the central methane carbon (C-7). The synthetic procedure is general in scope so that it can be extended to the preparation off-demethylated metabolites of other structurally related N-methylated triphenylmethane dyes. C1 Univ Rhode Isl, Coll Pharm, Dept Biomed Sci, Kingston, RI 02881 USA. Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Cho, BP (reprint author), Univ Rhode Isl, Coll Pharm, Dept Biomed Sci, Kingston, RI 02881 USA. NR 31 TC 86 Z9 86 U1 0 U2 14 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 MAR PY 2003 VL 16 IS 3 BP 285 EP 294 DI 10.1021/tx0256679 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 661QL UT WOS:000181901200005 PM 12641428 ER PT J AU da Costa, GG Marques, MM Beland, FA Freeman, JP Churchwell, MI Doerge, DR AF da Costa, GG Marques, MM Beland, FA Freeman, JP Churchwell, MI Doerge, DR TI Quantification of tamoxifen DNA adducts using on-line sample preparation and HPLC-electrospray ionization tandem mass spectrometry SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID LAMBDA/LACI TRANSGENIC RATS; BREAST-CANCER PATIENTS; ALPHA-HYDROXYTAMOXIFEN; N-DESMETHYLTAMOXIFEN; IN-VIVO; ENDOMETRIAL SAMPLES; GENE-MUTATIONS; LIVER; IDENTIFICATION; SULFOTRANSFERASE AB The nonsteroidal antiestrogen tamoxifen is used as an adjuvant chemotherapeutic agent for the treatment of all stages of hormone-dependent breast cancer and more recently as a chemopreventive agent in women with elevated risk of developing the disease. While clearly beneficial for the treatment of breast cancer, tamoxifen has been reported to increase the risk of endometrial cancer in women. Furthermore, it has been shown to be hepatocarcinogenic in rats. Tamoxifen is clearly genotoxic in rat liver, as indicated by the formation of DNA adducts; the occurrence of tamoxifen DNA adducts in human endometrial tissue is more controversial. The detection and quantitation of tamoxifen DNA adducts have relied primarily upon P-32-postlabeling, with other techniques, such as immunoassays and accelerator mass spectrometry, being used to a much lesser extent. To expand the range of available analytical methodologies for quantifying tamoxifen DNA adducts, we have developed an assay using on-line sample preparation, coupled with HPLC and electrospray ionization tandem mass spectrometry (ES-MS/MS). alpha-Acetoxytamoxifen was reacted with salmon testis DNA at ratios between 0.1 ng and 1 mg alpha-acetoxytamoxifen per mg DNA. After enzymatic hydrolysis to nucleosides, the most highly modified DNA samples were analyzed by HPLC-UV, which indicated the presence of two adduct peaks in approximately a 1:4 ratio. The major adduct was isolated, rigorously characterized as (E)-alpha-(deoxyguanosin-N-2-yl)tamoxifen, and quantified on the basis of its molar extinction coefficient. A similar reaction was conducted with [N(CD3)(2)]-alpha-acetoxytamoxifen to prepare a deuterated adduct that could serve as an internal standard for ES-MS/MS. The limit of detection for the HPLC-ES-MS/MS method was approximately 5 adducts/10(9) nucleotides, with an intra- and interassay precision of 3% relative standard deviation. The method was validated over the range of 8-1 520 000 adducts/10(8) nucleotides using 100 mug samples of DNA modified in vitro. Analysis of liver DNA from female Sprague-Dawley rats treated by gavage with seven daily doses of 20 mg tamoxifen/kg body weight gave a value of 496 +/- 16 adducts/10(8) nucleotides for (E)-alpha-(deoxyguanosin-N-2-yl)tamoxifen and 626 +/- 18 adducts/10(8) nucleotides for (E)-alpha-(deoxyguanosin-N-2-yl)-N-desmethyltamoxifen. These data indicate that the HPLC-ES-MS/MS methodology has sufficient sensitivity and precision to be useful in the analysis of tamoxifen DNA adducts formed in vivo in experimental models and may be able to detect tamoxifen DNA adduct formation in human tissue samples. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Marques, MM (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM matilde.marques@ist.utl.pt; ddoerge@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 77 TC 26 Z9 26 U1 0 U2 4 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 MAR PY 2003 VL 16 IS 3 BP 357 EP 366 DI 10.1021/tx020090g PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 661QL UT WOS:000181901200013 ER PT J AU Lenz, P Thompson, CD Day, PM Bacot, SM Lowy, DR Schiller, JT AF Lenz, P Thompson, CD Day, PM Bacot, SM Lowy, DR Schiller, JT TI Interaction of papillomavirus virus-like particles with human myeloid antigen-presenting cells SO CLINICAL IMMUNOLOGY LA English DT Article DE papillomavirus; virus-like particles; dendritic cells; monocytes; macrophages; inflammatory cytokines; vaccine ID DENDRITIC CELLS; CERVICAL-CANCER; L1; AUTOANTIBODIES; IMMUNIZATION; INDUCTION; IMMUNITY; VACCINES; PROTEIN AB Papillomavirus-like particles (VLPs) are potent inducers of humoral and cellular immune responses, making them attractive candidates for noninfectious viral subunit vaccines. To further our understanding of how VLPs activate the immune system, we have investigated their interaction with human myeloid antigen-presenting cells. We found that VLPs bound, with increasing density, to the cell surface of human monocytes, macrophages, and monocyte-derived dendritic cells (DCs). Interestingly, there was a negative correlation between binding intensity and CD83 expression in DCs, suggesting that the main receptor for binding of VLPs may be downregulated during maturation. Exposure to VLPs resulted in acute phenotypic activation of monocytes and DCs. Furthermore, VLPs rapidly induced production of inflammatory cytokines in monocytes, macrophages, and DCs, as assessed by intracellular cytokine staining. For each cell type, the patterns of interleukin-1beta, interleukin-12, tumor necrosis factor-alpha, and interleukin-6 production were distinct from the pattern induced by lipopolysaccharide (LPS), a bacterial activator of myeloid antigen-presenting cells. Our results indicate that VLPs target multiple cells of the immune system, which helps to account for VLPs being so effective in priming humoral and cellular immune responses even in the absence of adjuvant. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, NIH, 37,Rm 4106,36 Convent Dr,MSC4040, Bethesda, MD 20892 USA. NR 19 TC 54 Z9 58 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 2003 VL 106 IS 3 BP 231 EP 237 DI 10.1016/S1521-6616(02)00039-6 PG 7 WC Immunology SC Immunology GA 672DG UT WOS:000182505400009 PM 12706410 ER PT J AU Hill, JM Patel, A Bhattacharjee, P Krause, PR AF Hill, JM Patel, A Bhattacharjee, P Krause, PR TI An HSV-1 chimeric containing HSV-2 latency associated transcript (LAT) sequences has significantly reduced adrenergic reactivation in the rabbit eye model SO CURRENT EYE RESEARCH LA English DT Article ID SIMPLEX VIRUS TYPE-1; GENITAL HERPES; GENE; EXPRESSION; APOPTOSIS; GENOME; REGION; SITE AB Purpose. Both HSV-1 and HSV-2 express LAT during viral latency. Previous studies indicated that deletion of either LAY impairs viral reactivation from latency, but that the HSV-1 LAT confers the ability to reactivate efficiently from trigeminal ganglia onto HSV-2. We sought to determine whether the HSV-2 LAY could function in the context of HSV-1. Methods. A chimeric HSV-1 that expresses the HSV-2 LAY in place of both copies of its own LAT was constructed. A rescuant virus, in which the wild-type genotype was restored, was also constructed to demonstrate that any phenotypic differences between the mutant virus and wild-type virus were due to the introduced mutations rather than to inadvertent mutations elsewhere in the virus. All viruses were tested in vitro and in vivo (via inoculation of rabbit eyes and induction of reactivation via iontophoresis of epinephrine) to determine the ability of the HSV-2 LAY to substitute for the HSV-1 LAT during acute infection and reactivation from latency. Results. Substitution of the HSV-2 LAY for the HSV-1 LAT had no effect on acute replication or on the ability of the virus to cause disease in the rabbit ocular model. The ability of the mutant virus to reactivate from latency was substantially impaired relative to wild-type HSV-1. Conclusions. The HSV-2 LAT cannot substitute for the HSV-1 LAT in promoting reactivation from HSV-1 latency from rabbit trigeminal ganglia. This is consistent with the LAT being the major determinant of site-specific HSV reactivation. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Louisiana State Univ, Ctr Eye, New Orleans, LA 70112 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 12 TC 9 Z9 11 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAR-APR PY 2003 VL 26 IS 3-4 BP 219 EP 224 DI 10.1076/ceyr.26.3.219.14896 PG 6 WC Ophthalmology SC Ophthalmology GA 700VF UT WOS:000184131300010 PM 12815550 ER PT J AU Marti, GE Carter, P Abbasi, F Washington, GC Jain, N Zenger, VE Ishibe, N Goldin, L Fontaine, L Weissman, N Sgambati, M Fauget, G Bertin, P Vogt, RF Slade, B Noguchi, PD Stetler-Stevenson, MA Caporaso, N AF Marti, GE Carter, P Abbasi, F Washington, GC Jain, N Zenger, VE Ishibe, N Goldin, L Fontaine, L Weissman, N Sgambati, M Fauget, G Bertin, P Vogt, RF Slade, B Noguchi, PD Stetler-Stevenson, MA Caporaso, N TI B-cell monoclonal lymphocytosis and B-cell abnormalities in the setting of familial B-cell chronic lymphocytic leukemia SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE familial B-cell chronic leukemia; flow cytometry; immunophenotyping; cell cycle analysis; CD5; CD20; B-cell monoclonal lymphocytosis; kappa/lambda; absolute lymphocyte count ID FLOW CYTOMETRIC ANALYSIS; UNDETERMINED SIGNIFICANCE; LYMPHOID LEUKEMIAS; ANTICIPATION; EXPRESSION; DNA; CLL; IMMUNOGLOBULIN; GUIDELINES; RELATIVES AB Background: Among all hematologic malignancies, B-cell chronic lymphocytic leukemia (BCLL) has the highest familial clustering (three- to sevenfold increase), strongly suggesting a genetic component to its etiology. Familial BCLL can be used as a model to study the early pathogenesis of this disease. Methods: We examined nine kindreds from the National Cancer Institute's Familial BCLL Registry, consisting of 19 affected members,with BCLL and 33 clinically unaffected first-degree relatives. Flow cytometric immuno-phenotyping to detect a B-cell monoclonal lymphocytosis (BCML) was performed. Monoclonality was confirmed by polymerase chain reaction analysis of whole blood DNA. Cell cycle analysis for aneuploidy was conducted. Results: In all affected individuals, we observed the classic BCLL CD5/CD19/CD20/CD23 immunophenotypic patterns. Six of the 33 unaffected individuals (18%) had evidence of BCML. Additional individuals (13/33, 39%) showed some other abnormality, whereas 14 individuals (42%) were normal. Based on an estimated prevalence of 0.7% for BCML in the general population, the finding of six subjects (18%) with clonal abnormalities in this relatively modest sample was significantly greater than expected (i.e., 18% vs. 0.7%, P < 5.7 x 10(-9)). Conclusions: Individual components of BCML and other B-cell abnormalities were observed in almost half of the apparently unaffected individuals. Our findings suggested that BCML may be an early detectable abnormality in BCLL. The spectrum of some of these observed abnormalities suggested the involvement of different B-cell subpopulations or different pathways in clonal evolution. Population-based, longitudinal studies will be required to determine the incidence of BCML and other B-cell abnormalities and their relation to disease progression in BCLL and other closely related B-cell lymphoproliferative disorders. Published 2003 Wiley-Liss, Inc.(dagger). C1 FDA, CBER, DCGT, Lab Stem Cell Biol,Flow & Image Cytometry Sect, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Rockville, MD USA. Med Coll Georgia, Vet Adm Med Ctr, Augusta, GA 30912 USA. Pontificia Univ Catolica Chile, Escuela Med, Lab Hematol Oncol, Santiago, Chile. Ctr Dis Control, Ctr Environm Hlth, Clin Biochem Branch, Immunol Sect, Atlanta, GA 30333 USA. Agcy Tox Substances & Dis Registry, Hlth Invest Branch, Div Hlth Studies, Atlanta, GA USA. NIH, Clin Flow Cytometry Sect, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), FDA, CBER, DCGT, Lab Stem Cell Biol,Flow & Image Cytometry Sect, NIH Bldg,29B,Room 2NN08,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 59 TC 87 Z9 90 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAR PY 2003 VL 52B IS 1 BP 1 EP 12 DI 10.1002/cyto.b.10013 PG 12 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 670TY UT WOS:000182426300001 PM 12599176 ER PT J AU Myers, MJ Farrell, DE Evock-Clover, CM Steele, NC AF Myers, MJ Farrell, DE Evock-Clover, CM Steele, NC TI Long-term recombinant porcine somatotropin (PST) treatment mitigates the responses to subchronic lipopolysaccharide in swine SO DOMESTIC ANIMAL ENDOCRINOLOGY LA English DT Article DE heat shock protein 70; urea nitrogen; insulin; glucose; aspartate transaminase ID ACUTE-PHASE RESPONSE; GROWING PIGS; RECURRENT ENDOTOXEMIA; CYTOKINE PRODUCTION; GROWTH-PERFORMANCE; DIETARY-PROTEIN; CHALLENGE; TOLERANCE; IMMUNE; METABOLITES AB The effect of multiple lipopolysaccharide (LPS) challenges in swine undergoing long-term treatment with porcine somatotropin (PST) was determined. Changes in aspartate serine transaminase (AST) occurred only at 24 It following the first LPS challenge dose (P<0.05), while PST treatment moderated any change from occurring. Nonesterified free fatty acid (NEFA) levels were elevated in PST treated animals for the first 3 days following daily LPS treatment (P<0.05), while LPS treatment alone had no effect on plasma NEFA levels. Plasma urea nitrogen (PUN) levels were unchanged by LPS following the initial LPS challenge, but were decreased following the second challenge dose (P=0.014). These changes were long lasting, with a return to normal PUN levels not evident until Day 6. The PST treatment mitigated changes in PUN (P<0.05) when LPS was administered. Haptoglobin plasma levels, along with lipid peroxide production were not affected by LPS challenge or PST administration. LPS challenge reduced the levels of immunoreactive heat shock protein 70 (HSP70) throughout the entire challenge period (P<0.001). PST-LPS animals had normal levels of this protein. The results of the present study demonstrate that long-term PST treatment mitigates the adverse effects of subchronic LPS administration. (C) 2002 Elsevier Science Inc. All rights reserved. C1 US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. USDA ARS, Growth Biol Lab, Beltsville, MD 20705 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 42 TC 0 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0739-7240 J9 DOMEST ANIM ENDOCRIN JI Domest. Anim. Endocrinol. PD MAR PY 2003 VL 24 IS 2 BP 155 EP 170 DI 10.1016/S0739-7240(02)00234-5 PG 16 WC Agriculture, Dairy & Animal Science; Endocrinology & Metabolism SC Agriculture; Endocrinology & Metabolism GA 648JH UT WOS:000181147300005 PM 12586315 ER PT J AU Shade, L Beger, RD Wilkes, JG AF Shade, L Beger, RD Wilkes, JG TI The use of carbon thirteen nuclear magnetic resonance spectra to predict dioxin and furan binding affinities to the aryl hydrocarbon receptor SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE spectroscopic data-activity relationships; nuclear magnetic resonance; polychlorodibenzo-p-dioxins; polychlorodibenzofurans; aryl hydrocarbon receptor ID POLYCHLORINATED DIBENZOFURANS PCDFS; HYDROXYLASE INDUCTION POTENCIES; C-13 NMR; SPECTROMETRIC DATA; ESTROGEN-RECEPTOR; AROMATIC-HYDROCARBONS; AHH INDUCTION; P-DIOXINS; FLY-ASH; MECHANISM AB Four spectroscopic data-activity relationship (SDAR) models for polychlorinated dibenzofurans (PCDFs) and dibenzodioxins (PCDDs) binding to the aryl hydrocarbon receptor (AhR) have been developed based on simulated C-13 nuclear magnetic resonance (NMR) data. Models were developed using discriminant function analysis of the compounds' spectral data. An SDAR model with two classifications for 26 PCDF compounds had a leave-one-out (LOO) cross-validation accuracy of 89%. A two-classification SDAR model for 14 PCDD compounds had LOO cross-validation accuracy of 95%. A two-classification SDAR model combining 14 PCDD and 26 PCDF compounds had LOO cross-validation accuracy of 88%, while a four-classification SDAR model based on the same 14 PCDD and 26 PCDF compounds had LOO cross-validation accuracy of 92%. We used each appropriate SDAR model to classify 41 PCDD and/or 121 PCDF compounds with unknown binding affinities to the AhR. The SDAR models provide a rapid, simple, and valid way to model the PCDF and PCDD binding activity in relation to the AhR. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. NR 40 TC 11 Z9 11 U1 0 U2 1 PU SETAC PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3367 USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD MAR PY 2003 VL 22 IS 3 BP 501 EP 509 DI 10.1897/1551-5028(2003)022<0501:TUOCTN>2.0.CO;2 PG 9 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 647JE UT WOS:000181089000006 PM 12627635 ER PT J AU Ardekani, AM Petricoin, EF Hackett, JL AF Ardekani, AM Petricoin, EF Hackett, JL TI Molecular diagnostics: an FDA perspective SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material DE diagnostics; FDA; microarrays ID HUMAN PROSTATE-CANCER; PROTEIN MICROARRAYS; BREAST-CANCER; DNA; PHARMACOGENETICS; PATTERNS; SURVIVAL; PROFILES; DISEASE; GENOME AB The potential medical applications of microarrays and in vitro diagnostic devices for global assessments of DNA, sequence variations, relative RNA abundance and measurements of proteins have generated much excitement, and some skepticism, within the biomedical community. It has been suggested that within the next decade these microarrays and diagnostic devices will be routinely used in the selection, assessment and quality control of the best drugs for pharmaceutical development, at the bedside for diagnostics and for clinical monitoring of both desired and adverse outcomes of therapeutic interventions. Realizing such potential will be a challenge to the entire scientific community as often breakthroughs which show great promise at the bench fall to meet the requirements of clinicians and regulatory scientists, and to make the transition into common clinical and regulatory practice. The development of a co-operative framework between regulators, product sponsors and technology experts will be essential for realizing the revolutionary promise these platforms could have on the evolution of drug development, regulatory science, the practice of medicine and public health. C1 CLIA Special Program, Div Clin Lab Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NCI, FDA, Clin Proteom Program, Proteom Unit, Bethesda, MD 20892 USA. US FDA, CBER, Dept Therapeut Prot, Bethesda, MD 20892 USA. RP Hackett, JL (reprint author), OAK8, RM375, HFZ 440 2098, Gaither Rd Rockville, Rockville, MD 20850 USA. EM Ardekani@cber.fda.gov; Petricoin@cber.fda.gov; JLH@cdrh.fda.gov NR 34 TC 8 Z9 10 U1 0 U2 5 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAR PY 2003 VL 3 IS 2 BP 129 EP 140 DI 10.1586/14737159.3.2.129 PG 12 WC Pathology SC Pathology GA 767KA UT WOS:000188437700002 PM 12647991 ER PT J AU Ilev, IK Waynant, RW Byrnes, KR Anders, JJ AF Ilev, IK Waynant, RW Byrnes, KR Anders, JJ TI On-off laser delivery into a precise tissue area using smart tissue-activated fiber probes SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE laser delivery; mid-infrared (mid-IR) laser delivery; smart optical fiber probes; tissue illumination; total-internal reflectance ID UNCOATED HOLLOW TAPER AB A novel and simple concept for on-off switching laser radiation delivery into a precise tissue area using tissue-activated optical fiber probes is demonstrated. The authors present the operating principle and general optical features of the fiber-optic-based delivery technique. The basic idea includes the use of a single delivery fiber with a specially shaped angled tip. Because of the frustrated-total-internal reflectance caused by the refractive-index change of the surrounding medium, the angled fiber tip acts as a smart tissue-activated probe. It provides a safe way for laser delivery that includes only two states of tissue illumination: 1) off-state (no tissue illumination), when the fiber tip is out of the tissue area and the laser emission is backreflected due to total-internal-reflection and 2) on-state (maximum tissue illumination), when the fiber tip is on the absorbing tissue area and becomes "transparent" because of the frustrated-total-internal reflectance. Here, optical properties of tissue-activated fiber probes used for precise laser delivery are investigated both experimentally and theoretically by analyzing the backreflectance signal power. Optical fibers working in the visible and mid-infrared spectral regions with various geometrical parameters are used and a spatial resolution of 2 Am is achieved when the fiber tip is moved toward the absorption tissue surface. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. OI Byrnes, Kimberly/0000-0002-7501-7734 NR 13 TC 3 Z9 3 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD MAR-APR PY 2003 VL 9 IS 2 BP 331 EP 336 DI 10.1109/JSTQE.2003.814197 PG 6 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 735VK UT WOS:000186135100024 ER PT J AU Smith, WE Kane, AV Campbell, ST Acheson, DWK Cochran, BH Thorpe, CM AF Smith, WE Kane, AV Campbell, ST Acheson, DWK Cochran, BH Thorpe, CM TI Shiga toxin 1 triggers a ribotoxic stress response leading to p38 and JNK activation and induction of apoptosis in intestinal epithelial cells SO INFECTION AND IMMUNITY LA English DT Article ID PROTEIN-KINASE; PATHOGENESIS; EXPRESSION; GENE AB Shiga toxins made by Shiga toxin-producing Escherichia coli (STEC) are associated with hemolytic uremic syndrome. Shiga toxins (Stxs) may access the host systemic circulation by absorption across the intestinal epithelium. The effects of Stxs on this cell layer are not completely understood, although animal models of STEC infection suggest that, in the gut, Stxs may participate in both immune activation and apoptosis. Stxs have one enzymatically active A subunit associated with five identical B subunits. The A subunit inactivates ribosomes by cleaving a specific adenine from the 28S rRNA. We have previously shown that Stxs can induce multiple C-X-C chemokines in intestinal epithelial cells in vitro, including interieukin-8 (IL-8), and that Stx-induced IL-8 expression is linked to induction of c-Jun mRNA and p38 mitogen-activated protein (MAP) kinase pathway activity. We now report Stx1 induction of both primary response genes c-jun and c-fos and activation of the stress-activated protein kinases, JNK/SAPK and p38, in the intestinal epithelial cell line HCT-8. By I h of exposure to Stx1, mRNAs for c-jun and c-fos are induced, and both JNK and p38 are activated; activation of both kinases persisted up to 24 h. Stx1 enzymatic activity was required for kinase activation; a catalytically defective mutant toxin did not activate either. Stx1 treatment of HCT-8 cells resulted in cell death that was associated with caspase 3 cleavage and internucleosomal DNA fragmentation; this cytotoxicity also required Stx1 enzymatic activity. Blocking Stx1-induced p38 and JNK activation with the inhibitor SB202190 prevented cell death and diminished Stx1-associated caspase 3 cleavage. In summary, these data link the Stx1-induced ribotoxic stress response with both chemokine expression and apoptosis in the intestinal epithelial cell line HCT-8 and suggest that blocking host cell MAP kinases may prevent these Stx-associated events. C1 Tufts Univ, Div Geog Med & Infect Dis, New England Med Ctr, Dept Med, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Thorpe, CM (reprint author), Tufts Univ, Div Geog Med & Infect Dis, New England Med Ctr, Dept Med, 750 Washington St,Box 041, Boston, MA 02111 USA. OI Cochran, Brent/0000-0002-7598-5604 FU NIAID NIH HHS [AI-01715, AI-07389, T32 AI007389]; NIDDK NIH HHS [P30 DK034928, P30DK-34928] NR 26 TC 125 Z9 131 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2003 VL 71 IS 3 BP 1497 EP 1504 DI 10.1128/IAI.71.3.1497-1504.2003 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 650NU UT WOS:000181270900056 PM 12595468 ER PT J AU Smith, MA Takeuchi, K Brackett, RE McClure, HM Raybourne, RB Williams, KM Babu, US Ware, GO Broderson, JR Doyle, MP AF Smith, MA Takeuchi, K Brackett, RE McClure, HM Raybourne, RB Williams, KM Babu, US Ware, GO Broderson, JR Doyle, MP TI Nonhuman primate model for Listeria monocytogenes-induced stillbirths SO INFECTION AND IMMUNITY LA English DT Article ID SPORADIC LISTERIOSIS; SALMONELLA; CHOCOLATE; OUTBREAK; INFECTION; EPIDEMIC; CHEESE; FOODS AB Listeria monocytogenes, isolated from outbreaks in either human or nonhuman primate populations, was administered orally at doses ranging from 10(6) to 10(10) CFU. Four of 10 treated animals delivered stillborn infants. L. monocytogenes was isolated from fetal tissue, and the pathology was consistent with L. monocytogenes infection as the cause of pregnancy loss. For all pregnancies resulting in stillbirths, L. monocytogenes was isolated from maternal feces, indicating that L. monocytogenes had survived and had probably colonized the gastrointestinal tract. Antibodies and antigen-specific lymphocyte proliferation against Listeria increased in animals that had stillbirths. C1 Univ Georgia, Dept Environm Hlth Sci, Athens, GA 30602 USA. Univ Georgia, Off Vice President Res, Athens, GA 30602 USA. Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. US FDA, Laurel, MD 20708 USA. RP Smith, MA (reprint author), Univ Georgia, Dept Environm Hlth Sci, 206 Environm Hlth Sci Bldg, Athens, GA 30602 USA. FU NCRR NIH HHS [RR0016] NR 38 TC 45 Z9 49 U1 1 U2 3 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 2003 VL 71 IS 3 BP 1574 EP 1579 DI 10.1128/IAI.71.3.1574-1579.2003 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 650NU UT WOS:000181270900068 PM 12595480 ER PT J AU Debrabant, A Lee, N Bertholet, S Duncan, R Nakhasi, HL AF Debrabant, A Lee, N Bertholet, S Duncan, R Nakhasi, HL TI Programmed cell death in trypanosomatids and other unicellular organisms SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Review DE programmed cell death; unicellular organisms; multicellular organisms; parasites; cellular growth; anti parasitic drugs ID LEISHMANIA-DONOVANI PROMASTIGOTES; YEAST SACCHAROMYCES-CEREVISIAE; CYTOCHROME-C RELEASE; APOPTOSIS-LIKE DEATH; PARASITE LEISHMANIA; DNA FRAGMENTATION; ESCHERICHIA-COLI; OXIDATIVE STRESS; MAMMALIAN-CELLS; NITRIC-OXIDE AB In multicellular organisms. cellular growth and development can be controlled by programmed cell death (PCD). which is defined by a sequence of regulated events. However, PCD is thought to have evolved not only to regulate growth and development in multicellular organisms but also to have a functional role in the biology of unicellular organisms. In protozoan parasites and in other unicellular organisms. features of PCD similar to those in multicellular organisms have been reported. suggesting some commonality in the PCD pathway between unicellular and multicellular organisms. However er. more extensive Studies are needed to fully characterise the PCD pathway and to define the factors that control PCD in the unicellular organisms. The understanding of the PCD pathway in unicellular organisms Could delineate the evolutionary origin of this pathway . Further characterisation of the PCD pathway the unicellular parasites Could provide information regarding their pathogenesis, which could be exploited to target new drugs to limit their growth and treat the disease they cause. Published by Elsevier Science Ltd. on behalf of Australian Society for Parasitology Inc. C1 US FDA, OBRR, CBER, DETTD,Lab Bacterial Parasit & Unconvent Agents, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nakhasi, HL (reprint author), US FDA, OBRR, CBER, DETTD,Lab Bacterial Parasit & Unconvent Agents, HFM-310,Bldg 29,Room 222,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 76 TC 112 Z9 117 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD MAR PY 2003 VL 33 IS 3 BP 257 EP 267 DI 10.1016/S0020-7519(03)00008-0 PG 11 WC Parasitology SC Parasitology GA 669PF UT WOS:000182359100003 PM 12670511 ER PT J AU Sweeney, C Ambrosone, CB Joseph, L Stone, A Hutchins, LF Kadlubar, FF Coles, BF AF Sweeney, C Ambrosone, CB Joseph, L Stone, A Hutchins, LF Kadlubar, FF Coles, BF TI Association between a glutathione S-transferase A1 promoter polymorphism and survival after breast cancer treatment SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE glutathione S-transferase; polymorphism; breast cancer; survival ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CYCLOPHOSPHAMIDE; EXPRESSION; CHEMOTHERAPY; METHOTREXATE; FLUOROURACIL; CONJUGATION; ISOENZYMES; GSTM1; GSTT1 AB Glutathione S-transferase (GST) enzymes detoxify chemotherapeutic drugs, and several studies have reported differences in survival for cancer patients who have variant genotypes for GSTP1, GSTM1 or GSTT1 enzymes. A recently described polymorphism alters hepatic expression of GSTA1, a GST with high activity in glutathione conjugation of metabolites of cyclophosphamide (CP). To consider the possible influence of the reduced-expression GSTA1*B allele on cancer patient survival, we have conducted a pilot study of breast cancer patients treated with CP-containing combination chemotherapy. GSTA1 genotype was determined by polymerase chain reaction and restriction fragment length polymorphism. Kaplan-Meier methods and Cox proportional hazards models were used to evaluate survival in relation to genotype. Among 245 subjects, 35% were GSTA1*A/*A, 49% GSTA1*A/*B and 16% GSTA1*B/*B; the genotype distribution did not differ by ethnic group, age or stage at diagnosis. Among patients who had 0 or 1 GSTA1*B allele, the proportion surviving at 5 years was 0.66 (95% Cl = 0.59-0.72), whereas for GSTA1 *B/*B subjects the proportion was higher, 0.86 (95% Cl = 0.67-0.95). Significantly reduced hazard of death was observed for GSTA1*B/*8 subjects during the first 5 years after diagnosis, hazard ratio (HR) = 0.3, 95% CI = 0.1-0.8. The association varied with time, with no survival difference observed for subjects who survived beyond 5 years. These results, although based on a small study population, describe an apparent difference in survival after treatment for breast cancer according to GSTA I genotype. Further studies should consider the possible association between the novel GSTA 1 *B variant and outcomes of cancer therapy. (C) 2002 Wiley-Liss, Inc. C1 Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY USA. Univ Arkansas Med Sci, Coll Med, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Surg Serv, Little Rock, AR USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Sweeney, C (reprint author), Univ Minnesota, Div Epidemiol, 1300 S 2nd St 300, Minneapolis, MN 55454 USA. OI Sweeney, Carol/0000-0003-1113-7160 NR 26 TC 59 Z9 69 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 2003 VL 103 IS 6 BP 810 EP 814 DI 10.1002/ijc.10896 PG 5 WC Oncology SC Oncology GA 639PX UT WOS:000180639400017 PM 12516103 ER PT J AU Sheldon, AT AF Sheldon, AT TI Antibiotic resistance: Who is winning the war? Introductory remarks SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Editorial Material DE antimicrobial; interagency; resistance; surveillance; toxicology AB The evolutionary response of bacteria, fungi, viruses, and parasites to the selective pressure exerted by antimicrobial agents is the emergence of populations that resist the action of the antimicrobial. The emergence and dissemination of such resistance in a variety of these pathogens is a growing public health concern. In response, the scientific community developed an action plan to address this public health issue. Antimicrobial, antifungal, and antiviral drug development for the treatment of diseases caused by resistant pathogens is one component of this strategy. In addition, due to the targeting of specific drugs against resistant pathogens, we may more readily accept a given drugs toxicity profile for the added therapeutic benefit. This symposium provides a discussion of the modes of action and mechanisms of resistance to antimicrobial agents, and the use of surveillance systems to help understand the nature and magnitude of resistance. The goal is to help guide antimicrobial drug product development and use. Specific toxicity issues are presented that should be considered in phase 1 development of antimicrobial drug products for use in clinical medicine and veterinary medicine. Finally, the national and global strategies developed by federal agencies in the Public Health Action Plan to Combat Antimicrobial Resistance are outlined. C1 US FDA, Ctr Drug Evaluat & Res, Div Antiinfect Drug Prod, Rockville, MD 20850 USA. RP Sheldon, AT (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Antiinfect Drug Prod, 9201 Corp Blvd, Rockville, MD 20850 USA. NR 5 TC 4 Z9 4 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAR-APR PY 2003 VL 22 IS 2 BP 129 EP 130 DI 10.1080/10915810390198401 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 663UP UT WOS:000182024900008 PM 12745993 ER PT J AU Greenlees, KJ AF Greenlees, KJ TI Animal drug human food safety toxicology and antimicrobial resistance - The square peg SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 22nd Annual Conference of the American-College-of-Toxicology CY NOV 04-08, 2001 CL WASHINGTON, D.C. SP American Coll Toxicol DE animal drug; antimicrobial resistance; food safety; microbiology; toxicology; veterinary medicine ID ANTIBIOTIC USE; HEALTH AB This paper presents the traditional approach for the evaluation of human food safety used for animal drugs intended for food animals, and describes some of the difficulties posed by antimicrobial drug resistance. Like human drugs, animal drugs must be safe and effective for the patient. However, unlike human drugs, food derived from animals treated with the animal drug must also be shown to be safe for human consumption. The Food and Drug Administration has come to realize that antimicrobial drugs used in the treatment of the food animal have the potential to create a unique residue-increased numbers of microorganism that are resistant to antimicrobial drug treatment. The traditional toxicological paradigm for chemical residues does not apply to this unique microbiological residue. Information useful to a food safety evaluation may include the potential for the animal antimicrobial drug to diminish the susceptibility of microorganisms to human antimicrobial drugs, any human medical use of the drug, relationship to other human antimicrobial drugs, and the ability of the animal drug to alter the susceptibility of relevant microorganism to important human antimicrobial drugs. Yet to be developed are standardized approaches to quantify an acceptable level of resistant microorganism in food and to mitigate the hazard to assure that there is a reasonable certainty of no harm following the consumption of the edible food derived from the treated animal. C1 US FDA, DABT, Toxicol Team, Ctr Vet Med, Rockville, MD 20855 USA. RP Greenlees, KJ (reprint author), US FDA, DABT, Toxicol Team, Ctr Vet Med, HFV-153,7500 Standish Pl, Rockville, MD 20855 USA. NR 7 TC 11 Z9 11 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAR-APR PY 2003 VL 22 IS 2 BP 131 EP 134 DI 10.1080/10915810390198393 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 663UP UT WOS:000182024900009 PM 12745994 ER PT J AU McDermott, PF Walker, RD White, DG AF McDermott, PF Walker, RD White, DG TI Antimicrobials: Modes of action and mechanisms of resistance SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 22nd Annual Conference of the American-College-of-Toxicology CY NOV 04-08, 2001 CL WASHINGTON, D.C. SP American Coll Toxicol DE antimicrobial; DNA mobile elements; efflux; integrons; mutation; resistance ID GRAM-NEGATIVE BACTERIA; MOBILE GENE CASSETTES; ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; MULTIDRUG-RESISTANCE; CHLORAMPHENICOL RESISTANCE; FLUOROQUINOLONE RESISTANCE; MYCOBACTERIUM-SMEGMATIS; INTEGRONS; EPIDEMIOLOGY AB After six decades of widespread antibiotic use, bacterial pathogens of human and animal origin are becoming increasingly resistant to many antimicrobial agents. Antimicrobial resistance develops through a limited number of mechanisms: (a) permeability changes in the bacterial cell wall/membrane, which restrict antimicrobial access to target sites; (b) active efflux of the antimicrobial from the cell; (c) mutation in the target site; (d) enzymatic modification or degradation of the antimicrobial; and (e) acquisition of alternative metabolic pathways to those inhibited by the drug. Numerous bacterial antimicrobial resistance phenotypes result from the acquisition of external genes that may provide resistance to an entire class of antimicrobials. These genes are frequently associated with large transferable extrachromosomal DNA elements called plasmids, on which may be other mobile DNA elements such as transposons and integrons. An array of different resistance genes may accumulate on a single mobile element, presenting a situation in which multiple antibiotic resistance can be acquired via a single genetic event. The versatility of bacterial populations in adapting to toxic environments, along with their facility in exchanging DNA, signifies that antibiotic resistance is an inevitable biological phenomenon that will likely continue to be a chronic medical problem. Successful management of current antimicrobials, and the continued development of new ones, is vital to protecting human and animal health against bacterial pathogens. C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP McDermott, PF (reprint author), US FDA, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 42 TC 71 Z9 77 U1 9 U2 35 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAR-APR PY 2003 VL 22 IS 2 BP 135 EP 143 DI 10.1080/10915810390198410 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 663UP UT WOS:000182024900010 PM 12745995 ER PT J AU Luo, WH Ang, CYW Gehring, TA Heinze, TM Lin, LJ Mattia, A AF Luo, WH Ang, CYW Gehring, TA Heinze, TM Lin, LJ Mattia, A TI Determination of phenolic compounds in dietary supplements and tea blends containing Echinacea by liquid chromatography with coulometric electrochemical detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ALKAMIDE LEVELS; PURPUREA; ROOTS AB Analytical methodologies with ultrasonic extraction and liquid chromatography (LC) were developed for the determination of phenolic compounds in dietary supplements containing Echinacea. The phenolic compounds determined by these methods included caftaric acid, chlorogenic acid, cynarin, echinacoside, and cichoric acid. Samples from tablets, capsules, and bags of tea blends were extracted by sonication for less than or equal to30 min with methanol-water (60+40). The extracts were centrifuged and filtered, and the filtrates were diluted and analyzed by LC using a reversed-phase column and coulometric electrochemical (EC) detection. The mobile phase was acetonitrile-ammonium formate buffer, pH 3.5 (15.3+84.7) containing tetrabutyl ammonium hydrogen sulfate as an ion-pairing reagent. Extraction conditions (e.g., composition of the extraction solvent and sonication time) were optimized for different types of samples. Intra- and interday analytical variations were determined, and intraday analyses were performed by 2 independent analysts using 2 different LC systems. Results were generally comparable. The LC method with EC detection showed better sensitivity and selectivity when compared with LC with ultraviolet detection, although results were similar for the 2 methods for major compounds, i.e., caftaric acid, echinacoside, and cichoric acid. The identities of these major compounds found in samples were confirmed by LC/electrospray ionization mass spectrometry. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Shantou Univ, Coll Med, Cent Lab, Shantou 515031, Guangdong, Peoples R China. US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Petit Review, College Pk, MD 20740 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd,HFT-230, Jefferson, AR 72079 USA. EM cang@nctr.fda.gov NR 15 TC 15 Z9 19 U1 2 U2 3 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2003 VL 86 IS 2 BP 202 EP 208 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 665UC UT WOS:000182138800002 PM 12723906 ER PT J AU Ferreira, JL Maslanka, S Johnson, E Goodnough, M AF Ferreira, JL Maslanka, S Johnson, E Goodnough, M TI Detection of botulinal neurotoxins A, B, E, and F by amplified enzyme-linked immunosorbent assay: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TOXIN; ELISA AB An amplified enzyme-linked immunosorbent assay (amp-ELISA) was compared with the AOAC Official Method 977.26 for detection of Clostridium botulinum and its toxins in foods. Eleven laboratories participated and the results of 10 laboratories were used in the study. Two anaerobic culture media, tryptone peptone glucose yeast extract (TPGY) and cooked meat medium (CMM) were used to generate toxic samples with types A, B, E, and F botulinal strains. Nonbotulinal clostridia were also tested. The toxicity of each botulinal culture was determined by the AOAC method, and the cultures were then diluted, if necessary, to high (about 10 000 minimal lethal dose [MLD]/mL) and low (about 100 MLD/mL) test samples. The overall sensitivity of detection in TPGY and CMM cultures with the amp-ELISA was 94.7% at about 100 MLD/mL and 99.6% for samples with greater than or equal to10 000 MLD/mL toxicity. The amp-ELISA detection sensitivity for low toxin samples was 92.3% in TPGY and 99.4%, in CMM. The false-positive rate ranged from 1.5% for type A to 28.6% for type F in TPGY, and from 2.4% for type A to 11.4% for type F in CMM. Most of the cross-reactivity was due to detection of other botulinal types, especially in high toxin samples. The amp-ELISA could be used to screen suspect cultures for botulinal toxins. Positive amp-ELISA samples would be confirmed by the AOAC reference method. C1 US FDA, Atlanta, GA 30309 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Univ Wisconsin, Dept Food Microbiol & Toxicol, Madison, WI 53706 USA. RP Ferreira, JL (reprint author), US FDA, 60 8th St NE, Atlanta, GA 30309 USA. NR 7 TC 57 Z9 60 U1 0 U2 13 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 2003 VL 86 IS 2 BP 314 EP 331 PG 18 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 665UC UT WOS:000182138800013 PM 12723917 ER PT J AU Anastassiades, M Lehotay, SJ Stajnbaher, D Schenck, FJ AF Anastassiades, M Lehotay, SJ Stajnbaher, D Schenck, FJ TI Fast and easy multiresidue method employing acetonitrile extraction/partitioning and "dispersive solid-phase extraction" for the determination of pesticide residues in produce SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID GAS-CHROMATOGRAPHIC DETERMINATION; SUPERCRITICAL-FLUID EXTRACTION; ACCELERATED SOLVENT-EXTRACTION; GEL-PERMEATION CHROMATOGRAPHY; FLAME PHOTOMETRIC DETECTION; PULSED SPLITLESS INJECTION; MASS-SPECTROMETRY; ORGANOPHOSPHORUS PESTICIDES; SAMPLE PREPARATION; MEASUREMENT UNCERTAINTY AB A simple, fast, and inexpensive method for the determination of pesticide residues in fruits and vegetables is introduced. The procedure involves initial single-phase extraction of 10 g sample with 10 mL acetonitrile, followed by liquid-liquid partitioning formed by addition of 4 g anhydrous MgSO(4) Plus 1 g NaCl. Removal of residual water and cleanup are performed simultaneously by using a rapid procedure called dispersive solid-phase extraction (dispersive-SPE), in which 150 mg anhydrous MgSO(4) and 25 mg primary secondary amine (PSA) sorbent are simply mixed with 1 mL acetonitrile extract. The dispersive-SPE with PSA effectively removes many polar matrix components, such as organic acids, certain polar pigments, and sugars, to some extent from the food extracts. Gas chromatography/mass spectrometry (GC/MS) is then used for quantitative and confirmatory analysis of GC-amenable pesticides. Recoveries between 85 and 101% (mostly >95%) and repeatabilities typically <5% have been achieved for a wide range of fortified pesticides, including very polar and basic compounds such as methamidophos, acephate, omethoate, imazalil, and thiabendazole. Using this method, a single chemist can prepare a batch of 6 previously chopped samples in <30 min with approximately $1 (U.S.) of materials per sample. C1 ARS, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. Inst Publ Hlth, Environm Protect Inst, Maribor 2000, Slovenia. US FDA, Off Regulatory Affairs, SE Reg Lab, Atlanta, GA 30309 USA. RP Lehotay, SJ (reprint author), ARS, USDA, Eastern Reg Res Ctr, 600 E Mermaid Ln, Wyndmoor, PA 19038 USA. EM slehotay@arserrc.gov NR 68 TC 1797 Z9 2034 U1 67 U2 553 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2003 VL 86 IS 2 BP 412 EP 431 PG 20 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 665UC UT WOS:000182138800023 PM 12723926 ER PT J AU Boam, AB Eydelman, MB Lum, FC Silverman, PM Apple, DJ Werner, L Pandey, SK AF Boam, AB Eydelman, MB Lum, FC Silverman, PM Apple, DJ Werner, L Pandey, SK TI Retrospective evaluation of intraocular lenses in adults younger than 60 years SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT 105th Annual Meeting of the American-Academy-of-Ophthalmology CY NOV 11-14, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Acad Ophthalmol ID ANTERIOR-CHAMBER LENSES; 10-YEAR FOLLOW-UP; LONG-TERM SAFETY; CLINICAL-ASSESSMENT; CAPSULAR BAG; IMPLANTATION; COMPLICATIONS; PRESSURE; EFFICACY; 3-PIECE AB Data from the U.S. Food and Drug Administration, the American Academy of Ophthalmology's National Eyecare Outcomes Network, and Storm Eye Institute databases were analyzed for short- and long-term safety and efficacy outcomes of intraocular lens (IOL) implantation in adults younger than 60 years and 60 years and older. Statistical analyses for significance were performed where appropriate. A comprehensive literature review was conducted to identify safety and efficacy outcomes and their relationship to patient age at the time of implantation. Analyses established that the performance of IOLs in adults younger than 60 years was comparable to that in adults older than 60 years and supported the use of IOLs in the younger adult population. C1 US FDA, Rockville, MD 20850 USA. Amer Acad Ophthalmol, San Francisco, CA USA. Med Univ S Carolina, Storm Eye Inst, Ctr Res Ocular Therapeut & Biodevices, Charleston, SC 29425 USA. RP Boam, AB (reprint author), US FDA, 9200 Corp Blvd,HFS-460, Rockville, MD 20850 USA. NR 31 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD MAR PY 2003 VL 29 IS 3 BP 575 EP 587 DI 10.1016/S0886-3350(02)01845-X PG 13 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 663KQ UT WOS:000182005100039 PM 12663027 ER PT J AU Tong, WD Hong, HX Fang, H Xie, Q Perkins, R AF Tong, WD Hong, HX Fang, H Xie, Q Perkins, R TI Decision forest: Combining the predictions of multiple independent decision tree models SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Chemical Structures CY JUN, 2002 CL NOORDWIJKERHOUT, NETHERLANDS SP Amer Chem Soc, Div Chem Informat, Chem Struct Assoc Trust, Soc German Chemists, Chem Informat Comp Div, Chem Soc Japan, Div Chem Informat & Comp Sci, Swiss Chem Soc, Royal Netherlands Chem Soc, Royal Soc Chem, Chem Informat Grp ID ESTROGEN-RECEPTOR; CLASSIFICATION; SET AB The techniques of combining the results of multiple classification models to produce a single prediction have been investigated for many years. In earlier applications, the multiple models to be combined were developed by altering the training set. The use of these so-called resampling techniques, however, poses the risk of reducing predictivity of the individual models to be combined and/or over fitting the noise in the data, which might result in poorer prediction of the composite model than the individual models. In this paper, we suggest a novel approach, named Decision Forest, that combines multiple Decision Tree models. Each Decision Tree model is developed using a unique set of descriptors. When models of similar predictive quality are combined using the Decision Forest method, quality compared to the individual models is consistently and significantly improved in both training and testing steps. An example will be presented for prediction of binding affinity of 232 chemicals to the estrogen receptor. C1 Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Northrop Grunman Informat Technol, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, 3900 NCTR Rd,HFT 20, Jefferson, AR 72079 USA. NR 37 TC 117 Z9 123 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD MAR-APR PY 2003 VL 43 IS 2 BP 525 EP 531 DI 10.1021/ci020058s PG 7 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 661KF UT WOS:000181889200024 PM 12653517 ER PT J AU Beck, P Wysowski, DK Downey, W Butler-Jones, D AF Beck, P Wysowski, DK Downey, W Butler-Jones, D TI Statin use and the risk of breast cancer SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE statin drugs; breast cancer; lipid-lowering drugs; hormone replacement therapy; postmenopausal women; Saskatchewan ID REPLACEMENT THERAPY; CHOLESTEROL; HYPERCHOLESTEROLEMIA; PRAVASTATIN; HEALTH; DRUGS AB The study objective was to investigate a possible association between statin use and breast cancer (BRCA). An historical cohort design based on Saskatchewan's population health services databases was used. All eligible women with greater than or equal to1 statin prescription from 1989 to mid-1997 and an age-sex-matched nonexposed group were followed up to 8.5 years (mean 4.2 years). Relative rates (RR) of BRCA were estimated and stratified by age, statin exposure time, and prior hormone use. Thirteen thousand five hundred ninety-two statin users and 53,880 nonexposed subjects were identified. Eight hundred seventy-nine incident BRCA cases were identified. Statins were not associated with BRCA risk in women less than or equal to55 years. Among subjects >55 years, the RR for BRCA was 1.15 (0.97, 1.37). Stratified analyses revealed increases in risk in short-term statin users and statin users with long-term hormone replacement therapy (HRT) exposure. More studies are needed to determine if short-term statin use and statin use with long-term HRT exposure increases postmenopausal BRCA risk. Published by Elsevier Science Inc. C1 Saskatchewan Hlth, Populat Hlth Branch, Regina, SK S4S 6X6, Canada. US FDA, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Beck, P (reprint author), Saskatchewan Hlth, Populat Hlth Branch, 3475 Albert St, Regina, SK S4S 6X6, Canada. NR 23 TC 65 Z9 66 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAR PY 2003 VL 56 IS 3 BP 280 EP 285 DI 10.1016/S0895-4356(02)00614-5 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 674HQ UT WOS:000182631700011 PM 12725884 ER PT J AU Donabedian, SM Thal, LA Hershberger, E Perri, MB Chow, JW Bartlett, P Jones, R Joyce, K Rossiter, S Gay, K Johnson, J Mackinson, C Debess, E Madden, J Angulo, F Zervos, MJ AF Donabedian, SM Thal, LA Hershberger, E Perri, MB Chow, JW Bartlett, P Jones, R Joyce, K Rossiter, S Gay, K Johnson, J Mackinson, C Debess, E Madden, J Angulo, F Zervos, MJ TI Molecular characterization of gentamicin-resistant enterococci in the United States: Evidence of spread from animals to humans through food SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AMINOGLYCOSIDE RESISTANCE; ANTIMICROBIAL RESISTANCE; GLYCOPEPTIDE RESISTANCE; STREPTOCOCCUS-FAECALIS; FAECIUM; LEVEL; IDENTIFICATION; COMMUNITY; GENE; ORIGIN AB We evaluated the molecular mechanism for resistance of 360 enterococci for which the gentamicin MICs were greater than or equal to128 mug/ml. The aac(6')-Ie-aph(2")-Ia, aph(2")-Ic, and aph(2")-Id genes were identified by PCR in isolates from animals, food, and humans. The aph(2")-Ib gene was not identified in any of the isolates. Two Enterococcus faecalis isolates (MICs > 1,024 mug/ml) from animals failed to generate a PCR product for any of the genes tested and likely contain a new unidentified aminoglycoside resistance gene. Pulsed-field gel electrophoresis (PFGE) analysis showed a diversity of strains. However, 1 human and 18 pork E. faecalis isolates from Michigan with the aac(6')-Ie-aph(2")-Ia gene had related PFGE patterns and 2 E. faecalis isolates from Oregon (1 human and 1 grocery store chicken isolate) had indistinguishable PFGE patterns. We found that when a gentamicin-resistant gene was present in resistant enterococci from animals, that gene was also present in enterococci isolated from food products of the same animal species. Although these data indicate much diversity among gentamicin-resistant enterococci, the data also suggest similarities in gentamicin resistance among enterococci isolated from humans, retail food, and farm animals from geographically diverse areas and provide evidence of the spread of gentamicin-resistant enterococci from animals to humans through the food supply. C1 William Beaumont Hosp, Inst Res, Royal Oak, MI 48073 USA. William Beaumont Hosp, Div Infect Dis, Dept Med, Royal Oak, MI 48073 USA. John D Dingell VA Med Ctr, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Univ Maryland, Baltimore, MD 21201 USA. Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA USA. Oregon Hlth Div, Portland, OR USA. Dept Agr, Portland, OR USA. RP Zervos, MJ (reprint author), William Beaumont Hosp, Inst Res, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. FU FDA HHS [FD-U-001577-01] NR 34 TC 102 Z9 119 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2003 VL 41 IS 3 BP 1109 EP 1113 DI 10.1128/JCM.41.3.1109-1113.2003 PG 5 WC Microbiology SC Microbiology GA 656PQ UT WOS:000181616500029 PM 12624037 ER PT J AU Jinneman, KC Hunt, JM Eklund, CA Wernberg, JS Sado, PN Johnson, JM Richter, RS Torres, ST Ayotte, E Eliasberg, SJ Istafanos, P Bass, D Kexel-Calabresa, N Lin, W Barton, CN AF Jinneman, KC Hunt, JM Eklund, CA Wernberg, JS Sado, PN Johnson, JM Richter, RS Torres, ST Ayotte, E Eliasberg, SJ Istafanos, P Bass, D Kexel-Calabresa, N Lin, W Barton, CN TI Evaluation and interlaboratory validation of a selective agar for phosphatidylinositol-specific phospholipase C activity using a chromogenic substrate to detect Listeria monocytogenes from foods SO JOURNAL OF FOOD PROTECTION LA English DT Article AB Phosphatidylinositol-specific phospholipase C (PI-PLC) activity is a potential virulence factor and is exhibited only by the Listeria species Listeria monocytogenes and Listeria ivanovii. A chromogenic substrate for the direct detection of PI-PLC activity is available in a new medium (BCM L. monocytogenes plating agar). The use of a chromogenic substrate offers a mechanism with which to directly screen for L. monocytogenes and L. ivanovii other than the esculin used in Oxford (OXF) and Palcam, (PAL) agars, which screen for all Listeria species. The specificity levels of BCM plating agar and of BCM confirmation and rhamnose agars were evaluated with 107 Listeria and 10 Bacillus species isolates. In addition, BCM L. monocytogenes plating agar was compared with standard Listeria selective agars (OXF and PAL agars) with regard to the recovery of L. monocytogenes from 2,000 food and environmental samples obtained from eight participating laboratories. A Listeria species was isolated from at least one of the agars in 209 analyses, and L. monocytogenes was isolated in 135 of these analyses. In 27 of the analyses in which L. monocytogenes was isolated, one or more of the selective differential agars used failed to isolate L. monocytogenes, and therefore the results of these analyses were discrepant. Relative to a reference method involving the use of all three agars (OXF, PAL, and BCM agars), the OXF-BCM, PAL-BCM, and OXF-PAL combinations had sensitivities of 99.3, 99.2, and 90.2%, respectively. In statistical analyses of the different combinations of agars, the OXF-BCM and BCM-PAL combinations were found to be superior to the OXF-PAL combination for the detection of L. monocytogenes. C1 US FDA, Off Regulatory Affairs, Pacific Reg Lab NW, Bothell, WA 98021 USA. US FDA, Off Regulatory Affairs, Pacific Reg Lab SW, Los Angeles, CA 90015 USA. US FDA, Off Regulatory Affairs, San Francisco Dist Off, Alameda, CA 94502 USA. US FDA, Off Regulatory Affairs, SE Reg Lab, Atlanta, GA 30309 USA. US FDA, Off Regulatory Affairs, NE Reg Lab, Jamaica, NY USA. US FDA, Off Regulatory Affairs, Arkansas Reg Lab, Jefferson, AR 72079 USA. Cherney Micobiol Serv Ltd, Green Bay, WI 54311 USA. USA, Food Anal Lab Branch, Cent Pacific Dist Vet Command, Honolulu, HI USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Jinneman, KC (reprint author), US FDA, Off Regulatory Affairs, Pacific Reg Lab NW, 2201 23rd Dr SE, Bothell, WA 98021 USA. NR 13 TC 11 Z9 12 U1 1 U2 3 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 MAR PY 2003 VL 66 IS 3 BP 441 EP 445 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 656HG UT WOS:000181602100014 PM 12636298 ER PT J AU Mazzoni, A Leifer, CA Mullen, GED Kennedy, MN Klinman, DM Segal, DM AF Mazzoni, A Leifer, CA Mullen, GED Kennedy, MN Klinman, DM Segal, DM TI Cutting edge: Histamine inhibits IFN-alpha release from plasmacytoid dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; INTERFERON-ALPHA; INFLUENZA-VIRUS; CPG-DNA; EXPRESSION; MONOCYTES; IMMUNITY; RESPOND; BLOOD AB Plasmacytoid dendritic cells (DC) are professional APC and a major source of type I IFN following viral infection. We previously showed that histamine alters the cytokine profiles of maturing monocyte-derived DC resulting in a change from Th1 to Th2 in their T cell polarizing function. In this study, we show that human plasmacytoid DC, activated by either CpG oligodeoxynucleotides or viral infection, also respond to histamine through H2 receptors, leading to a marked down-regulation of IFN-alpha and TNF-alpha and a moderate switch in their capacity to polarize naive T cells. Our findings provide an explanation for low levels of type I IFN frequently observed in atopic individuals. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Segal, DM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 28 TC 54 Z9 59 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 MAR 1 PY 2003 VL 170 IS 5 BP 2269 EP 2273 PG 5 WC Immunology SC Immunology GA 648JD UT WOS:000181146800003 PM 12594246 ER PT J AU Kinter, AL Umscheid, CA Arthos, J Cicala, C Lin, Y Jackson, R Donoghue, E Ehler, L Adelsberger, J Rabin, RL Fauci, AS AF Kinter, AL Umscheid, CA Arthos, J Cicala, C Lin, Y Jackson, R Donoghue, E Ehler, L Adelsberger, J Rabin, RL Fauci, AS TI HIV envelope induces virus expression from resting CD4(+) T cells isolated from HIV-infected individuals in the absence of markers of cellular activation or apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; BLOOD MONONUCLEAR-CELLS; FOCAL ADHESION KINASE; MACROPHAGE-TROPIC HIV; CROSS-LINKING; TYPE-1 RNA; REPLICATION; INDUCTION; SIGNAL AB Resting CD4(+) T cells containing integrated HIV provirus constitute one of the long-lived cellular reservoirs of HIV in vivo. This cellular reservoir of HIV had been thought to be quiescent with regard to virus replication based on the premise that HIV production in T cells is inexorably linked to cellular activation as determined by classical activation markers. The transition of T cells within this HIV reservoir from a resting state to an activated HIV-producing state is believed to be associated with a shorten life span due to susceptibility to activation-associated apoptosis. Evidence is mounting, however, that HIV production may occur in T cells that have not undergone classic T cell activation. HIV encodes several proteins, including envelope and Nef, which trigger a variety of signaling pathways associated with cellular activation, thereby facilitating HIV replication in nondividing cells. The present study demonstrates that production of infectious virus from resting CD4(+) T cells isolated from HIV-infected individuals can be induced following exposure of these cells to HIV-1 recombinant (oligomeric gp140) envelope protein. Envelope-mediated induction of HIV expression occurs in the presence of reverse transcriptase inhibitors and is not associated with markers of classic T cell activation, proliferation, or apoptosis. The ability of HIV envelope to induce virus replication in HIV-infected resting CD4(+) T cells without triggering apoptosis provides a mechanism for the virus itself to directly participate in the maintenance of HIV production from this cellular reservoir. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, AIDS Monitoring Lab, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kinter, AL (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A17,10 Ctr Dr,MSC-1576, Bethesda, MD 20892 USA. FU PHS HHS [N01-C012400] NR 44 TC 41 Z9 42 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2003 VL 170 IS 5 BP 2449 EP 2455 PG 7 WC Immunology SC Immunology GA 648JD UT WOS:000181146800026 PM 12594269 ER PT J AU Bebia, Z Frye, RF Romkes, M Wilson, JW Cecchetti, A Chaves-Gnecco, D Cannon, Y Huang, SM Branch, RA AF Bebia, Z Frye, RF Romkes, M Wilson, JW Cecchetti, A Chaves-Gnecco, D Cannon, Y Huang, SM Branch, RA TI Selective regulation of individual CYP enzymes by age and gender. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Clinical Research 2003 Meeting CY MAR 13-16, 2003 CL BALTIMORE, MARYLAND C1 Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA USA. US FDA, OCPB CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2003 VL 51 SU 2 BP S376 EP S376 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 652QW UT WOS:000181390700118 ER PT J AU Wysowski, DK Swann, J AF Wysowski, DK Swann, J TI Use of medications for erectile dysfunction in the United States, 1996 through 2001 SO JOURNAL OF UROLOGY LA English DT Article DE penis; impotence; sildenafil; alprostadil ID SEXUAL RISK BEHAVIOR; BISEXUAL MEN; GAY; VIAGRA; DRUG AB Purpose: We describe the use during 1996 through 2001 of the primary medications approved in the United States for treatment of erectile dysfunction, namely alprostadil injection and urethral suppository, and sildenafil. Materials and Methods: Two pharmaceutical research data bases, the National Prescription Audit Plus, and National Disease and Therapeutic Index, were accessed and analyzed. Ancillary data were obtained from 2 health plans. Results: Increases in the number of dispensed prescriptions for alprostadil injection and urethral suppository marketed in 1995 and 1996, respectively, were reversed in 1998 by the marketing of sildenafil. From 1998 through 2001 the estimated number of prescriptions for sildenafil increased 1.87-fold or 87% from 7.5 million to 14 million, while those for alprostadil injection decreased 33% from 239,000 to 159,000 and those for alprostadil suppository decreased 67% from 400,000 to 132,000. Sildenafil was prescribed proportionately more frequently for younger men than alprostadil injection or suppository (p < 0.0001). Compared with men for whom sildenafil was prescribed in 1998 those prescribed the drug in 2001 were younger (p < 0.0001). Alprostadil injection and suppository were prescribed proportionately more frequently by urologists than sildenafil. Ancillary data from 2 health plans indicated a 173% increase in 1 plan and a 25% decrease in the other due to restrictions in sildenafil prescriptions from 1998 through 2001. Conclusions: Due to the marketing of sildenafil in 1998 through 2001 the use of 2 approved medications for erectile dysfunction, namely alprostadil injection and alprostadil urethral suppository, decreased, while the use of sildenafil increased. Sildenafil was prescribed proportionately more frequently for younger men than alprostadil injection or suppository. Alprostadil was prescribed proportionately more frequently by urologists than sildenafil, which was most commonly prescribed by family and general practitioners, and internists. The data indicate the wide adoption and use of sildenafil for erectile dysfunction. C1 Off Drug Safety Food & Drug Adm, Rockville, MD USA. RP Wysowski, DK (reprint author), Off Drug Safety Food & Drug Adm, Rockville, MD USA. NR 18 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2003 VL 169 IS 3 BP 1040 EP 1042 DI 10.1097/01.ju.0000045707.96565.cd PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 644KM UT WOS:000180916500057 PM 12576841 ER PT J AU Sears, JF Khan, AS AF Sears, JF Khan, AS TI Single-tube fluorescent product-enhanced reverse transcriptase assay with Ampliwax (TM) (STF-PERT) for retrovirus quantitation SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE TaqMan fluorescent probe-based product enhanced reverse transcriptase assay; reverse transcriptase; polymerase chain reaction; retrovirus; avian myeloblastosis virus; murine leukemia virus ID HUMAN-IMMUNODEFICIENCY-VIRUS AB A TaqMan fluorescent probe-based product enhanced reverse transcriptase (RT) assay is described in which the RT and polymerase chain reaction (PCR) steps are set-up in a single tube, in two compartments separated by Ampliwax(TM) (designated as single-tube fluorescent product-enhanced reverse transcriptase assay (STF-PERT)). This simplification of the two-step method resulted in increased assay reproducibility and handling efficiency while maintaining the sensitivity of the PERT assay ( < 10 virions). The STF-PERT assay can be used to quantitate low amounts of retrovirus in clinical and research materials and to evaluate retrovirus contamination in cell substrates and biological products in human use. (C) 2002 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Retrovirus Res, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), 1401 Rockville Pike,HFM-454, Rockville, MD 20852 USA. NR 12 TC 14 Z9 16 U1 0 U2 0 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 MAR PY 2003 VL 108 IS 1 BP 139 EP 142 DI 10.1016/S0166-0934(02)00287-2 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 647LH UT WOS:000181093900018 PM 12565165 ER PT J AU Pavio, N Romano, PR Graczyk, TM Feinstone, SM Taylor, DR AF Pavio, N Romano, PR Graczyk, TM Feinstone, SM Taylor, DR TI Protein synthesis and endoplasmic reticulum stress can be modulated by the hepatitis C virus envelope protein E2 through the eukaryotic initiation factor 2 alpha kinase PERK SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSLATIONAL CONTROL; AUTOPHOSPHORYLATION SITES; DIABETES-MELLITUS; ENTRY SITE; PKR; ACTIVATION; RNA; INTERFERON; INHIBITION; RETENTION AB The hepatitis C virus envelope protein, E2, is an endoplasmic reticulum (ER)-bound protein that contains a region of sequence homology with the double-stranded RNA-activated protein kinase PKR and its substrate, the eukaryotic translation initiation factor 2 (eIF2). We previously reported that E2 modulates global translation through inhibition of the interferon-induced antiviral protein PKR through its PKR-eIF2alpha phosphorylation site homology domain (PePHD). Here we show that the PKR-like ER-resident kinase (PERK) binds to and is also inhibited by E2. At low expression levels, E2 induced ER stress, but at high expression levels, and in vitro, E2 inhibited PERK kinase activity. Mammalian cells that stably express E2 were refractory to the translation-inhibitory effects of ER stress inducers, and E2 relieved general translation inhibition induced by PERK. The PePHD of E2 was required for the rescue of translation that was inhibited by activated PERK, similar to our previous findings with PKR. Here we report the inhibition of a second eIF2alpha kinase by E2, and these results are consistent with a pseudosubstrate mechanism of inhibition of eIF2alpha kinases. These findings may also explain how the virus promotes persistent infection by overcoming the cellular ER stress response. C1 Univ So Calif, Sch Med, Dept Mol Microbiol & Immunol, Howard Hughes Med Inst, Los Angeles, CA 90033 USA. Thomas Jefferson Univ, Jefferson Ctr Biomed Res, Dept Biochem & Mol Pharmacol, Doylestown, PA 18901 USA. US FDA, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Taylor, DR (reprint author), 8800 Rockville Pike,HFM-448, Bethesda, MD 20892 USA. NR 24 TC 99 Z9 107 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2003 VL 77 IS 6 BP 3578 EP 3585 DI 10.1128/JVI.77.6.3578-3585.2003 PG 8 WC Virology SC Virology GA 652FZ UT WOS:000181370300024 PM 12610133 ER PT J AU Carr, A Emery, S Law I Puls, R Lundgren, JD Powderly, WG Carr, B Cooper, DA Grinspoon, S Ioannidis, J Lewis, R Law, M Lichtenstein, K Murray, J Pizzuti, D Rozenbaum, W Schambelan, M Moore, A Miller, J AF Carr, A Emery, S Law, I Puls, R Lundgren, JD Powderly, WG Carr, B Cooper, DA Grinspoon, S Ioannidis, J Lewis, R Law, M Lichtenstein, K Murray, J Pizzuti, D Rozenbaum, W Schambelan, M Moore, A Miller, J CA HIV Lipodystrophy Case Definition TI An objective case definition of lipodystrophy in HIV-infected adults: a case-control study SO LANCET LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; REVERSE-TRANSCRIPTASE INHIBITORS; PROTEASE INHIBITORS; PREADIPOCYTE DIFFERENTIATION; METABOLIC ABNORMALITIES; INSULIN-RESISTANCE; COHORT; RISK AB Background Lipodystrophy (peripheral lipoatrophy, central fat accumulation, and lipomatosis) is a common and disfiguring problem in adult patients with HIV-1 infection on antiretrovirals. However, an objective, validated definition of the disorder does not exist. We aimed to develop an objective, sensitive, specific, and broadly applicable case definition of HIV lipodystrophy. Methods In a case-control study, 1081 consecutive, HIV-infected, adult outpatients (261 [15%] women) without active AIDS were recruited from 32 sites worldwide. We classed patients with at least one moderate or severe subjective lipodystrophic feature, identified by lipodystrophy-specific physical examination and patient questionnaire, and apparent to both doctor and patient as cases (n=417). We classed patients with no such feature as controls (n=371), and patients without a clear diagnosis as non-assigned. We used objective clinical, metabolic, and body composition measurements to construct a logistic regression model with a subset of randomly selected cases and controls. The model was validated in the remaining patients. Findings A model including age, sex, duration of HIV infection, HIV disease stage, waist to hip ratio, anion gap, serum HDL cholesterol concentration, trunk to peripheral fat ratio, percentage leg fat, and intra-abdominal to extra-abdominal fat ratio had 79% (95% CI 70-85) sensitivity and 80% (95% Cl 71-87) specificity for diagnosis of lipodystrophy. Models that incorporated only clinical, or only clinical and metabolic variables had lower sensitivity and specificity than the inclusive model. Models for lipoatrophy, fat accumulation, and lipomatosis could not be developed since pure phenotypes occurred in fewer than 10% of patients with clinical diagnoses of these disorders. Interpretation Our objective case definition of HIV-associated lipodystrophy should improve assessment of lipodystrophy prevalence, risk factors, and pathogenesis; prevention and treatment approaches; and assist in diagnosis. C1 St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Hvidovre Univ Hosp, Copenhagen, Denmark. Washington Univ, Sch Med, St Louis, MO USA. Forum Collaborat HIV Res, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Ioannina, GR-45110 Ioannina, Greece. Agouron Pharmaceut, San Diego, CA USA. HIV Outpatient Study Ctr Dis Control & Prevent, Denver, CO USA. US FDA, US Dept HHS, Washington, DC 20204 USA. Bristol Myers Squibb Co, Princeton, NJ USA. Hop Rothschild, F-75571 Paris, France. Agence Natl Res SIDA, Paris, France. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Carr, A (reprint author), St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia. EM acarr@stvincents.com.au RI Ioannidis, John/G-9836-2011; Puls, Rebekah/A-3992-2013; OI Lundgren, Jens/0000-0001-8901-7850; Rozenbaum, Willy/0000-0003-1975-3566 NR 32 TC 307 Z9 316 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR 1 PY 2003 VL 361 IS 9359 BP 726 EP 735 DI 10.1016/S0140-6736(03)12656-6 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 649WY UT WOS:000181232000007 PM 12620736 ER PT J AU Shakarian, AM Joshi, MB Yamage, M Ellis, SL Debrabant, A Dwyer, DM AF Shakarian, AM Joshi, MB Yamage, M Ellis, SL Debrabant, A Dwyer, DM TI Members of a unique histidine acid phosphatase family are conserved amongst a group of primitive eukaryotic human pathogens SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Leishmania; trypanosomatid; protozoan parasite; human pathogen; pulse field gel electrophoresis; histidine acid phosphatase; enzyme; genome; chromosome ID LEISHMANIA-DONOVANI PROMASTIGOTES; SURFACE-MEMBRANE; TRYPANOSOMA-BRUCEI; CELLULAR-LOCALIZATION; MEXICANA; CLONING; GENE; IDENTIFICATION; PURIFICATION; AMASTIGOTES AB Recently, we identified and characterized the genes encoding several distinct members of the histidine-acid phosphatase enzyme family from Leishmania donovani, a primitive protozoan pathogen of humans. These included genes encoding the heavily phosphorylated/glycosylated, tartrate-sensitive, secretory acid phosphatases (Ld SAcP-1 and Ld SAcP-2) and the unique, tartrate-resistant, externally-oriented, surface membrane-bound acid phosphatase (Ld MAcP) of this parasite. It had been previously suggested that these enzymes may play essential roles in the growth, development and survival of this organism. In this report, to further examine this hypothesis, we assessed whether members of the L. donovani histidine-acid phosphatase enzyme family were conserved amongst other pathogenic Leishmania and related trypanosomatid parasites. Such phylogenetic conservation would clearly indicate an evolutionary selection for this family of enzymes and strongly suggest and support an important functional role for acid phosphatases to the survival of these parasites. Results of pulsed field gel electrophoresis and Southern blotting showed that homologs of both the Ld SAcPs and Ld MAcP were present in each of the visceral and cutaneous Leishmania species examined (i.e. isolates of L. donovani, L. infantum, L. tropica, L. major and L. mexicana, respectively). Further, results of enzyme assays showed that all of these organisms expressed both tartrate-sensitive and tartrate-resistant acid phosphatase activities. In addition, homologs of both the Ld SAcPs and Ld MAcP genes and their corresponding enzyme activities were also identified in two Crithidia species (C. fasciculata and C. luciliae) and in Leptomonas seymouri. In contrast, Trypanosoma brucei, Trypanosoma cruzi and Phytomonas serpens had only very-low levels of such enzyme activities. Cumulatively, results of this study showed that homologs of the Ld SAcPs and Ld MAcP are conserved amongst all pathogenic Leishmania sps. suggesting that they may play significant functional roles in the growth, development and survival of all members of this important group of human pathogens. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Salve Regina Univ, Dept Biol & Biomed Sci, Newport, RI USA. US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC-0425, Bethesda, MD 20892 USA. EM ddwyer@niaid.nih.gov NR 38 TC 17 Z9 18 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAR PY 2003 VL 245 IS 1-2 BP 31 EP 41 DI 10.1023/A:1022851914014 PG 11 WC Cell Biology SC Cell Biology GA 658YC UT WOS:000181747800004 PM 12708742 ER PT J AU Janssen, RAJ Kim, PN Mier, JW Morrison, DK AF Janssen, RAJ Kim, PN Mier, JW Morrison, DK TI Overexpression of kinase suppressor of Ras upregulates the high-molecular-weight tropomyosin isoforms in ras-transformed NIH 3T3 fibroblasts SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN BREAST-LESIONS; RHO-KINASE; SIGNAL-TRANSDUCTION; ALPHA-TROPOMYOSIN; DOWN-REGULATION; MAP KINASE; POLYPEPTIDE EXPRESSION; NONMUSCLE TROPOMYOSIN; FOCAL ADHESIONS; CULTURED-CELLS AB The down-regulation of the high-molecular-weight isoforms of tropomyosin (TM) is considered to be an essential event in cellular transformation. In ras-transformed fibroblasts, the suppression of TM is dependent on the activity of the Raf-1 kinase; however, the requirement for other downstream effectors of Ras, such as MEK and ERK, is less clear. In this study, we have utilized the mitogen-activated protein kinase scaffolding protein Kinase Suppressor of Ras (KSR) to further investigate the regulation of TM and to clarify the importance of MEK/ERK signaling in this process. Here, we report that overexpression of wild-type KSR1 in ras-transformed fibroblasts restores TM expression and induces cell flattening and stress fiber formation. Moreover, we find that the transcriptional activity of a TM-alpha promoter is decreased in ras-transformed cells and that the restoration of TM by KSR1 coincides with increased transcription from this promoter. Although ERK activity was suppressed in cells overexpressing KSR1, ERK inhibition alone was insufficient to upregulate TM expression. The KSR1-mediated effects on stress fiber formation and TM transcription required the activity of the ROCK kinase, because these effects could be suppressed by the ROCK inhibitor, Y27632. Overexpression of KSR1 did not directly regulate ROCK activity, but did permit the recoupling of ROCK to the actin polymerization machinery. Finally, all of the KSR1-induced effects were mediated by the C-terminal domain of KSR1 and were dependent on the KSR-MEK interaction. C1 Natl Canc Inst, Regulat Cell Growth Lab, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Janssen, RAJ (reprint author), Univ Nijmegen, Ctr Med, Ctr Mol Life Sci, TIL 187,POB 9101, NL-6500 HB Nijmegen, Netherlands. FU NCI NIH HHS [CA74401] NR 66 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2003 VL 23 IS 5 BP 1786 EP 1797 DI 10.1128/MCB.23.5.1786-1797.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 651AJ UT WOS:000181297000028 PM 12588996 ER PT J AU Husain, SR Kawakami, K Kawakami, M Puri, RK AF Husain, SR Kawakami, K Kawakami, M Puri, RK TI Interleukin-4 receptor-targeted cytotoxin therapy of androgen-dependent and -independent prostate carcinoma in xenograft models SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; PSEUDOMONAS EXOTOXIN; CANCER-THERAPY; PHASE-II; ANTITUMOR-ACTIVITY; FUSION PROTEIN; CELL CARCINOMA; GROWTH-FACTORS; ANIMAL-MODELS; TOXIN AB Prostate cancer is the most commonly diagnosed solid tumors in United States men. Survival with advanced prostate cancer is dismal because of a lack of effective treatments. Overexpression of interleukin 4 receptors (IL-4R) on prostate carcinoma cells makes them suitable targets for the interleukin 4 (IL-4) fused Pseudomonas exotoxin, IL-4 cytotoxin (IL4-CTx). Androgen-dependent (LNCaP) and -independent (DU145) human prostate cancer cell lines overexpress IL-4Rs and are exquisitely sensitive to IL4-CTx. Using LNCaP and DU145 cell lines, IC50 values of 4.5 +/- 2.0 and 6.5 +/- 0.5 ng/ml, respectively, were obtained for IL4-CTx in protein synthesis inhibition assays. Primary cultures established from prostate tumor biopsies were equally sensitive to the cytotoxic effects of IL4-CTx. Reverse transcription-PCR analysis, although not quantitative, indicated the presence of mRNA for IL-4Ralpha, a primary subunit of the IL-4R receptor complex in prostate carcinoma cell lines, primary cultures, benign prostatic hyperplasia, and prostate carcinoma tissues. Immunohistochemistry studies revealed the presence of IL-4R in benign prostatic hyperplasia and prostate carcinomas. Five daily (QD) injections of IL4-CTx (100 mug/kg) administered im., i.p., or intratumoral (i.t.) caused several complete responses in nude mice with s.c. DU145 and LNCaP tumors. i.t. injections of IL4-CTx elicited tumor regression in a dose-dependent manner with complete responses occurring in 100% of the animals when treated with IL4-CTx (500 mug/kg) given five OD injections. Administration of IL4-CTx i.t. (500 mug/kg) either 10 times OD or six injections on alternate days elicited complete responses in 40% of mice with DU145 tumors that were three times larger (67 mm(2)) on initiation of treatments. IL4-CTx appeared to be well tolerated. On the basis of these results, combining i.t. injections of IL4-CTx with systemic administration may provide an effective strategy for treating patients with advanced, refractory prostate cancer. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. EM Puri@cber.fda.gov NR 43 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2003 VL 2 IS 3 BP 245 EP 254 PG 10 WC Oncology SC Oncology GA 659BL UT WOS:000181757100007 PM 12657719 ER PT J AU Thai, SF Allen, JW DeAngelo, AB George, MH Fuscoe, JC AF Thai, SF Allen, JW DeAngelo, AB George, MH Fuscoe, JC TI Altered gene expression in mouse livers after dichloroacetic acid exposure SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article DE mice; dichloroacetic acid; gene expression ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER CELLS; MALE B6C3F1 MICE; TUMOR-GROWTH; CARCINOMA-CELLS; UP-REGULATION; ANGIOGENESIS; MATRIX; ANGIOSTATIN; INVASION AB Dichloroacetic acid (DCA) is a major by-product of water disinfection by chlorination. Several studies have demonstrated that DCA exhibits hepatocarcinogenic effects in rodents when administered in-drinking water. This chemical does not appear to be highly mutagenic, and the mechanism(s) involved in DCA induction-of cancer are not clear. The present work was aimed at identifying changes in gene expression which may indicate critical alterations/pathways involved in this chemical's carcinogenic activities. We used cDNA microarray methods for analyses of gene expression in livers of mice treated with the tumorigenic dose of 2 g/l DCA in drinking water for 4 weeks. Total RNA samples obtained from livers of the control and DCA-treated mice were evaluated for gene expression patterns with Clontech Atlas(TM) Mouse 1.2 cDNA and Atlas(TM) mouse stress/toxicology arrays, and the data analyzed with AtlasImage 2.01 and one-way ANOVA in JMP4 software. From replicate experiments, we identified 24 genes with altered expression, of which 15 were confirmed by Northern blot analysis. Of the 15 genes, 14 revealed expression suppressed two- to five-fold; they included the following: MHR 23A, cytochrome P450 (CYP) 2C29, CYP 3A11, serum paraoxonase/arylesterase 1 (PON 1), liver carboxylesterase, alpha- 1 antitrypsin, ER p72, glutathione S-transferase (GST) Pi 1, angiogenin, vitronectin precursor, cathepsin D (CTSD), plasminogen precursor (contains angiostatin), prothrombin precursor and integrin alpha 3 precursor (ITGA 3). An additional gene, CYP 2A4/5, had a two-fold elevation in expression. Further, in ancillary Northern analyses of total RNA isolated from DCA-induced hepatocellular carcinomas (from earlier reported studies of mice treated with 3.5 g/l DCA for 93 weeks), many of the same genes (11 of 15) noted above showed a similar alteration in expression. In summary, we have identified specific genes involved in the functional categories of cell growth, tissue remodeling, apoptosis, cancer progression and xenobiotic metabolism that have altered levels of expression following exposures to DCA. These findings serve to highlight new pathways in which to further probe DCA effects that may be critical to its tumorigenic activity. Published by Elsevier Science B.V. C1 US EPA, Natl Hlth & Environm Effects Res Lab, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. RP Thai, SF (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Div Environm Carcinogenesis, Mail Drop 68, Res Triangle Pk, NC 27711 USA. NR 56 TC 20 Z9 22 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD MAR PY 2003 VL 543 IS 2 BP 167 EP 180 DI 10.1016/S1383-5742(03)00014-0 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 661PT UT WOS:000181899500012 PM 12644186 ER PT J AU Slikker, W AF Slikker, W TI Neuroimaging as a new approach to neurotoxicology SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 2 BP 287 EP 287 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000013 ER PT J AU Bowyer, JF Harris, A Jakab, R Delongchamp, R Miller, DB O'Callaghan, JP AF Bowyer, JF Harris, A Jakab, R Delongchamp, R Miller, DB O'Callaghan, JP TI cDNA array analysis of the changes in gene expression specifically produced by neurotoxic doses of amphetamine: Not quite mission impossible SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet Testing, Jefferson, AR 72079 USA. NIOSH, Ctr Dis Control & Prevent, Morgantown, WV USA. RI O'Callaghan, James/O-2958-2013 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 MAR PY 2003 VL 24 IS 2 MA 11 BP 289 EP 290 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000022 ER PT J AU Casciano, DA AF Casciano, DA TI There is no place like ome: Omics at the NCTR: Genomics-proteomics-metabonomics-bioinformatics SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAR PY 2003 VL 24 IS 2 MA 10 BP 289 EP 289 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000021 ER PT J AU Canady, RA AF Canady, RA TI Acrylamide contamination of food: Risk assessment and regulatory issues SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, CFSAN, Div Risk Assessment, College Pk, MD 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 MAR PY 2003 VL 24 IS 2 MA 14 BP 291 EP 291 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000025 ER PT J AU Paule, MG Fogle, CM Allen, RR Pearson, E Hammond, T Popke, EJ AF Paule, MG Fogle, CM Allen, RR Pearson, E Hammond, T Popke, EJ TI Chronic exposure to NMDA receptor and sodium channel blockers during development in monkeys and rats: Long-term effects on cognitive function SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Peak Stat Serv, Evergreen, CO USA. AstraZeneca Safety Assessment, 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 MAR PY 2003 VL 24 IS 2 MA 32 BP 298 EP 299 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000043 ER PT J AU Ali, SF Oetinger, M Skinner, JT Schmued, LC Slikker, W Cawthon, D Imam, SZ AF Ali, SF Oetinger, M Skinner, JT Schmued, LC Slikker, W Cawthon, D Imam, SZ TI Specific caspase-3 inhibition attenuates methamphetamine-induced dopaminergic changes and proapoptotic alterations SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Div Neurotoxicol, Neurochem Lab, Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 48 BP 304 EP 304 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000057 ER PT J AU Jakab, RL Bowyer, JF AF Jakab, RL Bowyer, JF TI Parvalbumin Interneurons in dopamine-poor cortex are susceptible to amphetamine toxicity SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 53 BP 306 EP 306 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000062 ER PT J AU Schmued, L Xu, L AF Schmued, L Xu, L TI Demonstration and localization of MDMA induced neuronal degeneration SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 54 BP 306 EP 307 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000063 ER PT J AU Xu, ZA Seidler, FJ Slikker, W Slotkin, TA AF Xu, ZA Seidler, FJ Slikker, W Slotkin, TA TI Adolescent nicotine elicits glial and neuronal damage in rat brain SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 Duke Univ, Med Ctr, Durham, NC USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NCTR, Div Neurotoxicol, Jefferson, AR 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 MAR PY 2003 VL 24 IS 2 MA 55 BP 307 EP 307 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000064 ER PT J AU Patterson, TA Kant, AC Slikker, W AF Patterson, TA Kant, AC Slikker, W TI Using laser capture microdissection to compare age-related transcription factor expression differences in the mouse hippocampus SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 59 BP 308 EP 308 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000068 ER PT J AU Duhart, HM Imam, SZ Skinner, JT Ali, SF AF Duhart, HM Imam, SZ Skinner, JT Ali, SF TI Cocaine induces a dose dependent alteration in the expression immediate early genes c-fos and SP-1 and in nuclear factor NF-K beta in PC12 cells SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 61 BP 309 EP 309 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000070 ER PT J AU Scallet, AC Binienda, ZK AF Scallet, AC Binienda, ZK TI EEG, behavioral, and c-fos immunohistochemical correlates of seizures in rats following exposure to domoic acid SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 65 BP 310 EP 311 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000074 ER PT J AU Wright, LKM Gillam, MP Thorn, BT Paule, MG AF Wright, LKM Gillam, MP Thorn, BT Paule, MG TI Acute effects of the GABA(B) receptor agonist baclofen (BAC) on aspects of rhesus monkey cognition SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, ROW Sci, Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 63 BP 310 EP 310 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000072 ER PT J AU Fogle, CM Allen, RR Pearson, E Hammond, T Popke, EJ Paule, MG AF Fogle, CM Allen, RR Pearson, E Hammond, T Popke, EJ Paule, MG TI Effects of chronic blockade of sodium channels and NMDA receptors during development on the acquisition and performance of several cognitive function tasks in rats SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Peak Stat Serv, Evergreen, CO USA. AstraZeneca Safety Assessment, Loughborough LE11 5RH, 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 MAR PY 2003 VL 24 IS 2 MA 68 BP 311 EP 312 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000077 ER PT J AU Gray, EP Ferguson, SA AF Gray, EP Ferguson, SA TI Decreased anxiety levels measured by the elevated plus maze in the spontaneously hypertensive rat (SHR) SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 66 BP 311 EP 311 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000075 ER PT J AU Chelonis, JJ Gillam, MP Paule, MG AF Chelonis, JJ Gillam, MP Paule, MG TI Diminished cognitive adaptability in adult rhesus monkeys exposed to cocaine during gestation SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 Univ Arkansas, Little Rock, AR 72204 USA. Natl Ctr Toxicol Res, 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 MAR PY 2003 VL 24 IS 2 MA 70 BP 312 EP 312 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000079 ER PT J AU Calvo, MS Whiting, SJ AF Calvo, MS Whiting, SJ TI Prevalence of vitamin D insufficiency in Canada and the United States: Importance to health status and efficacy of current food fortification and dietary supplement use SO NUTRITION REVIEWS LA English DT Review DE 25-hydroxyvitamin D; vitamin D intake; latitude; season; race ID FORTIFIED MILK; BREAST-CANCER; WHITE WOMEN; 25-HYDROXYVITAMIN-D; MORTALITY; SKIN; POPULATION; SUNLIGHT; AMERICAN; ADULTS AB This review was prepared by Mona S. Calvo, Ph.D., Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, Food and Drug Administration, HFS-025, 8301 Muirkirk Road, Laurel, MD, 20708, USA, and Susan J. Whiting, Ph.D., College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon SK S7N 5C9, Canada. otherwise healthy adults living in Canada and the United States. Most striking are the effects of latitude, season, and race. Also noteworthy is that dietary vitamin D is not reaching the population in greatest need, nor is it very protective against insufficiency. Fluid milk, as the predominant vehicle for vitamin D fortification, is apparently not very effective in staving off vitamin D insufficiency in adults in all populations at all times of the year. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. RP Calvo, MS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 30 TC 106 Z9 107 U1 0 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 MAR PY 2003 VL 61 IS 3 BP 107 EP 113 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 738NR UT WOS:000186295200005 PM 12723644 ER PT J AU Boehm, G Clark, J Dietrick, J Foust, L Garcia, T Gavini, M Gelber, L Geoffroy, JM Hoblitzell, J Jimenez, P Mergen, G Muzzio, F Planchard, J Prescott, J Timmermans, J Takiar, N AF Boehm, G Clark, J Dietrick, J Foust, L Garcia, T Gavini, M Gelber, L Geoffroy, JM Hoblitzell, J Jimenez, P Mergen, G Muzzio, F Planchard, J Prescott, J Timmermans, J Takiar, N TI The use of stratefied sampling of blend and dosage units to demonstrate adequacy of mix for powder blends SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Article AB In response to concerns expressed by applicants regarding inconsistent policies in establishing blend uniformity acceptance criteria to demonstrate adequacy of mix, the FDA Office of Generic Drugs (OGD) issued the draft document Guidance for Industry, ANDAs: Blend Uniformity Analysis (August 1999)(2). Both generic and innovator pharmaceutical companies raised a number of concerns following the publication of this document. As a result, the Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) was established in February 2000. One of the primary goals of this group was to draft a scientifically based alternative to the OGD document. The resulting recommendation addresses both FDA and industry concerns by substantially enhancing product quality assurance without increasing regulatory burden. The PQRI BUWG recommends that these blend and dosage unit uniformity requirements be administered uniformly throughout the industry. PQRI submitted the following recommendation to the FDA on December 3 1, 2002, providing the Agency with an alternative strategy to consider when drafting future regulatory policy to assess blend and dosage unit uniformity. C1 US FDA, CDER, Rockville, MD 20857 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Pfizer Inc, Groton, CT 06340 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Rutgers State Univ, Piscataway, NJ 08855 USA. NR 4 TC 9 Z9 9 U1 0 U2 1 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1079-7440 J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD MAR-APR PY 2003 VL 57 IS 2 BP 64 EP 74 PG 11 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 664JJ UT WOS:000182057700002 PM 14674508 ER PT J AU Knudsen, JF Thambi, LR Kapcala, LP Racoosin, JA AF Knudsen, JF Thambi, LR Kapcala, LP Racoosin, JA TI Oligohydrosis and fever in pediatric patients treated with zonisamide SO PEDIATRIC NEUROLOGY LA English DT Article ID DRUG AB Zonisamide is an antiepileptic drug developed and first marketed in Japan in 1989. Cases of oligohydrosis, characterized by deficient production and secretion of sweat, were reported in children treated with zonisamide in Japan during development and in the post-marketing period. Zonisamide was approved in the United States in March 2000 for adjunctive treatment of partial seizures in adults. Searching the Food and Drug Administration's Adverse Events Reporting System, we identified six domestic cases of zonisamide-associated oligohydrosis and/or fever, all in patients less than or equal to 18 18 years of age. The calculated reporting rate was 13 cases per 10,000 pediatric-years of exposure, approximately 10-fold the reporting rate in Japan. A possible risk factor for the development of oligohydrosis in these cases was pediatric age, leading to exposure to elevated zonisamide blood levels relative to patient size. Although the mechanism for zonisamide-associated oligohydrosis has not been fully elucidated, the drug may mediate its effect on eccrine sweat glands by inhibiting carbonic anhydrase, thereby influencing pH dynamics, hydrogen ion concentration, and available calcium transients. Awareness of zonisamide-associated oligohydrosis may prevent morbidity, especially in the pediatric population. (C) 2003 by Elsevier Inc. All rights reserved. C1 US FDA, CDER, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Knudsen, JF (reprint author), US FDA, CDER, Div Neuropharmacol Drug Prod, 5600 Fishers Lane,HFD-120, Rockville, MD 20857 USA. NR 22 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD MAR PY 2003 VL 28 IS 3 BP 184 EP 189 DI 10.1016/S0887-8994(02)00511-8 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 684LV UT WOS:000183209600004 PM 12770670 ER PT J AU Rosebraugh, CJ Tsong, Y Zhou, F Chen, M Mackey, AC Flowers, C Toyer, D Flockhart, DA Honig, PK AF Rosebraugh, CJ Tsong, Y Zhou, F Chen, M Mackey, AC Flowers, C Toyer, D Flockhart, DA Honig, PK TI Improving the quality of adverse drug reaction reporting by 4th-year medical students SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE adverse drug reaction; MedWatch; Food and Drug Administration; adverse drug reaction reporting; standardize patient ID SURVEILLANCE AB Purpose Evaluate whether a 15-minute lecture intervention will improve adverse drug reaction reporting quality on standard MedWatch forms. Methods Seventy-eight 4th-year medical students were randomized to intervention 'Group-A' or non-intervention 'Group-B' on the first day of a required five-day clinical pharmacology rotation. Group-A participants attended a 15-minute lecture on completing a MedWatch form with quality information considered by the Food and Drug Administration as critical to adequate adverse drug reaction reporting. Group-B participants did not attend this lecture. Both groups then watched a standardized patient interview of a recognizable adverse drug reaction and completed MedWatch forms. Four Safety Evaluators from the Food and Drug Administration (FDA) rated student responses in a blinded fashion for the primary efficacy variable of Overall Impression and six informational domins using a standardized data quality analysis form that was developed within the Office of Postmarketing Drug Risk Assessment of the FDA. Results Seventy-eight MedWatch forms were evaluated (Group-A=40, Group-B=38). Overall MedWatch information quality scores for the intervention group were significantly higher than the non-intervention group (p < 0.004). Conclusions As little as a 15-minute intervention can significantly improve the quality of adverse drug reaction reporting by 4th-year medical students. Academic medical centers should consider incorporating adverse drug reaction reporting curriculum into the clinical training of medical students. Published in 2003 by John Wiley Sons, Ltd. C1 US FDA, Rockville, MD 20857 USA. Div Clin Pharmacol, Indianapolis, IN USA. RP Rosebraugh, CJ (reprint author), US FDA, Room 10B-45,HFD-570,5600 Fishers Lane, Rockville, MD 20857 USA. NR 18 TC 9 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAR PY 2003 VL 12 IS 2 BP 97 EP 101 DI 10.1002/pds.797 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 652FD UT WOS:000181368400003 PM 12642973 ER PT J AU Temple, RJ AF Temple, RJ TI Defining dose decrease SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Letter C1 Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Temple, RJ (reprint author), Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD 40, Rockville, MD 20857 USA. EM temple@cder.fda.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAR PY 2003 VL 12 IS 2 BP 151 EP 152 DI 10.1002/pds.812 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 652FD UT WOS:000181368400010 PM 12642979 ER PT J AU Itzhak, Y Ali, SF Achat, CN Anderson, KL AF Itzhak, Y Ali, SF Achat, CN Anderson, KL TI Relevance of MDMA ("ecstasy")-induced neurotoxicity to long-lasting psychomotor stimulation in mice SO PSYCHOPHARMACOLOGY LA English DT Article DE MDMA; cocaine; neurotoxicity; sensitization; hyperlocomotion ID INDUCED DOPAMINERGIC NEUROTOXICITY; NITRIC-OXIDE SYNTHASE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; BEHAVIORAL SENSITIZATION; IN-VIVO; METHYLENEDIOXYMETHAMPHETAMINE; RATS; METHAMPHETAMINE; BRAIN; SEROTONIN AB Rationale: Although many studies have focused on the mechanisms underlying MDMA-induced neurotoxicity, little is known about the subsequent longterm response to psychostimulants following exposure to a neurotoxic dose of MDMA. Objectives: We investigated the effect of pre-exposure to neurotoxic and non-neurotoxic doses of MDMA on the response of mice to the psychomotor stimulating effects of MDMA and cocaine. Methods: To investigate MDMA-induced neurotoxicity, male Swiss Webster mice were subjected to three regimens of MDMA: i) 40 mg/kgx2, ii) 30 mg/kgx2, and iii) 15 mg/kgx2 for 2 days. On day 5 following the last exposure to MDMA, the levels of dopaminergic and serotonergic markers were determined. For the behavioral experiments, mice received either a single injection of 10 mg/kg MDMA [MDMA(L)] or one of the following doses of MDMA: 30 mg/kgx2 or 15 mg/kgx2 for 2 days [MDMA (H)]. A third group received saline as a control. On day 5 after the last pretreatment injection, the first MDMA (10 mg/kg) challenge was given, and on day 12, cocaine (20 mg/kg) was administered. Subsequently, mice were re-challenged with MDMA on days 35, 50 and 80, after which locomotor activity was monitored by infrared beam-interrupts. On day 83, mice were killed to detect the levels of doparninergic and serotonergic markers. Results: MDMA-induced mortality and depletion of dopaminergic and serotonergic markers were dose-dependent. MDMA (H) mice endured a sensitized response to MDMA challenge from days 5 through 80, e.g. a persistent 3-fold increase in locomotor activity compared to the response of mice that were not pretreated with a neurotoxic dose of MDMA. The depletion of DAT and 5-HTT binding sites was sustained throughout this time period (64-68% of control). The MDMA (L) mice showed a sensitized response to MDMA only on day 5. Both MDMA (L) and MDMA (H) mice were sensitized to the cocaine challenge. Conclusions: The induction of sensitization to the locomotor stimulating effects of MDMA and cocaine was independent of MDMA-induced neurotoxicity. However, the long-lasting maintenance of the sensitized response to MDMA may be related to the enduring neurotoxicity caused by MDMA. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Miami, FL 33136 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Gautier Bldg Room 503,1011 NW 15th St, Miami, FL 33136 USA. FU NIDA NIH HHS [DA12867, DA08584] NR 24 TC 37 Z9 37 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 2003 VL 166 IS 3 BP 241 EP 248 DI 10.1007/S00213-002-1320-y PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 666XP UT WOS:000182202000007 PM 12590354 ER PT J AU Paul, B Hirshfield, I AF Paul, B Hirshfield, I TI The effect of acid treatment on survival and protein expression of a laboratory K-12 strain Escherichia coli SO RESEARCH IN MICROBIOLOGY LA English DT Article DE acid tolerance; Escherichia coli; proteins; gel electrophoresis ID SALMONELLA-TYPHIMURIUM; TOLERANCE RESPONSE; SHOCK PROTEINS; PH; GROWTH; HABITUATION; RESISTANCE; GENES; RPOS AB Pre-exposure of log phase enteric bacteria to nonlethal acidic pH induces phenotypic changes that protect the organisms against subsequent lethal acidity. Studies have revealed that when Salmonella typhimurium is grown in minimal medium at pH 5.5 and 4.3 the organism develops a biphasic acid tolerance. This two-stage response has not been reported at present in Escherichia coli; rather it is thought that when this organism is grown in rich medium there is a single stress response throughout the pH range of 4 to 6. We believe that the evidence for such a report is lacking; therefore, in this study the acid response of log phase E. coli was examined in rich medium (LB). The pH 3.0 acid survival assays of a laboratory strain of E. coli K-12 MG1655, after cultures had been exposed to LB acidified to pH 5.5 or pH 4.3 indicate that like S. typhimurium, E. coli shows both an acid tolerance and an acid-shock response to pH 5.5 and 4.3 exposure, respectively. It was consistently found, however, that longer pre-exposure (60 min rather than 15 min) at either pH afforded better protection against the lethal pH 3.0 challenge. Analysis of polypeptide induction at pH 5.5 and 4.3 by two-dimensional gel electrophoresis clearly shows different profiles. Together the results show that in E. coli, pre-treatment between pH 4 and 6 does not result in a flat protective response. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 St Johns Univ, Dept Biol Sci, Jamaica, NY 11439 USA. US FDA, NE Reg Lab, Jamaica, NY 11433 USA. RP Paul, B (reprint author), St Johns Univ, Dept Biol Sci, Utopia & Grand Cent Pkwy, Jamaica, NY 11439 USA. NR 22 TC 10 Z9 10 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0923-2508 J9 RES MICROBIOL JI Res. Microbiol. PD MAR PY 2003 VL 154 IS 2 BP 115 EP 121 DI 10.1016/S0923-2508(02)00011-6 PG 7 WC Microbiology SC Microbiology GA 667YA UT WOS:000182261400007 PM 12648726 ER PT J AU Jacobs, AC Wester, RC Auletta, CS Ryan, CA Monteiro-Riviere, NA AF Jacobs, AC Wester, RC Auletta, CS Ryan, CA Monteiro-Riviere, NA TI Cutaneous toxicity current methods and concepts in safety evaluation and relevance to human exposure. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 N Carolina State Univ, Raleigh, NC 27695 USA. Procter & Gamble Co, Cincinnati, OH USA. Huntingdon Life Sci, E Millstone, NJ USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 6 BP 1 EP 2 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500007 ER PT J AU Hastings, K Bussiere, J House, RV Dean, J AF Hastings, K Bussiere, J House, RV Dean, J TI Evaluation of immunomodulation in safety assessment SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Sanofi Synthelabo, Malvern, PA USA. Dynport Vaccine Co, Frederick, MD USA. Immunex Corp, Seattle, WA USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 11 BP 2 EP 2 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500012 ER PT J AU Scott, GN Betz, J Yetley, EA Smith, CS AF Scott, GN Betz, J Yetley, EA Smith, CS TI Medicinal herbals and dietary supplements. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Natl Inst Environm Hlth, Res Triangle Pk, NC USA. US FDA, College Pk, MD USA. NIH, Bethesda, MD 20892 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 7 BP 2 EP 2 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500008 ER PT J AU Zhang, J Honchel, R Herman, EH Weaver, JL Knapton, A Sistare, ED AF Zhang, J Honchel, R Herman, EH Weaver, JL Knapton, A Sistare, ED TI Mesenteric and pancreatic vascular injury induced by fenoldopam in Sprague-Dawley (SD) rats: Evidence for mast cell mediated pathogenesis. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 2003 VL 72 SU S MA 151 BP 31 EP 32 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500154 ER PT J AU Ferguson, SA Gough, BJ AF Ferguson, SA Gough, BJ TI In vivo basal and amphetamine-stimulated striatal dopamine (DA) release is similar in adult spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) male rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR FDA, Neurotoxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 345 BP 71 EP 71 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500348 ER PT J AU Deldos, KB Weis, CC Olson, G Bucci, TJ Newbold, RR AF Deldos, KB Weis, CC Olson, G Bucci, TJ Newbold, RR TI A five generation reproductive toxicity assessment of the soy isoflavone genistein in CD Sprague-Dawley rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Jefferson, AR USA. Pathol Associates Int, Jefferson, AR USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 368 BP 76 EP 76 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500371 ER PT J AU Disch, AD Imam, SZ Jankovic, J Skinner, JT Xie, W Conneely, OM Ali, S Le, W AF Disch, AD Imam, SZ Jankovic, J Skinner, JT Xie, W Conneely, OM Ali, S Le, W TI Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 deficient mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 USFDA, NCTR, Neurotoxicol, Jefferson, AR USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 378 BP 78 EP 78 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500381 ER PT J AU Duhart, HM Imam, SZ Skinner, JT Slikker, W Ali, S AF Duhart, HM Imam, SZ Skinner, JT Slikker, W Ali, S TI Cocaine induces a dose dependent alteration in gene expression of apoptotic cascade in PC12 cells. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 USFDA, NCTR, Neurotoxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 379 BP 78 EP 78 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500382 ER PT J AU Cheeseman, MA Collazo-Braier, N Twaroski, ML Mayer, J Yang, C Myatt, GJ Blower, PE AF Cheeseman, MA Collazo-Braier, N Twaroski, ML Mayer, J Yang, C Myatt, GJ Blower, PE TI Comparison of compound classifications determined from structural alerts for rodent carcinogenicity extracted from different databases. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 LeadScope Inc, Columbus, OH USA. US FDA, CFSAN, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 400 BP 83 EP 83 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500403 ER PT J AU Desai, VG Moland, CL Branham, WS Duffy, PH Delongchamp, RR Fang, H Peterson, CA Beggs, ML Fuscoe, JC AF Desai, VG Moland, CL Branham, WS Duffy, PH Delongchamp, RR Fang, H Peterson, CA Beggs, ML Fuscoe, JC TI Microarray analysis to examine changes in expression level of genes as a function of time of day in Fischer 344 rat liver. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Ctr Funct Genom, Jefferson, AR USA. NCTR, DGRT, Jefferson, AR USA. NCTR, Div Biometry, Jefferson, AR USA. NCTR, ROW, Jefferson, AR USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 451 BP 93 EP 93 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500454 ER PT J AU Roberts, ES Charboneau, L Liotta, L Petricoin, E Dreher, KL AF Roberts, ES Charboneau, L Liotta, L Petricoin, E Dreher, KL TI Alterations in airway intracellular signaling pathways following air pollution particle (PM) exposure using laser capture microdissection and protein array technologies. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. NIH, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. US EPA, NHEERL, Res Triangle Pk, NC 27711 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 513 BP 106 EP 106 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500516 ER PT J AU Fu, X Blaydes, B Roberts, DW Weist, C Latendresse, JR Muskhelishvili, L Sutter, TR Delclos, B AF Fu, X Blaydes, B Roberts, DW Weist, C Latendresse, JR Muskhelishvili, L Sutter, TR Delclos, B TI Effects of estrous cycle and soy on cytochrome P4501B1 (CYP1B1) protein expression in female rat adrenal glands. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Memphis, Memphis, TN 38152 USA. Pathol Associates Int, Jefferson, AR USA. RI Latendresse, John/A-9215-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 527 BP 108 EP 108 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500530 ER PT J AU Papaconstantinou, AD Goering, PL Umbreit, TH Brown, KM AF Papaconstantinou, AD Goering, PL Umbreit, TH Brown, KM TI Regulation of uterine HSP90 alpha, HSP72 and HSF-1e expression in B6C3F1 mice by beta-estradiol and bisphenol A: Involvement of the estrogen receptor and protein kinase C. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 653 BP 134 EP 134 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500656 ER PT J AU Harris, AJ Dial, S Casciano, DA AF Harris, AJ Dial, S Casciano, DA TI Cluster analysis of gene expression in primary human hepatocytes and HepG2 cells treated with hepatotoxicants and hepatocarcinogens. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Ctr Hepatotox, Jefferson, AR USA. NCTR, Off Director, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 726 BP 150 EP 150 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500732 ER PT J AU Young, JF Luecke, RH Doerge, DR AF Young, JF Luecke, RH Doerge, DR TI Interspecies physiologically based pharmacokinetic modeling of genistein. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Jefferson, AR USA. Univ Missouri, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 877 BP 180 EP 180 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500883 ER PT J AU Shankar, K Vaidya, VS Manautou, JE Corron, JC Bucci, TJ Liu, J Waalkes, MP Mehendale, HM AF Shankar, K Vaidya, VS Manautou, JE Corron, JC Bucci, TJ Liu, J Waalkes, MP Mehendale, HM TI PPAR-alpha activation is essential for diabetes-induced resistance against acetaminophen hepatotoxicity. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NE Louisiana Univ, Monroe, LA 71209 USA. Univ Connecticut, Dept Pharmacol Sci, Storrs, CT 06269 USA. Toxicogenom, Chapel Hill, NC USA. Pathol Associates Intl, NCTR, Jefferson, AR USA. NIEHS, Inorgan Carcinogenesis Sect, NCI, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 946 BP 195 EP 195 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500952 ER PT J AU Limaye, PB Apte, UM Bocci, TJ Warbritton, A Mehendale, HM AF Limaye, PB Apte, UM Bocci, TJ Warbritton, A Mehendale, HM TI Why does injury progress even after toxicant is gone? A novel mechanism SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NE Louisiana Univ, Dept Toxicol, Monroe, LA 71209 USA. Pathol Associates Inc, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 950 BP 196 EP 196 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500956 ER PT J AU Sawant, SP Dnyanmote, AV Latendresse, JR Mehendale, HM AF Sawant, SP Dnyanmote, AV Latendresse, JR Mehendale, HM TI Mechanism of enhanced CCL4-induced hepatotoxicity in type 2 diabetes: Role of tissue repair. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. NCTR, Jefferson, AR USA. RI Latendresse, John/A-9215-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 956 BP 197 EP 197 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500962 ER PT J AU Dial, S Cromwell, A Harris, AJ AF Dial, S Cromwell, A Harris, AJ TI Analysis of gender differences in expression of IGF-1, CYPIA2 and CYP3A1 in human liver. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Ctr Hepatotox, Jefferson, AR USA. Hendrix Coll, Dept Biol, Conway, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 959 BP 198 EP 198 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500965 ER PT J AU Bendre, S Patton, RE Shaddock, JG Dobrovolsky, VN Heflich, RH AF Bendre, S Patton, RE Shaddock, JG Dobrovolsky, VN Heflich, RH TI Toxicity of chronic azathioprine administration in somatic and germ cells of C57BL/6 mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Genet Toxicol, Little Rock, AR USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 993 BP 205 EP 205 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500999 ER PT J AU Fu, PP Blankenship, LG Webb, PJ Wamer, WG Howard, PC Xia, Q AF Fu, PP Blankenship, LG Webb, PJ Wamer, WG Howard, PC Xia, Q TI Photostability and photogenotoxicity of retinyl palmitate. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Div Biochem Toxicol, Jefferson, AR USA. USFDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1007 BP 208 EP 208 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501013 ER PT J AU Tomazic-Jezic, VJ Sanchez, BA Lucas, AD AF Tomazic-Jezic, VJ Sanchez, BA Lucas, AD TI Factors affecting binding of natural rubber latex (NRL) proteins to glove dusting powder. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1116 BP 229 EP 230 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501122 ER PT J AU Pine, P Herman, EH Zhang, J Knapton, AD Holt, G Sistare, FD AF Pine, P Herman, EH Zhang, J Knapton, AD Holt, G Sistare, FD TI Identification of doxorubicin-induced changes in protein features in rat sera using cluster analysis and expression profiling. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US FDA, CDER, DAPR, Laurel, MD USA. Oxford Glycosci Ltd, Abingdon, Oxon, England. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1167 BP 240 EP 240 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501173 ER PT J AU Luu, HD Kim, CS Sapienza, FF Ross, IA Johnson, WD Hutter, JC AF Luu, HD Kim, CS Sapienza, FF Ross, IA Johnson, WD Hutter, JC TI Bioavailability of bisphenol A: Prediction of estrogen disruption in humans. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US FDA, CDRH, Rockville, MD 20857 USA. US FDA, CFSAN, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1170 BP 241 EP 241 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501176 ER PT J AU Binienda, ZK Skinner, RD Summage, JL Thorn, BT Slikker, W AF Binienda, ZK Skinner, RD Summage, JL Thorn, BT Slikker, W TI Electroencephalographic response to acute 3-nitropropionic acid (3-NPA) exposure. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. ROW, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1183 BP 243 EP 243 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501188 ER PT J AU Carrington, CD Bolger, M AF Carrington, CD Bolger, M TI An intervention analysis for the reduction of exposure to methylmercury from the consumption of seafood. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1194 BP 246 EP 246 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501199 ER PT J AU Xia, Q Chou, MW Lin, G Fu, PP AF Xia, Q Chou, MW Lin, G Fu, PP TI Formation of DHP-derived DNA adducts from metabolic activation of clivorine, a representative otonecine-type pyrrolizidine alkaloid, and Ligularia hodgsonnii hook plant extract SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Biochem Toxicol Div, Jefferson, AR USA. Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1214 BP 250 EP 250 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501219 ER PT J AU Haschek, WM Waggoner, AL Hsiao, S Smith, GW Tumbleson, ME Eppley, RM Foreman, JH Constable, PD AF Haschek, WM Waggoner, AL Hsiao, S Smith, GW Tumbleson, ME Eppley, RM Foreman, JH Constable, PD TI Clinicopathologic characterization of fumonisin B-1 (FB1) induced hepato, nephro-and neuro-toxicity in horses. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Illinois, Urbana, IL 61801 USA. US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1224 BP 252 EP 252 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501229 ER PT J AU Tumbleson, ME Haschek, WM Waggoner, AL Constable, PD Smith, GW Foreman, JH Eppley, RM AF Tumbleson, ME Haschek, WM Waggoner, AL Constable, PD Smith, GW Foreman, JH Eppley, RM TI Fumonisin B-1 (FB1) alters sphinganine (SA) and sphingosine (SO) concentrations in serum, tissue, urine and cerebrospinal fluid (CSF) of horses. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Illinois, Urbana, IL 61801 USA. US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 2003 VL 72 SU S MA 1235 BP 254 EP 254 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501240 ER PT J AU Ali, A He, Y Dong, Z Jankovic, J Appel, SH Le, W Slikker, W Imam, SZ AF Ali, A He, Y Dong, Z Jankovic, J Appel, SH Le, W Slikker, W Imam, SZ TI Role of nitric oxide in rotenone-induced nigro-striatal injury. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1246 BP 256 EP 256 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501251 ER PT J AU Choudhuri, S Cherrington, N Li, N Klaassen, CD AF Choudhuri, S Cherrington, N Li, N Klaassen, CD TI Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroid plexus of adult Sprague-Dawley rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1257 BP 258 EP 258 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501262 ER PT J AU Rosenzweig, BA Pine, PS Domon, OE Sistare, ED Morris, S AF Rosenzweig, BA Pine, PS Domon, OE Sistare, ED Morris, S TI A practical experimental design to correct for dye bias in dual-labeled cDNA microarray experiments without sacrificing precision. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US FDA, CDER, Laurel, MD USA. NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1280 BP 263 EP 263 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501285 ER PT J AU Petricoin, E AF Petricoin, E TI Serum proteomic pattern diagnostics: Use of artificial intelligence bioinformatics to discover surrogate markers for early disease. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 2003 VL 72 SU S MA 1346 BP 277 EP 277 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501353 ER PT J AU Slikker, W Wallace, KB AF Slikker, W Wallace, KB TI Dose-dependent transitions in toxic mechanisms. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 USFDA, Div Neurotoxicol, NCTR, Jefferson, AR USA. Univ Minnesota, Dept Biochem & Mol Biol, Minneapolis, MN 55455 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 2003 VL 72 SU S MA 1352 BP 278 EP 278 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501359 ER PT J AU Wallace, KB Slikker, W AF Wallace, KB Slikker, W TI Strategies to identify saturable and/or inducible kinetic and dynamic stages of dose-dependent transitions in toxic mechanism. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Minnesota, Minneapolis, MN 55455 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1357 BP 279 EP 279 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501364 ER PT J AU Goodsaid, FM Smith, R Mandakas, G Rosenblum, IY Zhang, J Honchel, R Knapton, A Rosenzweig, BA Sistare, FD AF Goodsaid, FM Smith, R Mandakas, G Rosenblum, IY Zhang, J Honchel, R Knapton, A Rosenzweig, BA Sistare, FD TI Quantitative gene expression changes in peripheral blood leukocytes (PBL) of rats with fenoldopam-induced vascular injury. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Schering Plough Corp, Res Inst, Lafayette, NJ USA. USFDA, Ctr Drug Evaluat & Res, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1388 BP 286 EP 286 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501395 ER PT J AU Thompson, K Rosenzweig, BA Pine, P Zhang, J Herman, EH Knapton, AD Honchel, R Shimada, B Kassam, S Finkelstein, DB Lescallet, J Retief, JD Sistare, FD AF Thompson, K Rosenzweig, BA Pine, P Zhang, J Herman, EH Knapton, AD Honchel, R Shimada, B Kassam, S Finkelstein, DB Lescallet, J Retief, JD Sistare, FD TI Identification of genes linked to doxorubicin cardiotoxicity and to the cardioprotectant effect of dexrazoxane in rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 USFDA, CDER, DAPR, Laurel, MD USA. Affymetrix Inc, Santa Clara, CA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1389 BP 286 EP 286 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501396 ER PT J AU Heussner, AH O'Brien, E Stack, ME Dietrich, DR AF Heussner, AH O'Brien, E Stack, ME Dietrich, DR TI Alterations in human and porcine renal cells after repeated exposure to OTA and OTB. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Konstanz, D-7750 Constance, Germany. USFDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 2003 VL 72 SU S MA 1683 BP 346 EP 347 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501690 ER PT J AU Blaydes, B Muskhelishvili, L Latendress, JR Delclos, KB AF Blaydes, B Muskhelishvili, L Latendress, JR Delclos, KB TI Modulation of renal cyclooxygenase-2 (cox-2) by diet and stage of estrous in CD Sprague-Dawley rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Jefferson, AR USA. Pathol Associates Int, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1691 BP 348 EP 348 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501698 ER PT J AU Dnyanmote, AV Sawant, SP Lock, EA Latandresse, JR Mehendale, HM AF Dnyanmote, AV Sawant, SP Lock, EA Latandresse, JR Mehendale, HM TI Nephroprotection from S-1, 2-dichlorovinyl-(L)-cysteine in diabetic mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NE Louisiana Univ, Monroe, LA 71209 USA. Syngenta, CTL, Macclesfield, Cheshire, England. Pathol Associates Int, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1689 BP 348 EP 348 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501696 ER PT J AU Kraeling, ME Bronaugh, RL AF Kraeling, ME Bronaugh, RL TI In vitro percutaneous absorption of acrylamide and styrene in human skin SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 USFDA, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1844 BP 380 EP 380 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501851 ER PT J AU Yourick, JJ Bronaugh, RL AF Yourick, JJ Bronaugh, RL TI Methyleugenol skin absorption in human and fuzzy rat skin. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 USFDA, Cosmet Toxicol Branch, Laurel, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 2003 VL 72 SU S MA 1846 BP 380 EP 380 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501853 ER PT J AU Bolger, PM Carrington, C Canady, R AF Bolger, PM Carrington, C Canady, R TI Framework for assessing dietary chemical threats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 USFDA, Dept Hlth & Human Serv, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 72 SU S MA 1897 BP 391 EP 391 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501905 ER PT J AU Humphreys, SH Bolger, PM Canady, RA AF Humphreys, SH Bolger, PM Canady, RA TI Acrylamide: A case study in hazard assessment of genetic toxicity SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Ctr Food Safety & Appl Nutr, Div Risk Assessmente, College Pk, MD USA. NR 0 TC 0 Z9 0 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 MAR PY 2003 VL 72 SU S MA 1902 BP 392 EP 392 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501909 ER PT J AU Mohan, KVK Kulkarni, S Glass, RI Bai, ZS Atreya, CD AF Mohan, KVK Kulkarni, S Glass, RI Bai, ZS Atreya, CD TI A human vaccine strain of lamb rotavirus (Chinese) NSP4 gene: Complete nucleotide sequence and phylogenetic analyses SO VIRUS GENES LA English DT Article DE enterotoxin; genotypes; homology; NS28; phylogeny ID NONSTRUCTURAL GLYCOPROTEIN NSP4; GROUP-C ROTAVIRUSES; GROUP-A; ENDOPLASMIC-RETICULUM; MUTATIONS; PROTEIN; VIRUS; ENTEROTOXIN; DIARRHEA; VP4 AB A lamb strain of rotavirus has recently been licensed for use in China as a live vaccine to prevent rotavirus diarrhea in children. As rotavirus NSP4, especially the cytotoxic domain alone is considered to be associated with diarrhea, we sequenced gene segment 10, which encodes NSP4, of lamb rotavirus. Comparative analyses was performed to identify differences from human rotavirus strains, that might be associated with attenuation, and to ascertain whether the lamb rotavirus gene fits among the NSP4 of other sequenced rotavirus strains. Our comparative nucleotide sequence analysis suggests its close identity (91.17% homology) with that of group-A equine rotavirus (strain H123). Multiple alignment of the deduced amino acid sequence of lamb NSP4 with that of other group A rotaviruses demonstrated homology ranging from 63.42% with that of porcine YM strain to 93.71% with equine H123 strain of rotavirus. A group A-specific NSP4 monoclonal antibody recognized the glycosylated and unglycosylated forms of the protein from virus-infected lysates, suggesting a well-conserved group-specificity of the lamb NSP4. Phylogenetic analysis of the lamb rotavirus gene, with 60 other NSP4 gene sequences of human and animal rotavirus strains, demonstrated that the lamb rotavirus strain belongs to genotype A. Comparative analysis also revealed that although it is a vaccine strain, the NSP4 cytotoxic domain of lamb strain demonstrated an overall amino acid conservation similar to that of other strains, whose NSP4 alone causes diarrhea in animal models. These results taken together with our previous observations clearly reaffirm the idea that the attenuation phenotype of rotaviruses does not involve NSP4 cytotoxic domain, perhaps due to the suppression of NSP4 cytotoxic activity by other rotaviral proteins. C1 US FDA, Sect Viral Pathogenesis & Vaccine Adverse React, Lab Pediat & Resp Viral Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. CDCP, Viral Gastroenteritis Sect, Resp & Enter Viruses Branch, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. Lanzhou Inst Biol Prod, Lanzhou 730046, Gansu Province, Peoples R China. RP Atreya, CD (reprint author), US FDA, Sect Viral Pathogenesis & Vaccine Adverse React, Lab Pediat & Resp Viral Dis, Ctr Biol Evaluat & Res, Bldg 29A,Room 2C-11,HFM-460,NIH Campus,8800 Rockv, Bethesda, MD 20892 USA. NR 32 TC 9 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD MAR PY 2003 VL 26 IS 2 BP 185 EP 192 DI 10.1023/A:1023491514820 PG 8 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 671JT UT WOS:000182462200009 PM 12803470 ER PT J AU Dolan, SP Nortrup, DA Bolger, PM Capar, SG AF Dolan, SP Nortrup, DA Bolger, PM Capar, SG TI Analysis of dietary supplements for arsenic, cadmium, mercury, and lead using inductively coupled plasma mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE dietary supplements; arsenic; cadmium; mercury; lead; microwave digestion; high-resolution ICP-MS ID TRADITIONAL CHINESE MEDICINE; HEAVY-METALS; ICP-MS; MICROWAVE DIGESTION; DRUGS AB The arsenic, cadmium, mercury, and lead contents of 95 dietary supplement products were determined using microwave digestion and high-resolution inductively coupled plasma mass spectrometry. Precision and accuracy were demonstrated by element recovery from 17 dietary supplements and replicates of 8 reference materials. The concentration ranges were as follows: arsenic, <5-3770 mug/kg; cadmium, <10-368 mug/kg; mercury, <80-16800 mug/kg; and lead, <20-48600 mug/kg. An assessment of estimated exposures/intakes of the four elements is presented. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Capar, SG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 26 TC 88 Z9 94 U1 5 U2 32 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 26 PY 2003 VL 51 IS 5 BP 1307 EP 1312 DI 10.1021/jf026055x PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 647HJ UT WOS:000181087100033 PM 12590474 ER PT J AU Colman, E AF Colman, E TI Mercury in infants given vaccines containing thiomersal SO LANCET LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Colman, E (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD FEB 22 PY 2003 VL 361 IS 9358 BP 698 EP 698 DI 10.1016/S0140-6736(03)12572-X PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 648BG UT WOS:000181129500027 PM 12606188 ER PT J AU Hill, DM Kasliwal, T Schwarz, E Hebert, AM Chen, T Gubina, E Zhang, L Kozlowski, S AF Hill, DM Kasliwal, T Schwarz, E Hebert, AM Chen, T Gubina, E Zhang, L Kozlowski, S TI A dominant negative mutant beta 2-microglobulin blocks the extracellular folding of a major histocompatibility complex class I heavy chain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MHC CLASS-I; INDUCED CONFORMATIONAL CHANGE; CELL-SURFACE EXPRESSION; T-CELL; HUMAN BETA(2)-MICROGLOBULIN; ANTIGEN PRESENTATION; CRYSTAL-STRUCTURE; PEPTIDE BINDING; ALPHA-3 DOMAIN; MOLECULES AB The major histocompatibility complex class I (MHC1) molecule plays a crucial role in cytotoxic lymphocyte function. beta2-Microglobutin (beta2m) has been demonstrated to be both a structural component of the MHC1 complex and a chaperone-like molecule for MHC1 folding. beta2m binding to an isolated alpha3 domain of MHC1 heavy chain at micromolar concentrations has been shown to accurately model the biochemistry and thermodynamics of beta2m-driven MHC1 folding. These results suggested a model in which the chaperone-like role of beta2m is dependent on initial binding to the alpha3 domain interface of MHC1 with beta2m. Such a model predicts that a mutant beta2m molecule with an intact MHC1 alpha3 domain interaction but a defective MHC1 alpha1alpha2 domain interaction would block beta2m-driven folding of MHC1. In this study we generated such a beta2m mutant and demonstrated that it blocks MHC1 folding by normal beta2m at the expected micromolar concentrations. Our data support an initial interaction of beta2m with the MHC1 alpha3 domain in MHC I folding. In addition, the dominant negative mutant beta2m can block T-cell functional responses to antigenic peptide and MHC1. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Kozlowski, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 29 Lincoln Dr,Bldg 29B-3NN08,HFM-561, Bethesda, MD 20892 USA. NR 68 TC 16 Z9 17 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 21 PY 2003 VL 278 IS 8 BP 5630 EP 5638 DI 10.1074/jbc.M208381200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400020 PM 12454016 ER PT J AU Uhl, K Kennedy, DL AF Uhl, K Kennedy, DL TI Accurate information on drug effects on pregnancy is crucial SO AMERICAN FAMILY PHYSICIAN LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Team, Rockville, MD 20852 USA. RP Uhl, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Team, 1451 Rockville Pike,HFD-040, Rockville, MD 20852 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD FEB 15 PY 2003 VL 67 IS 4 BP 700 EP 701 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 648EG UT WOS:000181136400003 PM 12613724 ER PT J AU Aoki, Y Feldman, GM Tosato, G AF Aoki, Y Feldman, GM Tosato, G TI Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma SO BLOOD LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKINS-LYMPHOMA; ENDOTHELIAL GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; LEUKEMIA-CELLS; VIRAL IL-6; ACTIVATION; TRANSDUCER; TRANSCRIPTION-3 AB Despite some exciting new leads in molecular pathogenesis, AIDS-defining primary effusion lymphoma (PEL) remains a fatal malignancy. The lack of substantial progress in the management of PEL demands innovative treatment approaches. Targeting intracellular molecules critical to cell survival is one unexplored strategy for treating PEL. Here we show that inhibition of signal transducer and activator of transcription-3 (STAT3) leads to apoptosis in PEL cells. STAT3 is constitutively phosphorylated in PEL cell lines BC-1, BCBL-1, and VG-1. Transduction of dominant-negative STAT3 and pharmacological STAT3 inhibition caused caspase-dependent cell death. Although STAT3 activation is known to induce expression of Bcl-2 family proteins, PEL cell apoptosis was independent of Bcl-2, BCI-X-L, or Mcl-1 protein expression. Instead, STAT3 inhibition induced transcriptional repression of survivin, a recently identified inhibitor of apoptosis. Forced overexpression of survivin rescued VG-1 cells from apoptosis induced by STAT3 inhibition. Our findings suggest that activated STAT3 signaling directly contributes to malignant progression of PEL by preventing apoptosis, acting through the prosurvival protein survivin. Since constitutive STAT3 activation and survivin expression have been widely documented in different types of cancers, their linkage may extend to many malignancies and be critical to their pathogenesis. (C) 2003 by The American Society of Hematology. C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20014 USA. RP Aoki, Y (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,12N226, Bethesda, MD 20892 USA. NR 52 TC 291 Z9 304 U1 0 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2003 VL 101 IS 4 BP 1535 EP 1542 DI 10.1182/blood-2002-07-2130 PG 8 WC Hematology SC Hematology GA 643DM UT WOS:000180846700049 PM 12393476 ER PT J AU Shvartsburg, AA Wilkes, JG AF Shvartsburg, AA Wilkes, JG TI Chemistry in aldol complexes of metal dications: dehydration of the bisligand species SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE multiply charged ions; metal cations; ion solvation; electrospray ionization; dehydration ID ELECTROSPRAY MASS-SPECTROMETRY; CHARGED ALKALINE-EARTH; GAS-PHASE REACTIONS; M = MG; HYDRATION ENERGIES; PHOTODISSOCIATION DYNAMICS; EQUILIBRIA DETERMINATIONS; GOLD(II) COMPLEXES; BINDING-ENERGIES; IONS M2+ AB The advent of electrospray has enabled the generation of microsolvated multiply charged metal ions. For dications, these had been produced for most common organic ligand classes including simple alcohols and ketones, but not aldols. Solution-phase aldol chemistry is reknown for dehydration and retro-aldol reactions. One of the simplest aldols is the acetone dimer, known as diacetone alcohol (DAA). It has recently been shown to coordinate gas-phase metal trications-the first precedent thereof for any protic solvent. Here we report on the formation and collisional fragmentation of DAA complexes for dications of divalent metals (M = Mg, Ca, Ba, Mn, Ni, Co, Fe, and Cu). Both retro-aldol and dehydration processes were observed in these species. Most notable is the extreme size-specificity of dehydration. Sequential loss of two waters dominates the dissociation of M2+(DAA)(2) for all metals studied, yielding extraordinary M2+(mesityl oxide)(2) peaks. However, M2+ (DAA)(3) essentially do not dehydrate. This suggests a geometry of complexes with two DAA in the first solvation shell, perhaps in a bidentate arrangement involving both carbonyl and hydroxyl. Similarly to their simple alcohol analogs, charge-reduction of M2+(DAA), proceeds via proton transfer, except in the case of Cu where proton and electron transfers compete. A comparison of the critical and minimum sizes for M2+(DAA)(n) and M3+ (DAA), reveals a major intrinsic gap between the stabilities of metal di- and trications in protic solvent complexes. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Shvartsburg, AA (reprint author), Natl Ctr Toxicol Res, Div Chem, HFT-233,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 50 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD FEB 15 PY 2003 VL 225 IS 2 BP 155 EP 166 DI 10.1016/S1387-380602)01112-0 PG 12 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 641WV UT WOS:000180770800005 ER PT J AU Racoosin, JA AF Racoosin, JA TI Mortality in epilepsy - Searching for clues in populations and patients SO NEUROLOGY LA English DT Editorial Material ID SUDDEN UNEXPECTED DEATH; PROGRAM; COHORT C1 US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Racoosin, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. NR 9 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 11 PY 2003 VL 60 IS 3 BP 363 EP 364 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 646BG UT WOS:000181014500002 PM 12578914 ER PT J AU Hanson, EM Dickensheets, H Qu, CK Donnelly, RP Keegan, AD AF Hanson, EM Dickensheets, H Qu, CK Donnelly, RP Keegan, AD TI Regulation of the dephosphorylation of Stat6 - Participation of TYR-713 in the interleukin-4 receptor alpha, the tyrosine phosphatase SHP-1, and the proteasome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; NUCLEAR-LOCALIZATION; NEGATIVE REGULATION; GENE-EXPRESSION; IL-4 RECEPTOR; CUTTING EDGE; MOTH-EATEN; T-CELLS; B-CELLS; PROTEIN AB Signal transducer and activator of transcription 6 (Stat6) plays an important role in interleukin (IL)-4-induced responses. To analyze the regulation of Stat6 phosphorylation, cells were cultured in the continuous presence of IL-4 or after a pulse and washout. In the continual presence of IL-4, Stat6 remained phosphorylated for an extended period. After IL-4 removal and inhibition of the Janus family kinase, tyrosine-phosphorylated Stat6 decayed at a rate dependent upon the length of IL-4 stimulation. The decay of tyrosine-phosphorylated Stat6 was similar in the presence or absence of either cycloheximide or actinomycin D. In the absence of functional Src homology-containing phosphatase-1 (SHP-1), the early loss of tyrosine-phosphorylated Stat6 was substantially reduced. Furthermore, the rate of loss of tyrosine-phosphorylated Stat6 in cells expressing a mutation of the human IL-4 receptor a in the immunoreceptor tyrosine-based inhibitory motif sequence (Y5F) was dramatically decreased compared with wild-type cells. The early rate of decay was similar in the presence or absence of MG132, an inhibitor of the proteasome, but the later rate of decay was decreased 5-fold. These results suggest that the loss of tyrosine phosphorylation of Stat6 is regulated by the action of SHP-1 and the proteasome but is not dependent on new protein synthesis. C1 Amer Red Cross, Holland Lab, Dept Immunol, Rockville, MD 20855 USA. Amer Red Cross, Holland Lab, Dept Hematopoiesis, Rockville, MD 20855 USA. Fed Drug Adm, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. George Washington Univ, Ctr Med, Inst Biomed Sci, Bethesda, MD 20892 USA. RP Keegan, AD (reprint author), Amer Red Cross, Holland Lab, Dept Immunol, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. FU NIAID NIH HHS [AI38985] NR 50 TC 45 Z9 47 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 7 PY 2003 VL 278 IS 6 BP 3903 EP 3911 DI 10.1074/jbc.M211747200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 643PM UT WOS:000180869700051 PM 12459556 ER PT J AU Wagner, RF Beiden, SV AF Wagner, RF Beiden, SV TI Independent versus sequential reading in roc studies of computer-assist modalites: Analysis of components of variance SO ACADEMIC RADIOLOGY LA English DT Letter C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ-142, Rockville, MD 20857 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2003 VL 10 IS 2 BP 211 EP 212 DI 10.1016/S1076-6332(03)80047-8 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 640QB UT WOS:000180698500013 PM 12583574 ER PT J AU Slifman, NR Gershon, SK Lee, JH Edwards, ET Braun, MM AF Slifman, NR Gershon, SK Lee, JH Edwards, ET Braun, MM TI Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor alpha-neutralizing agents SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; FACTOR RECEPTOR; TNF-ALPHA; INFLIXIMAB; THERAPY; TUBERCULOSIS; RESISTANCE; MONOCYTES; PATIENT AB Objective. Tumor necrosis factor alpha (TNFalpha) has been implicated in the pathogenesis of certain inflammatory diseases. Two TNFalpha-neutralizing agents are licensed in the US. Infliximab is licensed for the treatment of Crohn's disease (CD) and, when used with methotrexate, for the treatment of rheumatoid arthritis (RA). Etanercept is licensed for the treatment of RA, including juvenile RA, and, more recently, was licensed for the treatment of psoriatic arthritis. Because of the potential for decreased host resistance to infectious agents due to treatment with anti-TNFalpha agents, we sought to evaluate postlicensure cases of opportunistic infection, including Listeria monocytogenes, in patients treated with these products. Methods. The FDA Adverse Event Reporting System, a passive monitoring system, was reviewed to identify all reports of adverse events (through December 2001) associated with L monocytogenes infection in patients treated with infliximab or etanercept. Results. Fifteen cases of L monocytogenes infection associated with infliximab or etanercept treatment were identified. In 14 of these cases, patients had received infliximab. The median age of all patients was 69.5 years (range 17-80 years); 53% were female. Six deaths were reported. Among patients for whom an indication for use was reported, there were 9 patients (64%) with RA and 5 patients (36%) with CD (information was not reported for 1 patient). All patients for whom information was reported were receiving concurrent immunosuppressant drugs. Conclusion. Postlicensure surveillance suggests that L monocytogenes infection may be a serious complication of treatment with TNFalpha-neutralizing agents, particularly infliximab. C1 FDA, CBER, Off Biostat & Epidemiol, Div Epidemiol, Rockville, MD 20852 USA. RP Braun, MM (reprint author), FDA, CBER, Off Biostat & Epidemiol, Div Epidemiol, HFM-220,1401 Rockville Pike, Rockville, MD 20852 USA. NR 39 TC 230 Z9 236 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 2003 VL 48 IS 2 BP 319 EP 324 DI 10.1002/art.10758 PG 6 WC Rheumatology SC Rheumatology GA 645CG UT WOS:000180958200006 PM 12571839 ER PT J AU Murray, D Venable, RM Pastor, RW AF Murray, D Venable, RM Pastor, RW TI Computational models for the structures of phosphoinositides SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. US FDA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 46A EP 46A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800219 ER PT J AU Lague, P Roux, B AF Lague, P Roux, B TI Perturbation free energy profile of alpha-helix insertion into lipid bilayer SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 US FDA, CBER, Biophys Lab, Rockville, MD 20852 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 58A EP 58A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800282 ER PT J AU Kang, H Hwang, SY Kim, YM Kim, E Kim, YS Kim, SK Kim, SW Cerniglia, CE Shuttleworth, KL Zylstra, GJ AF Kang, H Hwang, SY Kim, YM Kim, E Kim, YS Kim, SK Kim, SW Cerniglia, CE Shuttleworth, KL Zylstra, GJ TI Degradation of phenanthrene and naphthalene by a Burkholderia species strain SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE Burkholderia; phenanthrene; naphthalene; phthalate; protocatechuate ID PSEUDOMONAS-PUTIDA; MYCOBACTERIUM SP; CATABOLISM; OXIDATION; PATHWAY; GENES; DIOXYGENASE; BACTERIA; OPERONS; RP007 AB Burkholderia sp. TNFYE-5 was isolated from soil for the ability to grow on phenanthrene as sole carbon and energy source. Unlike most other phenanthrene-degrading bacteria, TNFYE-5 was unable to grow on naphthalene. Growth substrate range experiments coupled with the ring-cleavage enzyme assay data suggest that TNFYE-5 initially metabolizes phenanthrene to 1-hydroxy-2-naphthoate with subsequent degradation through the phthalate and protocatechuate and beta-ketoadipate pathway. A metabolite in the degradation of naphthalene by TNFYE-5 was isolated by high-pressure liquid chromatography (HPLC) and was identified as salicylate by UV-visible spectral and gas chromatography - mass spectrometry analyses. Thus, the inability to degrade salicylate is apparently one major reason for the incapability of TNFYE-5 to grow on naphthalene. C1 Yonsei Univ, Dept Biol, Seoul 120749, South Korea. Yonsei Univ, Inst Life Sci, Seoul 120749, South Korea. Chung Ang Univ, Dept Life Sci, Seoul 156756, South Korea. Chosun Univ, Dept Environm Engn, Kwangju 501759, South Korea. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Rutgers State Univ, Cook Coll, Biotechnol Ctr Agr & Environm, New Brunswick, NJ 08901 USA. RP Kim, E (reprint author), Yonsei Univ, Dept Biol, Seoul 120749, South Korea. NR 31 TC 31 Z9 32 U1 0 U2 7 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD FEB PY 2003 VL 49 IS 2 BP 139 EP 144 DI 10.1139/W03-009 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 664UH UT WOS:000182079800009 PM 12718402 ER PT J AU Ahmad, SR Lee, L Brinker, P Beitz, J AF Ahmad, SR Lee, L Brinker, P Beitz, J TI Comparative risks of myocardial infarction with triptans. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, CDER, Off Drug Safety, DDRE, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P40 EP P40 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100145 ER PT J AU Booth, BP Rahman, A Ibrahim, A Scher, N Williams, G Schran, H Ma, P Hsu, C Gobburu, JV AF Booth, BP Rahman, A Ibrahim, A Scher, N Williams, G Schran, H Ma, P Hsu, C Gobburu, JV TI Population pharmacokinetic model for zoledronic acid (zometa) in patients with bone metastases. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 Novartis Pharmaceut Inc, FDA, CDER, OCPB,OND, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P67 EP P67 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100247 ER PT J AU Booth, BP Rahman, A Dagher, RN Griebel, D Lai, A Lennon, S Fuller, D Gobburu, JV AF Booth, BP Rahman, A Dagher, RN Griebel, D Lai, A Lennon, S Fuller, D Gobburu, JV TI Population pharmacokinetic (PPK) modeling and simulation-derived dosing of intravenous Busulfan (Busulfex) in pediatric patients. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 Orphan Med Inc, CPKD Solut, FDA, CDER,OCPB,OND, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P66 EP P66 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100244 ER PT J AU Brinker, A Senior, J Beitz, J AF Brinker, A Senior, J Beitz, J TI Misdiagnosis of ischemic colitis as irritable bowel syndrome. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, CDER, Off Drug Safety, Rockville, MD 20857 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P33 EP P33 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100120 ER PT J AU Chen, M Huang, S AF Chen, M Huang, S TI Drugs withdrawn in recent years have greater risk in women? Findings from postmarketing reporting of adverse events data. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P95 EP P95 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100350 ER PT J AU Chou, W Huang, S Sahajwalla, CG Lesko, LJ AF Chou, W Huang, S Sahajwalla, CG Lesko, LJ TI Informal survey of pharmacogenetics/pharmacogenomics (PGTX) in a sample of IND's and NDA's. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P33 EP P33 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100117 ER PT J AU Chung, S Ahn, H Wei, X AF Chung, S Ahn, H Wei, X TI Effects of drug treatment on osteoporosis using a disease progress model. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P33 EP P33 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100119 ER PT J AU Duan, JZ Gobburu, JV AF Duan, JZ Gobburu, JV TI Understanding schedule dependence of an irreversible aromatase inhibitor via simulations. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P24 EP P24 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100086 ER PT J AU Fineman, MS Johnson, SB AF Fineman, MS Johnson, SB TI Mealtime pramlintide administration reduces early postprandial glucose excursions when added to regular insulin or insulin lispro in patients with diabetes: A dose-timing study. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 FDA, San Diego, CA USA. Amylin Pharmaceut, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P90 EP P90 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100330 ER PT J AU Gorski, JC Huang, S Zaheer, NA Desai, M Pinto, A Miller, M Hall, SD AF Gorski, JC Huang, S Zaheer, NA Desai, M Pinto, A Miller, M Hall, SD TI The effect of echinacea on CYP3A activity in vivo. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 Indiana Univ, Indianapolis, IN 46204 USA. US FDA, Indianapolis, IN USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P94 EP P94 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100344 ER PT J AU Ma, JD Nafziger, AN Kashuba, AD Rowland, E Gaedigk, A Kim, JS Kim, M Bertino, JS AF Ma, JD Nafziger, AN Kashuba, AD Rowland, E Gaedigk, A Kim, JS Kim, M Bertino, JS TI Use of limited sampling strategy (LSS) of S-warfarin (S-W) concentrations or warfarin (W) S/R ratios as a biomarker for CYP2C9 activity. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 Univ N Carolina, Sch Pharm, Chapel Hill, NC 27515 USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. US FDA, Rockville, MD 20857 USA. Bassett Healthcare, Cooperstown, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P15 EP P15 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100051 ER PT J AU Mackey, AC Brinker, A Beitz, J Kress, S AF Mackey, AC Brinker, A Beitz, J Kress, S TI Alosetron postmarketing experience. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P34 EP P34 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100121 ER PT J AU Mishina, EV Booth, BP Gobburu, JV AF Mishina, EV Booth, BP Gobburu, JV TI Comparison of confidence intervals derived using asymptotic standard errors and boot-strapping. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P24 EP P24 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100085 ER PT J AU Nguyen, B Marroum, PJ Gobburu, JV AF Nguyen, B Marroum, PJ Gobburu, JV TI Quantitative risk-benefit analysis of a calcium channel antagonist during regulatory review. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P33 EP P33 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100118 ER PT J AU Uhl, K Peat, R Toigo, T Kennedy, DL Kweder, SL AF Uhl, K Peat, R Toigo, T Kennedy, DL Kweder, SL TI Review of drug labeling for information regarding lactation. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P39 EP P39 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100142 ER PT J AU Uhl, K Miller, M Chapman, KK Kennedy, DL AF Uhl, K Miller, M Chapman, KK Kennedy, DL TI Identifying the barriers to conducting pharmacokinetic and pharmacodynamic studies in pregnant women. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2003 CL WASHINGTON, D.C. SP American Soc Clin Pharmacol Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2003 VL 73 IS 2 SU S BP P39 EP P39 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648UY UT WOS:000181170100141 ER PT J AU Burns, DL AF Burns, DL TI Type IV transporters of pathogenic bacteria SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID PERTUSSIS TOXIN SECRETION; LEGIONELLA-PNEUMOPHILA DOTA; AGROBACTERIUM-TUMEFACIENS VIRB; BORDETELLA-PERTUSSIS; T-PILUS; INTRACELLULAR SURVIVAL; HELICOBACTER-PYLORI; BARTONELLA-HENSELAE; BRUCELLA-SUIS; PROTEIN SUBASSEMBLIES AB Type IV transporters are produced by several bacterial pathogens such as Agrobacterium tumefaciens, Bordetella pertussis, Brucella spp., Bartonella henselae, Helicobacter pylori and Legionella pneumophila. These transporters are critical for the pathogenic process in that they export important virulence factors across the membranes of the bacteria. Although the virulence factors that are exported by these transporters can be either nucleic acid or protein, the general mechanism of transport appears to be similar for members of this family. Recent findings have shed light on the architecture of type IV transporters and the roles that these transporters play in pathogenesis. C1 United States Food & Drug Adm, Bethesda, MD 20892 USA. RP Burns, DL (reprint author), United States Food & Drug Adm, HFM-434,Bldg 29,Rm 130,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 76 Z9 87 U1 0 U2 3 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 2003 VL 6 IS 1 BP 29 EP 34 DI 10.1016/S1369-5274(02)00006-1 PG 6 WC Microbiology SC Microbiology GA 668NT UT WOS:000182300600005 PM 12615216 ER PT J AU Hayes, SM Shores, EW Love, PE AF Hayes, SM Shores, EW Love, PE TI An architectural perspective on signaling by the pre-, alpha beta and gamma delta T cell receptors SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ANTIGEN RECEPTOR; POSITIVE SELECTION; LYMPHOCYTES-T; TCR COMPLEX; THYMOCYTE SELECTION; IMMATURE THYMOCYTES; THYMUS DEVELOPMENT; CD3 COMPLEX; MUTANT MICE; ZETA-CHAIN AB The T cell antigen receptor (TCR) is a multimeric complex composed of an antigen-binding clonotypic heterodimer and a signal transducing complex consisting of the CD3 dimers (CD3gammaepsilon and CD3deltaepsilon) and a TCR-zeta homodimer. In all jawed vertebrates there are two T cell lineages, alphabeta and gammadelta, distinguished by the clonotypic subunits contained within their TCRs (TCR-alpha and -beta or TCR-gamma and -delta, respectively). A third receptor complex, the preTCR, is only expressed on immature T cells. The preTCR, which contains the invariant pre-Talpha (pTalpha) chain in lieu of TCR-alpha, plays a critical role in the early development of alphabeta lineage cells. The subunit composition of the signal transducing complexes of the pre-, alphabeta- and gammadeltaTCRs was previously thought to be identical. However, recent data demonstrate that there are significant differences in the signal transducing complexes of these three TCRs. For example, alphabetaTCRs contain both CD3gammaepsilon and CD3deltaepsilon dimers, whereas gammadeltaTCRs contain only CD3gammaepsilon dimers. Moreover, preTCR function appears to be unaffected in the absence of CD3delta, suggesting that CD3deltaepsilon dimers are dispensable for pre-TCR assembly. In this review, we summarize current data relating to the subunit composition of the pre-, alphabeta- and gammadeltaTCRs and discuss how these structural differences may impact receptor signaling and alphabeta/gammadelta lineage determination. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, MSC 2780,Bldg 6B,Room 2B-210,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 60 TC 51 Z9 51 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2003 VL 191 IS 1 BP 28 EP 37 DI 10.1034/j.1600-065X.2003.00011.x PG 10 WC Immunology SC Immunology GA 652GY UT WOS:000181372500003 PM 12614349 ER PT J AU Fishman, PH Orlandi, PA AF Fishman, PH Orlandi, PA TI Cholera toxin internalization and intoxication SO JOURNAL OF CELL SCIENCE LA English DT Letter ID GPI-ANCHORED PROTEINS; PLASMA-MEMBRANE; CELL-SURFACE; CAVEOLAE; ACTIVATION; MECHANISM; DOMAINS; DYNAMIN C1 NIH, Bethesda, MD 20892 USA. US FDA, Washington, DC 20204 USA. RP Fishman, PH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 13 TC 6 Z9 7 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB 1 PY 2003 VL 116 IS 3 BP 431 EP 432 DI 10.1242/jcs.00199 PG 2 WC Cell Biology SC Cell Biology GA 645VC UT WOS:000180999400001 PM 12508102 ER PT J AU Jung, YS Frank, JF Brackett, RE Chen, JR AF Jung, YS Frank, JF Brackett, RE Chen, JR TI Polymerase chain reaction detection of Listeria monocytogenes on frankfurters using oligonucleotide primers targeting the genes encoding internalin AB SO JOURNAL OF FOOD PROTECTION LA English DT Article ID RAPID DETECTION; SURFACE-ADHESION; PCR; FOOD; PRODUCTS; MEAT; IDENTIFICATION; HYBRIDIZATION; EXTRACTION; PATHOGEN AB A polymerase chain reaction (PCR) assay targeting the genes encoding internalin AB (inlAB) was developed for detecting Listeria monocytogenes in pure cell cultures and on artificially contaminated frankfurters. Four sets of oligonucleotide primers were evaluated. The set targeting a 902-bp region of the inlAB gene was the most specific. This PCR product was detected in 51 L monocytogenes strains belonging to four different serogroups (1/2a, 1/2b, 1/2c, and 4b). In contrast, the PCR product was not detected in other Listeria spp. (Listeria innocua, Listeria ivanovii, Listeria seeligeri, Listeria welshimeri, or Listeria grayi) or in gram-positive, non-Listeria bacteria, indicating that the primer set was highly specific for L. monocytogenes. The detection limit of the PCR assay was 10(5) CFU per ml of pure cell culture. However, the assay could detect as few as 10, CFU of L. monocytogenes in 25 g of frankfurter with 16 h of enrichment in modified Listeria enrichment broth at 30degreesC. The total assay time including enrichment was approximately 24 h. These results suggest that the PCR assay can be used to rapidly detect L monocytogenes on frankfurters and possibly other types of ready-to-eat meat products. C1 Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. Univ Georgia, Dept Food Sci & Technol, Griffin, GA 30223 USA. US FDA, Off Plant Dairy Foods & Beverages, Washington, DC 20204 USA. RP Chen, JR (reprint author), Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. NR 29 TC 25 Z9 30 U1 0 U2 3 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 FEB PY 2003 VL 66 IS 2 BP 237 EP 241 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 643YA UT WOS:000180890100011 PM 12597483 ER PT J AU Brown, RM Cruz, O Brennan, M Gennaro, ML Schlesinger, L Skeiky, YAW Hoft, DF AF Brown, RM Cruz, O Brennan, M Gennaro, ML Schlesinger, L Skeiky, YAW Hoft, DF TI Lipoarabinomannan-reactive human secretory immunoglobulin A responses induced by mucosal bacille Calmette-Guerin vaccination SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUBERCULOSIS; DIAGNOSIS; ANTIBODIES AB The ability of 17 recombinant mycobacterial proteins, native antigen 85 complex, lipoarabinomannan (LAM), and Mycobacterium tuberculosis lysate to detect antibody responses induced by bacille Calmette-Guerin (BCG) vaccination and active tuberculosis infection were studied in enzyme-linked immunosorbent assays. Only LAM-reactive serum immunoglobulin G responses were significantly increased in both BCG-vaccinated patients and patients with active tuberculosis (P < .05), and oral BCG vaccination also induced significant increases in LAM-reactive secretory immunoglobulin A (P < .05). LAM-reactive antibody assays can serve as markers of humoral and mucosal immunity in future trials of BCG and newer attenuated mycobacterial vaccines. C1 St Louis Univ, Hlth Sci Ctr, Dept Internal Med,Vaccine & Treatment Evaluat Uni, Div Infect Dis & Immunol, St Louis, MO 63110 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Publ Hlth Res Inst City New York Inc, New York, NY 10016 USA. Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. Univ Iowa, Dept Med, Div Infect Dis, Iowa City, IA 52242 USA. Univ Iowa, Program Immunol, Iowa City, IA 52242 USA. Corixa, Seattle, WA USA. RP Hoft, DF (reprint author), St Louis Univ, Hlth Sci Ctr, Dept Internal Med,Vaccine & Treatment Evaluat Uni, Div Infect Dis & Immunol, 3635 Vista Ave,FDT-8N, St Louis, MO 63110 USA. FU NIAID NIH HHS [R01-AI36989, N01-AI-45211] NR 14 TC 20 Z9 21 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2003 VL 187 IS 3 BP 513 EP 517 DI 10.1086/368096 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 639NU UT WOS:000180636800022 PM 12552438 ER PT J AU Piroozi, A Melnyk, S Jernigan, S MacLennan, NK Chiu, CT James, SP Lane, RH AF Piroozi, A Melnyk, S Jernigan, S MacLennan, NK Chiu, CT James, SP Lane, RH TI Altered fetal one-carbon metabolism and gene expression in rat model of IUGR that is charcterized by abnormal DNA methylation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 485 BP S176 EP S176 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600491 ER PT J AU Fukasawa, LO Gorla, MCO Lemos, APS Schenkman, RPF Brandileone, MCC Fox, JW Raw, I Frasch, CE Tanizaki, MM AF Fukasawa, LO Gorla, MCO Lemos, APS Schenkman, RPF Brandileone, MCC Fox, JW Raw, I Frasch, CE Tanizaki, MM TI Immune response to native NadA from Neisseria meningitidis and its expression in clinical isolates in Brazil SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID MEMBRANE PROTEIN VACCINE; C-POLYSACCHARIDE; CONJUGATE VACCINE; MENINGOCOCCAL VACCINE; IMMUNOGENICITY; ADULTS; PROTECTION; CANDIDATE; EFFICACY; SAFETY AB A mAb against the NadA protein from Neisseria meningitidis strain 3006 (serosubtype B: 2b: P1.2: P5.2,8) demonstrated strong bactericidal activity against Brazilian epidemic serogroup B strain N44/89 (B: 4,7: P1.19,115: P5.5,7) and a serogroup C strain, IMC 2135 (C: 2a: P1.5,2), but not against another serogroup C strain, N1002/90 (C: 2b: P1.3: P5.8). The immunogenicity of native NadA in an outer-membrane vesicle (OMV) preparation was also tested. Serum from mice immunized with CMIV from serogroup B strain N44/89, which contains the NadA protein, showed bactericidal activity against serogroup B and C strains possessing NadA. In dot-blot analysis of 100 serogroup B and 100 serogroup C isolates from Brazilian patients, the mAb to NadA recognized about 60 % of the samples from both serogroups. The molecular mass of the NadA protein from strain N44/89 determined by mass spectrometry was 37 971 Da and the peptide sequences were identical to those of NadA from N. meningitidis strain MC58. C1 Inst Butantan, Ctr Biotechnol, BR-05504900 Sao Paulo, Brazil. USP, Butantan IPT, Curso Pos Graduacao Biotecnol, Sao Paulo, Brazil. Inst Adolf Lutz, Serv Bacteriol, Sao Paulo, Brazil. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Tanizaki, MM (reprint author), Inst Butantan, Ctr Biotechnol, Avenida Vital Brasil 1500, BR-05504900 Sao Paulo, Brazil. RI Tanizaki, Martha /F-8169-2012 NR 24 TC 9 Z9 9 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD FEB PY 2003 VL 52 IS 2 BP 121 EP 125 DI 10.1099/jmm.0.05017-0 PG 5 WC Microbiology SC Microbiology GA 648UL UT WOS:000181168900004 PM 12543917 ER PT J AU Nordstrom, JL DePaola, A AF Nordstrom, JL DePaola, A TI Improved recovery of pathogenic Vibrio parahaemolyticus from oysters using colony hybridization following enrichment SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Vibrio parahaemolyticus; DNA probe; tdh gene ID UNITED-STATES; GENE AB The traditional streak plating and alternative spread-plating methods were compared for detection of pathogenic Vibrio parahaemolyticus (Vp) in oyster enrichments. We found the alternative method to be more efficient: it was quicker (2d vs. 3d) and had a significantly (p < 0.05) greater detection rate than streak plating. Published by Elsevier Science B.V. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Nordstrom, JL (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Isl, AL 36528 USA. NR 12 TC 15 Z9 16 U1 3 U2 3 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 2003 VL 52 IS 2 BP 273 EP 277 AR PII S0167-7012(02)00188-4 DI 10.1016/S0167-7012(02)00188-4 PG 5 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 638YD UT WOS:000180599700012 PM 12459249 ER PT J AU Post, LO Farrell, DE Cope, CV Baker, JD Myers, MJ AF Post, LO Farrell, DE Cope, CV Baker, JD Myers, MJ TI The effect of endotoxin and dexamethasone on enrofloxacin pharmacokinetic parameters in swine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INFECTION ACTINOBACILLUS-PLEUROPNEUMONIAE; P450-MEDIATED DRUG-METABOLISM; ACUTE-PHASE RESPONSE; BACTERIAL LIPOPOLYSACCHARIDE; FEBRILE GOATS; DISPOSITION; GENTAMICIN; ANIMALS; RATS; PIGS AB The impact of Escherichia coli-derived lipopolysaccharide (LPS) on the pharmacokinetic parameters of enrofloxacin in swine was assessed to determine whether this model would substitute for a pleuropneumonia infection model for pharmacokinetic evaluation of drugs. All animals received a single i.v. dose of enrofloxacin (5 mg/kg). Half the animals also received dexamethasone (0.5 mg/kg) to determine the impact of inflammation on any changes in enrofloxacin pharmacokinetics, as most of the effects of LPS are due to elaboration of inflammatory mediators. Administration of LPS alone (2.0 mug/kg) was associated with a decrease in clearance of enrofloxacin. Volume of distribution at steady state was increased in the dexamethasone-treated animals. The terminal elimination half-life of enrofloxacin was significantly increased in the LPS group. Dexamethasone administration, either alone or in combination with LPS challenge, increased the volume of distribution both at steady state and during the elimination phase. Lipopolysaccharide challenge did not affect the volume of distribution. Lipopolysaccharide challenge did not affect urinary excretion of enrofloxacin but did increase the urinary excretion of its principal metabolite, ciprofloxacin. However, the increased excretion did not begin until 24 h after administration of enrofloxacin. Because these pharamcokinetic results are different from those obtained with the pleuropneumonia model using the bacteria Actinobacillus pleuropneumoniae, the results of this study demonstrate that LPS is not a generic substitute for infection for the pharmacokinetic evaluation of drugs. C1 US FDA, Ctr Vet Med, Res Off, Div Anim Res, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Off Surveillance & Compliance, Div Surveillance, Rockville, MD 20857 USA. RP Myers, MJ (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim Res, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 32 TC 21 Z9 22 U1 1 U2 10 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2003 VL 304 IS 2 BP 889 EP 895 DI 10.1124/jpet.102.042416 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 637RL UT WOS:000180526600050 PM 12538847 ER PT J AU Bonnel, RA La Grenade, L Karwoski, CB Beitz, JG AF Bonnel, RA La Grenade, L Karwoski, CB Beitz, JG TI Allergic contact dermatitis from topical doxepin: Food and Drug Administration's postmarketing surveillance experience SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CREAM; RANITIDINE AB A total of 26 postmarketing cases of allergic contact dermatitis to doxepin 5% cream were reported to the Food and Drug Administration. Our findings suggest that allergic contact dermatitis was more common when treatment duration exceeded the recommended 8 days. Allergic contact dermatitis to doxepin cream should be considered in patients whose condition fails to improve or worsens with doxepin use. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Bonnel, RA (reprint author), 5600 Fishers Ln,Room 15B-23,HFD-430, Rockville, MD 20857 USA. NR 16 TC 15 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2003 VL 48 IS 2 BP 294 EP 296 DI 10.1067/mjd.2003.46 PG 3 WC Dermatology SC Dermatology GA 646TH UT WOS:000181050000024 PM 12582408 ER PT J AU O'Connell, KA Wilkin, JK Pitts, M AF O'Connell, KA Wilkin, JK Pitts, M TI Isotretinoin (Accutane) and serious psychiatric adverse events SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Dermatol & Dental Drug Products, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Rockville, MD 20857 USA. RP O'Connell, KA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Dermatol & Dental Drug Products, Rockville, MD 20857 USA. NR 7 TC 10 Z9 10 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2003 VL 48 IS 2 BP 306 EP 308 DI 10.1067/mjd.2002.12 PG 3 WC Dermatology SC Dermatology GA 646TH UT WOS:000181050000032 PM 12582415 ER PT J AU He, Y Vassell, R Zaitseva, M Nguyen, N Yang, ZN Weng, YK Weiss, CD AF He, Y Vassell, R Zaitseva, M Nguyen, N Yang, ZN Weng, YK Weiss, CD TI Peptides trap the human immunodeficiency virus type 1 envelope glycoprotein fusion intermediate at two sites SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSMEMBRANE PROTEIN GP41; MEMBRANE-FUSION; HIV-1 GP41; LEUCINE ZIPPER; SIV GP41; INHIBITION; ECTODOMAIN; DOMAIN; ENTRY; CONFORMATION AB Human immunodeficiency virus type 1 (HIV-1) entry into target cells requires folding of two heptad-repeat regions (N-HR and C-HR) of gp41 into a trimer of N-HR and C-HR hairpins, which brings viral and target cell membranes together to facilitate membrane fusion. Peptides corresponding to the N-HR and C-HR of gp41 are potent inhibitors of HIV infection. Here we report new findings on the mechanism of inhibition of a N-HR peptide and compare these data with inhibition by a C-HR peptide. Using intact envelope glycoprotein (Env) under fusogenic conditions, we show that the N-HR peptide preferentially binds receptor-activated Env and that CD4 binding is sufficient for triggering conformational changes that allow the peptide to bind Env, results similar to those seen with the C-HR peptide. However, activation by both CD4 and chemokine receptors further enhances Env binding by both peptides. We also show that a nonconservative mutation in the N-HR of gp41 abolishes C-HR peptide but not N-HR peptide binding to gp41. These results indicate that there are two distinct sites in receptor-activated Env that are potential targets for drug or vaccine development. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMD, NIH, Bethesda, MD 20892 USA. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-466,NIH Bldg,29 Rm 532,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 28 TC 93 Z9 98 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2003 VL 77 IS 3 BP 1666 EP 1671 DI 10.1128/JVI.77.3.1666-1671.2003 PG 6 WC Virology SC Virology GA 637AD UT WOS:000180488700002 PM 12525600 ER PT J AU Elkins, KL Cowley, SC Bosio, CM AF Elkins, KL Cowley, SC Bosio, CM TI Innate and adaptive immune responses to an intracellular bacterium, Francisella tularensis live vaccine strain SO MICROBES AND INFECTION LA English DT Review DE Francisella tularensis; mice; T-lymphocytes; B-lymphocytes; bacterial vaccines; interferon type II; immunity, natural ID PROTECTIVE IMMUNITY; T-CELLS; GAMMA-INTERFERON; B-CELLS; PRIMARY INFECTION; LVS INFECTION; HOST-DEFENSE; MICE; MACROPHAGES; RESISTANCE AB The immune response to intracellular bacterium, Francisella tularensis, which causes tularemia and is proposed to be a potential bioterrorism pathogen, has been studied in mice using the attenuated live vaccine strain (LVS). Here we review this infection model, which provides a convenient means of studying protective immune mechanisms not only for Francisella, but also for the large and important class of intracellular pathogens. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 US FDA, Lab Mycobacteria, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Elkins, KL (reprint author), US FDA, Lab Mycobacteria, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. RI Bosio, Catharine/D-7456-2015 NR 44 TC 110 Z9 112 U1 0 U2 5 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD FEB PY 2003 VL 5 IS 2 BP 135 EP 142 DI 10.1016/S1286-4579(02)00084-9 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 664RN UT WOS:000182074800007 PM 12650771 ER PT J AU Lin, DX Thompson, PA Teitel, C Chen, JS Kadlubar, FF AF Lin, DX Thompson, PA Teitel, C Chen, JS Kadlubar, FF TI Direct reduction of N-acetoxy-PhIP by tea polyphenols: a possible mechanism for chemoprevention against PhIP-DNA adduct formation SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT Conference on Dietary and Medicinal Antimutagens and Anticarcinogens - Molecular Mechanisms and Chempreventive Potential CY OCT 17-19, 2001 CL SEOUL, SOUTH KOREA DE chemoprevention; tea polyphenols; heterocyclic amines; foodborne carcinogens ID FOOD-BORNE CARCINOGEN; RAT-LIVER MICROSOMES; PHASE-II ENZYMES; GREEN TEA; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; BLACK TEA; A/J MICE; METABOLIC-ACTIVATION; HETEROCYCLIC AMINES; LUNG TUMORIGENESIS AB The chemopreventive effect of tea against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adduct formation and its mechanism were studied. Rats were exposed to freshly prepared aqueous extracts of green tea (3% (w/v)) as the sole source of drinking water for 10 days prior to administration with a single dose of PhIP (10 mg/kg body weight) by oral gavage. PhIP-DNA adducts in the liver, colon, heart, and lung were measured using the P-32-postlabelling technique. Rats pre-treated with tea and given PhIP 20 h before sacrifice had significantly reduced levels of PhIP-DNA adducts as compared with controls given PhIP alone. The possible mechanism of protective effect of tea on PhIP-DNA adduct formation was then examined in vitro. It was found that an aqueous extract of green and black tea, mixtures of green and black tea polyphenols, as well as purified polyphenols could strongly inhibit the DNA binding of N-acetoxy-PhIP, a putative ultimate carcinogen of PhIP formed in vivo via metabolic activation. Among these, epigallocatechin gallate was exceptionally potent. HPLC analyses of these incubation mixtures containing N-acetoxy-PhIP and the tea polyphenols each revealed the production of the parent amine, PhIP, indicating the involvement of a redox mechanism. In view of the presence of relatively high levels of tea polyphenols in rat and human plasma after ingestion of tea, this study suggests that direct reduction of the ultimate carcinogen N-acetoxy-PhIP by tea polyphenols is likely to be involved in the mechanism of chemoprotection of tea against this carcinogen. Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Beijing Union Med Univ, Chinese Acad Med Sci, Inst Canc, Div Canc Etiol, Beijing 100021, Peoples R China. Chinese Acad Prevent Med, Inst Nutr & Food Hyg, Beijing 100050, Peoples R China. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. EM fkadlubar@nctr.fda.gov NR 37 TC 11 Z9 13 U1 0 U2 3 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 FEB-MAR PY 2003 VL 523 SI SI BP 193 EP 200 DI 10.1016/S0027-5107(02)00335-4 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 658RH UT WOS:000181733900020 PM 12628517 ER PT J AU Kaidbey, K Sutherland, B Bennett, P Wamer, WG Barton, C Dennis, D Kornhauser, A AF Kaidbey, K Sutherland, B Bennett, P Wamer, WG Barton, C Dennis, D Kornhauser, A TI Topical glycolic acid enhances photodamage by ultraviolet light SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE alpha-hydroxy acid; erythema; glycolic acid; phototoxicity ID HUMAN-SKIN; PERCUTANEOUS-ABSORPTION; IN-VITRO; RADIATION; DIMERS; DNA AB Background: Alpha-hydroxy acids (AHAs) are widely used as ingredients in cosmetics. Several studies suggest that AHAs can increase the sensitivity of skin to ultraviolet (UV) light. Purpose: This study was performed in order to determine whether short-term dermal treatment with glycolic acid, a representative AHA, can enhance the damaging effects of UV light. The duration of the effect of AHAs on the sensitivity of skin to UV light was also examined. Methods: The backs of 29 Caucasian subjects were treated, once daily, 6 days per week with either 10% glycolic acid (pH 3.5) or placebo in a randomized double-blinded study. At the end of 4 weeks, sites within each treated area were exposed to 1.5 MED of UV light, determined on previously untreated skin. Specimens were obtained for enumeration of sunburn cells (SBCs) in the first group of subjects (n = 16), whereas cyclobutyl pyrimidine dimers (CPDs) in DNA were determined in the second group (n = 13). The minimal erythema dose (MED) in each site was also determined in the first group of subjects. Sunburn cells and MEDs were re-evaluated in the first group 1 week after discontinuing AHA applications. Results: Glycolic acid caused enhanced sensitivity to UV light measured as increased SBC induction and lowered MEDs. Cyclobutyl pyrimidine dimers were elevated but not to a statistically significant level. No differences in SBCs or MEDs were evident after a week of discontinued treatments. Conclusion: Short-term application of 10% glycolic acid sensitizes the skin to the damaging effects of UV light. This photosensitivity is reversed within a week of terminating treatments. C1 US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, HFS 128, Washington, DC 20204 USA. Ivy Labs, Philadelphia, PA 19104 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Wamer, WG (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, HFS 128, 5100 Paint Branch Pkwy, Washington, DC 20204 USA. NR 17 TC 18 Z9 18 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD FEB PY 2003 VL 19 IS 1 BP 21 EP 27 DI 10.1034/j.1600-0781.2003.00013.x PG 7 WC Dermatology SC Dermatology GA 655KF UT WOS:000181550300006 PM 12713551 ER PT J AU Wolff, GL AF Wolff, GL TI Regulation of yellow pigment formation in mice: A historical perspective SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the PanAmerican-Society-for-Pigment-Cell-Research CY 2000 CL COLLEGE STN, TEXAS SP PanAmer Soc Pigment Cell Res DE Agouti signaling protein; cysteine; growth; melanocortin receptors; obesity ID AGOUTI GENE-EXPRESSION; MAMMALIAN TYROSINASE; MURINE MELANOCYTES; HIMALAYAN MOUSE; SIGNAL PROTEIN; HAIR-FOLLICLES; GLUTATHIONE; MUTATION; CYSTEINE; LOCUS AB Pigment synthesis by hair follicle melanocytes is modulated by a large number of environmental and genetic factors, many of which are discussed in this review. Eumelanic (non-yellow) pigment is produced by hair follicle melanocytes following the binding of alpha-melanocyte stimulating hormone to melanocortin receptor 1. Binding of this hormone to the melanocyte membrane is blocked by agouti signaling protein (ASP) which is encoded by the agouti locus and results in the synthesis of yellow pigment, instead of non-yellow (black/brown) pigment. The cyclical release of ASP by hair follicle cells results in a black/brown hair with a subapical yellow band. This is the wild-type coat color pattern of many mammals and is called agouti. Several dominant mutations at the agouti locus in mice, induced by retrotransposon-like intracisternal A particles, result in ectopic over-expression of ASP and animals with much higher proportions of all-yellow hairs. This abnormal presence of ASP in essentially all body cells results in the 'yellow agouti obese mouse syndrome.' The obesity has been associated with binding of ASP to melanocortin receptor 4 inactivating the latter. The syndrome also includes hyperinsulinemia, increased somatic growth, and increased susceptibility to hyperplasia and carcinogenesis. The physiologic and molecular bases for these syndrome components have not yet been elucidated. This historically orientated review is subdivided, where applicable, into pre- and post-1992 subsections to emphasize the impact of the cloning of the agouti and extension loci and their protein products on the identification of the molecular and physiological pathways modulating the manifold aspects of pheomelanogenesis. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. RP Wolff, GL (reprint author), 2802 Millbrook Rd, Little Rock, AR 72227 USA. NR 100 TC 24 Z9 25 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD FEB PY 2003 VL 16 IS 1 BP 2 EP 15 DI 10.1034/j.1600-0749.2003.00012.x PG 14 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 640HE UT WOS:000180682100001 PM 12519120 ER PT J AU Nawaz, MS Khan, SA Khan, AA Nayak, R Steele, R Paine, D Jones, R AF Nawaz, MS Khan, SA Khan, AA Nayak, R Steele, R Paine, D Jones, R TI Molecular characterization of fluoroquinolone-resistant Campylobacter spp. isolated from poultry SO POULTRY SCIENCE LA English DT Article DE fluroquinolone resistance; multiple antibiotic resistance; campylobacters; pulsed field gel electrophoresis; molecular typing ID FIELD GEL-ELECTROPHORESIS; QUINOLONE RESISTANCE; INVITRO ACTIVITIES; JEJUNI; DNA; PATHOGENS; DIARRHEA; STRAINS; GENE AB Campylobacteriosis, an infectious disease caused by Campylobacter jejuni and Campylobacter coli, is treated by fluoroquinolone antibiotics in clinical practices. However, use of these drugs in animal husbandry may select for fluoroquinolone-resistant campylobacters and, thereby, compromise the clinical treatment of infection. In this study, 21 fluoroquinolone-resistant campylobacters were isolated from poultry samples. Morphological and biochemical characteristics indicated that 19 isolates were C. jejuni and two were C. coli. All isolates were resistant to multiple antibiotics but sensitive to chloramphenicol and gentamicin. These isolates were characterized at the molecular level by amplifying the flagellin gene (flaA) by PCR. The PCR protocol amplified a 1.7-kb flaA gene from all isolates. RFLP analysis of the 1.7-kb amphicons, after digestion with DdeI yielded four distinct patterns. The 21 fluoroquinolone-resistant campylobacter isolates were further characterized by pulsed-field gel electrophoresis (PFGE) and compared with the PFGE patterns of nine fluoroquinolone-sensitive campylobacter strains. Four of the 21 fluoroquinolone-resistant isolates were untypable by the PFGE protocol. The PFGE analysis with SalI or SmaI indicated that seven or five, respectively, of the 17 resistant isolates had identical macrorestriction profiles (mrps). However, PFGE analysis with a combination of SalI and SmaI indicated that four of the 17 isolates had similar macrorestriction profiles. The PFGE patterns of the 17 fluoroquinolone-resistant isolates were different from the nine sensitive campylobacter strains. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Div Epidemiol, Washington, DC USA. RP Nawaz, MS (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 30 TC 6 Z9 7 U1 0 U2 1 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD FEB PY 2003 VL 82 IS 2 BP 251 EP 258 PG 8 WC Agriculture, Dairy & Animal Science SC Agriculture GA 645XU UT WOS:000181006400010 PM 12619802 ER PT J AU Sacks, WM AF Sacks, WM TI Estimating the effect of computer-aided detection on the sensitivity of screening mammography SO RADIOLOGY LA English DT Letter C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Sacks, WM (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2003 VL 226 IS 2 BP 597 EP 598 DI 10.1148/radiol.2262020688 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 639YC UT WOS:000180657000050 PM 12563163 ER PT J AU Vallejo, A Gurtler, L Zekeng, L Hewlett, IK AF Vallejo, A Gurtler, L Zekeng, L Hewlett, IK TI Nucleotide sequence analysis of the accessory genes of HIV-1 group O isolates SO VIRUS RESEARCH LA English DT Article DE HIV-1 group O; sequencing; accessory genes; phylogenetic analysis ID TYPE-1 GROUP-O; REVERSE TRANSCRIPTION; VIF PROTEIN; VPU PROTEIN; CAMEROON; AFRICA; IDENTIFICATION; INFECTION; STRAINS AB Human immunodeficiency virus type 1 group O strains have been described as highly divergent, compared with the majority of the viruses classified in group M. To study the diversity and genetic characteristics of group O, we have sequenced the accessory genes of 7 isolates. Analysis of the deduced amino acid sequences for Vif, Vpr, Tat, Vpu, and Rev indicate that most of the functional domains of these proteins, as described for group M viruses, are highly conserved and retained among all the group O strains we have characterized. The only difference concerns the Vif phosphorylation sites, which are absent in all of the group O isolated we have sequence with the exception of two isolates in which only one phosphorylation site was conserved. These sites, present in nearly all of the group M isolates, play a critical role in the regulation of viral replication and infectivity. As described for group M isolates, the vpu gene is the one with the highest diversity among group O viruses. Phylogenetic analysis of these sequences suggests that group O viruses could be differentiated into at least four different clusters. (C) 2002 Elsevier Science B.V. All rights reserved. C1 US FDA, Mol Virol Lab, Bethesda, MD 20014 USA. Univ Greifswald, Inst Med Microbiol, Greifswald, Germany. Hlth Minister, Yaounde, Cameroon. RP Vallejo, A (reprint author), Hosp Univ Virgen Rocio, Mol Biol Lab, Edificio Lab,Planta 6a,Ave Manuel Siurot S-N, Seville 41013, Spain. RI Vallejo, Alejandro/I-5881-2015 OI Vallejo, Alejandro/0000-0001-5360-878X NR 24 TC 4 Z9 4 U1 0 U2 0 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 2003 VL 91 IS 2 BP 189 EP 193 AR PII S0168-1702(02)00270-8 DI 10.1016/S0168-1702(02)00270-8 PG 5 WC Virology SC Virology GA 644FK UT WOS:000180907100004 PM 12573497 ER PT J AU Hung, HMJ Wang, SJ Tsong, YL Lawrence, J O'Neil, RT AF Hung, HMJ Wang, SJ Tsong, YL Lawrence, J O'Neil, RT TI Some fundamental issues with non-inferiority testing in active controlled trials SO STATISTICS IN MEDICINE LA English DT Article DE efficacy; non-inferiority margin; preservation of active control effect; historical trial; alpha error ID PLACEBO-CONTROLLED TRIALS; EQUIVALENCE TRIALS; PRACTICAL ISSUES; CLINICAL-TRIALS; DESIGN AB In an active controlled non-inferiority trial without a placebo arm, it is often not entirely clear what the primary objective is. In many cases the considered goal is to demonstrate that the experimental treatment preserves at least some fraction of the effect of the active control. The active control effect is a parameter, the value of which is unknown. To test the hypothesis of effect preservation, the classical confidence interval approach requires specification of a non-inferiority margin which is a function of the unknown active control effect. When the margin is estimated, it is also not clear what is the relevant type I error of making a false assertion about preservation of the active control effect. The statistical uncertainty of the estimated margin arguably needs to be incorporated in evaluation of the type I error. In this paper we discuss these fundamental issues. We show that the classical confidence interval approach cannot attain the target type I error exactly since this error varies as the sample size or as the values of the nuisance parameters in the active controlled trial change. In contrast, the preservation tests, as proposed in literature, can attain the target type I error rate exactly, regardless of the sample size and the values of the nuisance parameters, but can do so only at the price of several strong assumptions holding that may not be directly verifiable. One assumption is the constancy condition holding whereby the effect of the active control in the historical trial populations is assumed to carry to the population of the active control trial. When this condition is violated, both the confidence interval approach and the preservation test method may be problematic. Copyright (C) 2003 John Wiley Sons, Ltd. C1 US FDA, CDER, Div Biometr 1, PKLN,OB,OPaSS, Rockville, MD 20857 USA. US FDA, CDER, Div Biometr 2, OB,OPaSS, Rockville, MD 20857 USA. US FDA, CDER, Quantitat Methods & Res Staff, OB,OPaSS, Rockville, MD 20857 USA. US FDA, CDER, Off Biostat, OPaSS, Rockville, MD 20857 USA. RP Hung, HMJ (reprint author), US FDA, CDER, Div Biometr 1, PKLN,OB,OPaSS, HFD-710,15B45,5600 Fishers Lane, Rockville, MD 20857 USA. FU PHS HHS [01-20, 02-19] NR 25 TC 110 Z9 115 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2003 VL 22 IS 2 BP 213 EP 225 DI 10.1002/sim.1315 PG 13 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 639ZK UT WOS:000180660500005 PM 12520558 ER PT J AU Wang, SJ Hung, HMJ AF Wang, SJ Hung, HMJ TI TACT method for non-inferiority testing in active controlled trials SO STATISTICS IN MEDICINE LA English DT Article DE efficacy; non-inferiority margin; preservation of control effect; alpha error and power; confidence interval method; synthesis method ID PLACEBO-CONTROLLED TRIALS; MOLECULAR-WEIGHT HEPARIN; CORONARY-ARTERY DISEASE; CLINICAL-TRIALS; EQUIVALENCE TRIALS; PRACTICAL ISSUES; SAMPLE-SIZE; DESIGN AB In active controlled trials without a placebo arm, non-inferiority testing is often considered but has different objectives. For the objective of demonstrating the efficacy of an experimental treatment or retention of a fraction of the control effect by the treatment, there are two types of statistical methods for testing - the synthesis method and the confidence interval method. According to the study of Wang, Hung and Tsong, the former is efficient under the so-called constancy condition but may have the alpha error rate inflate rapidly if the condition does not hold. In contrast, the latter method with careful selection of the non-inferiority margin tends to be conservative if the condition holds and may still have a valid alpha error otherwise unless the effect of the active control is less to a large extent in the active controlled trial than in the historical trials. We developed the TACT method, Two-stage Active Control Testing, as a viable compromise between the two methods. Through the TACT method, tile uninterpretable non-inferiority testing may be avoided prior to the end of the trial. The TACT method carefully constructed can have a valid alpha error rate and the power close to the synthesis method if the constancy condition holds. In addition, the TACT rnethod is more powerful than the confidence interval method for testing for the efficacy of the new treatment relative to the putative placebo and for showing that the new treatment is not inferior to the active control comparator. Copyright (C) 2003 John Wiley Sons, Ltd. C1 US FDA, CDER, Div Biometr 2, OB,OPaSS,PKLN, Rockville, MD 20857 USA. US FDA, CDER, Div Biometr 1, OB,OPaSS, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, CDER, Div Biometr 2, OB,OPaSS,PKLN, HFD-715,9B07,5600 Fishers Lane, Rockville, MD 20857 USA. FU PHS HHS [01-20, 01-19] NR 27 TC 26 Z9 28 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2003 VL 22 IS 2 BP 227 EP 238 DI 10.1002/sim.1316 PG 12 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 639ZK UT WOS:000180660500006 PM 12520559 ER PT J AU Rothmann, M Li, N Chen, G Chi, GYH Temple, R Tsou, HH AF Rothmann, M Li, N Chen, G Chi, GYH Temple, R Tsou, HH TI Design and analysis of non-inferiority mortality trials in oncology SO STATISTICS IN MEDICINE LA English DT Article DE non-inferiority trials; active control trials ID ACTIVE-CONTROL TRIALS; PLACEBO-CONTROLLED TRIALS; CLINICAL-TRIALS; ISSUES AB The recent revision of the Declaration of Helsinki and the existence of many new therapies that affect survival or serious morbidity, and that therefore cannot be denied patients, have generated increased interest in active-control trials, particularly those intended to show equivalence or non-inferiority to the active-control. A non-inferiority hypothesis has historically been formulated in terms of a fixed margin. This margin was historically designed to exclude a 'clinically meaningful difference', but has become recognized that the margin must also be no larger than the assured effect of the control in the new study. Depending on how this 'assured effect' is determined or estimated, the selected margin may be very small, leading to very large sample sizes, especially when there is an added requirement that a loss of some specified fraction of the assured effect must be ruled out. In cases where it is appropriate, this paper proposes non-inferiority analyses that do not involve a fixed margin, but can be described as a two confidence interval procedure that compares the 95 per cent two-sided Cl for the difference between the treatment and the control to a confidence interval for the control effect (based on a meta-analysis of historical data comparing the control to placebo) that is chosen to preserve a study-wide type I error rate of about 0.025 (similar to the usual standard for a superiority trial) for testing for retention of a prespecified fraction of the control effect. The approach assumes that the estimate of the historical active-control effect size is applicable in the current study. If there is reason to believe that this effect size is diminished (for example, improved concomitant therapies) the estimate of this historical effect could be reduced appropriately. The statistical methodology for testing this non-inferiority hypothesis is developed for a hazard ratio (rather than an absolute difference between treatments, because a hazard ratio seems likely to be less population dependent than the absolute difference). In the case of oncology, the hazard ratio is the usual way of comparing treatments with respect to time to event (time to progression or survival) endpoints. The proportional hazards assumption is regarded as reasonable (approximately holding). The testing procedures proposed are conditionally equivalent to two confidence interval procedures that relax the conservatism of two 95 per cent confidence interval testing procedures and preserve the type I error rate at a one-sided 0.025 level. An application of this methodology to Xeloda, a recently approved drug for the treatment of metastatic colorectal cancers, is illustrated. Other methodologies are also described and assessed including a point estimate procedure, a Bayesian procedure and two delta-method confidence interval procedures. Published in 2003 by John Wiley Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Div Biometr 1, WOCII,OB,OPaSS, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 1, WOCII,ORM, Rockville, MD 20857 USA. RP Rothmann, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Biometr 1, WOCII,OB,OPaSS, 5600 Fishers Lane,HFD-710, Rockville, MD 20857 USA. EM rothmannm@cder.fda.gov RI Tsou, Hsiao-Hui /E-3837-2010 OI Tsou, Hsiao-Hui /0000-0001-6773-4111 FU DRS NIH HHS [RSR-01-14] NR 16 TC 138 Z9 141 U1 0 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2003 VL 22 IS 2 BP 239 EP 264 DI 10.1002/sim.1400 PG 26 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 639ZK UT WOS:000180660500007 PM 12520560 ER PT J AU Rashid, MM AF Rashid, MM TI Rank-based tests for non-inferiority and equivalence hypotheses in multi-centre clinical trials using mixed models SO STATISTICS IN MEDICINE LA English DT Article DE dispersion function; gradient vector; R-estimators; simulation AB Rank-based procedures for testing non-inferiority and equivalence hypotheses for data (continuous) arising from multi-centre clinical trials are developed using mixed models. The centres are presumed to be a random sample from the population of centres which might conceivably use the treatments under investigation, and the treatment effects are assumed to be fixed. It is assumed that there are no interactions between treatments and centres. Non-inferiority and equivalence hypotheses are tested using rank (R) estimators. The R-estimators are obtained by minimizing a combined dispersion function. The combined dispersion function is a sum of separate dispersion functions from each centre. Both the combined dispersion function and the centre-specific dispersion functions are piecewise linear functions. As a result, the R-estimates are expected to be less influenced by outliers. Large sample properties of the R-estimators including efficiencies are developed. A small scale simulation study is conducted to compare the performances (empirical levels and powers) of the non-parametric procedures and the normal theory based procedures. Published in 2003 by John Wiley Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Div Biometr 2, Off Biostat, Rockville, MD 20857 USA. RP Rashid, MM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Biometr 2, Off Biostat, PKLN 9B07,HFD-715,5600 Fishers Lane, Rockville, MD 20857 USA. FU DRS NIH HHS [RSR-FY99-015] NR 13 TC 8 Z9 8 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2003 VL 22 IS 2 BP 291 EP 311 DI 10.1002/sim.1424 PG 21 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 639ZK UT WOS:000180660500010 PM 12520563 ER PT J AU Meyer, JM Hopkins, RJ AF Meyer, JM Hopkins, RJ TI Helicobacter pylori SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20850 USA. Dynport Vaccine, Frederick, MD 21702 USA. RP Meyer, JM (reprint author), US FDA, Rockville, MD 20850 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 23 PY 2003 VL 348 IS 4 BP 363 EP 364 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 637JD UT WOS:000180507200029 PM 12540657 ER PT J AU Senior, JR AF Senior, JR TI Healthy ranges for alanine aminotransferase levels SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Senior, JR (reprint author), US FDA, Rockville, MD 20857 USA. NR 5 TC 3 Z9 3 U1 0 U2 1 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 21 PY 2003 VL 138 IS 2 BP 156 EP 156 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 646CY UT WOS:000181018300012 PM 12529102 ER PT J AU Padilla, A Noiva, R Lee, N Mohan, KVK Nakhasi, HL Debrabant, A AF Padilla, A Noiva, R Lee, N Mohan, KVK Nakhasi, HL Debrabant, A TI An atypical protein disulfide isomerase from the protozoan parasite Leishmania containing a single thioredoxin-like domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTIST GIARDIA-LAMBLIA; CHAPERONE-LIKE ACTIVITY; ENDOPLASMIC-RETICULUM; DONOVANI PROMASTIGOTES; ACID-PHOSPHATASE; BOND FORMATION; IN-VITRO; GENE; CLONING; HOMOLOG AB In higher eukaryotes, secretory proteins are under the quality control of the endoplasmic reticulum for their proper folding and release into the secretory pathway. One of the proteins involved in the quality control is protein disulfide isomerase, which catalyzes the formation of protein disulfide bonds. As a first step toward understanding the endoplasmic reticulum quality control of secretory proteins in lower eukaryotes, we have isolated a protein disulfide isomerase gene from the protozoan parasite Leishmania donovani. The parasite enzyme shows high sequence homology with homologs from other organisms. However, unlike the four thioredoxin-like domains found in most protein disulfide isomerases, of which two contain an active site, the leishmanial enzyme possesses only one active site present in a single thioredoxin-like domain. When expressed in Escherichia coli, the recombinant parasite enzyme shows both oxidase and isomerase activities. Replacement of the two cysteins with alanines in its active site results in loss of both enzymatic activities. Further, overexpression of the mutated/inactive form of the parasite enzyme in L. donovani significantly reduced their release of secretory acid phosphatases, suggesting that this single thioredoxin-like domain protein disulfide isomerase could play a critical role in the Leishmania secretory pathway. C1 US FDA, Ctr Biol Evaluat & Res, OBRR, DETTD,LBPUA, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. Univ S Dakota, Sch Med, Div Basic Biomed Sci, Vermillion, SD 57069 USA. RP Debrabant, A (reprint author), US FDA, Ctr Biol Evaluat & Res, OBRR, DETTD,LBPUA, Bldg 29,Rm 425,HFM-310,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 53 TC 26 Z9 27 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 JAN 17 PY 2003 VL 278 IS 3 BP 1872 EP 1878 DI 10.1074/jbc.M210322200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636NK UT WOS:000180462200068 PM 12427741 ER PT J AU Feigal, DW Gardner, SN McClellan, M AF Feigal, DW Gardner, SN McClellan, M TI Ensuring safe and effective medical devices SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Feigal, DW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 44 Z9 46 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 16 PY 2003 VL 348 IS 3 BP 191 EP 192 DI 10.1056/NEJMp020170 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 635GJ UT WOS:000180390600001 PM 12529457 ER PT J AU Noguchi, P AF Noguchi, P TI Risks and benefits of gene therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Noguchi, P (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 46 Z9 51 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 16 PY 2003 VL 348 IS 3 BP 193 EP 194 DI 10.1056/NEJMp020184 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 635GJ UT WOS:000180390600002 PM 12529458 ER PT J AU Kang, HK Natelson, BH Mahan, CM Lee, KY Murphy, FM AF Kang, HK Natelson, BH Mahan, CM Lee, KY Murphy, FM TI Post-traumatic stress disorder and chronic fatigue syndrome-like illness among Gulf War veterans: A population-based survey of 30,000 veterans SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE fatigue syndrome, chronic; Persian Gulf syndrome; stress disorders, post-traumatic; veterans ID HEALTH-STATUS; DESERT-STORM; SYMPTOMS; REGISTRY; CARE AB The authors estimated the prevalence of post-traumatic stress disorder (PTSD) and illness resembling chronic fatigue syndrome (CFS) in the entire population of Gulf War and non-Gulf-War veterans. They also evaluated the relation between the extent of deployment-related stress and the risk of either PTSD or CFS. In 1995-1997, the authors conducted a health survey in which these two symptom-based medical diagnoses in a population-based sample of 15,000 Gulf War veterans representing four military branches and three unit components (active, reserve, and National Guard) were compared with those of 15,000 non-Gulf veteran controls. Gulf War veterans, compared with non-Gulf veteran controls, reported significantly higher rates of PTSD (adjusted odds ratio = 3.1, 95% confidence interval: 2.7, 3.4) and CFS (adjusted odds ratio = 4.8, 95% confidence interval: 3.9, 5.9). The prevalence of PTSD increased monotonically across six levels of deployment-related stress intensity (test for trend: p < 0.01), while the prevalence of CFS rose only at the low end of the stress spectrum. While deployment-related stress could account for the higher risks of both PTSD and CFS, additional factor(s) unique to the Gulf environment may have contributed to the risk of CFS among Gulf War veterans. C1 Vet Hlth Adm, Dept Vet Affairs, Environm Epidemiol Serv, Washington, DC 20036 USA. Vet Hlth Adm, Dept Vet Affairs, E Orange, NJ USA. US FDA, US Dept HHS, Rockville, MD 20857 USA. RP Kang, HK (reprint author), Vet Hlth Adm, Dept Vet Affairs, Environm Epidemiol Serv, 1120 20th St NW,Suite 950, Washington, DC 20036 USA. NR 35 TC 226 Z9 230 U1 0 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 2003 VL 157 IS 2 BP 141 EP 148 DI 10.1093/aje/kwf187 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 634UG UT WOS:000180359300007 PM 12522021 ER PT J AU Wamer, WG Vath, P Falvey, DE AF Wamer, WG Vath, P Falvey, DE TI In vitro studies on the photobiological properties of aloe emodin and aloin A SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE aloe emodin; aloin; metabolism; oxidation; phototoxicity; UV; free radicals ID ANTITUMOR AGENTS; PLANT DEFENSE; OXIDATIVE DNA; BASE DAMAGE; IN-VITRO; CELLS; PHOTOSENSITIZATION; ARBORESCENS; MECHANISMS; BARBALOIN AB Plants containing aloin A, aloe emodin, and structurally related anthraquinones have long been used as traditional medicines and in the formulation of retail products such as laxatives, dietary supplements, and cosmetics. Since a recent study indicated that topically applied aloe emodin increases the sensitivity of skin to UV light, we examined the events following photoexcitation of aloin A and aloe emodin. We determined that incubation of human skin fibroblasts with 20 muM aloe emodin for 18 h followed by irradiation with UV or visible light resulted in significant photocytotoxicity. This photocytotoxicity was accompanied by oxidative damage in both cellular DNA and RNA. In contrast, no photocytotoxicity was observed following incubation with up to 500 muM aloin A and irradiation with UVA light. In an attempt to explain the different photobiological properties of aloin A and aloe emodin, laser flash photolysis experiments were performed. We determined that the triplet state of aloe emodin was readily formed following photoexcitation. However, Do transient intermediates were formed following photoexcitation of aloin A. Therefore, generation of reactive oxygen species and oxidative damage after irradiation of aloin A is unlikely. Although aloin A was not directly photocytotoxic, we found that human skin fibroblasts can metabolize aloin A to aloe emodin. (C) 2003 Elsevier Science Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Wamer, WG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 128,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. RI Falvey, Daniel/B-7817-2009 NR 39 TC 34 Z9 38 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 15 PY 2003 VL 34 IS 2 BP 233 EP 242 AR PII S0891-5849902)01242-X DI 10.1016/S0891-5849(02)01242-X PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 633RJ UT WOS:000180296000009 PM 12521605 ER PT J AU Pfefer, TJ Matchette, LS Ross, AM Ediger, MN AF Pfefer, TJ Matchette, LS Ross, AM Ediger, MN TI Selective detection of fluorophore layers in turbid media: the role of fiber-optic probe design SO OPTICS LETTERS LA English DT Article ID FLUORESCENCE SPECTROSCOPY; TISSUE; PROPAGATION; DEPTH; LIGHT AB Experimental verification of the ability to alter the sensitivity to fluorophore layers in turbid media by varying illumination-collection geometry is presented. Fiber-optic probes and two-layer, fluorophore-doped, turbid phantoms are used to elucidate the roles of spot size, illumination-collection fiber separation, and probe-sample spacing. Variations in single-and multiple-fiber probe design parameters produce significant changes in the relative sensitivity to sample layers in a manner that agrees with prior computational studies. (C) 2003 Optical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy, Rockville, MD 20857 USA. RI Pfefer, Josh/I-9055-2012 NR 9 TC 55 Z9 55 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JAN 15 PY 2003 VL 28 IS 2 BP 120 EP 122 DI 10.1364/OL.28.000120 PG 3 WC Optics SC Optics GA 636BA UT WOS:000180433600018 PM 12656504 ER PT J AU Somerville, L Krynetski, EY Krynetskaia, NF Beger, RD Zhang, WX Marhefka, CA Evans, WE Kriwacki, RW AF Somerville, L Krynetski, EY Krynetskaia, NF Beger, RD Zhang, WX Marhefka, CA Evans, WE Kriwacki, RW TI Structure and dynamics of thioguanine-modified duplex DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FREE-ENERGY CALCULATIONS; IMINO PROTON-EXCHANGE; BASE-PAIR; MOLECULAR-DYNAMICS; MISMATCH REPAIR; CANCER-THERAPY; CYTO-TOXICITY; 6-THIOGUANINE; NMR; MECHANISM AB Mercaptopurine and thioguanine, two of the most widely used antileukemic agents, exert their cytotoxic, therapeutic effects by being incorporated into DNA as deoxy-6-thioguanosine. However, the molecular mechanism(s) by which incorporation of these thiopurines into DNA translates into cytotoxicity is unknown. The solution structure of thioguanine-modified duplex DNA presented here shows that the effects of the modification on DNA structure were subtle and localized to the modified base pair. Specifically, thioguanine existed in the keto form, formed weakened Watson-Crick hydrogen bonds with cytosine and caused a modest similar to10degrees opening of the modified base pair toward the major groove. In contrast, thioguanine significantly altered base pair dynamics, causing an similar to80-fold decrease in the base pair lifetime with cytosine compared with normal guanine. This perturbation was consistent with the similar to6 degreesC decrease in DNA melting temperature of the modified oligonucleotide, the 1.13 ppm upfield shift of the thioguanine imino proton resonance, and the large increase in the exchange rate of the thioguanine imino proton with water. Our studies provide new mechanistic insight into the effects of thioguanine incorporation into DNA at the level of DNA structure and dynamics, provide explanations for the effects of thioguanine incorporation on the activity of DNA-processing enzymes, and provide a molecular basis for the specific recognition of thioguanine-substituted sites by proteins. These combined effects likely cooperate to produce the cellular responses that underlie the therapeutic effects of thiopurines. C1 St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Biol Struct, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Clin Pharm, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Evans, WE (reprint author), St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 332 N Lauderdale St, Memphis, TN 38105 USA. EM William.Evans@stjude.org; Richard.Kriwacki@stjude.org FU NCI NIH HHS [R37 CA36401] NR 49 TC 57 Z9 59 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 JAN 10 PY 2003 VL 278 IS 2 BP 1005 EP 1011 DI 10.1074/jbc.M204243200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 634CF UT WOS:000180321900042 PM 12401802 ER PT J AU Babu, U Scott, M Myers, MJ Okamura, M Gaines, D Yancy, HF Lillehoj, H Heckert, RA Raybourne, RB AF Babu, U Scott, M Myers, MJ Okamura, M Gaines, D Yancy, HF Lillehoj, H Heckert, RA Raybourne, RB TI Effects of live attenuated and killed Salmonella vaccine on T-lymphocyte mediated immunity in laying hens SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE Salmonella enteritidis; Con A; flagella; splenic lymphocytes; proliferation; CD4(+); CD8(+); gamma delta T-cells; alpha beta T-cells; vaccines ID MESSENGER-RNA EXPRESSION; AVIRULENT STRAIN; TYPHIMURIUM; INFECTION; CHICKENS; ENTERITIDIS; MICE; CYTOKINE; CELLS; SUBPOPULATIONS AB The impact of live and killed Salmonella vaccines on cell-mediated immunity (CMI) was investigated in 18- and 32-week-old White Leghorn chickens, by assessing splenic lymphocyte proliferation, expression of IL-2 mRNA in concanavalin A (Con A) stimulated cells and flow cytometric analysis of cell subpopulations. Con A and Salmonella enteritidis (SE) flagella induced proliferation of splenocytes were enhanced in the 18- and 32-week-old chickens treated with live vaccine, compared to the corresponding control chickens. Among the killed vaccine treated birds, Con A-mediated response was higher in the 18-week-old chickens compared to the corresponding control birds. Increased proliferation was accompanied by increased CD4 and reduced CD8 and gammadelta T-lymphocytes in the 18-week-old live vaccine treated chickens. Relative expression of IL-2 mRNA in Con A-stimulated splenocytes from 18-week-old birds was not affected by vaccine treatment. Overall, live vaccine was more effective in increasing the lymphocyte proliferation to Con A as well as SE antigen. This enhanced CMI may prove beneficial in protecting chickens against SE infection. (C) 2002 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. USDA ARS, Parasite Biol Epidemiol Systemat Lab, Anim & Nat Resources Inst, Beltsville, MD 20705 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. USDA, Natl Program Staff, Beltsville, MD 20705 USA. RP Babu, U (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd HFS 326, Laurel, MD 20708 USA. NR 31 TC 46 Z9 47 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN 10 PY 2003 VL 91 IS 1 BP 39 EP 44 AR PII S0165-2427(02)00265-9 DI 10.1016/S0165-2427(02)00265-9 PG 6 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 637AV UT WOS:000180490200005 PM 12507848 ER PT S AU Ilev, IK Waynant, RW Romanczyk, TB Gorman, EH Moore, CA Anders, JJ AF Ilev, IK Waynant, RW Romanczyk, TB Gorman, EH Moore, CA Anders, JJ GP IEEE IEEE TI In-vivo precise brain tissue ablation using smart infrared optical fibers SO 2003 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 16th Annual Meeting of the IEEE Lasers and Electro-Optics Society CY OCT 27-30, 2003 CL TUCSON, AZ SP IEEE Lasers & Electro Opt Soc ID HOLLOW-TAPER C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. 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 0-7803-7888-1 J9 IEEE LEOS ANN MTG PY 2003 BP 374 EP 375 PG 2 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BY23D UT WOS:000188359700190 ER PT J AU Martinez, MN McGilveray, L AF Martinez, MN McGilveray, L TI AAPS/RAPS/CAPRA collaborative program: Exploring the challenges of drug regulation in a global environment: Clinical concerns SO AAPS PHARMSCI LA English DT Review DE clinical trials; regulatory requirements; international harmonization; foreign clinical data ID ANTIMICROBIAL SURVEILLANCE PROGRAM; PYLORI CONSENSUS CONFERENCE; ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; WESTERN PACIFIC REGION; HELICOBACTER-PYLORI; INTERNATIONAL DIFFERENCES; UNITED-STATES; HIP FRACTURE; MEDICAL RESOURCES AB Globalization of the pharmaceutical industry has led to a need to harmonize the regulatory requirements governing the marketing of medicinal products. To minimize the barriers impeding global drug product registration, the International Conference on the Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH) was established in 1990. The ICH has developed a series of guidelines that reflect agreements reached by participating nations on aspects of the chemistry and clinical technical sections that will fulfill the regulatory requirements of these various jurisdications. Nevertheless, there continue to be points of divergent perspectives and barriers that can impede the use of foreign clinical data. Given the importance of these issues, the Regulatory Science (RS) section of the American Association of Pharmaceutical Scientists (AAPS), in conjunction with the Regulatory Affairs Professional Society (RAPS) and the Canadian Association of Professional Regulatory Affairs (CAPRA) cosponsored a public forum on this topic. This manuscript provides a summary of the speaker presentations and audience discussions regarding the design of clinical trials and the extrapolation of results from these trials to support international drug registration. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. EM mmartin1@cvm.fda.gov NR 57 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201-3042 USA SN 1522-1059 J9 AAPS PHARMSCI JI AAPS Pharmsci PY 2003 VL 5 IS 4 AR 27 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 820AL UT WOS:000221358700001 ER PT S AU Bonvini, E DeBell, KE Veri, MC Graham, L Stoica, B Laborda, J Aman, MJ DiBaldassarre, A Miscia, S Rellahan, BL AF Bonvini, E DeBell, KE Veri, MC Graham, L Stoica, B Laborda, J Aman, MJ DiBaldassarre, A Miscia, S Rellahan, BL BE Weber, G TI On the mechanism coupling phospholipase C gamma 1 to the B- and T-cell antigen receptors SO ADVANCES IN ENZYME REGULATION, VOL 43 SE Advances in Enzyme Regulation LA English DT Review CT 43rd International Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY SEP 23-24, 2002 CL INDIANA UNIV SCH MED, INDIANAPOLIS, IN HO INDIANA UNIV SCH MED ID PROTEIN-TYROSINE KINASE; EPIDERMAL GROWTH-FACTOR; FACTOR-INDUCED ACTIVATION; HOMOLOGY 3 DOMAIN; C-GAMMA; SIGNAL-TRANSDUCTION; SH2 DOMAINS; PLASMA-MEMBRANE; EGF RECEPTOR; BINDING-SITE C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Dept Biochem & Cell Biol, Frederick, MD 21702 USA. Univ G dAnnunzio, Dipartimeno Biomorfologia, I-66100 Chieti, Italy. RP US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, HFM-564,NIH Campus,Bldg 29B,Rm 3NN10,8800 Rockvil, Bethesda, MD 20892 USA. EM bonvini@mail.nih.gov RI STOICA, BOGDAN/H-9782-2013; Laborda, Jorge/L-5726-2014 OI STOICA, BOGDAN/0000-0002-2501-6434; Laborda, Jorge/0000-0002-9210-838X NR 105 TC 11 Z9 11 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI KIDLINGTON PA THE BOULEVARD, LANGFORD LANE,, KIDLINGTON OX5 1GB, OXFORD, ENGLAND SN 0065-2571 BN 0-08-044294-3 J9 ADV ENZYME REGUL JI Adv. Enzym. Regul. PY 2003 VL 43 BP 245 EP 269 DI 10.1016/S0065-2571(02)00033-X PG 25 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX22L UT WOS:000184694600018 PM 12791395 ER PT J AU Hisada, M Yao, K Maloney, EM Yamano, Y Wilks, RJ Rios, M Jacobson, S AF Hisada, M Yao, K Maloney, EM Yamano, Y Wilks, RJ Rios, M Jacobson, S TI HTLV-I/II western blot seroindeterminates represent exposure to prototype HTLV-I. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 11th International Conference on Human Retrovirology: HTLV and Related Viruses CY JUN 09-12, 2003 CL SAN FRANCISCO, CALIFORNIA C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. Univ W Indies, Kingston 7, Jamaica. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2003 VL 19 SU S MA P51 BP S44 EP S44 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 685TU UT WOS:000183280000127 ER PT J AU Hisada, M LaGrenade, L Manns, A Maloney, EM Dotrang, M Sawada, T Li, H Jack, N Morgan, O Hanchard, B Bartholomew, CF Wilks, RJ AF Hisada, M LaGrenade, L Manns, A Maloney, EM Dotrang, M Sawada, T Li, H Jack, N Morgan, O Hanchard, B Bartholomew, CF Wilks, RJ TI Evaluation of viral markers in families with HTLV-I-associated diseases in the Caribbean. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 11th International Conference on Human Retrovirology: HTLV and Related Viruses CY JUN 09-12, 2003 CL SAN FRANCISCO, CALIFORNIA C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. Dept Clin Practice, Kensington, MD USA. Comp Sci Corp, Rockville, MD USA. Eisai & Co Ltd, Diagnost Dept, Tsukuba, Ibaraki, Japan. Univ W Indies, Port Of Spain, Trinid & Tobago. Univ W Indies, Kingston 7, Jamaica. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2003 VL 19 SU S MA P23 BP S35 EP S35 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 685TU UT WOS:000183280000099 ER PT J AU Puccioni-Sohler, M Yamano, Y Papaiz-Alvarenga, R Goncalves, RR Carvalho, S Rios, M Jacobson, S AF Puccioni-Sohler, M Yamano, Y Papaiz-Alvarenga, R Goncalves, RR Carvalho, S Rios, M Jacobson, S TI HTLV-I proviral load in PBMC and CSF can differentiate HAM/TSP from patients with other neurological disorders infected with HTLV-I. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 11th International Conference on Human Retrovirology: HTLV and Related Viruses CY JUN 09-12, 2003 CL SAN FRANCISCO, CALIFORNIA C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD USA. US FDA, Rockville, MD 20857 USA. HEMORIO, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Neurolife Lab, Rio De Janeiro, Brazil. Univ Rio de Janeiro, Rio De Janeiro, Brazil. NIH, Rockville, MD USA. NIH, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, BR-21941 Rio De Janeiro, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2003 VL 19 SU S MA P67 BP S48 EP S48 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 685TU UT WOS:000183280000143 ER PT J AU Al-Khatib, SM LaPointe, NMA Curtis, LH Kramer, JM Swann, J Honig, P Califf, RM AF Al-Khatib, SM LaPointe, NMA Curtis, LH Kramer, JM Swann, J Honig, P Califf, RM TI Outpatient prescribing of antiarrhythmic drugs from 1995 to 2000 SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; RANDOMIZED TRIAL; THERAPY; AMIODARONE; MORTALITY; METAANALYSIS; GENERALIST; PHYSICIANS AB In a review of data from retail and mail-order pharmacies and survey data from 343,655 office-based physicians, we noted that prescriptions for class I agents decreased by, >50% (to 2.4 million in 2000), whereas those for class III agents doubled (to 2.7 million in 2000). The most common associated diagnoses were atrial arrhythmias, ischemic heart disease, and hypertensive heart disease; prescriptions for the latter 2 conditions represent a practice not based on evidence from clinical trials. C1 Duke Clin Res Inst, Duke Ctr Educ & Res Therapeut, Durham, NC 27715 USA. US FDA, Rockville, MD 20857 USA. RP Al-Khatib, SM (reprint author), Duke Clin Res Inst, Duke Ctr Educ & Res Therapeut, POB 17969, Durham, NC 27715 USA. FU AHRQ HHS [HS 10548] NR 18 TC 25 Z9 26 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2003 VL 91 IS 1 BP 91 EP + AR PII S0002-9149(02)03008-4 DI 10.1016/S0002-9149(02)03008-4 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 632AP UT WOS:000180201000021 PM 12505582 ER PT J AU Hu, Y Shahidi, A Park, S Guilfoyle, D Hirshfield, I AF Hu, Y Shahidi, A Park, S Guilfoyle, D Hirshfield, I TI Detection of extrahepatic hepatitis C virus replication by a novel, highly sensitive, single-tube nested polymerase chain reaction SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE hepatitis C virus; lymphocyte; complementary DNA; PCR; polymerase chain reaction; nested PCR; DNA sequencing ID BLOOD MONONUCLEAR-CELLS; FOLLOW-UP; RNA; INFECTION; STRAND; LINE; PCR; ASSAY; LIVER AB We established a cell culture system for the replication of hepatitis C virus (HCV) by using human T and B leukemia cell lines. These 2 cell lines were infected in vitro by using HCV-positive pooled patient serum samples. HCV RNA was extracted from infected cell lines at different times after infection, and a sequence of the virus 5' untranslated region was analyzed. Hepatitis C minus-strand RNA was detected in the infected cell lines by highly strand-specific rTth (recombinant Thermus thermophilus DNA polymerase)based reverse transcription followed by a novel, highly sensitive, single-tube nested polymerase chain reaction (PCR) method. PCR products were analyzed by direct DNA sequencing. These results indicate that the HCV can replicate in T and B lymphocytes. This model should represent a valuable tool for the detailed study of the initial steps of the HCV replication cycle and for the evaluation of antiviral molecules. C1 US FDA, Microbiol Sci Branch, NE Reg Lab, Jamaica, NY 11433 USA. US Dept Vet Affairs, Med Ctr, Clin Microbiol Lab, Bronx, NY USA. St Johns Univ, Dept Biol Sci, Jamaica, NY 11439 USA. RP Hu, Y (reprint author), US FDA, Microbiol Sci Branch, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 33 TC 29 Z9 30 U1 1 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2003 VL 119 IS 1 BP 95 EP 100 DI 10.1092/MG0L7NK6P9WE37RJ PG 6 WC Pathology SC Pathology GA 630VN UT WOS:000180131000013 PM 12520703 ER PT J AU Graham, DJ Drinkard, CR Shatin, D AF Graham, DJ Drinkard, CR Shatin, D TI Incidence of idiopathic acute liver failure and hospitalized liver injury in patients treated with troglitazone SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NONALCOHOLIC STEATOHEPATITIS; MITOCHONDRIAL ABNORMALITIES; INSULIN-RESISTANCE; HEPATIC-FAILURE; DISEASE; ETIOLOGY; AUTOPSY; OBESITY; DRUG AB OBJECTIVE: Troglitazone, a thiazolidinedione antidiabetic agent, was withdrawn from the U.S. market in March, 2000, after 94 cases of acute liver failure (ALF) were reported with its use. Based on a literature review, the estimated background rate of hospitalization for idiopathic acute liver injury is 22 per million person-years and for idiopathic ALF, less than 1 per million person-years. This study was conducted to estimate the incidence rates of hospitalized idiopathic acute liver injury and ALF among troglitazone-treated patients. METHODS: An observational retrospective inception cohort of patients treated with troglitazone was assembled using claims data from a large multistate health care organization. Patients with at least 90 days of health plan enrollment before their first troglitazone prescription between April, 1997 and December, 1998 were enrolled. Hospitalized cases of potential troglitazone-induced acute liver injury or ALF were identified from claims data based on International Classification of Diseases, 9th Revision, coding. Primary medical records were reviewed for case validation, and incidence rates of acute liver injury were calculated using person-years of troglitazone exposure as the denominator. RESULTS: A total of 7568 patients contributed 4020 person-years of troglitazone exposure. Of these, five were hospitalized with acute liver injury attributed to the drug and not explained by other causes. Incidence rates (95% CI) per million person-years of acute idiopathic liver injury were as follows: hospitalization (n = 5), 1244 (404, 2900); hospitalized jaundice (n = 4), 995 (271, 2546); and ALF (n = 1), 240 (6.3, 1385). CONCLUSION: Troglitazone use was associated with a marked increase in risk of hospitalized acute idiopathic liver injury and ALF. (Am J Gastroenterol 2003;98:175-179. (C) 2003 by Am. Coll. of Gastroenterology). C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Rockville, MD 20857 USA. UnitedHlth Grp, Ctr Hlth Care Policy & Res, Minnetonka, MN USA. RP Graham, DJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, 5600 Fishers Lane,HFD-400, Rockville, MD 20857 USA. NR 42 TC 55 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2003 VL 98 IS 1 BP 175 EP 179 AR PII S0002-9270(02)05843-4 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 639NQ UT WOS:000180636400029 PM 12526954 ER PT J AU Cleveland, A Westergaard, GC Hoos, B Chavanne, TJ Shoaf, SE Snoy, PJ Suomi, SJ Higley, JD AF Cleveland, A Westergaard, GC Hoos, B Chavanne, TJ Shoaf, SE Snoy, PJ Suomi, SJ Higley, JD TI Serotonergic influences on life history outcomes in free-ranging male primates SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 LABS Virginia Inc, Div Res & Dev, Yemassee, SC USA. NIAAA, Clin Studies Lab, NIH, Bethesda, MD USA. US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NICHHD, Lab Comparat Ethol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2003 SU 36 BP 77 EP 77 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 657MB UT WOS:000181670000088 ER PT J AU Baldwin, AL Wiley, EB Summers, AG Alayash, AI AF Baldwin, AL Wiley, EB Summers, AG Alayash, AI TI Sodium selenite reduces hemoglobin-induced venular leakage in the rat mesentery SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE blood substitutes; fluorescence microscopy; mast cells; antioxidant ID LIPID-PEROXIDATION; INORGANIC SELENIUM; BLOOD SUBSTITUTES; BOVINE HEMOGLOBIN; ENDOTHELIAL-CELLS; OXYGEN CARRIERS; METHEMOGLOBIN; OXIDATION; RADICALS AB Modified Hbs are being developed as "blood substitutes," but intravascular injection of diaspirin cross-linked Hb (DBBF-Hb) can produce venular leakage. Hb toxicity may arise from reactive oxygen species, so the antioxidant sodium selenite (Na2SeO3) was used in an attempt to reduce leak formation. In anesthetized Sprague-Dawley rats, one-half of which received 2 x 10(-6) g/ml Na2SeO3 in their drinking water for 3 wk, the mesenteric microvasculature was perfused with 2 mg/ml DBBF-Hb (N = 8) for 10 min. Controls (N = 7) received saline. This was followed by perfusion with FITC-albumin for 3 min, fixation, and microscopic examination. In rats given DBBF- Hb, Na2SeO3 significantly reduced leak number, leak area, and mast cell degranulation. Venular leakage was also reduced in rats that only received Na2SeO3 locally during DBBF-Hb perfusion. However, Na2SeO3 did not affect animals receiving cyanomet-DBBF-Hb instead of DBBF- Hb and significantly increased leak number and mast cell degranulation in animals receiving saline. In vitro, Na2SeO3 reduced the oxidation rate of DBBF-Hb while in the presence of oxidants. These results suggest that Na2SeO3 reduces DBBF- Hb-induced microvascular leakage partly by retarding the oxidation of its heme iron. C1 Univ Arizona, Coll Med, Dept Physiol, Tucson, AZ 85724 USA. US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Baldwin, AL (reprint author), Univ Arizona, Coll Med, Dept Physiol, Tucson, AZ 85724 USA. FU NHLBI NIH HHS [HL-53047] NR 43 TC 15 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2003 VL 284 IS 1 BP H81 EP H91 DI 10.1152/ajpheart.00562.2002 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 626DW UT WOS:000179857900011 PM 12388216 ER PT J AU Kanal, E Borgstede, JP Barkovich, AJ Bell, C Bradley, WG Felmlee, JP Froelich, JW Kaminski, EM Keeler, EK Lester, JW Scoumis, EA Zaremba, LA Zinninger, MD AF Kanal, E Borgstede, JP Barkovich, AJ Bell, C Bradley, WG Felmlee, JP Froelich, JW Kaminski, EM Keeler, EK Lester, JW Scoumis, EA Zaremba, LA Zinninger, MD TI ACR blue ribbon panel response to the AJR commentary by Shellock and Crues on the ACR white paper on MR safety SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material C1 Amer Coll Radiol, Reston, VA 20191 USA. Univ Pittsburgh, Med Ctr, Dept Radiol, Magnet Resonance Serv, Pittsburgh, PA 15213 USA. Penrose St Francis Hlth Syst, Colorado Springs, CO 80907 USA. Univ Calif San Francisco, Dept Neuroradiol, San Francisco, CA 94143 USA. Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06520 USA. Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. Mayo Clin, Dept Radiol, Rochester, MN 55902 USA. Hennepin Cty Med Ctr, Dept Radiol, Minneapolis, MN 55415 USA. Univ Minnesota, Minneapolis, MN 55415 USA. Natl Elect Manufacturers Assoc, Philips Med Syst, Cleveland, OH 44143 USA. Durham Radiol Associates, Durham, NC 27704 USA. US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20850 USA. RP Zinninger, MD (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. NR 4 TC 8 Z9 8 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2003 VL 180 IS 1 BP 31 EP 35 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 628EJ UT WOS:000179979400007 PM 12490473 ER PT J AU Bryan, WW Hoagland, RJ Murphy, J Armon, C Barohn, RJ Goodpasture, JC Miller, RG Parry, GJ Petajan, JH Ross, MA Stromatt, SC AF Bryan, WW Hoagland, RJ Murphy, J Armon, C Barohn, RJ Goodpasture, JC Miller, RG Parry, GJ Petajan, JH Ross, MA Stromatt, SC CA rhCNTF ALS Study Grp TI Can we eliminate placebo in ALS clinical trials? SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Article DE amyotrophic lateral sclerosis; motor neuron disease; natural history; neuromuscular diseases; placebo ID AMYOTROPHIC-LATERAL-SCLEROSIS; NATURAL-HISTORY AB BACKGROUND: Previous studies concluded that the decline in strength in patients with amyotrophic lateral sclerosis (ALS) is a linear function. If so, a patient's natural history might serve as the control, instead of placebo, in a clinical trial. METHODS: A placebo-controlled ALS clinical trial included a natural history phase, followed by a 6-month treatment phase. Each patient's forced vital capacity (FVC) score and maximal voluntary isometric contraction (MVIC) raw scores were measured monthly, standardized, and averaged into megascores. For 138 patients, the arm, leg, FVC, arm+leg combination, and arm+leg+FVC combination megascore slopes during the natural history phase and during the placebo phase were compared. RESULTS: The mean slope of megascores during the natural history phase and the mean slope during the placebo phase were not different for the arm, leg, and arm+leg megascores, but were different for the FVC and arm+leg+FVC combination megascores. CONCLUSIONS: Natural history controls may be useful in ALS exploratory trials that use arm megascore slope as the primary outcome measure. However, there are distinct limitations to the use of natural history controls, so that Phase 3 ALS clinical trials require placebo controls. C1 Univ Texas, SW Med Sch, Dept Neurol, Dallas, TX 75230 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Loma Linda Univ, Sch Med, Dept Neurol, Loma Linda, CA USA. Calif Pacific Med Ctr, Forbes Norris MDA ALS Ctr, Dept Neurol, San Francisco, CA USA. Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. RP Bryan, WW (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Clin Trial Design & Anal, 1401 Rockville Pike,Room 230N, Rockville, MD 20852 USA. OI Rubin, Mark/0000-0002-8321-9950 NR 15 TC 31 Z9 31 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PY 2003 VL 4 IS 1 BP 11 EP 15 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 673RG UT WOS:000182593500004 PM 12745612 ER PT J AU Ratnasinghe, DL Yao, SX Forman, M Oiao, YL Andersen, MR Giffen, CA Erozan, Y Tockman, MS Taylor, PR AF Ratnasinghe, DL Yao, SX Forman, M Oiao, YL Andersen, MR Giffen, CA Erozan, Y Tockman, MS Taylor, PR TI Gene-environment interactions between the codon 194 polymorphism of XRCC1 and antioxidants influence lung cancer risk SO ANTICANCER RESEARCH LA English DT Article DE lung cancer; XRCC1; polymorohisms; antioxidants ID DNA-REPAIR PROFICIENCY; TIN MINERS; BREAST-CANCER; DAMAGE; SENSITIVITY; FREQUENCY; PROTEINS; EXPOSURE; YUNNAN; COHORT AB X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene whose polymorphisms appear to influence the risk of lung cancer. We explored the influence of antioxidants on the association between the codon 194 arganine to tryptophan substitution polymorphism of XRCC1 and lung cancer risk. In a case-control study nested within a cohort of tin miners the cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Individuals with the variant Arg194Trp allele seemed to be at lower risk for lung cancer (odds ratio (OR): 0.7, 95% confidence interval (95%CL): 0.4-1.2). Furthermore, high serum alpha-tocopherol (OR: 0.4, 95%CL: 0.2-0.9) and retinol (OR: 0.4, 95%CL: 0.2-0.9) levels were associated with significantly reduced risk of lung cancer among individuals with the Arg194Trp variant allele, but not among individuals with the wild-type genotype. In addition, the Arg194Trp variant reduced the risk of lung cancer associated with increased serum carotenoids compared to those with the homozygous wild-type allele. Our results show that Arg194Trp XRCC1 variant modifies the association between serum antioxidants and lung cancer risk. C1 US FDA, Natl Ctr Toxicol Res, Ctr Struct Genom, Jefferson, AR 72079 USA. NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Yunnan Tin Corp, Gejiu, Yunnan Prov, Peoples R China. Appl Biosyst Inc, Foster City, CA USA. Chinese Acad Med Sci, Inst Canc, Beijing 100037, Peoples R China. Informat Management Serv Inc, Silver Spring, MD USA. Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. RP Ratnasinghe, DL (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Struct Genom, 3900 NCTR Dr, Jefferson, AR 72079 USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 24 TC 25 Z9 26 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 2003 VL 23 IS 1B BP 627 EP 632 PG 6 WC Oncology SC Oncology GA 657LR UT WOS:000181669100020 PM 12680158 ER PT J AU DeVito, JA Morris, S AF DeVito, JA Morris, S TI Exploring the structure and function of the mycobacterial KatG protein using trans-dominant mutants SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; CATALASE-PEROXIDASE GENE; ESCHERICHIA-COLI; ISONIAZID RESISTANCE; NUCLEOTIDE-SEQUENCE; TUBERCULOSIS KATG; GLOBAL BURDEN; EXPRESSION; ETHIONAMIDE; KATG(S315T) AB In order to probe the structure and function of the mycobacterial catalase-peroxidase enzyme (KatG), we employed a genetic approach using dominant-negative analysis of katG merodiploids. Transformation of Mycobacterium bovis BCG with various katG point mutants (expressed from low-copy-number plasmids) resulted in reductions in peroxidase and catalase activities as measured in cell extracts. These reductions in enzymatic activity usually correlated with increased resistance to the antituberculosis drug isoniazid (INH). However, for the N138S trans-dominant mutant, the catalase-peroxidase activity was significantly decreased while the sensitivity to INH was retained. trans-dominance required katG expression from multicopy plasmids and could not be demonstrated with katG mutants integrated elsewhere on the wild-type M. bovis BCG chromosome. Reversal of the mutant phenotype through plasmid exchange suggested the catalase-peroxidase deficiency occurred at the protein level and that INH resistance was not due to a second site mutation(s). Electrophoretic analysis of KatG proteins from the trans-dominant mutants showed a reduction in KatG dimers compared to WT and formation of heterodimers with reduced activity. The mutants responsible for these defects cluster around proposed active site residues: N138S, T275P, S315T, and D381G. In an attempt to identify mutants that might delimit the region(s) of KatG involved in subunit interactions, C-terminal truncations were constructed (with and without the D381G dominant-negative mutation). None of the C-terminal deletions were able to complement a DeltakatG strain, nor could they cause a dominant-negative effect on the WT. Taken together, these results suggest an intricate association between the amino- and carboxyterminal regions of KatG and may be consistent with a domain-swapping mechanism for KatG dimer formation. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. RP Morris, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 39 TC 9 Z9 9 U1 0 U2 2 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 JAN PY 2003 VL 47 IS 1 BP 188 EP 195 DI 10.1128/AAC.47.1.188-195.2003 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 631CL UT WOS:000180149600030 PM 12499190 ER PT J AU Foley, SL Horne, SM Giddings, CW Gustad, TR Handegard, ED Robinson, M Nolan, LK AF Foley, SL Horne, SM Giddings, CW Gustad, TR Handegard, ED Robinson, M Nolan, LK TI Monoclonal antibodies to avian Escherichia coli iss SO AVIAN DISEASES LA English DT Article DE avian Escherichia coli; avian colibacillosis; Iss; complement resistance; monoclonal antibody development; virulence ID COMPLEMENT RESISTANCE; HELIGMOSOMOIDES-POLYGYRUS; SERUM RESISTANCE; VIRULENCE; COLV,I-K94; GENES; TRAT; IGG1 AB Escherichia coli infections are a major problem for the poultry industry in the United States. Yet, the virulence mechanisms operative in avian E. coli are poorly understood. In the present studies, monoclonal antibodies (MAbs) have been generated that may facilitate study of the pathogenesis of avian colibacillosis. These MAbs are directed against the Iss protein because results from our laboratory have shown that the possession of iss DNA sequences is strongly correlated with the E coli implicated in avian colibacillosis. As part of an overall effort to explore the role of iss/Iss in colibacillosis pathogenesis, Iss protein has been purified, MAbs to Iss have been generated, and the MAbs are being evaluated. B cells from mice immunized with an Iss fusion to glutathione-S-transferase produced antibodies specifically against Iss, and these cells were used to generate the MAbs. These anti-Iss MAbs, when used in western blotting assays, can be used to distinguish iss-positive and -negative E. coli isolates, suggesting that they may be useful as reagents in the detection and study of virulent avian E. coli. C1 N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Nolan, LK (reprint author), N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. NR 22 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC AVIAN PATHOLOGISTS PI KENNETT SQ PA UNIV PENN, NEW BOLTON CENTER, KENNETT SQ, PA 19348-1692 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD JAN-MAR PY 2003 VL 47 IS 1 BP 79 EP 86 DI 10.1637/0005-2086(2003)047[0079:MATAEC]2.0.CO;2 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 665AN UT WOS:000182097600008 PM 12713161 ER PT J AU White, DG Ayers, S Maurer, JJ Thayer, SG Hofacre, C AF White, DG Ayers, S Maurer, JJ Thayer, SG Hofacre, C TI Antimicrobial susceptibilities of Staphylococcus aureus isolated from commercial broilers in northeastern Georgia SO AVIAN DISEASES LA English DT Article DE poultry; Staphylococcus aureus; antimicrobial resistance; MIC ID TETRACYCLINE RESISTANCE GENES; AVIAN ESCHERICHIA-COLI; MASTITIS PATHOGENS; BOVINE MASTITIS; PREVALENCE; POULTRY; INFECTION; CHICKENS; DOGS AB Staphylococcus aureus is an important opportunist that can cause superficial to life-threatening illnesses in a variety of animal species. In poultry, this organism has been implicated in osteomyelitis, synovitis, and cellulitis. Whereas most infections can be treated with antibiotics, because of the organism's propensity to acquire antimicrobial resistance, it is important to continually monitor antibiotic susceptibilities of clinical isolates. We surveyed 77 clinical poultry S. aureus isolates, collected from 1998 to 2000, for susceptibilities to a panel of 18 antimicrobial agents. Thirty-six percent of isolates were susceptible to all antibiotics. Forty-three and 16% of avian S. aureus were resistant to one and two antibiotics respectively. Staphylococcus aureus isolates were commonly resistant to tetracycline (40%; minimal inhibitory concentration [MIC](90) > 32 mug/ml), lincomycin (19%; MIC90 > 32 mug/ml), erythromycin (12%; MIC90 > 8 mug/ml), and kanamycin (8%; MIC90 < 128 mug/ml). All S. aureus isolates were susceptible to chloramphenicol, gentamicin, streptomycin, nitrofurantion, linezolid, quinupristin/dalfopristin, vancomycin, and the production antimicrobials virginiamycin, salinomycin, and flavomycin. A periodic assessment of antimicrobial susceptibilities of important avian pathogens like S. aureus will be important in helping the clinician's choice of antibiotic to control infection. C1 Univ Georgia, Dept Avian Med, Athens, GA 30602 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Hofacre, C (reprint author), Univ Georgia, Dept Avian Med, Athens, GA 30602 USA. NR 36 TC 10 Z9 10 U1 1 U2 6 PU AMER ASSOC AVIAN PATHOLOGISTS PI KENNETT SQ PA UNIV PENN, NEW BOLTON CENTER, KENNETT SQ, PA 19348-1692 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD JAN-MAR PY 2003 VL 47 IS 1 BP 203 EP 210 DI 10.1637/0005-2086(2003)047[0203:ASOSAI]2.0.CO;2 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 665AN UT WOS:000182097600026 PM 12713179 ER PT J AU Zhou, GY Jiang, W Zhao, Y Ma, GG Xin, WJ Yin, JJ Zhao, BL AF Zhou, GY Jiang, W Zhao, Y Ma, GG Xin, WJ Yin, JJ Zhao, BL TI Sodium tanshinone IIA sulfonate mediates electron transfer reaction in rat heart mitochondria SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE sodium tanshinone IIA sulfonate (STS); mitochondria; respiratory chain; free radicals; antioxidant; electron spin resonance (ESR) ID FREE-RADICALS; REPERFUSION INJURY; LIPID-PEROXIDATION; NADH; PROTECTION; MYOCARDIUM; ISCHEMIA AB In this paper, an electron transfer reaction mediated by sodium tanshinone IIA sulfonate (STS) was studied in rat heart mitochondria. It was found that STS could stimulate mitochondrial NADH oxidation dose-dependently and partly restore NADH oxidation in the presence of respiratory inhibitor (rotenone or antimycin A or KCN). It was likely that STS could accept electrons from complex I similar to ferricyanide and could be converted to its semiquinone form that could then reduce oxygen molecule. The data also showed that cytochrome c (Cyt c) could be reduced by STS in the presence of KCN, or STS could transfer the electron to oxygen directly. Free radicals were involved in the process. The results suggest that STS may protect ischemia-reperfusion injury through an electron transfer reaction in mitochondria against forming reactive oxygen radicals. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Acad Sinica, Inst Biophys, Dept Mol & Cell Biophys, Lab Visual Informat Proc, Beijing 100101, Peoples R China. Natl Inst Pharmaceut Res & Dev, Beijing 102206, Peoples R China. US FDA, CFSAN, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. RP Zhao, BL (reprint author), Acad Sinica, Inst Biophys, Dept Mol & Cell Biophys, Lab Visual Informat Proc, Beijing 100101, Peoples R China. RI Yin, Jun Jie /E-5619-2014 NR 24 TC 46 Z9 55 U1 0 U2 5 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 JAN 1 PY 2003 VL 65 IS 1 BP 51 EP 57 AR PII S0006-2952(02)01447-8 DI 10.1016/S0006-2952(02)01447-8 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 633FW UT WOS:000180272800007 PM 12473378 ER PT J AU Johnson, EL Schmidt, WF Emche, SD Mossoba, MM Musser, SM AF Johnson, EL Schmidt, WF Emche, SD Mossoba, MM Musser, SM TI Kaempferol (rhamnosyl) glucoside, a new flavonol from Erythroxylum coca. var.ipadu SO BIOCHEMICAL SYSTEMATICS AND ECOLOGY LA English DT Article DE Erythroxylum coca var. ipadu; E. c. var. ipadu; Amazonian coca; flavonoids; flavonol; kaempferol; rhamnoside; glucoside ID CHRYSOSPLENIUM-AMERICANUM; POLYMETHYLATED FLAVONOLS; ENZYMATIC-SYNTHESIS; CHEMOTAXONOMIC MARKERS; TAXA AB A new flavonol, kaempferol rhamnosyl diglycoside, was isolated from leaf tissue of Amazonian field-grown coca Erythroxylum coca var. ipadu Plowman. The structure of the flavonol has been determined as kaempferol 4'-O-(rhamnosyl)glucoside by spectral analyses. The array of flavonoids present in E. c. var. ipadu currently under cultivation in Colombian fields is indicative of a recent cross, consistent with ancestralship to E. c. var: coca and the flavonol is useful as a chemotaxonomic marker for the taxon. Published by Elsevier Science Ltd. C1 USDA ARS, Alternate Crops & Syst Lab, Beltsville, MD 20705 USA. USDA, Environm Chem Lab, Beltsville, MD 20705 USA. US FDA, Instrumentat & Biophys Branch, Washington, DC 20204 USA. RP Johnson, EL (reprint author), USDA ARS, Alternate Crops & Syst Lab, Bldg 001 Rm 329 BARC-W, Beltsville, MD 20705 USA. NR 27 TC 10 Z9 13 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-1978 J9 BIOCHEM SYST ECOL JI Biochem. Syst. Ecol. PD JAN PY 2003 VL 31 IS 1 BP 59 EP 67 AR PII S0305-1978(02)00071-6 DI 10.1016/S0305-1978(02)00071-6 PG 9 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 636EW UT WOS:000180442500006 ER PT J AU Mohan, KVK Atreya, CD AF Mohan, KVK Atreya, CD TI Novel organelle-targeting signals in viral proteins SO BIOINFORMATICS LA English DT Article ID INFECTED-CELLS; PEROXISOMES; BIOGENESIS; IMPORT; IDENTIFICATION; RECOGNITION; MEMBRANE; YEAST; VIRUS; NEF C1 US FDA, Sect Viral Pathogenesis & Vaccine Adverse React, Lab Pediat & Resp Viral Dis,Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), US FDA, Sect Viral Pathogenesis & Vaccine Adverse React, Lab Pediat & Resp Viral Dis,Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 22 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN PY 2003 VL 19 IS 1 BP 10 EP 13 DI 10.1093/bioinformatics/19.1.10 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 636PA UT WOS:000180463900003 PM 12499287 ER PT J AU Naaz, A Yellayi, S Zakroczymski, MA Bunick, D Doerge, DR Lubahn, D Helferich, WG Cooke, PS AF Naaz, A Yellayi, S Zakroczymski, MA Bunick, D Doerge, DR Lubahn, D Helferich, WG Cooke, PS TI Dietary administration of the phytoestrogen genistein has anti-lipogenic effects. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Univ Illinois, Dept Vet Biosci, Urbana, IL 61801 USA. Univ Illinois, Div Nutr Sci, Urbana, IL 61801 USA. Natl Ctr Toxicol Res, Jefferson, AR USA. Univ Missouri, Dept Biochem, Columbia, MO USA. Univ Missouri, Dept Child Hlth, Columbia, MO USA. Univ Illinois, Dept Food Sci & Nutr, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 277 BP 226 EP 226 PG 1 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400332 ER PT S AU Ho, C Kurtzman, SB AF Ho, C Kurtzman, SB BE Benghuzzi, H Tucci, M TI Issues in using databases of pre-recorded physiological signals to test medical devices SO BIOMEDICAL SCIENCES INSTRUMENTATION, VOL 39 SE BIOMEDICAL SCIENCES INSTRUMENTATION LA English DT Proceedings Paper CT 40th Annual Rocky Mountain Bioengineering Symposium/40th International ISA Biomedical Sciences Instrumentation Symposium CY APR 10-13, 2003 CL BILOXI, MS SP Instrumentat Syst & Automat Soc DE apnea; bioimpedance; electrocardiographic; heart rate variability; multi-channel; pre-recorded physiological signals AB Bench testing wit h databases of pre-recorded physiological signals is a common step in the verification and validation of medical devices. For example, in the case of an electrocardiographic (ECG) monitor to be tested, the physiological signals are ECG tracings that have previously been recorded from patients using other ECG monitors. Human overreaders then annotate the tracings to determine the occurrence of significant clinical events such as ventricular tachycardia. These annotations can be used to determine the sensitivity and specificity of the ECG monitor to be tested. This article aims to highlight some issues associated with such bench testing, such as the way the prerecorded signals are presented to the medical device to be tested, the adequacy of single channel versus dual channel versus multi-channel testing in the bench testing, and the need for the human overreaders and the medical device to use the same set of rules for determining the occurrence of a clinical event. These issues are also applicable to other monitors such as the apnea monitor. Some suggestions for addressing the issues are presented. C1 US Dept HHS, US FDA, Rockville, MD 20850 USA. RP Ho, C (reprint author), US Dept HHS, US FDA, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU INSTRUMENT SOC AMER PI RESEARCH TRIANGLE PARK PA 67 ALEXANDER DR, PO BOX 12277, RESEARCH TRIANGLE PARK, NC 27709 USA SN 0067-8856 J9 BIOMED SCI INSTRUM PY 2003 VL 39 BP 169 EP 174 PG 6 WC Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Instruments & Instrumentation SC Biochemistry & Molecular Biology; Computer Science; Engineering; Instruments & Instrumentation GA BW53U UT WOS:000182321800030 PM 12724888 ER PT J AU Chen, JJ Hsueh, HM Liu, JP AF Chen, JJ Hsueh, HM Liu, JP TI Simultaneous non-inferiority test of sensitivity and specificity for two diagnostic procedures in the presence of a gold standard SO BIOMETRICAL JOURNAL LA English DT Article DE accuracy; correlated binary endpoints; diagnostic procedure or screening test; one-sided equivalence test; sample size ID SAMPLE-SIZE; EQUIVALENCE; DESIGN; PROPORTIONS; DIFFERENCE AB Sensitivity and specificity have traditionally been used to assess the performance of a diagnostic procedure. Diagnostic procedures with both high sensitivity and high specificity are desirable, but these procedures are frequently too expensive, hazardous, and/or difficult to operate. A less sophisticated procedure may be preferred, if the loss of the sensitivity or specificity is determined to be clinically acceptable. This paper addresses the problem of simultaneous testing of sensitivity and specificity for an alternative test procedure with a reference test procedure when a gold standard is present. The hypothesis is formulated as a compound hypothesis of two non-inferiority (one-sided equivalence) tests. We present an asymptotic test statistic based on the restricted maximum likelihood estimate in the framework of comparing two correlated proportions under the prospective and retrospective sampling designs. The sample size and power of an asymptotic test statistic are derived. The actual type I error and power are calculated by enumerating the exact probabilities in the rejection region. For applications that require high sensitivity as well as high specificity, a large number of positive subjects and a large number of negative subjects are needed. We also propose a weighted sum statistic as an alternative test by comparing a combined measure of sensitivity and specificity of the two procedures. The sample size determination is independent of the sampling plan for the two tests. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Chengchi Univ, Dept Stat, Taipei 11623, Taiwan. Natl Cheng Kung Univ, Dept Stat, Div Biostat & Bioinformat, Natl Hlth Res Inst, Tainan, Taiwan. EM jchen@nctr.fda.gov OI Liu, Jen-pei/0000-0002-9565-1812; HSUEH, HUEY-MIIN/0000-0003-0536-9440 NR 12 TC 8 Z9 8 U1 0 U2 3 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2003 VL 45 IS 1 BP 47 EP 60 DI 10.1002/bimj.200290015 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 641CJ UT WOS:000180726600004 ER PT J AU Lawrence, J Hung, HMJ AF Lawrence, J Hung, HMJ TI Estimation and confidence intervals after adjusting the maximum information SO BIOMETRICAL JOURNAL LA English DT Article DE adaptive test; interim analysis; consistent; coverage probability; sequential monitoring ID SAMPLE-SIZE; CLINICAL-TRIALS; TESTS AB In a comparative clinical trial, if the maximum information is adjusted on the basis of unblinded data, the usual test statistic should be avoided due to possible type I error inflation. An adaptive test can be used as an alternative. The usual point estimate of the treatment effect and the usual confidence interval should also be avoided. In this article, we construct a point estimate and a confidence interval that are motivated by an adaptive test statistic. The estimator is consistent for the treatment effect and the confidence interval asymptotically has correct coverage probability. C1 US FDA, Div Biometr 1, OB CDER, Rockville, MD 20857 USA. NR 11 TC 19 Z9 19 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2003 VL 45 IS 2 BP 143 EP 152 DI 10.1002/bimj.200390001 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 662LP UT WOS:000181948400002 ER PT J AU Hung, HMJ O'Neill, RT AF Hung, HMJ O'Neill, RT TI Utilities of the P-value distribution associated with effect size in clinical trials SO BIOMETRICAL JOURNAL LA English DT Article DE percentile; effect size; power; significance level; confidence interval; replication probability; interim analysis; robustness ID HYPOTHESIS AB The P-value, which is widely used for assessing statistical evidence in randomized comparative clinical trials, is a function of the observed effect size of the experimental treatment relative to the control treatment. The relationship of the P-value with the observed effect size at study completion and the effect size anticipated at the design stage has potential usefulness in providing guidance for planning and interpretation of a clinical trial. The post-trial power associated with a statistically significant P-value from a completed study is also a random variable and its use may assist in planning a follow-up trial to confirm the statistically significant findings in an initial study. A measure of robustness is explored to quantify the degree of sensitivity of the observed P-value to potential bias that may be contained in the observed effect size. C1 US FDA, CDER, OPaSS, Off Biostat,Div Biomat 1, Rockville, MD 20852 USA. US FDA, CDER, OPaSS, Off Biostat, Rockville, MD 20857 USA. RP Hung, HMJ (reprint author), US FDA, CDER, OPaSS, Off Biostat,Div Biomat 1, HFD-710,Room 5062,Woodmont 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 9 TC 14 Z9 14 U1 0 U2 2 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2003 VL 45 IS 6 BP 659 EP 669 DI 10.1002/bimj.200390040 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 722UX UT WOS:000185397300002 ER PT J AU Hinderling, PH AF Hinderling, PH TI Evaluation of a novel method to estimate absolute bioavailability of drugs from oral data SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Review DE absolute bioavailability; oral data; renal function; bias ID IMPAIRED RENAL-FUNCTION; AMBULATORY PERITONEAL-DIALYSIS; MULTIPLE-DOSE PHARMACOKINETICS; HEALTHY-VOLUNTEERS; FLECAINIDE PHARMACOKINETICS; ACEBUTOLOL DISPOSITION; CRITICAL-VIEW; FAILURE; SINGLE; KINETICS AB The goal of this investigation was to evaluate the performance of a novel method allowing estimation of absolute bioavailability from oral data only. In contrast to the traditional method, which compares areas under the drug concentration time curves after oral and intravenous administration in subjects with normal renal function, the novel method uses total and renal clearance values following oral administration from subjects with varying renal functions to estimate bioavailability. The novel method can also provide estimates for nonrenal clearance. Published data on total clearance and renal clearance of drugs obtained from subjects with variable renal functions were collected, the novel method applied, estimates of bioavailability and nonrenal clearance obtained and compared with reported estimates by the traditional methods. In addition computations were performed to assess various factors that could possibly affect the reliability of the novel method. The results indicated that the novel method provides accurate estimates for bioavailability of drugs meeting the prerequisites: linear kinetics, predominant renal excretion in normals, absence of metabolic polymorphism and independence of bioavailability and nonrenal clearance from renal function. The average (standard deviation) of the prediction error and bias of the bioavailability estimates by the novel method was 7.8 (6.0) and -1.4 (9.8)%, respectively The estimates for nonrenal clearance by the novel method were less accurate. The computations confirmed that the estimates by the novel method are sensitive to renal-function dependent changes in nonrenal clearance and bioavailability and also depend on the extent of renal excretion of a drug. In conclusion, the novel method's main use is to diagnose absence or presence of changes in bioavailability and non-renal clearance of drugs in populations with varying renal function. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Berlex Labs Inc, Montville, NJ 07045 USA. RP Hinderling, PH (reprint author), US FDA, CDER, DPEI, HFD 860, Room 5046,WOCII,1451 Rockville Pike, Rockville, MD 20852 USA. NR 129 TC 4 Z9 4 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD JAN PY 2003 VL 24 IS 1 BP 1 EP 16 DI 10.1002/bdd.320 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 637TT UT WOS:000180530400001 PM 12516074 ER PT J AU Arthanari, H McConnell, KJ Beger, R Young, MA Beveridge, DL Bolton, PH AF Arthanari, H McConnell, KJ Beger, R Young, MA Beveridge, DL Bolton, PH TI Assessment of the molecular dynamics structure of DNA in solution based on calculated and observed NMR NOESY volumes and dihedral angles from scalar coupling constants SO BIOPOLYMERS LA English DT Article DE molecular dynamics; nucleic acids; oligonucleotide duplex ID PARTICLE MESH EWALD; NUCLEAR MAGNETIC-RESONANCE; B-DNA; CONFORMATIONAL PREFERENCES; AQUEOUS-SOLUTION; FORCE-FIELD; A-TRACTS; R-FACTOR; SIMULATIONS; ACIDS AB To assess the accuracy of the molecular dynamics (MD) models of nucleic acids, a detailed comparison between MD-calculated and NMR-observed indices of the dynamical structure of DNA in solution has been carried out. The specific focus of our comparison is the oligonucleotide duplex, d(CGCGAATTCGCG)(2), for which considerable structural data have been obtained from crystallography and NMR spectroscopy. An MD model for the structure of d(CGCGAATTCGCG)(2) in solution, based on the AMBER force field, has been extended with a 14 ns trajectory. New NMR data for this sequence have been obtained in order to allow a detailed and critical comparison between the calculated and observed parameters. Observable two-dimensional (2D) nuclear Overhauser effect spectroscopy (NOESY) volumes and scalar coupling constants were back-calculated from the MD trajectory and compared with the corresponding NMR data. The comparison of these results indicate that the MD model is in generally good agreement with the NMR data, and shows closer accord with experiment than back-calculations based on the crystal structure of d(CGCGAATTCGCG)(2) or the canonical A or B forms of the sequence. The NMR parameters are not particularly sensitive to the known deficiency in the AMBER MD model, which is a tendency toward undertwisting of the double helix when the parm.94 force field is used. The MD results are also compared with a new determination of the solution structure of d(CGCGAATTCGCG)(2) using NMR dipolar coupling data. (C) 2002 Wiley Periodicals, Inc. C1 Wesleyan Univ, Dept Chem, Middletown, CT 06459 USA. Wesleyan Univ, Mol Biophys Program, Middletown, CT 06459 USA. Agilix Corp, New Haven, CT 06530 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Bolton, PH (reprint author), Wesleyan Univ, Dept Chem, Middletown, CT 06459 USA. RI Young, Matthew/D-2033-2011 OI Young, Matthew/0000-0003-2921-3432 FU PHS HHS [NIH 37909, NIH65871] NR 63 TC 30 Z9 30 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD JAN PY 2003 VL 68 IS 1 BP 3 EP 15 DI 10.1002/bip.10263 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 632ED UT WOS:000180210000002 PM 12579576 ER PT J AU Dragunsky, E Nomura, T Karpinski, K Furesz, J Woods, DJ Pervikov, Y Abe, S Kurata, T Vanloocke, O Karganova, G Tuffs, R Heath, A Ivshina, A Levenbook, I AF Dragunsky, E Nomura, T Karpinski, K Furesz, J Woods, DJ Pervikov, Y Abe, S Kurata, T Vanloocke, O Karganova, G Tuffs, R Heath, A Ivshina, A Levenbook, I TI Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article DE poliovirus vaccine, oral/toxicity; mice, transgenic/physiology; macaca mulatta; nervous system/virology; virulence; sensitivity and specificity; reproducibility of results; World Health Organization; comparative study; validation studies (source : MeSH, NLM) ID RECEPTOR; MODEL; VIRUS AB Objective Extensive WHO collaborative studies were performed to evaluate the suitability of transgenic mice susceptible to poliovirus (TgPVR mice, strain 21, bred and provided by the Central Institute for Experimental Animals, Japan) as an alternative to monkeys in the neurovirulence test (NVT) of oral poliovirus vaccine (OPV). Methods Nine laboratories,participated in the collaborative study on testing of 94 preparations of OPV and vaccine derivatives of all three serotypes in:TgPVR21 mice Findings Statistical analysis of the data demonstrated that the TgPVR21. mouse NVT was of comparable sensitivity and reproducibility to the conventional WHO NVT in simians. A statistical model for acceptance/rejection of OPV lots in the mouse test was developed, validated, and shown to be suitable for all three vaccine types. The assessment of the transgenic mouse NVT is based on clinical evaluation of paralysed mice; Unlike the monkey NVT, histological examination of central nervous system tissue of each mouse offered no advantage over careful and detailed clinical observation. Conclusions Based on data from the collaborative studies the WHO Expert Committee for Biological Standardization approved the mouse NVT as an alternative to the monkey test for all three OPV types and defined a standard implementation process for laboratories that wish to use the test. This represents the first successful introduction of transgenic animals into control of biologicals. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. GlaxoSmithKline Biol, In Vivo QC, Rixensart, Belgium. Natl Inst Infect Dis, Tokyo, Japan. Japan Poliomyelitis Res Inst, Tokyo, Japan. WHO, CH-1211 Geneva, Switzerland. Cent Inst Expt Anim, Kawasaki, Kanagawa, Japan. RP Dragunsky, E (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. RI Karganova, Galina/D-8601-2014 NR 25 TC 15 Z9 18 U1 0 U2 2 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2003 VL 81 IS 4 BP 251 EP 260 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 672AE UT WOS:000182497600005 PM 12764491 ER PT J AU White, DG Zhao, SH McDermott, PF Ayers, S Friedman, S Sherwod, J Breider-Foley, M Nolan, LK AF White, DG Zhao, SH McDermott, PF Ayers, S Friedman, S Sherwod, J Breider-Foley, M Nolan, LK TI Characterization of integron mediated antimicrobial resistance in Salmonella isolated from diseased swine SO CANADIAN JOURNAL OF VETERINARY RESEARCH-REVUE CANADIENNE DE RECHERCHE VETERINAIRE LA English DT Article ID MULTIPLE-ANTIBIOTIC-RESISTANCE; ENTERICA SEROTYPE TYPHIMURIUM; ORGANIC-SOLVENT TOLERANCE; ESCHERICHIA-COLI; SEROVAR TYPHIMURIUM; ANIMAL PRODUCTION; UNITED-STATES; MAR LOCUS; GENES; DT104 AB Forty-two Salmonella isolates obtained from diseased swine were genetically characterized for the presence of specific antimicrobial resistance mechanisms. Twenty of those isolates were characterized as S. Typhimurium DT104 strains. Pulsed-field gel electrophoresis was used to determine genetic relatedness and revealed 20 distinct genetic patterns among the 42 isolates. However, all DT104 isolates fell within 2 closely related genetic clusters. Other Salmonella isolates were genetically grouped together according to serotype. All DT104 isolates displayed the penta-resistance phenotype to ampicillin, chloramphenicol,, streptomycin, sulfamethoxazole, and tetracycline. Resistance to sulfamethoxazole, tetracycline, streptomycin, kanamycin, and ampicillin was most common among the non-DT104 Salmonella isolates. All DT104 strains contained 2 chromosomal integrons of 1000 and 1200 base pairs. The DNA sequencing revealed that the 2 integrons contained genes encoding a resistance to streptomycin and ampicillin, respectively. None of the non-DT104 strains showed the same pattern, although several strains possessed integrons of 1000 base pairs or larger. However, the majority of non-DT104 Salmonella strains did not possess any integrons. Two Salmonella isolates displayed tolerance to the organic solvent cyclohexane, indicating the possibility that they are overexpressing chromosomal regulatory genes marA or soxS or the associated multidrug efflux pump, acrAB. This research suggests that integrons contribute to antimicrobial resistance among specific swine Salmonella serotypes; however, they are not as widely disseminated among non-Typhimurium swine Salmonella serotypes as previously thought. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. RP White, DG (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 36 TC 21 Z9 21 U1 2 U2 2 PU CANADIAN VET MED ASSOC PI OTTAWA PA 339 BOOTH ST ATTN: KIMBERLY ALLEN-MCGILL, OTTAWA, ONTARIO K1R 7K1, CANADA SN 0830-9000 J9 CAN J VET RES JI Can. J. Vet. Res.-Rev. Can. Rech. Vet. PD JAN PY 2003 VL 67 IS 1 BP 39 EP 47 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 632TW UT WOS:000180239800005 PM 12528827 ER PT J AU Trasler, J Deng, LY Melnyk, S Pogribny, I Hiou-Tim, F Sibani, S Oakes, C Li, E James, SJ Rozen, R AF Trasler, J Deng, LY Melnyk, S Pogribny, I Hiou-Tim, F Sibani, S Oakes, C Li, E James, SJ Rozen, R TI Impact of Dnmt1 deficiency, with and without low folate diets, on tumor numbers and DNA methylation in Min mice SO CARCINOGENESIS LA English DT Article ID MULTIPLE INTESTINAL NEOPLASIA; NESTED CASE-CONTROL; PLASMA HOMOCYSTEINE; COLORECTAL-CANCER; GENE-EXPRESSION; SUPPRESSOR GENE; COLON-CANCER; P53 GENE; HYPOMETHYLATION; RISK AB Although a number of studies have suggested that diets with low intake of folate, an important methyl donor, are associated with increased risks of colon cancer and its precursor the adenomatous polyp, the underlying mechanisms are poorly understood. Dysregulation and instability of DNA methylation and alterations in the levels of the predominant DNA methylating enzyme, DNA (cytosine-5)methyltransferase 1 (Dnmt1), have also been linked to tumorigenesis. We have used a combination of genetic and dietary manipulation to assess the effects of reduced Dnmt1 expression with and without folate deficiency on tumor induction in the Apc(Min) mouse. Apc(Min) mice with a reduction in Dnmt1 expression (Apc(Min/+) /Dnmt1(C/+)) had significantly lower tumor numbers than Ape(Min) mice with normal Dnmt1 (Apc(Min/+) /Dnmt1(+/+)). Dietary folate deficiency from weaning to 13 weeks of age did not affect tumor number or size in Apc(Min/+) /Dnmt(+/+) mice. However, in Apc(Min/+) /Dnmt1(C/+) mice with high baseline tumor numbers (41 4), folate deficiency was associated with a decreased absolute number of tumors (27 3), but a higher proportion of larger tumors as compared with mice on the control diet. In the repeat experiment, Apc(Min/+) / Dnmt1(C/+) mice had low baseline tumor numbers (20 +/- 2) and folate deficiency did not affect tumor number (23 +/- 4) or size as compared with the same mice on the control diet. These results suggest that, in the presence of Dnmt1 deficiency, the effects of folate deficiency on tumor number and size may depend on the stage of adenoma development when folate deficiency is initiated. We also show that folate deficiency with or without reductions in Dnmt1 did not affect overall genomic DNA methylation or the methylation levels of two candidate genes, E-cadherin or p53, in normal or neoplastic intestinal tissue. In conclusion, genetic deficiency in Dnmt1 with or without folate deficiency decreases tumor number in the Apc(Min) mouse model, but this effect may not be mediated by changes in SAM or SAH levels, nor by alterations in global methylation in the pre-neoplastic intestinal tissue. C1 McGill Univ, Dept Pediat, Montreal Childrens Hosp, Montreal, PQ H3Z 2Z3, Canada. McGill Univ, Dept Human Genet, Montreal Childrens Hosp, Montreal, PQ H3Z 2Z3, Canada. McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Med Sch, Boston, MA USA. RP Rozen, R (reprint author), McGill Univ, Dept Pediat, Montreal Childrens Hosp, 4060 St Catherine St W, Montreal, PQ H3Z 2Z3, Canada. RI Oakes, Christopher/H-7288-2014 NR 38 TC 43 Z9 46 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2003 VL 24 IS 1 BP 39 EP 45 DI 10.1093/carcin/24.1.39 PG 7 WC Oncology SC Oncology GA 644AP UT WOS:000180896000006 PM 12538347 ER PT J AU Pletnikov, MV Rubin, SA Moran, TH Carbone, KM AF Pletnikov, MV Rubin, SA Moran, TH Carbone, KM TI Exploring the cerebellum with a new tool: neonatal Borna disease virus (BDV) infection of the rat's brain SO CEREBELLUM LA English DT Article DE Borna; cerebellum; developmental disorders; animal models ID CENTRAL-NERVOUS-SYSTEM; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; PURKINJE-CELL DEGENERATION; HIPPOCAMPAL DENTATE GYRUS; RECEPTOR GENE-EXPRESSION; NEURODEVELOPMENTAL DAMAGE; POSTNATAL-DEVELOPMENT; PERSISTENT INFECTION; CHEMOKINE RECEPTOR; BIPOLAR DISORDER AB Cerebellar pathology has been associated with a number of developmental behavioral disorders, including autism spectrum disorders. Despite the fact that perinatal virus infections have been implicated in neurodevelopmental damage, few animal models have been developed to study the pathogenesis involved. One of the most interesting in vivo models of virus-induced cerebellar damage is the neonatal Borna disease virus (BDV) infection of the rat brain. The present review describes molecular, cellular, neuroanatomical, neurochemical and behavioral features of the BDV model and also provides a basis for a new understanding of the pathogenic mechanisms of cerebellar malformation and associated behavioral deficits. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, OD, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, LPRVD, DVP,OVRR, Bethesda, MD USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA. FU NIMH NIH HHS [R01 MH48948-08A1] NR 88 TC 11 Z9 14 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1473-4222 J9 CEREBELLUM JI Cerebellum PY 2003 VL 2 IS 1 BP 62 EP 70 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 739NC UT WOS:000186352500008 PM 12882236 ER PT J AU Xia, QS Chou, MW Kadlubar, FF Chan, PC Fu, PP AF Xia, QS Chou, MW Kadlubar, FF Chan, PC Fu, PP TI Human liver microsomal metabolism and DNA adduct formation of the tumorigenic pyrrolizidine alkaloid, riddelliine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID FLAVIN-CONTAINING MONOOXYGENASE; PROTEIN CROSS-LINKS; MAMMALIAN-CELLS; N-OXIDATION; GUINEA-PIG; RAT-LIVER; IN-VITRO; SENECIONINE; BIOACTIVATION; TOXICITY AB Riddelliine, a widespread naturally occurring genotoxic pyrrolizidine alkaloid, induced liver tumors in rats and mice in an NTP 2-year carcinogenicity bioassay. We have determined that riddelline induces liver tumors in rats through a genotoxic mechanism involving the formation of (+/-)-6,7-dlhydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), which reacts with DNA to form a set of eight DNA adducts. To determine the relevance to humans of the results obtained in experimental animals, the metabolism of riddelline was conducted using human liver microsomes. As with rat liver microsomes, DHP and riddelline N-oxide were major metabolites in incubations conducted with human liver microsomes. The levels of DHP and riddelliine N-oxide were 0.20-0.62 and 0.03-0.15 nmol/min/mg protein, respectively, which are comparable to those obtained from rat liver microsomal metabolism. When metabolism was conducted in the presence of calf thymus DNA, the same set of eight DHP-derived DNA adducts was formed. Both the metabolism pattern and DNA adduct profile were very similar to those obtained from rat liver microsomes. When metabolism was conducted in the presence of the P450 3A4 enzyme inhibitor triacetyleandomycin, the formation of DHP and riddelline N-oxide was reduced 84 and 92%, respectively. For DHP formation, the K-m values were determined to be 0.37 +/- 0.05 and 0.66 +/- 0.08 mM from female rats and female humans; the V-max values from female rat and human liver microsomal metabolism were 0.48 +/- 0.03 and 1.70 +/- 0.09 nmol/min/mg protein, respectively. These results strongly indicate the mechanistic data on liver tumor induction obtained for riddelliine in laboratory rodents is highly relevant to humans. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 43 TC 47 Z9 48 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2003 VL 16 IS 1 BP 66 EP 73 DI 10.1021/tx025605i PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 638PC UT WOS:000180578600009 PM 12693032 ER PT J AU Jones, MB Michener, CM Blanchette, JO Kuznetsov, VA Raffeld, M Serrero, G Emmert-Buck, MR Petricoin, EF Krizman, DB Liotta, LA Kohn, EC AF Jones, MB Michener, CM Blanchette, JO Kuznetsov, VA Raffeld, M Serrero, G Emmert-Buck, MR Petricoin, EF Krizman, DB Liotta, LA Kohn, EC TI The granulin-epithelin precursor/PC-cell-derived growth factor is a growth factor for epithelial ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GRANULIN/EPITHELIN PRECURSOR; GENE-EXPRESSION; FACTOR PCDGF; FACTOR-BETA; IN-VITRO; CARCINOMA; TUMORS; CDNA; SEQUENCE; LINE AB Purpose: The role of growth factors in ovarian cancer development and progression is complex and multifactorial. We hypothesized that new growth factors may be identified through the molecular analysis of ovarian tumors as they exist in their native environment. Experimental Design: RNA extracted from microdissected serous low malignant potential (LMP) and invasive ovarian tumors was used to construct cDNA libraries. A total of 7300 transcripts were randomly chosen for sequencing, and those transcripts were statistically evaluated. Reverse transcription-PCR and immunohistochemistry were used to validate the findings in tumor tissue samples. Ovarian cancer cell lines were used to test gene effects on monolayer growth, proliferative capacity, and density-independent growth. Results: Analysis of the pooled library transcripts revealed 26 genes differentially expressed between LMP and invasive ovarian cancers. The granulin-epithelin precursor [GEP/PC-cell derived growth factor (PCDGF)] was expressed only in the invasive ovarian cancer libraries (P < 0.028) and was absent in the LMP libraries (0 of 2872 clones). All of the invasive tumor epithelia, 20% of the LMP tumor epithelia, and all of the stroma from both subsets expressed GEP by reverse transcription-PCR. Immunohistochemical staining for GEP was diffuse and cytosolic in invasive ovarian cancer tumor cells compared with occasional, punctate, and apical staining in LMP tumor epithelia. Antisense transfection of GEP into ovarian cancer cell lines resulted in down-regulation of GEP production, reduction in cell growth (P < 0.002), decrease in the S-phase fraction (P < 0.04), and loss of density-independent growth potential (P < 0.01). Conclusion: cDNA library preparation from microdissected tumor epithelium provided a selective advantage for the identification of growth factors for epithelial ovarian cancer. Differential granulin expression in tumor samples and the antiproliferative effects of its antisense down-regulation suggest that GEP may be a new autocrine growth factor and molecular target for epithelial ovarian cancer. C1 NCI, Mol Signaling Sect, Pathol Lab, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Kohn, EC (reprint author), NCI, Mol Signaling Sect, Pathol Lab, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 39 TC 55 Z9 60 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2003 VL 9 IS 1 BP 44 EP 51 PG 8 WC Oncology SC Oncology GA 635ZT UT WOS:000180430600006 PM 12538450 ER PT J AU Wysowski, DK Kornegay, C Nourjah, P Trontell, A AF Wysowski, DK Kornegay, C Nourjah, P Trontell, A TI Sex and age differences in serum potassium in the United States SO CLINICAL CHEMISTRY LA English DT Letter ID GENDER C1 US FDA, Off Drug Safety, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Off Drug Safety, Div Drug Risk Evaluat, HFD-430,Parklawn Bldg,Room 15B-08, Rockville, MD 20857 USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2003 VL 49 IS 1 BP 190 EP 192 DI 10.1373/49.1.190 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 631YK UT WOS:000180195700031 PM 12507983 ER PT J AU Burke, LB Patrick, D Scott, J Kammerman, LA AF Burke, LB Patrick, D Scott, J Kammerman, LA TI The US Food and Drug Administration perspective on assessing the clinical significance of quality-of-life outcomes SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 3rd Conference on Quality of Life - Translating the Science of Quality-of-Life Assessment into Clinical Practice CY OCT 02-04, 2003 CL MAYO CLINIC, SCOTTSDALE, ARIZONA HO MAYO CLINIC C1 US FDA, Rockville, MD 20857 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2003 VL 25 SU D MA 6 BP D10 EP D11 DI 10.1016/S0149-2918(03)80250-3 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742LN UT WOS:000186519000008 ER PT J AU Kammerman, LA AF Kammerman, LA TI A regulatory case study: Treatment of Dyspnea associated with chronic obstructive pulmonary disease SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 3rd Conference on Quality of Life - Translating the Science of Quality-of-Life Assessment into Clinical Practice CY OCT 02-04, 2003 CL MAYO CLINIC, SCOTTSDALE, ARIZONA HO MAYO CLINIC C1 US FDA, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2003 VL 25 SU D MA 10 BP D14 EP D16 DI 10.1016/S0149-2918(03)80254-0 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742LN UT WOS:000186519000012 ER PT J AU Banks, DL Olszewski, RT Maxion, RA AF Banks, DL Olszewski, RT Maxion, RA TI Comparing methods for multivariate nonparametric regression SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE multivariate nonparametric regression; projection pursuit regression; MARS; ACE; LOESS; neural networks ID ESTIMATING OPTIMAL TRANSFORMATIONS; LOCALLY WEIGHTED REGRESSION; MULTIPLE-REGRESSION; NEURAL NETWORKS; NOISY DATA; II METHOD; SPLINES; APPROXIMATION AB The ever-growing number of high-dimensional, superlarge databases requires effective analysis techniques to mine interesting information from the data. Development of new-wave methodologies for high-dimensional nonparametric regression has exploded over the last decade in an effort to meet these analysis demands. This article reports on an extensive simulation experiment that compares the performance of ten different, commonly-used regression techniques: linear regression, stepwise linear regression, additive models (AM), projection pursuit regression (PPR), recursive partitioning regression (RPR), multivariate adaptive regression splines (MARS), alternating conditional expectations (ACE), additivity and variance stabilization (AVAS), locally weighted regression (LOESS), and neural networks. Each regression technique was used to analyze multiple datasets each having a unique embedded structure; the accuracy of each technique was determined by its ability to correctly identify the embedded structure averaged over all the datasets. Datasets used in the experiment were constructed so as to have particular properties which varied across the datasets in order to determine each technique's accuracy within various environments. The dataset properties which were varied include dimension of the data, the true dimension of the embedded structure, the sample size, the amount of noise, and the complexity of the embedded structure. Analyses of the results show that all of these properties affect the accuracy of each regression technique under investigation. A mapping from data characteristics to the most effective regression technique(s) is suggested. C1 FDA CBER, Rockville, MD 20852 USA. Univ Pittsburgh, Ctr Biomed Informat, Pittsburgh, PA USA. Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA. EM banksd@cber.fda.gov NR 35 TC 5 Z9 5 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 2003 VL 32 IS 2 BP 541 EP 571 DI 10.1081/SAC-120017506 PG 31 WC Statistics & Probability SC Mathematics GA 685GV UT WOS:000183254800015 ER PT J AU Lee, CJ Lee, LH Frasch, CE AF Lee, CJ Lee, LH Frasch, CE TI Protective immunity of pneumococcal glycoconjugates SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; POLYSACCHARIDE CONJUGATE VACCINES; CELL-INDEPENDENT ANTIGENS; ZONE B-CELLS; INTRANASAL IMMUNIZATION; SURFACE PROTEIN; LYMPHOID-TISSUE; CHOLERA-TOXIN; UNITED-STATES; MARGINAL-ZONE AB Pneumococcal polysaccharides (PSs), designated as T-cell independent type 2 (TI-2) antigens, induce poor immune responses in young children. Splenic marginal zone B cells, associated with CD21, CD19 and C3d, play an important role in TI-2 antibody responses, and provide host defense against bacterial pathogens. Antibody response, avidity, and opsonophagocytic activity of antisera were examined in mice immunized with type 9V PS conjugated to inactivated pneulmolysin (Ply) or to autolysin (Aly). Compared to mice given 9V PS alone, serum IgG and IgM concentrations against the 9V PS were higher in mice immunized with conjugates. High concentrations of serum antibodies were maintained for over 12 weeks. The relative avidities of IgG and IgM antibodies and opsonophagocytic activity against 9V pneumococci were high in mice immunized with conjugates. Thus, conjugate vaccines can induce high as well as long duration of antibody response and effective functional activity. In another study, mice received intranasal immunization with type 9V conjugate or 9V PS. These animals produced 9V PS IgG and IgA antibodies in their serum, spleen, intestine, lung, Peyer's patch and fecal extract samples. Mice immunized with these glycoconjugates exhibited opsonophagocytic activity and rapid bacterial clearance from blood and provided homologous and cross-protection against challenge with virulent pneumococci. These results indicate that intranasal immunization with glycoconjugate vaccines may serve as an alternative and convenient approach for prevention of pneumococcal infection. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM lee_chi@cber.FDA.gov NR 77 TC 18 Z9 18 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1040-841X J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PY 2003 VL 29 IS 4 BP 333 EP 349 DI 10.1080/10408410390255260 PG 17 WC Microbiology SC Microbiology GA 746PK UT WOS:000186754600004 PM 14636043 ER PT J AU McCright, B AF McCright, B TI Notch signaling in kidney development SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE Alagille's syndrome; glomerular vascularization; Jagged1; kidney development; Notch2 ID ALAGILLE-SYNDROME; ARTERIOHEPATIC DYSPLASIA; CELL FATE; MICE; GENE; DELTA; ENDOTHELIUM; EXPRESSION; REQUIRES; MUTATION AB Purpose of review Notch signaling is a highly conserved mechanism used by multicellular animals to specify cell fate decisions during the formation of complex structures such as the kidney. A number of studies have recently identified requirements for Notch signaling during kidney organogenesis and tissue repair. This review will summarize these studies and compare Notch signaling in the mammalian kidney with Notch signaling in other organ systems. Recent findings A targeted mutation in the mouse Notch2 receptor resulted in kidneys that are devoid of glomerular endothelial and mesangial cells. The mutant epithelial cells of the developing glomerulus have reduced amounts of vascular endothelial growth factor expression, which may be responsible for the lack of vascularization observed in these glomeruli. Notch2 is expressed in the epithelial cells of the developing glomerulus, and a potential ligand, Jagged1, is expressed in the endothelial cells of the glomerulus. Mice simultaneously heterozygous for mutations in both Notch2 and Jagged1 phenocopy the kidney defects seen in mice homozygous for the Notch2 mutation. These doubly heterozygous mice also display liver and heart developmental abnormalities reminiscent of Alagille's syndrome. Summary Notch signaling is required for kidney development, and the expression of Notch genes is increased in response to kidney damage. Further studies of Notch signaling will be important in order to understand kidney development and tissue repair. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP McCright, B (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN13, Bethesda, MD 20892 USA. NR 41 TC 45 Z9 52 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JAN PY 2003 VL 12 IS 1 BP 5 EP 10 DI 10.1097/01.mnh.0000049802.69874.c0 PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 635MP UT WOS:000180403500002 PM 12496659 ER PT B AU Mariansky, JH AF Mariansky, JH GP CIP TI United States Food and Drug Administrations (FDA's) approach to the safety of bioengineered foods SO CURRENT STUDIES OF BIOTECHNOLOGY, VOL III: FOOD LA English DT Proceedings Paper CT Scientific Conference on Biotechnology and Food CY FEB 19-22, 2003 CL Zagreb, CROATIA SP Croatian Soc Biotechnol, Croatian Acad Sci & Arts, Sci Council Agr & Forestry, Croatian Acad Engn, Croatian Acad Med Sci, Univ Zagreb, Fac Food Technol & Biotechnol, PLIVA Inc Pharmaceut Ind C1 US FDA, Ctr Food Safety & Appl Nutr, Dept Hlth & Human Serv, Washington, DC 20204 USA. RP Mariansky, JH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Dept Hlth & Human Serv, Washington, DC 20204 USA. NR 3 TC 0 Z9 0 U1 1 U2 2 PU CROATIAN SOCIETY BIOTECHNOLOGY PI ZAGREB PA PIEROTI ST 6, 10000 ZAGREB, CROATIA BN 953-176-209-0 PY 2003 BP 375 EP 379 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA BY77E UT WOS:000189459300035 ER PT J AU Bracho, F van de Ven, C Areman, E Hughes, RM Davenport, V Bradley, MB Cai, JW Cairo, MS AF Bracho, F van de Ven, C Areman, E Hughes, RM Davenport, V Bradley, MB Cai, JW Cairo, MS TI A comparison of ex vivo expanded DCs derived from cord blood and mobilized adult peripheral blood plastic-adherent mononuclear cells: decreased alloreactivity of cord blood DCs SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Hematology CY DEC 07-11, 2001 CL ORLANDO, FLORIDA SP Amer Soc Hematol DE dendritic cell; cord blood; alloreactivity; monocyte peripheral blood; FLT-3 ligand ID COLONY-STIMULATING FACTOR; VERSUS-HOST-DISEASE; NECROSIS-FACTOR-ALPHA; CD34(+) HEMATOPOIETIC PROGENITORS; ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; GENE-EXPRESSION; UNRELATED DONORS; ACTIVATED CORD; BONE-MARROW AB Background Cord blood (CB) has been used as an alternative source of transplantable allogeneic stein cells for a variety of malignant and non-malignant diseases. However, we have demonstrated delayed recover), of T- and B-cell function, and T-cell subsets post unrelated CB transplantation (UCBT), and deficiencies of CB mononuclear cells (MNC) in producing cytokines, including G-CSF, GM-CSF, M-CSF, IL-12, and IL-15. In this study we have investigated the ex vivo generation of DC from CB versus mobilized adult peripheral blood of (APB) for later use as adoptive cellular immonotherapy. Methods CB and APB-adherent MNC were cultured in serum-free media with GM-CSF, IL-4, FLT-3 ligand, tumor growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha) for 7 days. Morphology, phenotype, immunohistochemistry clonogenic activity, and alloreactivity in MLR were evaluated. Results CB and APB monocyte-derived ex vivo expanded DC expressed similar DC markers CD83 (31.27 +/- 11.7% versus 34.0 +/- 5.2%, CB versus APB), CD1a (23.4 +/- 4.2% versus 27.6 +/- 63%), and CD80 (21.97 +/- 12.01% versus 27.7 +/- 5.95). Immunohistochemistry showed that cells with DC morphology expressed CD1a but not CD14. Neither FLT-3 ligand nor TGF-beta enhanced DC expansion. Addition of 10% autologous plasma to CB cultures promoted greater cell survival and a 150% increase in CD1a(+)/CD80(+) cell recovery. CB DC were 62% as effective stimulators of adult allogencic T-cells as APB DC (p < 0.05) in allogencic MLR. Discussion While phenotypically similar CB and APB DC have differential potency in allogeneic MLR, which may account for the difference in GvHD and infection incidence and severity between UCBT and allogeneic stem cell transplantation, and may require a different approach for adoptive cellular immunotherapy. The mechanism(s) associated with these differences require further elucidation. C1 Columbia Univ, Childrens Hosp New York Presbyterian, Dept Pediat, New York, NY 10032 USA. Georgetown Univ Hosp, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ Hosp, Lombardi Canc Ctr, Washington, DC 20007 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Beckman Coulter Inc, Miami, FL USA. RP Cairo, MS (reprint author), Columbia Univ, Childrens Hosp New York Presbyterian, Dept Pediat, 161 Ft Washington,Irving 7, New York, NY 10032 USA. FU NCI NIH HHS [5K12 CA76903-04] NR 50 TC 12 Z9 13 U1 1 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2003 VL 5 IS 5 BP 349 EP 361 DI 10.1080/14653240310003017 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 740TL UT WOS:000186417600001 PM 14578097 ER PT J AU Baratta, EJ AF Baratta, EJ TI Determination of radionuclides in foods from Minsk, Belarus, from Chernobyl to the present SO CZECHOSLOVAK JOURNAL OF PHYSICS LA English DT Article; Proceedings Paper CT 14th Radiochemical Conference CY APR 14-19, 2002 CL MARIANSKE LAZNE, CZECH REPUBLIC SP Czech Tech Univ, Czech Chem Soc, IM Marci Spectroscop Soc, Czech Radioecol Soc AB The U.S. Food and Drug Administration (FDA) are responsible for the wholesomeness of the food supply in the United States (US). The FDA has been monitoring the food supply in the United States for radioactivity since 1961, because of the Fallout generated by above the ground testing in the early 60's. This Radionuclide in Foods Program is maintained to allow the FDA to respond to any nuclear emergency that may affect the food supply. The Three Mile Island incident in 1979 was one of these. In 1986 the Chernobyl incident occurred. As a result, the FDA began extensive monitoring of imported foods, especially those from Europe. One of its sister agencies has personnel in the areas effected by the latter incident and requested that the FDA analyze selected food samples from these places. Since that time, they have requested on a periodic basis, selected food samples be analysed. One such city was Minsk in Belarus. This paper will discuss the radionuclides of interest such as iodine-131, cesium-134/137, strontium-90, ruthenium-106 and other short-lived ones. It will discuss the types of foods sampled and the methodology used in determining the concentrations found in these items. The results will be compared to the permissible levels allowed in the US. In addition it will show the lower limits of detection for each of the radionuclides of interest. C1 US FDA, Winchester, MA 01890 USA. RP Baratta, EJ (reprint author), US FDA, 109 Holton St, Winchester, MA 01890 USA. NR 6 TC 2 Z9 2 U1 0 U2 1 PU INST PHYSICS ACAD SCI CZECH REPUBLIC PI PRAGUE PA NA SLOVANCE 2, PRAGUE 182 21, CZECH REPUBLIC SN 0011-4626 J9 CZECH J PHYS JI Czech. J. Phys. PY 2003 VL 53 SU A BP A31 EP A37 DI 10.1007/s10582-003-0006-y PN 1 PG 7 WC Physics, Multidisciplinary SC Physics GA 705QJ UT WOS:000184405900006 ER PT B AU Petrick, N Woo, TH Chan, HP Sahiner, B Hadjiiski, LM AF Petrick, N Woo, TH Chan, HP Sahiner, B Hadjiiski, LM BE Peitgen, HO TI Evaluation of light collection in digital indirect detection x-ray imagers: Monte Carlo simulations with a more realistic phosphor screen model SO DIGITAL MAMMOGRAPHY, PROCEEDINGS SE DIGITAL MAMMOGRAPHY: INTERNATIONAL WORKSHOP ON DIGITAL MAMMOGRAPHY LA English DT Proceedings Paper CT 6th International Workshop on Digital Mammography CY JUN 22-25, 2002 CL BREMEN, GERMANY SP MeVis BreastCare, Siemens Med, GE, R2, Display Solut Siemens, HOLOGIC, BARCO ID ACTIVE-MATRIX; MAMMOGRAPHY AB We are performing simulation studies to investigate whether a microlens layer sandwiched between a phosphor screen and a photodetector will improve light collection in indirect-detection x-ray imagers. In this study, we examined the light collection efficiency after incorporating the spatial and angular spread of photons due to the phosphor screen in the model. Monte Carlo simulations of a uniform, planar x-ray source were conducted and the light collection efficiencies of two imager configurations were compared. Imager I had the screen in direct contact with the photodetector while Imager 2 had a microlens array sandwiched between the screen and the photodetector. A total of 72% of the scintillation light (31% in the "central" pixel directly below the x-ray interaction point and 41% in the 8 nearest neighbor pixels) was collected by the photodetector for Imager 2 compared with only 56% (28% in the central pixel and 28% by the nearest neighbor pixels) for Imager 1. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Petrick, N (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-00523-4 J9 DIGIT MAMMO PY 2003 BP 54 EP 58 PG 5 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Obstetrics & Gynecology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Obstetrics & Gynecology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW62K UT WOS:000182609000012 ER PT B AU Chakrabarti, K Kaczmarek, RV Thomas, JA Mahesh, M Fleischman, RC AF Chakrabarti, K Kaczmarek, RV Thomas, JA Mahesh, M Fleischman, RC BE Peitgen, HO TI Effect of detector noise on phantom image quality in a number of FFDM systems SO DIGITAL MAMMOGRAPHY, PROCEEDINGS SE DIGITAL MAMMOGRAPHY: INTERNATIONAL WORKSHOP ON DIGITAL MAMMOGRAPHY LA English DT Proceedings Paper CT 6th International Workshop on Digital Mammography CY JUN 22-25, 2002 CL BREMEN, GERMANY SP MeVis BreastCare, Siemens Med, GE, R2, Display Solut Siemens, HOLOGIC, BARCO AB We have assessed phantom image quality from a number of commercially available Full Field Digital Mammography (FFDM) systems. Image quality, contrast to noise ratio (CNR) and signal to noise ratio (SNR) were evaluated at various technique factors to assess the effect of detector noise on image quality, detector dynamic range and quantum limited operating region. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Chakrabarti, K (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-00523-4 J9 DIGIT MAMMO PY 2003 BP 95 EP 99 PG 5 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Obstetrics & Gynecology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Obstetrics & Gynecology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW62K UT WOS:000182609000021 ER PT J AU Mehta, AI Ross, S Lowenthal, MS Fusaro, V Fishman, DA Petricoin, EF Liotta, LA AF Mehta, AI Ross, S Lowenthal, MS Fusaro, V Fishman, DA Petricoin, EF Liotta, LA TI Biomarker amplification by serum carrier protein binding SO DISEASE MARKERS LA English DT Article ID MOLECULAR WEIGHT PROTEINS; PROSTATE-CANCER; PROTEOMIC PATTERNS; OVARIAN-CANCER; ALBUMIN; IDENTIFICATION; DISCOVERY; ELECTROPHORESIS; BIOINFORMATICS; MS AB Mass spectroscopic analysis of the low molecular mass (LMM) range of the serum/plasma proteome is a rapidly emerging frontier for biomarker discovery. This study examined the proportion of LMM biomarkers, which are bound to circulating carrier proteins. Mass spectroscopic analysis of human serum following molecular mass fractionation, demonstrated that the majority of LMM biomarkers exist bound to carrier proteins. Moreover, the pattern of LMM biomarkers bound specifically to albumin is distinct from those bound to non-albumin carriers. Prominent SELDI-TOF ionic species (m/z 6631.7043) identified to correlate with the presence of ovarian cancer were amplified by albumin capture. Several insights emerged: a) Accumulation of LMM biomarkers on circulating carrier proteins greatly amplifies the total serum/plasma concentration of the measurable biomarker, b) The total serum/plasma biomarker concentration is largely determined by the carrier protein clearance rate, not the unbound biomarker clearance rate itself, and c) Examination of the LMM species bound to a specific carrier protein may contain important diagnostic information. These findings shift the focus of biomarker detection to the carrier protein and its biomarker content. C1 Howard Hughes Med Inst, Bethesda, MD 20814 USA. US FDA, FDA NCI Clin Proteom Program, Off Director, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, FDA NCI Clin Proteom Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Natl Ovarian Canc Early Detect Program, Chicago, IL 60611 USA. RP Mehta, AI (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 2A33, Bethesda, MD 20892 USA. EM arpita.mehta@tufts.edu NR 34 TC 144 Z9 150 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 1 BP 1 EP 10 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 818TA UT WOS:000221266200001 PM 14757941 ER PT J AU Johann, DJ McGuigan, MD Tomov, S Fusaro, VA Ross, S Conrads, TP Veenstra, TD Fishman, DA Whiteley, GR Petricoin, EF Liotta, LA AF Johann, DJ McGuigan, MD Tomov, S Fusaro, VA Ross, S Conrads, TP Veenstra, TD Fishman, DA Whiteley, GR Petricoin, EF Liotta, LA TI Novel approaches to visualization and data mining reveals diagnostic information in the low amplitude region of serum mass spectra from ovarian cancer patients SO DISEASE MARKERS LA English DT Article DE ovarian cancer; SELDI-TOF MS; data visualization; diagnosis ID PROTEOMIC PATTERNS; PROSTATE-CANCER AB The ability to identify patterns of diagnostic signatures in proteomic data generated by high throughput mass spectrometry (MS) based serum analysis has recently generated much excitement and interest from the scientific community. These data sets can be very large, with high-resolution MS instrumentation producing 1-2 million data points per sample. Approaches to analyze mass spectral data using unsupervised and supervised data mining operations would greatly benefit from tools that effectively allow for data reduction without losing important diagnostic information. In the past, investigators have proposed approaches where data reduction is performed by a priori "peak picking" and alignment/warping/smoothing components using rule-based signal-to-noise measurements. Unfortunately, while this type of system has been employed for gene microarray analysis, it is unclear whether it will be effective in the analysis of mass spectral data, which unlike microarray data, is comprised of continuous measurement operations. Moreover, it is unclear where true signal begins and noise ends. Therefore, we have developed an approach to MS data analysis using new types of data visualization and mining operations in which data reduction is accomplished by culling via the intensity of the peaks themselves instead of by location. Applying this new analysis method on a large study set of high resolution mass spectra from healthy and ovarian cancer patients, shows that all of the diagnostic information is contained within the very lowest amplitude regions of the mass spectra. This region can then be selected and studied to identify the exact location and amplitude of the diagnostic biomarkers. C1 NCI, FDA, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Div Informat Technol, Upton, NY 11973 USA. SAIC Frederick Inc, NCI, Lab Proteom & Analyt Technol, Frederick, MD USA. Northwestern Univ, Sch Med, Natl Ovarian Canc Early Detect Program, Chicago, IL 60611 USA. SAIC Frederick, Clin Proteom Reference Lab, NCI FDA Clin Proteom Program, Gaithersburg, MD USA. NCI, FDA Clin Proteom Program, Off Cell & Gene Therapy, Ctr Biol Evaluat & Res Food & Drug Adm, Bethesda, MD 20892 USA. RP Johann, DJ (reprint author), NCI, FDA, Clin Proteom Program, Pathol Lab,Ctr Canc Res, 8800 Rockville Pike,Bldg 29A,Room 2A21, Bethesda, MD 20892 USA. EM dj151o@nih.gov NR 14 TC 9 Z9 9 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2003 VL 19 IS 4-5 BP 197 EP 207 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 837TY UT WOS:000222665000004 PM 15258334 ER PT J AU Sathe, PM Venitz, J AF Sathe, PM Venitz, J TI Comparison of neural network and multiple linear regression as dissolution predictors SO DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY LA English DT Article DE neural network; multiple linear regression; dissolution; prediction AB The predictive performance of an artificial neural network (NN) was compared with the first-order multiple linear regression (MLR) using mean dissolution data of 28 diltiazem immediate release tablet formulations. The performance was evaluated using "Weibull" function parameters alpha and beta. Weibull parameters were used as dissolution markers of the eight principal, mainly compositional, variables. The parameters were obtained by fitting the Weibull function to the mean (n = 12) dissolution profiles of 28 diltiazem hydrochloride tablet formulations. The generated set of 28 pairs of Weibull function parameters was evaluated for internal and external predictability using both the MLR and the artificial NN. A three-layered 8-5-2 feedforward NN was found to be an adequate descriptor of the dissolution data. Internal predictions were based on the data of 24 products. External predictions used the 24 product data to test four products not used in the training phase. The predictive performances of the two techniques were evaluated using bias (mean prediction error; MPE) and precision (mean absolute error; MAE). The study results suggested that, for the studied data set, NN is a superior internal and external predictor to MLR. [GRAPHICS] The artificial NN predicted order of the formulation composition variables, influencing the dissolution parameters as follows: hydrogenated oil > microcrystallinecellulose > ethyl cellulose > eudragit > hydroxypropylcellulose > coat > hydroxypropylmethylcellulose > Speed. C1 US FDA, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20855 USA. Virginia Commonwealth Univ, Richmond, VA USA. RP Sathe, PM (reprint author), US FDA, Off Gener Drugs, Div Bioequivalence, 7500 Standish Pl, Rockville, MD 20855 USA. NR 10 TC 22 Z9 22 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0363-9045 J9 DRUG DEV IND PHARM JI Drug Dev. Ind. Pharm. PY 2003 VL 29 IS 3 BP 349 EP 355 DI 10.1081/DDC-120018209 PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 673TR UT WOS:000182596700010 PM 12741616 ER PT J AU Haffner, ME AF Haffner, ME TI The current environment in orphan drug development SO DRUG INFORMATION JOURNAL LA English DT Article DE orphan drugs; The Orphan Drug act; Office of Orphan Drugs Development AB Pharmaceutical development over the past two decades has shown a substantial increase in the number of drugs available to treat rare ("orphan") diseases, largely due to the passage of the Orphan Drug Act. This article provides an overview of orphan diseases and conditions; the Orphan Drug Act; the Food and Drug Administration's Office of Orphan Products Development, which administers the Orphan Drug Act; the changing nature of rare disease treatment; and designing clinical trials to investigate rare diseases. The success of the Orphan Drug Act is far greater than anticipated; to date 242 orphan drugs have been approved. The Orphan Drug Act continues to encourage manufacturers to develop treatments to help more than 11 million patients in the United States who suffer from rare diseases. C1 US FDA, Off Orphan Prod Dev, Rockville, MD 20852 USA. US PHS, Washington, DC 20201 USA. RP Haffner, ME (reprint author), US FDA, Off Orphan Prod Dev, HF-35,Room 6A55,Parklawn Bldg,5600 Fishers Lane, Rockville, MD 20852 USA. NR 1 TC 5 Z9 6 U1 0 U2 1 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2003 VL 37 IS 4 BP 373 EP 379 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 745DF UT WOS:000186673100004 ER PT J AU Dai, RK Wei, XX Luo, G Sinz, M Marathe, P AF Dai, RK Wei, XX Luo, G Sinz, M Marathe, P TI Metabolism-dependent P450 3A4 inactivation with multiple substrates SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 12th North American ISSX Meeting CY OCT 12-16, 2003 CL PROVIDENCE, RHODE ISLAND SP Pfizer Inc, Boehringer Ingelheim, Novartis Pharmaceut, Purdue Pharma LP, Schering-Plough Res, Sanofi Synthelabo Res, Merck Res Lab, Otsuka Pharmaceut Co Ltd, Wyeth-Ayerst Res Lab C1 Bristol Myers Squibb Co, Pharmaceut Candidate Optimizat, Princeton, NJ 08543 USA. Bristol Myers Squibb Co, Pharmaceut Candidate Optimizat, Wallingford, CT 06492 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20875 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2003 VL 35 SU 2 MA 341 BP 171 EP 171 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734QX UT WOS:000186069300332 ER PT J AU Hess, JL Clark, LS Moore, MM AF Hess, JL Clark, LS Moore, MM TI Trp53 sequence analysis of L5178Y cell line derivatives SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE Trp53; mouse lymphoma assay ID MOUSE LYMPHOMA-CELLS; MUTATIONS; P53; MUTAGENICITY; LOCUS; GENE C1 Western Maryland Coll, Westminster, MA USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA. US EPA, Genet & Cellular Toxicol Branch, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. RP Moore, MM (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 12 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2003 VL 42 IS 2 BP 122 EP 124 DI 10.1002/em.10180 PG 3 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 718FC UT WOS:000185133600009 PM 12929125 ER PT J AU Cebula, TA AF Cebula, TA TI In memoriam - Remembering Philip E. Hartman SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Biographical-Item C1 Food & Drug Adm, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), Food & Drug Adm, Off Appl Res & Safety Assessment, HFS-25,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2003 VL 42 IS 3 BP 125 EP 126 DI 10.1002/em.10194 PG 2 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 740NF UT WOS:000186407900001 ER PT J AU Malling, HV Delongchamp, RR Valentine, CR AF Malling, HV Delongchamp, RR Valentine, CR TI Three origins of Phi X174 am39 revertants in transgenic cell culture SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE Phi X174; transgenic; embryonic cells; revertants; ENU; single burst assay ID ESCHERICHIA-COLI; PHIX174 AM3; IN-VITRO; DETECTING MUTATION; MICE; MUTAGENESIS; SINGLE; CS70; LINE; FREQUENCIES AB Transgenic systems for measuring mammalian mutagenesis often use recoverable viral vectors. We hypothesize that mutations in these transgenic systems can arise from three different origins of DNA damage and replication errors and that these three origins of mutations (in vivo, ex vivo, and in vitro) can be differentiated in the PhiX174 am3, cs70 single burst assay (SBA) on the basis of burst size (BS). In vivo mutations are fixed in the animal, ex vivo mutations are fixed in bacterial cells during recovery of the phage, and in vitro revertants arise during the first replications of nonmutant phages under selective conditions. PX-2 cells, derived from a homozygous embryo of a PhiX174 transgenic mouse, were treated with vehicle or N-ethyl-N-nitrosourea (ENU). An algorithm was developed to estimate the BS that resulted in the highest induced revertant frequency; the estimate was 56. In vivo revertants were defined as having BS >55, ex vivo revertants as having a BS of 13-56, and in vitro revertants as having a BS of <14. The frequencies of in vivo revertants at 0, 100, and 200 mg/kg ENU were 0.06, 0.36, and 4.10 x 10(-6) (dose response, P = 0.004); ex vivo revertants were 0.36, 0.46, and 0.41 x 10(-6) (P = 0.37), and in vitro revertants were 0.39, 0.46, and 0.41 x 10(-6) (P = 0.55), respectively. These results show that only in vivo revertants reflect mutagen treatment. They also provide a basis for identifying PhiX174 am3 revertants induced in vivo and may increase the sensitivity of the assay for in vivo mutation. Published 2003 Wiley-Liss, Inc.(dagger). C1 NIEHS, Mammalian Mutagenesis Grp, Lab Toxicol Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Malling, HV (reprint author), NIEHS, Mammalian Mutagenesis Grp, Lab Toxicol Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM mailing@niehs.nih.gov NR 23 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2003 VL 42 IS 4 BP 258 EP 273 DI 10.1002/em.10195 PG 16 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 760ZA UT WOS:000187864100005 PM 14673871 ER PT J AU Amirimani, B Ning, B Deitz, AC Weber, BL Kadlubar, FF Rebbeck, TR AF Amirimani, B Ning, B Deitz, AC Weber, BL Kadlubar, FF Rebbeck, TR TI Increased transcriptional activity of the CYP3A4* 1B promoter variant SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE CYP3A4; promoter; human hepatocytes; expression; polymorphism ID GENETIC VARIANT; CLINICAL PRESENTATION; HUMAN HEPATOCYTES; PROSTATE TUMORS; CYTOCHROME-P-450 ENZYMES; PRIMARY CULTURES; DRUG-METABOLISM; CYP3A4; LIVER; POLYMORPHISM AB Numerous single nucleotide polymorphisms (SNPs) have been identified in the human genome, yet the functional significance of most is unknown. CYP3A4 is a key enzyme in the metabolism of numerous compounds. An A-->G substitution 290 by upstream of the CYP3A4 transcription start site (CYP3A4* 1B) has been associated with cancer phenotypes, but its phenotypic effects are unclear. To investigate the functional significance of CYP3A4* 1B, we generated two luciferase reporter constructs: 1-kb (denoted L, long) and 0.5-kb (denoted S, short) promoter fragments containing either the variant (V-L,V-S) or the wild-type (W-L, W-S) sequences. We evaluated the effect of the variant sequence in the HepG2 and MCF-7 cell lines, and in primary human hepatocytes from three donors. Reporter constructs with the variant sequence had 1.2- to 1.9-fold higher luciferase activity than constructs with wild-type sequence in the cell lines (P < 0.0001) and hepatocytes (P = 0.021, P = 0.027, P = 0.061). The ratio of transcriptional activity for V-S:W-S was similar to the V-L:W-L ratio in HepG2 cells, but the V-S:W-S ratio was consistently less than the V-L:W-L ratio in MCF-7 cells. This suggests that CYP3A4 expression is higher from the variant promoter and that a repressor sequence may exist in the longer constructs. Electrophoretic mobility shift assays demonstrated specific binding of a component of HepG2 nuclear extract to both wild-type and variant promoters with consistently higher binding affinities to the wild-type sequence. This suggests the existence of a transcriptional repressor responsible for the lower CYP3A4* 1 A activity. Therefore, the phenotypic effects of the variant CYP3A4* 1 B may be associated with enhanced CYP3A4 expression due to reduced binding of a transcriptional repressor. (C) 2003 Wiley-Liss, Inc. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Canc, Philadelphia, PA 19104 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, 904 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM trebbeck@cceb.med.upenn.edu NR 27 TC 105 Z9 113 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2003 VL 42 IS 4 BP 299 EP 305 DI 10.1002/em.10199 PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 760ZA UT WOS:000187864100009 PM 14673875 ER PT J AU Slattery, SD Valentine, CR AF Slattery, SD Valentine, CR TI Development of a microplate assay for the detection of single plaque-forming units of bacteriophage Phi X174 in crude lysates SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE gene A forward mutational assay; Phi X174; single burst analysis ID TRANSGENIC MICE; IN-VIVO; MUTATIONS AB Mice containing the PhiX174 am3 transgene can be used for measuring in vivo mutation; however, the single burst analysis method used for distinguishing in vivo mutations from mutations generated during sample processing is labor-intensive. A liquid microplate assay was developed that detects a single mutant plaque-forming unit (PFU) of PhiX174 bacterial virus in the presence of excess nonmutant virus. The assay is based on inhibiting reduction of the tetrazolium dye, MTS, by bacterial cells selective for mutant virus. The assay is performed with crude lysates of infected bacteria and is as accurate as scoring viral plaques on a bacterial lawn. This microplate assay may have application in increasing throughput of the single burst analysis of PhiX174 in transgenic mouse mutation assays. Published 2003 Wiley-Liss, Inc.(dagger). C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Valentine, CR (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. NR 9 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2003 VL 41 IS 2 BP 121 EP 125 DI 10.1002/em.10140 PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 653HJ UT WOS:000181428900006 PM 12605381 ER PT S AU Jain, PK AF Jain, PK BE Verma, M Dunn, BK Umar, A TI Epigenetics: The role of methylation in the mechanism of action of tumor suppressor genes SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE epigenetics; hypermethylation; tumor suppressor genes; histone deacetylase (HDAC); histone methylase (HMT) ID HUMAN BREAST-CANCER; MAMMALIAN DNA METHYLTRANSFERASE; HISTONE DEACETYLASE INHIBITION; EMBRYONIC STEM-CELLS; CPG-BINDING-PROTEIN; PROMOTER HYPERMETHYLATION; DE-NOVO; TRANSCRIPTIONAL REPRESSOR; NASOPHARYNGEAL CARCINOMA; GASTRIC-CANCER AB Epigenetics is the study of mitotically heritable changes in gene expression without any changes in the primary DNA sequence. The major step in epigenetic gene regulation is gene inactivation by hypermethylation of CpG islands located in the promoter region. Specific enzymes and methylated DNA binding proteins play a major role in causing reduced expression of tumor suppressor genes, resulting in tumor formation and its progression. Prevention approaches are needed to avoid tumor formation. One approach to inhibiting inactivation of tumor suppressor genes is to use chemical agents such as 5-azacytidine to prevent hypermethylation of DNA. Increased understanding of the mechanism of epigenetic silencing and the identification of additional molecular mechanisms (e.g., histone methylases) that may be targeted by pharmaceutical interventions may lead to more preventive strategies. The current status of the epigenetic regulation of tumor suppressor genes is discussed in this review article. C1 US FDA, DETTD, OBRR, CBER, Rockville, MD 20852 USA. RP Jain, PK (reprint author), US FDA, DETTD, OBRR, CBER, 1401 Rockville Pike,HFM 310, Rockville, MD 20852 USA. NR 80 TC 31 Z9 33 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 71 EP 83 PG 13 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800007 PM 12724213 ER PT S AU Verma, M Dunn, BK Ross, S Jain, P Wang, W Hayes, R Umar, A AF Verma, M Dunn, BK Ross, S Jain, P Wang, W Hayes, R Umar, A BE Verma, M Dunn, BK Umar, A TI Early detection and risk assessment - Proceedings and recommendations from the workshop on epigenetics in cancer prevention SO EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Epigenetic in Cancer Prevention CY DEC 03-04, 2001 CL BETHESDA, MARYLAND SP Natl Canc Inst, Div Canc Prevent, Nalt Inst Hlth DE acetylatlon; biomarker; cancer detection; epigenetics; methylation; microarray; prevention; risk assessment ID CPG-ISLAND HYPERMETHYLATION; DNA METHYLATION; PROMOTER HYPERMETHYLATION; HISTONE-DEACETYLASE; LUNG-CANCER; PROSTATE ADENOCARCINOMA; NICKEL CARCINOGENESIS; MOLECULAR-BIOLOGY; COLORECTAL-CANCER; GENE-EXPRESSION AB Recent advances in molecular biology that have provided a greater understanding of multistage carcinogenesis include the use of biomarkers of early detection and risk assessment. Prominent among such biomarkers are epigenetic changes. The field of epigenetics has seen a recent surge of interest among cancer researchers since alterations in DNA methylation have emerged as one of the most consistent molecular alterations in multiple neoplasms. Chromatin condensation, histone deacetylation, and promoter methylation are major steps in the epigenetic regulation of gene expression. Epigenetic changes may occur due to environmental factors, aging, and genomic imprinting. An important distinction between genetic and epigenetic alterations in cancer prevention is that the latter might be more easily reversed using therapeutic interventions. In the workshop the following areas of research were recognized for emphasis in future work: (1) basic epigenetic mechanisms in cancer need further investigation; (2) technology development in the area of epigenetics, such as high-throughput quantitative assays and increased sensitivity/specificity, is essential for the early detection and risk assessment of cancer; (3) the clinical application of epigenetic changes to cancer prevention and risk assessment needs further investigation. Further research will lead to the identification of new targets for cancer prevention. C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Rockville, MD 20852 USA. US FDA, Rockville, MD 20857 USA. NCI, Div Epidemiol, NIH, Rockville, MD 20852 USA. RP Verma, M (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Execut Plaza N,Room 3144,6130 Execut Blvd, Rockville, MD 20852 USA. NR 82 TC 23 Z9 26 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-430-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 983 BP 298 EP 319 PG 22 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BW49W UT WOS:000182218800028 PM 12724234 ER PT J AU Katz, R AF Katz, R TI Issues in clinical trial design from the FDA perspective SO EPILEPSIA LA English DT Article ID ALZHEIMERS-DISEASE; ATROPHY C1 US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Off Drug Evaluat 1, Rockville, MD 20852 USA. RP Katz, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Off Drug Evaluat 1, HFD-120,WOC,Rm 4049,1451 Rockville Pike, Rockville, MD 20852 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2003 VL 44 SU 7 BP 9 EP 15 DI 10.1046/j.1528-1157.44.s7.7.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 722JQ UT WOS:000185372300003 PM 12919333 ER PT J AU Yoneda, O Imai, T Nishimura, M Miyaji, M Mimori, T Okazaki, T Domae, N Fujimoto, H Minami, Y Kono, T Bloom, ET Umehara, H AF Yoneda, O Imai, T Nishimura, M Miyaji, M Mimori, T Okazaki, T Domae, N Fujimoto, H Minami, Y Kono, T Bloom, ET Umehara, H TI Membrane-bound form of fractalkine induces IFN-gamma production by NK cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE fractalkine; NK cell; IFN-gamma; chemokine; cytokine ID NATURAL-KILLER-CELLS; ENDOTHELIAL-CELLS; CHEMOKINE RECEPTORS; IMMUNE-RESPONSE; ADHESION; ACTIVATION; CX(3)CR1; TH1; CX3C-CHEMOKINE; MOBILIZATION AB Natural killer (NK) cells participate in both innate and adaptive immunity, in part by their prompt secretion of cytokines including IFN-gamma, a pro-inflammatory cytokine with an important role in Th1 polarization. To assess the involvement of fractalkine in inflammatory processes, we examined the effect of fractalkine on IFN-gamma production by NK cells. Although soluble chemokines, including MCP-1 and RANTES as well as fractalkine, had a negligible effect on IFN-gamma production, immobilized fractalkine markedly induced IFN-gamma production by NK cells in a dose-dependent manner. Pretreatment of NK cells with the phosphatidylinositol 3-kinase (PI 3-K) inhibitor, wortmannin, completely inhibited the production of IFN-gamma induced by fractalkine, and pretreatment with the protein tyrosine kinase inhibitor, herbimycin A, partially suppressed the response, suggesting that augmentation of IFN-gamma production in response to fractalkine treatment of NK cells involves signaling through PI 3-K and protein tyrosine kinases. Furthermore, co-culture of NK cells with fractalkine-transfected 293E cells markedly enhanced IFN-gamma production by NK cells compared with co-culture with control 293E cells. These findings may indicate a paracrine feedback loop system in which endothelial cells may be activated to produce more fractalkine, and also suggest a role for fractalkine expressed on endothelial cells in Th1 polarization through the stimulation of IFN-gamma production by NK cells. C1 Kyoto Univ, Dept Rheumatol & Clin Immunol, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan. US FDA, Div Cellular & Gene Therapies HFM518, Ctr Biol Evaluat Res, Bethesda, MD 20014 USA. Nippon Boehringer Ingelheim, Kawanishi Pharma Inst, Dept Mol Cell Biol, Kawanishi, Japan. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto, Japan. Kan Res Inst, Kyoto, Japan. Kobe Univ, Sch Med, Dept Biomed Regulat, Kobe, Hyogo 650, Japan. Osaka Dent Univ, Dept Internal Med, Osaka, Japan. RP Umehara, H (reprint author), Kyoto Univ, Dept Rheumatol & Clin Immunol, Grad Sch Med, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan. NR 41 TC 39 Z9 45 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2003 VL 33 IS 1 BP 53 EP 58 DI 10.1002/immu.200390007 PG 6 WC Immunology SC Immunology GA 639HU UT WOS:000180623100007 PM 12594832 ER PT J AU Risitano, AM Holada, K Chen, GB Simak, J Vostal, JG Young, NS Maciejewski, JP AF Risitano, AM Holada, K Chen, GB Simak, J Vostal, JG Young, NS Maciejewski, JP TI CD34(+) cells from paroxysmal nocturnal hemoglobinuria (PNH) patients are deficient in surface expression of cellular prion protein (PrPc) SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID PERIPHERAL-BLOOD LEUKOCYTES; SOMATIC MUTATIONS; FLOW-CYTOMETRY; SCRAPIE; HEMATOPOIESIS; ACTIVATION; DISEASES; FAILURE; BIOLOGY; GENE AB Objective. Cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI)-anchored protein (GPI-AP) constitutively expressed by neurons but also in hematopoietic cells. In trasmissible spongiform encephalopathies, the protease-resistant form of prion (PrPsc) converts the host PrPc into the pathologic form. We have investigated PrPc expression in hematopoietic cells from paroxysmal nocturnal hemoglobinuria (PNH). In this disease, due to somatic mutations in PIG-A gene, biosynthesis of the (GPI)-anchor is impaired and affected cells lack membrane expression of all GPI-AP. Methods. Normal and PNH hematopoietic progenitors and paired wild-type (WT) and PIG-A mutant cell lines were used for analysis of intracellular and surface PrPc expression using flow cytometry and Western blot. Results. By flow cytometry, PrPc was constitutively present on normal CD34(+) cells, including more immature CD38(dim) cells, as well as hernatopoietic cell lines. Similar results were obtained in purified CD34(-). Phospholipase C treatment confirmed that PrPc, was expressed on the membrane via the GPI-anchor. In PNH patients, GPI-AP-deficient CD34(-) cells lacked PrPc membrane expression. PIG-A-mutated cell lines (Jurkat, K562, C-EBV, A(EBV)), in contrast to their normal counterparts, did not express surface PrPc. However, we detected intracellular PrPc at approximately equivalent levels in both normal and PIG-A-mutated cells using intracellular flow, cytometry and Western blotting. Conclusion. Cells and cell lines with PNH phenotype together with their normal counterparts may be a suitable system to explore the function of membrane PrPc in the hernatopoietic system. Conversely, PrPc is a good model to elucidate the fate of GPI-AP in PIG-A-deficient cells. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Maciejewski, JP (reprint author), Taussig Canc Ctr, Expt Hematol & Hematopoiesis Sect, R40,9500 Euclid Ave, Cleveland, OH 44195 USA. RI Simak, Jan/C-1153-2011 NR 30 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JAN PY 2003 VL 31 IS 1 BP 65 EP 72 AR PII S0301-472(02)01011-1 DI 10.1016/S0301-472X(02)01011-1 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 639CT UT WOS:000180610600007 PM 12543108 ER PT J AU Markoff, L AF Markoff, L TI 5 '- and 3 '-noncoding regions in flavivirus RNA SO FLAVIVIRUSES: STRUCTURE, REPLICATION AND EVOLUTION SE ADVANCES IN VIRUS RESEARCH LA English DT Review ID YELLOW-FEVER VIRUS; HEPATITIS-C VIRUS; WEST-NILE-VIRUS; JAPANESE ENCEPHALITIS-VIRUS; 3' NONCODING REGION; SECONDARY STRUCTURE-ANALYSIS; CELLULAR-PROTEINS BIND; REPLICATIVE-FORM RNA; STEM-LOOP STRUCTURE; TICK-BORNE C1 US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Bethesda, MD 20892 USA. RP Markoff, L (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Bethesda, MD 20892 USA. NR 102 TC 108 Z9 113 U1 5 U2 14 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 J9 ADV VIRUS RES JI Adv.Virus Res. PY 2003 VL 59 BP 177 EP 228 DI 10.1016/S0065-3527(03)59006-6 PG 52 WC Virology SC Virology GA BY24F UT WOS:000188415900006 PM 14696330 ER PT J AU Levitt, JA AF Levitt, JA TI CFSAN's program priorities: From food safety to food security SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, College Pk, MD USA. RP Levitt, JA (reprint author), US FDA, College Pk, MD USA. NR 10 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 2003 VL 58 IS 1 BP 19 EP 24 PG 6 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 674QN UT WOS:000182647600003 PM 12739581 ER PT J AU Blumberg, EM AF Blumberg, EM TI Universal Management, Abbott, Wyeth, Schering-Plough, and ... : Restitution and disgorgement find another home at the food and drug administration SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Blumberg, EM (reprint author), US FDA, Rockville, MD 20857 USA. NR 10 TC 5 Z9 5 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 2003 VL 58 IS 2 BP 169 EP 190 PG 22 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 703NB UT WOS:000184285000003 PM 12866551 ER PT J AU McClellan, MB AF McClellan, MB TI Remarks of the commissioner of food and drugs SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT 46th Annual Educational Conference CY APR 01-02, 2003 CL WASHINGTON, D.C. C1 US FDA, Rockville, MD 20857 USA. RP McClellan, MB (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 4 Z9 4 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 2003 VL 58 IS 2 BP 191 EP 204 PG 14 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 703NB UT WOS:000184285000004 PM 12866552 ER PT J AU Gilman, DJ AF Gilman, DJ TI Protecting protected speech: First Amendment taxonomy and the Food and Drug Administration's regulation of "enduring materials" SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 Hogan & Hartson LLP, FDA Practice Grp, Washington, DC 20004 USA. Georgetown Univ, Ctr Law, Washington, DC 20057 USA. RP Gilman, DJ (reprint author), Hogan & Hartson LLP, FDA Practice Grp, Washington, DC 20004 USA. NR 6 TC 2 Z9 2 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 2003 VL 58 IS 3 BP 463 EP 471 PG 9 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 739GP UT WOS:000186337000009 PM 14626986 ER PT J AU Dercova, K Tandlich, R Brezna, B AF Dercova, K Tandlich, R Brezna, B TI Application of terpenes as possible inducers of biodegradation of PCBs SO FRESENIUS ENVIRONMENTAL BULLETIN LA English DT Article; Proceedings Paper CT 2nd PCB Workshop on Recent Advances in the Environmental Toxicology and Health Effects of PCBs CY MAY 07-11, 2002 CL BRNO, CZECH REPUBLIC DE polychlorinated biphenyls; PCBs; terpenes; carvone; Pseudomonas; bioremediation ID POLYCHLORINATED-BIPHENYLS; DEGRADING BACTERIA; CONTAMINATED SOIL; DEGRADATION; STRAIN AB The study evaluates the effect of two terpenes, carvone and limonene, as potential inducers of the PCB-degrading pathway of a commercial mixture of PCBs, DELOR 103. The purpose was to find out whether addition of terpenes stimulates biodegradation and how this effect depends on terpene concentrations. The addition of the studied terperies, which could not serve as a sole carbon source, exerted an enhancing effect on PCB degradation when xylose was used as the carbon source and carvone as the possible inducer. In this case, already 7-37% of the individual PCB congeners were degraded without carvone addition. while 30-70% of the congeners were degraded after carvone addition. Good water solubility of carvone, its low costs and effectiveness make it a potential inducer for practical cleanup of DELOR-contaminated soil. C1 Slovak Univ Technol Bratislava, Fac Chem & Food Technol, Dept Biochem Technol, Bratislava 81237, Slovakia. N Dakota State Univ, Coll Pharm, Dept Pharmaceut Sci, Fargo, ND 58105 USA. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Dercova, K (reprint author), Slovak Univ Technol Bratislava, Fac Chem & Food Technol, Dept Biochem Technol, Radlinskeho 9, Bratislava 81237, Slovakia. EM dercova@chtf.stuba.sk NR 13 TC 5 Z9 5 U1 0 U2 2 PU PARLAR SCIENTIFIC PUBLICATIONS (P S P) PI FREISING PA ANGERSTR. 12, 85354 FREISING, GERMANY SN 1018-4619 J9 FRESEN ENVIRON BULL JI Fresenius Environ. Bull. PY 2003 VL 12 IS 3 SI SI BP 286 EP 290 PG 5 WC Environmental Sciences SC Environmental Sciences & Ecology GA 680WM UT WOS:000183002500004 ER PT J AU Liotta, LA Petricoin, EF Ardekani, AM Hitt, BA Levine, PJ Fusaro, VA Steinberg, SM Mills, GB Simone, C Fishman, DA Kohn, EC AF Liotta, LA Petricoin, EF Ardekani, AM Hitt, BA Levine, PJ Fusaro, VA Steinberg, SM Mills, GB Simone, C Fishman, DA Kohn, EC TI General keynote: Proteomic patterns in sera serve as biomarkers of ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN C1 US FDA, NCI, Clin Proteom Program, Rockville, MD 20857 USA. NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Northwestern Univ, Sch Med, Evanston, IL 60208 USA. RP Liotta, LA (reprint author), US FDA, NCI, Clin Proteom Program, Rockville, MD 20857 USA. NR 7 TC 20 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S25 EP S28 DI 10.1006/gyno.2002.6679 PN 2 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000008 PM 12586081 ER PT J AU Kirman, JR Turon, T Su, H Li, A Kraus, C Polo, JM Belisle, J Morris, S Seder, RA AF Kirman, JR Turon, T Su, H Li, A Kraus, C Polo, JM Belisle, J Morris, S Seder, RA TI Enhanced immunogenicity to Mycobacterium tuberculosis by vaccination with an alphavirus plasmid replicon expressing antigen 85A SO INFECTION AND IMMUNITY LA English DT Article ID REPLICATING RNA VACCINE; DOUBLE-STRANDED-RNA; DENDRITIC CELLS; DNA VACCINES; PROTECTIVE EFFICACY; VIRUS; IMMUNIZATION; VECTORS; HEAT-SHOCK-PROTEIN-70; ACTIVATION AB The immunogenicity of a plasmid DNA vaccine incorporating Sindbis virus RNA replicase functions (pSINCP) and expressing antigen 85A (Ag85A) from Mycobacterium tuberculosis was compared with a conventional plasmid DNA vector encoding Ag85A. pSINCP-85A was highly immunogenic in mice and gave enhanced long-term protection against M. tuberculosis compared with the conventional vector. C1 Vaccine Res Ctr, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Natl Allergy & Infect Dis, Immunogenet Lab, NIH, Bethesda, MD USA. Food & Drug Adm, Bethesda, MD USA. Chiron Corp, Vaccines Res, Emeryville, CA USA. Colorado State Univ, Dept Microbiol, Ft Collins, CO USA. RP Seder, RA (reprint author), Vaccine Res Ctr, Cellular Immunol Sect, NIH, 40 Convent Dr,Rm 40-3512, Bethesda, MD 20892 USA. RI Belisle, John/B-8944-2017 OI Belisle, John/0000-0002-2539-2798 NR 19 TC 48 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2003 VL 71 IS 1 BP 575 EP 579 DI 10.1128/IAI.71.1.575-579.2003 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 632EZ UT WOS:000180212000073 PM 12496215 ER PT J AU Raybourne, RB Williams, KM Vogt, R Reissman, DB Winterton, BS Rubin, C AF Raybourne, RB Williams, KM Vogt, R Reissman, DB Winterton, BS Rubin, C TI Development and use of an ELISA test to detect IgE antibody to Cry9c following possible exposure to bioengineered corn SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE IgE; Cry9C; allergy; corn ID FOODS; DIGESTION; PROTEIN; PLANTS AB Background: Starlink(TM), a variety of corn genetically engineered to contain the insecticidal protein Cry9c, had not been approved for human consumption because it possessed some characteristics associated with allergenic proteins. However, in the fall of 2000 cry9c DNA was detected in several corn-containing products, suggesting that Starlink corn had entered the human food supply. Subsequently, consumers, following consumption of corn products, reported a number of adverse health events, possibly consistent with allergic reaction. Methods: To investigate the possibility of allergic reactions due to Cry9c in these consumers an ELISA test was developed for the purpose of detecting IgE antibodies to Cry9c and blood samples were taken from a total of 18 people who self-reported allergic reactions. Sera collected prior to the 1996 development of Starlink were used as negative controls. Results: None of the adverse event sera were found to be reactive with recombinant Cry9c antigen, based on comparison with normal controls. Although a known human positive control serum containing IgE specific for Cry9c was not available, other controls were incorporated into the ELISA protocol, including the use of sera from subjects allergic to other allergens and their homologous antigens ( cat, grass, peanut) to validate the IgE detection reagents. Conclusions: While the results do not support the likely occurrence of allergic reactions to Cry9c, such reactions cannot be ruled out, nor can the possibility that sera might react with unique glycosylated epitopes of Cry9c that may be expressed in the corn plant/seed. Copyright (C) 2003 S. Karger AG, Basel. C1 US FDA, Immunobiol Branch, Laurel, MD 20708 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Raybourne, RB (reprint author), US FDA, Immunobiol Branch, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 14 TC 8 Z9 11 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2003 VL 132 IS 4 BP 322 EP 328 DI 10.1159/000074899 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 760CW UT WOS:000187794600004 PM 14707463 ER PT J AU Kawakami, M Kawakami, K Puri, RK AF Kawakami, M Kawakami, K Puri, RK TI Tumor regression mechanisms by IL-13 receptor-targeted cancer therapy involve apoptotic pathways SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE IL-13 receptor; head-and-neck squamous cell carcinoma; cytotoxin; apoptosis; athymic nu/nu mice ID CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; INTERLEUKIN-13 RECEPTOR; CYTOCHROME-C; NECK-CANCER; HUMAN HEAD; PROTEIN; MITOCHONDRIA; RELEASE; GROWTH AB IL-13 cytotoxin, composed of IL-13 and a truncated form of Pseudomonas exotoxin, targets IL-13R-overexpressing tumor cell lines in vitro and in vivo. To reveal the molecular mechanism of IL-13 cytotoxin-induced cell death in vivo, we demonstrate activation of apoptotic pathways in 2 s.c. growing human SCCHN tumor models in immunodeficient mice after i.t. administration of IL-13 cytotoxin. Treatment of HN 12 tumor bearing mice with Lp. or i.t. administration of IL-13 cytotoxin mediated marked regression of established tumors with complete remission. Interestingly, after a single i.t. administration, IL-13 cytotoxin disappeared within 6 hr but accumulation of caspase-3, -8 and -9 and cleavage of procaspase-3 and PARP continued within the tumors for a prolonged period. We further demonstrate that IL-13 cytotoxin also utilizes an alternate pathway of cell death via the release of cytochrome c from mitochondria to the cytosol. Our results indicate that IL-13 cytotoxin induces 2 major pathways of apoptosis, which may play a role in tumor regression. In addition, apoptotic molecules may serve as surrogate molecular markers of tumor response to IL-13R-directed cytotoxin therapy. (C) 2002 Wiley-Liss, Inc. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bldg 29B,Rm 2NN10,29 Lincoln Dr,MSC4555, Bethesda, MD 20892 USA. NR 31 TC 13 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2003 VL 103 IS 1 BP 45 EP 52 DI 10.1002/ijc.10778 PG 8 WC Oncology SC Oncology GA 623GZ UT WOS:000179696100007 PM 12455052 ER PT J AU Fang, GC Wu, YS Chang, CN Yang, IL Chang, SC Chu, CC Fu, PPC AF Fang, GC Wu, YS Chang, CN Yang, IL Chang, SC Chu, CC Fu, PPC TI Study of particulates and metallic elements at a farm sampling site in central Taiwan SO INTERNATIONAL JOURNAL OF ENVIRONMENT AND POLLUTION LA English DT Article DE dry deposition; metallic elements; Taiwan; TSP ID PARTICLE-SIZE DISTRIBUTIONS; SOUTHERN LAKE-MICHIGAN; DRY DEPOSITION FLUXES; UNITED-STATES; AIR-POLLUTION; TRACE-METALS; MASS; MATTER; AEROSOLS; AEOLOS AB The total suspended particle (TSP) concentration, dry deposition and wind speed were measured with a PS-I sampler, a dry deposition plate and a Weather Monitor II (#7440), respectively, at the Experimental Farm of Thunghai University in Taiwan. Taiching Industrial Park, Taichung Cong Road (traffic) and a hospital incinerator are close to the sampling site. The sampling time was from August 2001 to December 2001. The average dry deposition flux, the TSP concentration, dry deposition velocities, average wind speed and maximum wind speed were recorded as 617.7 +/- 281.4 mg/day/m(2), 117.5 +/- 17.6 mug/m(3), 5.9 +/- 2.2 cm/s, 2.7 +/- 1.3 m/s and 7.6 +/- 2.3 m/s, respectively, at this sampling site. Good correlation coefficients (R) of the TSP concentration and the dry deposition flux with wind speed were found, with values of 0.46 and 0.50, respectively. The concentrations and dry deposition of the total metallic elements were also obtained. The results indicated that the concentrations of anthropogenic elements (Pb, Mn, Cd, Ni, Cr and Zn) were mostly higher than those obtained in other studies around the world. The average dry deposition fluxes and TSP concentrations for Zn and Pb were 0.45 and 0.42, respectively. The same phenomenon was also observed for Fe and Mg (R = 0.59 and 0.65). The results indicate that these elements were all coming from the same emission sources at the farm sampling site. C1 Hungkuang, Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. Cien Yu Reg Teaching Hosp, Dept Internal Med, Kaohsiung 832, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, GC (reprint author), Hungkuang, Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. NR 26 TC 0 Z9 0 U1 0 U2 2 PU INDERSCIENCE ENTERPRISES LTD PI GENEVE 15 PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 896, CH-1215 GENEVE 15, SWITZERLAND SN 0957-4352 J9 INT J ENVIRON POLLUT JI Int. J. Environ. Pollut. PY 2003 VL 19 IS 3 BP 243 EP 258 DI 10.1504/IJEP.2003.003316 PG 16 WC Environmental Sciences SC Environmental Sciences & Ecology GA 691WC UT WOS:000183628100003 ER PT J AU Fang, GC Chu, CC Wu, YS Fu, PPC AF Fang, GC Chu, CC Wu, YS Fu, PPC TI Metallic elements in particulates released during incense-burning at Tzu Yun Yen temple, Taichung, Taiwan SO INTERNATIONAL JOURNAL OF ENVIRONMENT AND POLLUTION LA English DT Article DE dry deposition velocities; incense; metallic elements; particulate matter; temple ID DRY DEPOSITION; AMBIENT AIR; MATTER; PM2.5; PM10 AB Concentrations of ambient suspended particulates were measured at Tzu Yun Yen temple (120degrees, 34', 10" E; 24degrees, 16', 12" N), using a Universal sampler and dry deposition plates. The temple is a characteristic incense-burning and semi-open sampling site. PM2.5 concentrations for Period 1 (average 90 mug/m(3)) were higher than those for Period 2 (average 70 mug/m(3)). Results for average PM2.5-10 concentrations showed equal distributions in Period 1 and Period 2. Average ratios of PM2.5/PM10 were higher in Period 1 (74%) than Period 2 (71%). In addition, the suspended particulate (PM10) elements concentrations during Zhong Yuan Jie, and the first and 15th days of nong li for each month (Chinese lunar calendar) were all higher than duringnon-Zhong Yuan he and non-first and non-15th days. Furthermore, the dry deposition velocities of manganese in fine particulates (PM2.5) and suspended particulates (PM10) were 1.43 and 0.75cm/s, respectively, and the dry deposition velocities of cadmium in fine particulates (PM2.5) and suspended particulates (PM10) were 1.86 and 0.99cm/s, respectively. C1 Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Chien Yu Reg Teaching Hosp, Intens Care Unit, Dept Internal Med, Kaohsiung 832, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, GC (reprint author), Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. NR 12 TC 1 Z9 1 U1 0 U2 4 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 896, CH-1215 GENEVA, SWITZERLAND SN 0957-4352 J9 INT J ENVIRON POLLUT JI Int. J. Environ. Pollut. PY 2003 VL 19 IS 6 BP 567 EP 575 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 740MP UT WOS:000186406400003 ER PT J AU Oliva, A Mani, R Katz, R AF Oliva, A Mani, R Katz, R TI Regulatory aspects of vascular dementia in the United States SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article; Proceedings Paper CT Conference on Vascular Burden of the Brain: New therapeutic Directions CY NOV, 2001 CL MADRID, SPAIN DE vascular dementia; drug development; treatment; US regulatory; food and drug administration; FDA AB There is significant interest in the development of new drugs to treat vascular dementia. However, before US approval of new drugs for this entity is possible, certain issues with regulatory implications need to be addressed. Is vascular dementia a distinct clinical syndrome with valid diagnostic criteria? Can this entity be distinguished from Alzheimer's disease (AD) and other causes of dementia? What design features are important for clinical trials in this disorder? The US Food and Drug Administration (FDA) convened a special meeting of the Peripheral and Central Nervous System Advisory Committee in an attempt to answer these questions. The conclusions from this meeting indicate that vascular dementia (VaD) is a pathologically heterogeneous disorder but appears to be reasonably distinguishable from AD dementia. The NINDS-AIREN diagnostic criteria are suitable as entry criteria for vascular dementia trials. trials should be similar in duration to AD dementia trials and should employ a dual outcome strategy (cognitive + global/functional measures). For drugs that are believed to have a disease-modifying effect, clinical trials should study specific vascular dementia subtypes and would need to employ substantially different designs from those used currently. The term "vascular dementia" may not be entirely appropriate to describe this population. C1 US FDA, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Oliva, A (reprint author), US FDA, Div Neuropharmacol Drug Prod, 5600 Fishers Lane,JFD-120, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2003 VL 15 SU 1 BP 293 EP 295 DI 10.1017/S1041610203009360 PG 3 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 727RJ UT WOS:000185672000048 PM 16191257 ER PT J AU McGhee, HW AF McGhee, HW CA Fed Inst Drugs Med Devices Bonn Ge TI Hepatic toxicity possibly associated with kava-containing products - United States, Germany, and Switzerland, 1999-2002 (Reprinted from MMWR, vol 51, pg 1065-1067, 2002) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Fed Inst Drugs & Med Devices, Bonn, Germany. Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Pittsburgh, PA USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. CDC, Div Environmental Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. RP McGhee, HW (reprint author), Fed Inst Drugs & Med Devices, Bonn, Germany. NR 10 TC 20 Z9 20 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 1 PY 2003 VL 289 IS 1 BP 36 EP 37 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 630XL UT WOS:000180136600009 ER PT J AU Wilson, J Margolin, AB AF Wilson, J Margolin, AB TI Efficacy of glutaraldehyde disinfectant against Cryptosporidium parvum in the presence of various organic soils SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ENDOSCOPES; OOCYSTS AB The opportunistic protozoan Cryptosporidium parvum is highly resistant to disinfectants, including those specifically used for processing reused medical equipment in hospitals. C. parvum oocysts were dried onto glass and steel grooved penicylinders and challenged with 2.5% glutaraldehyde solution in the presence of 3 types of soil with exposures at 10 min, 90 min, and 10 h. The influence of organic soils on disinfection was measured with 5% fetal bovine serum (FBS), 10% FBS, and 5 mg mucin/mL. An in vitro excystation procedure and cell culture infection assay were used to determine survivability of oocysts after the germicide challenge. In the presence of organic soil, all oocysts; removed from carriers excysted and infected cell monolayers after all germicide contact times. However, excystation was observed only from oocysts that received no protection from organic soil after 10 h exposure. In these samples, no infection was observed in the cell monolayers. The results of this research demonstrate the importance of thorough cleaning of medical equipment before disinfection. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. Univ New Hampshire, Dept Microbiol, Durham, NH 03824 USA. RP Wilson, J (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. NR 14 TC 6 Z9 6 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 JAN-FEB PY 2003 VL 86 IS 1 BP 96 EP 100 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 642DV UT WOS:000180789700014 PM 12607746 ER PT J AU Olsen, AR AF Olsen, AR TI Committee on additives, beverages, and food process related analytes - Filth and extraneous materials in foods and drugs SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID REGULATORY ACTION CRITERIA C1 US FDA, College Pk, MD 20740 USA. RP Olsen, AR (reprint author), US FDA, Room 2E-021,HFS-315,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 5 TC 0 Z9 0 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 JAN-FEB PY 2003 VL 86 IS 1 BP 128 EP 128 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 642DV UT WOS:000180789700019 PM 12607750 ER PT J AU Trucksess, MW AF Trucksess, MW TI Committee on natural toxins and food allergens - Mycotoxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID PERFORMANCE LIQUID-CHROMATOGRAPHY; IMMUNOAFFINITY COLUMN CLEANUP; OCHRATOXIN-A; AFLATOXIN M-1; FUMONISIN B-1; CYCLOPIAZONIC ACID; GAS-CHROMATOGRAPHY; APPLE JUICE; ERGOT ALKALOIDS; DAIRY-PRODUCTS C1 US FDA, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 113 TC 5 Z9 5 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 JAN-FEB PY 2003 VL 86 IS 1 BP 129 EP 138 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 642DV UT WOS:000180789700020 PM 12607751 ER PT J AU Andrews, WH AF Andrews, WH TI Committee on microbiology and extraneous materials - Food microbiology - Non-dairy SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, College Pk, MD 20740 USA. RP Andrews, WH (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 8 TC 0 Z9 1 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 JAN-FEB PY 2003 VL 86 IS 1 BP 154 EP 159 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 642DV UT WOS:000180789700026 PM 12607757 ER PT J AU Davis, KC Nakatsu, CH Turco, R Weagant, SD Bhunia, AK AF Davis, KC Nakatsu, CH Turco, R Weagant, SD Bhunia, AK TI Analysis of environmental Escherichia coli isolates for virulence genes using the TaqMan((R)) PCR system SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE environmental isolates; Escherichia coli O157 : H7; food isolates; multiplex PCR; ribotyping; TaqMan (R) ID HEMOLYTIC-UREMIC SYNDROME; SHIGA TOXIN; FLUOROGENIC PROBE; MULTIPLEX PCR; O157-H7; STRAINS; PREVALENCE; ASSAY; WATER; IDENTIFICATION AB Aims: To assess the presence of virulence genes in environmental and foodborne Escherichia coli isolates using the TaqMan((R)) PCR system. Methods and Results: Three TaqMan pathogen detection kits called O157:H7, StxI and StxII were used to investigate the presence of virulence genes in Escherichia coli isolates. All 54 foodborne E. coli O157:H7 isolates showed expected results using these kits. Ninety (15%) of 604 environmental isolates gave positive amplification with an O157:H7-specific kit. TaqMan PCR amplification products from these 90 isolates were analysed by agarose gel electrophoresis, and 90% (81 of 90) of the environmental samples contained the expected PCR product. Sixty-six of these 90 were chosen for serotyping tests and only 35% (23 of 66) showed agglutination with both anti-O157 and anti-H7 antibodies. Further ribotyping of 16 sero-positive isolates in an automated Riboprinter((R)) did not identify these to be O157:H7. Multiplex PCR with primers for eaeA , stxI and stxII genes was used to confirm the TaqMan results in 10 selected environmental isolates. Conclusions: All three TaqMan pathogen detection kits were useful for virulence gene analysis of prescreened foodborne O157:H7 isolates, while the O157:H7-specific kit may not be suitable for virulence gene analysis of environmental E. coli isolates, because of high false positive identification. Significance and Impact of the Study: The ability to rapidly identify the presence of pathogenic E. coli in food or environmental samples is essential to avert outbreaks. These results are of importance to microbiologists seeking to use TaqMan PCR to rapidly identify pathogenic E. coli in environmental samples. Furthermore, serotyping may not be a reliable method for identification of O157:H7 strains. C1 Purdue Univ, Dept Food Sci, Mol Food Microbiol Lab, W Lafayette, IN 47907 USA. Purdue Univ, Dept Agron, W Lafayette, IN 47907 USA. US FDA, Pacific Reg Lab NW, Bothell, WA USA. RP Bhunia, AK (reprint author), Purdue Univ, Dept Food Sci, Mol Food Microbiol Lab, 745 Agr Mall Dr, W Lafayette, IN 47907 USA. RI Turco, Ronald/B-8739-2008; Bhunia, Arun/K-7639-2012; OI Turco, Ronald/0000-0002-1794-1486; Bhunia, Arun/0000-0003-3640-1554 NR 26 TC 17 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PY 2003 VL 95 IS 3 BP 612 EP 620 DI 10.1046/j.1365-2672.2003.02023.x PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 711CG UT WOS:000184720600023 PM 12911710 ER PT J AU Dargatz, DA Fedorka-Cray, PJ Ladely, SR Kopral, CA Ferris, KE Headrick, ML AF Dargatz, DA Fedorka-Cray, PJ Ladely, SR Kopral, CA Ferris, KE Headrick, ML TI Prevalence and antimicrobial susceptibility of Salmonella spp. isolates from US cattle in feedlots in 1999 and 2000 SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE antimicrobial resistance; cattle; feedlot; Salmonella ID AMPC BETA-LACTAMASE; UNITED-STATES; TYPHIMURIUM DT104; BEEF CARCASSES; INFECTION; SEROTYPES; ANIMALS; PLANTS; COWS AB Aims: Faecal samples from cattle in US feedlots were evaluated for the presence of Salmonella. When Salmonella isolates were recovered the antimicrobial resistance patterns were determined. Methods and Results: Faecal samples were collected from pen floors in 73 feedlots in 12 states during the period from October 1999 to September 2000. Pens of cattle selected for sampling were those that had been in the feedlot for the shortest period of time, the longest period of time and a randomly selected pen from the remaining pens. Faecal samples were cultured for Salmonella spp. and all Salmonella isolates were categorized by serotype. The susceptibilities of all isolates were determined using a panel of 17 antimicrobials. Overall, 6.3% ( 654/10 417) of the samples cultured positive for Salmonella spp. and 22.2% (94/422) of pens and 50.7% (37/73) of feedlots had one or more positive samples. There was little difference in the proportion of positive samples from short-fed ( 6.1%, 212/ 3482), random ( 6.4%, 217/3400) and long-fed ( 6.4%, 224/3485) pens of cattle. One of two pens of cattle that could not be attributed to a pen type had a single positive sample (2.0%, 1/50). Samples collected during the period of April to June ( 6.8%, 209/3054) and July to September ( 11.4%, 286/2500) were more likely to be positive than those collected during October to December (4.0%, 73/1838) and January to March (2.8%, 86/3025). The most common serotypes of Salmonella were dissimilar from those that are typically seen in human illness and cattle illness. The majority of isolates (62.8%, 441/702) were sensitive to all of the antimicrobials tested. Resistance was most frequently observed to tetracycline ( 35.9%, 252/702) followed by streptomycin ( 11.1%, 78/702), ampicillin (10.4%, 73/702) and chloramphenicol ( 10.4%, 73/702). Multiple resistance ( resistance to greater than or equal to 2 antimicrobials) was observed for 11.7% (82/702) of the isolates. Conclusions: Salmonella was isolated at low frequency from faeces of feedlot cattle and the serotypes were not those commonly associated with human illness. In addition most of the Salmonella isolates were sensitive to all the antimicrobials tested. Significance and Impact of the Study: This study contributes to understanding the ecology of Salmonella in cattle feedlots and the prevalence of resistance among potential food-borne pathogens. C1 APHIS, Ctr Epidemiol & Anim Hlth, USDA, Ft Collins, CO USA. ARS, Antimicrobial Resistance Res Unit, USDA, Athens, GA USA. APHIS, Natl Vet Serv Labs, USDA, Ames, IA USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Dargatz, DA (reprint author), 2150 Ctr Ave,Bldg B,Mail Stop 2E7, Ft Collins, CO 80526 USA. NR 27 TC 47 Z9 50 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PY 2003 VL 95 IS 4 BP 753 EP 761 DI 10.1046/j.1365-2672.2003.02034.x PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 719VU UT WOS:000185226400014 PM 12969289 ER PT J AU Volokhov, D Chizhikov, V Chumakov, K Rasooly, A AF Volokhov, D Chizhikov, V Chumakov, K Rasooly, A TI Microarray analysis of erythromycin resistance determinants SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE antibiotics; erythromycin; microarray; oligonucleotides; S. aureus ID NUCLEOTIDE-SEQUENCE; OLIGONUCLEOTIDE MICROCHIPS; ANTIBIOTIC-RESISTANCE; ANTIMICROBIAL RESISTANCE; ENTEROCOCCUS-FAECALIS; ALEXANDER PROJECT; ESCHERICHIA-COLI; MULTIPLEX-PCR; HUMAN-ORIGIN; MACROLIDE AB Aims: To develop a DNA microarray for analysis of genes encoding resistance determinants to erythromycin and the related macrolide, lincosamide and streptogramin B (MLS) compounds. Methods and Results: We developed an oligonucleotide microarray containing seven oligonucleotide probes (oligoprobes) for each of the six genes ( ermA, ermB, ermC, ereA, ereB and msrA/B) that account for more than 98% of MLS resistance in Staphylococcus aureus clinical isolates. The microarray was used to test reference and clinical S. aureus and Streptococcus pyrogenes strains. Target genes from clinical strains were amplified and fluorescently labelled using multiplex PCR target amplification. The microarray assay correctly identified the MLS resistance genes in the reference strains and clinical isolates of S. aureus, and the results were confirmed by direct DNA sequence analysis. Of 18 S. aureus clinical strains tested, 11 isolates carry MLS determinants. One gene ( ermC) was found in all 11 clinical isolates tested, and two others, ermA and msrA/B, were found in five or more isolates. Indeed, eight (72%) of 11 clinical isolate strains contained two or three MLS resistance genes, in one of the three combinations ( ermA with ermC, ermC with msrA/B, ermA with ermC and msrA/B). Conclusions: Oligonucleotide microarray can detect and identify the six MLS resistance determinants analysed in this study. Significance and Impact of the Study: Our results suggest that microarray-based detection of microbial antibiotic resistance genes might be a useful tool for identifying antibiotic resistance determinants in a wide range of bacterial strains, given the high homology among microbial MLS resistance genes. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Rasooly, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-517,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 41 TC 42 Z9 47 U1 2 U2 8 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PY 2003 VL 95 IS 4 BP 787 EP 798 DI 10.1046/j.1365-2672.2003.02046.x PG 12 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 719VU UT WOS:000185226400018 PM 12969293 ER PT J AU Wagner, RD Paine, DD Cerniglia, CE AF Wagner, RD Paine, DD Cerniglia, CE TI Phenotypic and genotypic characterization of competitive exclusion products for use in poultry SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE anaerobic; competitive exclusion; food safety; genotypic; microbial identification; phenotypic; poultry; 16S rRNA ID 16S RIBOSOMAL-RNA; SALMONELLA; IDENTIFICATION; CULTURE; LACTOBACILLUS; COLONIZATION; SEQUENCES; CHICKS; GENES; ACID AB Aims: Phenotypic and genotypic bacteria identification methods were compared for their efficacy in determining the composition of competitive exclusion ( CE) products. Methods and Results: Phenotypic methods used for bacterial identification were fatty acid methyl ester profiles, biochemical assays and carbohydrate utilization profiles. Genotypic methods were MicroSeq16S rRNA sequence analysis and BLAST searches of the GenBank sequence database. Agreement between phenotypic and genotypic methods for identification of bacteria isolated from the Preempt CE product was 20%. A defined test mixture of bacteria was identified to the species level 100% by BLAST analysis, 64% by MicroSeq and 36% by phenotypic techniques. Conclusions: The wide range of facultative and obligate anaerobic bacteria present in a CE product are more accurately identified with 16S rRNA sequence analyses than with phenotypic identification techniques. Significance and Impact of the Study: These results will provide guidelines for manufacturers of CE products to submit more reliable product information for market approval by regulatory agencies. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Wagner, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, HFT-250,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 23 TC 14 Z9 14 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PY 2003 VL 94 IS 6 BP 1098 EP 1107 DI 10.1046/j.1365-2672.2003.01944.x PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 678FP UT WOS:000182855200020 PM 12752820 ER PT J AU Zhu, PX Tsang, RSW Tsai, CM AF Zhu, PX Tsang, RSW Tsai, CM TI Nonencapsulated Neisseria meningitidis strain produces amylopectin from sucrose: Altering the concept for differentiation between N-meningitidis and N. polysaccharea SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; MENINGOCOCCAL POLYSACCHARIDES; CHEMICAL PROPERTIES; PHASE VARIATION; GENE; AMYLOSUCRASE; LIPOOLIGOSACCHARIDE; IDENTIFICATION; EXPRESSION; SEQUENCE AB Neisseria meningitidis is the causative agent of meningococcal sepsis and meningitis. Neisseria polysaccharea is a nonpathogenic species. N. polysaccharea is able to use sucrose to produce amylopectin, a starch-like polysaccharide, which distinguishes it biochemically from the pathogenic species N. meningitidis. The data presented here indicate that this may be an insufficient criterion to distinguish between these two species. The nonencapsulated Neisseria strain 93246 expressed a phenotype of amylopectin production similar to that of N. polysaccharea. However, strain 93246 reacted with N. meningitidis serotype 4 and serosubtype P1.14 monoclonal antibodies and showed the N. meningitidis L1(8) lipo-oligosaccharide immunotype. Further analyses were performed on four genetic loci in strain 93246, and the results were compared with 7 N. meningitidis strains, 13 N. polysaccharea strains, and 2 N. gonorrhoeae strains. Three genetic loci, opcA, siaD, and lgt-1 in strain 93246, were the same as in N. meningitidis. Particularly, the siaD gene encoding polysialyltransferase responsible for biosynthesis of N. meningitidis group B capsule was detected in strain 93246. This siaD gene was inactivated by a frameshift mutation at the poly(C) tract, which makes strain 93246 identical to other nonencapsulated N. meningitidis strains. As expected, the ants gene encoding amylosucrase, responsible for production of amylopectin from sucrose, was detected in strain 93246 and all 13 N. polysaccharea strains but not in N. meningitidis and N. gonorrhoeae strains. These data suggest that strain 93246 is nonencapsulated N. meningitidis but has the ability to produce extracellular amylopectin from sucrose. The gene for amylopectin production in strain 93246 was likely imported from N. polysaccharea by horizontal genetic exchange. Therefore, we conclude that genetic analysis is required to complement the traditional phenotypic classification for the nonencapsulated Neisseria strains. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Zhu, PX (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. FU FDA HHS [369VFFD018551] NR 37 TC 7 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2003 VL 41 IS 1 BP 273 EP 278 DI 10.1128/JCM.41.1.273-278.2003 PG 6 WC Microbiology SC Microbiology GA 635NY UT WOS:000180406700043 PM 12517860 ER PT J AU Nilsson, WB Paranjype, RN DePaola, A Strom, MS AF Nilsson, WB Paranjype, RN DePaola, A Strom, MS TI Sequence polymorphism of the 16S rRNA gene of Vibrio vulnificus is a possible indicator of strain virulence SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; RIBOSOMAL-SUBUNIT RNA; DNA ANALYSIS; AP-PCR; INFECTION; EPIDEMIOLOGY; OYSTERS; PROBES AB Vibrio vulnificus exhibits considerable strain-to-strain variation in virulence. Attempts to associate phenotypic or genotypic characteristics with strain virulence have been largely unsuccessful. Based on a 17-nucleotide difference throughout the sequence of the small subunit 16S rRNA gene, there are two major groups of V. vulnificus designated types A and B. In a survey of the 16S rRNA genotype in 67 V. vulnificus human clinical and nonclinical strains, we determined that the majority of nonclinical isolates are type A (31 of 33) and that there is a statistically significant association between the type B genotype and human clinical strains (26 of 34). C1 NOAA, Natl Marine Fisheries Serv, NW Fisheries Sci Ctr, US Dept Commerce, Seattle, WA 98112 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Strom, MS (reprint author), 2725 Montlake Blvd E, Natori, Miyagi 98112, Japan. NR 29 TC 114 Z9 119 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2003 VL 41 IS 1 BP 442 EP 446 DI 10.1128/JCM.41.1.442-446.2003 PG 5 WC Microbiology SC Microbiology GA 635NY UT WOS:000180406700072 PM 12517889 ER PT J AU Fu, PP Cheng, SH Coop, L Xia, Q Culp, SJ Tolleson, WH Wamer, WG Howard, PC AF Fu, PP Cheng, SH Coop, L Xia, Q Culp, SJ Tolleson, WH Wamer, WG Howard, PC TI Photoreaction, phototoxicity, and photocarcinogenicity of retinoids SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE retinol; vitamin A; retinoid acid; retinyl palmitate; phototoxicity; photocarcinogenicity ID PIGMENT EPITHELIAL-CELLS; SKIN IN-VIVO; CULTURED HUMAN KERATINOCYTES; CIS-TRANS ISOMERIZATION; VITAMIN-A PALMITATE; ULTRAVIOLET-RADIATION; LIPID-PEROXIDATION; RETINYL PALMITATE; 1,N-2-PROPANODEOXYGUANOSINE ADDUCTS; RETRO-RETINOIDS AB Sunlight is a human carcinogen. Many retinoid-containing cosmetics are used to protect damages caused by sunlight irradiation. Since retinol is thermally unstable and retinyl palmitate (RP) is relatively more stable, RP is also widely used as an ingredient in cosmetic formulations. In general, little is known about the photodecomposition of retinoids and the toxicity of retinoids and their photodecomposition products on the skin's responses to sunlight. This review focuses on the update information on photoreactions, phototoxicity, and photocarcinogenicity of the natural retinoids including retinol, retinal, retinoid acid (RA), retinyl acetate, and RP. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Coll Med, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 152 TC 26 Z9 26 U1 4 U2 13 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2003 VL 21 IS 2 BP 165 EP 197 DI 10.1081/GNC-120026235 PG 33 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 748FE UT WOS:000186851200003 PM 15845224 ER PT J AU Grant, MA AF Grant, MA TI Evaluation of methods to improve detection of Escherichia coli O157 : H7 in fresh produce by multiplex polymerase chain reaction SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LISTERIA-MONOCYTOGENES; PCR DETECTION; INHIBITION; VEGETABLES; SOIL; AMPLIFICATION; INTERFERENCE; SALMONELLA; BACTERIA; FRUITS AB Multiplex polymerase chain reaction (PCR) analysis was used to detect two genes encoding Shiga-like toxins (stx1 and stx2) and a universal Escherichia coli gene (gadA[B) in fresh produce spiked with E. coli O157:H7. Current U.S. Food and Drug Administration procedures for the analysis of fresh produce include the use of the rinsate from an initial rinse for the analysis of several potential pathogens, including E. coli O157:H7. In this study, several procedures were evaluated for their ability to increase the sensitivity of PCR analysis of rinsates from 15 types of produce. The procedures evaluated included the preliminary clarification and concentration of templates by centrifugation and the treatment of templates with compounds reported to facilitate nucleic acid amplification, including polyvinlypolypyrrolidone (PVPP), nonfat dry milk (NFDM), and InstaGene. The preliminary concentration of rinsates resulted in moderate improvements in detection sensitivity. The use of PVPP-treated templates in PCR reaction mixtures did not further improve sensitivity, but the inclusion of NFDM-treated templates increased sensitivity by an order of magnitude for 12 rinsates. The incorporation of InstaGene also improved the detection capability of the analysis; this procedure yielded the strongest gel bands for eight rinsates. However, for four other rinsates, the use of this reagent decreased sensitivity; these four rinsates were those for the produce varieties with the largest surface areas and were the most turbid rinsates. The use of facilitating compounds to block PCR inhibition may enable an analysis for Shiga toxin-producing E. coli in fresh produce to be completed in 1 to 2 days, rather than the 5 days required for current methods. C1 US FDA, Bothell, WA 98021 USA. RP Grant, MA (reprint author), US FDA, Bothell, WA 98021 USA. EM mgrant@ora.fda.gov NR 22 TC 17 Z9 17 U1 0 U2 6 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 2003 VL 66 IS 1 BP 18 EP 24 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 635DP UT WOS:000180383000003 PM 12540176 ER PT J AU Kaufman, GE Bej, AK Bowers, J DePaola, A AF Kaufman, GE Bej, AK Bowers, J DePaola, A TI Oyster-to-oyster variability in levels of Vibrio parahaemolyticus SO JOURNAL OF FOOD PROTECTION LA English DT Article ID PROBES; GENE AB This study examined the variability in the levels of total and pathogenic Vibrio parahaemolyticus in individual oysters. Twenty oysters were collected on three occasions (in June, July, and September 2001) from a site near Mobile Bay, Ala. Ten of these oysters were tested immediately, and 10 were tested after 24 h of storage at 26degreesC. Levels of total and pathogenic V. parahaemolyticus were determined by alkaline phosphatase-labeled DNA probe procedures targeting the thermolabile hemolysin and thermostable direct hemolysin genes, respectively. Similar V. parahaemolyticus levels (200 to 2,000 CFU/g) were found in nearly 90% of the oysters (for all sampling occasions) prior to storage. The log-transformed densities (means standard deviations) of V. parahaemolyticus in oysters immediately after harvest were 2.90 +/- 0.91, 2.88 +/- 0.36, and 2.47 +/- 0.26 log(10) CFU/g for June, July, and September, respectively. After storage for 24 h at 26degreesC, the mean V. parahaemolyticus densities increased approximately 13- to 26-fold. Before storage, pathogenic V. parahaemolyticus was detected in 40% (10 to 20 CFU/g) of the oysters collected in June and July but was not detected in any oysters collected in September. After storage, pathogenic V. parahaemolyticus was detected in some oysters at levels of >100 CFU/g. These data should aid in the development of sampling protocols for oyster monitoring programs and in the determination of exposure distributions associated with raw oyster consumption. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ Alabama, Dept Biol, Birmingham, AL 35294 USA. US FDA, Div Math, College Pk, MD 20740 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Isl, AL 36528 USA. NR 18 TC 18 Z9 18 U1 1 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 2003 VL 66 IS 1 BP 125 EP 129 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 635DP UT WOS:000180383000020 PM 12540193 ER PT J AU Ahmad, SR AF Ahmad, SR TI Adverse drug event monitoring at the Food and Drug Administration - Your report can make a difference SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE Food and Drug Administration (FDA); adverse drug events; postmarketing surveillance; MedWatch; drug withdrawals ID ASSOCIATION; CISAPRIDE AB The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk. C1 US FDA, Div Drug Risk Evaluat, Off Drug Safety, Ctr Drug Evaluat & Res HFD430, Rockville, MD 20857 USA. RP Ahmad, SR (reprint author), US FDA, Div Drug Risk Evaluat, Off Drug Safety, Ctr Drug Evaluat & Res HFD430, Room 15B-08,5600 Fishers Lane, Rockville, MD 20857 USA. NR 26 TC 83 Z9 86 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2003 VL 18 IS 1 BP 57 EP 60 DI 10.1046/j.1525-1497.2003.20130.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 634QU UT WOS:000180352600009 PM 12534765 ER PT J AU Lankford, CSR Frucht, DM AF Lankford, CSR Frucht, DM TI A unique role for IL-23 in promoting cellular immunity SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE IL-23R; IL-12; IL-12R; Stat4 ID IFN-GAMMA-PRODUCTION; I CYTOKINE RECEPTOR; DENDRITIC CELLS; IL-12 RECEPTOR; IL-12-DEFICIENT MICE; TRANSCRIPTION FACTOR; LINEAGE COMMITMENT; INTERLEUKIN-12; STAT4; EXPRESSION AB Recent discoveries of interleukin (IL)-23, its receptor, and its signal-transduction pathway add to our understanding of cellular immunity. IL-23 is a heterodimer, comprising IL-12 p40 and the recently cloned IL-23-specific p19 subunit. IL-23 uses many of the same signal-transduction components as IL-12, including IL-12Rbeta1, Janus kinase 2, Tyk2, signal transducer and activator of transcription (Stat)1, Stat3, Stat4, and Stat5. This may explain the similar actions of IL-12 and IL-23 in promoting cellular immunity by inducing interferon-gamma production and proliferative responses in target cells. Additionally, both cytokines promote the T helper cell type 1 costimulatory function of antigen-presenting cells. IL-23 does differ from IL-12 in the T cell subsets that it targets. Whereas IL-12 acts on naive CD4(+) T cells, IL-23 preferentially acts on memory CD4(+) T cells. This review summarizes recent advances regarding IL-23, providing a functional and mechanistic basis for the unique niche that IL-23 occupies in cellular immunity. C1 US FDA, DMA, CBER, Cell Biol Lab, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, DMA, CBER, Cell Biol Lab, Bldg 29B,Room 3NN22, Bethesda, MD 20892 USA. NR 42 TC 141 Z9 151 U1 2 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2003 VL 73 IS 1 BP 49 EP 56 DI 10.1189/jlb.0602326 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 636MY UT WOS:000180460900004 PM 12525561 ER PT J AU Elkins, CA Savage, DC AF Elkins, CA Savage, DC TI BsT2 from Lactobacillus johnsonii 100-100 is a transport protein of the major facilitator superfamily that facilitates bile acid antiport SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE major facilitator superfamily; Lactobacillus; bile acids; antiport; bile salt hydrolysis ID MULTIDRUG EFFLUX PUMPS; SALT HYDROLASE; ESCHERICHIA-COLI; GENES; OXALOBACTER; EXPRESSION; EXCHANGE; ACRB AB We previously identified two conjugated bile acid transporters, CbsT1 and CbsT2, in Lactobacillus johnsonii 100-100 and Lactobacillus acidophilus KS-13 that are gene duplicates encoded in tandem with a conjugated bile salt hydrolase (BSH) [Elkins and Savage, J. Bacteriol. 180:4344-4349, 1998; Elkins et al., Microbiology 147: 3403-3412, 2001]. CbsT2 from 100-100 was shown to increase taurocholic acid (TCA) uptake in Escherichia coli; however, higher levels were achieved when an extracellular factor (EF) from 100-100 was present in the assay medium (spent medium from 100-100, pH 4.2). We continued this study here to determine the role of EF in this transport system. Kinetic studies revealed that the previously observed CbsT2- and EF-mediated TCA accumulation is rapid (<15 s) but not saturable, suggesting that EF is limiting. In addition, uptake of TCA by E. coli expressing CbsT2 was insensitive to ionophores, 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone, and thus, is independent of the proton motive force. Since BSH converts [24-C-14]TCA to [24-C-14]cholic acid (CA), we measured net radiolabel uptake in E. coli cells expressing transporter(s) and BSH. Interestingly, such cells accumulated less C-14 radiolabel (by approximately half) than cells expressing CbsT2 alone. These data can be explained if CA diffuses out of E. coli through the transporter(s). We, therefore, added exogenous, unlabeled CA to EF-spent media, which under our assay conditions, performed similarly to EF+ culture supernatant in TCA and CA uptake assays. Thus, unlabeled CA (a protonated, neutral lipophile) can partition directly into E. coli cells especially at low pH. These findings were validated in uptake assays with [H-3]TCA, which yields [H-3]taurine (a hydrophilic moiety) upon hydrolysis by the BSH. Amounts of cell-associated H-3 radiolabel remained similar in cells expressing CbsT2 and BSH versus cells expressing only CbsT2, both of which were higher than in cells expressing BSH alone. Our data support a hypothesis that these transporters, which comprise a new subfamily of the major facilitator superfamily, facilitate antiport of TCA and CA. Copyright (C) 2003 S. Karger AG, Basel. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. RP Elkins, CA (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM Caelkins@ncti.fda.gov NR 32 TC 15 Z9 16 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2003 VL 6 IS 2 BP 76 EP 87 DI 10.1159/000076738 PG 12 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 810QZ UT WOS:000220720100002 PM 15044826 ER PT J AU Cooney, CA Dave, AA Siegel, ER Wolff, GL AF Cooney, CA Dave, AA Siegel, ER Wolff, GL TI Do maternal methyl supplements in mice affect DNA methylation of offspring? - Reply SO JOURNAL OF NUTRITION LA English DT Letter ID AGOUTI LOCUS C1 Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Harnwell, Philadelphia, PA 19104 USA. Univ Arkansas Med Sci, Div Biometry, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Cooney, CA (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2003 VL 133 IS 1 BP 239 EP 239 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 633VV UT WOS:000180305900043 ER PT J AU Basrur, V Yang, F Kushimoto, T Higashimoto, Y Yasumoto, K Valencia, J Muller, J Vieira, WD Watabe, H Shabanowitz, J Hearing, VJ Hunt, DF Appella, E AF Basrur, V Yang, F Kushimoto, T Higashimoto, Y Yasumoto, K Valencia, J Muller, J Vieira, WD Watabe, H Shabanowitz, J Hearing, VJ Hunt, DF Appella, E TI Proteomic analysis of early melanosomes: Identification of novel melanosomal proteins SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE melanoma; proteomics; melanosome ID HERMANSKY-PUDLAK-SYNDROME; TYROSINASE-RELATED PROTEIN-1; MONOCLONAL-ANTIBODIES; VESICULAR TRAFFICKING; MASS-SPECTROMETRY; HUMAN MELANOCYTES; MEMBRANE-PROTEIN; MELANOMA-CELLS; BIOGENESIS; EXPRESSION AB Melanin is a heterogeneous biopolymer produced only by specific cells termed melanocytes, which synthesize and deposit the pigment in specialized membrane-bound organelles known as melanosomes. Although melanosomes have been suspected of being closely related to lysosomes and platelets, the total number of melanosomal proteins is still unknown. Thus far, six melanosome-specific proteins have been identified, and the challenge is to characterize the complete proteome of the melanosome to further understand its mechanism of biogenesis. In this report, we used mass spectrometry and subcellular fractionation to identify protein components of early melanosomes. Using this approach, we have identified all 6 of the known melanosome-specific proteins, 56 proteins that are shared with other organelles, and confirmed the presence of 6 novel melanosomal proteins using western blotting and by immunohistochemistry. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA. RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B03, Bethesda, MD 20892 USA. RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 FU NIGMS NIH HHS [GM 37537] NR 72 TC 100 Z9 132 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JAN-FEB PY 2003 VL 2 IS 1 BP 69 EP 79 DI 10.1021/pr025562r PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 643RN UT WOS:000180874400008 PM 12643545 ER PT J AU Temple, RJ AF Temple, RJ TI Implications of effects in placebo groups SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID POWERLESS C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Temple, RJ (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-40, Rockville, MD 20857 USA. NR 10 TC 1 Z9 1 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 1 PY 2003 VL 95 IS 1 BP 2 EP 3 PG 2 WC Oncology SC Oncology GA 629YB UT WOS:000180079200001 PM 12509388 ER PT J AU Kraeling, MEK Bronaugh, RL AF Kraeling, MEK Bronaugh, RL TI In vitro absorption of triethanolamine through human skin SO JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY LA English DT Article DE triethanolamine; TEA; human skin; skin absorption; in vitro ID INVITRO PERCUTANEOUS-ABSORPTION; METABOLISM AB The human skin penetration of triethanolamine (TEA) was measured using in vitro diffusion cell techniques. [C-14]TEA was applied to viable skin in an oil-in-water emulsion containing TEA stearate as an emulsifying agent to simulate cosmetic exposure. The percent of the applied dose of TEA absorbed into the receptor fluid was similar with both 1% and 5% TEA formulations. Absorption of TEA was reduced by lowering the pH of the formulation, presumably due to the increased ionization of TEA. Absorption of TEA into the receptor fluid (1% formulation, pH 7.0) was 0.43% of the applied dose in a 24 h study. Substantial amounts of TEA remained in the skin at the end of the study (9.4% of dose), but only minimal amounts diffused into the receptor fluid when the collection time was extended to 72 h in separate studies. The amount of TEA remaining in skin at the end of the 24 h studies should not be included in estimates of systemic absorption. C1 US FDA, Off Cosmet & Colors, BRF, Laurel, MD 20708 USA. RP Kraeling, MEK (reprint author), US FDA, Off Cosmet & Colors, BRF, HFS-128,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 12 TC 3 Z9 3 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3829 J9 J TOXICOL-CUTAN OCUL JI J. Toxicol.-Cutan. Ocul. Toxicol. PY 2003 VL 22 IS 3 BP 137 EP 145 DI 10.1081/CUS-120022754 PG 9 WC Ophthalmology; Toxicology SC Ophthalmology; Toxicology GA 706LZ UT WOS:000184456300003 ER EF